1 00:00:05,800 --> 00:00:08,800 >>WELCOME TO 2 00:00:08,800 --> 00:00:10,680 THE SECOND DAY OF THIS 3 00:00:10,680 --> 00:00:13,120 INCREDIBLY INTERESTING AND 4 00:00:13,120 --> 00:00:14,320 CREATIVE MEETING. YOU KNOW, 5 00:00:14,320 --> 00:00:17,520 MANY YEARS AGO, WHEN I WAS A 6 00:00:17,520 --> 00:00:22,800 JERAT TRIGS ON THE FRONT LINE 7 00:00:22,800 --> 00:00:24,800 CARING FOR OLDER PATIENT REALLY 8 00:00:24,800 --> 00:00:27,200 IN THE BED AND OUTPATIENT 9 00:00:27,200 --> 00:00:32,000 CLINIC, I THOUGHT I DIDN'T HAVE 10 00:00:32,000 --> 00:00:36,600 THE WEAPONS I WANTED TO FIGHT 11 00:00:36,600 --> 00:00:38,480 THE DEADLY FORTH MAKING MY 12 00:00:38,480 --> 00:00:41,520 PATIENTS DISABLED AND ILL MY 13 00:00:41,520 --> 00:00:43,760 PATIENTS. WE ARE MAKING 14 00:00:43,760 --> 00:00:46,000 INCREDIBLE EFFORT TO GET GAIN IN 15 00:00:46,000 --> 00:00:48,760 FUNCTION AND SEE COMING BACK 16 00:00:48,760 --> 00:00:50,200 AFTER THE WEEK THAT HAVE LOST 17 00:00:50,200 --> 00:00:53,520 EVERYTHING WE HAD GAINED AND MY 18 00:00:53,520 --> 00:00:56,960 DREAM WAS THE SOME POINT THERE 19 00:00:56,960 --> 00:01:01,640 WILL BE A SCIENCE THAT WILL HELP 20 00:01:01,640 --> 00:01:03,640 JERAT TRIGS TO DO BETTER THAN 21 00:01:03,640 --> 00:01:07,640 THAT AND THIS SUMMIT GAVE ME 22 00:01:07,640 --> 00:01:08,120 INCREDIBLE HOPE THIS IS 23 00:01:08,120 --> 00:01:10,360 HAPPENING IN OUR SCIENCE TO BE 24 00:01:10,360 --> 00:01:12,440 TRANSLATED TO HEALTH OF OUR 25 00:01:12,440 --> 00:01:19,640 PATIENT NOT IN 25 YEARS OR MAYBE 26 00:01:19,640 --> 00:01:22,440 IN NEXT FIVE YEARS THAT IS A 27 00:01:22,440 --> 00:01:25,160 MIRACLE AND FOR ME A TRULY DREAM 28 00:01:25,160 --> 00:01:26,760 COME TRUE AND WE SAW YESTERDAY 29 00:01:26,760 --> 00:01:28,920 THE DIVERSITY AND INEQUALITY IN 30 00:01:28,920 --> 00:01:39,400 THE DISTRIBUTION OF HEALTH. 31 00:01:48,920 --> 00:01:50,320 WE CAN UNDERSTAND BETTER 32 00:01:50,320 --> 00:01:52,680 MECHANISM OF AGING PROCESS AND 33 00:01:52,680 --> 00:01:56,000 LOOKING AT DIFFERENT POPULATION 34 00:01:56,000 --> 00:02:01,080 AND SENTINARIAN AND PEOPLE 35 00:02:01,080 --> 00:02:02,800 LIVING IN COUNTRIES WHERE HEALTH 36 00:02:02,800 --> 00:02:05,000 CARE IS NOT AS DEVELOPED AND WE 37 00:02:05,000 --> 00:02:07,800 LOOKED AT THE REALLY CLINICAL 38 00:02:07,800 --> 00:02:12,280 RELEVANCE OF MULTIMORBIDITY AND 39 00:02:12,280 --> 00:02:14,120 EXPLORE THROUGH ANIMAL MODEL HOW 40 00:02:14,120 --> 00:02:16,840 TO DO TRANSLATION AND BAD 41 00:02:16,840 --> 00:02:20,080 TRANSLATION AND HOW PEOPLE THAT 42 00:02:20,080 --> 00:02:30,600 DO SCIENCE WITH PATIENTS AND 43 00:02:49,160 --> 00:02:49,720 RESEARCH IN ANIMAL MODEL DO WITH 44 00:02:49,720 --> 00:02:50,240 EACH OTHER AND REACH MORE 45 00:02:50,240 --> 00:02:50,840 KNOWLEDGE AND TODAY WILL BE 46 00:02:50,840 --> 00:02:51,320 TECHNICAL BUT NOT LESS 47 00:02:51,320 --> 00:02:51,920 INTERESTING AND EXCITING AND 48 00:02:51,920 --> 00:02:52,480 TALKING ABOUT MATHEMATICAL 49 00:02:52,480 --> 00:02:53,120 MODELS AND BIOMARKERS TO ME THAT 50 00:02:53,120 --> 00:02:53,760 IS THE MOST INTERESTING SESSION 51 00:02:53,760 --> 00:02:54,160 FOR THIS MEETING. 52 00:02:54,160 --> 00:02:54,760 SO, I WILL BE THERE WITH YOU 53 00:02:54,760 --> 00:02:55,440 LISTENING AND HOPING THAT THIS 54 00:02:55,440 --> 00:02:56,840 DISCUSSION AT LEAST A LITTLE BIT 55 00:02:56,840 --> 00:03:00,200 WILL HAVE A FEW OF THE OLDER 56 00:03:00,200 --> 00:03:01,840 PATIENTS OF THE FUTURE. THANK 57 00:03:01,840 --> 00:03:03,000 YOU VERY MUCH FOR PARTICIPATION 58 00:03:03,000 --> 00:03:04,720 FOR THOSE THAT ARE HERE AND TO 59 00:03:04,720 --> 00:03:07,840 THOSE THAT ARE LISTENING FROM 60 00:03:07,840 --> 00:03:11,120 THE VIRTUAL CONNECTION. 61 00:03:11,120 --> 00:03:21,640 NOW, WE HAVE THE FIRST SPEAKER. 62 00:03:25,720 --> 00:03:28,080 >>HELLO, EVERYONE. WELCOME. 63 00:03:28,080 --> 00:03:31,240 IT IS MY PLEASURE TO INTRODUCE 64 00:03:31,240 --> 00:03:33,280 SESSION 4 AND BE THE CHAIR FOR 65 00:03:33,280 --> 00:03:36,120 SESSION ON METHODS FOR MEASURING 66 00:03:36,120 --> 00:03:39,880 HEALTH. I'M LOLITA AN ASSISTANT 67 00:03:39,880 --> 00:03:42,520 PROFESSOR AT JOHNS HOPKINS 68 00:03:42,520 --> 00:03:43,760 UNIVERSITY AND WILL INTRODUCE 69 00:03:43,760 --> 00:03:46,360 THE SPEAKERS AND FIRST THEY WILL 70 00:03:46,360 --> 00:03:50,360 SPEAK AND THERE IS TIME AT THE 71 00:03:50,360 --> 00:04:00,880 END FOR QUESTIONS. NEXT WE WILL 72 00:04:25,160 --> 00:04:28,400 HAVE DR. EILEEN CRIMMONS AND 73 00:04:28,400 --> 00:04:33,520 DIRECTOR AT UCLA CENTER FOR 74 00:04:33,520 --> 00:04:34,480 BIODEMOGRAPHY AND POPULATION 75 00:04:34,480 --> 00:04:40,600 HEALTH AT USC LEONARD SCHOOL OF 76 00:04:40,600 --> 00:04:43,720 GERONTOLOGY SPEAKING ON 77 00:04:43,720 --> 00:04:47,360 MULTILEVEL BIOMARKERS WITH HUMAN 78 00:04:47,360 --> 00:04:49,240 AGING AND VICE PRESIDENT AND 79 00:04:49,240 --> 00:04:51,240 PROFESSOR AT ACADEMIC AFFAIRS 80 00:04:51,240 --> 00:04:52,880 FOR BUCK INSTITUTE FOR RESEARCH 81 00:04:52,880 --> 00:04:56,400 AND AGING SPEAKING ABOUT THE 82 00:04:56,400 --> 00:05:06,920 AGING INTERVENTION PIPELINE. 83 00:05:16,720 --> 00:05:18,400 >>GOOD MORNING, EVERYONE. 84 00:05:18,400 --> 00:05:20,360 THANK YOU TO THE ORGANIZERS FOR 85 00:05:20,360 --> 00:05:22,000 LETTING ME COME TO TALK TO YOU 86 00:05:22,000 --> 00:05:23,360 ABOUT WORK I HAVE DONE IN 87 00:05:23,360 --> 00:05:26,320 COLLABORATION WITH OTHERS ON 88 00:05:26,320 --> 00:05:29,000 DEFICIT ACCUMULATION ON AGING IN 89 00:05:29,000 --> 00:05:34,920 ANIMAL MODELS AND WILL DO A 90 00:05:34,920 --> 00:05:38,240 LITTLE BIT ON HUMANS AS WELL. 91 00:05:38,240 --> 00:05:46,520 OKAY. SLIDE IS ADVANCING. 92 00:05:46,520 --> 00:05:54,320 IT WAS WORKING BEFORE. 93 00:05:54,320 --> 00:05:59,040 30 SECONDS ARE GONE. OKAY. I 94 00:05:59,040 --> 00:06:09,600 LOST 30 SECONDS. IS IT BACK? 95 00:06:14,560 --> 00:06:18,320 YOU MIGHT CONSIDER THIS CHEEKY 96 00:06:18,320 --> 00:06:20,680 UK ROADSIDE, EXCUSE ME. 97 00:06:20,680 --> 00:06:23,040 DEPICTING A SENSE OF OLDER 98 00:06:23,040 --> 00:06:25,000 ADULTS AND YOU MIGHT THINK ABOUT 99 00:06:25,000 --> 00:06:28,480 SOMEBODY LIKE EDWHIT LOCK, A 100 00:06:28,480 --> 00:06:29,440 CANADIAN SETTING WORLD RECORD IN 101 00:06:29,440 --> 00:06:32,600 THE MARATHON FOR 85 YEARS OF AGE 102 00:06:32,600 --> 00:06:37,800 IN 2016 FOR SUB TIME AND PRETTY 103 00:06:37,800 --> 00:06:41,920 IMPRESSIVE FETE AND IS CLEAR 104 00:06:41,920 --> 00:06:43,520 THAT AGING IS HETEROGENOUS AND 105 00:06:43,520 --> 00:06:46,120 CONCEPT OF FRAILTY WE HEARD 106 00:06:46,120 --> 00:06:47,280 EXTENSIVELY AND COMES FROM OR IS 107 00:06:47,280 --> 00:06:49,280 INITIALLY USED TO REFER TO 108 00:06:49,280 --> 00:06:51,360 VARIABILITY IN THE RISK OF 109 00:06:51,360 --> 00:06:54,000 HAVING ADVERSE HEALTH OUTCOME IN 110 00:06:54,000 --> 00:06:56,840 INDIVIDUALS WHO ARE THE SAME AGE 111 00:06:56,840 --> 00:06:59,280 THAT COMES FROM DEMOGRAPHER 112 00:06:59,280 --> 00:07:00,800 LITERATURE ACTUIARYIES LOOKING 113 00:07:00,800 --> 00:07:02,920 AT LIFE TABLES AND HOW LONG 114 00:07:02,920 --> 00:07:05,960 SOMEONE IS EXPECTED TO SURVIVE 115 00:07:05,960 --> 00:07:07,440 AND COME TO OPERATIONALIZE 116 00:07:07,440 --> 00:07:10,360 FRAILTY IN SEVERAL WAYS 117 00:07:10,360 --> 00:07:11,720 CLINICALLY AND 2001 TWO 118 00:07:11,720 --> 00:07:13,240 APPROACHES DEVELOPED FOR 119 00:07:13,240 --> 00:07:14,240 CLINICAL SAMPLES AND MANY 120 00:07:14,240 --> 00:07:17,080 INSTRUMENTS I WOULD LIKE TO ADD 121 00:07:17,080 --> 00:07:18,640 AND TWO HAVE BECOME WELL-KNOWN 122 00:07:18,640 --> 00:07:21,520 AND ONE IS FRAILTY PHENOTYPE 123 00:07:21,520 --> 00:07:23,360 LOOKING AT DEFICITS IN FIVE 124 00:07:23,360 --> 00:07:25,760 PHYSICAL DOMAINS AND WON'T TALK 125 00:07:25,760 --> 00:07:28,160 ABOUT THAT ONE. I WILL POINT OUT 126 00:07:28,160 --> 00:07:32,400 IT IS OPERATIONALIZED FOR USE IN 127 00:07:32,400 --> 00:07:36,040 ANIMAL MODELS AND FRAILTY INDEX 128 00:07:36,040 --> 00:07:37,880 IN A LARGE NUMBER OF HEALTH 129 00:07:37,880 --> 00:07:41,400 DOMAINS THAT IS A PRETTY SIMPLE 130 00:07:41,400 --> 00:07:43,200 CONCEPT DEVELOPED BY KEN 131 00:07:43,200 --> 00:07:44,040 ROBBINGWOOD AND [INDISCERNIBLE] 132 00:07:44,040 --> 00:07:46,440 AT HOUSING UNIVERSITY WHERE I 133 00:07:46,440 --> 00:07:49,440 WORK AND IDEA IS EXCUSE ME IF 134 00:07:49,440 --> 00:07:51,560 YOU HAVE A NUMBER OF POTENTIAL 135 00:07:51,560 --> 00:07:53,840 HEALTH DEFICITS YOU LOOK AT 136 00:07:53,840 --> 00:07:55,280 DEFICITS IN INDIVIDUAL AND 137 00:07:55,280 --> 00:07:57,680 DIVIDE BY TOTAL DEFICITS 138 00:07:57,680 --> 00:07:59,240 MEASURED TO GET A NUMBER BETWEEN 139 00:07:59,240 --> 00:08:03,400 0 AND 1 AND THIS DATA YOU IS 140 00:08:03,400 --> 00:08:08,040 OBTAINED FROM OUR UNIVERSITY 141 00:08:08,040 --> 00:08:10,280 FROM COMPREHENSIVE GERIATRIC 142 00:08:10,280 --> 00:08:12,000 FORM. YOU CAN'T SEE BUT IF YOU 143 00:08:12,000 --> 00:08:15,200 ZOOM IN YOU SEE ON FAR 144 00:08:15,200 --> 00:08:16,360 RIGHT-HAND SIDE OF THE SLIDE 145 00:08:16,360 --> 00:08:17,880 CURRENT STAGE OF THE INDIVIDUAL 146 00:08:17,880 --> 00:08:20,240 THEY ARE INCONTINENT AND 147 00:08:20,240 --> 00:08:22,640 INDEPENDENT IN ACTIVITIES OF 148 00:08:22,640 --> 00:08:24,040 DAILY LIVING AND SEE WHAT THEY 149 00:08:24,040 --> 00:08:25,400 LOOK LIKE TWO WEEKS AGO IF THEY 150 00:08:25,400 --> 00:08:27,800 CAME IN TO SEE YOU AND SEE THEY 151 00:08:27,800 --> 00:08:30,080 PREVIOUSLY WERE CONTINENT AND 152 00:08:30,080 --> 00:08:32,000 INDEPENDENT AND ALL THESE THINGS 153 00:08:32,000 --> 00:08:34,920 CAN BE CALLED DEFICITS AND FORM 154 00:08:34,920 --> 00:08:37,040 LIKE THIS CAN GENERATE 70 155 00:08:37,040 --> 00:08:38,720 POTENTIAL HEALTH DEFICITS AND 156 00:08:38,720 --> 00:08:41,000 WHEN YOU LOOK AT FRAILTY INDEX 157 00:08:41,000 --> 00:08:42,960 SCORES IN PEOPLE, WHAT YOU SEE 158 00:08:42,960 --> 00:08:45,560 IS THIS IS PEOPLE FROM 15 TO 159 00:08:45,560 --> 00:08:47,720 102. YOU CAN SEE FRAILTY STARTS 160 00:08:47,720 --> 00:08:50,240 TO ACCELERATE IN THE LAST FEW 161 00:08:50,240 --> 00:08:52,520 DECADES OF LIFE AND THESE ARE 162 00:08:52,520 --> 00:08:54,920 MEAN DATA. YOU CAN SEE 163 00:08:54,920 --> 00:08:56,320 EXPONENTIAL INCREASE IN FRAILTY 164 00:08:56,320 --> 00:08:58,000 INDEX SCORES AND IN PEOPLE THAT 165 00:08:58,000 --> 00:09:01,520 ARE 102 YEARS OLD YOU CAN SEE 166 00:09:01,520 --> 00:09:02,840 AVERAGE IS .4 THAT SUGGESTS 167 00:09:02,840 --> 00:09:04,480 SOMETHING INTERESTING ABOUT THE 168 00:09:04,480 --> 00:09:06,480 IDEA OF FRAILTY THAT IS THAT 169 00:09:06,480 --> 00:09:09,320 THERE IS A LIMIT. EXCUSE ME. 170 00:09:09,320 --> 00:09:10,520 TO HOW FRAIL SOMEONE CAN BECOME. 171 00:09:10,520 --> 00:09:14,080 THAT LIMIT SEEMS TO BE AT .67. 172 00:09:14,080 --> 00:09:17,680 WHEN YOU ACCUMULATED 2/3 OF ALL 173 00:09:17,680 --> 00:09:20,600 POSSIBLE DEFICITS IN A LIST YOU 174 00:09:20,600 --> 00:09:22,800 CAN'T TOLERATE ONE MORE DEFICIT 175 00:09:22,800 --> 00:09:25,440 EVEN IF FAIRLY SMALL AND 7 176 00:09:25,440 --> 00:09:27,680 CYCLES OF NATIONAL POPULATION 177 00:09:27,680 --> 00:09:28,840 HEALTH SURVEY REFLECTING LARGE 178 00:09:28,840 --> 00:09:30,440 NUMBER OF PEOPLE SAMPLES OVER 179 00:09:30,440 --> 00:09:33,360 AND OVER A GAIN. YOU CAN SEE IT 180 00:09:33,360 --> 00:09:38,600 IS A CONSISTENT FUNCTION. SO, 181 00:09:38,600 --> 00:09:40,400 WE HAVE BEEN IN MY LAB USING 182 00:09:40,400 --> 00:09:42,880 OLDER MOOIS TO TRY TO BETTER 183 00:09:42,880 --> 00:09:45,080 MODEL HUMAN DISEASES OF AGING 184 00:09:45,080 --> 00:09:47,400 AND HAVE DONE CARDIOVASCULAR 185 00:09:47,400 --> 00:09:48,760 RESEARCH FOR MANY YEARS LOOKING 186 00:09:48,760 --> 00:09:51,000 AT IDEA WE SHOULD DO WORK IN 187 00:09:51,000 --> 00:09:53,560 OLDER ANIMALS AND NOTICED THAT 188 00:09:53,560 --> 00:09:56,080 WHILE SOME OF OUR OLD MICE 189 00:09:56,080 --> 00:09:58,240 LOOKED REALLY QUITE GOOD LIKE 190 00:09:58,240 --> 00:10:02,760 THIS YOUNG ADULT C57 BLACK 191 00:10:02,760 --> 00:10:04,640 [INDISCERNIBLE] OTHERS START TO 192 00:10:04,640 --> 00:10:08,920 DEVELOP DEFICITS. YOU SEE HERE 193 00:10:08,920 --> 00:10:11,560 KYPHOSIS ON MOUSE ON LEFT AND 194 00:10:11,560 --> 00:10:14,040 CURVATURE OF SPINE AND PATCHY 195 00:10:14,040 --> 00:10:16,720 HAIR LOSS AND ALOPECIA AND 196 00:10:16,720 --> 00:10:18,760 STIFFENING IN MICE AS THEY 197 00:10:18,760 --> 00:10:20,920 DEVELOP IN AGE AND LOOKED LIKE 198 00:10:20,920 --> 00:10:24,840 MICE LOOK LIKE THEY EXHIBIT 199 00:10:24,840 --> 00:10:25,960 HETEROGENOUS AGING AND SOUGHT 200 00:10:25,960 --> 00:10:28,800 OUT A WAY TO QUANTIFY THAT AND 201 00:10:28,800 --> 00:10:31,240 DRAWING ON THE CLINICAL TOOL WE 202 00:10:31,240 --> 00:10:33,000 DEVELOPED A MOST COMPREHENSIVE 203 00:10:33,000 --> 00:10:34,640 GERIATRIC ASSESSMENT TOOL AND 204 00:10:34,640 --> 00:10:37,240 PROJECT I DID WITH JOCELYN 205 00:10:37,240 --> 00:10:39,320 WHITEHEAD IN LAB BACK IN 2014 206 00:10:39,320 --> 00:10:41,960 AND A LITTLE EARLIER AND WE 207 00:10:41,960 --> 00:10:46,880 LOOKED AT MANY DIFFERENT DOMAINS 208 00:10:46,880 --> 00:10:48,520 MUSCULOSKELETAL DOMAIN AND WE 209 00:10:48,520 --> 00:10:49,880 LOOKED AT WHETHER MOUSE THAT WE 210 00:10:49,880 --> 00:10:52,440 WERE EXAMINING HAD A DEFICIT. 211 00:10:52,440 --> 00:10:54,680 WE ARE SEEING FOR EXAMPLE A 212 00:10:54,680 --> 00:10:58,040 SCORE OF 0 FOR TUMORS AND 0 FOR 213 00:10:58,040 --> 00:11:01,800 EXTENDED ABDOMEN BUT 1 FOR 214 00:11:01,800 --> 00:11:03,200 KYPHOSIS. IT IS SIMPLE AS THEY 215 00:11:03,200 --> 00:11:06,320 DO FOR HUMAN INSTRUMENT WE ADD 216 00:11:06,320 --> 00:11:06,960 DEFICITS IN INDIVIDUAL ANIMAL 217 00:11:06,960 --> 00:11:09,160 AND DIVIDE BY TOTAL NUMBER TO 218 00:11:09,160 --> 00:11:13,440 GET A FRAILTY INDEX SCORE. 219 00:11:13,440 --> 00:11:15,080 IN WORK DONE WITH KIM 220 00:11:15,080 --> 00:11:18,360 ROBBINGWOOD, WE COMPARED HUMAN 221 00:11:18,360 --> 00:11:23,720 AND MOUSE CLINICAL FRAILTY DATA. 222 00:11:23,720 --> 00:11:27,160 YOU SEE HERE MOUSE DATA AND 14 223 00:11:27,160 --> 00:11:30,840 MICE AND 14 PEOPLE AND YOU SEE 224 00:11:30,840 --> 00:11:34,280 THEY ARE SIMILAR NORMALIZING TO 225 00:11:34,280 --> 00:11:37,000 MAXIMUM LIFESPAN OF SPECIES AND 226 00:11:37,000 --> 00:11:38,840 FRAILTY INDEX SCORES AT EXTREMES 227 00:11:38,840 --> 00:11:43,720 OF LIFE SHOW LIMITS OF .4 TO .5 228 00:11:43,720 --> 00:11:45,400 AND DON'T SEE INCREASE IN 229 00:11:45,400 --> 00:11:48,760 FRAILTY BEYOND THAT BECAUSE IT 230 00:11:48,760 --> 00:11:50,680 IS LETHAL BEYOND .67. WE 231 00:11:50,680 --> 00:11:53,960 PUBLISHED A NUMBER OF PAPERS ON 232 00:11:53,960 --> 00:11:56,480 THIS AND ROBBINGWOOD 2017 PAPER 233 00:11:56,480 --> 00:11:58,400 DOES HEAD TO HEAD COMPARISON 234 00:11:58,400 --> 00:12:00,640 WITH MICE AND HUMANS AND REVIEW 235 00:12:00,640 --> 00:12:02,560 IN NATURE FOR AGING FOR ANYONE 236 00:12:02,560 --> 00:12:04,440 THAT IS INTERESTED. WHY IS THIS 237 00:12:04,440 --> 00:12:06,160 IMPORTANT AND INTERESTING? 238 00:12:06,160 --> 00:12:09,240 IF YOU LOOK AT FACTORS THAT 239 00:12:09,240 --> 00:12:10,240 PREDISPOSE INDIVIDUALS TO BECOME 240 00:12:10,240 --> 00:12:16,040 FIT OR FRAIL, YOU CAN SEE 241 00:12:16,040 --> 00:12:17,880 BALANCE IS TIPPED IN FAVOR OF 242 00:12:17,880 --> 00:12:20,520 FITNESS IF EATING A BALANCED 243 00:12:20,520 --> 00:12:22,640 DIET AND EDUCATION IS HIGHLY 244 00:12:22,640 --> 00:12:23,560 PROTECTIVE AND [INDISCERNIBLE] 245 00:12:23,560 --> 00:12:24,880 COULD BE OF INTEREST AND 246 00:12:24,880 --> 00:12:28,320 EXERCISE AND THINGS LIKE SOCIAL 247 00:12:28,320 --> 00:12:30,280 ENGAGEMENTS LIVING IN SAFE 248 00:12:30,280 --> 00:12:31,720 NEIGHBORHOOD ARE PREDISPOSED 249 00:12:31,720 --> 00:12:33,880 TOWARDS FITNESS AND HIGH FAT 250 00:12:33,880 --> 00:12:35,400 DIET AND RADIATION THERAPY AND 251 00:12:35,400 --> 00:12:44,920 POOR MATERNAL HEALTH AND LOW 252 00:12:44,920 --> 00:12:46,800 WEALTH AND PHARMACY, ET CETERA 253 00:12:46,800 --> 00:12:47,840 AND LOOKED AT BALANCE AND 254 00:12:47,840 --> 00:12:49,360 TALKING ABOUT THINGS WE HAVE 255 00:12:49,360 --> 00:12:51,480 DONE TO LOOK AT FACTORS 256 00:12:51,480 --> 00:12:54,720 PROMOTING FITNESS AND WORK DONE 257 00:12:54,720 --> 00:12:57,360 WITH ALICE CANE POST DOCKED IN 258 00:12:57,360 --> 00:12:58,840 LAB AND AUDIENCE AND YOU WILL 259 00:12:58,840 --> 00:13:01,480 HEAR FROM LATER AND CAITLIN 260 00:13:01,480 --> 00:13:04,000 KELLER A GRADUATE STUDENT TAKING 261 00:13:04,000 --> 00:13:07,760 SAMPLE OF MAIL MALE AND FEMALE 262 00:13:07,760 --> 00:13:10,360 MICE AND FOLLOWED THEM AND 263 00:13:10,360 --> 00:13:11,760 MATCHED THEM FOR BASELINE 264 00:13:11,760 --> 00:13:13,840 FRAILTY SCORES AND TREATED THEM 265 00:13:13,840 --> 00:13:19,480 WITH ACE INHIBITOR CALLED 266 00:13:19,480 --> 00:13:21,840 ANALOPRIL AND MEDICATION WITH 267 00:13:21,840 --> 00:13:23,720 BENEFIT ROOZ HE DEUCE 268 00:13:23,720 --> 00:13:25,440 INFLAMMATION IMPROVING MUSCLE 269 00:13:25,440 --> 00:13:27,600 MASS AND STRENGTH AND HERE 270 00:13:27,600 --> 00:13:31,720 LOOKING AT FRAILTY SCORES LEFT 271 00:13:31,720 --> 00:13:38,160 SIDE ON MOOIS AND RIGHT SIDE ON 272 00:13:38,160 --> 00:13:38,400 HUMANS. 273 00:13:38,400 --> 00:13:40,760 THIS IS SEEN CLINICALLY. IN 274 00:13:40,760 --> 00:13:44,080 ADDITION YOU SEE TREATMENT OF 275 00:13:44,080 --> 00:13:47,600 ANALO INVENTED INCREASE WITH 276 00:13:47,600 --> 00:13:50,240 FRAILTY IN OLDER LIFESPAN THAT 277 00:13:50,240 --> 00:13:51,960 WAS HIGHLY SIGNIFICANT IN 278 00:13:51,960 --> 00:13:56,760 FEMALES BY 20 MONTHS OF AGE. 279 00:13:56,760 --> 00:14:00,720 WE LOOKED AT EXERCISE AS A 280 00:14:00,720 --> 00:14:02,280 GERALD PROTECTIVE INTERVENTION 281 00:14:02,280 --> 00:14:04,720 AND MICE THAT ARE SEDENTARY FOR 282 00:14:04,720 --> 00:14:07,680 THEIR ENTIRE LIFE AT 22 MONTHS 283 00:14:07,680 --> 00:14:09,320 SUDDENLY OPPORTUNITY TO USE 284 00:14:09,320 --> 00:14:10,840 VOLUNTARY EXERCISE WHEEL AND 285 00:14:10,840 --> 00:14:13,560 STARTED A 13 WEEK TRIAL OF 286 00:14:13,560 --> 00:14:14,840 RUNNING VERSUS SEDENTARY. 287 00:14:14,840 --> 00:14:17,480 THIS IS WORK DONE WITH SCOTT 288 00:14:17,480 --> 00:14:21,600 GRANDY A COLLEAGUE OF MINE IN 289 00:14:21,600 --> 00:14:23,640 KINESIOLOGY IN MY DEPARTMENT AND 290 00:14:23,640 --> 00:14:26,360 ELISE WHO IS A GRADUATE STUDENT 291 00:14:26,360 --> 00:14:27,960 IN MY LAB AND SAW SOMETHING 292 00:14:27,960 --> 00:14:29,640 INTERESTING HERE. GIVING OLDER 293 00:14:29,640 --> 00:14:31,400 MICE THE CHANCE TO EXERCISE, YOU 294 00:14:31,400 --> 00:14:33,200 SEE FRAILTY INCREASED WITH TIME 295 00:14:33,200 --> 00:14:35,440 IN FEMALES AND MALES AND WHEN 296 00:14:35,440 --> 00:14:37,680 THEY EXERCISED, WE DIDN'T SEE 297 00:14:37,680 --> 00:14:40,280 INCREASE IN FRAILTY AND IN FACT 298 00:14:40,280 --> 00:14:42,400 MALES DIFFERENCE WAS SMALLER AND 299 00:14:42,400 --> 00:14:43,920 FEMALES WE SAW SIGNIFICANT 300 00:14:43,920 --> 00:14:48,080 DECREASE IN FRAILTY IN MICE WHO 301 00:14:48,080 --> 00:14:48,360 EXERCISED. 302 00:14:48,360 --> 00:14:50,000 WE HAVE ALSO DONE SOME OTHER 303 00:14:50,000 --> 00:14:52,360 WORK WITH THIS MODEL. 304 00:14:52,360 --> 00:14:54,400 SO, WE HAVE BEEN INTERESTED IN 305 00:14:54,400 --> 00:14:56,360 THE IDEA THAT SOME OF THE 306 00:14:56,360 --> 00:14:58,160 CHANGES THAT YOU SEE, YOU KNOW, 307 00:14:58,160 --> 00:15:00,720 CAN BE DUE TO CHANGES IN THE 308 00:15:00,720 --> 00:15:02,320 RELATIONSHIP BETWEEN DAMAGE AND 309 00:15:02,320 --> 00:15:03,120 REPAIR. 310 00:15:03,120 --> 00:15:04,720 SO, THIS IS WORK THAT IS DONE 311 00:15:04,720 --> 00:15:07,640 DURING THE PANDEMIC WITH TWO 312 00:15:07,640 --> 00:15:10,680 PHYSICISTS AT MY UNIVERSITY AND 313 00:15:10,680 --> 00:15:12,120 PUBLISHED LAST YEAR IN ELIFE. 314 00:15:12,120 --> 00:15:15,760 WE TRIED TO LOOK AT TRANSITIONS 315 00:15:15,760 --> 00:15:19,080 THAT YOU CAN GELT LONGITUDINALLY 316 00:15:19,080 --> 00:15:21,400 COLLECTING DATA FROM MICE 317 00:15:21,400 --> 00:15:22,920 BETWEEN A DEFICIT BEING PRESENT 318 00:15:22,920 --> 00:15:26,600 OR BEING ABSENT AND SEE WHILE 319 00:15:26,600 --> 00:15:28,400 TRANSITION IS TO HIGHER STATE OF 320 00:15:28,400 --> 00:15:30,800 FRAILTY SO ACCUMULATING MORE 321 00:15:30,800 --> 00:15:32,640 DEFICITS YOU GET THINGS THAT 322 00:15:32,640 --> 00:15:34,240 REPAIR AND WERE A DEFICIT EARLY 323 00:15:34,240 --> 00:15:37,040 ON AND NO LONGER A DEFICIT 324 00:15:37,040 --> 00:15:38,120 LATER. 325 00:15:38,120 --> 00:15:40,840 WE MODELED THIS YOU SEE HERE AT 326 00:15:40,840 --> 00:15:42,760 TOP THIS IS MOST DATA SET FROM 327 00:15:42,760 --> 00:15:45,400 PAPER WE PUBLISHED FROM ALLISON 328 00:15:45,400 --> 00:15:49,160 AND KAIN AND DAVID SINCLAIR'S 329 00:15:49,160 --> 00:15:52,680 LAB MODELING DATA FROM MALE MICE 330 00:15:52,680 --> 00:15:54,680 ON TOP AND DAMAGED RATES ON 331 00:15:54,680 --> 00:15:57,200 BOTTOM AND AGE LOOKING AT AGE 26 332 00:15:57,200 --> 00:15:59,320 TO TLOO HE 6 MONTHS AND YOU SEE 333 00:15:59,320 --> 00:16:02,160 AGING PROCESS NEEDS TO BE 334 00:16:02,160 --> 00:16:03,000 ASSOCIATED WITH DECREASE IN 335 00:16:03,000 --> 00:16:10,200 REPAIR AND INCREASE IN DAMAGE. 336 00:16:10,200 --> 00:16:12,440 SO, THAT IS SUMMARIZED HERE. 337 00:16:12,440 --> 00:16:14,480 SO, WHAT WE THEN THOUGHT WAS, 338 00:16:14,480 --> 00:16:16,280 WELL, WHAT ARE INTERVENTIONS 339 00:16:16,280 --> 00:16:18,480 DOING TO THE RATES OF REPAIR AND 340 00:16:18,480 --> 00:16:20,280 OF DAMAGE AND ARE WE DERIVING 341 00:16:20,280 --> 00:16:22,400 ONE IN FAVOR OF THE OTHER? 342 00:16:22,400 --> 00:16:25,320 WHAT WE SEE HERE IS THE DATA SET 343 00:16:25,320 --> 00:16:27,240 FROM [INDISCERNIBLE] TREATED 344 00:16:27,240 --> 00:16:29,200 ANIMALS YOU SEE REPAIR RATES ARE 345 00:16:29,200 --> 00:16:31,440 HIGHER IN MALE AND FEMALE MICE 346 00:16:31,440 --> 00:16:34,680 IN PRESENCE OF ANALOPRIL AND 347 00:16:34,680 --> 00:16:36,480 DAMAGE RATES ARE LOWER AND DOING 348 00:16:36,480 --> 00:16:39,200 THIS I'M LOOKING AT EXERCISE 349 00:16:39,200 --> 00:16:42,360 GROUP. YOU SEE THROUGH REPAIR 350 00:16:42,360 --> 00:16:44,200 RATES IN EXERCISE-TREATED MICE 351 00:16:44,200 --> 00:16:46,920 ARE HIGHER ESPECIALLY IN FEMALES 352 00:16:46,920 --> 00:16:49,240 AND DAMAGE RATES ARE LOWER. 353 00:16:49,240 --> 00:16:52,080 TRYING TO LOOK AT THIS AND 354 00:16:52,080 --> 00:16:53,280 COMPARING WHETHER ONE EFFECT WAS 355 00:16:53,280 --> 00:16:55,120 STRONGER THAN THE OTHER, WE 356 00:16:55,120 --> 00:16:59,280 FOUND THAT BOTH EXERCISE AND 357 00:16:59,280 --> 00:17:02,160 ANALOPRIL APPEAR TO REDUCE DANL 358 00:17:02,160 --> 00:17:04,560 RATE AND DON'T KNOW WHETHER WE 359 00:17:04,560 --> 00:17:08,320 CAN SAY WHETHER ONE WAS MORE 360 00:17:08,320 --> 00:17:09,960 POTENT THAN THE OTHER AND 361 00:17:09,960 --> 00:17:11,720 REDEUCE REPAIR RATE AND TREATING 362 00:17:11,720 --> 00:17:17,920 WITH EXERCISE AND ANALOPRIL YOU 363 00:17:17,920 --> 00:17:23,280 GET DAMAGE AND REPAIR AND 364 00:17:23,280 --> 00:17:25,680 FACTORS PREDISPOSE TO FRAILTY 365 00:17:25,680 --> 00:17:28,920 AND STUDY WITH SARA AT 366 00:17:28,920 --> 00:17:30,640 UNIVERSITY OF SIDNEY AND JOHN 367 00:17:30,640 --> 00:17:33,720 MAC AND OTHERS AND HAVE POLICY 368 00:17:33,720 --> 00:17:34,960 DIET THEY DEVELOPED FOR MANY 369 00:17:34,960 --> 00:17:37,320 YEARS AND LOOK AT DRUGS WITH 370 00:17:37,320 --> 00:17:40,080 HIGH BURDENED INDEX AND TAKEN BY 371 00:17:40,080 --> 00:17:46,840 OLDER ADULTS IN AUSTRALIA AND 372 00:17:46,840 --> 00:17:47,920 WHERE IN THE WORLD AND HAVE 373 00:17:47,920 --> 00:17:49,360 SEDATIVE EFFECTS AND TREAT MICE 374 00:17:49,360 --> 00:17:51,680 WITH FIVE DRUGS AND TAKING YOU 375 00:17:51,680 --> 00:17:53,840 THROUGH SLIDES. THIS IS A 376 00:17:53,840 --> 00:17:55,240 FRAILTY INDEX SCORE. YOU CAN 377 00:17:55,240 --> 00:17:57,320 SEE CONTROL IS THE BLACK LINE AT 378 00:17:57,320 --> 00:17:59,520 BOTTOM AND YOU CAN SEE CONTROL 379 00:17:59,520 --> 00:18:01,320 FRAILTY SCORES ARE LOWER THAN 380 00:18:01,320 --> 00:18:04,320 SCORES WITH MICE TAKING THIS 381 00:18:04,320 --> 00:18:06,720 POLY PHARMACY DIET WITH ZERO 382 00:18:06,720 --> 00:18:10,480 DRUG BURDEN INDEX AND LEAST 383 00:18:10,480 --> 00:18:11,760 PROBLEMATIC DRUGS IF YOU WILL 384 00:18:11,760 --> 00:18:14,360 AND LOW AND HIGH DBI AND YOU SEE 385 00:18:14,360 --> 00:18:17,000 FRAILTY IS HIGHEST IN MICE 386 00:18:17,000 --> 00:18:18,400 TAKING DRUGS WITH HIGH DRUG 387 00:18:18,400 --> 00:18:20,360 BURDEN INDEX AND IS INTERESTING 388 00:18:20,360 --> 00:18:22,200 THEN THAT THEY DEPRESCRIBED FOR 389 00:18:22,200 --> 00:18:23,720 THREE MONTHS AT THE END AND YOU 390 00:18:23,720 --> 00:18:26,560 SEE THAT IS THE DASHED LINE AND 391 00:18:26,560 --> 00:18:28,640 FRAILTY ACTUALLY GOES DOWN WHEN 392 00:18:28,640 --> 00:18:32,280 YOU DEPRESCRIBE. 393 00:18:32,280 --> 00:18:36,720 THIS IS WORK DONE BY A GROUP IN 394 00:18:36,720 --> 00:18:38,120 N 395 00:18:38,120 --> 00:18:42,480 NEWCASTLE LED BY THOMAS ZALINKY. 396 00:18:42,480 --> 00:18:43,760 MISPRONOUNCING HIS NAME AND THEY 397 00:18:43,760 --> 00:18:45,240 DO SOMETHING INTERESTING LOOKING 398 00:18:45,240 --> 00:18:49,480 AT FRAILTY INDEX AND DO A BRIEF 399 00:18:49,480 --> 00:18:53,800 EXPOSURE OF YOUNGER ANIMALS TO 400 00:18:53,800 --> 00:18:55,440 AN X RADIATION AND LOOK AT 401 00:18:55,440 --> 00:18:57,640 FRAILTY SCORES AND RED LINE, 402 00:18:57,640 --> 00:19:00,120 FRAILTY YOU SEE INCREASES 403 00:19:00,120 --> 00:19:01,800 DRAMATICALLY AFTER EXPOSURE TO 404 00:19:01,800 --> 00:19:03,040 RADIATION AND THEY TREATED A 405 00:19:03,040 --> 00:19:05,120 GROUP OF MOOIS WITH MET FOR MIN 406 00:19:05,120 --> 00:19:09,040 WITH IDEA IT COULD BE ASEINO 407 00:19:09,040 --> 00:19:11,120 LYTIC RESTATIC INTERVENTION AND 408 00:19:11,120 --> 00:19:12,840 DID IT FOR A PERIOD OF SEVERAL 409 00:19:12,840 --> 00:19:17,600 MONTHS AND WITHDRAW THE MET FOR 410 00:19:17,600 --> 00:19:19,800 MEN TREATMENT AND WHEN TREATED 411 00:19:19,800 --> 00:19:22,800 WITH MET FOR MEN FRAILTY 412 00:19:22,800 --> 00:19:27,000 PARALLELED THAT CONTROL OF 413 00:19:27,000 --> 00:19:30,520 NONRADIATED MICE DIDN'T 414 00:19:30,520 --> 00:19:32,480 DEVELOPED ACCELERATED PHENOTYPE 415 00:19:32,480 --> 00:19:36,920 IN MICE THAT WERE EXPOSED TO 416 00:19:36,920 --> 00:19:39,720 RADIATION I'D LIKE TO TOUCH ON 417 00:19:39,720 --> 00:19:42,120 TRANSLATING MODELS TO USE IN 418 00:19:42,120 --> 00:19:43,720 HUMANS AND WORK STARTED WITH 419 00:19:43,720 --> 00:19:46,760 BRANDY PARKS A PHD STUDENT IN MY 420 00:19:46,760 --> 00:19:48,960 LAB. WHAT WE DID IDEA STARTING 421 00:19:48,960 --> 00:19:50,520 TO FIRST QUANTIFY FRAILTY IN 422 00:19:50,520 --> 00:19:52,800 MICE I DIDN'T THINK OF CLINICAL 423 00:19:52,800 --> 00:19:55,920 FRAILTY FIRST THIS IS OLDER 424 00:19:55,920 --> 00:19:57,640 PAPER FIRST APPROACH LOOKING AT 425 00:19:57,640 --> 00:20:00,160 WANTING TO GET MORE THAN 30 426 00:20:00,160 --> 00:20:01,840 PARAMETERS TO MEASURE LOOKING AT 427 00:20:01,840 --> 00:20:04,040 ACTIVITY LEVELS AND BODY 428 00:20:04,040 --> 00:20:07,320 COMPOSITION STORE AND MEASURE 429 00:20:07,320 --> 00:20:08,080 HEMODYNAMIC PARAMETERS WITH CALE 430 00:20:08,080 --> 00:20:10,880 CUFF AND INTERESTING PARAMETERS 431 00:20:10,880 --> 00:20:13,120 LIKE TAIL BLOOD VOLUME AND WE 432 00:20:13,120 --> 00:20:15,720 HAD A POINT OF CARE EYE STAT 433 00:20:15,720 --> 00:20:18,880 BLOOD ANALYZER TO DO ROUTINE 434 00:20:18,880 --> 00:20:20,480 BLOOD WORK AND DEVELOPED A 435 00:20:20,480 --> 00:20:23,800 FRAILTY INDEX FROM ALL MEASURES 436 00:20:23,800 --> 00:20:25,840 BY LOOKING AT THINGS WITHIN OR 437 00:20:25,840 --> 00:20:27,960 MANY STANDARD DEVIATIONS AWAY 438 00:20:27,960 --> 00:20:29,640 FROM THE AVERAGE PERFORMANCE BY 439 00:20:29,640 --> 00:20:31,600 YOUNG AND HEALTHY MICE. 440 00:20:31,600 --> 00:20:33,680 WE THOUGHT, WITH THIS WORK AND 441 00:20:33,680 --> 00:20:37,800 PEOPLE, COULD WE USE CLINICAL 442 00:20:37,800 --> 00:20:40,240 DATA AND DEVELOP A -- WHAT WE 443 00:20:40,240 --> 00:20:43,720 CALLED FI LAB FOR USE IN PEOPLE 444 00:20:43,720 --> 00:20:45,520 AND WORK DONE WITH KEN AND 445 00:20:45,520 --> 00:20:48,480 JOANNA AND OTHERS AND THIS IS 446 00:20:48,480 --> 00:20:50,640 THE FI LAB AND WE USE THE SAME 447 00:20:50,640 --> 00:20:53,600 SORT OF APPROACH AND DOG IN THIS 448 00:20:53,600 --> 00:20:57,760 CASE FOR EXAMPLE SERUM POTASSIUM 449 00:20:57,760 --> 00:21:00,280 AND VALUE IN INDIVIDUAL IS LOW 450 00:21:00,280 --> 00:21:02,480 AND HIGH CUTOFFS RANGE OF 0 AND 451 00:21:02,480 --> 00:21:04,760 HIGHER OR LOWER GET A 1 AND ADD 452 00:21:04,760 --> 00:21:07,200 UP AND DIVIDE BY TOTAL NUMBER OF 453 00:21:07,200 --> 00:21:09,160 VARIABLES TO GET A FRAILTY 454 00:21:09,160 --> 00:21:09,520 SCORE. 455 00:21:09,520 --> 00:21:11,440 THIS JUST SHOWS ONE PAPER WE 456 00:21:11,440 --> 00:21:13,120 HAVE DONE THAT WE HAVE DONE A 457 00:21:13,120 --> 00:21:17,360 FEW IN THE EUROPEAN MALE AGING 458 00:21:17,360 --> 00:21:21,680 STUDY DATA BASE LOOKING AT 3,000 459 00:21:21,680 --> 00:21:23,520 COMMUNITY DWELLING MEN WITH 7 460 00:21:23,520 --> 00:21:26,760 YEAR FOLLOW UP AND SEE FI SCORE 461 00:21:26,760 --> 00:21:29,320 ON LEFT PANEL D AND FI CLINICAL 462 00:21:29,320 --> 00:21:31,800 SCORE IN MIDDLE AND FI COMBINED 463 00:21:31,800 --> 00:21:33,840 SCORE. I THINK WHAT THIS SHOWS 464 00:21:33,840 --> 00:21:37,200 IS THIS FRAILTY INDEX BASED ON 465 00:21:37,200 --> 00:21:38,840 LABORATORY DATA YOU CAN SEE IT 466 00:21:38,840 --> 00:21:43,640 IS SEPARATED BY NET FI SCORE AND 467 00:21:43,640 --> 00:21:49,480 SEE THOSE WITH FRAILTY SCORES OF 468 00:21:49,480 --> 00:21:53,080 .4 ON FI LAB ARE MORE LIKELY TO 469 00:21:53,080 --> 00:21:55,000 LOW FRAILTY SKO R TO BE DEAD AT 470 00:21:55,000 --> 00:21:58,240 7 YEAR FOLLOW UP AND COLLECTED 471 00:21:58,240 --> 00:21:59,520 CLINICAL FRAILTY DATA WITH REAL 472 00:21:59,520 --> 00:22:01,360 GOOD SEPARATION AND GAIN OF 473 00:22:01,360 --> 00:22:03,040 DIFFERENT FRAILTY LEVELS AND 474 00:22:03,040 --> 00:22:04,760 CHANCE OF BEING OR DYING WITHIN 475 00:22:04,760 --> 00:22:06,640 7 YEARS AND BEST SEPARATION OF 476 00:22:06,640 --> 00:22:09,120 THE GROUPS TURN WHEN YOU 477 00:22:09,120 --> 00:22:11,360 ACTUALLY COMBINED FI LAB AND FI 478 00:22:11,360 --> 00:22:12,400 CLINICAL READINGS TOGETHER. 479 00:22:12,400 --> 00:22:14,600 THIS IS AN INTERESTING TOOL. 480 00:22:14,600 --> 00:22:16,880 MANY LABS ARE NOW USING IT TO 481 00:22:16,880 --> 00:22:19,000 ASSESS FRAILTY AND IS NICE 482 00:22:19,000 --> 00:22:21,080 BECAUSE YOU CAN RETROSPECT IT 483 00:22:21,080 --> 00:22:24,600 AND APPLY IT TO DATA YOU HAVE ON 484 00:22:24,600 --> 00:22:26,520 HAND ALREADY ABOUT YOUR PATIENTS 485 00:22:26,520 --> 00:22:29,920 OR IN SOME CASES IN ANIMALS AND 486 00:22:29,920 --> 00:22:33,680 WOULD LIKE TO CONCLUDE BY SAYING 487 00:22:33,680 --> 00:22:37,160 FRAILTY INDEX ALLOWS TO QUANTIFY 488 00:22:37,160 --> 00:22:39,720 INDEX IN HEALTH AND PEOPLE AND 489 00:22:39,720 --> 00:22:41,200 IN PRECLINICAL MODELS AND SHOULD 490 00:22:41,200 --> 00:22:43,720 ADD WE HAD A REALLY INTERESTING 491 00:22:43,720 --> 00:22:47,320 TALK YESTERDAY ABOUT FRAILTY IN 492 00:22:47,320 --> 00:22:49,880 PRIMATES AND FRAILTY IN DOGS AND 493 00:22:49,880 --> 00:22:51,400 SOME INSTRUMENTS ARE TRANSLATED 494 00:22:51,400 --> 00:22:53,080 OR BEING TRANSLATED FOR USE IN 495 00:22:53,080 --> 00:22:54,840 DIFFERENT ANIMAL MODELS AND 496 00:22:54,840 --> 00:22:57,480 WORKS IN RATS AS WELL, I SHOULD 497 00:22:57,480 --> 00:22:59,080 ADD AND FRAILTY SCORES RESPOND 498 00:22:59,080 --> 00:23:03,160 AND THEY DO SO IN A DYNAMIC WAY 499 00:23:03,160 --> 00:23:04,480 TO DELETERIOUS OR BENEFICIAL 500 00:23:04,480 --> 00:23:09,680 CHANGES IN CIRCUMSTANCES SUCH AS 501 00:23:09,680 --> 00:23:12,440 GEROPROTECTORS AND LIFESTYLE 502 00:23:12,440 --> 00:23:14,960 EXERCISE AND DELETERIOUS BEING 503 00:23:14,960 --> 00:23:16,440 ABBREVIATION AND POLYPHARMACY 504 00:23:16,440 --> 00:23:18,800 AND LIKELY OTHER INTERVENTIONS 505 00:23:18,800 --> 00:23:20,600 AS WELL AND WOULD LIKE TO POINT 506 00:23:20,600 --> 00:23:23,640 OUT FRAILTY INDEX CREATED FROM 507 00:23:23,640 --> 00:23:26,200 ENTIRELY LAB-BASED VALUES 508 00:23:26,200 --> 00:23:28,800 DEVELOPED IN MICE CAN PREDICT 509 00:23:28,800 --> 00:23:30,040 ADVERSE OUTCOMES IN PEOPLE AND 510 00:23:30,040 --> 00:23:31,760 FINALLY, I THINK THESE -- REAL 511 00:23:31,760 --> 00:23:34,200 POWER OF THIS TYPE OF INSTRUMENT 512 00:23:34,200 --> 00:23:37,320 IN A MOUSE MODEL IS IT CAN BE 513 00:23:37,320 --> 00:23:40,040 USED TO TEST GEROPROTECTIVE 514 00:23:40,040 --> 00:23:41,920 INTERVENTIONS TO HEALTHY AGING 515 00:23:41,920 --> 00:23:44,720 LIMITING LATE LIFE ILLNESSES 516 00:23:44,720 --> 00:23:46,560 COMPRESSED AT LATE LIFE 517 00:23:46,560 --> 00:23:48,280 MORBIDITY SO PEOPLE COULD QUOTE 518 00:23:48,280 --> 00:23:50,960 ON QUOTE DIE HEALTHIER AND 519 00:23:50,960 --> 00:23:51,600 MODELS PROVIDE OPPORTUNITY TO 520 00:23:51,600 --> 00:23:53,400 TEST COMBINATIONS OF 521 00:23:53,400 --> 00:23:55,040 INTERVENTIONS AND SEE WHETHER OR 522 00:23:55,040 --> 00:23:57,920 NOT WE CAN ACTUALLY REALLY 523 00:23:57,920 --> 00:23:59,200 OPTIMIZE PEOPLE'S HEALTH IN 524 00:23:59,200 --> 00:24:01,080 LATER LIFE. I WOULD JUST LIKE 525 00:24:01,080 --> 00:24:02,360 TO THANK THAT I MENTIONED MOST 526 00:24:02,360 --> 00:24:05,280 PEOPLE THAT WORKED ON THIS AND 527 00:24:05,280 --> 00:24:07,680 FUNDING AGENCIES AND CANADIAN 528 00:24:07,680 --> 00:24:09,040 INSTITUTES FOR HEALTH AND 529 00:24:09,040 --> 00:24:11,200 RESEARCH AND HEALTH AND STROKE 530 00:24:11,200 --> 00:24:12,480 FOUNDATION AND PEOPLE IN MY LA B 531 00:24:12,480 --> 00:24:14,760 THAT CONTRIBUTED TO THIS IN 532 00:24:14,760 --> 00:24:19,960 BOLD. THANK YOU VERY MUCH. 533 00:24:19,960 --> 00:24:23,720 >>[APPLAUSE]. 534 00:24:23,720 --> 00:24:34,000 >>[APPLAUSE]. 535 00:24:39,160 --> 00:24:49,640 >>>>GOOD MORNING. MY CHARGE 536 00:24:58,880 --> 00:25:00,920 IS DISCUSSING GERIATRIC 537 00:25:00,920 --> 00:25:03,040 ASSESSMENT. I WILL FOCUS MOST 538 00:25:03,040 --> 00:25:13,520 OF MY COMMENTS ON MOBILITY. 539 00:25:14,600 --> 00:25:16,600 ONE QUESTION: WHY IS THIS 540 00:25:16,600 --> 00:25:17,800 IMPORTANT TO DO? 541 00:25:17,800 --> 00:25:20,440 FIRST, IT IS CONSIDERED FINAL 542 00:25:20,440 --> 00:25:23,280 COMMON PATHWAY REFLECTING IMPACT 543 00:25:23,280 --> 00:25:25,960 OF DISEASE, COMORBIDITY AND 544 00:25:25,960 --> 00:25:30,120 AGING AND SECOND IT IS OFRNL THE 545 00:25:30,120 --> 00:25:32,360 PRIMARY OR IMPORTANT FOCUS OF 546 00:25:32,360 --> 00:25:35,000 THERAPY AND POTENTIALLY 547 00:25:35,000 --> 00:25:37,160 INCLUDING GEROTHERAPEUTICS AND 548 00:25:37,160 --> 00:25:39,160 THIRD IS IMPORTANT FROM A 549 00:25:39,160 --> 00:25:42,680 REGULATOR PERSPECTIVE. IT IS 550 00:25:42,680 --> 00:25:45,360 INCLUDED AMONG THREE FDA KEY 551 00:25:45,360 --> 00:25:49,040 OUTCOMES OF FEEL, FUNCTION, 552 00:25:49,040 --> 00:25:49,680 SURVIVE. 553 00:25:49,680 --> 00:25:51,520 LASTLY AND PERHAPS MORE OR MOST 554 00:25:51,520 --> 00:25:53,480 IMPORTANTLY IT IS WHAT OLDER 555 00:25:53,480 --> 00:25:55,160 PERSONS WANT IN LIFE, 556 00:25:55,160 --> 00:25:56,760 PARTICULARLY LATER IN LIFE TO 557 00:25:56,760 --> 00:26:01,880 MAINTAIN INDEPENDENCE AND THEIR 558 00:26:01,880 --> 00:26:02,160 FUNCTION. 559 00:26:02,160 --> 00:26:09,040 THIS IS A SLIDE, I BELIEVE, I 560 00:26:09,040 --> 00:26:12,200 BORROWED FROM LOU EEJI YEARS AGO 561 00:26:12,200 --> 00:26:14,400 THAT HAS A LIFESPAN PERSPECTIVE 562 00:26:14,400 --> 00:26:16,560 TO MOBILITY EARLY IN LIFE 563 00:26:16,560 --> 00:26:18,520 SHORTLY AFTER BIRTH TO LATER IN 564 00:26:18,520 --> 00:26:22,920 LIFE AND ADVANCED OLD AGE AND 565 00:26:22,920 --> 00:26:25,080 MOBILITY LIKE HIGHER LEVEL 566 00:26:25,080 --> 00:26:26,800 FUNCTIONS TYPICALLY PEAK IN THE 567 00:26:26,800 --> 00:26:29,760 LATE 20S AND EARLY 30S AND 568 00:26:29,760 --> 00:26:35,960 DECLINE AGGRESSIVELY THEREAFTER. 569 00:26:35,960 --> 00:26:37,440 MOBILITY IS CONSIDERED ONE OF 570 00:26:37,440 --> 00:26:41,520 THE STRONGEST SINGLE PREDICTORS 571 00:26:41,520 --> 00:26:43,240 OF MOST RELEVANT MORE DISTAL 572 00:26:43,240 --> 00:26:47,320 OUTCOMES SUCH AS SURVIVAL AND 573 00:26:47,320 --> 00:26:51,520 LONG-TERM DISABILITY THAT IS 574 00:26:51,520 --> 00:26:54,480 OFTEN CONSIDERED ESSENTIAL TO 575 00:26:54,480 --> 00:26:57,800 MAINTAINING HIGH QUALITY OF LIFE 576 00:26:57,800 --> 00:27:00,640 IN ADVANCING AGE. 577 00:27:00,640 --> 00:27:03,760 THIS IS A SLIDE BASED ON DATA 578 00:27:03,760 --> 00:27:11,160 FROM IN KIANTI AND LUIGI LEADING 579 00:27:11,160 --> 00:27:13,800 THE CHARGE. POINTS TO MAKE LEFT 580 00:27:13,800 --> 00:27:16,120 SIDE OF THE SLIDE IS MALES AND 581 00:27:16,120 --> 00:27:18,360 RIGHT SIDE IS FEMALES AND SHOWS 582 00:27:18,360 --> 00:27:21,760 THREE TYPES OF MOBILITY TESTS 583 00:27:21,760 --> 00:27:24,560 WITH USUAL DATE SPEED AT TOP AND 584 00:27:24,560 --> 00:27:26,320 MIDDLE RAPID GAD SPEED AND 585 00:27:26,320 --> 00:27:32,320 BOTTOM IS 400 METER WALK. 586 00:27:32,320 --> 00:27:35,320 YOU WILL SEE WHEN PERSONS ARE 587 00:27:35,320 --> 00:27:36,760 NOT CHALLENGED WITH USUAL GAD 588 00:27:36,760 --> 00:27:38,520 SPEED AND LEAST STRENUOUS OF 589 00:27:38,520 --> 00:27:42,120 THAT, THAT PERSONS TYPICALLY 590 00:27:42,120 --> 00:27:46,600 DON'T FALL BELOW THERE ARE NOT 591 00:27:46,600 --> 00:27:48,280 REDUCTIONS OBSERVED FOR FOLKS 592 00:27:48,280 --> 00:27:51,640 BETWEEN 50 OR 60 OR 70 AND SLAT 593 00:27:51,640 --> 00:27:54,880 OR HORIZONTAL LINE, ANYTHING 594 00:27:54,880 --> 00:27:58,800 BELOW THAT REPRESENTS DECLINE. 595 00:27:58,800 --> 00:28:01,360 MIDDLE PANEL YOU WILL SEE 596 00:28:01,360 --> 00:28:04,200 STRENUOUS TEST AND THIS CASE 597 00:28:04,200 --> 00:28:07,280 RAPID GATE AND AGE RELATED 598 00:28:07,280 --> 00:28:08,760 CHANGES OCCUR EARLIER IN PERHAPS 599 00:28:08,760 --> 00:28:11,560 THE 30S AND 40S AND STRENUOUS 600 00:28:11,560 --> 00:28:14,520 TEST IN THIS CASE 400 METER WALK 601 00:28:14,520 --> 00:28:17,000 THERE IS DECLINES OBSERVED IN 602 00:28:17,000 --> 00:28:19,920 EARLY 20S RELATIVE TO EARLIER IN 603 00:28:19,920 --> 00:28:21,080 LIFE. THIS IS SOMETHING TO 604 00:28:21,080 --> 00:28:22,720 CONSIDER WHEN YOU ARE DEPENDING 605 00:28:22,720 --> 00:28:26,640 ON THE POPULATION THAT YOU ARE 606 00:28:26,640 --> 00:28:30,040 TARGET 607 00:28:30,040 --> 00:28:30,320 TARGETING. 608 00:28:30,320 --> 00:28:31,480 YOU MAY SELECT DIFFERENT 609 00:28:31,480 --> 00:28:34,200 MOBILITY TESTS AND FIRST 610 00:28:34,200 --> 00:28:35,360 IDENTIFYING POPULATIONS THAT ARE 611 00:28:35,360 --> 00:28:39,120 VULNERABLE AND SERVING RELEVANT 612 00:28:39,120 --> 00:28:43,280 OUTCOME MEASURES. 613 00:28:43,280 --> 00:28:46,560 NEXT SEVERAL SLICES ASSESSMENT 614 00:28:46,560 --> 00:28:47,720 OF SELF-REPORTED FUNCTION OR 615 00:28:47,720 --> 00:28:49,800 PATIENT REPORTED OUTCOMES IT IS 616 00:28:49,800 --> 00:28:53,040 REFERRED TO ALSO. AND THERE ARE 617 00:28:53,040 --> 00:28:55,440 DOZENS OF DIFFERENT 618 00:28:55,440 --> 00:28:56,080 SELF-REPORTED INSTRUMENTS OF 619 00:28:56,080 --> 00:28:57,560 PHYSICAL FUNCTION. THIS IS ONE 620 00:28:57,560 --> 00:28:59,760 OF THE MOST COMMONLY USED TESTS 621 00:28:59,760 --> 00:29:02,880 PARTICULARLY IN HIGHER 622 00:29:02,880 --> 00:29:06,880 FUNCTIONING PERSONS INCLUDING 623 00:29:06,880 --> 00:29:10,360 OLDER ADULTS PF10 COMPONENT OF 624 00:29:10,360 --> 00:29:12,440 MLS36 DEVELOPED MANY YEARS AGO 625 00:29:12,440 --> 00:29:14,520 AND 10 ITEMS LISTED HERE AND 626 00:29:14,520 --> 00:29:16,320 MAJORITY OF THEM ARE MOBILITY 627 00:29:16,320 --> 00:29:19,720 RELATED SUCH AS CLIMBING STAIRS 628 00:29:19,720 --> 00:29:24,320 AND WALKING DIFFERENT DISTANCES 629 00:29:24,320 --> 00:29:25,880 THERE IS DIFFERENT CATEGORIES OF 630 00:29:25,880 --> 00:29:27,720 LIMITATIONS FROM LIMITED A LOT 631 00:29:27,720 --> 00:29:30,440 TO NOT AT ALL AND SCALED ON 0 TO 632 00:29:30,440 --> 00:29:33,640 100 BASIS WITH 100 BEING A 633 00:29:33,640 --> 00:29:37,160 PERFECT SCORE AND 0 BEING WORST 634 00:29:37,160 --> 00:29:43,720 POSSIBLE SCORE AND PF10 HAS 635 00:29:43,720 --> 00:29:45,680 SIGNIFICANT LIMITATIONS IN THOSE 636 00:29:45,680 --> 00:29:47,640 LOWER FUNCTIONING FLORO FECHL 637 00:29:47,640 --> 00:29:49,680 AND CAN'T DETECT CHANGES IN 638 00:29:49,680 --> 00:29:52,160 PERSONS WITH LOWER LEVELS OF 639 00:29:52,160 --> 00:29:52,800 FUNCTIONING. THERE HAVE BEEN 640 00:29:52,800 --> 00:29:56,280 DIFFERENT STRATEGIES TO ADDRESS 641 00:29:56,280 --> 00:30:02,240 THAT AND WHAT ARE CONSIDERED 642 00:30:02,240 --> 00:30:03,760 TEMPORARY TECHNOLOGY AND THESE 643 00:30:03,760 --> 00:30:07,720 ARE DESIGNED TO ADDRESS 644 00:30:07,720 --> 00:30:08,920 COMPETING CONSIDERATIONS 645 00:30:08,920 --> 00:30:11,720 ASSESSING FUNCTION IN TERMS OF 646 00:30:11,720 --> 00:30:13,200 CONCEPTUAL BREADTH AND WHAT 647 00:30:13,200 --> 00:30:15,000 ELEMENTS YOU THINK SHOULD BE 648 00:30:15,000 --> 00:30:17,520 INCLUDED IN THAT ASSESSMENT 649 00:30:17,520 --> 00:30:18,920 VERSUS DEPTH OF THE MEASUREMENT 650 00:30:18,920 --> 00:30:22,960 AND YOU HAVE TO DEAL WITH ISSUES 651 00:30:22,960 --> 00:30:26,120 RELATED TO FEASIBILITY AND 652 00:30:26,120 --> 00:30:27,760 PRECISION AND TRADE OFFS THERE 653 00:30:27,760 --> 00:30:31,240 WITH CONVENTIONAL SELF-REPORTED 654 00:30:31,240 --> 00:30:32,320 MEASURES AND MESHED ALREADY 655 00:30:32,320 --> 00:30:34,800 FLOOR EFFECTS AND COULD ALSO BE 656 00:30:34,800 --> 00:30:36,840 CEILING EFFECTS DEPENDING ON THE 657 00:30:36,840 --> 00:30:40,040 INSTRUMENT AND POPULATION 658 00:30:40,040 --> 00:30:42,800 STUD 659 00:30:42,800 --> 00:30:43,080 STUDIED. 660 00:30:43,080 --> 00:30:46,320 ITEM RESPONSE THEORY ALLOWS YOU 661 00:30:46,320 --> 00:30:48,520 TO CREATE HIERARCHICAL BANK OF 662 00:30:48,520 --> 00:30:50,520 ITEMS YOU CAN DRAW UPON THAT 663 00:30:50,520 --> 00:30:52,680 COULD BE IMPLEMENTED USING 664 00:30:52,680 --> 00:30:54,840 COMPUTER ADAPTIVE TEST TG THAT 665 00:30:54,840 --> 00:30:57,480 IS ALGORITHM THAT HAS ITEMS 666 00:30:57,480 --> 00:30:58,960 DIRECTLY THAT ARE TAILORED TO 667 00:30:58,960 --> 00:31:01,720 THE PERSON TO BE SHORTENED OR 668 00:31:01,720 --> 00:31:03,440 LENGTHENED DEPENDING ON 669 00:31:03,440 --> 00:31:04,400 PRECISION OF THE INSTRUMENTS 670 00:31:04,400 --> 00:31:11,760 THAT YOU ARE HOPING TO GENERATE 671 00:31:11,760 --> 00:31:14,600 OR PREDEFINED SHOPPING ROLES AND 672 00:31:14,600 --> 00:31:18,360 NEXT SLIDE ILLUSTRATES HOW 673 00:31:18,360 --> 00:31:20,280 PROCESS WORKS AND THERE IS ITEM 674 00:31:20,280 --> 00:31:22,800 POOL NO. 1. ITEM IS SELECTED 675 00:31:22,800 --> 00:31:24,120 FROM THAT POOL AND PATIENT 676 00:31:24,120 --> 00:31:26,720 RESPONDS AND BASED ON RESPONSE, 677 00:31:26,720 --> 00:31:30,240 INITIAL SCORE IS CALCULATED. 678 00:31:30,240 --> 00:31:34,160 YOU HAVE PRE-SPECIFIED RULES AND 679 00:31:34,160 --> 00:31:35,640 TERMS OF PRECISION OF ESTIMATES 680 00:31:35,640 --> 00:31:39,400 AROUND THE SCORE YOU ARE LOOKING 681 00:31:39,400 --> 00:31:42,480 FOR. 682 00:31:42,480 --> 00:31:44,920 ESTIMATES NOT PRECISIONLY 683 00:31:44,920 --> 00:31:47,480 PRECISE AND ANOTHER ITEM AND 684 00:31:47,480 --> 00:31:49,560 CORE WILL BE RECALCULATED AND 685 00:31:49,560 --> 00:31:51,400 CONTINUE GOING AROUND UNTIL YOU 686 00:31:51,400 --> 00:31:53,720 REACH A PRE-SPECIFIED PRECISION 687 00:31:53,720 --> 00:31:55,600 ESTIMATE OR IF YOU HAVE SET YOUR 688 00:31:55,600 --> 00:31:58,160 MAX AT 6 OR 7 OR 8 QUESTIONS AND 689 00:31:58,160 --> 00:32:00,320 THEN YOU WILL END UP AT A 690 00:32:00,320 --> 00:32:02,120 FUNCTIONAL OUTCOME, TYPICALLY A 691 00:32:02,120 --> 00:32:05,720 SCORE ON A SCALE THAT COULD BE 0 692 00:32:05,720 --> 00:32:08,680 TO 100. 693 00:32:08,680 --> 00:32:12,200 THIS IS THE BASIS OF PROMISE 694 00:32:12,200 --> 00:32:17,240 ITEM BANK OF 162 AND 695 00:32:17,240 --> 00:32:17,960 HIERARCHICALLY ORDERED 696 00:32:17,960 --> 00:32:21,080 FUNCTIONAL ITEMS. YOU CAN SEE A 697 00:32:21,080 --> 00:32:23,480 SELECTION OF FIVE DIFFERENT 698 00:32:23,480 --> 00:32:28,240 ITEMS SCALED WOULT DIFFICULTY TO 699 00:32:28,240 --> 00:32:29,600 UNABLE TO DO. 700 00:32:29,600 --> 00:32:32,800 AND ITEMS FROM THIS ITEM BANK 701 00:32:32,800 --> 00:32:36,600 ARE BEING USED FOR DIFFERENT 702 00:32:36,600 --> 00:32:38,040 APPLICATIONS AND IN THIS CASE 703 00:32:38,040 --> 00:32:44,000 FOR SARCOPENIA AND PHARMACOLOGIC 704 00:32:44,000 --> 00:32:45,800 AND PHARMACEUTICAL COMPANIES ARE 705 00:32:45,800 --> 00:32:47,840 INTERESTED IN DEMONSTRATING 706 00:32:47,840 --> 00:32:52,360 BENEFITS OF AGENTS ON SARCOPENIA 707 00:32:52,360 --> 00:32:56,280 AND FDA REQUIRES IMPROVEMENT IN 708 00:32:56,280 --> 00:32:57,680 PATIENT-REPORTED OUTCOMES AND 709 00:32:57,680 --> 00:33:00,280 FDA IS SUPPORTING A GRANT THAT 710 00:33:00,280 --> 00:33:01,600 IS [INDISCERNIBLE] AT 711 00:33:01,600 --> 00:33:04,840 NORTHWESTERN WHO IS A LEADING 712 00:33:04,840 --> 00:33:07,440 FIGURE IN PROMISE TO IDENTIFY 713 00:33:07,440 --> 00:33:09,800 AND TEST AND EVALUATE A SHORT 714 00:33:09,800 --> 00:33:14,160 FORM FROM PROMISE 162 ITEM 715 00:33:14,160 --> 00:33:17,080 PHYSICAL FUNCTION BANK FOR USE 716 00:33:17,080 --> 00:33:19,120 IN SASHGOPENIA TRIALS AND FIRST 717 00:33:19,120 --> 00:33:20,880 BASE IS COMPLETED AND REDUCED TO 718 00:33:20,880 --> 00:33:23,480 30 ITEMS AND SECOND PHASE IS 719 00:33:23,480 --> 00:33:26,680 ONGOING AND GOAL IS TO GET DOWN 720 00:33:26,680 --> 00:33:29,080 TO LESS THAN 10 ITEMS FROM THAT 721 00:33:29,080 --> 00:33:30,880 ORIGINAL BANK. THIS IS ANOTHER 722 00:33:30,880 --> 00:33:33,040 WAY THAT SUCH ITEM BANKS COULD 723 00:33:33,040 --> 00:33:34,560 BE USED YOU CAN PULL UPON THEM 724 00:33:34,560 --> 00:33:37,480 AND HEAVY LIFTING IS ALREADY 725 00:33:37,480 --> 00:33:39,120 DONE AND YOU WOULD PULL ITEMS 726 00:33:39,120 --> 00:33:41,520 FROM THE BANK DEPENDING ON YOUR 727 00:33:41,520 --> 00:33:43,480 STUDY POPULATION AND APPLICATION 728 00:33:43,480 --> 00:33:48,560 IN THIS CASE SARCOPENIA. 729 00:33:48,560 --> 00:33:51,320 I WILL TRANSITION TO PHYSICAL 730 00:33:51,320 --> 00:33:53,920 PERFORMANCE MEASURES INVOLVING 731 00:33:53,920 --> 00:33:54,560 ASSESSMENT IN WHICH AN 732 00:33:54,560 --> 00:33:57,160 INDIVIDUAL IS ASKED TO PERFORM A 733 00:33:57,160 --> 00:33:59,400 SPECIFIC TASK AND IS EVALUATED 734 00:33:59,400 --> 00:34:01,360 IN OBJECTIVE AND STANDARDIZED 735 00:34:01,360 --> 00:34:03,680 MANNER USING PREDETERMINED 736 00:34:03,680 --> 00:34:05,360 CRITERIA INCLUDING COUNTING 737 00:34:05,360 --> 00:34:08,960 REPETITIONS OR TIMING OF 738 00:34:08,960 --> 00:34:19,360 ACTIVITY AS APPROPRIATE 739 00:34:20,120 --> 00:34:23,200 RELATIVELY SHORT REPORTED 740 00:34:23,200 --> 00:34:26,880 MEASURES NEITHER ARE BETTER 741 00:34:26,880 --> 00:34:30,520 NECESSARILY THAN OTHER AND ARE 742 00:34:30,520 --> 00:34:31,720 CONSIDERED COMPLEMENTARY 743 00:34:31,720 --> 00:34:39,120 PERFORMANCE BASED MEASURES 744 00:34:39,120 --> 00:34:41,800 ADVANTAGEOUS VALIDITY FOR TASKS 745 00:34:41,800 --> 00:34:43,120 PERFORMED AND STAFF PROPERLY 746 00:34:43,120 --> 00:34:47,440 TRAINED ARE TENDING TO BE HIGHLY 747 00:34:47,440 --> 00:34:48,480 REPRODUCIBLE AND OFTEN 748 00:34:48,480 --> 00:34:51,760 RESPONDING TO CHANGES THAT ARE 749 00:34:51,760 --> 00:34:54,160 CLINICALLY MEANINGFUL AND BE 750 00:34:54,160 --> 00:34:55,120 ADMINISTERED TO PERSONS 751 00:34:55,120 --> 00:34:57,200 COGNITIVE DEFICITS UNLESS THEY 752 00:34:57,200 --> 00:35:00,400 HAVE MOST ADVANCED DEMENTIA AND 753 00:35:00,400 --> 00:35:03,800 COGNITIVE IMPAIRMENT OFTEN 754 00:35:03,800 --> 00:35:05,640 IMPEDIMENT TO COMPLETION OF 755 00:35:05,640 --> 00:35:08,800 SELF-REPORTED INSTRUMENTS AND 756 00:35:08,800 --> 00:35:11,480 THENL CULTURE AND LANGUAGE IS 757 00:35:11,480 --> 00:35:13,680 LESS PROBLEMATIC WITH 758 00:35:13,680 --> 00:35:15,560 PERFORMANCE BASED SELF-REPORTED 759 00:35:15,560 --> 00:35:18,520 MEASURES AND NONETHELESS, 760 00:35:18,520 --> 00:35:19,280 DISADVANTAGES TO CONSIDER AND 761 00:35:19,280 --> 00:35:23,760 TAKE MORE TIME TO COMPLETE AND 762 00:35:23,760 --> 00:35:32,800 EXAMINERS HAVE TO BE TRAINED 763 00:35:32,800 --> 00:35:38,360 HAVING STANDARDIZE THE VALID 764 00:35:38,360 --> 00:35:39,680 MEASUREMENT AND THIS IN OUR 765 00:35:39,680 --> 00:35:42,440 EXPERIENCE HAS BEEN AN UNCOMMON 766 00:35:42,440 --> 00:35:46,080 PROBLEM AND SIMPLE TEST MAY NOT 767 00:35:46,080 --> 00:35:47,480 REFLECT PERFORMANCE OF COMPLEX 768 00:35:47,480 --> 00:35:50,720 TASKS AND DON'T CONSIDER 769 00:35:50,720 --> 00:35:55,240 ENVIRONMENT AT ALL AND FUNCTION 770 00:35:55,240 --> 00:35:56,920 INHERENTLY IS INTERPRETED IN 771 00:35:56,920 --> 00:35:59,080 CONTEXT OF ONE'S ENVIRONMENT AND 772 00:35:59,080 --> 00:36:07,760 ONE OF MOST COMMONLY USED TESTS 773 00:36:07,760 --> 00:36:18,480 IS PERFORMANCE BATTERY HAVING 774 00:36:18,480 --> 00:36:19,640 THREE COMPONENTS BALANCE 775 00:36:19,640 --> 00:36:21,560 MANEUVER SIDE BY SIDE AND TANDEM 776 00:36:21,560 --> 00:36:26,120 AND TWO TIMED TESTS FOUR METER 777 00:36:26,120 --> 00:36:28,920 WALK AND SECOND IS A 5 TIME 778 00:36:28,920 --> 00:36:29,240 STANCE. 779 00:36:29,240 --> 00:36:31,160 THERE IS HUNDREDS OF ARTICLES 780 00:36:31,160 --> 00:36:34,080 THAT HAVE BEEN PUBLISHED ABOUT 781 00:36:34,080 --> 00:36:38,240 SBBB. IT IS A REALLY ROBUST 782 00:36:38,240 --> 00:36:41,600 PREDICTOR OF MORTALITY AND OTHER 783 00:36:41,600 --> 00:36:43,120 OUTCOMES AND LONG-TERM 784 00:36:43,120 --> 00:36:44,320 DISABILITY AND NURSING HOME 785 00:36:44,320 --> 00:36:46,240 ADMISSIONS AND EACH OF THE THREE 786 00:36:46,240 --> 00:36:48,320 COMPONENTS IS A GRADED 787 00:36:48,320 --> 00:36:51,200 RELATIONSHIP BETWEEN PERFORMANCE 788 00:36:51,200 --> 00:36:55,720 AND IN THIS CASE MORTALITY AND 789 00:36:55,720 --> 00:37:00,720 WITH WALK WITH MORTALITY BEING 790 00:37:00,720 --> 00:37:02,880 1.9 WITH ROBUST GROUP WITH SCORE 791 00:37:02,880 --> 00:37:05,240 OF 4 AND ALMOST 12 WITH FOLKS 792 00:37:05,240 --> 00:37:08,200 THAT COULDN'T COMPLETE THE 793 00:37:08,200 --> 00:37:13,200 WALKING TEST AND OTHER TWO 794 00:37:13,200 --> 00:37:15,760 COMPONENTS OF SBB ARE NOT AS 795 00:37:15,760 --> 00:37:17,480 GREAT AND GRADED R- 796 00:37:17,480 --> 00:37:18,640 HELATIONSHIPS WITH BEST SCORE OF 797 00:37:18,640 --> 00:37:22,600 4 HAVING LOWEST MORTALITY AND 798 00:37:22,600 --> 00:37:24,520 WORST SCORE OF 0 WITH HIGHEST 799 00:37:24,520 --> 00:37:26,360 MORTALITY AND WHAT YOU SEE WHEN 800 00:37:26,360 --> 00:37:30,160 YOU TALLY THEM UP AND USUAL 12 801 00:37:30,160 --> 00:37:32,320 POINT SCALE WITH 12 BEING A 802 00:37:32,320 --> 00:37:34,640 PERFECT SCORE AND MORTALITY IN 803 00:37:34,640 --> 00:37:36,400 YELLOW AND SEEING MORTALITY AT 804 00:37:36,400 --> 00:37:38,560 SCORE OF 12 IS VERY LOW AND THIS 805 00:37:38,560 --> 00:37:40,760 IS OVER A FOUR YEAR PERIOD THAT 806 00:37:40,760 --> 00:37:43,720 YOU CAN SEE IT PROGRESSIVELY 807 00:37:43,720 --> 00:37:45,480 INCREASES TO IN THIS CASE WORST 808 00:37:45,480 --> 00:37:47,960 SCORE OF 4 IN WHICH MORTALITY IS 809 00:37:47,960 --> 00:37:52,440 NEARLY 50% AND ABOVE THAT IS 810 00:37:52,440 --> 00:37:53,200 ONSET OF MOBILITY DISABILITY AND 811 00:37:53,200 --> 00:37:59,760 IN WHITE IS ONSET OF DISABILITY 812 00:37:59,760 --> 00:38:00,880 AND ACTUALLY NO DISABILITY THAT 813 00:38:00,880 --> 00:38:03,280 IS PROTECTED AND VERY UNLIKELY 814 00:38:03,280 --> 00:38:05,920 TO BECOME DISABLED OVER COURSE 815 00:38:05,920 --> 00:38:11,960 OF FOURIES WITH 12 ON SBBB. 816 00:38:11,960 --> 00:38:15,160 AND JAX SPENT MANY YEARS 817 00:38:15,160 --> 00:38:16,920 REFINING AND PERFECTING 818 00:38:16,920 --> 00:38:20,320 MEASUREMENT TO POINT THAT IS NOT 819 00:38:20,320 --> 00:38:22,600 A SMART PHONE APP THAT PROVIDES 820 00:38:22,600 --> 00:38:25,160 INSTRUCTIONS TO ASSESSORS AND 821 00:38:25,160 --> 00:38:28,320 SKIP PATTERNS ARE BUILT IN AND 822 00:38:28,320 --> 00:38:29,960 BUTTON ON THE PHONE FOR STOPPING 823 00:38:29,960 --> 00:38:31,720 AND STARTING AND STOPPING THE 824 00:38:31,720 --> 00:38:34,880 TEST AND DATA ENTERED IN 825 00:38:34,880 --> 00:38:36,920 AUTOMATICALLY AND THERE IS A 826 00:38:36,920 --> 00:38:38,320 WIRELESS UPLOAD THAT REALLY 827 00:38:38,320 --> 00:38:39,920 SIMPLIFIES WHAT USED TO BE DONE 828 00:38:39,920 --> 00:38:44,160 IN PEN AND PAPER WITH A STOP 829 00:38:44,160 --> 00:38:46,280 WATCH. 830 00:38:46,280 --> 00:38:48,640 HE ALSO HAS DONE WORK LOOKING AT 831 00:38:48,640 --> 00:38:51,000 EACH OF THE THREE COMPONENTS IN 832 00:38:51,000 --> 00:38:53,400 TERMS OF PREDICTIVE VALUE 833 00:38:53,400 --> 00:38:56,360 RELATIVE TO ENTIRE SBBB. IT IS 834 00:38:56,360 --> 00:38:59,480 VERY CLEAR THAT MOST PREDICTIVE 835 00:38:59,480 --> 00:39:02,880 VALUE OF SBBB IS FROM THE GATE 836 00:39:02,880 --> 00:39:05,000 SPEED COMPONENT AND ARE ROC 837 00:39:05,000 --> 00:39:08,960 CURVES THAT ON THE LEFT IS ADL 838 00:39:08,960 --> 00:39:10,440 DISABILITY AT ONE YEAR. 839 00:39:10,440 --> 00:39:13,120 ON RIGHT IS ANOTHER FOUR-YEAR 840 00:39:13,120 --> 00:39:14,680 PERIOD AND BOTTOM IS MOBILITY 841 00:39:14,680 --> 00:39:16,560 DISABILITY AND AGAIN OVER A 1 IN 842 00:39:16,560 --> 00:39:19,400 FOUR YEAR PERIOD. YOU CAN SEE 843 00:39:19,400 --> 00:39:22,000 CURVES, TOP CURVE BEING ENTIRE 844 00:39:22,000 --> 00:39:27,280 SBBB AND ONE BELOW ON SOLID LINE 845 00:39:27,280 --> 00:39:30,840 BEING GATE SPEED ALONE THAT 846 00:39:30,840 --> 00:39:33,840 NEARLY IS AS STRONG AS ENTIRE 847 00:39:33,840 --> 00:39:38,360 SBBB AND IS SHOWN IN SEVERAL 848 00:39:38,360 --> 00:39:41,560 STUDIES AND BASED ON THOSE 849 00:39:41,560 --> 00:39:43,720 RESULTS STEPHANIE SADIN SKI 850 00:39:43,720 --> 00:39:45,880 LOOKED CAREFULLY THROUGHOUT 851 00:39:45,880 --> 00:39:49,360 LITERATURE IN DIFFERENT COHORTS 852 00:39:49,360 --> 00:39:54,560 FOCUSING ON GAIT SPEED ALONE 853 00:39:54,560 --> 00:39:56,880 WITH DATA AND TALLYING STUDIES 854 00:39:56,880 --> 00:40:00,040 DEMONSTRATING REDUCTIONS IN 855 00:40:00,040 --> 00:40:02,680 MORTALITY PER .1 METER PER 856 00:40:02,680 --> 00:40:04,960 SECOND INCREASED IN GATE SPEED 857 00:40:04,960 --> 00:40:07,760 AND FINAL ESTIMATE IS AT BOTTOM 858 00:40:07,760 --> 00:40:11,720 THAT IS ABOUT A 10% RELATIVE 859 00:40:11,720 --> 00:40:15,600 REDUCTION IN MORTALITY FOR EACH 860 00:40:15,600 --> 00:40:22,480 .1 INCREASE IN GAIT SPEED. 861 00:40:22,480 --> 00:40:25,200 SHE HAS DONE WORK WITH A 4 METER 862 00:40:25,200 --> 00:40:29,120 WALK AND WITH THESE CATEGORIES 863 00:40:29,120 --> 00:40:32,560 AND WITH THE FOLKS WITH GAIT 864 00:40:32,560 --> 00:40:35,880 SPEEDS ABOVE 1 THAT IS OFTEN 865 00:40:35,880 --> 00:40:37,400 CONSIDERED THRESHOLD THAT FOLKS 866 00:40:37,400 --> 00:40:40,040 ARE GENERALLY AT LOWER RISK WITH 867 00:40:40,040 --> 00:40:42,440 OUTCOMES AND IN THIS CASE 868 00:40:42,440 --> 00:40:43,360 DECLINING GLOBAL FUNCTION AND ON 869 00:40:43,360 --> 00:40:45,600 LEFT IS A NEW DIFFICULTY AND 870 00:40:45,600 --> 00:40:47,320 PERSONAL CARE ON THE RIGHT. YOU 871 00:40:47,320 --> 00:40:49,640 SEE THOSE RATES ARE RELATIVELY 872 00:40:49,640 --> 00:40:53,880 LOW OVER THE YEAR AT 6% AND 873 00:40:53,880 --> 00:40:57,760 11.9% AND 8 SPEEDS BELOW .6 ARE 874 00:40:57,760 --> 00:40:59,480 IDENTIFYING A HIGH-RISK GROUP 875 00:40:59,480 --> 00:41:02,080 WITH OUTCOME RATES THAT ARE 876 00:41:02,080 --> 00:41:04,840 NEARLY 36% FOR DECLINING GLOBAL 877 00:41:04,840 --> 00:41:08,240 HEALTH AND 69% FOR NEW 878 00:41:08,240 --> 00:41:09,760 DIFFICULTY AND PERSONAL CARE 879 00:41:09,760 --> 00:41:14,720 WITH INTERMEDIATE GROUP OF .6 TO 880 00:41:14,720 --> 00:41:17,040 1. 881 00:41:17,040 --> 00:41:19,080 THOSE ARE SHORT DISTANCE WALK 882 00:41:19,080 --> 00:41:22,480 RESULTS AND IS PROBABLY FAMILIAR 883 00:41:22,480 --> 00:41:25,280 ALSO WITH LONGER DISTANCE WALK 884 00:41:25,280 --> 00:41:26,840 RESULTS AND TWO BEING 6 MINUTE 885 00:41:26,840 --> 00:41:29,760 WALK USED FOR MANY YEARS 886 00:41:29,760 --> 00:41:32,360 INITIALLY IN PULMONARY 887 00:41:32,360 --> 00:41:35,400 LITERATURE AND MORE IN THE LAST 888 00:41:35,400 --> 00:41:38,000 DECADE OR SO IN GERIATRIC 889 00:41:38,000 --> 00:41:43,720 LITERATURE AND KUDZIN IS 400 890 00:41:43,720 --> 00:41:45,720 METER WALK AND 6 MINUTE WALK AND 891 00:41:45,720 --> 00:41:47,640 MEASURE DISTANCE WALKED IN 6 892 00:41:47,640 --> 00:41:50,440 MINUTES AND 400 METER WALK IS 893 00:41:50,440 --> 00:41:52,280 ABOUT A QUARTER MILE THAT IS 894 00:41:52,280 --> 00:41:54,880 DEVELOPED FOR THE LIFE TRIAL AS 895 00:41:54,880 --> 00:41:56,040 A DICHOTOMOUS OUTCOME AND 896 00:41:56,040 --> 00:41:58,640 ABILITY TO WALK 400 METERS 897 00:41:58,640 --> 00:41:59,800 WITHIN 15 MINUTES. 898 00:41:59,800 --> 00:42:05,040 AND YOU CAN SEE ON THIS VIDEO 899 00:42:05,040 --> 00:42:06,920 THERE IS [INDISCERNIBLE] AT 900 00:42:06,920 --> 00:42:08,160 PARTICIPATANT'S SIDE THAT IS 901 00:42:08,160 --> 00:42:09,600 DEMONSTRATING, YOU KNOW, HOW TO 902 00:42:09,600 --> 00:42:14,200 WALK A LAP. IT IS USUALLY A 20 903 00:42:14,200 --> 00:42:16,880 METER COURSE WITH CONES AT ONE 904 00:42:16,880 --> 00:42:20,040 END OR ANOTHER AND 6 MINUTE WALK 905 00:42:20,040 --> 00:42:22,200 MEASURING DISTANCE AND WALKING 6 906 00:42:22,200 --> 00:42:24,120 METERS AND YOU BEGIN TIMING WHEN 907 00:42:24,120 --> 00:42:28,080 THEY START THEIR FIRST STEP. 908 00:42:28,080 --> 00:42:31,800 FOR SAFETY REASONS AND TRAINER 909 00:42:31,800 --> 00:42:34,280 OR OBSERVER IS AT THE SIDE AND 910 00:42:34,280 --> 00:42:36,840 TEST FOR 400 METER WALK IS DONE 911 00:42:36,840 --> 00:42:40,080 AND COMPLETED OR PASSED LINE FOR 912 00:42:40,080 --> 00:42:45,680 10 COMPLETE LOOPS. 913 00:42:45,680 --> 00:42:49,640 THERE IS CRITERIA FOR 914 00:42:49,640 --> 00:42:52,600 RESPONSIVENESS CONSIDERING WHAT 915 00:42:52,600 --> 00:42:54,440 MEANINGFUL CHANGES ARE FOR EACH 916 00:42:54,440 --> 00:42:57,440 MESH YOOSHS AND SMALL CHANGES 917 00:42:57,440 --> 00:42:59,880 ARE DETECTIBLE AND POTENTIALLY 918 00:42:59,880 --> 00:43:02,240 CLINICALLY MEANINGFUL AND 919 00:43:02,240 --> 00:43:03,760 SUBSTANTIAL CHANGES ARE 920 00:43:03,760 --> 00:43:07,720 DETECTIBLE CONSIDERED CLINICALLY 921 00:43:07,720 --> 00:43:14,360 MEANINGFUL FOUR YEAR WALK. 922 00:43:14,360 --> 00:43:17,400 5 POINTS AND ONE POINT AND 12 923 00:43:17,400 --> 00:43:21,160 POINT SCALE AND 6 MINUTE WALK IS 924 00:43:21,160 --> 00:43:25,280 A SMALL CHANGE IS CONSIDERED 20 925 00:43:25,280 --> 00:43:26,560 METERS AND SUBSTANTIAL CHANGE IS 926 00:43:26,560 --> 00:43:31,640 50 METERS AND IN GAINING AND 927 00:43:31,640 --> 00:43:42,120 INCREASING APPRECIATION ON 928 00:43:42,440 --> 00:43:43,440 MEANINGFUL CHANGES DIFFER 929 00:43:43,440 --> 00:43:44,760 PURPOSE BEING STUDIED AND 930 00:43:44,760 --> 00:43:47,640 PURPOSE OF MEASURE ANALYSIS 931 00:43:47,640 --> 00:43:50,600 COMPLETED FROM NIA SPONSORED 932 00:43:50,600 --> 00:43:53,840 TESTOSTERONE TRIALS AND WERE MEN 933 00:43:53,840 --> 00:43:59,400 AT BASELINE WITH GATE SPOOED OF 934 00:43:59,400 --> 00:44:02,360 LESS THAN 1.2 AND BASED ON 935 00:44:02,360 --> 00:44:05,360 ANCHORING METHODS AFTER TRIAL IS 936 00:44:05,360 --> 00:44:10,600 DONE CLINICALLY IMPORTANT 937 00:44:10,600 --> 00:44:15,720 DIFFERENCES FRAFRNG 6 TA ENTO 30 938 00:44:15,720 --> 00:44:17,920 METERS THAT IS LOW IN STANDARD 939 00:44:17,920 --> 00:44:20,400 IN PRIOR STUDIES AND SLIDE FROM 940 00:44:20,400 --> 00:44:23,160 WORK JAMIE JUSTICE HAS DONE 941 00:44:23,160 --> 00:44:26,280 ABOUT TRANSLATION AND MOBILITY 942 00:44:26,280 --> 00:44:29,160 ACROSS SPECIES I WILL FOCUS ON 943 00:44:29,160 --> 00:44:30,240 FUNCTIONAL LIMITATION COLUMN AND 944 00:44:30,240 --> 00:44:34,640 SEEING AT TOP HUMANS TALKING 945 00:44:34,640 --> 00:44:35,560 ABOUT LOCOMOTOR FUNCTION GAIT 946 00:44:35,560 --> 00:44:38,040 SPEED AND SBB AND VARIATIONS ON 947 00:44:38,040 --> 00:44:41,800 THAT SUCH AS TUG AND TIMED UP 948 00:44:41,800 --> 00:44:45,840 AND GO WALKING ACROSS ROOM AND 949 00:44:45,840 --> 00:44:48,960 RODENT AND MICE MODELS 950 00:44:48,960 --> 00:44:51,720 LOCOMOTION WITH GAIT SPEED AND 951 00:44:51,720 --> 00:44:54,920 NONPRIMATE HUMAN MODELS UNDER 952 00:44:54,920 --> 00:44:56,160 LOCOMOTION GAIT SPEED. GAIT 953 00:44:56,160 --> 00:44:57,600 SPEED IS SOMETHING THAT COULD BE 954 00:44:57,600 --> 00:45:01,480 MEASURED HEARING EARLIER IN THE 955 00:45:01,480 --> 00:45:06,240 MEETING ACROSS SPECIES PROVIDING 956 00:45:06,240 --> 00:45:08,440 EVIDENCE IN USE OF HUMANS 957 00:45:08,440 --> 00:45:11,520 INCREASING VALUE AND ANIMAL 958 00:45:11,520 --> 00:45:13,080 MODELS AND ANOTHER SLIDE FROM 959 00:45:13,080 --> 00:45:18,520 SAME PAPER BY JAMIE JUSTICE WITH 960 00:45:18,520 --> 00:45:29,040 HUMAN PRIMATE MODELS AND RATS 961 00:45:39,440 --> 00:45:43,400 AND RODENANT AND -- GOING TO RIT 962 00:45:43,400 --> 00:45:46,680 79 FOR HUMANS EQUIVALENT AGES 963 00:45:46,680 --> 00:45:49,800 FOR LOWER SPECIES AND LOWER 964 00:45:49,800 --> 00:45:53,600 SURVIVAL AND WORK DONE IN BOTTOM 965 00:45:53,600 --> 00:45:56,760 PANEL WITH THE SURVIVOR OR 966 00:45:56,760 --> 00:46:00,240 MORTALITY RATE AT DIFFERENT AGES 967 00:46:00,240 --> 00:46:03,400 AT DIFFERENT SPECIES THAT ARE 968 00:46:03,400 --> 00:46:06,240 RELEVANT TO EACH OTHER AND IN 969 00:46:06,240 --> 00:46:08,400 50S SURVIVED MORTALITY THAT ARE 970 00:46:08,400 --> 00:46:10,000 ABOUT 10% AND THERE IS NO OTHER 971 00:46:10,000 --> 00:46:11,960 SPECIES IN THOSE DATA AND TO THE 972 00:46:11,960 --> 00:46:18,680 RIGHT IN 60S YOU CAN SEE THAT 973 00:46:18,680 --> 00:46:19,680 MORTALITY IS COMPARABLE AND TO 974 00:46:19,680 --> 00:46:25,240 FAR RIGHT WITH HUMANS IN 80S IN 975 00:46:25,240 --> 00:46:29,200 COMPARABLE WHO ARE MICE AND 976 00:46:29,200 --> 00:46:30,760 RODANT MODELS SEEING 977 00:46:30,760 --> 00:46:34,160 RELATIONSHIP WITH SURVIVAL AND 978 00:46:34,160 --> 00:46:39,280 THIS ALLOWS TO DO TRANSLATIONAL 979 00:46:39,280 --> 00:46:42,400 RESEARCH ACROSS SPECIES. 980 00:46:42,400 --> 00:46:45,960 IT HAS LED TO WORK DONE BY. 981 00:46:45,960 --> 00:46:46,600 >>COUNTY ADMINISTRATOR VOSBURG: 982 00:46:46,600 --> 00:46:50,440 IAL AND LOU EEJI WAS INVOLVED 983 00:46:50,440 --> 00:47:00,920 PROBABLY IN THIS THIS IS A 984 00:47:03,960 --> 00:47:06,520 TRANSFERABLE RATE AND SPECIES 985 00:47:06,520 --> 00:47:08,600 DIFFERENCES AT TOP AND 986 00:47:08,600 --> 00:47:10,240 NON-LINEAR DECLINE IN GAIT SPEED 987 00:47:10,240 --> 00:47:15,000 AND IN HUMANS ON LEFT AND MICE 988 00:47:15,000 --> 00:47:17,600 ON RIGHT AND LATER IN LIFE AND 989 00:47:17,600 --> 00:47:19,280 ARE DRIVEN BY DIFFERENT FACETS 990 00:47:19,280 --> 00:47:23,080 OF GAIT IN HUMANS THAT IT TENDS 991 00:47:23,080 --> 00:47:25,040 TO BE WITH GAIT STEP LENGTH AND 992 00:47:25,040 --> 00:47:28,400 THAT IS THE MIDDLE PANEL AND YOU 993 00:47:28,400 --> 00:47:31,720 CAN SEE THERE IS A DIMMIN USHIA 994 00:47:31,720 --> 00:47:35,720 OF STEP LENG NNL HUMANS NOT SEEN 995 00:47:35,720 --> 00:47:39,480 IN MICE AND LOWER PANEL, HUMANS 996 00:47:39,480 --> 00:47:41,560 MAINTAIN CADENCE IT THIS AIS 997 00:47:41,560 --> 00:47:44,080 REDUCED DRIVING REDUCTIONS IN 998 00:47:44,080 --> 00:47:45,800 GAIT SPEED IN MICE AND IS WORK 999 00:47:45,800 --> 00:47:48,080 THAT HAS LED TO A NEW 1000 00:47:48,080 --> 00:47:49,480 PERSPECTIVE STUDY IN MICE THAT 1001 00:47:49,480 --> 00:47:53,440 IS EQUIVALENT TO THE BSLA AND 1002 00:47:53,440 --> 00:47:56,880 BALTIMORE LONGITUDINAL AGING 1003 00:47:56,880 --> 00:47:59,280 CALLED SLAM STUDY OF 1004 00:47:59,280 --> 00:48:01,280 LONGITUDINAL AGING IN MICE THAT 1005 00:48:01,280 --> 00:48:05,080 IS LED BY RAFAEL. IN SUMMARY, 1006 00:48:05,080 --> 00:48:09,000 MOBILITY IS ESSENTIAL ELEMENT OF 1007 00:48:09,000 --> 00:48:11,480 GERIATRIC ASSESSMENT MOBILITY IS 1008 00:48:11,480 --> 00:48:13,760 IMPORTANT FUNCTION OF TESTING IN 1009 00:48:13,760 --> 00:48:17,000 AGENTS AND ABILITY CAN BE 1010 00:48:17,000 --> 00:48:19,720 ASSESSED RELIABLY IN 1011 00:48:19,720 --> 00:48:21,000 SELF-REPORTED PERFORMANCE 1012 00:48:21,000 --> 00:48:23,680 MEASURES MEASURES OF DISABILITY 1013 00:48:23,680 --> 00:48:26,200 AND BEING REVERSE TRANSLATED TO 1014 00:48:26,200 --> 00:48:30,280 COMPARABLE MEASURES IN RODENTS 1015 00:48:30,280 --> 00:48:34,040 AND NONPRIMATES AND TRANSLATED 1016 00:48:34,040 --> 00:48:37,120 ACROSS SPECIES AND THANK YOU. 1017 00:48:37,120 --> 00:48:38,400 >>[APPLAUSE]. 1018 00:48:38,400 --> 00:48:48,960 >>THANK YOU AND TO ORGANIZERS 1019 00:49:01,440 --> 00:49:04,280 FOR INVITING ME AND TURNING TO A 1020 00:49:04,280 --> 00:49:06,040 MORE HIGH-LEVEL COMPLEXITY TALK. 1021 00:49:06,040 --> 00:49:09,200 I THINK IT IS HIGHLY RELEVANT 1022 00:49:09,200 --> 00:49:11,520 FOR THE MATHEMATICAL MODELING 1023 00:49:11,520 --> 00:49:12,880 PIECE THAT WILL COME LATER TODAY 1024 00:49:12,880 --> 00:49:15,440 AND BIOMARKERS PIECE AND HEARING 1025 00:49:15,440 --> 00:49:18,840 ABOUT HOW TO MEASURE FRAILTY AND 1026 00:49:18,840 --> 00:49:20,520 RESILIENCE AND BIOLOGY THAT WE 1027 00:49:20,520 --> 00:49:23,600 THINK UNDERLIES IT WE NEED LOTS 1028 00:49:23,600 --> 00:49:25,800 OF DIFFERENT BIOMARKERS AND 1029 00:49:25,800 --> 00:49:28,040 MODELS TO COME UP WITH MORE 1030 00:49:28,040 --> 00:49:31,560 PRECISE MEASURES OF FRAILTY AND 1031 00:49:31,560 --> 00:49:34,080 MORE PRECISE WAYS TO ULTIMATELY 1032 00:49:34,080 --> 00:49:36,720 INTERVENE ON FRAILTY AND PROMOTE 1033 00:49:36,720 --> 00:49:39,840 RESILIENCE IN OLDER ADULTS AND 1034 00:49:39,840 --> 00:49:42,280 LIKE LUIGI SAID EARLIER IN FIELD 1035 00:49:42,280 --> 00:49:44,720 OF GERIATRICS AND SEEING END 1036 00:49:44,720 --> 00:49:47,360 STAGE OF MANY DIFFERENT 1037 00:49:47,360 --> 00:49:48,960 CONDITIONS IN LIFE, BUT, 1038 00:49:48,960 --> 00:49:50,880 EVERYBODY SORT OF WANTS THE SAME 1039 00:49:50,880 --> 00:49:53,080 THING AS THEY AGE AND WANT TO 1040 00:49:53,080 --> 00:49:55,600 MAINTAIN HIGH ENERGY LEVELS AND 1041 00:49:55,600 --> 00:49:57,480 ROBUST GOOD HEALTH DON'T WANT TO 1042 00:49:57,480 --> 00:49:59,440 BE IN HOSPITAL OR MEDICAL 1043 00:49:59,440 --> 00:50:01,800 SYSTEMS AND WANT TOIN DEPENDENT 1044 00:50:01,800 --> 00:50:04,840 IN CLEAR THINKING AND ENJOYING 1045 00:50:04,840 --> 00:50:06,400 SOCIAL CONTEXT IN MEANINGFUL 1046 00:50:06,400 --> 00:50:07,920 ACTIVITIES AND WHAT WE ARE DOING 1047 00:50:07,920 --> 00:50:09,920 HERE REMINDING OURSELVES DIVING 1048 00:50:09,920 --> 00:50:12,280 INTO PATHWAYS, BIG PURPOSE IS 1049 00:50:12,280 --> 00:50:14,440 OUT THERE TO TRY TO KEEP THESE 1050 00:50:14,440 --> 00:50:15,800 THINGS IN TACT AS PEOPLE AGE. 1051 00:50:15,800 --> 00:50:17,720 SO, I WILL TALK ABOUT 1052 00:50:17,720 --> 00:50:19,000 DEFINITIONS AND 1053 00:50:19,000 --> 00:50:20,200 CONCEPTUALIZATION AND FRAILTY 1054 00:50:20,200 --> 00:50:23,960 AND RESILIENCY AND BIOLOGIC 1055 00:50:23,960 --> 00:50:25,160 DISCOVERY AND I PROBABLY WON'T 1056 00:50:25,160 --> 00:50:27,280 HAVE TIME TO GET INTO THE 1057 00:50:27,280 --> 00:50:28,520 CLINICAL UTILITY PIECE TODAY. 1058 00:50:28,520 --> 00:50:31,520 WHY DO WE MEASURE IT? 1059 00:50:31,520 --> 00:50:33,920 IN CLINICAL PRACTICE, FRAILTY 1060 00:50:33,920 --> 00:50:36,800 HELPS US REALLY TO IDENTIFY HIGH 1061 00:50:36,800 --> 00:50:38,880 RISK INDIVIDUALS AS SUSAN 1062 00:50:38,880 --> 00:50:39,840 POINTED OUT EARLIER. 1063 00:50:39,840 --> 00:50:43,720 WHEN WE DO THAT, WE CAN OFTEN 1064 00:50:43,720 --> 00:50:46,080 HELP PREVENT CATASTROPHIC 1065 00:50:46,080 --> 00:50:49,320 CLINICAL OUTCOMES MODIFYING CARE 1066 00:50:49,320 --> 00:50:51,320 ACCORDINGLY AND RED FLAG PUT ON 1067 00:50:51,320 --> 00:50:52,560 THOSE PARTICULAR SUBSET OF 1068 00:50:52,560 --> 00:50:54,600 INDIVIDUALS THAT WE KNOW ARE 1069 00:50:54,600 --> 00:50:55,720 HIGH RISK AND WE SHOULDN'T BE 1070 00:50:55,720 --> 00:50:58,000 DOING ALL THINGS WE CAN DO TO 1071 00:50:58,000 --> 00:51:00,120 PATIENTS TRYING TO PROTECT THEM 1072 00:51:00,120 --> 00:51:01,400 A LITTLE BETTER. 1073 00:51:01,400 --> 00:51:03,320 WITH RESILIENCE, I THINK THAT 1074 00:51:03,320 --> 00:51:04,680 THE REASON THAT WE TRY TO 1075 00:51:04,680 --> 00:51:07,480 MEASURE RESILIENCE THAT IS A 1076 00:51:07,480 --> 00:51:08,440 WORK IN PROGRESS AS YOU WILL 1077 00:51:08,440 --> 00:51:12,120 HEAR REALLY IS TO ENABLE OPTIMAL 1078 00:51:12,120 --> 00:51:13,720 PERFORMANCE OF STRESS RESPONSE 1079 00:51:13,720 --> 00:51:15,720 PATHWAYS THAT EVERYBODY HAS 1080 00:51:15,720 --> 00:51:17,080 IMBEDDED IN THEM. 1081 00:51:17,080 --> 00:51:19,280 AND ULTIMATELY FOR PREVENTIVE 1082 00:51:19,280 --> 00:51:28,160 AND RECOVERY PURPOSES. 1083 00:51:28,160 --> 00:51:36,320 EXCUSE ME A SECOND. 1084 00:51:36,320 --> 00:51:39,520 I WILL GET INTO FRAILTY HERE 1085 00:51:39,520 --> 00:51:41,800 FIRST. SUSAN MENTIONED HUNDREDS 1086 00:51:41,800 --> 00:51:45,040 OF FRAILTY MODELS AND THERE IS 1087 00:51:45,040 --> 00:51:47,040 HUNDREDS TO MEASURE FRAILTY AND 1088 00:51:47,040 --> 00:51:50,520 OUR GROUP AT HOPKINS AND IN 1089 00:51:50,520 --> 00:51:54,440 CANADA 20 PLUS YEARS AGO REALLY 1090 00:51:54,440 --> 00:51:56,440 STARTED TO DESIGN THESE TOOLS 1091 00:51:56,440 --> 00:51:57,440 CALLED MEASUREMENT OF FRAILTY 1092 00:51:57,440 --> 00:52:01,040 THAT ARE CONCEPTUALLY DIFFERENT 1093 00:52:01,040 --> 00:52:03,760 AND CHEN LEE AND OTHERS HAVE 1094 00:52:03,760 --> 00:52:06,160 PUBLISHED PAPERS ON THAT AND ON 1095 00:52:06,160 --> 00:52:08,760 RIGHT SUSAN TALKED ABOUT DEFICIT 1096 00:52:08,760 --> 00:52:10,600 ACCUMULATION APPROACH TO FRAILTY 1097 00:52:10,600 --> 00:52:14,280 AND LOTS OF DEFICITS COMING INTO 1098 00:52:14,280 --> 00:52:17,800 THIS MAIN CONCEPT THAT COULD BE 1099 00:52:17,800 --> 00:52:20,280 CHRONIC ILLNESSES OR MOBILITY 1100 00:52:20,280 --> 00:52:22,120 DISABILITY AND COULD BE SOCIAL 1101 00:52:22,120 --> 00:52:23,240 SITUATIONS AND LOTS OF DIFFERENT 1102 00:52:23,240 --> 00:52:25,600 THINGS AND MORE DEFICITS AN 1103 00:52:25,600 --> 00:52:26,440 INDIVIDUAL HAS MORE LIKELY THEY 1104 00:52:26,440 --> 00:52:29,400 ARE TO BE FRAIL BY THIS MODEL 1105 00:52:29,400 --> 00:52:31,720 THAT WE CAME AT IT FROM A 1106 00:52:31,720 --> 00:52:33,720 DIFFERENT PERSPECTIVE THINKING 1107 00:52:33,720 --> 00:52:35,400 ABOUT THE FIRST DEEPER BUY OL 1108 00:52:35,400 --> 00:52:37,160 THAT IS HAPPENING AS PEOPLE AGE 1109 00:52:37,160 --> 00:52:40,520 AND DEEP AGING RELATED CHANGES 1110 00:52:40,520 --> 00:52:44,440 THAT THEN LEAD TO THESE SORT OF 1111 00:52:44,440 --> 00:52:46,360 CLINICAL CHARACTERISTICS WE SEE 1112 00:52:46,360 --> 00:52:51,440 IN A SUBSET OF VULNERABLE 1113 00:52:51,440 --> 00:52:53,040 PATIENTS WE CALL PHYSICAL 1114 00:52:53,040 --> 00:52:55,280 FRAILTY AND FRAILTY DEFICIT 1115 00:52:55,280 --> 00:52:56,960 ACCUMULATION INDEX AND MANY, 1116 00:52:56,960 --> 00:52:58,840 MANY DIFFERENT TOOLS HAVE SPUN 1117 00:52:58,840 --> 00:53:00,760 OFF FROM UNDERLYING CONCEPTS AND 1118 00:53:00,760 --> 00:53:03,520 WILL TALK TODAY ABOUT BIOLOGIC 1119 00:53:03,520 --> 00:53:04,800 UNDERPINNINGS WE THINK IS 1120 00:53:04,800 --> 00:53:06,920 RELATED TO PHYSICAL FRAILTY THAT 1121 00:53:06,920 --> 00:53:09,960 MAY WELL BE IN THE END AS WE 1122 00:53:09,960 --> 00:53:12,320 COME TO DISCOVER THE GEROSCIENCE 1123 00:53:12,320 --> 00:53:15,160 AGING RELATED BIOLOGY THAT IS 1124 00:53:15,160 --> 00:53:16,640 DRIVING BOTH CAUSES OF FRAILTY 1125 00:53:16,640 --> 00:53:18,600 AND REASON THAT OLDER PEOPLE 1126 00:53:18,600 --> 00:53:20,440 COLLECT ALL THESE COMORBIDITIES 1127 00:53:20,440 --> 00:53:21,960 AND CHANGES OVER TIME IS BECAUSE 1128 00:53:21,960 --> 00:53:26,600 OF THE SAME AGING RELATED 1129 00:53:26,600 --> 00:53:27,040 BIOLOGY. 1130 00:53:27,040 --> 00:53:29,840 IN PHYSICAL FRAILTY WORLD, WE 1131 00:53:29,840 --> 00:53:32,480 USE FIVE MEASURES PUTTING 1132 00:53:32,480 --> 00:53:33,440 TOGETHER OPERATIONALIZING IT IN 1133 00:53:33,440 --> 00:53:36,680 AN EXAM AND IF PEOPLE HAVE THREE 1134 00:53:36,680 --> 00:53:40,240 OR 4 OR FIVE OF THESE CRITERIA, 1135 00:53:40,240 --> 00:53:42,560 THEY WERE PUT IN A FRAIL 1136 00:53:42,560 --> 00:53:44,960 CATEGORY AND 0 WITH ROBUST AND 1 1137 00:53:44,960 --> 00:53:47,640 OR 2 IN NEBULOUS PREFRAIL 1138 00:53:47,640 --> 00:53:48,800 CATEGORY AND WHEN PEOPLE ARE 1139 00:53:48,800 --> 00:53:50,600 PREFRAIL THEY ARE HEADED TOWARDS 1140 00:53:50,600 --> 00:53:55,840 FRAILTY IN A FEW YEARS AND THIS 1141 00:53:55,840 --> 00:53:57,720 CHARACTERIZATION OF HUMAN 1142 00:53:57,720 --> 00:54:00,360 SUBJECTS MADE US TO BE ABLE TO 1143 00:54:00,360 --> 00:54:02,440 DIFFERENTIATE AND STUDY BIOLOGY 1144 00:54:02,440 --> 00:54:03,720 AND ROBUST AND FRAIL GROUPS TO 1145 00:54:03,720 --> 00:54:05,920 SEE WHAT HAPPENS TO THEM OVER 1146 00:54:05,920 --> 00:54:10,040 TIME. IT THIS IS JUST A 1147 00:54:10,040 --> 00:54:11,680 PREVALENCE STUDY THAT KAREN AND 1148 00:54:11,680 --> 00:54:13,720 OTHERS DID SEVERAL YEARS AGO IN 1149 00:54:13,720 --> 00:54:17,000 US POPULATION AND SHOWS THAT 1150 00:54:17,000 --> 00:54:19,160 ABOUT 15% OF OLDER ADULTS LIVING 1151 00:54:19,160 --> 00:54:21,760 IN COMMUNITY FELL INTO THE 1152 00:54:21,760 --> 00:54:23,600 FRAILTY CATEGORY AND 40% IN 1153 00:54:23,600 --> 00:54:26,440 ROBUST AND LOTS OF OTHER PEOPLE 1154 00:54:26,440 --> 00:54:29,080 WERE IN-BETWEEN. AS PEOPLE GET 1155 00:54:29,080 --> 00:54:30,760 OLDER, THEY ARE CERTAINLY MORE 1156 00:54:30,760 --> 00:54:32,640 LIKELY TO FALL INTO FRAIL 1157 00:54:32,640 --> 00:54:33,040 CATEGORIES. 1158 00:54:33,040 --> 00:54:35,400 WE OFTEN -- WE -- AGAIN, WE 1159 00:54:35,400 --> 00:54:38,160 THOUGHT OF THIS AS A BIOLOGIC 1160 00:54:38,160 --> 00:54:39,600 CONSTRUCT AND THINKING VERY 1161 00:54:39,600 --> 00:54:42,680 EARLY ON ABOUT WHAT IS IT ABOUT 1162 00:54:42,680 --> 00:54:45,400 AGING THAT MAKES OLDER PEOPLE 1163 00:54:45,400 --> 00:54:46,920 MORE VULNERABLE? 1164 00:54:46,920 --> 00:54:49,320 AGE RELATED CHANGES IN MANY 1165 00:54:49,320 --> 00:54:51,720 MOLECULAR AND PHYSIOLOGICAL 1166 00:54:51,720 --> 00:54:54,040 SYSTEMS PROVIDE A PLATFORM FOR 1167 00:54:54,040 --> 00:54:56,000 VULNERABILITY AND ALTERATIONS WE 1168 00:54:56,000 --> 00:54:58,160 THOUGHT PROBABLY PERSISTED FOR 1169 00:54:58,160 --> 00:54:59,640 YEARS BEFORE THEY END UP 1170 00:54:59,640 --> 00:55:01,840 BECOMING CLINICALLY MANIFESTED 1171 00:55:01,840 --> 00:55:04,400 IN SIGNS AND SYMPTOMS AND SAME 1172 00:55:04,400 --> 00:55:06,800 THING. WE -- THINKING WAS 1173 00:55:06,800 --> 00:55:13,640 ALWAYS THAT THE SAME AGE ALT 1174 00:55:13,640 --> 00:55:16,920 ALTERALTERED 1175 00:55:16,920 --> 00:55:18,800 BIOLOGIC CHANGE -- HIGH RISK OF 1176 00:55:18,800 --> 00:55:20,960 FALLING AND MANY CHRONIC DISEASE 1177 00:55:20,960 --> 00:55:23,960 STATES TRAVEL TOGETHER WITH 1178 00:55:23,960 --> 00:55:25,440 FRAILTY. HEART FAILURE AND 1179 00:55:25,440 --> 00:55:27,720 HYPERTENSION AND DEPRESSION AND 1180 00:55:27,720 --> 00:55:30,160 ANXIETY AND DIFFERENT CONDITIONS 1181 00:55:30,160 --> 00:55:33,000 TEND TO AGGRIFATE LATER IN LIFE 1182 00:55:33,000 --> 00:55:35,480 AND WE PUT TOGETHER A BIOLOGIC 1183 00:55:35,480 --> 00:55:37,720 CYCLE OF FRAILTY THAT, AGAIN, I 1184 00:55:37,720 --> 00:55:39,680 TELL MY JUNIOR FOLKS WORKING 1185 00:55:39,680 --> 00:55:42,240 WITH ME THAT WE GENERALLY 1186 00:55:42,240 --> 00:55:43,480 RECOMMEND AGAINST WRITING A 1187 00:55:43,480 --> 00:55:44,880 CHAPTER THAT NEVER SEEMS TO HELP 1188 00:55:44,880 --> 00:55:47,240 YOUR CAREER. THIS REALLY HELPED 1189 00:55:47,240 --> 00:55:49,080 MINE. WE PUT THIS MODEL 1190 00:55:49,080 --> 00:55:51,640 TOGETHER VERY EARLY ON WITH A 1191 00:55:51,640 --> 00:55:55,400 CYCLE OF DECLINE AND WITH 1192 00:55:55,400 --> 00:55:56,960 FRAILTY AND SARCOPENIA THAT IS 1193 00:55:56,960 --> 00:55:58,560 PUT TOGETHER AND YOU CAN SEE 1194 00:55:58,560 --> 00:56:00,360 LOTS OF DIFFERENT PIECES THERE 1195 00:56:00,360 --> 00:56:02,400 WITH SOME MOLECULAR MEASURES AND 1196 00:56:02,400 --> 00:56:04,400 SOME PHYSIOLOGIC MEASURES AND 1197 00:56:04,400 --> 00:56:06,520 SOME MOBILITY MEASURES AND GIVES 1198 00:56:06,520 --> 00:56:09,400 YOU A SENSE OF THE SORT OF MESSY 1199 00:56:09,400 --> 00:56:11,240 MEASUREMENT ISSUES RELATED TO 1200 00:56:11,240 --> 00:56:13,240 FRAILTY AND I THINK THAT I HAVE 1201 00:56:13,240 --> 00:56:15,760 SPENT MOST OF MY CAREER NOW 1202 00:56:15,760 --> 00:56:18,040 TRYING TO UNRAVEL SOME PIECES 1203 00:56:18,040 --> 00:56:21,640 AND BECOMING MORE PRECISE IN THE 1204 00:56:21,640 --> 00:56:21,960 MEASUREMENT. 1205 00:56:21,960 --> 00:56:24,520 FAST FORWARD 20 YEARS, LOTS AND 1206 00:56:24,520 --> 00:56:26,960 LOTS OF EPIDEMIOLOGIC STUDIES, 1207 00:56:26,960 --> 00:56:30,160 HUNDREDS IF NOT THOUSANDS OF 1208 00:56:30,160 --> 00:56:33,000 EPIDEMIOLOGIC STUDIES LOOKING AT 1209 00:56:33,000 --> 00:56:34,560 RELATIONSHIP BETWEEN VARIOUS 1210 00:56:34,560 --> 00:56:36,840 BIOLOGIC INDICATORS OR MEASURES 1211 00:56:36,840 --> 00:56:37,840 AND OUTCOMES AND ON RIGHT YOU 1212 00:56:37,840 --> 00:56:40,440 SEE OUTCOMES THAT ARE RELATED TO 1213 00:56:40,440 --> 00:56:42,440 PHYSICAL FRAILTY AND HIGH RISK 1214 00:56:42,440 --> 00:56:44,440 OF BECOMING DEPENDENT AND HIGH 1215 00:56:44,440 --> 00:56:46,360 RISK OF BECOMING DISABLED AND 1216 00:56:46,360 --> 00:56:48,520 LOTS OF CHRONIC DISEASE BURDEN 1217 00:56:48,520 --> 00:56:50,480 AND EARLY MORTALITY AND MEASURES 1218 00:56:50,480 --> 00:56:52,160 OUT THERE IN OUTCOMES AND 1219 00:56:52,160 --> 00:56:54,720 SYMPTOMS AND SIGNS AND SYMPTOMS 1220 00:56:54,720 --> 00:56:56,760 OF PHYSICAL FRAILTY MENTIONING 1221 00:56:56,760 --> 00:56:59,120 EARLIER DETERMINING WHO IS FRAIL 1222 00:56:59,120 --> 00:57:02,000 AND NOT FRAIL IN THE YELLOW BOX 1223 00:57:02,000 --> 00:57:06,000 AND BIG SUMMARY OF EPIRELATED 1224 00:57:06,000 --> 00:57:08,960 STUDIES SHOWING DETAIL ON THIS 1225 00:57:08,960 --> 00:57:11,200 IN PAIL MRU BOX ALTERED STRESS 1226 00:57:11,200 --> 00:57:13,720 RESPONSE SYSTEMS THAT ARE VERY 1227 00:57:13,720 --> 00:57:14,680 CHARACTERISTIC OF SOMEBODY THAT 1228 00:57:14,680 --> 00:57:16,560 IS FRAIL AND I WILL TALK ABOUT 1229 00:57:16,560 --> 00:57:19,480 THEM AND ENERGY METABOLISM AND 1230 00:57:19,480 --> 00:57:22,720 CHANGES IN WAY THAT PEOPLE 1231 00:57:22,720 --> 00:57:24,680 PROCESS ENERGY MITOCHONDRIAL 1232 00:57:24,680 --> 00:57:28,080 ENERGY AND PCA CYCLE AND GLUCOSE 1233 00:57:28,080 --> 00:57:29,640 TOLERANCE AND THERE IS TWO ARMS 1234 00:57:29,640 --> 00:57:32,160 THERE AND FINALLY OUT ON FAR 1235 00:57:32,160 --> 00:57:37,320 LEFT, DARK BLUE BOXES BIOLOGIC 1236 00:57:37,320 --> 00:57:39,040 AGING HEART OF GEROSCIENCE WE 1237 00:57:39,040 --> 00:57:41,560 HAVE THOUGHT ABOUT MANY YEARS 1238 00:57:41,560 --> 00:57:43,600 WHAT MOLECULAR CHANGESES 1239 00:57:43,600 --> 00:57:44,880 TRIGGERING THIS PHYSIOLOGY IS 1240 00:57:44,880 --> 00:57:47,760 AND ULTIMATELY SYNDROMES WE SEE 1241 00:57:47,760 --> 00:57:49,480 LATER IN LIFE AND BAD OUTCOMES 1242 00:57:49,480 --> 00:57:53,440 AND CERTAINLY GENES AND HEARING 1243 00:57:53,440 --> 00:57:54,040 YESTERDAY SOCIOECONOMIC 1244 00:57:54,040 --> 00:57:56,520 CONDITIONS AND DIET AND ACTIVITY 1245 00:57:56,520 --> 00:57:59,000 PLAY CERTAINLY BIG ROLES IN THAT 1246 00:57:59,000 --> 00:58:02,040 AND CHRONIC DISEASES ALSO CAN 1247 00:58:02,040 --> 00:58:04,240 DRIVE THAT SAME PHYSIOLOGY IN 1248 00:58:04,240 --> 00:58:07,600 LIGHT BLUE BOX AND ALSO 1249 00:58:07,600 --> 00:58:08,480 ALTERNATIVELY PROBABLY 1250 00:58:08,480 --> 00:58:10,320 PHYSIOLOGY IS MAKING MANY 1251 00:58:10,320 --> 00:58:11,440 DISEASE CONDITIONS WORSEN. 1252 00:58:11,440 --> 00:58:14,160 SO, THIS IS A KIND OF BIG 1253 00:58:14,160 --> 00:58:15,760 PICTURE HOW WE TRIED TO 1254 00:58:15,760 --> 00:58:17,280 CONSTRUCT THINKING ABOUT THAT. 1255 00:58:17,280 --> 00:58:19,720 AND PERFORMING MEASURES ALONG 1256 00:58:19,720 --> 00:58:21,160 PATHWAYS TRYING TO RELATE THEM 1257 00:58:21,160 --> 00:58:23,040 OUT TO EITHER THE SIGNS AND 1258 00:58:23,040 --> 00:58:25,280 SYMPTOMS OF FRAILTY OR 1259 00:58:25,280 --> 00:58:26,480 ULTIMATELY TO OUTCOMES THAT HAS 1260 00:58:26,480 --> 00:58:29,120 BEEN SORT OF THE WAY THAT WE 1261 00:58:29,120 --> 00:58:30,560 TRIED TO EXPLORE THE BIOLOGY. 1262 00:58:30,560 --> 00:58:32,040 THIS IS ANOTHER WAY OF LOOKING 1263 00:58:32,040 --> 00:58:38,200 AT IT A LITTLE BIT MORE DETAILED 1264 00:58:38,200 --> 00:58:41,360 ON LEFT THERE AND POINTING TO 1265 00:58:41,360 --> 00:58:45,760 MOLECULAR AGES AND MEASURES OF 1266 00:58:45,760 --> 00:58:48,560 MITOCHONDRIAL DESIGNS 1267 00:58:48,560 --> 00:58:51,480 DEMETHYLATION AND SIN ESSENCE 1268 00:58:51,480 --> 00:58:53,720 CELL MEASUREMENTS AND THOSE ARE 1269 00:58:53,720 --> 00:58:56,080 DEEPLY MOLECULAR MEASURES HARD 1270 00:58:56,080 --> 00:58:59,600 TO DO IN HUMAN SUBJECTS YOU CAN 1271 00:58:59,600 --> 00:59:01,080 DO THEM SUPER EXPENSIVE TISSUES 1272 00:59:01,080 --> 00:59:03,640 SOMETIMES AND SPECIAL ASSAYS NOT 1273 00:59:03,640 --> 00:59:04,760 READY FOR CLINICAL PRIME TIME 1274 00:59:04,760 --> 00:59:08,480 AND THINGS WE WOULD LOVE TO GET 1275 00:59:08,480 --> 00:59:12,920 TO IN NEXT FEW YEARS IN PATHWAYS 1276 00:59:12,920 --> 00:59:15,560 THAT COULD BE DONE ON SERUM 1277 00:59:15,560 --> 00:59:17,320 SAMPLES AND THINGS THAT WOULD BE 1278 00:59:17,320 --> 00:59:19,720 RELATIVELY EASY TO MEASURE IN 1279 00:59:19,720 --> 00:59:26,200 HUMAN SUBJECTS AND PATIENTS 1280 00:59:26,200 --> 00:59:28,200 OTHER BOXES I WON'T TALK ABOUT 1281 00:59:28,200 --> 00:59:29,440 TODAY AND [INDISCERNIBLE] IS 1282 00:59:29,440 --> 00:59:32,000 RIPE FOR EXPLORATIONINATE IMMUNE 1283 00:59:32,000 --> 00:59:34,480 SYSTEM CHRONIC INFLAMMATION 1284 00:59:34,480 --> 00:59:35,720 ASSOCIATED WITH THAT IS CLEARLY 1285 00:59:35,720 --> 00:59:38,440 NOT ONLY HIGHLY RELATED TO 1286 00:59:38,440 --> 00:59:40,760 ADVERSE OUTCOMES SEEING IN OLDER 1287 00:59:40,760 --> 00:59:42,560 ADULTS AND FRAILTY AND 1288 00:59:42,560 --> 00:59:45,280 PHENOTYPES IN OLDER ADULTS AND 1289 00:59:45,280 --> 00:59:47,200 KNOW NOW IS DRIVING MANY OTHER 1290 00:59:47,200 --> 00:59:50,480 PROCESSES THAT ULTIMATELY SEEM 1291 00:59:50,480 --> 00:59:53,600 TO MAKE OLDER ADULTS VULNERABLE 1292 00:59:53,600 --> 00:59:57,680 TO LOTS OF CONDITIONS NOT JUST 1293 00:59:57,680 --> 00:59:59,160 EPIPHENOMENON COMMONLY SAID TO 1294 00:59:59,160 --> 01:00:02,240 20 YEARS AGO THERE IS BUY LOGIC 1295 01:00:02,240 --> 01:00:03,760 STUDIES CONNECTING CHRONIC 1296 01:00:03,760 --> 01:00:05,520 INFLAMMATION AND MEDIATORS TO 1297 01:00:05,520 --> 01:00:07,760 CHANGES IN MUSCLE AND IN IMMUNE 1298 01:00:07,760 --> 01:00:09,680 SYSTEM AND CHANGES IN BRAIN 1299 01:00:09,680 --> 01:00:11,760 TISSUE FOR EXAMPLE IN THE END 1300 01:00:11,760 --> 01:00:14,080 DRIVE SOME PHENOTYPES WE SEE AND 1301 01:00:14,080 --> 01:00:17,320 THERE IS A STRESS RESPONSE 1302 01:00:17,320 --> 01:00:20,520 SYSTEM HPA ACCESS SYMPATHETIC 1303 01:00:20,520 --> 01:00:23,000 NERVOUS SYSTEM THAT IS IN FRAIL 1304 01:00:23,000 --> 01:00:24,600 PEOPLE TENDING TO GET TURNED ON 1305 01:00:24,600 --> 01:00:27,760 NOT OFF AND ENERGY PRODUCTION 1306 01:00:27,760 --> 01:00:30,200 ANANABOLIC HORMONES AS WELL AND 1307 01:00:30,200 --> 01:00:32,240 OTHER MARKERS TO PICK UP ON 1308 01:00:32,240 --> 01:00:34,160 CHANGES IN FIZZ LOGIC SYSTEMS NO 1309 01:00:34,160 --> 01:00:37,040 THE SORT OF NECESSARILY READY 1310 01:00:37,040 --> 01:00:38,880 FOR CLINICAL PRIMETIME AND 1311 01:00:38,880 --> 01:00:40,840 ASSOCIATED IN EPISTUDIES AND IS 1312 01:00:40,840 --> 01:00:44,160 ANOTHER WAY THAT WE TRY TO THINK 1313 01:00:44,160 --> 01:00:48,160 ABOUT IT IN CLINICAL PRACTICE 1314 01:00:48,160 --> 01:00:49,960 AND ABOVE OLDER PERSON THAT IS 1315 01:00:49,960 --> 01:00:51,680 FRAIL AND WE KNOW WHAT THEY CAN 1316 01:00:51,680 --> 01:00:53,120 LOOK LIKE AND CHARACTERIZE THEM 1317 01:00:53,120 --> 01:00:56,000 BY FRAILTY AND TOP OF RIM OVER 1318 01:00:56,000 --> 01:00:58,560 THERE WEAKNESS LOW ACTIVITY AND 1319 01:00:58,560 --> 01:01:01,760 SLOW WALKING SPEED FOR EXAMPLE. 1320 01:01:01,760 --> 01:01:04,640 THERE IS LAB TESTS WE PICK UP 1321 01:01:04,640 --> 01:01:08,520 AND IN PEOPLE WE SEE LOW 1322 01:01:08,520 --> 01:01:09,880 ALBUMINCHOLESTEROL LEVELS AND 1323 01:01:09,880 --> 01:01:12,320 ANEMIA AND INCREASING CLOTTING 1324 01:01:12,320 --> 01:01:14,920 FACTORS AND THINGS DO YOU 1325 01:01:14,920 --> 01:01:16,880 ROUTINELY IN CLINICAL PRACTICE 1326 01:01:16,880 --> 01:01:19,720 YOU MIGHT SEE THAT AND THEY 1327 01:01:19,720 --> 01:01:20,600 ASSOCIATE WITH FRAILTY AND 1328 01:01:20,600 --> 01:01:22,760 UNDERNEATH THAT LINE AND OVALS 1329 01:01:22,760 --> 01:01:26,720 ARE THINGS GETTING RAMPED UP IN 1330 01:01:26,720 --> 01:01:27,720 FRAIL OLDER PEOPLE. 1331 01:01:27,720 --> 01:01:29,920 WE DON'T REALLY KNOW HOW TO 1332 01:01:29,920 --> 01:01:31,760 CAPTURE THEM CLINICALLY IN 1333 01:01:31,760 --> 01:01:34,520 CLINICALLY MEANINGFUL WAYS AND 1334 01:01:34,520 --> 01:01:37,640 ARE DOZENS IF NOT HUNDREDS OF 1335 01:01:37,640 --> 01:01:39,120 IMBEDDED BIOMARKERS DOWN THERE 1336 01:01:39,120 --> 01:01:40,880 AND WE WILL HOPEFULLY HEAR MORE 1337 01:01:40,880 --> 01:01:42,280 ABOUT THAT TODAY AND ULTIMATELY 1338 01:01:42,280 --> 01:01:44,520 THINKING ABOUT MEASURES AROUND 1339 01:01:44,520 --> 01:01:49,440 CIRCLES AT BOTTOM MOLECULAR 1340 01:01:49,440 --> 01:01:51,080 MEASURES AND SIN ESSENCE AND BIG 1341 01:01:51,080 --> 01:01:52,920 GROUPS ACTIVELY WORKING IN THESE 1342 01:01:52,920 --> 01:01:57,200 AREAS THINKING ABOUT HOW TO GET 1343 01:01:57,200 --> 01:02:01,440 TRANSLATED INTO CLINICALLY 1344 01:02:01,440 --> 01:02:03,160 MEANINGFUL MEASUREMENTS ARE 1345 01:02:03,160 --> 01:02:04,160 SUPER IMPORTANT AND ONE THING 1346 01:02:04,160 --> 01:02:06,360 THAT COULD COME OUT OF THIS 1347 01:02:06,360 --> 01:02:08,760 MEETING THAT WILL NEED A LOT OF 1348 01:02:08,760 --> 01:02:11,760 BIOLOGISTS WORKING ON THIS AND 1349 01:02:11,760 --> 01:02:13,000 STATISTICIANS THINKING ABOUT 1350 01:02:13,000 --> 01:02:14,600 MATHEMATICAL MODELING THINKING 1351 01:02:14,600 --> 01:02:18,440 ABOUT HOW TO PUT THESE TOGETHER 1352 01:02:18,440 --> 01:02:21,000 THINKING OF WHICH IS MOST 1353 01:02:21,000 --> 01:02:23,040 PREDICTIVE PATHWAY TO INTEGRATE 1354 01:02:23,040 --> 01:02:25,280 AND RESILIENCE I WILL SPEND REST 1355 01:02:25,280 --> 01:02:27,720 OF TIME TALKING ABOUT THAT, THAT 1356 01:02:27,720 --> 01:02:29,080 IS SOMETIMES THOUGHT OF AS 1357 01:02:29,080 --> 01:02:31,080 FLIPSIDE OF FRAILTY AND PEOPLE 1358 01:02:31,080 --> 01:02:34,360 THAT ARE RESILIENT OLDER PEOPLE 1359 01:02:34,360 --> 01:02:35,480 ARE GENERALLY NOT FRAIL AND 1360 01:02:35,480 --> 01:02:38,520 BEING RESILIENT IS NOT 1361 01:02:38,520 --> 01:02:40,360 NECESSARILY MEASURED IN SAME 1362 01:02:40,360 --> 01:02:40,960 WAY. 1363 01:02:40,960 --> 01:02:43,120 THESE ARE THEORIES PUT OUT OVER 1364 01:02:43,120 --> 01:02:53,520 LAST 20 OR 30 YEARS NOW 1365 01:02:54,600 --> 01:02:56,480 MAINTENANCE OF COMPLEXITY LOU IS 1366 01:02:56,480 --> 01:02:59,280 SITTING THERE GIVING SHOUTOUT TO 1367 01:02:59,280 --> 01:03:01,880 20-SOME YEARS AGO AND THOUGHT OF 1368 01:03:01,880 --> 01:03:04,360 HOMEO STATIC REGULATION AND DEEP 1369 01:03:04,360 --> 01:03:06,800 INTERNAL BUY LOGIC RESPONSES AND 1370 01:03:06,800 --> 01:03:11,080 IN STRESS SYSTEMS AND OTHER 1371 01:03:11,080 --> 01:03:13,960 AREAS THAT HOLD FUNCTION AND 1372 01:03:13,960 --> 01:03:15,160 SYSTEMIC FUNCTION TOGETHER AND 1373 01:03:15,160 --> 01:03:17,400 AS THOSE THINGS BECOME 1374 01:03:17,400 --> 01:03:20,440 UNRAVELLED THEY TEND TO BE LESS 1375 01:03:20,440 --> 01:03:28,240 COMPLEX AND SYSTEMS BECOME LESS 1376 01:03:28,240 --> 01:03:32,240 COMPLEX AND REGULATIONS WANE AND 1377 01:03:32,240 --> 01:03:34,040 COLLABORATORS FROM DUKE AND 1378 01:03:34,040 --> 01:03:35,200 INFORMATIVE THINKING ABOUT MODEL 1379 01:03:35,200 --> 01:03:38,080 OF RESILIENCY AND THINK OF IT AS 1380 01:03:38,080 --> 01:03:40,800 SORT OF COMMON UNDERPINNINGS 1381 01:03:40,800 --> 01:03:43,240 WITH FRAILTY AND NOT QUITE THE 1382 01:03:43,240 --> 01:03:45,440 FLIPSIDE AND ABILITY WE DEFINE 1383 01:03:45,440 --> 01:03:47,960 IT AS OBLT TO RECOVER FROM 1384 01:03:47,960 --> 01:03:49,960 POTENTIALLY DANLING STRESSORS 1385 01:03:49,960 --> 01:03:52,600 RETURNING TO HOMEO STATIC 1386 01:03:52,600 --> 01:03:54,720 FUNCTIONAL BASELINE AND 1387 01:03:54,720 --> 01:03:55,720 UNDERLYING HYPOTHESIS HAS BEEN 1388 01:03:55,720 --> 01:03:59,560 AGING RELATED LOSS OF PHYSICAL 1389 01:03:59,560 --> 01:04:01,600 REDISTILL YENLS HAPPENS WHEN 1390 01:04:01,600 --> 01:04:03,400 PHYSIOLOGIC SYSTEMS ARE UNABLE 1391 01:04:03,400 --> 01:04:05,400 TO MAINTAIN EQUILIBRIUM AND FACE 1392 01:04:05,400 --> 01:04:07,600 OF STRESSORS PEOPLE HAMMERED 1393 01:04:07,600 --> 01:04:09,960 WITH PSYCH LOGIC OR PHYSICAL 1394 01:04:09,960 --> 01:04:13,120 STRESS OR ILLNESS AND BODY CAN 1395 01:04:13,120 --> 01:04:15,080 GENERALLY BOUNCE BACK. 1396 01:04:15,080 --> 01:04:16,880 PHYSIOLOGICAL SYSTEMS ARE IN 1397 01:04:16,880 --> 01:04:18,360 TACT AND PEOPLE BECOMING LESS 1398 01:04:18,360 --> 01:04:20,440 AND LESS REDISTILLENT GET TO 1399 01:04:20,440 --> 01:04:23,280 TRANSITION TOWARDS FRAILTY THAT 1400 01:04:23,280 --> 01:04:24,720 IS A FIGURE THAT CHEN LEE AND 1401 01:04:24,720 --> 01:04:26,520 OTHERS HAVE USED OVER YEARS AND 1402 01:04:26,520 --> 01:04:28,680 YOU SEE STRESSORS HAPPENING IN 1403 01:04:28,680 --> 01:04:30,560 PEOPLE'S LIVE AND YOUNGER 1404 01:04:30,560 --> 01:04:32,000 NONFRAIL PEOPLE CAN GENERALLY 1405 01:04:32,000 --> 01:04:33,840 BOUNCE BACK YOU SEE IN CLINICAL 1406 01:04:33,840 --> 01:04:35,440 PRACTICE ALL THE TIME AND SOME 1407 01:04:35,440 --> 01:04:37,520 PEOPLE DON'T BOUNCE BACK AND 1408 01:04:37,520 --> 01:04:39,720 GENERALLY PEOPLE ARE BELOW FRAIL 1409 01:04:39,720 --> 01:04:45,800 THRESHOLD IN THE MIDDLE THERE 1410 01:04:45,800 --> 01:04:48,520 THEY ARE NOT AGE TO WITHSTAND 1411 01:04:48,520 --> 01:04:49,960 STRESSORS DOING POORLY 1412 01:04:49,960 --> 01:04:51,760 CLINICALLY AND FIGURE OUT HOW TO 1413 01:04:51,760 --> 01:04:55,720 MEASURE RESILIENCE THAT LED TO 1414 01:04:55,720 --> 01:04:57,600 US WORKING ON A GRANT THAT WAS 1415 01:04:57,600 --> 01:05:03,280 FUNDED 5 YEARS AGO NOW END 1416 01:05:03,280 --> 01:05:05,240 STAGES FOR COLLECTING DATA AND 1417 01:05:05,240 --> 01:05:08,560 ARM OF OLDER PEOPLE GETTING BONE 1418 01:05:08,560 --> 01:05:11,480 MARROW TRANSPLANTS AND GETTING 1419 01:05:11,480 --> 01:05:13,680 DIALYSIS AND GETTING KNEE 1420 01:05:13,680 --> 01:05:15,200 REPLACEMENTS BIG CLINICAL 1421 01:05:15,200 --> 01:05:16,600 STRESSORS HAPPENING IN HOSPITAL 1422 01:05:16,600 --> 01:05:18,600 GENERALLY AND WE HAVE AN 1423 01:05:18,600 --> 01:05:22,120 OPPORTUNITY TO MEASURE LOTS OF 1424 01:05:22,120 --> 01:05:23,600 BIOMARKERS AND FUNCTION AND 1425 01:05:23,600 --> 01:05:24,280 COGNITION BEFOREHAND AROUND TIME 1426 01:05:24,280 --> 01:05:25,960 OF THE STRESSOR AND WE FOLLOW 1427 01:05:25,960 --> 01:05:28,840 THEM OUT FOR A YEAR AND PICKED 1428 01:05:28,840 --> 01:05:31,200 UP LOTS OF BIOLOGIC AND CLINICAL 1429 01:05:31,200 --> 01:05:33,280 MARKERS DURING THAT PERIOD AND 1430 01:05:33,280 --> 01:05:36,640 HOPEFULLY SOON WE WILL BE ABLE 1431 01:05:36,640 --> 01:05:38,760 TO START ANALYSIS THAT IS A 1432 01:05:38,760 --> 01:05:40,520 GREAT RESOURCE FOR YEARS TO COME 1433 01:05:40,520 --> 01:05:43,040 FOR PEOPLE THAT WANT TO 1434 01:05:43,040 --> 01:05:45,080 COLLABORATE WITH US. 1435 01:05:45,080 --> 01:05:47,720 THIS IS THE BIG MODEL WE PUT 1436 01:05:47,720 --> 01:05:50,200 TOGETHER AND CENTER IS 1437 01:05:50,200 --> 01:05:55,720 EDISTILLIENCE CAPACITY OF AN 1438 01:05:55,720 --> 01:05:57,640 ORGANISM TO WITHSTAND STRESS AND 1439 01:05:57,640 --> 01:05:59,840 THINGS WHAT YOU ARE TRYING TO 1440 01:05:59,840 --> 01:06:01,840 MEASURE THERE AND BOXES WE CAN 1441 01:06:01,840 --> 01:06:04,800 MEASURE AND VARIOUS CLINICAL OR 1442 01:06:04,800 --> 01:06:06,640 BIOLOGIC OR OTHER KINDS OF 1443 01:06:06,640 --> 01:06:09,000 MACCERS AND AT LEFT YOU SEE 1444 01:06:09,000 --> 01:06:11,640 STRESSORS THAT WE SEE NOW THAT 1445 01:06:11,640 --> 01:06:13,920 ARE BONE MARROW TRANSPLANT BIG 1446 01:06:13,920 --> 01:06:15,760 HAMMER AND KNEE REPLACEMENT THAT 1447 01:06:15,760 --> 01:06:18,000 IS MODERATE HAMMER AND DIALYSIS 1448 01:06:18,000 --> 01:06:20,640 THAT IN SOME PEOPLE ARE REALLY 1449 01:06:20,640 --> 01:06:24,480 BAD HAMMERS AS WELL. 1450 01:06:24,480 --> 01:06:27,320 WE CAN CHARACTERIZE THEM AND 1451 01:06:27,320 --> 01:06:28,760 MEASURE THEM AND BEFOREHAND 1452 01:06:28,760 --> 01:06:31,560 PEOPLE'S AGE AND PHYSIOLOGIC AND 1453 01:06:31,560 --> 01:06:35,600 PSYCHOSOCIAL HEALTH PROFILES, 1454 01:06:35,600 --> 01:06:38,160 BEHAVIORS AHEAD OF TIME AND 1455 01:06:38,160 --> 01:06:42,600 DISEASE BURDEN. 1456 01:06:42,600 --> 01:06:45,480 FUNCTIONAL AND COGNITIVE MARKERS 1457 01:06:45,480 --> 01:06:48,360 AND JERO SCIENCE MARKERS RELATED 1458 01:06:48,360 --> 01:06:51,720 TO SIN ESSENCE AND GROUP AT MAYO 1459 01:06:51,720 --> 01:06:55,200 AND EPIGENETICS AND BIOPHYSICAL 1460 01:06:55,200 --> 01:06:57,120 PROPERTIES OF SELVES AND AGE 1461 01:06:57,120 --> 01:06:59,040 RELATED UNIQUE MARKERS HERE 1462 01:06:59,040 --> 01:07:01,560 THOSE ARE DUMPED INTO THAT 1463 01:07:01,560 --> 01:07:03,680 CENTER AND WE KNOW THOSE THINGS 1464 01:07:03,680 --> 01:07:08,800 WILL CONTRIBUTE TO SOMEBODY'S 1465 01:07:08,800 --> 01:07:09,160 RESILIENCE. 1466 01:07:09,160 --> 01:07:11,600 WE THINK IT IS PHYSIOLOGIC 1467 01:07:11,600 --> 01:07:14,560 SYSTEMS THAT DRIVE THAT AND WAY 1468 01:07:14,560 --> 01:07:17,600 TO STUDY SYSTEMS IS TWEAKING 1469 01:07:17,600 --> 01:07:19,680 THEM A BIT TO DO STRESS AND 1470 01:07:19,680 --> 01:07:22,160 YELLOW BOX AT LEFT AND DYNAMIC 1471 01:07:22,160 --> 01:07:23,720 STIMULATION OF VARIOUS 1472 01:07:23,720 --> 01:07:25,240 COMPONENTS OF STRESS RESPONSE 1473 01:07:25,240 --> 01:07:26,560 SYSTEMS WE HAVE IMBEDDED THAT I 1474 01:07:26,560 --> 01:07:28,200 WILL TALK ABOUT A BIT ABOUT THAT 1475 01:07:28,200 --> 01:07:31,720 STATIC MEASURES OF RESILIENCE 1476 01:07:31,720 --> 01:07:33,680 AND THINGS LIKE FRAILTY AND 1477 01:07:33,680 --> 01:07:36,080 FATIGUE FOR EXAMPLE COLLECTING 1478 01:07:36,080 --> 01:07:37,640 DATA IN LIGHT BLUE BOX AND WHAT 1479 01:07:37,640 --> 01:07:41,560 PEOPLE ARE LOOKING LIKE OVER 1, 1480 01:07:41,560 --> 01:07:46,000 3, 6, ONE YEAR OUT AND SEE WHAT 1481 01:07:46,000 --> 01:07:49,760 HAPPENS TO THEM IN END 1482 01:07:49,760 --> 01:07:51,720 TRAJECTORIES OF THOSE WITH BONE 1483 01:07:51,720 --> 01:07:52,760 MARROW TRANSPLANT AND DIE IN 1484 01:07:52,760 --> 01:07:55,440 THREE MONTHS AND DO OKAY 1485 01:07:55,440 --> 01:07:56,880 FUNCTIONALLY AND COGNITIVELY 1486 01:07:56,880 --> 01:07:59,360 PROBABLY DIMINISHED BUT ARE 1487 01:07:59,360 --> 01:08:02,480 STILL ALIVE AND HAVEN'T DIED AND 1488 01:08:02,480 --> 01:08:08,000 OTHER PEOPLE ARE COMPLETELY 1489 01:08:08,000 --> 01:08:09,600 CURED AND CHARACTERIZING SYSTEMS 1490 01:08:09,600 --> 01:08:15,520 THAT ARE DRIVING OUTCOMES AND SO 1491 01:08:15,520 --> 01:08:18,680 I WHETHER QUICKLY MOVE THROUGH 1492 01:08:18,680 --> 01:08:23,600 DYNAMIC SYSTEMS STUDIES AND STEM 1493 01:08:23,600 --> 01:08:27,040 TESTS HPA AXIS WITH -- WE HAVE 1494 01:08:27,040 --> 01:08:31,720 HOLTER MONITORING GIVING 1495 01:08:31,720 --> 01:08:34,960 AUTONOMIC NERVOUS SYSTEM 1496 01:08:34,960 --> 01:08:36,800 ACTIVITY VARIABILITY AND 1497 01:08:36,800 --> 01:08:38,080 CONTRASTING VARIABILITY BETWEEN 1498 01:08:38,080 --> 01:08:41,160 HIGH FREQUENCY VARIATION AND 1499 01:08:41,160 --> 01:08:44,840 TOTAL HEART RATE VARIABILITY 1500 01:08:44,840 --> 01:08:48,760 MEASURED ON HOLTER MODELS 1501 01:08:48,760 --> 01:08:53,200 OBSERVED FATIGUABLE ON HOLTER 1502 01:08:53,200 --> 01:08:57,440 SITES AND LYMPHOCYTES IMAGINING 1503 01:08:57,440 --> 01:09:00,320 IN HAMMER AND TEST TUBE AND WHAT 1504 01:09:00,320 --> 01:09:04,160 EXPLODES OUT OF THEM AND 1505 01:09:04,160 --> 01:09:07,280 ORTHOSTATIC BLOOD PRESSURE 1506 01:09:07,280 --> 01:09:09,400 MEASUREMENTS MODERATE TWEAKS IN 1507 01:09:09,400 --> 01:09:11,080 SYSTEMS AND HYPOTHESIZE THOSE 1508 01:09:11,080 --> 01:09:13,480 THAT ARE EDISTILLIENT WILL DO 1509 01:09:13,480 --> 01:09:15,400 LOW ON TEST AND THOSE THAT ARE 1510 01:09:15,400 --> 01:09:17,960 NOT WILL GIVE INSIGHTS INTO 1511 01:09:17,960 --> 01:09:19,440 WHICH STRESS RESPONSE SYSTEM 1512 01:09:19,440 --> 01:09:21,880 MAIZE BE IMPACTED IN RESILIENCE 1513 01:09:21,880 --> 01:09:25,720 OR LACK OF RESILIENCE. 1514 01:09:25,720 --> 01:09:27,600 AGAIN, WE MENTION MANY 1515 01:09:27,600 --> 01:09:28,680 GEROSCIENCE MEASUREMENT DOMAINS 1516 01:09:28,680 --> 01:09:30,240 WE PUT IN THERE AND LOOKING 1517 01:09:30,240 --> 01:09:32,200 FORWARD TO TALKS LATER TODAY. 1518 01:09:32,200 --> 01:09:33,920 I THINK THAT ONE THING THAT WE 1519 01:09:33,920 --> 01:09:35,720 THOUGHT THROUGH THIS IS AN AIR 1520 01:09:35,720 --> 01:09:37,280 WHY THAT REALLY NEEDS TO BE 1521 01:09:37,280 --> 01:09:39,640 MOVED FORWARD IS TAKING THESE 1522 01:09:39,640 --> 01:09:41,480 SORT OF VERY DEEP MOLECULAR 1523 01:09:41,480 --> 01:09:43,680 MEASURES PEOPLE ARE WORKING ON 1524 01:09:43,680 --> 01:09:54,040 IN MITOCHONDRIA FOR EXAMPLE OR 1525 01:09:54,040 --> 01:09:56,560 ETOPAGY AND SYNESSENCE AND 1526 01:09:56,560 --> 01:09:59,200 THINGS RELATE TODAY THAT PROET 1527 01:09:59,200 --> 01:10:02,040 TEOMICS AND METABOLOMICS ARE 1528 01:10:02,040 --> 01:10:03,680 MOVING MORE INTO THE MAINSTREAM 1529 01:10:03,680 --> 01:10:05,240 BUT HAVEN'T SEEN LOTS OF 1530 01:10:05,240 --> 01:10:06,760 PRODUCTS GETTING PUSHED INTO THE 1531 01:10:06,760 --> 01:10:08,440 SORT OF CLINICAL SIDE AND 1532 01:10:08,440 --> 01:10:11,040 HOPEFULLY AS WE MOVE FORWARD IN 1533 01:10:11,040 --> 01:10:12,920 RESEARCH FIELDS IN COMING YEARS 1534 01:10:12,920 --> 01:10:16,560 WE WILL BE ABLE TO CHERRY PICK 1535 01:10:16,560 --> 01:10:18,120 HOPEFULLY IMPORTANT MARKERS FROM 1536 01:10:18,120 --> 01:10:19,480 THESE INSTEAD OF SPENDING 1537 01:10:19,480 --> 01:10:21,040 THOUSANDS AND THOUSANDS OF 1538 01:10:21,040 --> 01:10:23,160 DOLLARS ON TESTS WITH ASSAY THAT 1539 01:10:23,160 --> 01:10:28,400 IS $50 LIKE HEMOGLOBIN OR 1540 01:10:28,400 --> 01:10:29,200 SOMETHING. 1541 01:10:29,200 --> 01:10:31,800 I WILL SKIP THAT. SUMMARY AND 1542 01:10:31,800 --> 01:10:34,280 PHYSICAL FRAILTY AND PHYSICAL 1543 01:10:34,280 --> 01:10:35,800 RESILIENCE ARE NOT SAME BUT 1544 01:10:35,800 --> 01:10:39,360 LIKELY HAVE COMMON BIOLOGIC 1545 01:10:39,360 --> 01:10:39,920 UNDERPINNINGS AND DEFICIT 1546 01:10:39,920 --> 01:10:42,080 ACCUMULATION AS WELL PROBABLY. 1547 01:10:42,080 --> 01:10:44,120 THAT TYPE OF FRAILTY AND 1548 01:10:44,120 --> 01:10:46,800 IDENTIFICATION OF FRAILTY 1549 01:10:46,800 --> 01:10:48,280 ENABLES DEVELOPMENT OF 1550 01:10:48,280 --> 01:10:50,480 PROTECTIVE CARE PLAN WE USE IN 1551 01:10:50,480 --> 01:10:51,400 CLINICAL PRACTICE LIKE THAT TO 1552 01:10:51,400 --> 01:10:53,880 FIND PEOPLE THAT ARE VULNERABLE 1553 01:10:53,880 --> 01:10:55,720 PUTTING A SHIELD AROUND THEM AND 1554 01:10:55,720 --> 01:10:56,560 IDENTIFICATION AND 1555 01:10:56,560 --> 01:10:58,600 CHARACTERIZATION OF RESILIENCE 1556 01:10:58,600 --> 01:11:00,360 FROM BUY LOGIC PERSPECTIVES YOU 1557 01:11:00,360 --> 01:11:02,760 SEE IS A WORK IN PROGRESS 1558 01:11:02,760 --> 01:11:04,000 BETWEEN OUR GROUP AND OTHERS 1559 01:11:04,000 --> 01:11:05,520 AROUND THE COUNTRY WE WILL HAVE 1560 01:11:05,520 --> 01:11:06,800 LOTS OF INFORMATION COMING OUT 1561 01:11:06,800 --> 01:11:10,560 OF THAT IN THE NEXT COUPLE YEARS 1562 01:11:10,560 --> 01:11:18,520 AND I WILL ACKNOWLEDGE 1563 01:11:18,520 --> 01:11:20,080 RESILIENCE AND FRAILTY GROUP WE 1564 01:11:20,080 --> 01:11:22,520 HAVE AT HOPKINS AND WE HAVE 1565 01:11:22,520 --> 01:11:23,720 TUESDAY MORNING CALLS AND 1566 01:11:23,720 --> 01:11:25,760 WEDNESDAY MORNING EVERY OTHER 1567 01:11:25,760 --> 01:11:27,520 WEEK AND WELCOME PEOPLE TO JOIN 1568 01:11:27,520 --> 01:11:28,720 CALLS AND HAVE PEOPLE FROM ALL 1569 01:11:28,720 --> 01:11:30,960 OVER THE COUNTRY THAT JUMPED IN 1570 01:11:30,960 --> 01:11:32,560 AND HAVE REALLY HELPED TO INFORM 1571 01:11:32,560 --> 01:11:34,160 THE FIELD THROUGH THEIR INPUT 1572 01:11:34,160 --> 01:11:37,080 AND NIA I HAVE TO ACKNOWLEDGE 1573 01:11:37,080 --> 01:11:38,680 HAS BEEN INCREDIBLY SUPPORTIVE 1574 01:11:38,680 --> 01:11:41,000 OF FRAILTY FOR MORE THAN 20 1575 01:11:41,000 --> 01:11:43,720 YEARS IN OUR CENTER AND THROUGH 1576 01:11:43,720 --> 01:11:47,600 PHYSICAL RESILIENCY AWARDS THAT 1577 01:11:47,600 --> 01:11:49,360 WILL ENABLE LOTS OF DATA TO COME 1578 01:11:49,360 --> 01:11:59,920 OUT. I WILL STOP. THANK YOU. 1579 01:12:32,760 --> 01:12:34,920 GOOD MORNING. HAPPY TO BE HERE. 1580 01:12:34,920 --> 01:12:36,800 THIS SESSION IS HANGING TOGETHER 1581 01:12:36,800 --> 01:12:39,080 PRETTY WELL THAT IS SOMEWHAT A 1582 01:12:39,080 --> 01:12:40,560 SURPRISE GIVEN THREE WEEKS AGO 1583 01:12:40,560 --> 01:12:42,440 OR SOMETHING WHEN WE HAD A CALL 1584 01:12:42,440 --> 01:12:44,600 AND NONE OF US HAD A CLUE WHAT 1585 01:12:44,600 --> 01:12:48,600 THIS WAS ALL ABOUT. I WANT TO 1586 01:12:48,600 --> 01:12:51,720 NOTE THAT I -- WHAT -- I WASN'T 1587 01:12:51,720 --> 01:12:55,920 SUPPOSED TO SAY THAT? 1588 01:12:55,920 --> 01:12:59,760 YOU HAD A CLUE. IT CAME 1589 01:12:59,760 --> 01:13:02,600 TOGETHER SO NOTE THAT I WILL 1590 01:13:02,600 --> 01:13:06,520 TALK ABOUT MATERIAL THAT I HAVE 1591 01:13:06,520 --> 01:13:08,760 PRODUCED WITH MY POST DOC ERIC 1592 01:13:08,760 --> 01:13:11,160 AND GIVEN MY ABILITIES, ERIC 1593 01:13:11,160 --> 01:13:14,440 PROBABLY DID MOST OF IT. I WANT 1594 01:13:14,440 --> 01:13:16,480 TO JUST MAKE THAT CLEAR FROM THE 1595 01:13:16,480 --> 01:13:17,720 BEGINNING. WE WERE TOLD THIS 1596 01:13:17,720 --> 01:13:21,840 WAS A SESSION ON MEASUREMENT AND 1597 01:13:21,840 --> 01:13:25,720 SYSTEMS AND IT SEEMED TO FIT IN 1598 01:13:25,720 --> 01:13:27,560 PRETTY WELL WITH WHAT WE WERE 1599 01:13:27,560 --> 01:13:28,840 DOING AT THE TIME. 1600 01:13:28,840 --> 01:13:31,720 FOR A LONG TIME, I HAVE WORKED 1601 01:13:31,720 --> 01:13:36,640 ON TRYING TO GET AT MEASURES OF 1602 01:13:36,640 --> 01:13:38,600 BIOLOGICAL AGING AND ALLOSTATIC 1603 01:13:38,600 --> 01:13:42,400 LOAD. I MEAN, WE GO BACK 1604 01:13:42,400 --> 01:13:44,080 DECADES HERE. 1605 01:13:44,080 --> 01:13:47,240 THINGS GET SOME HANDLE ON WHAT 1606 01:13:47,240 --> 01:13:51,440 IT IS IN THIS MULTISYSTEM 1607 01:13:51,440 --> 01:13:54,800 PROCESS THAT ACTUALLY UNDERLIES 1608 01:13:54,800 --> 01:13:58,000 THIS AGING EXPERIENCE AND CAN BE 1609 01:13:58,000 --> 01:14:00,400 USED TO PREDICT AGING OUTCOMES 1610 01:14:00,400 --> 01:14:03,480 AND SO WE HAD THIS IDEA THAT 1611 01:14:03,480 --> 01:14:05,280 MANY SYSTEMS WERE INVOLVED IN 1612 01:14:05,280 --> 01:14:08,600 AGING FOR QUITE A WHILE. AND 1613 01:14:08,600 --> 01:14:10,280 THEN GEROSCIENCE KIND OF CAME 1614 01:14:10,280 --> 01:14:12,360 ALONG AND SAID, WELL, THERE IS 1615 01:14:12,360 --> 01:14:13,800 ACTUALLY ANOTHER LEVEL. IT IS 1616 01:14:13,800 --> 01:14:16,440 NOT JUST SYSTEMS AND THERE IS A 1617 01:14:16,440 --> 01:14:18,360 MORE BASIC MOLECULAR AND 1618 01:14:18,360 --> 01:14:19,960 CELLULAR LEVEL OF AGING. IT IS 1619 01:14:19,960 --> 01:14:24,320 -- IT WORKS ACROSS SYSTEMS AND 1620 01:14:24,320 --> 01:14:26,680 BOTH SYSTEMS AND LEVELS SHOULD 1621 01:14:26,680 --> 01:14:28,800 BE CONSIDERED HERE. 1622 01:14:28,800 --> 01:14:30,840 SO, I'M RETURNING TO THIS SAME 1623 01:14:30,840 --> 01:14:33,600 QUESTION THAT I PROBABLE WILL I 1624 01:14:33,600 --> 01:14:35,440 ADDRESSED A FEW TIMES ALREADY. 1625 01:14:35,440 --> 01:14:37,480 BUT, WHAT HAPPENS IS THAT EVERY 1626 01:14:37,480 --> 01:14:39,480 TIME WE GET A LOT MORE MARKERS 1627 01:14:39,480 --> 01:14:42,480 AND A LOT MORE MEASURES. 1628 01:14:42,480 --> 01:14:47,520 NOW WITH THE WEALTH OF 1629 01:14:47,520 --> 01:14:49,240 BIOMARKERS WE NOW HAVE AND 1630 01:14:49,240 --> 01:14:51,400 MULTISYSTEM APPROACH CAN WE 1631 01:14:51,400 --> 01:14:54,760 BETTER UNDERSTAND AGING HEALTH 1632 01:14:54,760 --> 01:14:55,080 OUTCOMES? 1633 01:14:55,080 --> 01:14:59,320 WE ALSO HAVE NEW ANALYTIC 1634 01:14:59,320 --> 01:15:03,720 TECHNIQUES TO APPROACH THIS. 1635 01:15:03,720 --> 01:15:06,000 AS NUMBER OF MARKERS GROWS 1636 01:15:06,000 --> 01:15:07,880 ABILITY TO USE OLD TECHNIQUES IS 1637 01:15:07,880 --> 01:15:11,760 REDUCED GETTING TO NEW WAYS OF 1638 01:15:11,760 --> 01:15:14,520 ACTUALLY ANALYZING THINGS. 1639 01:15:14,520 --> 01:15:17,040 I WILL USE A MACHINE LEARNING 1640 01:15:17,040 --> 01:15:19,000 APPROACH TODAY. 1641 01:15:19,000 --> 01:15:21,520 I'M ALWAYS DOING THIS FROM THE 1642 01:15:21,520 --> 01:15:22,640 PERSPECTIVE OF SOCIAL SCIENTISTS 1643 01:15:22,640 --> 01:15:26,640 THAT I AM. WHAT I'M REALLY 1644 01:15:26,640 --> 01:15:28,240 INTERESTED IN IS WHAT UNDERLIES 1645 01:15:28,240 --> 01:15:35,160 THE DIFFERENCES IN SOCIETY IN 1646 01:15:35,160 --> 01:15:38,040 TERMS OF PACE OF AGING AND 1647 01:15:38,040 --> 01:15:39,480 HEALTH OUTCOMES AND SOCIAL 1648 01:15:39,480 --> 01:15:40,600 VARIABLES CONNECTED TO IT AND 1649 01:15:40,600 --> 01:15:44,680 CAN I USE BIOLOGY TO BETTER 1650 01:15:44,680 --> 01:15:47,240 UNDERSTAND SOCIAL DIFFERENCES? 1651 01:15:47,240 --> 01:15:49,040 THAT IS WHERE I WILL END UP. 1652 01:15:49,040 --> 01:15:51,240 THIS IS THE MODEL OF HEALTH WE 1653 01:15:51,240 --> 01:15:55,000 ARE FITTING ALL THE TIME NOW 1654 01:15:55,000 --> 01:15:57,360 MOST SOCIAL SCIENTISTS WITH -- 1655 01:15:57,360 --> 01:16:02,240 OH, SUPPOSED TO DEMOGRAPHIC 1656 01:16:02,240 --> 01:16:09,800 DOCTORS AND SOCIOECONOMIC STATUS 1657 01:16:09,800 --> 01:16:11,800 BEING MOTIVATING FACTORS TO 1658 01:16:11,800 --> 01:16:13,320 UNDERSTAND HOW THEY ARE LINKED 1659 01:16:13,320 --> 01:16:16,040 TO HEALTH OUTCOMES ON THE 1660 01:16:16,040 --> 01:16:17,440 RIGHT-HAND SIDE. 1661 01:16:17,440 --> 01:16:20,280 WHAT ARE PHYSIOLOGICAL MEASURES 1662 01:16:20,280 --> 01:16:22,840 AND WHAT ARE THE MOLECULAR AND 1663 01:16:22,840 --> 01:16:25,760 CELLULAR MEASURES THAT ACTUALLY 1664 01:16:25,760 --> 01:16:27,120 INTERVENE TO MEDIATE THAT 1665 01:16:27,120 --> 01:16:30,880 PROCESS AND ACTUALLY HELP US TO 1666 01:16:30,880 --> 01:16:34,320 UNDERSTAND THAT PROCESS? 1667 01:16:34,320 --> 01:16:36,160 THAT -- THIS IS KIND OF THE 1668 01:16:36,160 --> 01:16:38,560 MODEL I'M FITTING AND I WILL 1669 01:16:38,560 --> 01:16:40,520 TALK ABOUT THESE TWO LEVELS 1670 01:16:40,520 --> 01:16:42,600 MOLECULAR AND CELLULAR HALLMARKS 1671 01:16:42,600 --> 01:16:45,280 THAT WE CAN MEASURE NOW ABOUT 1672 01:16:45,280 --> 01:16:47,480 HALF -- OF WHICH WE CAN GET AN 1673 01:16:47,480 --> 01:16:49,440 INDICATOR OF ABOUT HALF. THEN I 1674 01:16:49,440 --> 01:16:54,520 WILL LOOK AT INDICATORS THAT ARE 1675 01:16:54,520 --> 01:17:01,520 IN 12 DIFFERENT PHYSIOLOGICAL 1676 01:17:01,520 --> 01:17:03,720 SYSTEMS THAT ARE SYSTEMS AND -- 1677 01:17:03,720 --> 01:17:07,760 I WILL TREAT GENERAL AGING AS A 1678 01:17:07,760 --> 01:17:10,360 SEPARATE LEVEL. I WILL TREAT 1679 01:17:10,360 --> 01:17:12,560 THESE SYSTEMS THAT ARE LISTED 1680 01:17:12,560 --> 01:17:14,680 HERE, 12 DIFFERENT SYSTEMS. 1681 01:17:14,680 --> 01:17:18,600 I WILL INCLUDE IN THEM 75 1682 01:17:18,600 --> 01:17:21,200 DIFFERENT BIOMARKERS AND I WILL 1683 01:17:21,200 --> 01:17:26,680 USE AN APPROACH TO BUILDING 1684 01:17:26,680 --> 01:17:29,200 SYSTEM-BASED RISK INDICATORS 1685 01:17:29,200 --> 01:17:31,800 THAT WAIT THE DIFFERENT 1686 01:17:31,800 --> 01:17:35,440 BIOMARKERS WITHIN SYSTEMS AND 1687 01:17:35,440 --> 01:17:38,440 TODAY I WILL TALK ABOUT 1688 01:17:38,440 --> 01:17:40,960 PREDICTION OF MORTALITY AND THE 1689 01:17:40,960 --> 01:17:43,760 SYSTEMS ONLY HAVE ONE MEASURE 1690 01:17:43,760 --> 01:17:48,680 AND ENDOCRINE HAS DHES IN 1691 01:17:48,680 --> 01:17:56,520 RESPIRATORY AS A PEAK FLOW 1692 01:17:56,520 --> 01:17:59,800 OTHERS HAVE MULTIPLE MEASURES I 1693 01:17:59,800 --> 01:18:02,600 WILL USE EXTREME GRADIENT 1694 01:18:02,600 --> 01:18:06,120 APPROACHING TO MACHINE LEARNING 1695 01:18:06,120 --> 01:18:09,160 THAT IS A FLEXIBLE APPROACH IN 1696 01:18:09,160 --> 01:18:11,240 TERMS OF ASSESSING RELATIONSHIPS 1697 01:18:11,240 --> 01:18:13,800 OF VARIABLES THAT DOESN'T 1698 01:18:13,800 --> 01:18:17,440 REQUIRE LINEARITY OR THINGS LIKE 1699 01:18:17,440 --> 01:18:17,960 THAT. 1700 01:18:17,960 --> 01:18:20,640 I WILL TAKE A SAMPLE AND DIVIDE 1701 01:18:20,640 --> 01:18:23,720 IT IN HALF INTO A TESTING OR 1702 01:18:23,720 --> 01:18:25,640 TRAINING SAMPLE AND TESTING 1703 01:18:25,640 --> 01:18:27,920 SAMPLE AND I WILL FIRST TAKE THE 1704 01:18:27,920 --> 01:18:31,200 MARKERS THAT ARE WITHIN EACH 1705 01:18:31,200 --> 01:18:35,720 SYSTEM AND I WILL USE MACHINE 1706 01:18:35,720 --> 01:18:37,920 LEARNING APPROACH TO DEFINING 1707 01:18:37,920 --> 01:18:40,520 WHICH MARKERS WITHIN THAT SYSTEM 1708 01:18:40,520 --> 01:18:43,240 THAT ELATE MOST STRONGLY TO 1709 01:18:43,240 --> 01:18:44,480 MORTALITY AND DEVELOP AN INDEX 1710 01:18:44,480 --> 01:18:49,400 THAT IS BASED ON THE VALUES OF 1711 01:18:49,400 --> 01:18:51,600 THOSE MARKERS AND WEIGHTS THAT 1712 01:18:51,600 --> 01:18:53,600 THEY SHOULD HAVE IN THE 1713 01:18:53,600 --> 01:18:54,960 MORTALITY INDEX AND I WILL DO 1714 01:18:54,960 --> 01:18:58,440 THAT FOR ALL OF THE SYSTEMS 1715 01:18:58,440 --> 01:18:59,800 INDIVIDUALLY AND I WILL TAKE 1716 01:18:59,800 --> 01:19:03,000 THOSE INDICATORS THAT I HAVE 1717 01:19:03,000 --> 01:19:07,720 BUILT BY SYSTEM AND USE THEM IN 1718 01:19:07,720 --> 01:19:10,840 THE TESTING SAMPLE TO THEN 1719 01:19:10,840 --> 01:19:12,160 ESTIMATE MORTALITY. 1720 01:19:12,160 --> 01:19:15,720 AND TO SEE WHICH SYSTEMS ARE 1721 01:19:15,720 --> 01:19:19,160 STRONGEST IN ESTIMATING 1722 01:19:19,160 --> 01:19:20,640 MORTALITY AND TO ASSESS WHETHER 1723 01:19:20,640 --> 01:19:25,880 THESE SYSTEMS ACTUALLY DO 1724 01:19:25,880 --> 01:19:27,400 EXPLAIN SOCIAL DIFFERENCES WE 1725 01:19:27,400 --> 01:19:28,960 START WITH IN MORTALITY AND 1726 01:19:28,960 --> 01:19:32,760 BEGINNING WITH, I WILL SHOW YOU 1727 01:19:32,760 --> 01:19:37,480 HOW THE VARIOUS INDIVIDUAL 1728 01:19:37,480 --> 01:19:44,480 BIOMARKERS ARE RELATED TO 1729 01:19:44,480 --> 01:19:47,160 MORTALITY CHOSEN BY MACHINE 1730 01:19:47,160 --> 01:19:49,320 LEARNING APPROACH IN TERMS OF 1731 01:19:49,320 --> 01:19:51,720 STRENGTH AND RELATIONSHIP AND 1732 01:19:51,720 --> 01:19:54,360 HEALTH AND RETIREMENT STUDY MANY 1733 01:19:54,360 --> 01:19:56,160 PEOPLE KNOW ABOUT ACTUALLY THAT 1734 01:19:56,160 --> 01:19:58,160 IS A NATIONALLY REPRESENTATIVE 1735 01:19:58,160 --> 01:19:59,800 SAMPLE OF AMERICANS OVER AGE OF 1736 01:19:59,800 --> 01:20:06,320 50 AND IS 30 YEARS OF DATA. 1737 01:20:06,320 --> 01:20:11,080 ONLY EXTENSIVE BIOMARKER DATA 1738 01:20:11,080 --> 01:20:14,560 FROM 2006 TAENTHAT CAME FROM A 1739 01:20:14,560 --> 01:20:16,280 SAMPLE HERE OF ABOUT 4 THOUSAND 1740 01:20:16,280 --> 01:20:19,040 PEOPLE THAT IS GROUP ON WHICH WE 1741 01:20:19,040 --> 01:20:21,400 HAVE ALL THESE BIOMARKERS AND 1742 01:20:21,400 --> 01:20:26,200 TESTING AND TRAINING SAMPLES ARE 1743 01:20:26,200 --> 01:20:27,440 APPROXIMATELY 2000 PEOPLE A 1744 01:20:27,440 --> 01:20:30,120 PIE 1745 01:20:30,120 --> 01:20:30,520 PIECE. 1746 01:20:30,520 --> 01:20:34,160 I WILL BEGIN WITH GENERAL AGING 1747 01:20:34,160 --> 01:20:40,840 AND I WILL INDICATE RELATIVE 1748 01:20:40,840 --> 01:20:46,200 IMPORTANCE OF 7 FACTORS IN 1749 01:20:46,200 --> 01:20:47,760 GENERAL AGING INDICATOR THAT ARE 1750 01:20:47,760 --> 01:20:50,680 NUMBER OF EPIGENETIC CLOCKS THAT 1751 01:20:50,680 --> 01:20:52,720 WE INCLUDED ALL OF THEM. THEY 1752 01:20:52,720 --> 01:20:55,720 ARE NOT THAT HIGHLY RELATED TO 1753 01:20:55,720 --> 01:21:01,560 EACH OTHER AND TELOMERE LENGTH 1754 01:21:01,560 --> 01:21:03,080 MITOCHONDRIAL NUMBER IN THIS. 1755 01:21:03,080 --> 01:21:06,800 YOU SEE THAT IN ALL CASES WHAT 1756 01:21:06,800 --> 01:21:14,040 WE ARE -- THE RANGE OF EFFECT 1757 01:21:14,040 --> 01:21:19,360 HERE IS FROM 0 TO 1 AND SIZE OF 1758 01:21:19,360 --> 01:21:22,160 THE EFFECT REPRESENTS 1759 01:21:22,160 --> 01:21:26,120 EXPLANATORY POWER OF INDIVIDUAL 1760 01:21:26,120 --> 01:21:31,240 BIOMARKER THAT IS USED TO 1761 01:21:31,240 --> 01:21:36,240 CONSTRUCT INDEX AND EPIGENETIC 1762 01:21:36,240 --> 01:21:37,920 CLOCKS PHENOAND GRIM AGE IS 1763 01:21:37,920 --> 01:21:39,760 STRONG HERE AND ARE ONES THAT 1764 01:21:39,760 --> 01:21:42,680 ARE MOST IMPORTANT IN THIS 1765 01:21:42,680 --> 01:21:45,760 GENERAL AGING MEASURE. 1766 01:21:45,760 --> 01:21:51,440 IF I LOOK AT CARDIOVASCULAR 1767 01:21:51,440 --> 01:21:54,080 SYSTEM BY FAR PRO-BNP MEASURE IS 1768 01:21:54,080 --> 01:21:58,200 VERY STRONG. IT OUTWEIGHS EVERY 1769 01:21:58,200 --> 01:22:00,080 OTHER INDICATOR. 1770 01:22:00,080 --> 01:22:03,760 AND IF I LOOK AT MY INNATE 1771 01:22:03,760 --> 01:22:05,480 IMMUNE AND INFLAMMATORY SYSTEM 1772 01:22:05,480 --> 01:22:09,760 IT IS THE CYTOKINES THAT ARE 1773 01:22:09,760 --> 01:22:15,280 WAITING MOST HEAVILY UP NEAR TOP 1774 01:22:15,280 --> 01:22:17,360 AND THINGS THAT DON'T RELATE 1775 01:22:17,360 --> 01:22:18,880 THAT ARE SOMEWHAT INTERESTING 1776 01:22:18,880 --> 01:22:21,520 AND FOR INSTANCE CRP NEVER SEEMS 1777 01:22:21,520 --> 01:22:24,200 TO DO ANYTHING ANYMORE WHEN WE 1778 01:22:24,200 --> 01:22:28,360 GET ALL CYTOKINES MEASURED AND 1779 01:22:28,360 --> 01:22:32,360 LOOKING AT ADAPTIVE IMMUNE, 1780 01:22:32,360 --> 01:22:33,760 LYMPHOOCYTES ARE STRONGEST IN 1781 01:22:33,760 --> 01:22:35,320 TERMS OF RELATIONSHIP WITH 1782 01:22:35,320 --> 01:22:39,560 MORTALITY AND IF I LOOK AT 1783 01:22:39,560 --> 01:22:44,400 METABOLIC MARKERS BMI AND HB1C 1784 01:22:44,400 --> 01:22:47,760 AND GLUCOSE THAT ARE 1785 01:22:47,760 --> 01:22:51,720 APPROXIMATELY EQUAL IN SHARING 1786 01:22:51,720 --> 01:22:53,680 EXPLANATORY POWER AND HAVE 1787 01:22:53,680 --> 01:22:56,040 EXPLANATORY POWER IN TERMS OF 1788 01:22:56,040 --> 01:22:59,640 MORTALITY AND I INCLUDED 1789 01:22:59,640 --> 01:23:00,920 NEURODEGENERATIVE OR 1790 01:23:00,920 --> 01:23:03,720 NEUROLOGICAL MEASURES BASICALLY 1791 01:23:03,720 --> 01:23:05,520 BECAUSE THEY ARE SORT OF SENT 1792 01:23:05,520 --> 01:23:11,680 AND BRAIN AGING IS CENTRAL TO 1793 01:23:11,680 --> 01:23:13,360 AGING IN GENERAL AND WHILE ONE 1794 01:23:13,360 --> 01:23:15,240 MIGHT NOT EXPECT IT TO BE 1795 01:23:15,240 --> 01:23:16,600 RELATED TO MORTALITY IN WAYS 1796 01:23:16,600 --> 01:23:19,720 THAT OTHER MEASURES ARE IT IS 1797 01:23:19,720 --> 01:23:22,200 INTERESTING TO TEST THAT. AMONG 1798 01:23:22,200 --> 01:23:24,760 BRAIN INDICATORS NORA FILAMENT 1799 01:23:24,760 --> 01:23:26,600 LIGHT IS STRONGEST HERE IN THIS 1800 01:23:26,600 --> 01:23:30,840 SAMPLE IN TERMS OF RELATIONSHIP 1801 01:23:30,840 --> 01:23:38,480 WITH MORTALITY. RENAL MEASURES 1802 01:23:38,480 --> 01:23:40,880 SIFT ATTIN C IS STRONGEST AND 1803 01:23:40,880 --> 01:23:42,320 QUITE STRONG AND NUTRITION IS A 1804 01:23:42,320 --> 01:23:45,240 SET OF MARKERS THAT ALL PROBABLY 1805 01:23:45,240 --> 01:23:51,360 RELATE FAIRLY SIMILAR LY. 1806 01:23:51,360 --> 01:23:55,720 LIPIDS, CHOLESTEROLS AND 1807 01:23:55,720 --> 01:23:58,360 TRIGLYCERIDES RELATE FAIRLY 1808 01:23:58,360 --> 01:24:04,240 SIMILARLY AND CIRCULATORY LIVER. 1809 01:24:04,240 --> 01:24:10,400 NOW, I LOOKED AT THE SCORES 1810 01:24:10,400 --> 01:24:12,160 ACROSS ALL OF THE 12 SYSTEMS AND 1811 01:24:12,160 --> 01:24:14,720 GENERAL AGING MARKERS TO SAY 1812 01:24:14,720 --> 01:24:18,160 THAT ARE THEY TOO RELATED TO 1813 01:24:18,160 --> 01:24:22,320 EACH OTHER? 1814 01:24:22,320 --> 01:24:27,240 ARE THEY EXPLAINING SAME THING? 1815 01:24:27,240 --> 01:24:29,760 SENSES IS CORRELATION AS CROSS 1816 01:24:29,760 --> 01:24:31,280 ALL SYSTEMS ARE NOT THAT STRONG 1817 01:24:31,280 --> 01:24:32,880 AND STRONGEST WITH GENERAL AGING 1818 01:24:32,880 --> 01:24:35,000 MEASURE THAT IS PROBABLY GOOD, 1819 01:24:35,000 --> 01:24:36,440 SENSIBLE, FOR THE WAY THAT WE 1820 01:24:36,440 --> 01:24:39,400 LOOK AT THE WORLD. 1821 01:24:39,400 --> 01:24:42,120 NONE OF THEM REALLY REACH WHAT 1822 01:24:42,120 --> 01:24:45,720 WE WOULD SAY IS LEVEL OF 1823 01:24:45,720 --> 01:24:46,600 MULTI-COLLINIARITY THAT WOULD 1824 01:24:46,600 --> 01:24:48,120 PREVENT EVERYONE FROM LOOKING AT 1825 01:24:48,120 --> 01:24:50,720 MEASURES AT SAME TIME AND ONES 1826 01:24:50,720 --> 01:24:53,840 WITH HIGHEST LEVEL OF 1827 01:24:53,840 --> 01:24:57,360 CORRELATION OR RENAL MARKERS 1828 01:24:57,360 --> 01:25:01,160 RELATED TO SOME SYSTEMS WITH A 1829 01:25:01,160 --> 01:25:03,360 .6 CORRELATION COEFFICIENT AND 1830 01:25:03,360 --> 01:25:12,120 MOST OTHERS ARE RELATIVELY LOW 1831 01:25:12,120 --> 01:25:14,400 AND COULD END OF A LEVEL TO BE 1832 01:25:14,400 --> 01:25:15,800 ENTERED INTO A MODEL 1833 01:25:15,800 --> 01:25:18,080 SIMULTANEOUSLY. 1834 01:25:18,080 --> 01:25:22,120 THAT IS WHAT WE DO NEXT. 1835 01:25:22,120 --> 01:25:27,560 WE NOW GO TO THE TESTING SAMPLE. 1836 01:25:27,560 --> 01:25:31,640 WE TAKE INDICATORS FOR EACH 1837 01:25:31,640 --> 01:25:36,600 SYSTEM THAT WERE DEVELOPED USING 1838 01:25:36,600 --> 01:25:39,040 WEIGHTS ON BIOMARKERS SHOWN TO 1839 01:25:39,040 --> 01:25:40,320 MAKE INDIVIDUAL SYSTEM MEASURES 1840 01:25:40,320 --> 01:25:46,480 TO ELATE THEM TO MORTALITY DOING 1841 01:25:46,480 --> 01:25:53,120 THAT, WE REDUCED OUR 70 MEASURES 1842 01:25:53,120 --> 01:26:01,280 HERE TO 12 MEASURES DIDN'T 1843 01:26:01,280 --> 01:26:03,960 INCLUDE GENERAL AGING MEASURE IN 1844 01:26:03,960 --> 01:26:08,760 FIRST REGRESSION AND SYSTEM ON 1845 01:26:08,760 --> 01:26:16,400 MORTALITY 5 SYSTEMS ARE RELEVANT 1846 01:26:16,400 --> 01:26:25,240 AND CARDIOVASCULAR AND 1847 01:26:25,240 --> 01:26:27,720 RESPIRATORY AND NEXT STEP IS TO 1848 01:26:27,720 --> 01:26:31,000 THEN INTRODUCE GENERAL AGING 1849 01:26:31,000 --> 01:26:35,760 MEASURE AND IN THEORY THAT 1850 01:26:35,760 --> 01:26:38,000 PRECEDES THE DOWNSTREAM SYSTEM 1851 01:26:38,000 --> 01:26:39,080 MEASURES AND QUESTION IS WHETHER 1852 01:26:39,080 --> 01:26:44,640 GENERAL AGING MEASURE ACTUALLY 1853 01:26:44,640 --> 01:26:47,760 ELIMINATES THE SIGNIFICANCE OF 1854 01:26:47,760 --> 01:26:50,640 SOME DOWNSTREAM MEASURES AND HOW 1855 01:26:50,640 --> 01:26:53,400 IT EXPLAINS IN AND OF ITSELF AND 1856 01:26:53,400 --> 01:26:55,600 ANSWER IS STRONGEST MEASURE HERE 1857 01:26:55,600 --> 01:26:58,480 IN TERMS OF MORTALITY PREDICTION 1858 01:26:58,480 --> 01:27:00,440 IS GENERAL AGING MEASURE AND 1859 01:27:00,440 --> 01:27:03,200 THAT IS TOP LINE THAT IS BY FAR 1860 01:27:03,200 --> 01:27:05,160 STRONGEST AND WHAT IS MAINTAINED 1861 01:27:05,160 --> 01:27:08,760 AMONG OTHER SYSTEMS ARE 1862 01:27:08,760 --> 01:27:12,600 CARDIOVASCULAR MEASURE AND 1863 01:27:12,600 --> 01:27:15,720 RESPIRATORY MEASURE AND OTHER 1864 01:27:15,720 --> 01:27:22,720 SYSTEMS THAT WERE SIGNIFICANT 1865 01:27:22,720 --> 01:27:25,160 BECOMES INSIGNIFICANT AND STRONG 1866 01:27:25,160 --> 01:27:27,720 LENGTH OF GENERAL AGING MATTER 1867 01:27:27,720 --> 01:27:35,680 AND MORTALITY OUTCOME AND IF I 1868 01:27:35,680 --> 01:27:37,800 LOOK AT DIFFERENCES OBSERVED IN 1869 01:27:37,800 --> 01:27:39,560 MORTALITY IN AGE AND SEX AND 1870 01:27:39,560 --> 01:27:42,560 RACE AND EDUCATION MOST HAVE 1871 01:27:42,560 --> 01:27:49,920 BEEN EXPLAINED BY THESE SYSTEM 1872 01:27:49,920 --> 01:27:51,720 MEASURES IN GENERAL AGING SO 1873 01:27:51,720 --> 01:27:55,720 ALMOST NONE ARE SIGNIFICANT 1874 01:27:55,720 --> 01:27:56,440 ANYM 1875 01:27:56,440 --> 01:27:57,480 ANYMORE. 1876 01:27:57,480 --> 01:28:04,800 IT IS WHAT I WOULD EXPECT AS IF 1877 01:28:04,800 --> 01:28:07,040 THEORETICALLY POZITIED THAT 1878 01:28:07,040 --> 01:28:11,840 THOSE ARE METHODS BY WHICH 1879 01:28:11,840 --> 01:28:15,240 SOCIAL STATUS GETS UNDER THE 1880 01:28:15,240 --> 01:28:20,760 SKIN AND IS FOR US TO EXPLAIN 1881 01:28:20,760 --> 01:28:23,880 DIFFERENCES AND SUMMARY I WOULD 1882 01:28:23,880 --> 01:28:27,720 SAY CARDIOVASCULAR RESPIRATORY 1883 01:28:27,720 --> 01:28:29,440 GENERAL SYSTEMS ARE SIGNIFICANT 1884 01:28:29,440 --> 01:28:32,480 EXPLAINING MORTALITY AND GENERAL 1885 01:28:32,480 --> 01:28:38,680 AGING MECHANISM ELIMINATES THREE 1886 01:28:38,680 --> 01:28:42,280 SYSTEMS EXPLAINING VARIANCE 1887 01:28:42,280 --> 01:28:47,720 ADAPTIVE IMMUNE CIRCULATORY AND 1888 01:28:47,720 --> 01:28:48,760 NEUROLOGICAL AND THINK 1889 01:28:48,760 --> 01:28:50,200 IMPORTANCE OF GENERAL AGING 1890 01:28:50,200 --> 01:28:52,800 MEASURE AND GRIM AGE IN PHENOAGE 1891 01:28:52,800 --> 01:28:56,040 RE-ENFORCE VALUE OF EPIGENETIC 1892 01:28:56,040 --> 01:28:59,160 DNAM AS AN UNDERLYING MECHANISM 1893 01:28:59,160 --> 01:29:05,800 OF THIS AGING PROCESS. 1894 01:29:05,800 --> 01:29:10,320 SOME OF THE MARKERS APPEARING TO 1895 01:29:10,320 --> 01:29:13,640 BE IMPORTANT FOR MORTALITY 1896 01:29:13,640 --> 01:29:15,720 PREDICTION ARE PERHAPS SOMEWHAT 1897 01:29:15,720 --> 01:29:18,000 SURPRISING IF GOING TO LOOK FOR 1898 01:29:18,000 --> 01:29:21,960 A HALF DOZEN MARKERS THEY MIGHT 1899 01:29:21,960 --> 01:29:24,040 NOT BE THESE. 1900 01:29:24,040 --> 01:29:28,600 MACHINE LEARNING DOES SORT OF 1901 01:29:28,600 --> 01:29:34,840 INDICATE THAT PRO-BNP IS AN 1902 01:29:34,840 --> 01:29:43,640 IMPORTANT MARKER MOMMING TO -- 1903 01:29:43,640 --> 01:29:50,720 AND GENERAL AGING IN SYSTEMS WE 1904 01:29:50,720 --> 01:29:52,600 INVESTIGATED EXPLAIN MOST SOCIAL 1905 01:29:52,600 --> 01:29:56,200 DIFFERENCE WRANDZ DO WE GO FROM 1906 01:29:56,200 --> 01:30:06,640 HERE? GENERAL AGING IS 1907 01:30:07,800 --> 01:30:09,360 STRONGEST PREDICTOR OF MORTALITY 1908 01:30:09,360 --> 01:30:11,880 AND OTHER PREDICTORS SEEM TO 1909 01:30:11,880 --> 01:30:15,720 INDICATE FAILURE OF SYSTEMS AND 1910 01:30:15,720 --> 01:30:19,720 PRO-BNP BEING STRONG IN 1911 01:30:19,720 --> 01:30:21,440 CARDIOVASCULAR SYSTEM IS 1912 01:30:21,440 --> 01:30:23,360 INDICATOR OF FAILING HARD AND 1913 01:30:23,360 --> 01:30:26,760 YOU HAVE A SET OF INDICATORS OF 1914 01:30:26,760 --> 01:30:28,800 SYSTEM FAILURE FOR PHYSIOLOGICAL 1915 01:30:28,800 --> 01:30:30,960 SYSTEMS ON TOP OF GENERAL AGING 1916 01:30:30,960 --> 01:30:34,160 MEASURE THAT IS WHAT EXPLAINS 1917 01:30:34,160 --> 01:30:38,200 THIS MORTALITY. NOW, I'M ONLY 1918 01:30:38,200 --> 01:30:42,120 ABLE -- I WAS ABLE TO 1919 01:30:42,120 --> 01:30:44,080 INVESTIGATE IN THIS ANALYSIS 1920 01:30:44,080 --> 01:30:47,440 MORTALITY WITHIN 4 YEARS AND 1921 01:30:47,440 --> 01:30:51,480 DATA THAT IS COLLECTED IN 2016 1922 01:30:51,480 --> 01:30:55,280 AND MORTALITY IS UP THROUGH 2020 1923 01:30:55,280 --> 01:30:57,920 AND IF INTERESTED IN AGING 1924 01:30:57,920 --> 01:31:00,240 PROCESS YOU DON'T WANT TO 1925 01:31:00,240 --> 01:31:02,760 PREDICT SHORT TERM MORTALITY YOU 1926 01:31:02,760 --> 01:31:07,200 WANT LONGER TERM MORTALITY MY 1927 01:31:07,200 --> 01:31:11,000 GUESS LOOKING AT LONGER TERM 1928 01:31:11,000 --> 01:31:11,760 MORTALITY, YOU WOULD GET A 1929 01:31:11,760 --> 01:31:15,360 DIFFERENT SET OF INDICATORS THAT 1930 01:31:15,360 --> 01:31:18,040 WOULD COME OUT STRONG. 1931 01:31:18,040 --> 01:31:20,800 THAT BUILDS ON EARLIER WORK AND 1932 01:31:20,800 --> 01:31:23,720 OTHER WORK WE HAVE DONE WHEN WE 1933 01:31:23,720 --> 01:31:27,760 LOOK AT WHAT ARE PREDICTORS OF 1934 01:31:27,760 --> 01:31:31,000 DIFFERENT OUTCOMES CLEARLY AGE 1935 01:31:31,000 --> 01:31:34,560 RELATED IMPORTANT HEALTH OURT 1936 01:31:34,560 --> 01:31:37,360 COMES INCLUDING COGNITIVE 1937 01:31:37,360 --> 01:31:39,600 FUNCTIONING AND LOSS OF PHYSICAL 1938 01:31:39,600 --> 01:31:47,560 FUNCTIONING AND MULTIMORBIDITY 1939 01:31:47,560 --> 01:31:48,920 WE END UP WITH DIFFERENT MARKERS 1940 01:31:48,920 --> 01:31:52,920 AND HOW THINGS WILL GO. MORE 1941 01:31:52,920 --> 01:31:56,120 MARKERS WE GET, MORE DIFFERENCES 1942 01:31:56,120 --> 01:31:59,520 WE WILL GET ACROSS INDIVIDUAL 1943 01:31:59,520 --> 01:32:00,600 BIOMARKERS PREDICTING OUTCOMES. 1944 01:32:00,600 --> 01:32:03,640 WE HAVE DONE THIS ALREADY FOR 1945 01:32:03,640 --> 01:32:07,760 COGNITION. WE KNOW THAT 1946 01:32:07,760 --> 01:32:10,360 NEUROLOGICAL MARK ERRS COME OUT 1947 01:32:10,360 --> 01:32:11,760 STRONGEST FOR COGNITION AND 1948 01:32:11,760 --> 01:32:14,800 GENERAL AGING MEASURE AND FEEL 1949 01:32:14,800 --> 01:32:16,480 LIKE WHILE WE HAVE BEEN DOING 1950 01:32:16,480 --> 01:32:18,560 THIS A LONG TIME, PREDICTORS 1951 01:32:18,560 --> 01:32:21,200 THAT AS WE GET MORE AND MORE 1952 01:32:21,200 --> 01:32:23,120 PREDICTORS TO ADD INTO MODELS, 1953 01:32:23,120 --> 01:32:24,640 WE GET DIFFERENT PREDICTORS 1954 01:32:24,640 --> 01:32:27,200 COMING OUT OF THE MODELS AND WE 1955 01:32:27,200 --> 01:32:28,560 ARE NOT DONE YET. 1956 01:32:28,560 --> 01:32:31,400 WE HAVE CERTAINLY MORE TO DO IN 1957 01:32:31,400 --> 01:32:35,440 TERMS OF INTEGRATING BASIC 1958 01:32:35,440 --> 01:32:38,320 HALLMARKS OF AGING OR 1959 01:32:38,320 --> 01:32:39,560 GEROSCIENCE MEASURES THAT ARE 1960 01:32:39,560 --> 01:32:41,960 INTO A GENERAL AGING MEASURE. 1961 01:32:41,960 --> 01:32:47,760 I THINK THAT THIS OFFERS A 1962 01:32:47,760 --> 01:32:51,520 POTENTIAL WAY TO GO IN THE 1963 01:32:51,520 --> 01:33:01,960 FUTURE TO DEVELOP BETTER 1964 01:33:02,840 --> 01:33:03,400 PREDICTOR MODELS AND 1965 01:33:03,400 --> 01:33:05,320 LONGITUDINAL MEASUREMENT HEALTH 1966 01:33:05,320 --> 01:33:07,360 AND RETIREMENT STUDY COMING OUT 1967 01:33:07,360 --> 01:33:08,720 OF FIELD FOR SECOND TIME 1968 01:33:08,720 --> 01:33:10,200 MEASUREMENT THAT WAS DELAYED BY 1969 01:33:10,200 --> 01:33:12,920 THE PAN DEM THAK WE WILL HAVE 1970 01:33:12,920 --> 01:33:15,240 MEASURES OF CHANGE THAT ARE 1971 01:33:15,240 --> 01:33:18,160 BEGINNING IN THE NEXT YEAR. 1972 01:33:18,160 --> 01:33:21,560 SO, THANK YOU. 1973 01:33:21,560 --> 01:33:24,840 >>[APPLAUSE]. 1974 01:33:24,840 --> 01:33:26,760 >>GOOD MORNING, EVERYONE. I 1975 01:33:26,760 --> 01:33:28,920 APOLOGIZE FOR NOT BEING THERE IN 1976 01:33:28,920 --> 01:33:30,480 PERSON TODAY. 1977 01:33:30,480 --> 01:33:32,040 HOW DOES THAT LOOK? 1978 01:33:32,040 --> 01:33:35,240 >>IT IS GOOD. GO AHEAD. 1979 01:33:35,240 --> 01:33:35,560 THANKS. 1980 01:33:35,560 --> 01:33:37,160 >>EXCELLENT. THANK YOU. FIRST 1981 01:33:37,160 --> 01:33:42,720 OF ALL, I'M SUPER EXCITED AND A 1982 01:33:42,720 --> 01:33:44,960 LITTLE HUMBLED TO HEAR 1983 01:33:44,960 --> 01:33:45,960 PRESENTATIONS YESTERDAY AND THIS 1984 01:33:45,960 --> 01:33:47,800 MORNING AND JUST THE IDEA THAT 1985 01:33:47,800 --> 01:33:50,360 SOME CONCEPTS FROM BASIC BIOLOGY 1986 01:33:50,360 --> 01:33:54,480 FROM AGING HAVE MADE IT INTO A 1987 01:33:54,480 --> 01:33:57,720 NEW WORLD OF HUMAN AGING IS 1988 01:33:57,720 --> 01:33:58,680 FANTASTICALLY EXCITING AND 1989 01:33:58,680 --> 01:34:01,360 THANKS TO ROHAN AND 1990 01:34:01,360 --> 01:34:02,480 [INDISCERNIBLE] BEFORE HIM TO 1991 01:34:02,480 --> 01:34:03,040 MAKE THAT HAPPEN. 1992 01:34:03,040 --> 01:34:05,560 THE TOPIC HERE IS A LITTLE BIT 1993 01:34:05,560 --> 01:34:07,680 OF AN OUTLIAR. REASON WE ARE 1994 01:34:07,680 --> 01:34:11,280 TALKING ABOUT IT, WE HAD A 1995 01:34:11,280 --> 01:34:12,720 PRESESSION CHAT. AND ONE 1996 01:34:12,720 --> 01:34:14,480 QUESTION THAT AROSE THAT I HAVE 1997 01:34:14,480 --> 01:34:16,400 BEEN THINKING ABOUT FOR A WHILE 1998 01:34:16,400 --> 01:34:18,520 ACTUALLY IS THE NOTION THAT WE 1999 01:34:18,520 --> 01:34:21,680 ARE TALKING ABOUT GEROPRETEKTORS 2000 01:34:21,680 --> 01:34:23,560 AND MEASURES OF AGING BUT IS NOT 2001 01:34:23,560 --> 01:34:25,880 REALLY CLEAR TO ME WE HAVE A 2002 01:34:25,880 --> 01:34:27,800 PATHWAY TOWARDS THE NEXT 2003 01:34:27,800 --> 01:34:29,000 GENERATION OR GENERATION AFTER 2004 01:34:29,000 --> 01:34:31,320 THAT OF INTERVENTIONS IN AGING. 2005 01:34:31,320 --> 01:34:34,080 SO, THE QUESTION IS REALLY, IS 2006 01:34:34,080 --> 01:34:36,880 THERE AN AGING INTERVENTION 2007 01:34:36,880 --> 01:34:37,320 PIPELINE? 2008 01:34:37,320 --> 01:34:39,640 I WOULD LIKE TO CONTRACT WHAT WE 2009 01:34:39,640 --> 01:34:41,800 HAVE BEEN CURRENTLY DOING IN 2010 01:34:41,800 --> 01:34:43,720 ACADEMIC RESEARCH TO WHAT YOU 2011 01:34:43,720 --> 01:34:46,520 WOULD SEE IN THE PHARMACEUTICAL 2012 01:34:46,520 --> 01:34:47,720 INDUSTRY WHERE PIPELINE IS QUITE 2013 01:34:47,720 --> 01:34:50,760 CLEAR STARTING WITH MILLIONS OF 2014 01:34:50,760 --> 01:34:51,960 DIFFERENT CHEMICAL STRUCTURES 2015 01:34:51,960 --> 01:34:54,960 AND GO AFTER A SINGLE PROTEIN 2016 01:34:54,960 --> 01:34:56,840 TARGET AND SINGLE ACTIVITY AND 2017 01:34:56,840 --> 01:34:59,080 NARROW DOWN QUICKLY TO SERIES OF 2018 01:34:59,080 --> 01:35:00,800 HITS AND LEAD COMPOUNDS THAT GO 2019 01:35:00,800 --> 01:35:03,760 INTO PRECLINICAL STUDIES. 2020 01:35:03,760 --> 01:35:05,640 THERE HAS BEEN SOME ACTIVITY 2021 01:35:05,640 --> 01:35:07,760 LIKE THAT IN AGING ITSELF. 2022 01:35:07,760 --> 01:35:10,600 BUT, IT IS NOT CLEAR THAT THIS 2023 01:35:10,600 --> 01:35:14,760 IS THE SAME KIND OF PROCESS THAT 2024 01:35:14,760 --> 01:35:20,520 PARTLY IS IN AGING OUTCOME IS 2025 01:35:20,520 --> 01:35:22,640 AGING PATHOLOGY OR LIFESPAN 2026 01:35:22,640 --> 01:35:26,320 ITSELF AND TEND TO BE LIMITED TO 2027 01:35:26,320 --> 01:35:28,200 FUNCTIONAL COMPOUNDS IN SCREENS 2028 01:35:28,200 --> 01:35:29,760 LAERNL THAN DIRECT SCREENS WE 2029 01:35:29,760 --> 01:35:31,960 THINK ABOUT IN PHARMACEUTICAL 2030 01:35:31,960 --> 01:35:34,000 COMPANY DO WE NEED A PIPELINE? 2031 01:35:34,000 --> 01:35:35,480 WHAT DOES IT LK LIKE NOW? 2032 01:35:35,480 --> 01:35:38,360 THERE IS OBVIOUSLY CHALLENGES 2033 01:35:38,360 --> 01:35:40,080 THINKING OF PROCESSES OF 2034 01:35:40,080 --> 01:35:41,800 DISCOVERY THAT ARE HUMAN 2035 01:35:41,800 --> 01:35:43,920 RELEVANT CLEARLY AND COSTS OF 2036 01:35:43,920 --> 01:35:45,280 TRANSLATION INTO THE PRECLINICAL 2037 01:35:45,280 --> 01:35:49,000 WORLD ARE LARGE THAT IS A MAJOR 2038 01:35:49,000 --> 01:35:52,120 BARRIER AND HUMAN TRIALS IS ON 2039 01:35:52,120 --> 01:35:53,680 AGING ITSELF THAT I WILL KEEP 2040 01:35:53,680 --> 01:35:55,720 SAYING THAT. IT IS REALLY A 2041 01:35:55,720 --> 01:35:58,040 SMALL NUMBER OF INTERVENTIONS 2042 01:35:58,040 --> 01:35:59,720 WITH ACTUALLY RELATIVELY SMALL 2043 01:35:59,720 --> 01:36:01,760 EFFECTS ON AGING AND ANIMAL 2044 01:36:01,760 --> 01:36:04,280 MODELS AND WE NEED TO REALLY 2045 01:36:04,280 --> 01:36:06,600 THINK ABOUT GENDER SPECIFIC 2046 01:36:06,600 --> 01:36:09,440 EFFECTS THAT IS CLEAR FROM MOST 2047 01:36:09,440 --> 01:36:10,680 EXPERIMENTS INCLUDING 2048 01:36:10,680 --> 01:36:12,320 INTERVENTIONAL TESTING PROGRAM 2049 01:36:12,320 --> 01:36:13,920 EXPERIMENTS GENDER SPECIFIC 2050 01:36:13,920 --> 01:36:15,200 EFFECTS ARE COMMON. 2051 01:36:15,200 --> 01:36:18,680 WE REALLY HAVE NOT GOTTEN INTO 2052 01:36:18,680 --> 01:36:20,280 GENETIC BACKGROUND OR 2053 01:36:20,280 --> 01:36:21,800 PERSONALIZED EFFECTS AT ALL. 2054 01:36:21,800 --> 01:36:22,560 HERE IS GOOD NEWS. 2055 01:36:22,560 --> 01:36:25,080 GOOD NEWS IS THAT WE HAVE 2056 01:36:25,080 --> 01:36:27,240 REASONABLE CANDIDATES THAT ARE 2057 01:36:27,240 --> 01:36:32,320 BEING TESTED IN -- IN CLINICAL 2058 01:36:32,320 --> 01:36:35,760 TRIALS. 2059 01:36:35,760 --> 01:36:38,160 RAPAMYCIN FORMIN AND METABOLITES 2060 01:36:38,160 --> 01:36:42,600 AND SO ON AND LOOKING AT NUMBER 2061 01:36:42,600 --> 01:36:47,800 OF PUBLICATIONS HERE CITING 2062 01:36:47,800 --> 01:36:51,560 COMPOUNDS AND DRUGS AND LIFESPAN 2063 01:36:51,560 --> 01:36:54,680 THERE IS [INDISCERNIBLE] AND 2064 01:36:54,680 --> 01:36:57,520 WHERE THIS STARTED FUNDAMENTAL 2065 01:36:57,520 --> 01:36:59,080 BIOLOGY THAT ILLUSTRATED THAT 2066 01:36:59,080 --> 01:37:02,680 COMPOUNDS WERE INTERACTING WITH 2067 01:37:02,680 --> 01:37:05,520 AGING ITSELF CAME FROM MODEL 2068 01:37:05,520 --> 01:37:06,160 SYSTEMS LIKE [INDISCERNIBLE] AND 2069 01:37:06,160 --> 01:37:10,240 YEAST AND GENETIC ANALYSIS AND 2070 01:37:10,240 --> 01:37:14,840 COMPOUND TREATMENTS. 2071 01:37:14,840 --> 01:37:23,800 HOW DO WE TARGET AGING? 2072 01:37:23,800 --> 01:37:26,680 GEROSCIENCE CONCEPT -- HOW DO 2073 01:37:26,680 --> 01:37:30,720 YOU TARGET AGING AND NEXT SLIDE 2074 01:37:30,720 --> 01:37:32,880 HOPEFULLY WON'T ANNOY TOO MANY 2075 01:37:32,880 --> 01:37:34,960 PEOPLE AND SOMETHING TO SAY TO 2076 01:37:34,960 --> 01:37:37,040 STUDENTS THAT I THINK IS WORTH 2077 01:37:37,040 --> 01:37:42,680 THINKING ABOUT THAT DOESN'T AMRI 2078 01:37:42,680 --> 01:37:47,120 TO VAST SWANLS OF AGING RESEARCH 2079 01:37:47,120 --> 01:37:50,160 IF NOT DOCTOR YOU MIGHT NOT BE 2080 01:37:50,160 --> 01:37:52,040 TARGETING AGING THAT IS OLD IDEA 2081 01:37:52,040 --> 01:37:55,240 GOING TO TOM JOHNSON IN EARLY 2082 01:37:55,240 --> 01:37:57,640 1990S WHO WAS YOU KNOW A PIONEER 2083 01:37:57,640 --> 01:38:00,840 IN DOG GENETIC RESEARCH IN 2084 01:38:00,840 --> 01:38:02,600 LIFESPAN AND ELEGANCE AND MADE A 2085 01:38:02,600 --> 01:38:05,480 SIMPLE POINT IT IS VERY EASY TO 2086 01:38:05,480 --> 01:38:07,200 MAKE ANIMALS SICK WITH GENETIC 2087 01:38:07,200 --> 01:38:10,720 MUTATIONS IT IS HARDER TO FIND 2088 01:38:10,720 --> 01:38:13,560 GENETIC MUTATIONS THAN HAVE 2089 01:38:13,560 --> 01:38:14,720 ANIMALS LIVE LONGER WHEN YOU 2090 01:38:14,720 --> 01:38:16,520 FIND MUTATIONS IT IS LIKELY YOU 2091 01:38:16,520 --> 01:38:18,400 ARE WORKING ON AGING PROCESS AND 2092 01:38:18,400 --> 01:38:20,680 WHAT HAS GIVEN US 20 YEARS OF 2093 01:38:20,680 --> 01:38:23,320 ENRICHED GENETIC ANALYSIS OF 2094 01:38:23,320 --> 01:38:25,640 LIFESPAN AND ESSENTIALLY MOST 2095 01:38:25,640 --> 01:38:27,840 HALLMARKS OF AGING COME FROM 2096 01:38:27,840 --> 01:38:29,840 CENTRAL PRINCIPLE AND THINKING 2097 01:38:29,840 --> 01:38:30,960 ABOUT INTERVENTIONS WHETHER 2098 01:38:30,960 --> 01:38:34,640 NUTRITIONAL OR CHEMICAL OR DRUG 2099 01:38:34,640 --> 01:38:36,560 DEVELOPMENT IS WORTH COMING BACK 2100 01:38:36,560 --> 01:38:39,440 TO CONCEPT AND ASSUMING TO MAKE 2101 01:38:39,440 --> 01:38:40,080 ANIMALS LIVE LONGER AND THING 2102 01:38:40,080 --> 01:38:43,640 THAT GETS YOU EXCITED A COUPLE 2103 01:38:43,640 --> 01:38:46,720 MORE SURVIVAL [INDISCERNIBLE] 2104 01:38:46,720 --> 01:38:47,800 FROM LAB AT [INDISCERNIBLE] AND 2105 01:38:47,800 --> 01:38:50,360 BLACK CURVE THAT IS HIDDEN BY 2106 01:38:50,360 --> 01:38:53,240 ORANGE CURVE IS CONTROL ANIMALS 2107 01:38:53,240 --> 01:38:55,360 TWOOND GENETIC INTERVENTIONS 2108 01:38:55,360 --> 01:38:58,480 HERE ONE IN SIGNALING PATHWAY 2109 01:38:58,480 --> 01:39:02,680 AND ONE IN MTORE PATHWAY AND 2110 01:39:02,680 --> 01:39:05,840 DRAMATIC CHANGES ON ANIMAL 2111 01:39:05,840 --> 01:39:09,040 INCREASING LIFESPAN HERE TO FIVE 2112 01:39:09,040 --> 01:39:11,880 FOLD AND REMARKABLE THINGS ARE 2113 01:39:11,880 --> 01:39:14,280 POSSIBLE AND SOME ACTIVITY IS IN 2114 01:39:14,280 --> 01:39:18,600 TRYING TO REPRODUCE THIS TO 2115 01:39:18,600 --> 01:39:29,160 GENERATION OF INTERVENTIONS AND 2116 01:39:29,800 --> 01:39:33,040 -- METABOLITES AND NUTRIENTS AND 2117 01:39:33,040 --> 01:39:35,840 NOT BY OUR LAB BUT MANY OTHER 2118 01:39:35,840 --> 01:39:38,240 LABS AND INCLUDING 2119 01:39:38,240 --> 01:39:44,560 [INDISCERNIBLE] WHO HAS DONE. 2120 01:39:44,560 --> 01:39:46,920 BLACK CURVE IS THE CONTROL WORMS 2121 01:39:46,920 --> 01:39:50,720 AND WE HAVE SERIES OF 2122 01:39:50,720 --> 01:39:52,560 CONCENTRATIONS OF COMPOUND HERE 2123 01:39:52,560 --> 01:39:54,520 THAT HAPPENS TO BIND AMILLOID 2124 01:39:54,520 --> 01:39:56,520 THAT I WILL COME BACK TO LATER 2125 01:39:56,520 --> 01:39:59,120 AND YOU SEE HERE OPTIMAL 2126 01:39:59,120 --> 01:40:01,880 CONCENTRATION IN THE BLUE IS 2127 01:40:01,880 --> 01:40:04,040 SHIFTING SURVIVAL CURVE 2128 01:40:04,040 --> 01:40:05,640 DRAMATICALLY TO RIGHT 70% 2129 01:40:05,640 --> 01:40:07,640 INCREASE IN LIFESPAN THAT IS 2130 01:40:07,640 --> 01:40:09,840 POSSIBLE TO FIND CHEMICAL 2131 01:40:09,840 --> 01:40:11,840 INTERVENTIONS THAT HAVE DRAMATIC 2132 01:40:11,840 --> 01:40:16,720 EFFECTS ON LIFESPAN IN THIS 2133 01:40:16,720 --> 01:40:20,800 SIMPLE CELEGANS AND COMPLEX 2134 01:40:20,800 --> 01:40:23,560 SLIDE TO ACKNOWLEDGE ROLE OF 2135 01:40:23,560 --> 01:40:24,960 THIS INTERVENTION TESTING 2136 01:40:24,960 --> 01:40:26,920 PROGRAM FUNDED BY NIA AND WHAT 2137 01:40:26,920 --> 01:40:30,920 WE HAVE HERE ARE TWO GRAPHS WITH 2138 01:40:30,920 --> 01:40:35,600 TWO DIFFERENT COMPOUNDS AND 2139 01:40:35,600 --> 01:40:38,080 THYOFLAVIN T COMPOUND ON RIGHT 2140 01:40:38,080 --> 01:40:40,960 AND TC CYCLE ON LEFT AND EACH 2141 01:40:40,960 --> 01:40:42,600 POINT ON GRAPHS IS THE 2142 01:40:42,600 --> 01:40:44,160 INDIVIDUAL LIFESPAN EXPERIMENT 2143 01:40:44,160 --> 01:40:48,360 WITH SOMETHING LIKE 100 2144 01:40:48,360 --> 01:40:52,480 INDIVIDUAL C ELE GANS WORMS AND 2145 01:40:52,480 --> 01:40:54,480 SHOWING ANYTHING ABOVE DOTTED 2146 01:40:54,480 --> 01:40:56,920 LINE IS LIFESPAN INTERVENTION 2147 01:40:56,920 --> 01:40:59,840 AND DESPITE VARIABILITY YOU SEE 2148 01:40:59,840 --> 01:41:04,200 HERE EKG METABOLITE AND COMPOUND 2149 01:41:04,200 --> 01:41:09,560 ARE DOG WELL AT EXTENDING WORM 2150 01:41:09,560 --> 01:41:11,960 LIFESPAN AND PATRICK AND MONICA 2151 01:41:11,960 --> 01:41:14,200 THERE IS COLOR CODING HERE IN 2152 01:41:14,200 --> 01:41:17,440 DIFFERENT LABS THREE LABS YOU 2153 01:41:17,440 --> 01:41:19,120 SEE LIFESPAN EXTENSION GIVING 2154 01:41:19,120 --> 01:41:20,160 CONFIDENCE AND SECOND POINT HERE 2155 01:41:20,160 --> 01:41:24,000 USING MULTIPLE STRAINS AND X 2156 01:41:24,000 --> 01:41:26,040 AXIS YOU SEE A LAB STRAIN AND 2157 01:41:26,040 --> 01:41:28,920 USUAL STRAIN EVERYBODY USES AND 2158 01:41:28,920 --> 01:41:31,600 TWO WILD STRAINS AND REMIT OF 2159 01:41:31,600 --> 01:41:35,280 THIS CITP IS LOOKING AT STRAINS 2160 01:41:35,280 --> 01:41:37,280 WITH GREAT GENETIC DIVERSITY AND 2161 01:41:37,280 --> 01:41:39,720 MAP HERE IS ILLUSTRATION OF 2162 01:41:39,720 --> 01:41:41,800 WHERE THESE COME FROM ALL OVER 2163 01:41:41,800 --> 01:41:44,360 THE WORLD YOU FIND SPECIES AND 2164 01:41:44,360 --> 01:41:46,680 STRAINS TESTING GENETIC 2165 01:41:46,680 --> 01:41:48,240 DIVERSITY RESPONSES TO DRUG 2166 01:41:48,240 --> 01:41:49,840 TREATMENT AND IN THESE TWO CASES 2167 01:41:49,840 --> 01:41:52,200 HERE YOU SEE THESE COMPOUNDS ARE 2168 01:41:52,200 --> 01:41:54,840 VERY ROBUSTLY EXTENDING LIFESPAN 2169 01:41:54,840 --> 01:41:57,280 ACROSS GENETIC DIVERSITY THAT 2170 01:41:57,280 --> 01:41:59,840 COULD BE IMPORTANT LATER IN 2171 01:41:59,840 --> 01:42:02,720 ASSESSING HOW TO TAKE COMPOUNDS 2172 01:42:02,720 --> 01:42:10,680 FORWARD AND IN A TRANSLATIONABLE 2173 01:42:10,680 --> 01:42:16,400 WAY. JUST ASIDE FOR NOW THAT IS 2174 01:42:16,400 --> 01:42:18,680 GRA GREAT AND PREMISE HERE 2175 01:42:18,680 --> 01:42:20,840 EXTENDING LIFESPAN YOU ARE 2176 01:42:20,840 --> 01:42:23,840 PROBABLY WORKING ON AGING AND 2177 01:42:23,840 --> 01:42:25,080 GEROSCIENCE CONCEPT COMPOUNDS 2178 01:42:25,080 --> 01:42:28,240 THEREFORE SHOULD HAVE EFFICACY 2179 01:42:28,240 --> 01:42:33,720 IN DISEASE ILLUSTRATING WITH 2180 01:42:33,720 --> 01:42:38,080 WORM EXAMPLE THEN A COUPLE MOUSE 2181 01:42:38,080 --> 01:42:40,360 EXAMP 2182 01:42:40,360 --> 01:42:40,600 EXAMPLES. 2183 01:42:40,600 --> 01:42:42,760 WHAT WE HAVE HERE IS A 2184 01:42:42,760 --> 01:42:43,880 COLLABORATION WITHBERG OT 2185 01:42:43,880 --> 01:42:49,360 SCHILLING AND WE ARE LOOKING AT 2186 01:42:49,360 --> 01:42:51,640 ACCUMULATION WITH INSOLUBLE 2187 01:42:51,640 --> 01:42:54,680 PROTEIN WITH AGE THAT IS RELATED 2188 01:42:54,680 --> 01:42:59,440 IN WAYS TO DISEASES TO ALT 2189 01:42:59,440 --> 01:43:02,080 SDIEMERS AND PAR KINSON AND 2190 01:43:02,080 --> 01:43:04,960 INSOLUBLE AGGREGATES AND FAIRLY 2191 01:43:04,960 --> 01:43:06,560 SIMPLE SYSTEM HERE THAT WE 2192 01:43:06,560 --> 01:43:09,720 EXPRESSED A HUMAN MUNO TOXIC 2193 01:43:09,720 --> 01:43:13,240 PROTEIN BETA ASSOCIATED WITH 2194 01:43:13,240 --> 01:43:14,800 ALZHEIMER'S DISEASE IN WORMS 2195 01:43:14,800 --> 01:43:17,200 COMPARING THOSE WORMS TO CONTROL 2196 01:43:17,200 --> 01:43:19,240 WORMS GOING FROM LEFT DOWN HERE 2197 01:43:19,240 --> 01:43:24,880 TO PROTOCOL DOING A DETERNLIENT 2198 01:43:24,880 --> 01:43:28,240 EXTRACTION AND DETERJIENT 2199 01:43:28,240 --> 01:43:31,880 INSOLUBLE PRAKS IS BEING 2200 01:43:31,880 --> 01:43:36,080 ANALYZED BY MASS SPECTROMETRY IN 2201 01:43:36,080 --> 01:43:41,640 BER GOTS LAB. 2202 01:43:41,640 --> 01:43:46,360 THE OTHER THING THAT HAPPENS IS 2203 01:43:46,360 --> 01:43:47,040 ACCUMULATING INSOLUBLE PROTEINS 2204 01:43:47,040 --> 01:43:50,720 AT RAPID RATE THAT IS QUANTITY 2205 01:43:50,720 --> 01:43:52,520 TITTATION ON RIGHT HERE AND 2206 01:43:52,520 --> 01:44:03,040 SEEING THESE PROTEINS IN FOLDING 2207 01:44:03,040 --> 01:44:05,200 THESE WORMS ARE DAY 1 OF 2208 01:44:05,200 --> 01:44:07,800 ADULTHOOD AND WE ARE TAKING 2209 01:44:07,800 --> 01:44:11,880 NEUROTOXIC PROTEIN ASSOCIATED 2210 01:44:11,880 --> 01:44:22,360 WITH INSOLUBLE PROTEIN AND 2211 01:44:34,440 --> 01:44:35,840 ACTIVE EXPRESSING DISEASE 2212 01:44:35,840 --> 01:44:37,880 RELATED PROTEIN IN WORMS IS 2213 01:44:37,880 --> 01:44:43,560 TAKING THIS MOLECULAR PHENOTYPE 2214 01:44:43,560 --> 01:44:44,160 ACCELERATING AGING. 2215 01:44:44,160 --> 01:44:46,720 THIS IS WHAT IT LOOKS LIKE THESE 2216 01:44:46,720 --> 01:44:49,520 WORMS ON THE LEFT HERE. LITTLE 2217 01:44:49,520 --> 01:44:53,680 WHITE ARROWS ARE POINTING TO 2218 01:44:53,680 --> 01:44:55,920 INSOLUBLE AGGREGATES OF A BETA 2219 01:44:55,920 --> 01:44:59,600 PROTEIN AND DRUG I MENTIONED SO 2220 01:44:59,600 --> 01:45:02,320 FAR COMPOUND THIGHO FLAFIN T 2221 01:45:02,320 --> 01:45:04,720 PRESENCE HERE WHERE INSOLUBLE 2222 01:45:04,720 --> 01:45:07,600 AGGREGATES FOR MUCH, MUCH LATER. 2223 01:45:07,600 --> 01:45:10,240 SO, HERE IS A EXAMPLE OF A 2224 01:45:10,240 --> 01:45:11,680 COMPOUND THAT EXTENDS LIFESPAN 2225 01:45:11,680 --> 01:45:14,040 IN THE WORM AND IS HAVING AN 2226 01:45:14,040 --> 01:45:17,640 EFFECT ON AGE-RELATED DISEASE 2227 01:45:17,640 --> 01:45:20,560 PANELOLOGY AND A BETA 2228 01:45:20,560 --> 01:45:20,920 AGGREGATION. 2229 01:45:20,920 --> 01:45:22,120 SO, COMPLEX GRAPH BUT IS SIMPLE 2230 01:45:22,120 --> 01:45:24,120 IN THE INTERPRETATION, I THINK. 2231 01:45:24,120 --> 01:45:26,720 WHAT WE HAVE GOT HERE IS A RANGE 2232 01:45:26,720 --> 01:45:29,840 OF COMPOUNDS NOW GOING BEYOND 2233 01:45:29,840 --> 01:45:33,320 THIGHO FLAFIN T AND RANGE THAT 2234 01:45:33,320 --> 01:45:35,680 EXTEND LIFESPAN IN THE WORM AND 2235 01:45:35,680 --> 01:45:38,200 ANALYSIS TAKEN BY UNIVERSITY OF 2236 01:45:38,200 --> 01:45:40,640 OREGON PART OF CIPT PROJECT 2237 01:45:40,640 --> 01:45:43,240 LOOKING AT RELATIVE RISK OF 2238 01:45:43,240 --> 01:45:45,320 PARALYSIS AND AMAZING TO EXPRESS 2239 01:45:45,320 --> 01:45:47,480 HUMAN PROTEIN IN WORMS 2240 01:45:47,480 --> 01:45:49,360 ASSOCIATED WITH ALZHEIMER'S THAT 2241 01:45:49,360 --> 01:45:52,720 MAKES THEM SICK AND IS EASY TO 2242 01:45:52,720 --> 01:45:55,040 SEE THAT WE BECOME PARALYZED AND 2243 01:45:55,040 --> 01:45:57,840 STOP MOVING ON AR PLATES YOU SEE 2244 01:45:57,840 --> 01:46:00,840 HERE A RANGE OF EFFECTS THAT IS 2245 01:46:00,840 --> 01:46:02,960 A REALLY EFFECTIVE THING THAT 2246 01:46:02,960 --> 01:46:04,640 FOCUSES ON COMPOUNDS TO RIGHT OF 2247 01:46:04,640 --> 01:46:07,520 THE GRAPH AND THESE COMPOUNDS 2248 01:46:07,520 --> 01:46:09,120 EXTEND LIFESPAN AND ARE 2249 01:46:09,120 --> 01:46:11,280 SUPPRESSING THE PARALYSIS 2250 01:46:11,280 --> 01:46:13,080 PHENOTYPE AND IN OTHER WORDS 2251 01:46:13,080 --> 01:46:15,640 THEY ARE -- THEY ARE PREVENTING 2252 01:46:15,640 --> 01:46:17,440 THE A BETA TOXICITY. 2253 01:46:17,440 --> 01:46:19,360 AND LOOK AT THE NUMBER OF 2254 01:46:19,360 --> 01:46:21,120 COMPOUNDS THAT ARE DOING THAT. 2255 01:46:21,120 --> 01:46:24,200 THIS IS AN INCREDIBLY HIGH HIT 2256 01:46:24,200 --> 01:46:25,760 RATE BASED ON ANY SCREEN YOU 2257 01:46:25,760 --> 01:46:27,320 WOULD WANT TO THINK ABOUT IN 2258 01:46:27,320 --> 01:46:29,960 TERMS OF, YOU KNOW, PREVENTING A 2259 01:46:29,960 --> 01:46:34,680 BETA TOXICITY IN ANY SYSTEM AND 2260 01:46:34,680 --> 01:46:37,760 ANY NORMAL SCREEN UNDERTAKEN BY 2261 01:46:37,760 --> 01:46:38,920 PHARMAINDUSTRY AND BY PERHAPS 2262 01:46:38,920 --> 01:46:41,680 MANY OF YOU WITH HIT RATES 2263 01:46:41,680 --> 01:46:43,920 AROUND ABOUT .1% AND HERE WE ARE 2264 01:46:43,920 --> 01:46:47,400 SEEING SOMETHING LIKE 40% OF 2265 01:46:47,400 --> 01:46:49,080 COMPOUNDS BECAUSE OF THE 2266 01:46:49,080 --> 01:46:50,360 PRESELECTION OF EXTENDING 2267 01:46:50,360 --> 01:46:53,040 LIFESPAN IN THE WORM, 40% IN 2268 01:46:53,040 --> 01:46:58,280 COMPOUNDS HAVE AN EFFECT ON THIS 2269 01:46:58,280 --> 01:46:58,920 PATHOL 2270 01:46:58,920 --> 01:47:03,680 PATHOLOGY. LOOKING AT MICE AND 2271 01:47:03,680 --> 01:47:06,560 PIO FLAFIN AND HBTX AND LARGE 2272 01:47:06,560 --> 01:47:08,960 STUDY WE DID A LATE LIFE 2273 01:47:08,960 --> 01:47:10,600 INTERVENTION WITH HBX. 2274 01:47:10,600 --> 01:47:13,200 AND WE MADE REGULAR ASSESSMENTS 2275 01:47:13,200 --> 01:47:15,800 OF FUNCTIONAL METRICS INCLUDING 2276 01:47:15,800 --> 01:47:17,080 BONE DENSITY AND HEART FUNCTION 2277 01:47:17,080 --> 01:47:19,840 AND SO ON AND OUTSTANDING RESULT 2278 01:47:19,840 --> 01:47:23,120 WAS THAT SIMON IDENTIFIED THE 2279 01:47:23,120 --> 01:47:23,800 FACT THAT MICE [INDISCERNIBLE] 2280 01:47:23,800 --> 01:47:26,680 AS HUMANS DO. THIS IS A 2281 01:47:26,680 --> 01:47:29,640 RELATIVELY GOOD SARCOPENIA 2282 01:47:29,640 --> 01:47:33,560 MODEL. OSTEOPOROSIS MODEL AND 2283 01:47:33,560 --> 01:47:35,720 COMPOUND THIGHO FLAFIN T REDUCES 2284 01:47:35,720 --> 01:47:37,280 BONE LOSS BY 30% THAT IS AS GOOD 2285 01:47:37,280 --> 01:47:39,480 AS MOST THINGS ON THE MARKET AND 2286 01:47:39,480 --> 01:47:41,920 HERE WE HAVE A COMPOUND THAT IS 2287 01:47:41,920 --> 01:47:44,360 DISCOVER THE IN WORM TO EXTEND 2288 01:47:44,360 --> 01:47:46,680 LIFESPAN TARGETING AGING 2289 01:47:46,680 --> 01:47:49,400 MECHANISM PREVENTING BETA 2290 01:47:49,400 --> 01:47:51,800 TOXICITY IN THE WORM AND MOVING 2291 01:47:51,800 --> 01:47:53,040 TO MICE HAS EFFECT ON BONE 2292 01:47:53,040 --> 01:47:54,760 HEALTH AND REMINDER THAT WORMS 2293 01:47:54,760 --> 01:47:58,320 DON'T HAVE BONES AND IS A 2294 01:47:58,320 --> 01:48:00,280 METABOLITE I MENTIONED EARLIER 2295 01:48:00,280 --> 01:48:02,560 EKG. IN THIS CASE WE DID A 2296 01:48:02,560 --> 01:48:04,280 SIMILAR STUDY DESIGN ORIGINALLY 2297 01:48:04,280 --> 01:48:06,120 AND DIDN'T DO FANCY SCANS AND 2298 01:48:06,120 --> 01:48:10,720 WHAT WE DID DO IS TO WITH 2299 01:48:10,720 --> 01:48:13,360 SUSAN'S HELP IS ADOPTING FANCY 2300 01:48:13,360 --> 01:48:15,160 REALTY INDEX THAT IS VERY 2301 01:48:15,160 --> 01:48:15,520 INTERESTING. 2302 01:48:15,520 --> 01:48:19,040 JUST LOOKING AT THE TOP LEFT 2303 01:48:19,040 --> 01:48:21,480 GRAPH HERE. THIS IS FOR A COAT 2304 01:48:21,480 --> 01:48:23,920 COLLAR. WHAT YOU SEE HERE IN 2305 01:48:23,920 --> 01:48:29,120 THE BLUE ARE THE CONTROL 2306 01:48:29,120 --> 01:48:29,640 ANIMALS. 2307 01:48:29,640 --> 01:48:32,000 YOU CAN SEE FRAILTY INDEX IS 2308 01:48:32,000 --> 01:48:34,280 RISING OVER PERT OF 18 TO 31 2309 01:48:34,280 --> 01:48:35,880 MONTHS AND RED IS WORMS ON A 2310 01:48:35,880 --> 01:48:38,680 DIET THAT IS CONTAINING ELEVATED 2311 01:48:38,680 --> 01:48:42,400 LEVELS OF EKG THAT GOES DOWN 2312 01:48:42,400 --> 01:48:44,800 WITH AGE AND IN OURSELVES AND IN 2313 01:48:44,800 --> 01:48:48,000 MICE. SO, WHAT WE ARE DOING IS 2314 01:48:48,000 --> 01:48:50,560 RESTORING EKG LEVELS TO 2315 01:48:50,560 --> 01:48:52,880 RELATIVELY NORMAL YOU SEE HERE 2316 01:48:52,880 --> 01:48:53,800 IS SUPPRESSING PARTICULAR 2317 01:48:53,800 --> 01:48:55,600 MEASURE OF FRAILTY AND GREAT 2318 01:48:55,600 --> 01:48:58,000 POWER OF FRAILTY INDEX IS 2319 01:48:58,000 --> 01:48:59,120 COMBINING SCORES TOGETHER. 2320 01:48:59,120 --> 01:49:02,520 JUST AS A QUICK VISUAL, MICE ON 2321 01:49:02,520 --> 01:49:04,040 THE RIGHT ARE CONTROLS AND IF 2322 01:49:04,040 --> 01:49:05,880 THIS IS A VIDEO THAW WOULD SEE 2323 01:49:05,880 --> 01:49:08,040 THEY WERE HAVING DIFFICULTY WITH 2324 01:49:08,040 --> 01:49:09,920 MOVEMENT AND THERE IS HIVOSIS 2325 01:49:09,920 --> 01:49:12,600 GOING ON AND YOU CAN SEE COAT 2326 01:49:12,600 --> 01:49:17,080 COLLAR AND LOSS OF FUR AND MICE 2327 01:49:17,080 --> 01:49:21,960 ON LEFT HAVE ATG-FED MICE THAT 2328 01:49:21,960 --> 01:49:23,640 ARE DOING QUITE A BIT BETTER IN 2329 01:49:23,640 --> 01:49:27,800 THIS CASE AND I GUESS THAT MAJOR 2330 01:49:27,800 --> 01:49:31,360 TAKE-HOME MESSAGE FROM EKG STORY 2331 01:49:31,360 --> 01:49:32,600 AND SOMETHING I HOPE CAN 2332 01:49:32,600 --> 01:49:33,920 EXTRAPOLATE TO OTHER THINGS THAT 2333 01:49:33,920 --> 01:49:36,440 IS BY USING FRAILTY INDEX WE ARE 2334 01:49:36,440 --> 01:49:38,320 ABLE TO ASK QUESTIONS ABOUT 2335 01:49:38,320 --> 01:49:40,360 PERIOD OF MORBIDITY THAT IS 2336 01:49:40,360 --> 01:49:44,000 CLEARLY AN INTERPRETATION OF THE 2337 01:49:44,000 --> 01:49:48,720 DATA. BUT, LET'S SEE WHAT YOU 2338 01:49:48,720 --> 01:49:52,160 THINK. ON LEFT HERE IS TWO LIFE 2339 01:49:52,160 --> 01:49:53,760 COURSES THAT IN ANY POPULATION 2340 01:49:53,760 --> 01:49:56,400 YOU HAVE ANIMALS LIVING SHORTER 2341 01:49:56,400 --> 01:49:58,720 AND LONGER TIME AND ON LEFT OF 2342 01:49:58,720 --> 01:50:01,240 CONTROL ANIMALS YOU SEE 2343 01:50:01,240 --> 01:50:04,920 DIFFERENT LIFESPANS HERE ANIMALS 2344 01:50:04,920 --> 01:50:09,120 LIVING 24 TO 32 MONTHS AND BASED 2345 01:50:09,120 --> 01:50:13,640 ON FRAILTY SCORE ASSIGNING 2346 01:50:13,640 --> 01:50:17,520 PERIOD OF MORBIDITY ANIMALS ON 2347 01:50:17,520 --> 01:50:28,080 RIGHT ALPHA KETOGLISERRATE 16% 2348 01:50:29,960 --> 01:50:32,640 GENDER SPECIFIC EFFECT WE SAW 2349 01:50:32,640 --> 01:50:34,000 ESSENTIALLY INCREASE IN HEALTH 2350 01:50:34,000 --> 01:50:35,920 SPAN BASED ON PERIOD OF TIME 2351 01:50:35,920 --> 01:50:39,320 BEFORE FRAILTY SCORES BEGIN TO 2352 01:50:39,320 --> 01:50:43,680 ARISE ON PREVIOUS SLIDE ANALYSIS 2353 01:50:43,680 --> 01:50:46,080 OF PERIOD THAT AT SCALE FRAILTY 2354 01:50:46,080 --> 01:50:48,720 SCORE TO LIFESPAN ITSELF TO 2355 01:50:48,720 --> 01:50:49,760 INDIVIDUAL ANIMALS YOU CAN COME 2356 01:50:49,760 --> 01:50:54,320 UP WITH A SCORE FOR PERIOD OF 2357 01:50:54,320 --> 01:51:04,840 MORBIDITY I'M SURPRISED BY THAT 2358 01:51:07,200 --> 01:51:11,320 AND DON'T KNOW WHY IT IS 2359 01:51:11,320 --> 01:51:14,760 HAPPENING AND MECHANISTIC WHY IT 2360 01:51:14,760 --> 01:51:23,120 IS HAPPENING GOOD NEWS WITH 2361 01:51:23,120 --> 01:51:32,600 INTERVENTION GO TO CLINICAL 2362 01:51:32,600 --> 01:51:34,320 STUDIES AND INTERVENTIONS FOR 2363 01:51:34,320 --> 01:51:37,200 HUMANS AND CLINICAL TRIALS AND 2364 01:51:37,200 --> 01:51:38,600 PERSONAL EXPERIENCE DOESN'T DO 2365 01:51:38,600 --> 01:51:40,200 LITERATURE IN FIELD AT ALL GOING 2366 01:51:40,200 --> 01:51:41,560 INTO THAT IN QUESTION SESSION 2367 01:51:41,560 --> 01:51:44,600 AND 40% OF COMPOUNDS EXTENDING 2368 01:51:44,600 --> 01:51:46,600 LIFESPAN AND WORKS SUPPRESS 2369 01:51:46,600 --> 01:51:47,520 AGING PATHOLOGY IN THE MOUSE 2370 01:51:47,520 --> 01:51:48,840 THAT IS PERSONAL EXPERIENCE 2371 01:51:48,840 --> 01:51:50,680 BASED IN PUBLISHED AND 2372 01:51:50,680 --> 01:51:53,880 UNPUBLISHED DATA THAT IS 2373 01:51:53,880 --> 01:51:58,680 EXTRAORDINARY AND HIT RATE THAT 2374 01:51:58,680 --> 01:52:05,920 IS UNSURPRISING TO ME AND 6 2375 01:52:05,920 --> 01:52:16,400 MILLION YEARS CONSERVE AGING 2376 01:52:17,000 --> 01:52:20,200 MECHANISMS AND WHAT DO CLINL CAL 2377 01:52:20,200 --> 01:52:22,680 SCIENTIST AND HUMAN RELATED 2378 01:52:22,680 --> 01:52:24,080 SCIENTISTS NEED FOR BASIC 2379 01:52:24,080 --> 01:52:27,200 BIOLOGY TO TAKE THINGS GOING 2380 01:52:27,200 --> 01:52:30,440 FORWARD IS THIS DATA IMPORTANT 2381 01:52:30,440 --> 01:52:33,520 TO YOU? WITH THAT COLLABORATION 2382 01:52:33,520 --> 01:52:36,520 WITH JULIE ANDERSON'S LAB HERE 2383 01:52:36,520 --> 01:52:38,880 AND WORMS AND NAMES WITH PEOPLE 2384 01:52:38,880 --> 01:52:41,960 INVOLVED ON SLIDES I WENT 2385 01:52:41,960 --> 01:52:45,640 THROUGH AND ARE FUNDING 2386 01:52:45,640 --> 01:52:56,040 PARTNERS. THANK YOU. 2387 01:53:00,120 --> 01:53:02,600 >>AGAIN SHGS THANK YOU TO 2388 01:53:02,600 --> 01:53:04,280 SPEAKERS FOR GREAT TALKS AN WOD 2389 01:53:04,280 --> 01:53:07,400 LIKE TO INVITE YOU TO COME UP TO 2390 01:53:07,400 --> 01:53:08,720 THE STAGE FOR THE DISCUSSION 2391 01:53:08,720 --> 01:53:10,120 SESSION. WE WILL OPEN IT TO THE 2392 01:53:10,120 --> 01:53:11,920 AUDIENCE FOR QUESTIONS AND AS 2393 01:53:11,920 --> 01:53:15,480 THEY COME UP I THINK TO 2394 01:53:15,480 --> 01:53:21,000 HIGHLIGHT A FEW COMMON THREADS 2395 01:53:21,000 --> 01:53:22,720 WOVEN THROUGH SERIES OF TALKS 2396 01:53:22,720 --> 01:53:24,600 THIS MORNING BUILDING OFF THESE 2397 01:53:24,600 --> 01:53:26,040 TALKS THAT ARE LOOKING AT 2398 01:53:26,040 --> 01:53:27,400 BENEFITS AND CONSIDERATIONS WITH 2399 01:53:27,400 --> 01:53:32,280 USING ANIMAL MODELS THAT IS 2400 01:53:32,280 --> 01:53:38,720 REALLY CRITICAL TO CONTINUE 2401 01:53:38,720 --> 01:53:41,920 DEVELOPING MEASURES FOR 2402 01:53:41,920 --> 01:53:44,880 COMPRESSION OF MORBIDITY DIBEING 2403 01:53:44,880 --> 01:53:49,520 CLINICAL MODEL FOR OLDER ADULTS 2404 01:53:49,520 --> 01:53:51,280 IN CLINIC WORKING WITH RESEARCH 2405 01:53:51,280 --> 01:53:53,560 AND IS A THREAD THAT IS SHOWING 2406 01:53:53,560 --> 01:53:55,400 ITERATIVE PROCESS OF TRANSLATION 2407 01:53:55,400 --> 01:53:58,040 AND REVERSE TRANSLATION AND 2408 01:53:58,040 --> 01:54:00,360 REALLY NOT ONLY BRINGING BENCH 2409 01:54:00,360 --> 01:54:02,040 RESEARCH TO BEDSIDE AND GOING 2410 01:54:02,040 --> 01:54:04,040 BACK TO THE BENCH TO REALLY 2411 01:54:04,040 --> 01:54:06,680 IDENTIFY FURTHER PATHWAYS FOR 2412 01:54:06,680 --> 01:54:09,080 INTERVENTION AND DEVELOPMENT AND 2413 01:54:09,080 --> 01:54:11,600 GOING FORWARD. 2414 01:54:11,600 --> 01:54:14,760 PLEASE THOSE WITH QUESTIONS COME 2415 01:54:26,200 --> 01:54:26,280 UP. 2416 01:54:26,280 --> 01:54:31,280 HELLO CAN YOU HEAR ME? MAYO 2417 01:54:31,280 --> 01:54:33,400 CLINIC AND QUESTION HOW SOME 2418 01:54:33,400 --> 01:54:37,920 BLOOD AND BIOMARKERS COMPARE TO 2419 01:54:37,920 --> 01:54:42,680 CLINICAL GOAL STANDARDS LIKE 2420 01:54:42,680 --> 01:54:46,960 GATE SPEED? 2421 01:54:46,960 --> 01:54:49,160 >>IS THIS -- OKAY. GREAT 2422 01:54:49,160 --> 01:54:53,640 QUESTION THAT I OFTEN WONDERED 2423 01:54:53,640 --> 01:54:56,560 THAT THERE HAVE NOT BEEN A LOT 2424 01:54:56,560 --> 01:55:00,320 OF GREAT HEAD TO HEAD 2425 01:55:00,320 --> 01:55:05,400 COMPARISONS OF THESE EMERGING 2426 01:55:05,400 --> 01:55:07,040 WITH POPULATION STUDIES TO SEE 2427 01:55:07,040 --> 01:55:09,600 IF ONE PERFORMS BETTER THAN 2428 01:55:09,600 --> 01:55:12,240 OTHER AND PUTTING AGGREGATE 2429 01:55:12,240 --> 01:55:13,520 MEASURES TOGETHER AND DON'T KNOW 2430 01:55:13,520 --> 01:55:17,200 IF ANYONE HAS KNOWLEDGE OF THOSE 2431 01:55:17,200 --> 01:55:23,440 COMPARI 2432 01:55:23,440 --> 01:55:23,760 COMPARISONS. 2433 01:55:23,760 --> 01:55:27,760 >>FASCINATING TALK, THOMAS FROM 2434 01:55:27,760 --> 01:55:30,760 KATELLA INSTITUTE AND WONDERING 2435 01:55:30,760 --> 01:55:34,720 HOW MUCH WORK IS DONE TO TEASE 2436 01:55:34,720 --> 01:55:36,600 OUT FRAILTY AND MENTAL DOUGH 2437 01:55:36,600 --> 01:55:39,520 KLEIN AND ARE THEY SILOED 2438 01:55:39,520 --> 01:55:40,200 DOMAINS? 2439 01:55:40,200 --> 01:55:42,000 I KNOW GATE SPEED AND GROUP 2440 01:55:42,000 --> 01:55:43,880 STRENGTH AND THOSE SORTS OF 2441 01:55:43,880 --> 01:55:45,360 THINGS AND EQUIVALENCE OF THEM 2442 01:55:45,360 --> 01:55:49,600 ARE BARELY STARTING OUT IN 2443 01:55:49,600 --> 01:55:51,240 COMPUTERIZED TESTING FOR MENTAL 2444 01:55:51,240 --> 01:55:53,240 ABILITY AND IF YOU CAN COMMENT 2445 01:55:53,240 --> 01:55:55,040 ON FRAILTY THAT IS MOST VISIBLE 2446 01:55:55,040 --> 01:55:57,160 SIGN OF AGING AND QUALITY OF 2447 01:55:57,160 --> 01:55:59,160 LIFE PEOPLE ARE VERY INTERESTED 2448 01:55:59,160 --> 01:56:02,200 IN MENTAL DECLINE AS WELL. 2449 01:56:02,200 --> 01:56:04,760 >>OKAY. SURE. I CAN COMMENT 2450 01:56:04,760 --> 01:56:05,960 SOMEWHAT AND THINK THAT 2451 01:56:05,960 --> 01:56:08,000 LIMITATION OF THE WORK WITH THE 2452 01:56:08,000 --> 01:56:11,720 MICE SO FAR IS THAT WE HAVE NOT 2453 01:56:11,720 --> 01:56:20,600 REALLY INCLUDED COGNITIVE 2454 01:56:20,600 --> 01:56:22,560 ASSESSMENT TEST AND COGNITIVE 2455 01:56:22,560 --> 01:56:24,560 ASSESSMENT WOULD BE INCLUDED IN 2456 01:56:24,560 --> 01:56:25,920 FRAILTY INDEX ASSESSMENTS FOR 2457 01:56:25,920 --> 01:56:27,320 PEOPLE AND SO THAT COULD BE PART 2458 01:56:27,320 --> 01:56:31,280 OF IT. IF DOING A LAB RATTORY 2459 01:56:31,280 --> 01:56:33,360 BASED FRAILTY INDEX BASED ON 2460 01:56:33,360 --> 01:56:35,560 MORE OR LESS BIOMARKERS IN THE 2461 01:56:35,560 --> 01:56:36,880 BLOOD YOU PROBABLY WOULDN'T HAVE 2462 01:56:36,880 --> 01:56:40,440 THAT UNLESS YOU ADDED IT AS A 2463 01:56:40,440 --> 01:56:42,000 SEPARATE CATEGORY TO -- FOLDED 2464 01:56:42,000 --> 01:56:44,200 INTO DATA IF YOU HAD THAT 2465 01:56:44,200 --> 01:56:46,280 AVAILABLE. I HOPE THAT ANSWERS 2466 01:56:46,280 --> 01:56:49,400 YOUR QUESTION. SOMEONE MIGHT 2467 01:56:49,400 --> 01:56:53,720 WANT TO COMMENT. 2468 01:56:53,720 --> 01:56:57,160 SORRY THERE WE GO. IN PHYSICAL 2469 01:56:57,160 --> 01:56:58,400 FRAILTY RESEARCH PROGRAM THAT WE 2470 01:56:58,400 --> 01:57:02,920 DO THERE, DEFINITELY PEOPLE 2471 01:57:02,920 --> 01:57:05,880 WORKING ON WHAT IS OFTEN A TERM 2472 01:57:05,880 --> 01:57:07,880 CLINICALLY MILD COGNITIVE 2473 01:57:07,880 --> 01:57:09,240 IMPAIRMENT AND TEND TO TRAVEL 2474 01:57:09,240 --> 01:57:10,320 TOGETHER CLOSELY AND PEOPLE AS 2475 01:57:10,320 --> 01:57:13,200 THEY AGE AND ESPECIALLY FRAIL 2476 01:57:13,200 --> 01:57:15,600 SUBSET. A LOT OF THE BIOMARKERS 2477 01:57:15,600 --> 01:57:20,200 THAT WE HAVE LOOKED AT AND TFN 2478 01:57:20,200 --> 01:57:24,400 ALPHA ECREPTOR ONE IS BEST 2479 01:57:24,400 --> 01:57:28,280 PREDICTOR OF FUTURE COGNITIVE 2480 01:57:28,280 --> 01:57:31,200 DECLINE IN COHORT POPULATIONS WE 2481 01:57:31,200 --> 01:57:33,880 LOOKED AT AND BIOOLG IS SIMILAR 2482 01:57:33,880 --> 01:57:36,520 AND SEPARATING THEM AND HONING 2483 01:57:36,520 --> 01:57:39,480 IN ON GEROSCIENCE SIGNAL AND 2484 01:57:39,480 --> 01:57:40,080 GETTING MORE AND MORE 2485 01:57:40,080 --> 01:57:41,800 INFORMATION TOGETHER WE ARE 2486 01:57:41,800 --> 01:57:43,720 PROBABLY IN PROCESS OF MERGING 2487 01:57:43,720 --> 01:57:48,560 THEM AND VERY INTERESTING THE 2488 01:57:48,560 --> 01:57:50,200 NEUROLOGIC PIECE THAT EILEEN 2489 01:57:50,200 --> 01:57:51,600 BROUGHT UP IS CERTAINLY AN 2490 01:57:51,600 --> 01:57:54,120 IMPORTANT PART OF FRAILTY 2491 01:57:54,120 --> 01:57:57,000 WHETHER PERIPHERAL, LOSS OF 2492 01:57:57,000 --> 01:57:59,880 PERIPHERAL NERVES AND SIGNALING 2493 01:57:59,880 --> 01:58:02,400 HAPPENING WITH SKELETAL MUSCLE 2494 01:58:02,400 --> 01:58:04,720 AND SARCOPENIA AND MILD 2495 01:58:04,720 --> 01:58:06,280 COGNITIVE THINGS HAPPENING THAT 2496 01:58:06,280 --> 01:58:09,000 IS IMPORTANT EMERGING AREA. 2497 01:58:09,000 --> 01:58:11,960 EILEEN, DO YOU WANT TO -- 2498 01:58:11,960 --> 01:58:12,880 >>YEAH. 2499 01:58:12,880 --> 01:58:16,400 >>ONE ISSUE ABOUT COGNITIVE 2500 01:58:16,400 --> 01:58:18,720 VERSUS NONCOGNITIVE PREDICTION 2501 01:58:18,720 --> 01:58:22,600 IS A LOT OF THE PREDICTION OF 2502 01:58:22,600 --> 01:58:26,040 COGNITIVE LOSS COMES FROM THE 2503 01:58:26,040 --> 01:58:28,400 FACT THAT PEOPLE HAVE EARLY LIFE 2504 01:58:28,400 --> 01:58:31,280 EXPERIENCES EFFECTING THEIR 2505 01:58:31,280 --> 01:58:33,600 COGNITIVE ABILITY AND SUBSEQUENT 2506 01:58:33,600 --> 01:58:36,160 DECLINE AND RATE OF DECLINE INTO 2507 01:58:36,160 --> 01:58:38,280 DEMENTIA AND DIFFERENT WAITING 2508 01:58:38,280 --> 01:58:41,520 OF FACTORS THAT ARE PREDICTING 2509 01:58:41,520 --> 01:58:43,520 COGNITIVE AND NONCOGNITIVE LOSS 2510 01:58:43,520 --> 01:58:45,720 BECAUSE OF DIFFERENT LIFECYCLE 2511 01:58:45,720 --> 01:58:47,520 PATTERNS THAT ARE DETERMINANTS 2512 01:58:47,520 --> 01:58:49,560 OF LONG-TERM OUTCOMES. 2513 01:58:49,560 --> 01:58:53,480 >>I WILL COMMENT ON INCREASING 2514 01:58:53,480 --> 01:58:55,200 EVIDENCE IN EPIDEMIOLOGIC 2515 01:58:55,200 --> 01:58:56,840 LITERATURE ABOUT COGNITIVE 2516 01:58:56,840 --> 01:59:00,000 FRAILTY AND IS DISTINCT FROM 2517 01:59:00,000 --> 01:59:06,680 PHYSICAL FRAILTY AND THAT IT IS 2518 01:59:06,680 --> 01:59:10,400 AN INTERACTION FRAIL IN BOTH 2519 01:59:10,400 --> 01:59:11,640 SPHERES DISPROPORTIONATE RISK 2520 01:59:11,640 --> 01:59:14,280 FOR ADVERSE OUTCOMES REFLECTING 2521 01:59:14,280 --> 01:59:17,600 CLINICAL EXPERIENCE WORKING ON 2522 01:59:17,600 --> 01:59:19,400 SERVICE AND SOMEONE THAT IS 2523 01:59:19,400 --> 01:59:20,880 PHYSICALLY FRAIL AND ABLE TO 2524 01:59:20,880 --> 01:59:22,600 MANAGE COGNITIVELY FRAIL AND 2525 01:59:22,600 --> 01:59:25,520 ABLE TO MANAGE AND GOD FORBID 2526 01:59:25,520 --> 01:59:27,720 THEY ARE FRAIL IN SPHERES AND 2527 01:59:27,720 --> 01:59:30,720 THEY WILL DO VERY POORLY IN THE 2528 01:59:30,720 --> 01:59:32,640 HOSPITAL AFTER THEY LEAVE THE 2529 01:59:32,640 --> 01:59:34,840 HOSPITAL AND INCREASING 2530 01:59:34,840 --> 01:59:37,240 EPIDEMIOLOGIC EVIDENCE TO 2531 01:59:37,240 --> 01:59:37,960 SUPPORT THAT. 2532 01:59:37,960 --> 01:59:40,880 >>SO, I WANTED TO CONGRATULATE 2533 01:59:40,880 --> 01:59:44,600 EVERYBODY FOR THE REALLY 2534 01:59:44,600 --> 01:59:47,640 INTERESTING SESSION THAT KIND OF 2535 01:59:47,640 --> 01:59:49,040 MELDED TOGETHER SO MANY 2536 01:59:49,040 --> 01:59:51,320 DIFFERENT EXPERTISE THAT SHOW 2537 01:59:51,320 --> 01:59:54,040 HOW THEY ARE COMPLEMENTARY TO 2538 01:59:54,040 --> 01:59:55,960 EACH OTHER AND MY QUESTION 2539 01:59:55,960 --> 01:59:57,280 REALLY COMES FROM THE LAST 2540 01:59:57,280 --> 01:59:59,160 QUESTION THAT GORDON ASKED. YOU 2541 01:59:59,160 --> 02:00:01,960 KNOW, I WANT TO ASK THESE TO 2542 02:00:01,960 --> 02:00:04,680 GORDON THAT IT IS TO ALL OF YOU 2543 02:00:04,680 --> 02:00:05,960 AS WELL. 2544 02:00:05,960 --> 02:00:08,240 I FEEL LIKE ALTHOUGH WE ALL TALK 2545 02:00:08,240 --> 02:00:10,680 ABOUT TRANSLATION FROM ANIMAL 2546 02:00:10,680 --> 02:00:15,040 MODEL TO HUMANS, THEY ARE STILL 2547 02:00:15,040 --> 02:00:17,040 NOT THERE MANY AND MOST OF THE 2548 02:00:17,040 --> 02:00:22,720 WORK DONE IN ANIMAL IS NOT 2549 02:00:22,720 --> 02:00:25,600 TRANSLATED MOST MODEL IN 2550 02:00:25,600 --> 02:00:28,960 BIOMARKET DEVELOPED IN HUMANS 2551 02:00:28,960 --> 02:00:33,720 ARE NOT PUT BACK INTO ANIMAL 2552 02:00:33,720 --> 02:00:37,040 MODEL WHAT IS GOING ON AND WILL 2553 02:00:37,040 --> 02:00:38,440 MAKE AN EXAMPLE. 2554 02:00:38,440 --> 02:00:42,040 WE DON'T KNOW WHY IS PREDICTOR 2555 02:00:42,040 --> 02:00:52,120 OF DEMENTIA AND SECOND IS GDF15 2556 02:00:52,120 --> 02:00:53,320 COMES OUT IN EVERYTHING WE DO 2557 02:00:53,320 --> 02:00:55,840 AND WHAT IS MISSING IN 2558 02:00:55,840 --> 02:00:58,320 TRANSLATION IN YOUR OPINION, OF 2559 02:00:58,320 --> 02:00:58,560 COURSE? 2560 02:00:58,560 --> 02:01:03,240 >>GORDON, GO AHEAD. 2561 02:01:03,240 --> 02:01:06,240 >>PHENOMENAL QUESTION THAT 2562 02:01:06,240 --> 02:01:09,200 WORRIES ME A LOT AND WE HAVE 2563 02:01:09,200 --> 02:01:11,720 AMAZING THINGS WE SEE IN ANIMAL 2564 02:01:11,720 --> 02:01:14,680 MODELS THAT WE THINK ARE 2565 02:01:14,680 --> 02:01:22,680 IMPORTANT AND WE DON'T HAVE 2566 02:01:22,680 --> 02:01:24,600 ORGANIZED PIPELINE FORWARD AND 2567 02:01:24,600 --> 02:01:26,720 HOW YOU GET FROM AGING ITSELF 2568 02:01:26,720 --> 02:01:28,520 LIFESPAN AND GETTING ALL THE WAY 2569 02:01:28,520 --> 02:01:30,240 TO SOMETHING HUMAN RELEVANT AND 2570 02:01:30,240 --> 02:01:36,240 DON'T HAVE ANSWER TO THAT AT ALL 2571 02:01:36,240 --> 02:01:40,000 OTHER THAN DOG MORE OF WHAT WE 2572 02:01:40,000 --> 02:01:43,080 ARE DOING TODAY. 2573 02:01:43,080 --> 02:01:45,000 IN OUR WORK WE ARE THINKING 2574 02:01:45,000 --> 02:01:48,040 ABOUT WAYS TO TRANSLATE 2575 02:01:48,040 --> 02:01:50,080 ESPECIALLY ANIMAL FINDINGS 2576 02:01:50,080 --> 02:01:53,280 TOWARDS HUMANS AND BIG BARRIERS 2577 02:01:53,280 --> 02:01:56,080 I SEE ARE COLLECTING HUMAN 2578 02:01:56,080 --> 02:01:58,400 SUBJECT SAMPLES AND TIMES WE 2579 02:01:58,400 --> 02:02:00,240 NEED MUSCLE AND BRAIN TISSUE AND 2580 02:02:00,240 --> 02:02:02,680 THINGS YOU CAN'T COLLECT FROM 2581 02:02:02,680 --> 02:02:13,200 HUMAN SUBJECTS AND THAT HAS BEEN 2582 02:02:14,120 --> 02:02:16,600 A HUGE STOPPING POINT AND DURING 2583 02:02:16,600 --> 02:02:19,760 MY TALK TALKING ABOUT NEEDING 2584 02:02:19,760 --> 02:02:21,560 ACCESSIBLE MEASURABLE BIOMARKERS 2585 02:02:21,560 --> 02:02:24,920 COMING OUT OF STUDIES SO 2586 02:02:24,920 --> 02:02:28,880 SYNESSENCE OR ETTO FANLY AND 2587 02:02:28,880 --> 02:02:31,360 GETTING TISSUE BIOPSIES AND 2588 02:02:31,360 --> 02:02:33,600 DISDAINS AND THINGS TO TRANSLATE 2589 02:02:33,600 --> 02:02:35,280 MEASUREMENTS MAKING THEM 2590 02:02:35,280 --> 02:02:36,320 CLINICALLY RELEVANT WE HAVE TO 2591 02:02:36,320 --> 02:02:38,120 MOVE INTO AREAS WHERE WE CAN GET 2592 02:02:38,120 --> 02:02:41,000 A BLOOD SAMPLE AND MEASURE 2593 02:02:41,000 --> 02:02:42,560 SOMETHING. THEN JUST HUMAN 2594 02:02:42,560 --> 02:02:46,360 SUBJECTS PROTECTIONS ARE 2595 02:02:46,360 --> 02:02:47,920 CERTAINLY SUPER IMPORTANT WE 2596 02:02:47,920 --> 02:02:50,520 JUST -- THAT IS A BIG BARRIER 2597 02:02:50,520 --> 02:02:53,160 THAT PREVENTS US FROM MOVING 2598 02:02:53,160 --> 02:02:53,920 FORWARD AND IS NECESSARY AND NO 2599 02:02:53,920 --> 02:02:57,320 THE ARGUING AGAINST THAT. 2600 02:02:57,320 --> 02:03:07,840 >>I WILL MAYBE COMMENT TOO. 2601 02:03:22,560 --> 02:03:24,400 THIS COULD BE POTENTIALLY TRIED. 2602 02:03:24,400 --> 02:03:27,320 >>COMMENTING ON THAT. 2603 02:03:27,320 --> 02:03:30,200 >>I TOTALLY AGREE. REPURPOSING 2604 02:03:30,200 --> 02:03:35,120 IS AN IMPORTANT WAY FORWARD. 2605 02:03:35,120 --> 02:03:37,280 EFFECTS ON AGING ITSELF IS 2606 02:03:37,280 --> 02:03:42,080 FAIRLY SMALL FOR SOME THINGS IN 2607 02:03:42,080 --> 02:03:43,960 ANIMAL SYSTEMS AND GUESS WHAT 2608 02:03:43,960 --> 02:03:47,800 I'M TRYING TO SAY IS WE HAVE NOT 2609 02:03:47,800 --> 02:03:48,640 EXPLORED CHEMICAL SPACE AND 2610 02:03:48,640 --> 02:03:50,720 HAVEN'T LOOKED AT WHAT IS OUT 2611 02:03:50,720 --> 02:03:54,080 THERE IN TERMS OF AGING 2612 02:03:54,080 --> 02:03:55,320 INTERVENTIONS IN ANY GRAND WAY 2613 02:03:55,320 --> 02:03:57,880 AND IN DOING SO MIGHT FIND 2614 02:03:57,880 --> 02:04:02,240 THINGS MUCH MORE POTENT THAN MET 2615 02:04:02,240 --> 02:04:05,960 FOR MEN AND APPOMYCIN. 2616 02:04:05,960 --> 02:04:07,440 >>RESPONDING TO GORDON A LITTLE 2617 02:04:07,440 --> 02:04:11,200 BIT. I FEEL SOME OF YOUR SLIDES 2618 02:04:11,200 --> 02:04:17,000 ARE REALLY SHOW IING STRONG 2619 02:04:17,000 --> 02:04:20,600 EFFECTS AT YOUNG ER AGES OF 2620 02:04:20,600 --> 02:04:23,200 ANIMALS AND MIGHT BE USEFUL FOR 2621 02:04:23,200 --> 02:04:26,040 YOUR GROUP TO SORT OF 2622 02:04:26,040 --> 02:04:29,280 DIFFERENTIATE ACROSS THE LIFE 2623 02:04:29,280 --> 02:04:31,520 CYCLE A LITTLE MORE IN TERMS 2624 02:04:31,520 --> 02:04:35,600 WHERE YOU ARE GETTING EFFECTS OF 2625 02:04:35,600 --> 02:04:37,040 CERTAIN THINGS THAT AID INTO 2626 02:04:37,040 --> 02:04:41,120 MOVING IDEAS TO HUMANS. 2627 02:04:41,120 --> 02:04:43,160 >>ECHOING WHAT IS SAID THERE IS 2628 02:04:43,160 --> 02:04:45,680 STUDIES LOOKING AT MIDLIFE 2629 02:04:45,680 --> 02:04:46,520 CHRONIC INFLAMMATION FOR EXAMPLE 2630 02:04:46,520 --> 02:04:49,920 AND HOW THAT IS ASSOCIATED WITH 2631 02:04:49,920 --> 02:04:50,960 ADVERSE COGNITION AND PHYSICAL 2632 02:04:50,960 --> 02:04:53,240 OUTCOMES AND REALLY GETTING OR 2633 02:04:53,240 --> 02:04:57,080 HONING IN ON WHAT IDEAL TIME TO 2634 02:04:57,080 --> 02:04:58,520 INITIATE AN INTERVENTION WOULD 2635 02:04:58,520 --> 02:05:00,560 BE ALSO IS ANOTHER CONSIDERATION 2636 02:05:00,560 --> 02:05:07,800 FOR THESE INTERVENTIONS. 2637 02:05:07,800 --> 02:05:12,360 >>HI, THANK YOU. QUESTIONS FOR 2638 02:05:12,360 --> 02:05:14,080 EILEEN AND HER TALK AND OTHERS 2639 02:05:14,080 --> 02:05:15,920 AND FEEL FREE TO CHIME IN AND IN 2640 02:05:15,920 --> 02:05:19,120 LIGHT OF SESSION ON HEALTH 2641 02:05:19,120 --> 02:05:20,720 DISPARITIES AND WORK ON SOCIAL 2642 02:05:20,720 --> 02:05:24,000 HALLMARKS OF AGING AND CURIOUS 2643 02:05:24,000 --> 02:05:26,280 YOU PUT EXPLAINS IN QUOTES WHEN 2644 02:05:26,280 --> 02:05:29,200 EDUCATION AND ETHNICITY AND SES 2645 02:05:29,200 --> 02:05:33,520 MEASURES AND GETS WASHED OUT IN 2646 02:05:33,520 --> 02:05:34,040 THE ANALYSIS. 2647 02:05:34,040 --> 02:05:38,200 BUT, CLEARLY, THERE IS STORIES 2648 02:05:38,200 --> 02:05:40,920 THERE. I WILL JUST BE KIND OF 2649 02:05:40,920 --> 02:05:42,680 CURIOUS IN LIGHT OF GEROSCIENCE 2650 02:05:42,680 --> 02:05:44,880 IDEA ABOUT AGING ABOVE AND 2651 02:05:44,880 --> 02:05:47,320 BEYOND SPECIFIC DISEASES AND 2652 02:05:47,320 --> 02:05:50,760 HEALTH DISPARITIES THAT ARE LIFE 2653 02:05:50,760 --> 02:05:52,680 LONG EXPERIENCES AND PROCESSES 2654 02:05:52,680 --> 02:05:54,720 IN DIFFERENT GROUPS AND STATES 2655 02:05:54,720 --> 02:05:57,000 OF DISADVANTAGE AND WHAT NOT. 2656 02:05:57,000 --> 02:05:59,560 ARE ALL OF THE EFFECTS 2657 02:05:59,560 --> 02:06:00,960 MODERATION EFFECTS INSTEAD OF 2658 02:06:00,960 --> 02:06:01,280 MEDIATION? 2659 02:06:01,280 --> 02:06:06,080 WHAT CAN YOU SAY FROM ANALYSIS 2660 02:06:06,080 --> 02:06:10,720 THAT STILL, YOU KNOW, INVOKES 2661 02:06:10,720 --> 02:06:14,400 THAT THESE SOCIAL EXPERIENCES 2662 02:06:14,400 --> 02:06:15,240 THROUGH DIFFERENTIAL EDUCATION 2663 02:06:15,240 --> 02:06:18,440 AND THROUGH SES ARE STILL HAVING 2664 02:06:18,440 --> 02:06:20,400 CASCADING EFFECTS OVER THE LIFE 2665 02:06:20,400 --> 02:06:23,560 COURSE. IF YOU HAVE BIOLOGICAL 2666 02:06:23,560 --> 02:06:25,040 MEASURES, SURE. THAT STUFF 2667 02:06:25,040 --> 02:06:26,720 WASHES OUT AND LEADS SOMEONE TO 2668 02:06:26,720 --> 02:06:28,520 THINK MAYBE THOSE THINGS DON'T 2669 02:06:28,520 --> 02:06:30,840 REALLY MATTER. I'M WONDERING 2670 02:06:30,840 --> 02:06:33,400 CAN I COMMENT A LITTLE BROADLY 2671 02:06:33,400 --> 02:06:35,400 TRYING TO UNITE PERSPECTIVES 2672 02:06:35,400 --> 02:06:38,760 ABOUT IMPORTANCE OF HEALTH 2673 02:06:38,760 --> 02:06:40,480 DISPARITIES AND DIFFERENTIAL 2674 02:06:40,480 --> 02:06:41,600 EXPERIENCES AND SOCIAL HALLMARKS 2675 02:06:41,600 --> 02:06:44,080 OF AGING AT SAME TIME 2676 02:06:44,080 --> 02:06:45,920 GEROSCIENCE IDEA AND IN WAY IF 2677 02:06:45,920 --> 02:06:48,240 YOU HAVE ALL BIOLOGICAL MEASURES 2678 02:06:48,240 --> 02:06:49,280 YOU DON'T NEED ANYTHING ELSE. 2679 02:06:49,280 --> 02:06:53,320 >>I DON'T THINK THAT MEANS YOU 2680 02:06:53,320 --> 02:06:54,080 DON'T NEED ANYTHING ELSE. 2681 02:06:54,080 --> 02:06:54,640 >>YEAH. 2682 02:06:54,640 --> 02:06:57,160 >>I GUESS WHAT IS DIFFERENT IS 2683 02:06:57,160 --> 02:06:59,880 WHAT I DID TODAY WIPED OUT 2684 02:06:59,880 --> 02:07:01,480 DIFFERENCES THAT HAVEN'T BEEN 2685 02:07:01,480 --> 02:07:03,960 WIPED OUT BEFORE WHEN WE HAVE 2686 02:07:03,960 --> 02:07:07,560 INCLUDED A VARIETY OF THINGS AND 2687 02:07:07,560 --> 02:07:09,560 BASICALLY SEEING THEM AS 2688 02:07:09,560 --> 02:07:12,040 MEDIATORS OF AN EXPERIENCE AND 2689 02:07:12,040 --> 02:07:13,280 MAYBE MODERATORS ALSO BUT 2690 02:07:13,280 --> 02:07:14,920 MEDIATORS BASICALLY. 2691 02:07:14,920 --> 02:07:18,000 I DON'T THINK THAT I ADDED MUCH 2692 02:07:18,000 --> 02:07:20,040 TO THE UNDERSTANDING OF SOCIAL 2693 02:07:20,040 --> 02:07:22,120 DIFFERENCES TODAY THAT ARE 2694 02:07:22,120 --> 02:07:23,000 EXTRAORDINARILY STRONG. 2695 02:07:23,000 --> 02:07:29,400 I DO THINK THAT UNDERSTANDING 2696 02:07:29,400 --> 02:07:32,120 THE SPECIFICS OF SOCIAL 2697 02:07:32,120 --> 02:07:34,400 DIFFERENCES AND SES AND 2698 02:07:34,400 --> 02:07:36,120 SPECIFICS OF BIOLOGICAL 2699 02:07:36,120 --> 02:07:39,160 MECHANISMS CAN LEAD US SOMEWHERE 2700 02:07:39,160 --> 02:07:42,680 BUT THIS INITIAL SAYING THAT 2701 02:07:42,680 --> 02:07:45,840 STATISTICALLY THEY ARE WIEBED 2702 02:07:45,840 --> 02:07:48,240 OUT AND I PUT QUOTES AROUND 2703 02:07:48,240 --> 02:07:49,800 EXPLANATION AND DON'T REALLY 2704 02:07:49,800 --> 02:07:51,160 THINK IT SAY FULL EXPLANATION 2705 02:07:51,160 --> 02:07:55,520 AND AGREE WITH YOU IN YOUR 2706 02:07:55,520 --> 02:08:01,640 ASSESSMENT OF THIS. 2707 02:08:01,640 --> 02:08:05,280 >>I WOULDN'T PROPOSE 2708 02:08:05,280 --> 02:08:06,600 MATHEMATICAL EXPERTISE 2709 02:08:06,600 --> 02:08:07,720 WHATSOEVER BUT CENTRAL BIOLOGY 2710 02:08:07,720 --> 02:08:10,040 THAT IS DRIVING THIS. AS WE PUT 2711 02:08:10,040 --> 02:08:11,800 MODELS TOGETHER AND ESPECIALLY 2712 02:08:11,800 --> 02:08:13,720 WITH STRESS RESPONSE SYSTEMS, I 2713 02:08:13,720 --> 02:08:15,680 MEAN, WE NEED TO HAVE SIDE 2714 02:08:15,680 --> 02:08:16,960 CONVERSATIONS ABOUT THIS. I 2715 02:08:16,960 --> 02:08:18,840 THINK THERE IS A LOT OF 2716 02:08:18,840 --> 02:08:20,600 COMMONALITIES IN THAT CENTER, 2717 02:08:20,600 --> 02:08:22,440 YOU KNOW, PHYSIOLOGY THAT IS 2718 02:08:22,440 --> 02:08:24,360 HAPPENING WHETHER IT IS A -- YOU 2719 02:08:24,360 --> 02:08:26,720 KNOW, SOCIAL STRESSOR OR SOME 2720 02:08:26,720 --> 02:08:29,040 CLINICAL STRESSOR OR SOME 2721 02:08:29,040 --> 02:08:30,160 GENETIC, YOU KNOW, 2722 02:08:30,160 --> 02:08:31,880 PREDISPOSITION TO ACTIVATING 2723 02:08:31,880 --> 02:08:33,240 STRESS RESPONSE SYSTEMS THAT I 2724 02:08:33,240 --> 02:08:36,120 THINK THAT THE CENTER WILL BE 2725 02:08:36,120 --> 02:08:37,080 VERY COMMON AMONGST ALL THESE 2726 02:08:37,080 --> 02:08:40,120 DIFFERENT THINGS AND FOR ME IS 2727 02:08:40,120 --> 02:08:42,240 THINKING ABOUT PREVENTION AND 2728 02:08:42,240 --> 02:08:44,560 PEOPLE WILL END UP IN CENTER BOX 2729 02:08:44,560 --> 02:08:48,200 WITH LOTS OF ADVERSE OUTCOMES 2730 02:08:48,200 --> 02:08:51,400 THAT ARE DRIVING ON OTHER SIDE 2731 02:08:51,400 --> 02:08:54,760 OF THAT AND WE HAVE TO CAREFULLY 2732 02:08:54,760 --> 02:08:58,440 DISSECT WHAT IS PUSHING THOSE IN 2733 02:08:58,440 --> 02:09:02,200 BOXES AND TRY TO PREVENT FROM 2734 02:09:02,200 --> 02:09:07,360 THERE AND IS PUBLIC HEALTH 2735 02:09:07,360 --> 02:09:07,800 THINKING. 2736 02:09:07,800 --> 02:09:09,240 >>THANK YOU. 2737 02:09:09,240 --> 02:09:12,280 >>EXPRESSING OBSERVATION AND 2738 02:09:12,280 --> 02:09:19,120 CONCERN ABOUT BIOMARKERS IF YOU 2739 02:09:19,120 --> 02:09:21,520 KNOW ONE OLDER PATIENT YOU KNOW 2740 02:09:21,520 --> 02:09:23,280 ONE OLDER PATIENT AND WE HAVE 2741 02:09:23,280 --> 02:09:27,800 SEEN 80 YEAR OLDS WITH A HOST OF 2742 02:09:27,800 --> 02:09:37,040 DISEASES IN PROBLEM LIST THAT IS 2743 02:09:37,040 --> 02:09:41,440 FUNCTIONAL AND SAME LIST TALKING 2744 02:09:41,440 --> 02:09:45,720 ABOUT NOW VARIETY OF THINGS 2745 02:09:45,720 --> 02:09:46,720 SEEMING CONTRADICTORY HOW WE 2746 02:09:46,720 --> 02:09:50,720 APPROACH BIOMARKERS TALKING 2747 02:09:50,720 --> 02:09:57,920 ABOUT TALKING ABOUT INTEGRATION 2748 02:09:57,920 --> 02:10:01,760 OF SYSTEMS AND DYNAMICS REFERRED 2749 02:10:01,760 --> 02:10:10,280 TO AND STRESS RESPONSES AND 2750 02:10:10,280 --> 02:10:13,560 APPROACHES BUNDLE OF MEASURES 2751 02:10:13,560 --> 02:10:16,280 ADDING THEM UP IN A LINEAR WAY 2752 02:10:16,280 --> 02:10:20,720 AND PREDICTORS WHAT A PERSON 2753 02:10:20,720 --> 02:10:22,120 MIGHT LOOK LIKE AND OUTCOME 2754 02:10:22,120 --> 02:10:24,120 MIGHT BE AND TROUBLED WITH THAT 2755 02:10:24,120 --> 02:10:25,520 BECAUSE OF FACT THAT IS 2756 02:10:25,520 --> 02:10:27,520 RECOGNIZED THAT ALL FACTORS THAT 2757 02:10:27,520 --> 02:10:29,920 WE TALK ABOUT ARE NON-LINEAR AND 2758 02:10:29,920 --> 02:10:32,920 ARE INTERACTING WITH EACH OTHER 2759 02:10:32,920 --> 02:10:34,200 AND OPERATING ON DIFFERENT 2760 02:10:34,200 --> 02:10:36,040 SCALES FROM MOLECULES TO 2761 02:10:36,040 --> 02:10:37,880 BIOCHEMICAL BIOMARKERS THROUGH 2762 02:10:37,880 --> 02:10:41,720 CELLS AND THROUGH ORGANS AND 2763 02:10:41,720 --> 02:10:43,680 ORGANISMS AND THROUGH SOCIAL 2764 02:10:43,680 --> 02:10:45,600 SYSTEMS AND NETWORKS AND 2765 02:10:45,600 --> 02:10:47,560 ENVIRONMENT AND CAN'T THINK 2766 02:10:47,560 --> 02:10:48,200 ABOUT LUMPING THEM TOGETHER 2767 02:10:48,200 --> 02:10:50,680 WITHOUT THINKING ABOUT HOW THEY 2768 02:10:50,680 --> 02:10:51,480 INTERACT WITHIN A GIVEN 2769 02:10:51,480 --> 02:10:52,480 INDIVIDUAL AND THINK WHAT WE 2770 02:10:52,480 --> 02:10:55,200 HAVE TO DO TO MOVE OUR SCIENCE 2771 02:10:55,200 --> 02:10:57,800 FORWARD IS DEVELOP MATHEMATICAL 2772 02:10:57,800 --> 02:10:59,640 MODELS CAPABLE OF NOT JUST SORT 2773 02:10:59,640 --> 02:11:03,960 OF LINEARLY ADDING THEM UP OR 2774 02:11:03,960 --> 02:11:06,600 WITH WEIGHTS AND STUFF BUT 2775 02:11:06,600 --> 02:11:08,400 FOCUSED ON EILEEN SPECIFICALLY 2776 02:11:08,400 --> 02:11:10,680 BUT HOW WE ACTUALLY INTEGRATE 2777 02:11:10,680 --> 02:11:14,680 THEM THINKING ABOUT ACTIVITY ON 2778 02:11:14,680 --> 02:11:18,080 DIFFERENT SCALES OVER TIME AND 2779 02:11:18,080 --> 02:11:21,040 INDIVIDUALS AND THINKING ABOUT 2780 02:11:21,040 --> 02:11:22,760 INDIVIDUAL AS A COMPLEX SYSTEM 2781 02:11:22,760 --> 02:11:25,680 AND HOW IT MIGHT BREAK DOWN WITH 2782 02:11:25,680 --> 02:11:27,040 AGING AND GOOD NEWS IS SOME 2783 02:11:27,040 --> 02:11:29,600 COMPLEXITY COULD BE RESTORED AND 2784 02:11:29,600 --> 02:11:32,520 SAW REALLY GOOD EXAMPLES WITH 2785 02:11:32,520 --> 02:11:35,400 THAT WITH NH INHIBITOR OR 2786 02:11:35,400 --> 02:11:37,800 EXERCISE AND OTHER INTERVENTIONS 2787 02:11:37,800 --> 02:11:40,440 AND WE NEED BIOMARKERS THAT 2788 02:11:40,440 --> 02:11:42,680 INTEGRATE SYSTEMS ACROSS 2789 02:11:42,680 --> 02:11:43,400 DIFFERENT SCALES AND WHAT 2790 02:11:43,400 --> 02:11:45,080 COMPLECHLTY SCIENCE IS ALL ABOUT 2791 02:11:45,080 --> 02:11:48,160 AND THANK YOU TO JEREMY ABOUT 2792 02:11:48,160 --> 02:11:52,720 THE CALLOUT TO COMPLEXITY. 2793 02:11:52,720 --> 02:11:54,800 >>CAN I COMMENT ON THAT? 2794 02:11:54,800 --> 02:11:57,480 I WOULD LIKE TO SUGGEST THAT 2795 02:11:57,480 --> 02:12:00,120 POWER OF TRAILTY INDEX AS AN 2796 02:12:00,120 --> 02:12:01,680 APPROACH IS WE ARE SAMPLING A 2797 02:12:01,680 --> 02:12:04,120 LARGE NUMBER OF ITEMS AND WORK 2798 02:12:04,120 --> 02:12:08,640 DONE WITH CLINICAL FRAILTY INDEX 2799 02:12:08,640 --> 02:12:10,760 DATA HAS SHOWN WHEN YOU GET TO 2800 02:12:10,760 --> 02:12:16,200 LARGER NUMBER OF ITEMS YOU CAN 2801 02:12:16,200 --> 02:12:18,680 SWAP ITEMS IN FRAILTY INDEX AND 2802 02:12:18,680 --> 02:12:19,920 IT WON'T CHANGE THE SCORE AND 2803 02:12:19,920 --> 02:12:23,440 FACT IT IS NOT WEIGHTED ON ONE 2804 02:12:23,440 --> 02:12:25,720 PARTICULAR THING AND FRAILTY 2805 02:12:25,720 --> 02:12:27,280 INDEX ON BLOOD MARKERS AGAIN YOU 2806 02:12:27,280 --> 02:12:30,120 ARE LOOKING AT ALMOST A FRAILTY 2807 02:12:30,120 --> 02:12:32,880 INDEX COMPOSED OF BIOMARKERS AND 2808 02:12:32,880 --> 02:12:34,360 ALLOWS PEOPLE TO BE FRAIL IN 2809 02:12:34,360 --> 02:12:35,880 MANY DIFFERENT WAYS SO THEY 2810 02:12:35,880 --> 02:12:37,240 TOENT HAVE TO TAKE SAME PATH IF 2811 02:12:37,240 --> 02:12:38,600 THAT IS WHAT YOU ARE SUGGESTING 2812 02:12:38,600 --> 02:12:42,680 THAT MIGHT BE A UTILITY OF THE 2813 02:12:42,680 --> 02:12:47,840 FRAILTY INDEX APPROACH. 2814 02:12:47,840 --> 02:12:49,800 I WAS GOING TO SAY MODELING AND 2815 02:12:49,800 --> 02:12:53,080 RESULTS COMING OUT OF THAT CAN 2816 02:12:53,080 --> 02:12:55,160 PROVIDE REALLY POTENT CLUZ FOR 2817 02:12:55,160 --> 02:12:58,680 THINGS WE SHOULD BE TARGETING 2818 02:12:58,680 --> 02:13:03,280 AND GOING BACK TO RECEPTOR 1 2819 02:13:03,280 --> 02:13:04,560 FINDING AND PB [INDISCERNIBLE] 2820 02:13:04,560 --> 02:13:08,600 AND FOR CLINICAL PRACTICE WE CAN 2821 02:13:08,600 --> 02:13:12,360 ULTIMATELY FIGURE OUT IN THIS 2822 02:13:12,360 --> 02:13:14,680 EVERY R- INVESTIGATIVE PHASE 2823 02:13:14,680 --> 02:13:16,040 FIGURE OUT WHERE IT IS COMING 2824 02:13:16,040 --> 02:13:17,840 FROM AND TARGET SYSTEMS 2825 02:13:17,840 --> 02:13:20,480 INDIVIDUALLY AND IN SOME PEOPLE 2826 02:13:20,480 --> 02:13:23,440 WILL BE MEANINGLESS AND NOT HAVE 2827 02:13:23,440 --> 02:13:25,600 INNOVATIONS OR CIRCULATORY OR 2828 02:13:25,600 --> 02:13:26,880 HEART FAILURES AND IN OTHERS 2829 02:13:26,880 --> 02:13:28,240 SHOULD BE ABLE TO SAY THIS IS 2830 02:13:28,240 --> 02:13:29,960 SOMETHING TO THINK ABOUT AND 2831 02:13:29,960 --> 02:13:31,280 FIGURE OUT IF THERE IS 2832 02:13:31,280 --> 02:13:33,120 DISREGULATION GOING ON IN 2833 02:13:33,120 --> 02:13:35,160 PARTICULAR AREAS AND SHOULD 2834 02:13:35,160 --> 02:13:38,160 TARGET IN THOSE PEOPLE AND GOES 2835 02:13:38,160 --> 02:13:40,880 BACK TO PRECISION MEDICINE AREAS 2836 02:13:40,880 --> 02:13:42,200 WE TALK ABOUT THAT ULTIMATELY 2837 02:13:42,200 --> 02:13:44,440 WILL GET US CLOSER TO BEING ABLE 2838 02:13:44,440 --> 02:13:50,440 TO IDENTIFY PEOPLE EARLY PUTTING 2839 02:13:50,440 --> 02:13:53,200 THEM ON DIFFERENT TRAJECTORY 2840 02:13:53,200 --> 02:13:56,520 AWAY FROM FRAILTY AND RESILIENT 2841 02:13:56,520 --> 02:13:57,600 SYSTEM AND. 2842 02:13:57,600 --> 02:13:58,400 >>I THINK YOUR SUGGESTIONS ARE 2843 02:13:58,400 --> 02:14:00,440 VERY GOOD. I THIS I THAT WHAT 2844 02:14:00,440 --> 02:14:03,840 WE ARE ON IS A PANEL OF 2845 02:14:03,840 --> 02:14:04,560 DISCOVERY. 2846 02:14:04,560 --> 02:14:10,680 AND THERE IS SORT OF A PATH TO 2847 02:14:10,680 --> 02:14:11,880 DETERMINING WHAT IS IMPORTANT 2848 02:14:11,880 --> 02:14:14,520 AND PERHAPS DETERMINING 2849 02:14:14,520 --> 02:14:15,760 INTERACTIONS OF THOSE THINGS AND 2850 02:14:15,760 --> 02:14:17,400 COMPLEXITY THAT IS REQUIRED TO 2851 02:14:17,400 --> 02:14:21,720 THINK ABOUT IT AND HOW TO DO IT 2852 02:14:21,720 --> 02:14:24,800 AND REALLY ASSESS IN INDIVIDUALS 2853 02:14:24,800 --> 02:14:28,720 IN PRECISION MEDICINE KIND OF 2854 02:14:28,720 --> 02:14:29,600 WAY IS TECHNICALLY DIFFICULT. 2855 02:14:29,600 --> 02:14:31,640 I THINK IT IS AN IMPORTANT AIM 2856 02:14:31,640 --> 02:14:37,560 THAT WE SHOULD TRY TO GET THERE 2857 02:14:37,560 --> 02:14:38,200 EVENTU 2858 02:14:38,200 --> 02:14:38,480 EVENTUALLY. 2859 02:14:38,480 --> 02:14:39,800 >>I'M HEATHER FROM DUKE AND 2860 02:14:39,800 --> 02:14:42,560 WANTED TO GET THE PANEL SORT OF 2861 02:14:42,560 --> 02:14:45,440 COMMENTS GOING BACK TO GORDON'S 2862 02:14:45,440 --> 02:14:47,120 STATEMENTS ABOUT BIOLOGICAL 2863 02:14:47,120 --> 02:14:49,680 AGING AND LONGEVITY AND THINK 2864 02:14:49,680 --> 02:14:51,080 THAT THE STATEMENT BEING THAT IN 2865 02:14:51,080 --> 02:14:54,160 ANIMAL MODELS IF YOU ARE 2866 02:14:54,160 --> 02:14:55,760 STUDYING BIOLOGICAL AGING YOU 2867 02:14:55,760 --> 02:14:57,200 SHOULD INCREASE LONGEVITY AND IF 2868 02:14:57,200 --> 02:14:59,560 YOU ARE NOT INCREASING LONGEVITY 2869 02:14:59,560 --> 02:15:02,600 YOU ARE PROBABLY NOT STUDYING 2870 02:15:02,600 --> 02:15:04,000 BIOLOGICAL AGING AND THINK 2871 02:15:04,000 --> 02:15:05,400 CERTAINLY IN HUMAN HEALTH THOSE 2872 02:15:05,400 --> 02:15:07,600 TWO THINGS WE CAN GET IN TROUBLE 2873 02:15:07,600 --> 02:15:09,960 CONFLATING THOSE THINGS AND CAN 2874 02:15:09,960 --> 02:15:12,160 ALSO REALLY APPRECIATE THAT IN 2875 02:15:12,160 --> 02:15:14,120 CONTROLLED ENVIRONMENT OF A LAB 2876 02:15:14,120 --> 02:15:16,880 ANIMAL THAT IT IS PROBABLY TRUE 2877 02:15:16,880 --> 02:15:18,680 THAT BIOLOGICAL AGING WE SHOULD 2878 02:15:18,680 --> 02:15:20,720 SEE INCREASED LONGEVITY AND 2879 02:15:20,720 --> 02:15:21,800 WONDER IF YOU THINK THERE IS 2880 02:15:21,800 --> 02:15:25,400 SOME VALUE IN LOOKING AT THOSE 2881 02:15:25,400 --> 02:15:28,520 THINGS SEPARATELY WE SAW AN 2882 02:15:28,520 --> 02:15:29,400 EXAMPLE OF INTERVENTION THAT 2883 02:15:29,400 --> 02:15:33,520 BOTH SAW INCREASED LONGEVITY AND 2884 02:15:33,520 --> 02:15:35,720 COMPRESSED MOSH ITDTY AND 2885 02:15:35,720 --> 02:15:38,080 IMAGINE AN INTERVENTION THOSE 2886 02:15:38,080 --> 02:15:41,680 ARE UNCOUPLED AND THINGS DIDN'T 2887 02:15:41,680 --> 02:15:43,320 SEE TOGETHER AND DO WE 2888 02:15:43,320 --> 02:15:45,240 POTENTIALLY SEE A MECHANISM 2889 02:15:45,240 --> 02:15:46,680 DOING ONE MORE THAN THE OTHER OR 2890 02:15:46,680 --> 02:15:49,880 SOME MECHANISMS WHERE WE MAY BE 2891 02:15:49,880 --> 02:15:51,720 SLOWING BIOLOGICAL AGING BUT NOT 2892 02:15:51,720 --> 02:15:53,720 EFFECTING LONGEVITY OR VICE 2893 02:15:53,720 --> 02:15:56,320 VERSA AND THINKING ABOUT 2894 02:15:56,320 --> 02:15:58,520 EILEEN'S HUMAN DATA THAT 2895 02:15:58,520 --> 02:16:00,160 CONFIRMED FIRST THING I SAID 2896 02:16:00,160 --> 02:16:01,600 THAT BIOLOGICAL AGING IS 2897 02:16:01,600 --> 02:16:03,920 IMPORTANT TO PREDICTING HUMAN 2898 02:16:03,920 --> 02:16:05,200 MORTALITY BUT THERE ARE -- CAN 2899 02:16:05,200 --> 02:16:07,000 YOU HAVE THINGS CAUSING CERTAIN 2900 02:16:07,000 --> 02:16:09,480 VERY IMPORTANT SYSTEMS TO GO 2901 02:16:09,480 --> 02:16:12,880 DOWN THAT WILL ALSO DRIVE 2902 02:16:12,880 --> 02:16:13,200 LONGEVITY. 2903 02:16:13,200 --> 02:16:15,080 >>MAYBE I CAN COMMENT IF YOU 2904 02:16:15,080 --> 02:16:16,480 CAN HEAR ME. 2905 02:16:16,480 --> 02:16:18,760 NO. ABSOLUTELY. WHAT I SAID 2906 02:16:18,760 --> 02:16:21,280 WAS A VERY SIMPLISTIC GUIDELINE 2907 02:16:21,280 --> 02:16:23,880 FOR HOW WE TRY TO FIND 2908 02:16:23,880 --> 02:16:25,480 INTERVENTIONS THAT TARGET AGING 2909 02:16:25,480 --> 02:16:27,920 AND WE KNOW ALREADY THAT THERE 2910 02:16:27,920 --> 02:16:31,600 ARE INTERVENTIONS AND GENETIC 2911 02:16:31,600 --> 02:16:33,800 INTERVENTIONS BY HEIDI AND WORM 2912 02:16:33,800 --> 02:16:36,040 FOR EXAMPLE SHOWING MUTATIONS 2913 02:16:36,040 --> 02:16:38,040 THAT EXTEND LIFESPAN DON'T 2914 02:16:38,040 --> 02:16:39,440 NECESSARILY IMPROVE HEALTH THAT 2915 02:16:39,440 --> 02:16:43,480 MUCH AND WORMS CAN SPEND A 2916 02:16:43,480 --> 02:16:44,280 LONGER TIME IN GENERAL PHASE 2917 02:16:44,280 --> 02:16:47,680 WHERE THEY ARE UNHEALTHY. 2918 02:16:47,680 --> 02:16:49,960 IT IS A STARTING POINT IS ALL I 2919 02:16:49,960 --> 02:16:51,400 WAS REALLY TRYING TO INDICATE. 2920 02:16:51,400 --> 02:16:54,680 YOU ARE ABSOLUTELY RIGHT. 2921 02:16:54,680 --> 02:16:57,400 RELATIONSHIP BETWEEN HEALTHSPAN 2922 02:16:57,400 --> 02:16:58,680 AND LIFESPAN IS COMPLEX AND NOT 2923 02:16:58,680 --> 02:17:02,040 WAY WE WANT IT TO BE AND 2924 02:17:02,040 --> 02:17:04,200 FANTASTIC AND SEEING EKG IN MICE 2925 02:17:04,200 --> 02:17:06,240 WE ACTUALLY SEE BOTH IMPROVING 2926 02:17:06,240 --> 02:17:10,080 IN SAME TIME AND IS JUST A 2927 02:17:10,080 --> 02:17:14,080 SOURCE OF HOPE. 2928 02:17:14,080 --> 02:17:18,360 >>SO, I THINK THAT WE HAVE TO 2929 02:17:18,360 --> 02:17:22,040 MONITOR LIFESPAN AND HEALTH SPAN 2930 02:17:22,040 --> 02:17:24,960 CONSTANTLY. HEALTH SPAN CAN BE 2931 02:17:24,960 --> 02:17:26,680 ASSESSED IN A NUMBER OF 2932 02:17:26,680 --> 02:17:28,520 DIFFERENT WAYS. 2933 02:17:28,520 --> 02:17:31,160 BUT, I THINK THAT SO FAR, IF WE 2934 02:17:31,160 --> 02:17:34,240 HAVE MADE IMPROVEMENTS AND IN 2935 02:17:34,240 --> 02:17:36,840 LENGTHENING LIFE, WE HAVE ALL -- 2936 02:17:36,840 --> 02:17:40,960 WE HAVE ALSO SORT OF PUSHED UP A 2937 02:17:40,960 --> 02:17:42,480 LITTLE BIT. 2938 02:17:42,480 --> 02:17:45,440 THE -- MORBIDITY. DISABILITY 2939 02:17:45,440 --> 02:17:47,480 AND FRAILTY MIGHT BE A DIFFERENT 2940 02:17:47,480 --> 02:17:50,640 ORDER OF MAGNITUDE. IT DOESN'T 2941 02:17:50,640 --> 02:17:53,480 APPEAR THAT WE HAVE ACTUALLY 2942 02:17:53,480 --> 02:17:57,040 CHANGED ALL THAT MUCH IN RECENT 2943 02:17:57,040 --> 02:17:58,320 DECADES AMONG AMERICANS, LET'S 2944 02:17:58,320 --> 02:17:58,520 SAY. 2945 02:17:58,520 --> 02:18:01,400 I THINK, YOU KNOW, IT IS A 2946 02:18:01,400 --> 02:18:02,960 COMPLEX SYSTEM THAT IS FITTING 2947 02:18:02,960 --> 02:18:05,280 TOGETHER HEALTH AND LENGTH OF 2948 02:18:05,280 --> 02:18:05,760 LIFE. 2949 02:18:05,760 --> 02:18:10,320 THAT -- WE ARE AIMING FOR LENGTH 2950 02:18:10,320 --> 02:18:14,840 OF HEALTHY LIFE AND THAT IS WHAT 2951 02:18:14,840 --> 02:18:17,040 WE HAVE TO MONITOR. 2952 02:18:17,040 --> 02:18:24,160 >>HI. MINA CRED RICK FROM CITY 2953 02:18:24,160 --> 02:18:30,200 OF HOPE AND APPRECIATE THIS 2954 02:18:30,200 --> 02:18:30,960 PRESENTATION AND WHAT LUIGI SAID 2955 02:18:30,960 --> 02:18:33,640 WHAT ARE THINGS WE CAN DO TO 2956 02:18:33,640 --> 02:18:35,640 MOVE PIPELINE FORWARD FOR THESE 2957 02:18:35,640 --> 02:18:37,000 AGING INTERVENTIONS? 2958 02:18:37,000 --> 02:18:40,840 AS A MEDICAL ONKOLGS AND 2959 02:18:40,840 --> 02:18:42,160 CLINICAL TRIALIST ONE THING THAT 2960 02:18:42,160 --> 02:18:44,840 ONCOLOGY HAS DONE REALLY WELL IS 2961 02:18:44,840 --> 02:18:46,200 DEVELOPED THESE -- THIS PIPELINE 2962 02:18:46,200 --> 02:18:48,200 TO TAKE DRUGS FROM THE LAB INTO 2963 02:18:48,200 --> 02:18:50,320 THE CLINIC AND THROUGH THE FDA. 2964 02:18:50,320 --> 02:18:53,960 ONE OF THE THINGS THAT THEY HAVE 2965 02:18:53,960 --> 02:18:56,800 DONE THAT I SEE THAT WE ARE 2966 02:18:56,800 --> 02:18:59,600 STILL STRUGGLING WITH IS THEY 2967 02:18:59,600 --> 02:19:00,760 HAVE VERY CLEAR DEFINITION ON 2968 02:19:00,760 --> 02:19:02,120 WHAT PURPOSE OF WHAT THEY ARE 2969 02:19:02,120 --> 02:19:05,160 DOING IS. IT IS OVERALL 2970 02:19:05,160 --> 02:19:07,520 SURVIVAL OR PROGRESSION-FREE 2971 02:19:07,520 --> 02:19:09,040 SURVIVAL OR OVERALL RESPONSE 2972 02:19:09,040 --> 02:19:10,680 RATE THAT IS VERY WELL DEFINED 2973 02:19:10,680 --> 02:19:12,480 AND MEASURED THE SAME WAY 2974 02:19:12,480 --> 02:19:14,720 THROUGHOUT ALL OF THE STUDIES 2975 02:19:14,720 --> 02:19:18,600 FROM PRECLINICAL TO CLINICAL 2976 02:19:18,600 --> 02:19:18,880 LEVEL. 2977 02:19:18,880 --> 02:19:22,080 IN AGING WE HAVE SEEN AND HEARD 2978 02:19:22,080 --> 02:19:23,440 IN THIS LAST PRESENTATION 2979 02:19:23,440 --> 02:19:26,320 MULTIPLE DIFFERENT STUDIES USING 2980 02:19:26,320 --> 02:19:29,920 DIFFERENT MEASURES OF AGING. 2981 02:19:29,920 --> 02:19:33,640 WHEN DEVELOPING THE TRIALS AND 2982 02:19:33,640 --> 02:19:35,200 TAKING DRUGS THAT GORDON HAS 2983 02:19:35,200 --> 02:19:37,120 STUDIED AND OTHERS IN MODEL IN 2984 02:19:37,120 --> 02:19:39,400 THE LAB AND WE WILL NOW DEVELOP 2985 02:19:39,400 --> 02:19:41,520 THEM INTO THE CLINIC, WHAT IS 2986 02:19:41,520 --> 02:19:43,320 THE MEASURE WE WILL BE CHANGING? 2987 02:19:43,320 --> 02:19:45,840 HAVE WE COME UP WITH A CONSENSUS 2988 02:19:45,840 --> 02:19:48,200 ON THIS IS WHAT WE ARE REALLY 2989 02:19:48,200 --> 02:19:49,400 TRYING TO HONE? 2990 02:19:49,400 --> 02:19:52,320 IS IT GOING TO BE SURVIVAL OR 2991 02:19:52,320 --> 02:19:53,720 GOING TO BE ANOTHER CLINICAL 2992 02:19:53,720 --> 02:19:54,200 MEASURE? 2993 02:19:54,200 --> 02:19:57,160 HOW DO WE RECONCILE THIS? 2994 02:19:57,160 --> 02:19:59,200 I THINK THERE ARE MANY BARRIERS 2995 02:19:59,200 --> 02:19:59,840 TO MOVING FORWARD. 2996 02:19:59,840 --> 02:20:02,760 I SEE IT AS A KEY IMPORTANT 2997 02:20:02,760 --> 02:20:05,200 BARRIER THAT WE AS, YOU KNOW, 2998 02:20:05,200 --> 02:20:09,680 NIA AND AS A SOCIETY NEED TO 2999 02:20:09,680 --> 02:20:15,040 IDENTIFY. 3000 02:20:15,040 --> 02:20:17,000 >>OKAY. ANY TAKERS? 3001 02:20:17,000 --> 02:20:18,720 >>I WILL LET YOU TAKE IT A 3002 02:20:18,720 --> 02:20:20,080 LITTLE LATER. 3003 02:20:20,080 --> 02:20:22,120 NO. REALLY IMPORTANT POINT. I 3004 02:20:22,120 --> 02:20:24,520 DO -- I THINK THAT IT HAS BEEN 3005 02:20:24,520 --> 02:20:26,720 HARD IN GERIATRICS AND TO FIND 3006 02:20:26,720 --> 02:20:28,640 THESE SORT OF OUTCOMES; RIGHT? 3007 02:20:28,640 --> 02:20:31,680 IN CANCER YOU HAVE A DISEASE; 3008 02:20:31,680 --> 02:20:33,360 RIGHT? A VERY CLEAR DISEASE AND 3009 02:20:33,360 --> 02:20:35,600 BIOPSIES YOU KNOW WHAT YOU HAVE 3010 02:20:35,600 --> 02:20:37,280 AND BIOLOGIC PATHWAYS THAT ARE, 3011 02:20:37,280 --> 02:20:39,120 YOU KNOW, COMPLEX. THEY AT 3012 02:20:39,120 --> 02:20:40,640 LEAST KNOW WHAT AND HOW THE 3013 02:20:40,640 --> 02:20:43,440 CANCER HAS BEEN DRIVEN AND WHY 3014 02:20:43,440 --> 02:20:46,040 IT IS GETTING MET ASS TA CRIED 3015 02:20:46,040 --> 02:20:48,200 AND IN AGING PHENOTYPES IT HAS 3016 02:20:48,200 --> 02:20:49,520 BEEN MORE DIFFICULT AND WE DON'T 3017 02:20:49,520 --> 02:20:52,240 HAVE GREAT DEFINITIONS YOU SEE 3018 02:20:52,240 --> 02:20:53,840 TWO MAJOR DEFINITIONS OF 3019 02:20:53,840 --> 02:20:54,600 FRAILTY; RIGHT? 3020 02:20:54,600 --> 02:20:56,920 YOU MIGHT BE ABLE TO IMPACT 3021 02:20:56,920 --> 02:20:58,720 BIOLOGY AND IN ANOTHER ONE IF 3022 02:20:58,720 --> 02:21:00,320 DIFFERENT VARIABLES IN ONE GROUP 3023 02:21:00,320 --> 02:21:03,360 OF PEOPLE THAT LEAD TO AN INDEX. 3024 02:21:03,360 --> 02:21:05,120 YOU KNOW, YOU DON'T KNOW WHICH 3025 02:21:05,120 --> 02:21:07,160 OF THE VARIABLES TO TARGET; 3026 02:21:07,160 --> 02:21:07,600 RIGHT? 3027 02:21:07,600 --> 02:21:10,680 THERE IS A COMPLEXITY IN THE 3028 02:21:10,680 --> 02:21:12,200 PHENOTYPIC MEASUREMENT THAT HAS 3029 02:21:12,200 --> 02:21:13,920 MADE IT A LITTLE MORE DIFFICULT 3030 02:21:13,920 --> 02:21:17,440 AND THERE HAS BEEN PROGRESS IN 3031 02:21:17,440 --> 02:21:20,080 SARCOPENIA FOR EXAMPLE AND 3032 02:21:20,080 --> 02:21:22,680 OSTEOPOROSIS AND THESE KIND OF 3033 02:21:22,680 --> 02:21:23,760 OVERALL PHENOTYPES THAT EMERGE 3034 02:21:23,760 --> 02:21:25,040 AS PEOPLE AGE AND SO I THINK 3035 02:21:25,040 --> 02:21:27,520 THAT THE BEST HOPE IS TO KIND OF 3036 02:21:27,520 --> 02:21:30,040 GO AFTER THESE SUBPHENOTYPES FOR 3037 02:21:30,040 --> 02:21:33,360 NOW AND NOT AFTER, YOU KNOW, 3038 02:21:33,360 --> 02:21:34,960 LONGEVITY. SOME HEALTH SPAN 3039 02:21:34,960 --> 02:21:36,360 RESEARCH I THINK WILL HELP US 3040 02:21:36,360 --> 02:21:37,920 FIGURE OUT WHAT SHOULD BE IN 3041 02:21:37,920 --> 02:21:40,160 THERE. I MEAN, IT MIGHT BE 3042 02:21:40,160 --> 02:21:41,400 WALKING SPEED THAT IS SOMETHING 3043 02:21:41,400 --> 02:21:43,520 THAT ENDS UP BEING A TARGET AND 3044 02:21:43,520 --> 02:21:46,120 WE TRIED THAT PATH YEARS AGO AND 3045 02:21:46,120 --> 02:21:49,240 FDA DIDN'T THINK IT WAS A GREAT 3046 02:21:49,240 --> 02:21:51,320 WAY TO GO. THINGS ARE EVOLVING 3047 02:21:51,320 --> 02:21:54,120 AND WE WILL HOPEFULLY GET TO 3048 02:21:54,120 --> 02:21:55,280 RIGHT PHENOTYPES EVENTUALLY. 3049 02:21:55,280 --> 02:21:56,480 >>HUH? 3050 02:21:56,480 --> 02:21:58,600 OKAY. SORRY YEAH. I GUESS 3051 02:21:58,600 --> 02:22:02,040 THERE IS ALSO THE IDEA IF YOU 3052 02:22:02,040 --> 02:22:04,720 INTERVENE WITH SOME SYNO LYTIC 3053 02:22:04,720 --> 02:22:06,200 OR SYNO STATIC INTERVENTION YOU 3054 02:22:06,200 --> 02:22:08,960 CAN LOOK AT REDUCTION IN CHRONIC 3055 02:22:08,960 --> 02:22:11,360 DISEASES OF AGING ONE COULD GET 3056 02:22:11,360 --> 02:22:13,560 THAT COULD BE A USEFUL OUTCOME 3057 02:22:13,560 --> 02:22:15,680 THAT IS BEING WORKED ON. 3058 02:22:15,680 --> 02:22:16,320 SO -- 3059 02:22:16,320 --> 02:22:20,240 >>I THINK WE WILL NEED TO AGREE 3060 02:22:20,240 --> 02:22:26,000 ON THE DEFINITION OF AGING 3061 02:22:26,000 --> 02:22:27,120 PROCESS THAT IS ONE THAT COULD 3062 02:22:27,120 --> 02:22:28,880 BE APPLIED EARLY IN LIFE AND 3063 02:22:28,880 --> 02:22:32,200 THINK WAY THAT PEOPLE ARE 3064 02:22:32,200 --> 02:22:33,920 STUDYING DEMENTIA AND 3065 02:22:33,920 --> 02:22:36,200 ALZHEIMER'S DISEASE NOW ARE 3066 02:22:36,200 --> 02:22:39,840 LOOKING FOR MARKERS TO INTERVENE 3067 02:22:39,840 --> 02:22:43,800 ON PEOPLE WHO ARE DECADES BEFORE 3068 02:22:43,800 --> 02:22:44,920 ACTUALLY HAVING THE DISEASE 3069 02:22:44,920 --> 02:22:46,520 OCCUR CLINICALLY. I THINK THAT 3070 02:22:46,520 --> 02:22:48,600 IS WHAT AGING IS GOING TO 3071 02:22:48,600 --> 02:22:50,480 REQUIRE. I THINK THAT WE ARE 3072 02:22:50,480 --> 02:22:52,880 GOING TO NEED A DEFINITION OF 3073 02:22:52,880 --> 02:22:59,440 WHO IS AGING RAPIDLY. THAT 3074 02:22:59,440 --> 02:23:02,560 ALLOWS US TO DEFINE PEOPLE INTO 3075 02:23:02,560 --> 02:23:04,360 THAT CATEGORY IF 30 OR 40 YEARS 3076 02:23:04,360 --> 02:23:06,720 OLD, ACTUALLY, IF WE HAVE AN 3077 02:23:06,720 --> 02:23:09,240 IMPACT WHEN WE INTERVENE. 3078 02:23:09,240 --> 02:23:11,520 >>ONE RELATED POINT IN MUCH OF 3079 02:23:11,520 --> 02:23:12,960 THE WORK THAT WE HAVE HEARD 3080 02:23:12,960 --> 02:23:15,880 DURING THE MEETING FOR ANIMAL 3081 02:23:15,880 --> 02:23:17,840 MODELS FOCUSING ON SURVIVAL OR 3082 02:23:17,840 --> 02:23:19,520 MORTALITY AS THE OUTCOME. I 3083 02:23:19,520 --> 02:23:22,600 THINK THAT THE ANIMAL MODEL WILL 3084 02:23:22,600 --> 02:23:26,200 NEED TO INCORPORATE NONMORTALITY 3085 02:23:26,200 --> 02:23:28,760 OUTCOMES THAT GET AT THE HEALTH 3086 02:23:28,760 --> 02:23:32,280 SPAN PART OF THE EQUATION AND 3087 02:23:32,280 --> 02:23:34,720 WHETHER IT IS GAIT SPEED OR 3088 02:23:34,720 --> 02:23:38,280 SOMETHING COMPARABLE SO WHEN 3089 02:23:38,280 --> 02:23:40,720 INVESTIGATING BIOMARKERS FOR 3090 02:23:40,720 --> 02:23:42,720 CHANGES IN MORE APPROXIMATE 3091 02:23:42,720 --> 02:23:45,920 INDICATORS OF SURVIVAL THAT 3092 02:23:45,920 --> 02:23:56,480 TRIALS WILL BE MORE FEASIBLE ONE 3093 02:23:58,280 --> 02:23:59,880 COMMENT ABOUT DISCUSSION BEFORE 3094 02:23:59,880 --> 02:24:04,240 ABOUT BIOMARKER COMPARED TO 3095 02:24:04,240 --> 02:24:05,280 CLINICAL FINDINGS. 3096 02:24:05,280 --> 02:24:07,440 YOU KNOW, ONE COMMENT I HAVE 3097 02:24:07,440 --> 02:24:10,000 THAT IN OUR STUDIES AND OUR 3098 02:24:10,000 --> 02:24:12,240 LONGITUDINAL STUDIES THAT WE 3099 02:24:12,240 --> 02:24:19,640 COLLECT A WEALTH OF INFORMATION 3100 02:24:19,640 --> 02:24:26,720 WE DO MRI AND MEASURE WALKING 3101 02:24:26,720 --> 02:24:30,880 SPEED AND BLOOD TEST AND KEEP 3102 02:24:30,880 --> 02:24:32,800 PARTICIPANT THREE DAYS IN UNIT 3103 02:24:32,800 --> 02:24:36,680 AND MEASURE BIOMARKER. WE CAN'T 3104 02:24:36,680 --> 02:24:38,400 REALLY COMPARE WHAT WE GET 3105 02:24:38,400 --> 02:24:41,120 CLINICALLY WITH BIOMARKER. 3106 02:24:41,120 --> 02:24:42,280 CLINICALLY THEY ARE MORE 3107 02:24:42,280 --> 02:24:46,000 POWERFUL AS PREDICTOR AND 3108 02:24:46,000 --> 02:24:47,040 PROVIDE MORE INFORMATION THAT IS 3109 02:24:47,040 --> 02:24:50,960 ABOUT HEALTH STATUS IN GENERAL 3110 02:24:50,960 --> 02:24:53,960 AND IN PARTICULAR AND HOWEVER WE 3111 02:24:53,960 --> 02:24:57,200 THINK ABOUT TRANSLATION THAT 3112 02:24:57,200 --> 02:24:58,720 PHENOTYPING WILL NEVER BE DONE 3113 02:24:58,720 --> 02:25:01,400 IN PATIENTS. TOO EXPENSIVE AND 3114 02:25:01,400 --> 02:25:04,440 REQUIRE SO MUCH MORE TIME. 3115 02:25:04,440 --> 02:25:05,560 CAPTURING THOSE INFORMATION 3116 02:25:05,560 --> 02:25:08,560 THROUGH LENS OF BIOMARKER REALLY 3117 02:25:08,560 --> 02:25:11,480 MAY FACILITATE TRANSLATION OF 3118 02:25:11,480 --> 02:25:14,680 THIS INFORMATION TO THE BED OF 3119 02:25:14,680 --> 02:25:15,840 THE PATIENT. 3120 02:25:15,840 --> 02:25:19,920 THINK ABOUT EPIGENETIC CLOCK I 3121 02:25:19,920 --> 02:25:22,400 CAN MEASURE IN A DROP OF A BLOOD 3122 02:25:22,400 --> 02:25:29,200 AND WE KNEE $1,000 NOW OR $250 3123 02:25:29,200 --> 02:25:30,720 NOW NO REASON IT SHOULDN'T COST 3124 02:25:30,720 --> 02:25:32,800 FIVE CENTS. IT SHOULD. IF YOU 3125 02:25:32,800 --> 02:25:36,520 SCALE IT UP, IT WILL COST 5 3126 02:25:36,520 --> 02:25:39,280 CENTS AND WORK ON BIOMARKER GOES 3127 02:25:39,280 --> 02:25:42,240 TOWARDS TRANSLATION AND 3128 02:25:42,240 --> 02:25:44,360 MEASURING BIOMARKER IS FAST AND 3129 02:25:44,360 --> 02:25:47,400 THEORETICAL WILL I COULD BE VERY 3130 02:25:47,400 --> 02:25:57,720 CHEAP AND ECONOMIC. 3131 02:26:00,880 --> 02:26:02,720 >>JUST TO COMMENT ON EXCELLENT 3132 02:26:02,720 --> 02:26:05,160 POINTS AND, AGAIN, BEING A 3133 02:26:05,160 --> 02:26:07,280 CLINICIAN AS WE INTEGRATE 3134 02:26:07,280 --> 02:26:08,840 TECHNOLOGIES FOR BIOMARKER 3135 02:26:08,840 --> 02:26:10,640 DEVELOPMENTS ARE REALLY KEEPING 3136 02:26:10,640 --> 02:26:13,480 IN MIND THAT CLINICAL RELEVANCE 3137 02:26:13,480 --> 02:26:15,000 AS WELL FOR PATIENT AND WHETHER 3138 02:26:15,000 --> 02:26:18,680 IN TERMS OF PRODUCING 3139 02:26:18,680 --> 02:26:21,880 COMORBIDITY BURDEN OR, AGAIN, 3140 02:26:21,880 --> 02:26:22,680 COMPRESSING THAT MORBID PHASE 3141 02:26:22,680 --> 02:26:25,800 THAT IS GOING TO BE CRITICAL FOR 3142 02:26:25,800 --> 02:26:27,720 CHOOSING WHICH BIOMARKERS WE END 3143 02:26:27,720 --> 02:26:34,680 UP USING TO COME UP WITH THIS 3144 02:26:34,680 --> 02:26:39,680 MORE -- A MORE WELL-DEFINED 3145 02:26:39,680 --> 02:26:41,200 DEFINITION FOR FUTURE STUDIES WE 3146 02:26:41,200 --> 02:26:51,200 ARE THINKING ABOUT. YEAH. 3147 02:26:51,200 --> 02:26:52,960 >>IF I CAN MAKE A QUICK 3148 02:26:52,960 --> 02:26:54,680 COMMENT. I THINK MAYBE WHAT I 3149 02:26:54,680 --> 02:26:57,920 HEARD IS THAT SOME FRAILTY 3150 02:26:57,920 --> 02:26:59,120 ASSESSMENTS ARE COMPLEX AND I -- 3151 02:26:59,120 --> 02:27:02,280 I KNOW IN THE UNITED KINGDOM, 3152 02:27:02,280 --> 02:27:05,320 FOR EXAMPLE, THEY ARE PRODUCING 3153 02:27:05,320 --> 02:27:07,280 ELECTRONIC FRAILTY INDEX OR EFI. 3154 02:27:07,280 --> 02:27:09,480 THEY HAVE THAT ON -- I DON'T 3155 02:27:09,480 --> 02:27:11,920 KNOW. ONE PAPER PUBLISHED 3156 02:27:11,920 --> 02:27:13,320 FAIRLY RECENTLY WAS HALF A 3157 02:27:13,320 --> 02:27:16,400 MILLION OR 600,000 PEOPLE AND 3158 02:27:16,400 --> 02:27:17,840 NOW IS NOR AND FOUND WAY TO AUTO 3159 02:27:17,840 --> 02:27:21,880 MA ET IT WITH ELECTRONIC DATA 3160 02:27:21,880 --> 02:27:24,160 CAPTURE AND DO IT INDEPENDENTLY 3161 02:27:24,160 --> 02:27:25,920 AND TECHNOLOGIES MIGHT BE ABLE 3162 02:27:25,920 --> 02:27:27,680 TO ALLOW YOU TO COLLECT DATA 3163 02:27:27,680 --> 02:27:31,880 THAT WOULD BE INTERESTING IF 3164 02:27:31,880 --> 02:27:36,120 LOOKING AT SPECIFIC BIOMARKERS. 3165 02:27:36,120 --> 02:27:38,520 >>HOW SHARP OF A DISTINCTION 3166 02:27:38,520 --> 02:27:41,160 SHOULD I DRAW BETWEEN DELAYING, 3167 02:27:41,160 --> 02:27:42,760 AGING, AND REJUVENATION? 3168 02:27:42,760 --> 02:27:46,560 IT IS ALL ONE STORY. 3169 02:27:46,560 --> 02:27:54,360 BUT -- 3170 02:27:54,360 --> 02:27:59,520 >>>>HEATHER CAN YOU HELP ME 3171 02:27:59,520 --> 02:28:02,600 OUT? IN MY TALK I TALK ABOUT 3172 02:28:02,600 --> 02:28:04,280 DIFFERENCE OF REDILIGENCE AND TO 3173 02:28:04,280 --> 02:28:07,360 ME IS BIT OF END STAGE GERIATRIC 3174 02:28:07,360 --> 02:28:09,520 CONDITION THAT IS HARD TO PULL 3175 02:28:09,520 --> 02:28:12,080 PEOPLE BACK FROM AND CLINICAL 3176 02:28:12,080 --> 02:28:14,680 PRACTICE SOMEBODY WITH 3 ORE 4 3177 02:28:14,680 --> 02:28:17,360 OR 5 OF PHYSICAL FRAILTY ISSUES 3178 02:28:17,360 --> 02:28:22,400 IS REALLY HARD TO MOVE THEM BACK 3179 02:28:22,400 --> 02:28:24,400 INTO PREVENTIVE CARE. 3180 02:28:24,400 --> 02:28:26,720 >>MED TECH FOR THEM OPPOSED TO 3181 02:28:26,720 --> 02:28:28,640 FARM COLONL CAL. 3182 02:28:28,640 --> 02:28:31,240 >>WE DO MORE PALLIATIVE CARE 3183 02:28:31,240 --> 02:28:34,680 THINGS ACTIVITIES AND DIETARY 3184 02:28:34,680 --> 02:28:36,760 CHANGE AND CAN YOU HELP TO KEEP 3185 02:28:36,760 --> 02:28:38,720 PEOPLE OUT OF THE HOSPITAL AND 3186 02:28:38,720 --> 02:28:40,880 PREVENT THEM FROM HAVING 3187 02:28:40,880 --> 02:28:42,360 CATASTROPHIC OUTCOMES AND USE IT 3188 02:28:42,360 --> 02:28:45,080 AS A BIT OF A RISK ASSESSMENT IN 3189 02:28:45,080 --> 02:28:48,880 CLINICAL PRACTICE AND PROBABLY 3190 02:28:48,880 --> 02:28:51,720 FOR THE INDEX. 3191 02:28:51,720 --> 02:28:53,640 RESILIENCY AND RESILIENCE 3192 02:28:53,640 --> 02:28:55,840 RESEARCH IS FOCUSED ON 3193 02:28:55,840 --> 02:29:00,280 PREVENTION AND THINKING ABOUT 3194 02:29:00,280 --> 02:29:03,720 PATHWAYS BECOMELE UNRAVELLED 3195 02:29:03,720 --> 02:29:06,160 PUTTING PEOPLE AT HIGHER RISK 3196 02:29:06,160 --> 02:29:08,080 DOWN THE ROAD AND WANT TO FIND 3197 02:29:08,080 --> 02:29:10,680 THEM EARLY AND TRY TO THINK OF 3198 02:29:10,680 --> 02:29:13,160 THEM AS SEPARATE IN REJUVENATION 3199 02:29:13,160 --> 02:29:16,000 WORD THAT YOU MEAN SETTING IN 3200 02:29:16,000 --> 02:29:17,760 MIDDLE THAT I DON'T KNOW IS HARD 3201 02:29:17,760 --> 02:29:20,520 TO MOVE PEOPLE BACKWARDS 3202 02:29:20,520 --> 02:29:22,960 PROBABLY OR BACK TOWARDS FULL 3203 02:29:22,960 --> 02:29:27,760 RESILIENCE AND MAY BE WAYS TO 3204 02:29:27,760 --> 02:29:28,600 DELAY TRAJECTORIES THAT IS HOW I 3205 02:29:28,600 --> 02:29:32,520 THINK ABOUT IT AND WILL LET 3206 02:29:32,520 --> 02:29:39,320 HAENLER TALK ABOUT IT TOMORROW. 3207 02:29:39,320 --> 02:29:41,920 >>THANK YOU FOR YOUR 3208 02:29:41,920 --> 02:29:42,960 PRESENTATIONS WHEN UNDERSTANDING 3209 02:29:42,960 --> 02:29:44,080 CREATURE AND UNDERSTANDING OF 3210 02:29:44,080 --> 02:29:46,080 HUMAN BEING THERE IS SUBJECTIVE 3211 02:29:46,080 --> 02:29:49,120 EXPERIENCES AND HUMAN MIND THAT 3212 02:29:49,120 --> 02:29:50,880 CAN REALLY INFLUENCE BIOLOGY AND 3213 02:29:50,880 --> 02:29:53,720 BIOMARKERS WE ARE LOOKING INTO 3214 02:29:53,720 --> 02:29:56,320 AND THINKING OF MOBILITY YOU CAN 3215 02:29:56,320 --> 02:29:58,720 TURN AROUND A 6 MINUTE WALK TO 3216 02:29:58,720 --> 02:30:01,520 AVERAGE ONE PRIMING THEM WITH 3217 02:30:01,520 --> 02:30:04,240 IMPLICIT BIAS AND AGEISM. 3218 02:30:04,240 --> 02:30:10,480 YOU CAN CHANGE ALSO PSYCHOSOCIAL 3219 02:30:10,480 --> 02:30:12,160 INFLUENCES AND SOCIAL 3220 02:30:12,160 --> 02:30:13,920 DETERMINANTS OF AGING GOING 3221 02:30:13,920 --> 02:30:15,760 THROUGH SUBJECTIVE EXPERIENCES 3222 02:30:15,760 --> 02:30:17,160 AND JEREMY I WAS STRUCK BY LIST 3223 02:30:17,160 --> 02:30:19,120 OF BEAUTIFUL ASSESSMENTS YOU ARE 3224 02:30:19,120 --> 02:30:21,760 RUNNING AND LOTS ARE KNOWN TO BE 3225 02:30:21,760 --> 02:30:23,520 DOWNSTREAM OF PSYCHOLOGICAL 3226 02:30:23,520 --> 02:30:27,560 STATES AND HP ACCESS AND 3227 02:30:27,560 --> 02:30:29,560 GLYCEMIC CONTROL AND THESE CAN 3228 02:30:29,560 --> 02:30:30,960 BE INFLUENCED IN RANGE OF 3229 02:30:30,960 --> 02:30:32,840 MINUTES, SECONDS TO MINUTES 3230 02:30:32,840 --> 02:30:39,160 BLOOD PRESSURE AUTONOMIC NERVOUS 3231 02:30:39,160 --> 02:30:40,760 SYSTEM WITH BILOGICAL FACTORS 3232 02:30:40,760 --> 02:30:42,840 AND HOW WE ARE THINKING ABOUT 3233 02:30:42,840 --> 02:30:45,680 THIS AND HUMAN MIND AS A 3234 02:30:45,680 --> 02:30:47,000 CONTRIBUTOR AND SOMETHING TO 3235 02:30:47,000 --> 02:30:49,080 BIOMARK IN WAY THAT IS NOT JUST 3236 02:30:49,080 --> 02:30:51,240 LOOKING AT CIRCULATING MOLECULES 3237 02:30:51,240 --> 02:30:54,280 AND IS THIS A REAL CONTRIBUTOR 3238 02:30:54,280 --> 02:30:57,440 TO HUMAN AGING AND SHOULD IT BE 3239 02:30:57,440 --> 02:31:00,040 PART OF GEROSCIENCE AGENDA? 3240 02:31:00,040 --> 02:31:02,320 WOULD LOVE TO HEAR YOUR THOUGHTS 3241 02:31:02,320 --> 02:31:03,520 ON THIS. 3242 02:31:03,520 --> 02:31:04,800 >>I GUESS THAT CERTAINLY PEOPLE 3243 02:31:04,800 --> 02:31:07,760 THINK OF THE STATE OF THE HUMAN 3244 02:31:07,760 --> 02:31:13,400 MIND AS AN INCREDIBLE INPUT INTO 3245 02:31:13,400 --> 02:31:18,240 THE AGING. AND THE CHANGES IN 3246 02:31:18,240 --> 02:31:19,760 BIOMARKERS AND IN HEALTH THAT 3247 02:31:19,760 --> 02:31:22,240 MIGHT OCCUR AND ISSUE IS SHOULD 3248 02:31:22,240 --> 02:31:24,280 IT BE INCORPORATED AS INDICATOR 3249 02:31:24,280 --> 02:31:29,000 OF AGING OR IS IT A CAUSE OF 3250 02:31:29,000 --> 02:31:32,080 FASTER OR SLOWER AGING? 3251 02:31:32,080 --> 02:31:36,120 I FEEL THE WAY IT IS BEING USED 3252 02:31:36,120 --> 02:31:39,600 NO YOU IS KIND OF APPROPRIATE. 3253 02:31:39,600 --> 02:31:40,760 >>UH-HUH. 3254 02:31:40,760 --> 02:31:43,360 >>WE TRY TO CAPTURE SOME OF THE 3255 02:31:43,360 --> 02:31:45,360 PSYCHOSOCIAL VARIABLES THAT I 3256 02:31:45,360 --> 02:31:48,120 THINK DO DRIVE KIND OF THE BRAIN 3257 02:31:48,120 --> 02:31:51,240 FUNCTION IN WAYS THAT IMPACT 3258 02:31:51,240 --> 02:31:51,640 PHYSIOLOGY. 3259 02:31:51,640 --> 02:31:54,520 YOU KNOW, HOW TO PUT IT ALL INTO 3260 02:31:54,520 --> 02:31:58,200 ONE BIG MODEL IS HOPEFULLY 3261 02:31:58,200 --> 02:31:59,480 FRIENDS FROM THIS AFTERNOON THAT 3262 02:31:59,480 --> 02:32:03,480 WILL TELL US HOW TO DO THAT. 3263 02:32:03,480 --> 02:32:05,320 IT IS COMPLEX AND TRYING TO 3264 02:32:05,320 --> 02:32:06,720 DISSECT OUT THINKING ABOUT 3265 02:32:06,720 --> 02:32:10,160 INDIVIDUAL PATIENTS AND I COME 3266 02:32:10,160 --> 02:32:13,320 BACK TO PRECISION APPROACH AND 3267 02:32:13,320 --> 02:32:16,600 PEOPLE WILL HAVE A BIG DRIVING 3268 02:32:16,600 --> 02:32:18,760 FACTOR BASED ON RECENT SPOUSAL 3269 02:32:18,760 --> 02:32:21,440 DEATH OR MAJOR OR CHILDHOOD 3270 02:32:21,440 --> 02:32:24,280 TRAUMA THAT KEEPS COMING UP AND 3271 02:32:24,280 --> 02:32:27,880 PATIENT ONCE IN WORLD WAR II 3272 02:32:27,880 --> 02:32:30,080 THAT WAS YEARS AGO AND AT END OF 3273 02:32:30,080 --> 02:32:33,640 THE WORLD NEXT TO FELLOW BRITISH 3274 02:32:33,640 --> 02:32:35,360 SOLDIER SHOT IN THE HEAD WALKING 3275 02:32:35,360 --> 02:32:37,880 DOWN STREET AND SURVIVED AND HAD 3276 02:32:37,880 --> 02:32:40,320 NIGHT TERRORS LASTING UNTIL HE 3277 02:32:40,320 --> 02:32:44,320 WAS IN 80S AND HAD HUGE IMPACT 3278 02:32:44,320 --> 02:32:45,320 THROUGH SYSTEMS THROUGHOUT HIS 3279 02:32:45,320 --> 02:32:46,880 WHOLE LIFE AND WHEN HE WAS OLDER 3280 02:32:46,880 --> 02:32:49,640 AND THERE ARE SORTS OF THINGS, 3281 02:32:49,640 --> 02:32:52,760 AGAIN, GOING BACK TO WHAT LIU 3282 02:32:52,760 --> 02:32:54,280 SAID AND THINKING ABOUT TAKING 3283 02:32:54,280 --> 02:32:55,680 INFORMATION THAT WE HAVE TO COME 3284 02:32:55,680 --> 02:32:58,680 UP WITH MUCH MORE SORT OF 3285 02:32:58,680 --> 02:33:00,480 PRECISE METHODS AND LIKE, YOU 3286 02:33:00,480 --> 02:33:02,280 KNOW, THIS PARTICULAR PIECE OF 3287 02:33:02,280 --> 02:33:05,600 THE PIE IS REALLY RELEVANT FOR 3288 02:33:05,600 --> 02:33:07,880 THIS PATIENT AND FOR SOMEBODY 3289 02:33:07,880 --> 02:33:09,440 ELSE IS TOTALLY IRRELEVANT AND 3290 02:33:09,440 --> 02:33:11,240 WE HAVE TO GET TO THAT POINT. I 3291 02:33:11,240 --> 02:33:13,400 DON'T KNOW IF IT GETS AT WHAT 3292 02:33:13,400 --> 02:33:16,200 YOU ARE ASKING? 3293 02:33:16,200 --> 02:33:18,680 >>YES. THANK YOU. 3294 02:33:18,680 --> 02:33:26,680 >>UNIVERSITY OF MONTREAL, 3295 02:33:26,680 --> 02:33:31,240 CANADA AND COMING BACK TO 3296 02:33:31,240 --> 02:33:34,720 OUTCOMES AND THINKING OF 3297 02:33:34,720 --> 02:33:36,480 CONSIDERATION FOR WHAT HEALTH 3298 02:33:36,480 --> 02:33:40,480 SYSTEM WANT AND MENTIONING 3299 02:33:40,480 --> 02:33:42,880 LONGER YEARS WITHOUT COMORBIDITY 3300 02:33:42,880 --> 02:33:45,200 AND LONGER YEARS WITHOUT 3301 02:33:45,200 --> 02:33:46,720 DISABILITY AND IN THAT SENSE ARE 3302 02:33:46,720 --> 02:33:50,720 WE DEFINING CLEARLY TARGET 3303 02:33:50,720 --> 02:33:52,760 ORGANS INSTEAD OF BEING 3304 02:33:52,760 --> 02:33:56,120 OVERAMBITIOUS IN STOP OF AGING 3305 02:33:56,120 --> 02:33:58,000 AND PROLONGING LIFE SURVIVAL ARE 3306 02:33:58,000 --> 02:34:00,640 WE TARGETING MOST IMPORTANT 3307 02:34:00,640 --> 02:34:02,520 DETERMINANTS OF DISABILITY AND 3308 02:34:02,520 --> 02:34:06,840 YEARS FREE OF THAT DISABILITY? 3309 02:34:06,840 --> 02:34:10,560 JEREMY MENTIONED OSTEOPOROSIS 3310 02:34:10,560 --> 02:34:14,360 AND SAR CO PINA FIELDS IN THAT 3311 02:34:14,360 --> 02:34:17,120 SENSE AND DETERMINING AND 3312 02:34:17,120 --> 02:34:18,200 TARGETING MECHANISMS THAT COULD 3313 02:34:18,200 --> 02:34:24,360 BE MORE VALUABLE AND EFFECTIVE 3314 02:34:24,360 --> 02:34:27,480 IMPROVING YEARS WITHOUT 3315 02:34:27,480 --> 02:34:37,880 DISABILITY? 3316 02:34:37,880 --> 02:34:38,640 >>I CAN TRY. 3317 02:34:38,640 --> 02:34:41,200 I KNOW WHAT YOU ARE SAYING. 3318 02:34:41,200 --> 02:34:42,080 PEOPLE GET FRAIL IN SO MANY 3319 02:34:42,080 --> 02:34:44,280 DIFFERENT WAYS IT MIGHT BE HARD 3320 02:34:44,280 --> 02:34:45,480 TO ACTUALLY SAY THESE ARE ONLY 3321 02:34:45,480 --> 02:34:47,040 THINGS I WILL TARGET, IF YOU 3322 02:34:47,040 --> 02:34:48,160 KNOW WHAT I MEAN. 3323 02:34:48,160 --> 02:34:50,720 SO, I THINK THAT DEVELOPING 3324 02:34:50,720 --> 02:34:55,800 THERAPIES THAT TEND TO ATTENUATE 3325 02:34:55,800 --> 02:34:58,200 FUNDAMENTAL PROCESSES THAT ARE 3326 02:34:58,200 --> 02:35:00,960 GOING AWRY IN AGING AND DRIVING 3327 02:35:00,960 --> 02:35:04,720 FRAILTY IN AGING IS A PROMISING 3328 02:35:04,720 --> 02:35:06,320 APPROACH AND RATHER THAN JUST 3329 02:35:06,320 --> 02:35:09,640 DECIDING ON ONE SPECIFIC 3330 02:35:09,640 --> 02:35:11,240 OUTCOME. LIKE YOU KNOW, I'M NOT 3331 02:35:11,240 --> 02:35:13,360 A CLINICIAN AND FEELING OUT OF 3332 02:35:13,360 --> 02:35:15,720 MY DEPTH ANSWERING SOME CLINICAL 3333 02:35:15,720 --> 02:35:16,200 QUESTIONS. 3334 02:35:16,200 --> 02:35:18,320 >>YEAH. I MEAN THAT WORK THAT 3335 02:35:18,320 --> 02:35:21,960 HAS BEEN PUBLISHED CONSISTENTLY 3336 02:35:21,960 --> 02:35:24,320 IS SHOWING WHAT OLDER PERSONS 3337 02:35:24,320 --> 02:35:28,240 VALUE ABOVE ANYTHING ELSE IS 3338 02:35:28,240 --> 02:35:33,560 THEIR INDEPENDENCE DEFINING AS 3339 02:35:33,560 --> 02:35:35,000 ABSENCE OF VARIABILITY AND NOT 3340 02:35:35,000 --> 02:35:37,640 RELYING ON SOMEONE ELSE TO CARRY 3341 02:35:37,640 --> 02:35:39,760 OUT ACTIVITIES OF DAILY LIVING, 3342 02:35:39,760 --> 02:35:43,840 THAT AND MOST SURVEYS WILL BE 3343 02:35:43,840 --> 02:35:47,320 TOP PRIORITY. 3344 02:35:47,320 --> 02:35:50,680 IT IS ALMOST ALWAYS TOP 3 3345 02:35:50,680 --> 02:35:53,240 PRIORITIES AND WHY WE HAVE TO BE 3346 02:35:53,240 --> 02:35:54,560 CONSIDERING COMPLEMENTARY HEALTH 3347 02:35:54,560 --> 02:35:57,760 SPAN INDICATORS AS OUTCOMES AND 3348 02:35:57,760 --> 02:35:59,880 FRAILTY INDEX HAS ATTRACTIVE 3349 02:35:59,880 --> 02:36:05,480 FACTORS BUT DIMINISHING THAT 3350 02:36:05,480 --> 02:36:09,240 SCORE MAY NOT BE MEANINGFUL TO 3351 02:36:09,240 --> 02:36:10,680 THE INDIVIDUAL PATIENT BECAUSE 3352 02:36:10,680 --> 02:36:12,320 THINGS THAT ARE CORRECTED ARE 3353 02:36:12,320 --> 02:36:16,000 NOT RELEVANT TO THEIR LIFE. 3354 02:36:16,000 --> 02:36:22,000 SO, I -- I WOULD ENCOURAGE, YOU 3355 02:36:22,000 --> 02:36:24,040 KNOW, AS THE FIELD MOVES FORWARD 3356 02:36:24,040 --> 02:36:26,680 TO REFLECT CAREFULLY WHAT 3357 02:36:26,680 --> 02:36:29,120 PATIENTS ARE TELLING US, YOU 3358 02:36:29,120 --> 02:36:31,160 KNOW, CONSISTENTLY WHEN THEY 3359 02:36:31,160 --> 02:36:34,960 COME INTO THE CLINIC AND OTHER 3360 02:36:34,960 --> 02:36:38,960 HEA 3361 02:36:38,960 --> 02:36:40,640 HEALTHCARE SETTINGS. 3362 02:36:40,640 --> 02:36:41,760 >>BEAUTIFUL SESSION THIS 3363 02:36:41,760 --> 02:36:43,400 MORNING AND FANTASTIC PANEL AND 3364 02:36:43,400 --> 02:36:45,640 WANT TO BRING YOU BACK TO SOME 3365 02:36:45,640 --> 02:36:47,680 THINGS THAT SUSAN WAS MENTIONING 3366 02:36:47,680 --> 02:36:50,760 WITH THE FRAILTY INDEX AND ALSO 3367 02:36:50,760 --> 02:36:54,760 TO BIOMARKERS FIELD. 3368 02:36:54,760 --> 02:36:58,200 SO, IN MOUSE BIOLOGY FIELD WE 3369 02:36:58,200 --> 02:36:59,800 HAVE DONE INTERVENTIONS AND 3370 02:36:59,800 --> 02:37:01,840 COLLECTING IN SOME CASES 3371 02:37:01,840 --> 02:37:03,400 MEASUREMENTS OF HEALTH SPAN AND 3372 02:37:03,400 --> 02:37:06,200 ALSO WHEN DOING INTERVENTIONS 3373 02:37:06,200 --> 02:37:09,680 DEPENDING WHEN WE START WITH 3374 02:37:09,680 --> 02:37:13,320 INTERVENTIONS WE SEE REVERSAL OF 3375 02:37:13,320 --> 02:37:16,600 TRENDS IN BIOMARKERS AND FIELD 3376 02:37:16,600 --> 02:37:20,200 IS NEEDING BIOMARKERS 3377 02:37:20,200 --> 02:37:22,920 RESPONSIBLE TO INTERVENTIONS AND 3378 02:37:22,920 --> 02:37:25,160 DESCRIBING PHARMACY MODEL WHEN 3379 02:37:25,160 --> 02:37:29,760 YOU ELIMINATE POLYPHARMACY HOW 3380 02:37:29,760 --> 02:37:33,520 QUICKLY MILES RETURN TO NORMAL 3381 02:37:33,520 --> 02:37:38,040 STATE OF TRANL JEKTTRY FOR 3382 02:37:38,040 --> 02:37:41,640 FRAILTY AND CAN WE DEFINE 3383 02:37:41,640 --> 02:37:42,360 BIOMARKERS ALTERED IN SHORT 3384 02:37:42,360 --> 02:37:45,280 PERIOD OF TIME THAT IS FOR LONG 3385 02:37:45,280 --> 02:37:46,360 TERM OR SHORT TERM INTERVENTIONS 3386 02:37:46,360 --> 02:37:49,800 AND HOW THAT CAN ACCELERATE 3387 02:37:49,800 --> 02:37:52,240 TRANSLATION INTO THE FIELD. 3388 02:37:52,240 --> 02:37:55,160 WHEN WE STARTED THIS PROJECT WAS 3389 02:37:55,160 --> 02:37:59,720 MENTIONED THANKS, TOM, FOR 3390 02:37:59,720 --> 02:38:01,880 MENTIONING IT TO PREDICT 3391 02:38:01,880 --> 02:38:04,080 TRAJECTORIES OF AGING IN MICE 3392 02:38:04,080 --> 02:38:08,080 AND TRYING INTERVENTION 3393 02:38:08,080 --> 02:38:14,520 MEASUREMENTS TO BE IS IN SHORT 3394 02:38:14,520 --> 02:38:17,560 TERM DECLINE IN SPEES AND 3395 02:38:17,560 --> 02:38:19,960 INTERVENTION WITH EXERCISE WILL 3396 02:38:19,960 --> 02:38:22,360 MOUSE RECOVER IN GAIT SPEED IN 3397 02:38:22,360 --> 02:38:24,160 THREE MONTHS LOST IN PRECEDING 3398 02:38:24,160 --> 02:38:26,240 THAT INTERVENTION AND WE HAVE TO 3399 02:38:26,240 --> 02:38:28,640 START THINKING AND US INCLUDING 3400 02:38:28,640 --> 02:38:30,320 CONCEPT EACH MOUSE WHEN 3401 02:38:30,320 --> 02:38:32,680 GENETICALLY IDENTICAL THEY HAVE 3402 02:38:32,680 --> 02:38:36,040 A DIFFERENT RESPONSE TO THAT 3403 02:38:36,040 --> 02:38:38,080 GIVEN INTERVENTION. 3404 02:38:38,080 --> 02:38:40,280 I WILL GIVE YOU WELL-KNOWN 3405 02:38:40,280 --> 02:38:41,200 ESTABLISHED THING ABOUT 3406 02:38:41,200 --> 02:38:41,720 [INDISCERNIBLE]. 3407 02:38:41,720 --> 02:38:44,640 YOU PUT IT ON HIGH FAT DIET AND 3408 02:38:44,640 --> 02:38:46,560 20% OF THAT POPULATION WOULD NOT 3409 02:38:46,560 --> 02:38:50,360 GAIN WEIGHT. WE DON'T EVEN 3410 02:38:50,360 --> 02:38:52,200 UNDERSTAND THAT AND WHY AND WE 3411 02:38:52,200 --> 02:38:55,600 KNOW THAT THERE IS A RESPONSE TO 3412 02:38:55,600 --> 02:38:58,400 INTERVENTIONS EVEN IN VERY WELL 3413 02:38:58,400 --> 02:38:59,440 CHARACTERIZED AND WELL 3414 02:38:59,440 --> 02:39:02,400 CONTROLLED STUDIES THAT I THINK 3415 02:39:02,400 --> 02:39:05,840 THAT CONCEPT OF PERSONALIZED 3416 02:39:05,840 --> 02:39:07,240 RESPONSES TO A TREATMENT IS ALSO 3417 02:39:07,240 --> 02:39:10,000 SOMETHING WE HAVE TO START TO 3418 02:39:10,000 --> 02:39:12,360 CONSIDER IN THE BROAD SPECTRUM 3419 02:39:12,360 --> 02:39:15,320 ON BASIC BIOLOGY OF AGING. 3420 02:39:15,320 --> 02:39:17,120 >>I THINK THAT IS REALLY 3421 02:39:17,120 --> 02:39:18,320 INTERESTING AND I MEAN THAT EVEN 3422 02:39:18,320 --> 02:39:22,080 IN MOST THINGS WE HAVE TRIED TO 3423 02:39:22,080 --> 02:39:23,960 DO TO ALTER TRAJECTORY OF 3424 02:39:23,960 --> 02:39:25,400 FRAILTY WE HAVE SEEN ARRESTING 3425 02:39:25,400 --> 02:39:30,360 THE DEVELOPMENT OF FRAILTY AND 3426 02:39:30,360 --> 02:39:34,720 NOT REVERSING IT. ONE EXCEPTION 3427 02:39:34,720 --> 02:39:36,040 I POINTED OUT WAS IMPACT OF AGE 3428 02:39:36,040 --> 02:39:37,720 AND INTERVENTION IMPACTFUL IN 3429 02:39:37,720 --> 02:39:40,040 FEMALE ANIMALS AND IN STUDIES 3430 02:39:40,040 --> 02:39:41,280 AND NOT ONLY PERSON THAT HAS 3431 02:39:41,280 --> 02:39:43,040 SEEN THAT AND THERE IS 3432 02:39:43,040 --> 02:39:45,280 DEFINITELY THAT MALE AND FEMALE 3433 02:39:45,280 --> 02:39:46,480 DIFFERENCE SHOWING UP AND SPEAKS 3434 02:39:46,480 --> 02:39:49,720 TO IDEA THAT THERE IS 3435 02:39:49,720 --> 02:39:50,560 HETEROGENEITY WITHIN THE 3436 02:39:50,560 --> 02:39:53,520 POPULATION AND WE HAVE TO REALLY 3437 02:39:53,520 --> 02:39:55,360 THINK ABOUT THAT. 3438 02:39:55,360 --> 02:39:59,360 >>BRIAN CHEN, FOXO TECHNOLOGIES 3439 02:39:59,360 --> 02:40:03,960 AND WANT TO GET EVERYONE'S 3440 02:40:03,960 --> 02:40:06,280 COMMENTS ON AGE IN WHICH THE 3441 02:40:06,280 --> 02:40:08,720 BIOMARKER OR CLINICAL MEASURES 3442 02:40:08,720 --> 02:40:10,720 ARE MEASURED AT AND WHETHER 3443 02:40:10,720 --> 02:40:12,480 UTILITY CHANGES DEPENDING ON AGE 3444 02:40:12,480 --> 02:40:15,680 AND SEEMS LIKE AN EASY WIN FOR 3445 02:40:15,680 --> 02:40:19,360 US TO STRATIFY BY AGE AND YOU 3446 02:40:19,360 --> 02:40:21,440 GET INTO SITUATIONS. 3447 02:40:21,440 --> 02:40:24,160 TWO EXAMPLES, ONE IS BMI THAT WE 3448 02:40:24,160 --> 02:40:26,920 KNOW IS BAD FOR YOU WHEN AGE 40 3449 02:40:26,920 --> 02:40:30,120 AND WHEN AGE 100 IT IS ACTUALLY 3450 02:40:30,120 --> 02:40:30,760 POSSIBLY BENEFICIAL AND THERE 3451 02:40:30,760 --> 02:40:33,480 ARE BIOMARKERS THAT COULD HAVE A 3452 02:40:33,480 --> 02:40:38,400 FLIPPED ASSOCIATION AND OTHER 3453 02:40:38,400 --> 02:40:42,760 QUESTION KIND OF MOST 3454 02:40:42,760 --> 02:40:44,360 HIGHLIGHTED IN DR. WALSTON'S 3455 02:40:44,360 --> 02:40:46,120 TALK WITH RESILIENCE IN 3456 02:40:46,120 --> 02:40:47,840 PHENOTYPES OR PHENOTYPES OF 3457 02:40:47,840 --> 02:40:49,600 AGING THAT IS PROBABLY GOOD FOR 3458 02:40:49,600 --> 02:40:52,280 OLDER INDIVIDUALS AND AS YOU GO 3459 02:40:52,280 --> 02:40:56,160 YOUNGER THEY MIGHT NOT HAVE ALL 3460 02:40:56,160 --> 02:40:57,520 PHENOTYPES SHOWING UP YET AND 3461 02:40:57,520 --> 02:40:59,880 WHAT YOU ARE LEFT WITH IS THE 3462 02:40:59,880 --> 02:41:01,000 CONTRIBUTORS THAT I THINK IS 3463 02:41:01,000 --> 02:41:04,560 WHAT YOU CALLED IT. IT COULD BE 3464 02:41:04,560 --> 02:41:06,720 PREDICTIVE THEMSELVES AND SO I 3465 02:41:06,720 --> 02:41:09,440 AM JUST THINKING THAT ACROSS THE 3466 02:41:09,440 --> 02:41:12,360 LIFE COURSE ARE WE LOOKING IN 3467 02:41:12,360 --> 02:41:14,680 THE FUTURE TO HAVE DIFFERENT 3468 02:41:14,680 --> 02:41:16,400 MODELS THAT USE DIFFERENT 3469 02:41:16,400 --> 02:41:17,680 COMPONENTS FOR DIFFERENT AGES? 3470 02:41:17,680 --> 02:41:20,040 SO, I WOULD LOVE TO GET ALL YOUR 3471 02:41:20,040 --> 02:41:24,080 THOUGHTS ON VARIOUS MARKERS YOU 3472 02:41:24,080 --> 02:41:24,320 HAVE. 3473 02:41:24,320 --> 02:41:24,880 >>THANK YOU. 3474 02:41:24,880 --> 02:41:26,600 >>I WILL TAKE THE LAST ONE 3475 02:41:26,600 --> 02:41:30,360 FIRST BEFORE WE FORGET IT. SO, 3476 02:41:30,360 --> 02:41:33,600 I THINK THAT WE -- WE NEED TO -- 3477 02:41:33,600 --> 02:41:36,120 I MEAN, I GUESS IN CLINICAL 3478 02:41:36,120 --> 02:41:37,400 PRACTICE THAT REALITY IS THAT 3479 02:41:37,400 --> 02:41:41,080 NOBODY IN EARLY WORKING LIFE 3480 02:41:41,080 --> 02:41:42,360 WITH KIDS RUNNING AROUND AND 3481 02:41:42,360 --> 02:41:43,600 NOBODY IS THINKING ABOUT THIS 3482 02:41:43,600 --> 02:41:47,320 STUFF. THAT IS JUST A -- I 3483 02:41:47,320 --> 02:41:49,040 PROBABLY -- AND PEOPLE TEND TO 3484 02:41:49,040 --> 02:41:51,840 BE LIKE IN THEIR 50S AND 60S AND 3485 02:41:51,840 --> 02:41:54,000 HAVE MONEY AND SUDDENLY THINK 3486 02:41:54,000 --> 02:41:56,560 THAT WE NEED TO GET THESE 3487 02:41:56,560 --> 02:41:57,880 GEROSCIENCE INITIATIVES GOING 3488 02:41:57,880 --> 02:41:59,200 AND I THINK THAT CHANGES 3489 02:41:59,200 --> 02:42:00,800 PROBABLY DO START TO HAPPEN. 3490 02:42:00,800 --> 02:42:04,000 YOU KNOW, I CAN'T REMEMBER WHO 3491 02:42:04,000 --> 02:42:06,360 MENTIONED LUIGI AND SORT OF YOU 3492 02:42:06,360 --> 02:42:08,640 PEAK IN 30S WITH PHYSICAL 3493 02:42:08,640 --> 02:42:10,560 FUNCTION AND I DON'T KNOW WHEN 3494 02:42:10,560 --> 02:42:11,360 COGNITION PEAKS. 3495 02:42:11,360 --> 02:42:12,760 THERE IS A PERIOD THAT PROBABLY 3496 02:42:12,760 --> 02:42:14,680 I WOULD GUESS IN THE TO URTIES 3497 02:42:14,680 --> 02:42:17,600 WHERE IT STARTS TO BE DECLINES 3498 02:42:17,600 --> 02:42:19,600 THAT PROBABLY IS AN AREA WE 3499 02:42:19,600 --> 02:42:21,680 SHOULD TARGET AND THAT IS WHEN 3500 02:42:21,680 --> 02:42:24,800 THE -- CLINICALLY, THAT IS WHEN 3501 02:42:24,800 --> 02:42:26,280 TRAJECTORIES START TO 3502 02:42:26,280 --> 02:42:27,720 DIFFERENTIATE. YOU KNOW, I 3503 02:42:27,720 --> 02:42:29,480 DON'T THINK WE CAN -- WE KNOW 3504 02:42:29,480 --> 02:42:32,560 THAT WORKING WITH, YOU KNOW, 3505 02:42:32,560 --> 02:42:34,680 EARLY STRESS RESPONSE PATHWAYS 3506 02:42:34,680 --> 02:42:37,600 AND PSYCHOSOCIAL DYNAMICS EARLY 3507 02:42:37,600 --> 02:42:39,120 IN LIFE WILL PROBABLY MAKE A BIG 3508 02:42:39,120 --> 02:42:41,120 DIFFERENCE THAT IS KIND OF A 3509 02:42:41,120 --> 02:42:42,360 DIFFERENT AREA OF CLINICAL 3510 02:42:42,360 --> 02:42:43,560 PRACTICE AND BACK TO YOUR 3511 02:42:43,560 --> 02:42:46,080 QUESTION. I THINK IN THE MID 3512 02:42:46,080 --> 02:42:48,800 40S THAT WE START TO SEE A 3513 02:42:48,800 --> 02:42:50,320 DIFFERENTIATION IN SOME SYSTEMS 3514 02:42:50,320 --> 02:42:52,760 IN GETTING BIOMARKERS IN 3515 02:42:52,760 --> 02:42:54,680 POPULATIONS WILL HELP US TO BE 3516 02:42:54,680 --> 02:42:57,440 PRECISE ABOUT SETTING UP 3517 02:42:57,440 --> 02:42:58,240 CLINICAL TREATMENT PLANS. 3518 02:42:58,240 --> 02:43:02,680 >>YEAH. I THINK THAT YOU ARE 3519 02:43:02,680 --> 02:43:06,080 -- YOUR ASSESSMENT IS RIGHT ON 3520 02:43:06,080 --> 02:43:08,080 AND THINK WHAT WE NEED TO DO IS 3521 02:43:08,080 --> 02:43:09,520 LOOK AT THESE ACROSS DIFFERENT 3522 02:43:09,520 --> 02:43:11,840 AGES AND DON'T KNOW IF DAN IS 3523 02:43:11,840 --> 02:43:14,680 STILL HERE BUT THINK WORK DONE 3524 02:43:14,680 --> 02:43:16,360 OUT OF DON HAS BEEN REALLY 3525 02:43:16,360 --> 02:43:19,400 IMPORTANT IN TERMS OF INDICATING 3526 02:43:19,400 --> 02:43:24,400 DIVERGENCE EARLY IN LIFE ON A 3527 02:43:24,400 --> 02:43:25,920 VARIETY OF THESE MARKERS AND 3528 02:43:25,920 --> 02:43:28,240 WILL SAY THAT WHAT I SHOWED 3529 02:43:28,240 --> 02:43:30,640 TODAY I WAS SURPRISED THAT DON 3530 02:43:30,640 --> 02:43:34,200 PACE DIDN'T DO WELL IN PICKING 3531 02:43:34,200 --> 02:43:37,200 UP MORTALITY WITHIN FOUR YEARS 3532 02:43:37,200 --> 02:43:39,040 AMONG THIS OLDER POPULATION AND 3533 02:43:39,040 --> 02:43:41,400 USUALLY IN TERMS OF HEALTH 3534 02:43:41,400 --> 02:43:43,480 OUTCOMES THAT DOES AS WELL AS 3535 02:43:43,480 --> 02:43:45,960 GRIM AGE AND THINK IT IS AN 3536 02:43:45,960 --> 02:43:49,120 INDICATION THAT DIFFERENT 3537 02:43:49,120 --> 02:43:50,720 MEASURES MAY PREDICT DIFFERENT 3538 02:43:50,720 --> 02:43:52,480 OR BETTER AT DIFFERENT AGES AND 3539 02:43:52,480 --> 02:43:54,160 ALSO DIFFERENT OUTCOMES AND I 3540 02:43:54,160 --> 02:43:58,040 THINK THAT IT IS THE BEGINNING 3541 02:43:58,040 --> 02:44:01,560 OF UNDERSTANDING A COMPLEX WORLD 3542 02:44:01,560 --> 02:44:04,640 AND THINK WE HAVE TO ADD TO 3543 02:44:04,640 --> 02:44:06,920 UNDERSTANDING AT A MUCH YOUNGER 3544 02:44:06,920 --> 02:44:07,120 AGE. 3545 02:44:07,120 --> 02:44:09,120 >>THANK YOU. 3546 02:44:09,120 --> 02:44:12,400 >>THANK YOU, DAN FOREMAN, 3547 02:44:12,400 --> 02:44:13,760 PITTSBURGH AND JEREMY I WANTED 3548 02:44:13,760 --> 02:44:15,520 TO RESPOND TO YOU PARTICULARLY 3549 02:44:15,520 --> 02:44:17,840 AND WHEN ONE IDENTIFIES THE 3550 02:44:17,840 --> 02:44:20,120 DEGREE OF RISK FROM FRAILTY AND 3551 02:44:20,120 --> 02:44:23,560 OTHER MEASURES ASSOCIATED WITH A 3552 02:44:23,560 --> 02:44:25,160 WONDERFUL TALK THIS MORNING AND 3553 02:44:25,160 --> 02:44:28,520 ARE OPPORTUNITIES TO INTERVENE I 3554 02:44:28,520 --> 02:44:30,960 DON'T THIS IS APPRECIATED AND 3555 02:44:30,960 --> 02:44:33,880 WORK IN CARDIAC REHABILITATION 3556 02:44:33,880 --> 02:44:35,360 AND DRAWS FOR CARDIAC CLINICIANS 3557 02:44:35,360 --> 02:44:37,520 AND OPPORTUNITY FOR TAKING 3558 02:44:37,520 --> 02:44:39,440 PEOPLE WITH CARDIAC DISEASE 3559 02:44:39,440 --> 02:44:41,640 PREDOMINANTLY IN OLD AGE WITH 3560 02:44:41,640 --> 02:44:42,480 BIOMARKERS AND WHO HAVE DISEASE 3561 02:44:42,480 --> 02:44:45,480 AND IN MANY CASES ARE BENEFITING 3562 02:44:45,480 --> 02:44:47,960 AT LEAST INITIALLY FROM THE 3563 02:44:47,960 --> 02:44:49,560 INTERVENTION THAT RESTORES BLOOD 3564 02:44:49,560 --> 02:44:53,000 FLOW AND RESTORES VAL VUL AR 3565 02:44:53,000 --> 02:44:54,520 FLOW THROUGH CRITICAL STENOSIS. 3566 02:44:54,520 --> 02:44:57,320 THAT IS AN OPPORTUNITY TO THINK 3567 02:44:57,320 --> 02:44:58,160 ABOUT SARCOPENIA AND OPPORTUNITY 3568 02:44:58,160 --> 02:45:00,400 TO THINK ABOUT MUSCLE MASS AND 3569 02:45:00,400 --> 02:45:02,680 IS AN OPPORTUNITY TO PERHAPS 3570 02:45:02,680 --> 02:45:04,920 INTEGRATE MET FOR MIN AND 3571 02:45:04,920 --> 02:45:06,200 INTERVENTIONS WITH JERO SCIENCE 3572 02:45:06,200 --> 02:45:07,440 BENEFIT AND THINK THERE ARE 3573 02:45:07,440 --> 02:45:09,200 TOOLS WE HAVE THAT ARE GENERALLY 3574 02:45:09,200 --> 02:45:12,320 NOT EMBRACED BY WAY THAT WE 3575 02:45:12,320 --> 02:45:14,680 MANAGE PATIENTS IN 2023 AND FOR 3576 02:45:14,680 --> 02:45:16,240 LAST DECADES AND AS POPULATION 3577 02:45:16,240 --> 02:45:18,800 AGES I THINK THAT THE NOTION OF 3578 02:45:18,800 --> 02:45:20,600 REJUVENATION IS REALLY CRITICAL. 3579 02:45:20,600 --> 02:45:23,000 IT IS ASSOCIATED WITH HIGH COST 3580 02:45:23,000 --> 02:45:25,960 AND HIGH MORBIDITY AND HIGH 3581 02:45:25,960 --> 02:45:28,240 DISABILITY AND HIGH LOSSIN 3582 02:45:28,240 --> 02:45:31,640 DEPENDENT AND ARE OPPORTUNITIES 3583 02:45:31,640 --> 02:45:34,680 TO INTERVENE AND RIGHT NOW 3584 02:45:34,680 --> 02:45:36,480 CARDIAC REHAB PROGRAMS ACROSS 3585 02:45:36,480 --> 02:45:38,720 COUNTRY ARE MASSIVELY 3586 02:45:38,720 --> 02:45:40,440 UNDERUTILIZED BY OLDER ADULTS 3587 02:45:40,440 --> 02:45:41,720 AND DOESN'T MAKE SENSE AND THERE 3588 02:45:41,720 --> 02:45:43,720 IS A VERY STRIKING PARADOX 3589 02:45:43,720 --> 02:45:45,640 BETWEEN USE OF PROGRAMS AND 3590 02:45:45,640 --> 02:45:49,880 NATURE OF PATIENTS THAT MIGHT 3591 02:45:49,880 --> 02:45:51,440 BENEFIT. 3592 02:45:51,440 --> 02:45:53,880 I TOTALLY AGREE DIDN'T MEAN TO 3593 02:45:53,880 --> 02:45:55,960 SAY WORD NO INTERVENTIONS NOT 3594 02:45:55,960 --> 02:45:57,280 COMING OUT OF MOUTH AND DON'T 3595 02:45:57,280 --> 02:45:59,920 KNOW WHAT TO SAY AND THANKS FOR 3596 02:45:59,920 --> 02:46:01,680 POINTING IT OUT AND AGAIN 3597 02:46:01,680 --> 02:46:03,640 EXERCISE AND DIET I HIGHLIGHTED 3598 02:46:03,640 --> 02:46:05,200 THEY ARE TWO THINGS THAT HAVE 3599 02:46:05,200 --> 02:46:06,600 BEEN SHOWN OVER AND OVER AND 3600 02:46:06,600 --> 02:46:11,200 OVER AGAIN TO IMPACT POSITIVELY 3601 02:46:11,200 --> 02:46:15,000 IMPACT EVEN MOST FRAIL 3602 02:46:15,000 --> 02:46:16,680 INDIVIDUALS AND WHAT I WAS 3603 02:46:16,680 --> 02:46:20,640 MEANING TO SAY IS HITTING 3 OR 4 3604 02:46:20,640 --> 02:46:23,600 OR 5 CRITERIAS YOU CAN'T REVERSE 3605 02:46:23,600 --> 02:46:25,880 THOSE THINGS BUT MAKE PEOPLE 3606 02:46:25,880 --> 02:46:27,720 FEEL BETTER IMPROVING QUALITY OF 3607 02:46:27,720 --> 02:46:30,120 LIFE AND KEEPING PEOPLE OUT OF 3608 02:46:30,120 --> 02:46:32,240 THE HOSPITAL AND IMPORTANT 3609 02:46:32,240 --> 02:46:33,880 MARKERS AND NOT EXPERT GETTING 3610 02:46:33,880 --> 02:46:36,360 PEOPLE TO EXERCISE THAT HAS 3611 02:46:36,360 --> 02:46:38,760 NEVER WORKED IN CLINICAL 3612 02:46:38,760 --> 02:46:42,680 PRACTICE AND MAYBE TOM HAS HAD 3613 02:46:42,680 --> 02:46:43,440 BETTER LUCK. 3614 02:46:43,440 --> 02:46:48,160 >>THERE ARE EXAMPLES SUCH AS 3615 02:46:48,160 --> 02:46:50,680 DELAYING KITSMAN AND SOME ARE 3616 02:46:50,680 --> 02:46:52,800 DISEASE SPECIFIC IN HIS CASE 3617 02:46:52,800 --> 02:46:55,080 HEART FAILURE AND I GENERALLY 3618 02:46:55,080 --> 02:46:57,360 AGREE WITH JEREMY IT IS A TOUGH 3619 02:46:57,360 --> 02:47:00,400 NUT TO CRACK WHEN YOU HAVE 3620 02:47:00,400 --> 02:47:04,400 SOMEONE WHO HAS MORE ADVANCED 3621 02:47:04,400 --> 02:47:06,640 PHASES OF FRAILTY PHENOTYPE THAT 3622 02:47:06,640 --> 02:47:09,680 IS HARD TO TURN BACK HANDS OF 3623 02:47:09,680 --> 02:47:12,120 TIME AND THINK THAT SOME 3624 02:47:12,120 --> 02:47:14,480 INTERVENTIONS BEING PLANNED ARE 3625 02:47:14,480 --> 02:47:18,400 ON THE MORE PREVENTIVE PHASE OF 3626 02:47:18,400 --> 02:47:20,920 THE SPECTRUM. 3627 02:47:20,920 --> 02:47:23,040 >>JUST TO ECHO WHAT HAS BEEN 3628 02:47:23,040 --> 02:47:26,520 SAID AND LOOKING AT SURGICAL 3629 02:47:26,520 --> 02:47:27,320 COMANAGEMENT SERVICES IN THE 3630 02:47:27,320 --> 02:47:28,960 HOSPITAL AND LIKE FOR EXAMPLE, 3631 02:47:28,960 --> 02:47:31,440 OUR HOSPITAL HAS A SERVICE WHERE 3632 02:47:31,440 --> 02:47:33,680 INDIVIDUALS COMING IN HAVE BEEN 3633 02:47:33,680 --> 02:47:36,400 IDENTIFIED AS FRAIL USING 3634 02:47:36,400 --> 02:47:38,320 ELECTRONIC MEDICAL RECORDS AND 3635 02:47:38,320 --> 02:47:41,600 VARIABLES TO HAVE CLOSE 3636 02:47:41,600 --> 02:47:42,400 GERIATRIC [INDISCERNIBLE] FROM 3637 02:47:42,400 --> 02:47:44,400 EVEN PRIOR TO ELECTIVE SURGERY 3638 02:47:44,400 --> 02:47:46,400 AND THERE ARE WAYS TO HELP FOLKS 3639 02:47:46,400 --> 02:47:49,800 ONCE THEY ARE IN THE HOSPITALS 3640 02:47:49,800 --> 02:47:52,680 AS WELL DESPITE BEING FRAIL TO 3641 02:47:52,680 --> 02:47:54,400 HELP SHEPHERD THEM THROUGH THAT 3642 02:47:54,400 --> 02:47:57,240 HOSPITALIZATION AND LAST TWO 3643 02:47:57,240 --> 02:47:57,520 QUESTIONS. 3644 02:47:57,520 --> 02:47:59,080 >>A FEW PANELISTS HAVE 3645 02:47:59,080 --> 02:48:00,280 MENTIONED ALREADY THINKING ABOUT 3646 02:48:00,280 --> 02:48:03,160 THE PATIENT AND IN CLINICAL 3647 02:48:03,160 --> 02:48:05,200 PRACTICE AND LUIGI ENCOURAGED US 3648 02:48:05,200 --> 02:48:06,440 TO THINK ABOUT PEOPLE THAT WE 3649 02:48:06,440 --> 02:48:11,600 ARE TRYING TO THINK ABOUT SEEMS 3650 02:48:11,600 --> 02:48:16,480 BUILDING ON RAPHAEL'S POINT 3651 02:48:16,480 --> 02:48:19,280 GENETICALLY MICE RESPONDING TO 3652 02:48:19,280 --> 02:48:21,480 DIET AND EXERCISE AND TO DRUGS 3653 02:48:21,480 --> 02:48:23,880 AND COULD THERE BE STRATEGIES TO 3654 02:48:23,880 --> 02:48:26,200 AGING AND PERHAPS FACTORS 3655 02:48:26,200 --> 02:48:29,240 MATTERING FOR PEOPLE AND NOT SO 3656 02:48:29,240 --> 02:48:32,480 MUCH FOR OTHER PEOPLE? 3657 02:48:32,480 --> 02:48:34,640 WONDERING STATISTICAL METHODS 3658 02:48:34,640 --> 02:48:36,720 USING AND GROUPS AND REGRESSION 3659 02:48:36,720 --> 02:48:40,040 METHODS SEEMING TO GET US AT 3660 02:48:40,040 --> 02:48:42,040 UNDERSTANDING MOST LIKELY OR 3661 02:48:42,040 --> 02:48:43,840 MOST COMMON PATH OR COMMON 3662 02:48:43,840 --> 02:48:45,480 ASSOCIATIONS GENERALLY TRUE 3663 02:48:45,480 --> 02:48:47,280 ACROSS PEOPLE THAT FOR SOME 3664 02:48:47,280 --> 02:48:50,040 PEOPLE THAT KNOW MIGHT NOT BE 3665 02:48:50,040 --> 02:48:52,120 ACCURATE OR MISSING OTHER THINGS 3666 02:48:52,120 --> 02:48:55,800 DO WE HAVE APPROACHES WE NEED TO 3667 02:48:55,800 --> 02:48:58,040 IDENTIFY INDIVIDUAL SPECIFIC 3668 02:48:58,040 --> 02:49:00,040 TRAJECTORIES OR PHYSIOLOGICAL 3669 02:49:00,040 --> 02:49:02,440 STRATEGIES TOWARDS RESILIENCE OR 3670 02:49:02,440 --> 02:49:04,640 TOWARDS AGING? 3671 02:49:04,640 --> 02:49:10,080 MAKE ANY SENSE? 3672 02:49:10,080 --> 02:49:12,200 >>THAT IS A REALLY IMPORTANT 3673 02:49:12,200 --> 02:49:13,680 POINT THAT HASN'T BEEN DONE YET 3674 02:49:13,680 --> 02:49:17,360 AND LOTS OF INFORMATION THAT WE 3675 02:49:17,360 --> 02:49:19,800 ARE LEARNING ABOUT TODAY AND 3676 02:49:19,800 --> 02:49:22,720 VARIABLES POPPING OUT OF 3677 02:49:22,720 --> 02:49:24,120 DIFFERENT ANALYSIS WILL HELP 3678 02:49:24,120 --> 02:49:25,560 INFORM DEVELOPMENT OF THAT AND 3679 02:49:25,560 --> 02:49:29,880 IT IS REALLY IMPORTANT TO HAVE 3680 02:49:29,880 --> 02:49:31,240 CLINICIANS AND BASIC SCIENCE 3681 02:49:31,240 --> 02:49:34,360 INVESTIGATORS AND PEOPLE IN 3682 02:49:34,360 --> 02:49:37,040 MIDDLE AND TRANSLATIONAL KIND OF 3683 02:49:37,040 --> 02:49:38,520 UNDERSTANDING BIOLOGY AND IS 3684 02:49:38,520 --> 02:49:41,400 IMPORTANT THAT PEOPLE ARE IN THE 3685 02:49:41,400 --> 02:49:43,400 ROOM TO HELP DESIGN THOSE THINGS 3686 02:49:43,400 --> 02:49:46,360 THAT MIGHT BE AN OUTCOME OF THE 3687 02:49:46,360 --> 02:49:48,120 MEETING TO REALLY THINK ABOUT 3688 02:49:48,120 --> 02:49:50,160 WAYS TO START TO PUT SOME OF 3689 02:49:50,160 --> 02:49:52,320 THIS INTO PRACTICE OR A ROAD MAP 3690 02:49:52,320 --> 02:49:56,520 FOR FUTURE PRACTICE PATTERN 3691 02:49:56,520 --> 02:49:56,920 DEVELOPMENT. 3692 02:49:56,920 --> 02:50:00,360 >>IT IS SETTING ASPIRATIONS IN 3693 02:50:00,360 --> 02:50:02,640 RIGHT PLACE THAT IS COMPLEX AND 3694 02:50:02,640 --> 02:50:05,040 THINK THAT LIFETIME OF 3695 02:50:05,040 --> 02:50:06,440 LONGITUDINAL DATA GOES A LONG 3696 02:50:06,440 --> 02:50:10,360 WAY TO DOING EXACTLY WHAT YOU 3697 02:50:10,360 --> 02:50:13,440 ARE PROPOSING AND WHAT WE SHOULD 3698 02:50:13,440 --> 02:50:14,200 AIM FOR. 3699 02:50:14,200 --> 02:50:17,080 >>I THINK IN THE WORLD WE ARE 3700 02:50:17,080 --> 02:50:20,320 LOOKING FORWARD TO SLAM STUDY 3701 02:50:20,320 --> 02:50:23,480 THAT RAFA IS DOING AND LONG TIME 3702 02:50:23,480 --> 02:50:26,680 PEOPLE THOUGHT OF ANIMALS AS 3703 02:50:26,680 --> 02:50:30,040 BEING SIMILAR AND C57 BLACK 6S 3704 02:50:30,040 --> 02:50:32,720 IS A FAIRLY NEW RECOGNITION THAT 3705 02:50:32,720 --> 02:50:36,680 I THINK I DON'T KNOW IF WE KNOW 3706 02:50:36,680 --> 02:50:39,000 ENOUGH TO COHORT THEM IN ANY WAY 3707 02:50:39,000 --> 02:50:42,320 AND IDENTIFYING ONE ASPECT 3708 02:50:42,320 --> 02:50:44,000 RESPONSE TO HIGH FAT FEEDING AND 3709 02:50:44,000 --> 02:50:45,240 FEMALE DIFFERENCES AND THERE IS 3710 02:50:45,240 --> 02:50:47,640 SOMETHING THERE AND INTERESTING 3711 02:50:47,640 --> 02:50:50,560 TO LEARN MORE. 3712 02:50:50,560 --> 02:50:51,680 >>THANK YOU. 3713 02:50:51,680 --> 02:50:52,880 >>NEXT QUESTION. 3714 02:50:52,880 --> 02:50:56,680 >>[INDISCERNIBLE] FROM JAIL AND 3715 02:50:56,680 --> 02:50:58,520 POINTING OUT EARLIER THAT MENTAL 3716 02:50:58,520 --> 02:51:01,520 HEALTH IS EXCLUDED FROM AGING 3717 02:51:01,520 --> 02:51:03,240 STUDIES AND DIFFERENT SYSTEM 3718 02:51:03,240 --> 02:51:07,520 EXCLUDED FROM STUDIES IS 3719 02:51:07,520 --> 02:51:08,280 REPRODUCTIVE AGEING THAT WILL BE 3720 02:51:08,280 --> 02:51:12,440 A SIGNIFICANT OUTCOME TO 3721 02:51:12,440 --> 02:51:14,800 CONSIDER IF THERE IS SYMPTOMS 3722 02:51:14,800 --> 02:51:20,080 RELATED TO REPRODUCTIVE SYSTEMS 3723 02:51:20,080 --> 02:51:22,280 IMPACTING QUALITY OF LIFE FOR 3724 02:51:22,280 --> 02:51:26,240 OLDER ADULTS AND SPECTRUM AS 35 3725 02:51:26,240 --> 02:51:28,640 YEAR OLD SPENDING TIME IN CAREER 3726 02:51:28,640 --> 02:51:31,880 PEERS ARE MOST CONCERNED ABOUT 3727 02:51:31,880 --> 02:51:33,080 REPRODUCTIVE AGING AND FERTILITY 3728 02:51:33,080 --> 02:51:35,760 AND QUESTION TO YOU IS HOW TO 3729 02:51:35,760 --> 02:51:39,840 INTEGRATE REPRODUCTIVE SYSTEM 3730 02:51:39,840 --> 02:51:43,720 MEASURES INTO CONSIDERING IT AS 3731 02:51:43,720 --> 02:51:45,680 AN OUTCOME? 3732 02:51:45,680 --> 02:51:52,120 >>DO YOU KNOW THE ANSWER? 3733 02:51:52,120 --> 02:51:54,440 >>I DO NOT. 3734 02:51:54,440 --> 02:51:56,280 >>CERTAINLY PEOPLE HAVE STARTED 3735 02:51:56,280 --> 02:51:58,520 TO INCORPORATE MEASURES OF 3736 02:51:58,520 --> 02:52:02,720 TIMING OF MENOPAUSE AND VARIETY 3737 02:52:02,720 --> 02:52:05,480 OF HORMONAL THINGS. 3738 02:52:05,480 --> 02:52:09,680 I THINK IT IS ANOTHER SYSTEM TO 3739 02:52:09,680 --> 02:52:14,680 BE ADDED TO THE MIX AND. 3740 02:52:14,680 --> 02:52:16,600 >>BRIEFLY CHIMING IN 3741 02:52:16,600 --> 02:52:18,560 CONSIDERATION EXPERIENCE WITH 3742 02:52:18,560 --> 02:52:22,080 MOUSE WORK AND FEMALE MICE WE 3743 02:52:22,080 --> 02:52:24,160 TYPICALLY USE ARE NOT BREEDERS 3744 02:52:24,160 --> 02:52:26,120 FOR STUDIES AND FACTORS WE ARE 3745 02:52:26,120 --> 02:52:27,880 NOT INCLUDING WITH MANY AGING 3746 02:52:27,880 --> 02:52:29,520 RELATED STUDIES WE ARE DOING 3747 02:52:29,520 --> 02:52:33,400 WITH MOUSE COHORTS GENERALLY. 3748 02:52:33,400 --> 02:52:41,680 >>I HAVE A QUESTION FOR EILEEN 3749 02:52:41,680 --> 02:52:43,320 PRETENDING I'M IN AUDIENCE IF 3750 02:52:43,320 --> 02:52:44,720 YOU HAVE OPPORTUNITY OR THOUGHT 3751 02:52:44,720 --> 02:52:46,640 LOOKING AT DISEASE SPECIFIC 3752 02:52:46,640 --> 02:52:48,440 MORTALITY AND FINDINGS IN 3753 02:52:48,440 --> 02:52:53,280 WHETHER BIOMARKERS YOU 3754 02:52:53,280 --> 02:52:54,440 IDENTIFIED MIGHT DIFFER 3755 02:52:54,440 --> 02:52:57,840 DEPENDING ON CAUSE OF DEATH? 3756 02:52:57,840 --> 02:53:03,640 >>ABSOLUTELY NOT TO DATE SHORT 3757 02:53:03,640 --> 02:53:06,280 TERM OF MORTALITY HARD TO 3758 02:53:06,280 --> 02:53:08,840 DIFFERENTIATE BUT THEY 3759 02:53:08,840 --> 02:53:09,760 ABSOLUTELY WOULD AND THINK THAT 3760 02:53:09,760 --> 02:53:12,440 THIS WILL OBVIOUSLY BE RELATE 3761 02:53:12,440 --> 02:53:15,840 TODAY HEARTDISEASE AND CANCER 3762 02:53:15,840 --> 02:53:20,280 COULD BE QUITE DIFFERENT. 3763 02:53:20,280 --> 02:53:23,520 >>JUST COMMENTING ON 3764 02:53:23,520 --> 02:53:25,600 REPRODUCTIVE BIOLOGY AND IN 3765 02:53:25,600 --> 02:53:26,960 GERIATRIC MEDICAL PRACTICE NOT A 3766 02:53:26,960 --> 02:53:29,280 BAD ISSUE AND SOME CONVERSATIONS 3767 02:53:29,280 --> 02:53:31,800 ABOUT SEX DIFFERENCES AND HOW 3768 02:53:31,800 --> 02:53:34,080 PEOPLE AGE THERE IS A HUGE 3769 02:53:34,080 --> 02:53:37,080 DIFFERENCE. THIS IS A BROAD 3770 02:53:37,080 --> 02:53:38,200 OVERGENERALIZATION PROBABLY 3771 02:53:38,200 --> 02:53:41,480 HOPEFULLY BACKED UP BY EPIDATA 3772 02:53:41,480 --> 02:53:43,640 AND WOMEN TEND TO DRIFT ON FOR 3773 02:53:43,640 --> 02:53:44,840 MANY, MANY YEARS BECOMING 3774 02:53:44,840 --> 02:53:51,800 DISABLED AND HAVING A LOT OF 3775 02:53:51,800 --> 02:53:53,680 THINGS WE ARE TALKING ABOUT 3776 02:53:53,680 --> 02:53:59,600 FRAILTY AND FRAILTY STUDIES THEY 3777 02:53:59,600 --> 02:54:08,440 DROP OUT FOR SOME REASON THERE 3778 02:54:08,440 --> 02:54:09,640 IS A SEX DIFFERENCE THERE 3779 02:54:09,640 --> 02:54:11,280 PULLING THEM APART AND STUDIES 3780 02:54:11,280 --> 02:54:12,480 WILL GET THERE AND NOT SURE IF 3781 02:54:12,480 --> 02:54:15,600 IT HAS TO DO WITH REPRODUCTIVE 3782 02:54:15,600 --> 02:54:18,480 SYSTEM OR NOT BUT IS AN 3783 02:54:18,480 --> 02:54:19,960 IMPORTANT THING TO THINK ABOUT. 3784 02:54:19,960 --> 02:54:26,720 >>ALBERT IT IS DOABLE AND 3785 02:54:26,720 --> 02:54:30,480 TAKING OVER MANAGEMENT OF ADD 3786 02:54:30,480 --> 02:54:32,640 HEALTH ADOLESCENT STUDY IT 3787 02:54:32,640 --> 02:54:34,720 STARTED OFF AS AND NOW THEY ARE 3788 02:54:34,720 --> 02:54:36,280 MIDDLE AGED AND THEY HAVE 3789 02:54:36,280 --> 02:54:37,440 RESPONDED TO LOTS OF INFORMATION 3790 02:54:37,440 --> 02:54:41,600 ON FERTILITY AND REPRODUCTION IN 3791 02:54:41,600 --> 02:54:45,960 REAL-TIME IN KONL TRAFT TO OLDER 3792 02:54:45,960 --> 02:54:48,800 PEOPLE WITH REPRODUCTIVE 3793 02:54:48,800 --> 02:54:50,720 HISTORIES IN THE PAST THAT GAVE 3794 02:54:50,720 --> 02:54:54,320 THIS PROJECT AND COHORT MERGING 3795 02:54:54,320 --> 02:54:58,320 WITH OLDER COHORTS AND THESE ARE 3796 02:54:58,320 --> 02:55:00,480 SAME AS BEING PICKED UP IN 3797 02:55:00,480 --> 02:55:02,440 HEALTH AND RETIREMENT STUDIES 3798 02:55:02,440 --> 02:55:04,200 AND THINK YOU CAN DO MORE 3799 02:55:04,200 --> 02:55:08,360 INFORMED WORK ON THAT TOPIC THAN 3800 02:55:08,360 --> 02:55:11,120 PERHAPS HAS BEEN AVAILABLE IN 3801 02:55:11,120 --> 02:55:11,440 THE PAST. 3802 02:55:11,440 --> 02:55:15,240 >>I WILL COMMENT ON IT TOO. MY 3803 02:55:15,240 --> 02:55:18,040 UNDERSTANDING RUTH HUB BARRED IN 3804 02:55:18,040 --> 02:55:19,960 UNIVERSITY OF QUEENSLAND IN 3805 02:55:19,960 --> 02:55:22,720 AUSTRALIA LOOKED AT PARITY AND 3806 02:55:22,720 --> 02:55:24,520 FRAILTY AND FOUND A NO CHILDREN 3807 02:55:24,520 --> 02:55:29,040 -- U-SHAPED RELATIONSHIP WITH NO 3808 02:55:29,040 --> 02:55:31,800 AND MANY CHILDREN AND SWEET SPOT 3809 02:55:31,800 --> 02:55:33,560 IN AND BETWEEN AND AROUND 2 AND 3810 02:55:33,560 --> 02:55:35,560 WHAT I HAVE DONE AND HAVEN'T 3811 02:55:35,560 --> 02:55:36,600 DONE WORK IN MICE. 3812 02:55:36,600 --> 02:55:40,360 >>THANK YOU AGAIN TO SPEAKERS 3813 02:55:40,360 --> 02:55:49,480 FOR A REALLY GREAT SESSION. 3814 02:55:49,480 --> 02:55:56,080 >> NEXT SESSION IS 3815 02:55:56,080 --> 02:55:57,760 MATHEMATICAL MODELING FOR BASIC 3816 02:55:57,760 --> 02:56:00,680 AND TRANSLATIONAL RESEARCH AND I 3817 02:56:00,680 --> 02:56:08,920 WILL CHAIR THIS SECTION. THIS 3818 02:56:08,920 --> 02:56:12,920 SECTION AIMS TO EXPLORE THE 3819 02:56:12,920 --> 02:56:16,840 STATE OF BIOLOGICAL AGING MAJORS 3820 02:56:16,840 --> 02:56:18,960 AND HIGHLIGHTING IMPORTANCE FOR 3821 02:56:18,960 --> 02:56:20,880 MODELING AND BASIC AND 3822 02:56:20,880 --> 02:56:22,640 TRANSLATIONAL RESEARCH AND THERE 3823 02:56:22,640 --> 02:56:24,120 WILL BE FOUR PRESENTATIONS 3824 02:56:24,120 --> 02:56:28,040 TODAY. AFTER THE PRESENTATIONS 3825 02:56:28,040 --> 02:56:29,960 OTHER TWO PANELISTS WILL JOIN 3826 02:56:29,960 --> 02:56:32,560 ME. WE WILL GIVE AN OVERVIEW 3827 02:56:32,560 --> 02:56:36,480 INCLUDING COMMENTS ON 3828 02:56:36,480 --> 02:56:36,840 PRESENTATIONS. 3829 02:56:36,840 --> 02:56:41,480 FIRST SPEAKER IS TREY IDEKER WHO 3830 02:56:41,480 --> 02:56:47,120 IS FROM THE UNIVERSITY F KALOF 3831 02:56:47,120 --> 02:56:51,080 CALIFORNIA, SAN DIEGO. LET'S 3832 02:56:51,080 --> 02:57:01,320 WELCOME HIM. 3833 02:57:05,640 --> 02:57:08,920 >>HOW IS THAT. CAN PEOPLE HEAR 3834 02:57:08,920 --> 02:57:13,440 MY SCREEN -- HEAR ME AND SEE MY 3835 02:57:13,440 --> 02:57:14,640 SCREEN? 3836 02:57:14,640 --> 02:57:16,440 >>WE CANNOT SEE YOUR SCREEN. 3837 02:57:16,440 --> 02:57:18,000 >>YOU CANNOT? 3838 02:57:18,000 --> 02:57:27,880 >>WE CANNOT HEAR YOU CLEARLY. 3839 02:57:27,880 --> 02:57:30,120 >>HELLO. CAN YOU HEAR ME? 3840 02:57:30,120 --> 02:57:30,840 >>YES. 3841 02:57:30,840 --> 02:57:32,800 >>YOU CAN HEAR ME NOW. OKAY. 3842 02:57:32,800 --> 02:57:35,520 LET ME TRY. YOU CANNOT SEE MY 3843 02:57:35,520 --> 02:57:35,960 SCREEN? 3844 02:57:35,960 --> 02:57:36,960 >>NOT YET. 3845 02:57:36,960 --> 02:57:47,520 >>OKAY. LET ME TRY ONCE MORE. 3846 02:57:50,600 --> 02:57:51,880 >>WHAT ABOUT NOW? 3847 02:57:51,880 --> 02:57:52,880 >>IT IS GOOD. 3848 02:57:52,880 --> 02:57:54,640 >>THANK YOU FOR THAT 3849 02:57:54,640 --> 02:57:56,240 INTRODUCTION AND OTHER 3850 02:57:56,240 --> 02:57:58,280 CONFERENCE ORGANIZERS FOR THE 3851 02:57:58,280 --> 02:57:59,600 INVITATION TO PARTICIPATE. 3852 02:57:59,600 --> 02:58:01,560 SORRY I COULDN'T BE THERE IN 3853 02:58:01,560 --> 02:58:05,720 PERSON. I WAS VERY HAPPY TO 3854 02:58:05,720 --> 02:58:08,560 ZOOM IN A TALK. I WAS JUST AT 3855 02:58:08,560 --> 02:58:12,560 NIH LAST WEEK FOR A MEETING AND 3856 02:58:12,560 --> 02:58:17,120 NOW I HAVE TEACH IING BACK HERE 3857 02:58:17,120 --> 02:58:18,800 THIS WEEK. I WAS ASKED TO TALK 3858 02:58:18,800 --> 02:58:21,320 ABOUT MULTIPLE WAYS OF MODELING 3859 02:58:21,320 --> 02:58:23,920 AGING AND AS YOU WILL SEE HERE 3860 02:58:23,920 --> 02:58:27,440 SHORTLY, ALMOST ALL OF MY LABS 3861 02:58:27,440 --> 02:58:29,720 RESEARCH HAS INVOLVED THIS 3862 02:58:29,720 --> 02:58:31,920 SO-CALLED EPIGENETIC MEASUREMENT 3863 02:58:31,920 --> 02:58:34,600 OF AGE. I WILL TALK ABOUT 3864 02:58:34,600 --> 02:58:35,680 HISTORICAL RESEARCH. I WILL TRY 3865 02:58:35,680 --> 02:58:37,880 TO GET THROUGH THE NARRATIVE 3866 02:58:37,880 --> 02:58:39,200 PRETTY QUICKLY TO WHAT WE ARE 3867 02:58:39,200 --> 02:58:42,040 WORKING ON CURRENTLY THAT IS 3868 02:58:42,040 --> 02:58:44,440 DISSECTING THIS EPIGENETIC AGE 3869 02:58:44,440 --> 02:58:46,680 AND MEASURE AS BEST AS WE CAN 3870 02:58:46,680 --> 02:58:48,600 AND IN TERMS WHAT MY LAB WORKS 3871 02:58:48,600 --> 02:58:52,200 ON MORE BROADLY, IT IS REALLY 3872 02:58:52,200 --> 02:58:53,800 FOUR POINTS HERE. 3873 02:58:53,800 --> 02:58:56,720 STARTING WITH A SORT OF GENOTYPE 3874 02:58:56,720 --> 02:58:59,120 AND PHENOTYPE EQUATION HOW WE 3875 02:58:59,120 --> 02:59:02,440 TAKE GENETIC VARIANCE AND 3876 02:59:02,440 --> 02:59:05,160 MUTATIONS AND UNDERSTAND 3877 02:59:05,160 --> 02:59:08,480 PATHWAYS BY WHICH THEY INFLUENCE 3878 02:59:08,480 --> 02:59:09,680 OUTCOMES AND DISEASE AND AGE AND 3879 02:59:09,680 --> 02:59:12,920 OF COURSE WHEN YOU START TO 3880 02:59:12,920 --> 02:59:15,520 STUDY IMPACTS OF MUTATIONS THAT 3881 02:59:15,520 --> 02:59:18,720 RAPIDLY GETS YOU INTO THE 3882 02:59:18,720 --> 02:59:22,160 EPIGENOME AS WELL. THERE IS 3883 02:59:22,160 --> 02:59:24,560 ESSENTIALLY THREE PHASES OF 3884 02:59:24,560 --> 02:59:28,960 RESEARCH IN MY LAB ON THE AGING 3885 02:59:28,960 --> 02:59:31,040 ANGLE AND TEAM OVER THREE PHASES 3886 02:59:31,040 --> 02:59:34,040 STARTING IN 2010 AND TALKING 3887 02:59:34,040 --> 02:59:38,200 ABOUT WORK BY GREG HANN EM AND 3888 02:59:38,200 --> 02:59:39,560 JUSTIN GRAY WITH [INDISCERNIBLE] 3889 02:59:39,560 --> 02:59:41,640 LAB AND TINA WONG I SHOULD SAY 3890 02:59:41,640 --> 02:59:47,320 ALL THESE ARE PHD STUDENTS AT 3891 02:59:47,320 --> 02:59:51,360 UCSD WHO IS A GRAD STUDENT IN 3892 02:59:51,360 --> 02:59:53,560 BIOENGINEERING AND TINA WONG 3893 02:59:53,560 --> 02:59:56,560 BIOMEDICAL SCIENCES HERE AT UCSD 3894 02:59:56,560 --> 02:59:58,520 AND DROVE SECOND WAVE INTO 3895 02:59:58,520 --> 03:00:00,240 MAMMALS AND DOGS YOU WILL SEE 3896 03:00:00,240 --> 03:00:01,880 AND RECENT IS COLLABORATION WITH 3897 03:00:01,880 --> 03:00:05,400 STEVE COMINGS AT CSF AND TALKING 3898 03:00:05,400 --> 03:00:08,680 ABOUT WORK LED BY SDAIN HOCK. 3899 03:00:08,680 --> 03:00:11,920 IN MY LAB, THIS STARTED IN A 3900 03:00:11,920 --> 03:00:13,280 COLLABORATION WITH CONJONG WHO 3901 03:00:13,280 --> 03:00:16,120 HE AND I BACK IN 2011 HAD JUST 3902 03:00:16,120 --> 03:00:18,800 WORKED WITH ILLUMINA DOWN HERE 3903 03:00:18,800 --> 03:00:21,520 IN THE STREET IN SAN DIEGO TO 3904 03:00:21,520 --> 03:00:23,920 GENERATE WHAT WERE SOME FIRST 3905 03:00:23,920 --> 03:00:27,120 METHO LOAMWIDE PROFILES OF 3906 03:00:27,120 --> 03:00:29,160 HUMANS THAT WERE STARTING THEN. 3907 03:00:29,160 --> 03:00:33,800 WE HAD 656 OR SO HUMANS WHERE WE 3908 03:00:33,800 --> 03:00:36,280 EXTRACTED WHOLE BLOOD AND 3909 03:00:36,280 --> 03:00:39,720 MEASURED CPG METHYLATION SITES 3910 03:00:39,720 --> 03:00:45,520 AND AT NEARLY 500,000 SITES 3911 03:00:45,520 --> 03:00:45,840 GENOMEWIDE. 3912 03:00:45,840 --> 03:00:48,880 ORIGINAL GOAL WAS TRYING TO 3913 03:00:48,880 --> 03:00:51,120 UNDERSTAND MARKERS FOR CANCER IN 3914 03:00:51,120 --> 03:00:51,760 THE BLOOD. 3915 03:00:51,760 --> 03:00:54,800 THOSE EFFORTS SINCE HAVE BEEN 3916 03:00:54,800 --> 03:00:55,920 MORE SUCCESSFUL FOR OTHER 3917 03:00:55,920 --> 03:00:58,040 PEOPLE'S HAND AND IN OUR CASE WE 3918 03:00:58,040 --> 03:01:00,920 KEPT GETTING, YOU KNOW, WASHED 3919 03:01:00,920 --> 03:01:02,800 OUT. ANY CANCER SIGNAL WAS 3920 03:01:02,800 --> 03:01:05,920 ENTIRELY WASHED OUT BY THE 3921 03:01:05,920 --> 03:01:08,000 OVERWHELMING CO-VARIATE THAT 3922 03:01:08,000 --> 03:01:09,560 GREG HANN EM FOUND TO BE AGED 3923 03:01:09,560 --> 03:01:11,800 AND WE RAPIDLY REALIZED WE HAD 3924 03:01:11,800 --> 03:01:12,920 TO PICK AND THAT WAS VERY 3925 03:01:12,920 --> 03:01:14,640 INTERESTING AND WE RAPIDLY 3926 03:01:14,640 --> 03:01:17,880 REALIZED WE HAD TO PIVOT AND 3927 03:01:17,880 --> 03:01:19,280 STUDY AGE FOR THIS WORK RATHER 3928 03:01:19,280 --> 03:01:21,880 THAN FOCUS ON CANCER THAT GIVES 3929 03:01:21,880 --> 03:01:24,840 YOU ONE EXAMPLE OF A CYTOSINE 3930 03:01:24,840 --> 03:01:28,920 MARK THAT IS IN DNA WHERE THE 3931 03:01:28,920 --> 03:01:30,840 FRACTION OF REEDS WITH THAT -- 3932 03:01:30,840 --> 03:01:33,360 WHERE THAT CYTOSINE IS MENL 3933 03:01:33,360 --> 03:01:36,960 ILLATED AND SO-CALLED MENL ILL 3934 03:01:36,960 --> 03:01:40,280 CPG INCREASES RELIABLY OVER YOUR 3935 03:01:40,280 --> 03:01:41,080 POPULATION WITH AGE. 3936 03:01:41,080 --> 03:01:43,800 EVERY POINT THERE IS A HUMAN AND 3937 03:01:43,800 --> 03:01:46,360 INDIVIDUAL AND THEIR AGE 3938 03:01:46,360 --> 03:01:49,760 CHRONOLOGICALLY ON X AXIS AND 3939 03:01:49,760 --> 03:01:55,720 FRACTION OF CPGS MEASURED AT 3940 03:01:55,720 --> 03:01:57,160 THAT SITE INDIVIDUAL AND IS 3941 03:01:57,160 --> 03:01:59,720 SHOWN AT Y AXIS THAT IS NOW AN 3942 03:01:59,720 --> 03:02:01,120 OLD HAT. 3943 03:02:01,120 --> 03:02:05,760 IT IS STILL GOOD TO LOOK AT EACH 3944 03:02:05,760 --> 03:02:09,720 INDIVIDUAL SIDE AND SEE HOW WELL 3945 03:02:09,720 --> 03:02:13,480 SITES TRACK AGE AND WE WENT ON 3946 03:02:13,480 --> 03:02:17,000 TO USE A LINEAR REGRESSION MODEL 3947 03:02:17,000 --> 03:02:22,400 BASED ON ELASTIC NET AND COMMON 3948 03:02:22,400 --> 03:02:24,280 REGULARIZATION TECHNIQUE FOR 3949 03:02:24,280 --> 03:02:26,080 LINEAR REGRESSION PREDICTING 3950 03:02:26,080 --> 03:02:29,120 CHRONOLOGICAL AGE USING A SMALL 3951 03:02:29,120 --> 03:02:31,240 NUMBER OF METHYLATION SITES IN 3952 03:02:31,240 --> 03:02:32,920 INDIVIDUALS AND COULD COME UP 3953 03:02:32,920 --> 03:02:34,520 WITH A QUITE GOOD PREDICTOR THAT 3954 03:02:34,520 --> 03:02:37,520 IS NOW CALLED EPIGENETIC CLOCK 3955 03:02:37,520 --> 03:02:39,920 AND NOW THESE POINTS ARE PEOPLE. 3956 03:02:39,920 --> 03:02:42,240 THEY ARE WHOSE AGES ARE 3957 03:02:42,240 --> 03:02:45,600 PREDICTED OR ARE ON THE Y AXIS 3958 03:02:45,600 --> 03:02:48,440 AND -- AND THE X AXIS IS THEY 3959 03:02:48,440 --> 03:02:50,720 ARE AN ACTUAL CHRONOLOGICAL AGE 3960 03:02:50,720 --> 03:02:53,240 AND OF COURSE PEOPLE WE AND 3961 03:02:53,240 --> 03:02:56,640 OTHERS HAVE SINCE BECOME VERY 3962 03:02:56,640 --> 03:02:59,200 INTERESTED IN OFF-AXIS 3963 03:02:59,200 --> 03:03:01,000 PREDICTION AND PEOPLE ABOVE 3964 03:03:01,000 --> 03:03:04,160 DIAGONAL ARE AGING QUICKLY BELOW 3965 03:03:04,160 --> 03:03:06,600 POPULATION AND DIAGONAL IS AGING 3966 03:03:06,600 --> 03:03:09,640 MORE SLOWLY THAN THE POPULATION 3967 03:03:09,640 --> 03:03:12,240 AND OF COURSE WE AND -- AND MANY 3968 03:03:12,240 --> 03:03:15,200 OTHERS NOW HAVE HAD -- HAVE 3969 03:03:15,200 --> 03:03:16,520 SHOWN THAT THERE IS A RELATION 3970 03:03:16,520 --> 03:03:19,280 FOR WHAT LOOKS LIKE ERROR HERE 3971 03:03:19,280 --> 03:03:21,400 IN THESE LINEAR REGRESSION PLOTS 3972 03:03:21,400 --> 03:03:24,560 THAT DO ACTUALLY ASSOCIATE WITH 3973 03:03:24,560 --> 03:03:28,600 DISEASE STATES OVERALL. 3974 03:03:28,600 --> 03:03:30,440 MARIONI BACK IN THE STUDY BACK 3975 03:03:30,440 --> 03:03:32,400 IN 2015 SHOWED THAT THIS TYPE OF 3976 03:03:32,400 --> 03:03:36,440 CLOCK ASSOCIATES WITH ALL CAUSE 3977 03:03:36,440 --> 03:03:36,920 MORTALITY. 3978 03:03:36,920 --> 03:03:40,840 AND, OF COURSE, YOU KNOW, 3979 03:03:40,840 --> 03:03:43,320 RAPIDLY FOLLOWING OUR STUDY WAS 3980 03:03:43,320 --> 03:03:45,760 FAMOUS STUDY WHERE HE USED OUR 3981 03:03:45,760 --> 03:03:48,760 DATA AND SOME MORE METHYLATION 3982 03:03:48,760 --> 03:03:51,160 PROFILES FOR HIS PAPER. HE 3983 03:03:51,160 --> 03:03:53,240 CHOSE A DIFFERENT SET OF SITES. 3984 03:03:53,240 --> 03:03:56,880 AGAIN, THERE IS A HUGE NUMBER OF 3985 03:03:56,880 --> 03:03:59,880 CPG SITES IN METHYL OHM THAT 3986 03:03:59,880 --> 03:04:02,200 APPEAR WITH TRACKING AGE AND 3987 03:04:02,200 --> 03:04:04,080 SIMPLY IN TWO MODELS YOU WANT TO 3988 03:04:04,080 --> 03:04:06,160 HAVE A GOOD SELECTION THAT IS 3989 03:04:06,160 --> 03:04:08,000 PREDICTIVE AND LOTS OF OTHERS 3990 03:04:08,000 --> 03:04:09,880 FOLLOWING THAT PAPER HAVE 3991 03:04:09,880 --> 03:04:13,480 REVISED SO-CALLED EPIGENETIC 3992 03:04:13,480 --> 03:04:15,400 CLOCKS IN DIFFERENT WAYS AND AS 3993 03:04:15,400 --> 03:04:16,800 WELL AS USE THEM IN SOME NEW 3994 03:04:16,800 --> 03:04:19,960 COMPANIES THAT WE ARE SEEING IN 3995 03:04:19,960 --> 03:04:21,000 THE WELLNESS SPACE. 3996 03:04:21,000 --> 03:04:23,520 WHAT DID MY LAB DO? DO ANYTHING 3997 03:04:23,520 --> 03:04:25,400 USEFUL FOR HUMANS AFTER THAT? 3998 03:04:25,400 --> 03:04:29,600 HECK NO. WE -- I SHOULD NOW SAY 3999 03:04:29,600 --> 03:04:32,600 TINA WONG ENTERED THE PICTURE 4000 03:04:32,600 --> 03:04:34,280 FRESH INTO GRAD SCHOOL AND CAME 4001 03:04:34,280 --> 03:04:36,080 INTO MY OFFICE AND SAID, YOU 4002 03:04:36,080 --> 03:04:38,120 KNOW, ALL THAT EPIGENETIC WORK 4003 03:04:38,120 --> 03:04:42,760 FOR HUMANS IS INTERESTING FOR A 4004 03:04:42,760 --> 03:04:46,520 PRETTY YOUNG AGE. YOU KNOW, 4005 03:04:46,520 --> 03:04:48,880 TREY, YOU KNOW PEOPLES AGE. 4006 03:04:48,880 --> 03:04:50,440 WHAT ABOUT PREDICTING SOMEBODY'S 4007 03:04:50,440 --> 03:04:52,520 AGE THAT YOU WANT TO KNOW BUT 4008 03:04:52,520 --> 03:04:55,520 YOU DON'T. DOGS WERE HER PRIME 4009 03:04:55,520 --> 03:04:56,400 EXAMPLE. 4010 03:04:56,400 --> 03:04:58,440 90% OF DOGS AND MIGHT BE MORE 4011 03:04:58,440 --> 03:05:00,280 THAN THAT IN AMERICA ARE 4012 03:05:00,280 --> 03:05:00,600 ADOPTED. 4013 03:05:00,600 --> 03:05:03,520 AND IN WHICH CASE THE OWNERS 4014 03:05:03,520 --> 03:05:04,560 TYPICALLY DO NOT KNOW THEIR AGE 4015 03:05:04,560 --> 03:05:07,000 OTHER THAN THIS IS A YOUNG DOG 4016 03:05:07,000 --> 03:05:09,720 OR THIS IS AN OLD DOG AND SHE 4017 03:05:09,720 --> 03:05:13,560 SPENT TWO YEARS AT THE BEFRNL 4018 03:05:13,560 --> 03:05:23,160 DESIGNING AN EQUIVALENT SOLID 4019 03:05:23,160 --> 03:05:28,280 PHASE TECHNOLOGY WENT LIQUID 4020 03:05:28,280 --> 03:05:30,840 PHASE CREATING EQUIVALENT DOG 4021 03:05:30,840 --> 03:05:33,680 METHYLATION ARRAY ENRICHED FOR 4022 03:05:33,680 --> 03:05:35,880 SEINETENIC CPG SITES AND REGIONS 4023 03:05:35,880 --> 03:05:39,640 THAT WERE ALREADY DESIGNED ON 4024 03:05:39,640 --> 03:05:42,120 THAT ALUM IN A CHIP. 4025 03:05:42,120 --> 03:05:44,560 THAT IS WHAT SHE DID. DID SHE 4026 03:05:44,560 --> 03:05:47,680 BUILD AN EPIGENETIC CLOCK? NO. 4027 03:05:47,680 --> 03:05:50,800 SHE DID NOT. SHE SIMPLY ALIGNED 4028 03:05:50,800 --> 03:05:55,600 EVERY DOG METHO LOAM 100 LAB RAD 4029 03:05:55,600 --> 03:05:58,720 DOR RETRIEVER MENLO LOAMS THAT 4030 03:05:58,720 --> 03:06:00,040 MOSTLY CAME FROM [INDISCERNIBLE] 4031 03:06:00,040 --> 03:06:04,360 AT UC DAVIS IN COLLABORATION 4032 03:06:04,360 --> 03:06:08,600 WITH NIH AND PETER WHO IS IN 4033 03:06:08,600 --> 03:06:10,640 TOUNL AT BURN HAM AND ALIGNED 4034 03:06:10,640 --> 03:06:12,920 EACH OF THE DOG METHO LOAMS 4035 03:06:12,920 --> 03:06:14,520 AGAINST POPULATION IN PUBLIC 4036 03:06:14,520 --> 03:06:18,120 DOMAIN BY THAT TIME HUMAN METHO 4037 03:06:18,120 --> 03:06:20,240 LOAMS LOOKING AT WHAT NEAREST 4038 03:06:20,240 --> 03:06:24,880 NEIGHBORS IN ALIGNMENT WERE AND 4039 03:06:24,880 --> 03:06:27,840 SIMILAR SPECIES YOUNG DOGS ARE 4040 03:06:27,840 --> 03:06:29,920 SIMILAR TO HUMAN METHO LOAMS AND 4041 03:06:29,920 --> 03:06:33,480 VICE VERSA AND YOU CAN IN FACT 4042 03:06:33,480 --> 03:06:34,360 QUANTITATIVELY DRAW A CURVE THAT 4043 03:06:34,360 --> 03:06:37,560 LOOKS LIKE THIS. WHAT YOU SEE 4044 03:06:37,560 --> 03:06:39,760 IS IN FACT NOT A LINEAR 4045 03:06:39,760 --> 03:06:42,600 RELATIONSHIP OR IS NOT THE SORT 4046 03:06:42,600 --> 03:06:46,240 OF 7 NUMON YEARS TO ONE DOG 4047 03:06:46,240 --> 03:06:48,040 ADAGE THAT MAY IN FACT BE TRUE 4048 03:06:48,040 --> 03:06:50,120 BY THE END OF LIFE. WAY YOU GET 4049 03:06:50,120 --> 03:06:55,640 THERE IS HIGHLY NON-LINEAR AND 4050 03:06:55,640 --> 03:06:58,800 ESSENTIALLY IS A ONE YEAR OLD 4051 03:06:58,800 --> 03:07:00,920 DOG OR NINE-MONTH OLD DOG LIKE 4052 03:07:00,920 --> 03:07:03,640 AN EARLY ADULT 20 TO 30 YEAR OLD 4053 03:07:03,640 --> 03:07:06,600 IN HUMAN SPACE IN RETROSPECT IS 4054 03:07:06,600 --> 03:07:08,640 NOT SURPRISING DOGS CAN'T 4055 03:07:08,640 --> 03:07:11,160 PUPPIES FAR WELL IN ADVANCE OF 4056 03:07:11,160 --> 03:07:16,080 ONE AGE. 7X MAP SIMPLY DOESN'T 4057 03:07:16,080 --> 03:07:17,080 WORK PHYSIOLOGICALLY EITHER. 4058 03:07:17,080 --> 03:07:19,440 WHAT WAS EXCITING ABOUT METHO 4059 03:07:19,440 --> 03:07:22,360 LOAM IS GETTING A QUANTITATIVE 4060 03:07:22,360 --> 03:07:23,840 CURVE AND WHAT WAS EVEN MORE 4061 03:07:23,840 --> 03:07:27,960 EXCITING IS YOU CAN NOW LOOK AT 4062 03:07:27,960 --> 03:07:34,320 THE GENOME OR EPIGENOME TO 4063 03:07:34,320 --> 03:07:36,520 FIGURE OUT WHAT REGIONS OF 4064 03:07:36,520 --> 03:07:39,960 GENOME ARE WITH SIMILARITY THAT 4065 03:07:39,960 --> 03:07:43,560 IS MAXIMAL OR SIMPLY DISTRIBUTED 4066 03:07:43,560 --> 03:07:48,760 WIDELY AND TURNS OUT SIMILARITY 4067 03:07:48,760 --> 03:07:59,080 DOES CLUSTER AND NAL THAT IS NOT 4068 03:07:59,080 --> 03:08:01,080 PERFECT AND FOUND TWO CLUSTERS 4069 03:08:01,080 --> 03:08:04,880 THROUGH ANALYSIS AND PROTEIN 4070 03:08:04,880 --> 03:08:07,240 INTERACTION NETWORKS ANATOMICAL 4071 03:08:07,240 --> 03:08:08,920 DEVELOPMENT 1 AND 2 AND HERE 4072 03:08:08,920 --> 03:08:11,160 SHOWN ABOVE EACH OF THESE 4073 03:08:11,160 --> 03:08:14,240 CLUSTERS SHOWN TO CONSERVE 4074 03:08:14,240 --> 03:08:16,760 METHYLATION COURSE OF GENOME 4075 03:08:16,760 --> 03:08:18,760 REALM THAT IS OVER LIFE COURSES 4076 03:08:18,760 --> 03:08:21,400 OF DOGS AND HUMANS AND WE ARE 4077 03:08:21,400 --> 03:08:25,120 ALIGNING MICE. YOU HAVE THREE 4078 03:08:25,120 --> 03:08:28,960 SPECIES THAT AGE WITH DIFFERENT 4079 03:08:28,960 --> 03:08:32,680 CHRONOLOGICAL LIFESPANS AND 4080 03:08:32,680 --> 03:08:34,080 ALIGNING THEM THROUGH FRACTION 4081 03:08:34,080 --> 03:08:35,480 OF LIFESPAN THEY ARE AND LOOK IN 4082 03:08:35,480 --> 03:08:39,280 ALL THREE SPECIES LOOKING AT 4083 03:08:39,280 --> 03:08:41,720 CONSENSUS METHYLATION PATTERNS 4084 03:08:41,720 --> 03:08:43,800 LOOKING MOSTLY AT GENES TOP AND 4085 03:08:43,800 --> 03:08:46,480 YOUNG AND BOTTOM INCREASING 4086 03:08:46,480 --> 03:08:51,080 METHYLATION AS WE AGE AND YOU 4087 03:08:51,080 --> 03:08:52,440 ASK OVER HERE DECREASING 4088 03:08:52,440 --> 03:08:54,200 METHYLATION AS WE AGE AND GENES 4089 03:08:54,200 --> 03:08:56,880 RESPONSIBLE FOR GROWING OF ARMS 4090 03:08:56,880 --> 03:09:00,720 AND LEGS AND TAILS. 4091 03:09:00,720 --> 03:09:03,760 SHE WENT ON IN A CONSERVATION 4092 03:09:03,760 --> 03:09:07,600 MODE TO LOOK WITH PETER ADAMS 4093 03:09:07,600 --> 03:09:13,720 AND HOLY BROWN MORGUE WITH MICE 4094 03:09:13,720 --> 03:09:17,160 RESTRICTION AND DOFSHISM AND 4095 03:09:17,160 --> 03:09:19,640 RAPPAMYCIN TREATMENT AND IS 4096 03:09:19,640 --> 03:09:20,680 SHOWING AMAZING WORK BY TINA 4097 03:09:20,680 --> 03:09:24,720 WONG WHEN SHE WAS HERE THAT WILD 4098 03:09:24,720 --> 03:09:30,720 TYPE MICE IN GRAY MOSTLY FALL ON 4099 03:09:30,720 --> 03:09:32,560 DIAGONAL THAT YOU WOULD EXPECT 4100 03:09:32,560 --> 03:09:35,000 AND DO BETTER ALREADY SORT OF 4101 03:09:35,000 --> 03:09:37,800 EPIGENETIC AGES YOUNGER YOU 4102 03:09:37,800 --> 03:09:39,000 EXPECT BY CHRONOLOGICAL AGE AND 4103 03:09:39,000 --> 03:09:41,960 LOOK WHAT HAPPENS WHEN YOU TREAT 4104 03:09:41,960 --> 03:09:47,160 WITH RAPPAMYCIN AND RETARD E 4105 03:09:47,160 --> 03:09:50,480 EPIGENETIC AGE AND REGRESSION OF 4106 03:09:50,480 --> 03:09:53,880 MENLO LOAM SHOWING THAT THESE 4107 03:09:53,880 --> 03:09:56,560 EPIGENETIC CLOCKS ARE GOOD 4108 03:09:56,560 --> 03:10:00,160 MEASURE OF WHATEVER LIFESPAN 4109 03:10:00,160 --> 03:10:01,840 EXTENDING TREATMENT YOU ARE 4110 03:10:01,840 --> 03:10:05,200 TRYING IS WORKING AND POINTING 4111 03:10:05,200 --> 03:10:07,720 OUT TWO PAPERS COMING OUT AROUND 4112 03:10:07,720 --> 03:10:09,720 THE SAME TIME WITH SIMILAR 4113 03:10:09,720 --> 03:10:11,880 RESULTS IN CASE OF AGING SELF 4114 03:10:11,880 --> 03:10:14,000 HAS MORE DATA THAN WE HAD AND 4115 03:10:14,000 --> 03:10:20,920 PLEASE TAKE A LOOK AT THOSE AS 4116 03:10:20,920 --> 03:10:24,040 WELL IN LAST MINUTE OR TWO I 4117 03:10:24,040 --> 03:10:24,920 RESERVE TIME TO TALK ABOUT WHAT 4118 03:10:24,920 --> 03:10:28,440 WE ARE DOING NOW THAT IS 4119 03:10:28,440 --> 03:10:31,120 UNPUBLISHED STUFF ALREADY AND SO 4120 03:10:31,120 --> 03:10:35,200 VERY PRELIMINARY BUT I THINK IS 4121 03:10:35,200 --> 03:10:36,400 INTERESTING AND WE ARE 4122 03:10:36,400 --> 03:10:39,040 INTERESTED IN WHAT DRIVES 4123 03:10:39,040 --> 03:10:41,440 EPIGENETIC AGING SIGNALS GOOD AS 4124 03:10:41,440 --> 03:10:44,840 DIAGNOSTIC BUT ARE CAUSAL FOR 4125 03:10:44,840 --> 03:10:46,240 SOMETHING OR REACTION FOR 4126 03:10:46,240 --> 03:10:47,080 SOMETHING AND BOTH AND WHAT 4127 03:10:47,080 --> 03:10:49,320 WOULD BE THOSE THINGS AND THAT 4128 03:10:49,320 --> 03:10:52,920 IS A NONEXHAUSTIVE LIST OF 4129 03:10:52,920 --> 03:10:53,600 EXPLANATIONS POSED BY MANY 4130 03:10:53,600 --> 03:10:57,880 PEOPLE OVER MANY DECADES NOW. 4131 03:10:57,880 --> 03:11:00,680 ONE, EPIGENETIC CHANGES ARE 4132 03:11:00,680 --> 03:11:02,240 CONSEQUENCES OF DAMAGE THAT IS 4133 03:11:02,240 --> 03:11:06,560 ACCRUING OVER TIME AND THIS IS A 4134 03:11:06,560 --> 03:11:08,920 CLASSIC, YOU KNOW, AGING THEORY 4135 03:11:08,920 --> 03:11:12,520 AND THESE DAYS IT IS POSITIED 4136 03:11:12,520 --> 03:11:16,520 FOLLOWED BY DAVID SINCLAIR AND 4137 03:11:16,520 --> 03:11:18,400 ALEX ANDROF IN CANCER COMMUNITY 4138 03:11:18,400 --> 03:11:20,680 AND OTHERS. SORRY LOTS OF 4139 03:11:20,680 --> 03:11:23,240 PEOPLE HERE. WANTED TO SAY A 4140 03:11:23,240 --> 03:11:27,360 FEW NAMES AND 5 TO OTHERS AND 4141 03:11:27,360 --> 03:11:32,920 THAT IS ONE THEORY AND OTHER 4142 03:11:32,920 --> 03:11:35,200 THEORY WITH DOG CONSERVATION 4143 03:11:35,200 --> 03:11:38,920 PAPER WITH OWN WORK ARE MAYBE 4144 03:11:38,920 --> 03:11:40,320 CHANGES HAPPENING DURING 4145 03:11:40,320 --> 03:11:42,680 DEVELOPMENT IN A CONSERVED WAY 4146 03:11:42,680 --> 03:11:44,240 AND AGING IS SIMPLY AN EXTENSION 4147 03:11:44,240 --> 03:11:45,600 OF THAT DEVELOPMENTAL PROGRAM 4148 03:11:45,600 --> 03:11:48,800 AND HERE ARE OTHERS WHO ARE 4149 03:11:48,800 --> 03:11:49,520 CERTAINLY PROPONENTS OF THIS 4150 03:11:49,520 --> 03:11:51,960 THEORY AND, YOU KNOW, THERE HAS 4151 03:11:51,960 --> 03:11:56,880 BEEN A BIT OF BUZZ LATELY ABOUT 4152 03:11:56,880 --> 03:11:59,040 RECENT ARTICLE AGING SOFTWARE 4153 03:11:59,040 --> 03:12:00,920 DESIGN FLAW THAT CAME OUT THAT 4154 03:12:00,920 --> 03:12:02,520 REALLY FALLS INTO THIS 4155 03:12:02,520 --> 03:12:03,800 PARTICULAR THEORY CLASS AND 4156 03:12:03,800 --> 03:12:08,920 PETER AND SEVERAL OTHERS HAVE 4157 03:12:08,920 --> 03:12:12,440 SAID YOU KNOW THIS IS ALL NOT AS 4158 03:12:12,440 --> 03:12:15,280 IMPORTANT AS LOOKING AT CHANGES 4159 03:12:15,280 --> 03:12:16,920 IN CELL TYPE COMPOSITION AS WE 4160 03:12:16,920 --> 03:12:18,840 AGE AND NOT HAPPENING WITH 4161 03:12:18,840 --> 03:12:22,320 INDIVIDUAL CELLS BY ANY MEANS 4162 03:12:22,320 --> 03:12:26,040 AND THINK THAT WE STARTED A FEW 4163 03:12:26,040 --> 03:12:27,520 LATE BUT WANT TO SAVE TIME FOR 4164 03:12:27,520 --> 03:12:29,200 QUESTIONS AND WHAT I WILL DO IS 4165 03:12:29,200 --> 03:12:32,520 SKIP TO THE END TAKING QUESTIONS 4166 03:12:32,520 --> 03:12:37,640 AND WE CERTAINLY THINK THERE ARE 4167 03:12:37,640 --> 03:12:39,400 INTERESTING ANALYSIS THAT COULD 4168 03:12:39,400 --> 03:12:43,160 BE DONE TO LOOK AT RELATIONSHIP 4169 03:12:43,160 --> 03:12:44,360 BETWEEN EPIGENETIC CHANGE AND 4170 03:12:44,360 --> 03:12:47,040 SOMATIC MUTATIONS IN EXISTING 4171 03:12:47,040 --> 03:12:48,840 DATA SETS OUT THERE IN THE 4172 03:12:48,840 --> 03:12:50,960 PUBLIC DOMAIN AND I'M HAPPY TO 4173 03:12:50,960 --> 03:12:52,880 ANSWER QUESTIONS ABOUT THAT 4174 03:12:52,880 --> 03:12:55,120 LATER. JUST AS A SUMMARY, YOU 4175 03:12:55,120 --> 03:12:58,880 KNOW, AGING, I THINK, IT IS 4176 03:12:58,880 --> 03:13:01,920 WELL-KNOWN NOW TO BE TRACKED 4177 03:13:01,920 --> 03:13:05,280 WELL BY METHYLATION CHANGES AND 4178 03:13:05,280 --> 03:13:07,320 CYTOSINE AND KWAUN EVEN SITES 4179 03:13:07,320 --> 03:13:10,240 OVER MANY DIFFERENT SITES AND 4180 03:13:10,240 --> 03:13:12,880 SIGNATURE SO-CALLED CLOCK IS 4181 03:13:12,880 --> 03:13:14,760 EFFECTED BY DISEASE STATES AND 4182 03:13:14,760 --> 03:13:16,880 SLOWED BY CLASSIC LIFESPAN 4183 03:13:16,880 --> 03:13:17,960 ENHANCING TREATMENTS. 4184 03:13:17,960 --> 03:13:23,200 IT IS CONSERVED IN MAMMALS AND 4185 03:13:23,200 --> 03:13:25,840 WHICH CAN PINPOINT -- PINPOINTS 4186 03:13:25,840 --> 03:13:28,760 DEVELOPMENTAL GENES AND THEORIES 4187 03:13:28,760 --> 03:13:33,080 OF AGING AND IN WORK THAT I RAN 4188 03:13:33,080 --> 03:13:35,800 OUT OF TIME TO SHOW ONE CAN ALSO 4189 03:13:35,800 --> 03:13:37,280 TURNS THROUGHOUT IS A GLIMMER 4190 03:13:37,280 --> 03:13:39,920 THERE IS A RELATIONSHIP BETWEEN 4191 03:13:39,920 --> 03:13:44,880 DNA MUTATIONS AND CHANGES IN 4192 03:13:44,880 --> 03:13:46,800 HYPOAND HYPERMETHYLATION 4193 03:13:46,800 --> 03:13:47,720 GENOMEWIDE SUPPORTING ANOTHER 4194 03:13:47,720 --> 03:13:49,840 THEORY OF AGING AND MUTATION 4195 03:13:49,840 --> 03:13:54,160 THEORY AND THANK YOU VERY MUCH. 4196 03:13:54,160 --> 03:13:58,360 >>THIS TALK IS ON HOW TO 4197 03:13:58,360 --> 03:14:01,080 MEASURE AGING AND LOTS OF WORK 4198 03:14:01,080 --> 03:14:09,400 IN PAST FEW DECADES FROM STUDIES 4199 03:14:09,400 --> 03:14:12,120 WE KNOW HUNDREDS IF NOT 4200 03:14:12,120 --> 03:14:14,960 THOUSANDS OF GENES EXTENDING 4201 03:14:14,960 --> 03:14:16,640 LIFESPAN ACROSS A RANGE OF 4202 03:14:16,640 --> 03:14:18,760 DIFFERENT MODEL ORGANISMS AND IN 4203 03:14:18,760 --> 03:14:23,000 FACT INSIGHTS DERIVED FROM 4204 03:14:23,000 --> 03:14:27,280 STUDIES ARE AT VERY HOERT AND 4205 03:14:27,280 --> 03:14:28,440 FOUNDATIONAL CONCEPTS TO BIOLOGY 4206 03:14:28,440 --> 03:14:31,720 OF AGING AND ONE REPRESENTATION 4207 03:14:31,720 --> 03:14:34,400 OF THAT HALLMARKS OF AGING HERE 4208 03:14:34,400 --> 03:14:36,360 NOT GOING INTO TOO MANY DETAILS 4209 03:14:36,360 --> 03:14:37,680 AND STRESSING FACT THAT IDEAS 4210 03:14:37,680 --> 03:14:40,240 ARE BASED ACTUALLY ON LIFESPAN 4211 03:14:40,240 --> 03:14:47,240 DATA THAT IS IN A WAY A BIT 4212 03:14:47,240 --> 03:14:50,440 PROBLEMATIC STRUDYING LIFESPAN 4213 03:14:50,440 --> 03:14:52,920 AND AGING IS NOT SAME THING AND 4214 03:14:52,920 --> 03:14:54,840 LIMITED DISEASES AND WE HEARD 4215 03:14:54,840 --> 03:14:56,720 TODAY AND YESTERDAY THAT RATHER 4216 03:14:56,720 --> 03:15:00,240 THAN GENERAL PHYSIOLOGICAL 4217 03:15:00,240 --> 03:15:01,600 DECLINE THAT IF YOU CONSIDER THE 4218 03:15:01,600 --> 03:15:04,480 CONTEXT IN MICE FOR EXAMPLE IS 4219 03:15:04,480 --> 03:15:06,000 PRETTY WELL KNOWN THAT CANCER IS 4220 03:15:06,000 --> 03:15:08,720 A MAJOR KILLER IN OLD AGE AND 4221 03:15:08,720 --> 03:15:12,840 ARE STUDIES SHOWING 70 TO 90% OF 4222 03:15:12,840 --> 03:15:17,520 MOUSE STRAINS CAN DIE TO CANCER 4223 03:15:17,520 --> 03:15:21,360 IN OLD AGE AND TRYING TO DO A 4224 03:15:21,360 --> 03:15:25,240 SCREEN FOR EXAMPLE GENETIC 4225 03:15:25,240 --> 03:15:26,760 LIFESPAN IN MICE YOU WOULD 4226 03:15:26,760 --> 03:15:29,000 LIKELY PICK UP MODIFIERS OF 4227 03:15:29,000 --> 03:15:31,280 PLASTIC DISEASE BASED ON 4228 03:15:31,280 --> 03:15:34,440 CONSIDERATIONS AND YOU WOULDN'T 4229 03:15:34,440 --> 03:15:38,320 NECESSARILY KNOW IF MODIFIERS OF 4230 03:15:38,320 --> 03:15:42,640 LIFESPAN REGULATE AGING AND IS 4231 03:15:42,640 --> 03:15:46,240 KIND OF SHOWN IN THIS CARTOON 4232 03:15:46,240 --> 03:15:48,760 HERE AND IF WE VIEW AGING AS 4233 03:15:48,760 --> 03:15:49,640 LARGE COLLECTION OF AGE 4234 03:15:49,640 --> 03:15:52,760 SENSITIVE PHENOTYPES AND USING 4235 03:15:52,760 --> 03:15:55,240 LIFE SPAN AS READ OUT WE WILL 4236 03:15:55,240 --> 03:16:02,760 LEARN ABOUT REGULATORS OF ORE 4237 03:16:02,760 --> 03:16:04,160 MECHANISMS THAT ARE LIFE 4238 03:16:04,160 --> 03:16:06,520 LIMITING CAUSES OF DEATH FOR 4239 03:16:06,520 --> 03:16:09,240 EXAMPLE AND WOULDN'T LEARN ABOUT 4240 03:16:09,240 --> 03:16:11,080 MODULATORS OF AGE SENSITIVE 4241 03:16:11,080 --> 03:16:13,240 PHENOTYPES THAT ARE NOT LIFE 4242 03:16:13,240 --> 03:16:19,240 LIMITING AND MIGHT BE MANY OF 4243 03:16:19,240 --> 03:16:27,440 THESE -- ORGANISMS WHETHER THEY 4244 03:16:27,440 --> 03:16:30,840 ARE MORE BROADLY HAVING EFFECTS 4245 03:16:30,840 --> 03:16:32,960 ON AGING AND AGE RELATED 4246 03:16:32,960 --> 03:16:35,080 MORTALITY AND APPROACH THAT WE 4247 03:16:35,080 --> 03:16:39,280 HAVE TAKEN IS TO PERFORM 4248 03:16:39,280 --> 03:16:41,880 PHENOTYPING ACROSS RANGE OF 4249 03:16:41,880 --> 03:16:47,240 TISSUES AND ORGAN SYSTEMS AND 4250 03:16:47,240 --> 03:16:48,560 BIOLOGICAL COMPLEXITY COMPARING 4251 03:16:48,560 --> 03:16:50,440 ORGAN MODELS AND LIKE GOING FROM 4252 03:16:50,440 --> 03:16:52,040 HOSPITAL TO HOSPITAL AND 4253 03:16:52,040 --> 03:16:53,400 SPECIALIST TO SPECIALIST GETTING 4254 03:16:53,400 --> 03:16:55,640 HEALTH CHECKS PUTTING DATA 4255 03:16:55,640 --> 03:16:58,800 TOGETHER TO BUILD 4256 03:16:58,800 --> 03:16:59,440 MULTIDIMENSIONAL REPRESENTATION 4257 03:16:59,440 --> 03:17:02,120 OF BIOLOGICAL AGE AND CAN USE TO 4258 03:17:02,120 --> 03:17:06,680 TEST POSSIBLE ANTIAGING 4259 03:17:06,680 --> 03:17:08,240 INTERVENTIONS AGAINST. 4260 03:17:08,240 --> 03:17:10,680 FRAMEWORK WHILE APPLYING CERTAIN 4261 03:17:10,680 --> 03:17:14,080 INTERVENTIONS TO MICE WE CAN TRY 4262 03:17:14,080 --> 03:17:17,120 TO UNDERSTAND WHICH POTENTIAL 4263 03:17:17,120 --> 03:17:19,240 PROCESS IS LINKED TO WHICH AGE 4264 03:17:19,240 --> 03:17:21,360 SPECIFIC PHENOTYPE THAT IS NOT 4265 03:17:21,360 --> 03:17:24,160 SUFFICIENT TO LOOK AT AGE 4266 03:17:24,160 --> 03:17:28,600 SENSITIVE PHENOTYPE IN OLD 4267 03:17:28,600 --> 03:17:29,200 ANIMALS BECAUSE A TREATMENT 4268 03:17:29,200 --> 03:17:33,040 COULD INFLUENCE A PHENOTYPE IN 4269 03:17:33,040 --> 03:17:35,760 MANY WAYS WHICH ALL ARE NOT 4270 03:17:35,760 --> 03:17:41,000 INFLUENCING AGE DEPENDENT 4271 03:17:41,000 --> 03:17:42,200 PHENOTIPIG CHANGE AND COST 4272 03:17:42,200 --> 03:17:43,160 EFFECTIVE TREATMENTS HERE AND 4273 03:17:43,160 --> 03:17:46,320 SHOWING TWO EXAMPLES TO 4274 03:17:46,320 --> 03:17:49,000 ILLUSTRATE THAT POINT. SO, FROM 4275 03:17:49,000 --> 03:17:51,120 SYMPTOMATIC TREATMENTS WE CAN'T 4276 03:17:51,120 --> 03:17:52,720 ACTUALLY INFER AGING MECHANISMS 4277 03:17:52,720 --> 03:17:59,160 WITH AGING MECHANISMS I MEAN 4278 03:17:59,160 --> 03:18:01,000 MECHANISMS THAT HAVE PHENOTYPIC 4279 03:18:01,000 --> 03:18:03,280 CHANGE TO GIVE YOU ONE EXAMPLE 4280 03:18:03,280 --> 03:18:07,240 AND AGING PHENOTYPE EFFECTING 4281 03:18:07,240 --> 03:18:15,240 HAIR AND LET'S ASSUME THAT 4282 03:18:15,240 --> 03:18:18,160 BIOLOGICAL MECHANISMS WITH AGE 4283 03:18:18,160 --> 03:18:19,480 SENSITIVE PHENOTYPE IS 4284 03:18:19,480 --> 03:18:22,080 DISFUNCTION OF [INDISCERNIBLE] 4285 03:18:22,080 --> 03:18:25,680 STEM CELLS AND ANY TREATMENT 4286 03:18:25,680 --> 03:18:27,960 THAT TARGETS ROOT CAUSES 4287 03:18:27,960 --> 03:18:31,240 PHENOTYPE ADDRESSING BUY LOGIC 4288 03:18:31,240 --> 03:18:34,320 CHAFKS AND IS POSSIBLE WE CAUSE 4289 03:18:34,320 --> 03:18:37,640 CHANGE SENSITIVE PHENOTYPE IN 4290 03:18:37,640 --> 03:18:41,480 SENSITIVE WAY WITHOUT ALTERING 4291 03:18:41,480 --> 03:18:45,280 -- WE COULD COLOR HAIR AND 4292 03:18:45,280 --> 03:18:46,000 POTENTIALLY CONVERT WHITE TO 4293 03:18:46,000 --> 03:18:47,480 BLACK HAIR FOR EXAMPLE AND 4294 03:18:47,480 --> 03:18:49,000 WOULDN'T BE ABLE TO LEARN 4295 03:18:49,000 --> 03:18:52,680 ANYTHING ABOUT AGING MECHANISMS 4296 03:18:52,680 --> 03:18:56,440 FROM THIS EFFECT GIVING A SECOND 4297 03:18:56,440 --> 03:19:00,640 EXAMPLE AGE RELATED COGNITIVE 4298 03:19:00,640 --> 03:19:04,480 DECLINE THAT IN A FICTITIOUS 4299 03:19:04,480 --> 03:19:05,480 PERFORMANCE ON COGNITIVE TEST 4300 03:19:05,480 --> 03:19:08,920 THAT IS STABLE FOR SOME TIME AND 4301 03:19:08,920 --> 03:19:15,000 IS DECLINE BASED ON WHEN DECLINE 4302 03:19:15,000 --> 03:19:17,560 OCCURS DISTINGUISH BETWEEN 4303 03:19:17,560 --> 03:19:21,080 ASYMPTOMATIC TO SYMPTOMATIC 4304 03:19:21,080 --> 03:19:26,400 PHASE AND TARGETS MECHANISMS 4305 03:19:26,400 --> 03:19:29,240 UNDERLYING AGE RELATED DECLINE 4306 03:19:29,240 --> 03:19:33,480 AND TREATMENT HERE AND IT SLOWS 4307 03:19:33,480 --> 03:19:39,280 DECLINE ONCE IT STARTED TO 4308 03:19:39,280 --> 03:19:41,880 EMERGE AND FICTITIOUS EXAMPLE IN 4309 03:19:41,880 --> 03:19:44,800 GENERATION AND CONTEXT OF 4310 03:19:44,800 --> 03:19:46,280 ALZHEIMER'S DISEASE AND IF WE 4311 03:19:46,280 --> 03:19:48,240 SEE TREATMENT EFFECTS IN YOUNG 4312 03:19:48,240 --> 03:19:50,440 AND HEALTHY INDIVIDUALS THAT 4313 03:19:50,440 --> 03:19:52,440 DON'T HAVE SDEESED AND TREATMENT 4314 03:19:52,440 --> 03:19:57,320 EFFECT IS TARGETING MECHANISMS 4315 03:19:57,320 --> 03:19:58,080 OF DISEASED AND TREATMENT EFFECT 4316 03:19:58,080 --> 03:20:02,920 IN PEOPLE GOING ON TO DEVELOP 4317 03:20:02,920 --> 03:20:04,760 COGNITIVE DECLINE AND 4318 03:20:04,760 --> 03:20:05,720 ALZHEIMER'S DISEASE AND SEE 4319 03:20:05,720 --> 03:20:08,320 EFFECT PRIOR TO BEGINNING OF 4320 03:20:08,320 --> 03:20:10,040 MANIFESTATION OF DISEASES THAT 4321 03:20:10,040 --> 03:20:12,000 WOULDN'T BE EVIDENCE THAT WE ARE 4322 03:20:12,000 --> 03:20:17,080 TARGETING MECHANISMS OF DISEASE. 4323 03:20:17,080 --> 03:20:21,440 EXAMPLE MIGHT BE WE COULD USE 4324 03:20:21,440 --> 03:20:21,960 PSYCHOSTIMULANTS FOR 4325 03:20:21,960 --> 03:20:24,400 [INDISCERNIBLE] FOR EXAMPLE TO 4326 03:20:24,400 --> 03:20:25,680 ENHANCE COGNITIVE NAUFRNGS WOULD 4327 03:20:25,680 --> 03:20:27,920 NOT BE EVIDENCE WE ARE TARGETING 4328 03:20:27,920 --> 03:20:29,800 MECHANISMS OF AGE RELATED 4329 03:20:29,800 --> 03:20:32,880 COGNITIVE DECLINE AND WITH THESE 4330 03:20:32,880 --> 03:20:35,280 CONSIDERATIONS WE CAN DESIGN 4331 03:20:35,280 --> 03:20:36,960 EXPERIMENTS WHERE WE TEST AND 4332 03:20:36,960 --> 03:20:41,800 WOULD INCLUDE YOUNGER ANIMALS TO 4333 03:20:41,800 --> 03:20:42,760 TEST BEFORE ONSET OF PHENOTYPIC 4334 03:20:42,760 --> 03:20:43,720 CHANGE TO DISSECT WHETHER 4335 03:20:43,720 --> 03:20:46,640 TREATMENT ACTS IN AGING 4336 03:20:46,640 --> 03:20:48,680 INDEPENDENT WAY OR IN FACT SLOWS 4337 03:20:48,680 --> 03:20:51,760 AGE DEPENDENT PHENOTYPIC CHANGE 4338 03:20:51,760 --> 03:20:54,240 AND IF YOU SEE TREATMENT EFFECTS 4339 03:20:54,240 --> 03:20:57,680 THAT ONLY EMERGE ONCE AGE 4340 03:20:57,680 --> 03:20:59,240 DEPENDENCE CHANGE STARTS TO 4341 03:20:59,240 --> 03:21:00,760 EMERGE AND NOT BEFORE IS 4342 03:21:00,760 --> 03:21:01,720 CONSISTENT WITH NOTION WHAT YOU 4343 03:21:01,720 --> 03:21:06,320 ARE DOING IS TARGETING AGE 4344 03:21:06,320 --> 03:21:07,280 DEPENDENT PHENOTYPIC CHANGE AND 4345 03:21:07,280 --> 03:21:09,240 IF YOU SEE TREATMENT EFFECTS 4346 03:21:09,240 --> 03:21:12,400 PRIOR TO EMERGENCE OF AGE 4347 03:21:12,400 --> 03:21:13,720 DEPENDENT PHENOTYPE THAT IS NOT 4348 03:21:13,720 --> 03:21:16,240 EVIDENCE YOU ARE ACTUALLY 4349 03:21:16,240 --> 03:21:17,000 TARGETING MECHANISMS THAT 4350 03:21:17,000 --> 03:21:19,720 UNDERLIE THIS AGE DEPENDENT 4351 03:21:19,720 --> 03:21:23,360 CHANGE IN PHENOTYPE. 4352 03:21:23,360 --> 03:21:25,720 TO BE ABLE TO USE THIS WE HAVE 4353 03:21:25,720 --> 03:21:28,480 TO KNOW WHAT TRAJECTORIES OF 4354 03:21:28,480 --> 03:21:30,440 PHENOTYPES ARE WE ARE USING IN 4355 03:21:30,440 --> 03:21:31,840 ANALYSIS AND WANTED TO APPROACH 4356 03:21:31,840 --> 03:21:34,520 IT BY ASKING FOR PHENOTYPES WE 4357 03:21:34,520 --> 03:21:39,080 ARE INCLUDING IN ANALYSIS WHAT 4358 03:21:39,080 --> 03:21:40,920 IS PHENOTYPIC TRAJECTORY OF 4359 03:21:40,920 --> 03:21:43,000 LIFESPAN OF ANIMAL AND DOG THIS 4360 03:21:43,000 --> 03:21:45,240 STARTING WITH CROSS-SECTIONAL 4361 03:21:45,240 --> 03:21:49,160 ANALYSIS IN CONTEXT COMPARING 4362 03:21:49,160 --> 03:21:53,280 3581420 END 6 MONTH OLD ANIMALS 4363 03:21:53,280 --> 03:21:55,200 AND ESTABLISHED PHENOTYPE 4364 03:21:55,200 --> 03:21:56,720 TRAJECTORIES AND PERFORMED 4365 03:21:56,720 --> 03:22:01,880 NUMBER OF MOLECULAR ANALYSIS AND 4366 03:22:01,880 --> 03:22:03,080 TRANSCRIPTOMICS AND WILL FOCUS 4367 03:22:03,080 --> 03:22:06,400 ON RESULTS HERE AND ALLOWS TO 4368 03:22:06,400 --> 03:22:10,040 HAVE EACH PHENOTYPE TO ESTIMATE 4369 03:22:10,040 --> 03:22:11,440 TRAJECTORIES AND HYPOTHESIZE 4370 03:22:11,440 --> 03:22:15,240 THERE IS LIKELY IN YOUNG 4371 03:22:15,240 --> 03:22:16,720 ADULTHOOD STAPLED PHASE THERE IS 4372 03:22:16,720 --> 03:22:19,120 NOT MUCH PHENOTYPIC CHANGE AND 4373 03:22:19,120 --> 03:22:22,160 IF TRUE WE CAN USE THIS TO TEST 4374 03:22:22,160 --> 03:22:26,400 WHETHER TREATMENTS HAS AGING 4375 03:22:26,400 --> 03:22:34,120 INDEPENDENT EFFECTS SUMMARY OF 4376 03:22:34,120 --> 03:22:37,680 PHENOTYPIC RESULTS I WOULD LIKE 4377 03:22:37,680 --> 03:22:40,240 TO HIGHLIGHT THEY ARE NOT BEING 4378 03:22:40,240 --> 03:22:41,760 SELECTIVE AND SELECT WHAT CAN BE 4379 03:22:41,760 --> 03:22:44,320 DONE WITH STATE OF THE ART 4380 03:22:44,320 --> 03:22:45,760 PHENOTYPING ACROSS RANGE OF 4381 03:22:45,760 --> 03:22:48,080 TISSUES AND ORGAN SYSTEMS 4382 03:22:48,080 --> 03:22:50,480 FINDING COMPARING ACROSS AGE 4383 03:22:50,480 --> 03:22:52,560 GROUPS THAT ROUGHLY OVER HALF OF 4384 03:22:52,560 --> 03:22:54,560 THEM TURN OUT TO BE AGE 4385 03:22:54,560 --> 03:22:56,560 SENSITIVE SHOWING FORMS OF 4386 03:22:56,560 --> 03:22:58,000 DIFFERENCE BETWEEN AGE GROUPS 4387 03:22:58,000 --> 03:23:01,360 AND WE CAN SEE AGE SENSITIVE 4388 03:23:01,360 --> 03:23:02,600 PHENOTIECHS ACROSS ALL DOMAINS 4389 03:23:02,600 --> 03:23:04,640 THAT IS NOT A SURPRISE AND WE 4390 03:23:04,640 --> 03:23:06,480 WANTED TO THEN KNOW IF WE 4391 03:23:06,480 --> 03:23:08,880 COMPARE ALL AGE GROUPS BACK TO 4392 03:23:08,880 --> 03:23:10,800 THE THREE MONTH YOUNG ADULT 4393 03:23:10,800 --> 03:23:12,240 REFERENCE GROUP WHEN WE WOULD 4394 03:23:12,240 --> 03:23:15,240 FIRST BE ABLE TO SEE DEPARTURES 4395 03:23:15,240 --> 03:23:20,920 FROM YOUNG ADULT BASELINE. 4396 03:23:20,920 --> 03:23:23,920 WE FOUND EXAMPLES OF PHENOTYPES 4397 03:23:23,920 --> 03:23:26,320 ALREADY SHOWING CHANGES EARLY ON 4398 03:23:26,320 --> 03:23:30,840 AND EXAMPLE HERE IS STARTLE 4399 03:23:30,840 --> 03:23:32,320 AMMRITTUDE AND MOTOR RESPONSE 4400 03:23:32,320 --> 03:23:34,480 FOR STIMULATION THAT DECLINES 4401 03:23:34,480 --> 03:23:36,600 EARLY ALREADY AND MAKES SENSE 4402 03:23:36,600 --> 03:23:40,440 GIVEN THAT MOUSE STRAIN WE USE 4403 03:23:40,440 --> 03:23:42,240 FOR STUDIES BECOME DEAF 4404 03:23:42,240 --> 03:23:44,040 RELATIVELY EARLY ON AND THINK 4405 03:23:44,040 --> 03:23:46,040 PHENOTYPE IS CONSISTENT WITH 4406 03:23:46,040 --> 03:23:48,760 THIS NOTION AND THERE ARE SOME 4407 03:23:48,760 --> 03:23:49,720 PHENOTYPES ALTHOUGH NOT MANY 4408 03:23:49,720 --> 03:23:52,560 THAT SHOWED FIRST DEPARTURES 4409 03:23:52,560 --> 03:23:54,920 FROM YOUNG ADULT BASELINE BY 8 4410 03:23:54,920 --> 03:23:56,920 MONTHS AND EXAMPLE SHOWN HERE IS 4411 03:23:56,920 --> 03:24:01,000 PROPORTION OF CD14 T-CELL AND 4412 03:24:01,000 --> 03:24:03,320 NUMBER OF PHENOTYPES SHOWING 4413 03:24:03,320 --> 03:24:05,040 SIGNIFICANT DIFFERENCES FROM 4414 03:24:05,040 --> 03:24:07,120 YOUNG ADULT BASELINE AND MIDLIFE 4415 03:24:07,120 --> 03:24:09,000 WITH 14 MONTHS AND EXAMPLE SHOWN 4416 03:24:09,000 --> 03:24:11,840 HERE IS ELECTROCARDIO GRAPHIC 4417 03:24:11,840 --> 03:24:14,240 PHENOTYPE AND LOOKING AT 4418 03:24:14,240 --> 03:24:17,280 DURATION OF S COMPLEX REFLECTING 4419 03:24:17,280 --> 03:24:20,000 DEPOLARIZATION OF THESE KNOWN TO 4420 03:24:20,000 --> 03:24:22,080 INCREASE IN MICE AND MEN WITH 4421 03:24:22,080 --> 03:24:23,280 AGING AND THERE WERE ALSO A 4422 03:24:23,280 --> 03:24:25,720 NUMBER OF PHENOTYPES SHOWING 4423 03:24:25,720 --> 03:24:28,240 FIRST DEPARTURES FROM YOUNG 4424 03:24:28,240 --> 03:24:30,520 ADULT BASELINE AT 20 MONTH THAT 4425 03:24:30,520 --> 03:24:33,960 IS SHOWN HERE AS EXPLORATORY 4426 03:24:33,960 --> 03:24:35,280 LOCOMOTOR NOVELTY IN LOCAL 4427 03:24:35,280 --> 03:24:37,760 ENVIRONMENT AND THERE IS A FEW 4428 03:24:37,760 --> 03:24:39,600 PHENOTYPES SHOWING FIRST 4429 03:24:39,600 --> 03:24:41,400 DEPARTURES FROM YOUNG ADULT 4430 03:24:41,400 --> 03:24:42,600 BASELINE IN OLDEST GROUP AND 4431 03:24:42,600 --> 03:24:45,680 EXAMPLE I SHOWED HERE IS 4432 03:24:45,680 --> 03:24:47,080 PLATELET MORPH LOGICAL PHENOTYPE 4433 03:24:47,080 --> 03:24:49,760 AND THERE WERE FINALLY ALSO 4434 03:24:49,760 --> 03:24:52,960 CASES WHERE WE DIDN'T HAVE THIS 4435 03:24:52,960 --> 03:24:54,080 MONOTONIC TYPE OF CHANGE I 4436 03:24:54,080 --> 03:24:57,320 DESCRIBED IN EXAMPLES BEFORE AND 4437 03:24:57,320 --> 03:25:00,720 EXAMPLE FOR THIS MIGHT BE 4438 03:25:00,720 --> 03:25:01,600 [INDISCERNIBLE] THAT PEAKS 4439 03:25:01,600 --> 03:25:04,360 MIDLIFE AND DECLINES AGAIN AND 4440 03:25:04,360 --> 03:25:06,120 GROUPING AGE SENSITIVE 4441 03:25:06,120 --> 03:25:07,760 PHENOTYPES INCLUDING IN ANALYSIS 4442 03:25:07,760 --> 03:25:10,960 INTO DIFFERENT CATEGORIES, WE 4443 03:25:10,960 --> 03:25:13,640 SEE VERY FEW SHOW CHANGES EARLY 4444 03:25:13,640 --> 03:25:16,600 ON AT 5 OR 8 MONTH AND MOST SHOW 4445 03:25:16,600 --> 03:25:18,400 SIGNIFICANT DEPARTURES FROM 4446 03:25:18,400 --> 03:25:20,480 BASELINE ONLY IN OLDER GROUPS 4447 03:25:20,480 --> 03:25:24,440 AND IF WE PERFORM PRINCIPLE 4448 03:25:24,440 --> 03:25:27,000 COMPONENT ANALYSIS ON PHENOTYPIC 4449 03:25:27,000 --> 03:25:28,200 VARIABLES INCLUDED A THOUGHT 4450 03:25:28,200 --> 03:25:30,680 HERE BASICALLY AN ANIMAL WE SEE 4451 03:25:30,680 --> 03:25:33,200 3 AND 5 MONTH ANIMALS ARE PRETTY 4452 03:25:33,200 --> 03:25:34,920 MUCH CLOSE ON TOP OF EACH OTHER 4453 03:25:34,920 --> 03:25:36,920 AND THERE IS A PROGRESSIVE SHIFT 4454 03:25:36,920 --> 03:25:39,720 TO THE RIGHT WITH ADVANCING AGE. 4455 03:25:39,720 --> 03:25:42,200 AND THAT WOULD SUGGEST THAT IN 4456 03:25:42,200 --> 03:25:44,800 FACT 3 AND 5 MONTH OLD ANIMALS 4457 03:25:44,800 --> 03:25:46,600 ARE PRETTY SIMILAR 4458 03:25:46,600 --> 03:25:48,040 PHENOTYPICALLY AT LEAST WITH 4459 03:25:48,040 --> 03:25:49,760 REGARDS TO PHENOTYPES REGARDED 4460 03:25:49,760 --> 03:25:51,000 IN ANALYSIS THAT IS IMPORTANT 4461 03:25:51,000 --> 03:25:53,640 BECAUSE IT ALLOWS US TO TEST 4462 03:25:53,640 --> 03:25:54,800 WHETHER TREATMENT EFFECTS IN 4463 03:25:54,800 --> 03:25:56,760 THAT PERIOD HAPPENED AND IF THEY 4464 03:25:56,760 --> 03:26:00,040 DO AT THEIR LIKELY INDEPENDENT 4465 03:26:00,040 --> 03:26:03,800 OR AGE DEPENDENT PHENOTYPIC 4466 03:26:03,800 --> 03:26:06,000 CHANGE AND WANTED TO USE 4467 03:26:06,000 --> 03:26:07,760 APPROACH IF LONG LIVED MICE AGE 4468 03:26:07,760 --> 03:26:10,320 MORE SLOWSLY AND INCLUDED IN 4469 03:26:10,320 --> 03:26:12,040 THIS STUDY THREE DIFFERENT 4470 03:26:12,040 --> 03:26:15,160 INTERVENTIONS AND ONE IS GENETIC 4471 03:26:15,160 --> 03:26:19,280 LOSS OF FUNCTION MODEL M TORE 4472 03:26:19,280 --> 03:26:21,560 AND HOMOZYGOUS MICE FOR ALLELE 4473 03:26:21,560 --> 03:26:25,520 THAT IS CREATED AT NATIONAL 4474 03:26:25,520 --> 03:26:28,320 CANCER INSTITUTE AND MICE SHOWN 4475 03:26:28,320 --> 03:26:31,040 TO BE LONG-LIVED AND INCLUDED 4476 03:26:31,040 --> 03:26:33,160 MOUSE MODEL WITH LOSS OF 4477 03:26:33,160 --> 03:26:36,200 FUNCTIONING GROWTH HORMONE 4478 03:26:36,200 --> 03:26:37,760 SIGNALING HAVING POINT MUTATION 4479 03:26:37,760 --> 03:26:40,480 GROWTH RELEASING HORMONE 4480 03:26:40,480 --> 03:26:42,280 RECEPTOR AND MICE ARE DWARFS AND 4481 03:26:42,280 --> 03:26:44,640 KNOWN TO BE LONG-LIVED AND 4482 03:26:44,640 --> 03:26:47,280 FINALLY WE HAD A DIETARY 4483 03:26:47,280 --> 03:26:48,560 RESTRICTION REGIME THAT WE 4484 03:26:48,560 --> 03:26:50,920 INCLUDED AND ONE THAT FOCUSED ON 4485 03:26:50,920 --> 03:26:54,640 INTERMITTENT FASTING AND MORE 4486 03:26:54,640 --> 03:26:57,640 SPECIFICALLY THIS INTERMITTENT 4487 03:26:57,640 --> 03:26:59,240 FASTING REGIME INCLUDED EVERY 4488 03:26:59,240 --> 03:27:01,680 OTHER DAY FEEDING REGIME 4489 03:27:01,680 --> 03:27:02,720 ALTERNATING PERIODS OF 4490 03:27:02,720 --> 03:27:04,880 STARVATION WITH PERIODS OF FREE 4491 03:27:04,880 --> 03:27:06,720 ACCESS TO FOOD AND EACH BEING 24 4492 03:27:06,720 --> 03:27:09,200 HOURS AND WE START AT 8 WEEKS OF 4493 03:27:09,200 --> 03:27:10,600 AGE AND CONTINUE THROUGHOUT 4494 03:27:10,600 --> 03:27:18,320 ENTIRE COURSE OF THE STUDY FOOD 4495 03:27:18,320 --> 03:27:20,480 INTAKE OVER ENTIRE STUDY PERIOD 4496 03:27:20,480 --> 03:27:22,800 WE SEE INITIALLY SIGNIFICANT 4497 03:27:22,800 --> 03:27:24,600 REDUCTION IN FOOD INTAKE IN 4498 03:27:24,600 --> 03:27:27,280 FASTED ANIMALS AND APPEARS THAT 4499 03:27:27,280 --> 03:27:29,360 THEY LEARN TO WATCH AND EAT MORE 4500 03:27:29,360 --> 03:27:31,240 WHEN FOOD IS AVAILABLE ON 4501 03:27:31,240 --> 03:27:33,840 FEEDING DAY THAT COMPENSATES 4502 03:27:33,840 --> 03:27:37,240 OVERALL FOR LACK OF FOOD ON 4503 03:27:37,240 --> 03:27:40,080 OTHER DAY LOOKING AT ENTIRE 4504 03:27:40,080 --> 03:27:43,280 STUDY PERIOD THERE IS MODEST 4505 03:27:43,280 --> 03:27:46,040 REDUCTION FOOD INTAKE OF 10% OR 4506 03:27:46,040 --> 03:27:49,680 SO AND NEVERTHELESS MICE STAY 4507 03:27:49,680 --> 03:27:51,240 SUBSTANTIALLY UNDERWEIGHT TO 4508 03:27:51,240 --> 03:27:54,160 LIMIT CONTROLS AND TWO CURVES 4509 03:27:54,160 --> 03:27:56,240 HERE CORRESPOND TO MEASUREMENTS 4510 03:27:56,240 --> 03:27:59,080 AND BOTH ARE CLEARLY UNDER 4511 03:27:59,080 --> 03:28:01,760 CONTROL VALUES. 4512 03:28:01,760 --> 03:28:04,720 WE CONFIRM THAT THESE LEAD TO 4513 03:28:04,720 --> 03:28:05,760 SIGNIFICANT SIZE OF EXTENSION IN 4514 03:28:05,760 --> 03:28:09,800 MICE AND WANTED TO KNOW WHAT 4515 03:28:09,800 --> 03:28:11,920 LIKELY CAUSE OF DEATH IN MICE IS 4516 03:28:11,920 --> 03:28:17,200 AND CARCASS ANIMALS 4517 03:28:17,200 --> 03:28:21,000 SPONTANEOUSLY DIED FOR AUTOPSY 4518 03:28:21,000 --> 03:28:24,200 ANALYSIS AND SHOWS CONTROLS 86% 4519 03:28:24,200 --> 03:28:27,240 OF MICE LIKELY DUE TO CANCER IN 4520 03:28:27,240 --> 03:28:29,280 FORMS THAT ARE COMMON AND NO 4521 03:28:29,280 --> 03:28:30,880 SURPRISE AND SHOW THAT MICE 4522 03:28:30,880 --> 03:28:34,120 COMMONLY DIE TO CANCER AND 72% 4523 03:28:34,120 --> 03:28:36,600 OF CASES PROPORTION BEING 4524 03:28:36,600 --> 03:28:38,240 SLIGHTLY REDUCED LOOKING AT 4525 03:28:38,240 --> 03:28:40,760 PROPORTION OF MICE WITH MULTIPLE 4526 03:28:40,760 --> 03:28:43,240 INDEPENDENT TUMORS THAT WE THEN 4527 03:28:43,240 --> 03:28:47,280 SEE IN CONTROLS THIS IS 1/3 4528 03:28:47,280 --> 03:28:49,680 REDUCED TO 10% IN FACET MICE AND 4529 03:28:49,680 --> 03:28:52,040 THESE DATA ARE CONSISTENT WITH 4530 03:28:52,040 --> 03:28:54,120 FASTING MIGHT LEAD TO EXTENSION 4531 03:28:54,120 --> 03:28:55,240 BY SUPPRESSING CANCER 4532 03:28:55,240 --> 03:28:57,160 DEVELOPMENT AND EVENTUALLY MOST 4533 03:28:57,160 --> 03:28:58,760 OF MICE STILL DEVELOP CANCER BUT 4534 03:28:58,760 --> 03:29:06,920 DO SO AT AN OLDER AGE BASICALLY 4535 03:29:06,920 --> 03:29:08,000 SUBJECT WILLING THREE 4536 03:29:08,000 --> 03:29:10,240 EXPERIMENTAL APPROACHES TO 4537 03:29:10,240 --> 03:29:12,400 ANALYSIS PIPELINE AND PERFORMED 4538 03:29:12,400 --> 03:29:14,360 ANALYSIS WHERE WE HAVE 4539 03:29:14,360 --> 03:29:16,560 INTERVENTION THAT WE TREATED 4540 03:29:16,560 --> 03:29:18,440 CONTROL GROUP IN YOUNG ADULTHOOD 4541 03:29:18,440 --> 03:29:23,000 AND OLDER AGE AND 20 MONTH AND 4542 03:29:23,000 --> 03:29:25,160 SUBJECTED THEM SIDE BY SIDE TO 4543 03:29:25,160 --> 03:29:28,440 LARGE SCALE PHENOTYPE APPROACH 4544 03:29:28,440 --> 03:29:29,880 AND SUMMARIZING FINDINGS AND 4545 03:29:29,880 --> 03:29:31,680 SHOWN HERE IS PROPORTION OF AGE 4546 03:29:31,680 --> 03:29:34,040 SENSITIVE PHENOTYPES AND EITHER 4547 03:29:34,040 --> 03:29:35,560 INTERVENTION THAT ARE NOT 4548 03:29:35,560 --> 03:29:36,760 EFFECTED BY TREATMENT IN GRADE 4549 03:29:36,760 --> 03:29:38,360 THAT WERE COUNTERED BY 4550 03:29:38,360 --> 03:29:42,360 TREATMENTS AND WOULD BE 4551 03:29:42,360 --> 03:29:45,400 ANTIAGING EFFECTS IN GREEN ALSO 4552 03:29:45,400 --> 03:29:50,200 SOME CASES PHENOTYPES ACKRENATED 4553 03:29:50,200 --> 03:29:53,920 AND ARE IN RED AND MIXTURE OF 4554 03:29:53,920 --> 03:30:00,360 CASES WE WANTED PRIMARILY KNOW 4555 03:30:00,360 --> 03:30:01,800 WHETHER AGE SENSITIVE PHENOTYPES 4556 03:30:01,800 --> 03:30:03,600 AND EFFECTS COUNTERED BY 4557 03:30:03,600 --> 03:30:05,520 TREATMENT AND WHETHER MORE 4558 03:30:05,520 --> 03:30:07,280 RELATED TO AGE INDEPENDENT 4559 03:30:07,280 --> 03:30:10,920 EFFECTS OR TO EFFECTS CONSISTENT 4560 03:30:10,920 --> 03:30:16,080 WITH SLOWING AGING LOOKING AT 4561 03:30:16,080 --> 03:30:18,840 THAT COMPARING EFFECT SIZES IN 4562 03:30:18,840 --> 03:30:21,640 ANIMALS AND EMERGENCE OF 4563 03:30:21,640 --> 03:30:23,240 PHENOTYPIC CHANGE TO EFFECT SIZE 4564 03:30:23,240 --> 03:30:26,400 IN AGE ANIMALS UNDER CHRONIC 4565 03:30:26,400 --> 03:30:29,040 TREATMENT AND EACH DOT 4566 03:30:29,040 --> 03:30:31,280 CORRESPONDS TO PHENOTYPE FOR 4567 03:30:31,280 --> 03:30:35,280 EACH INTERVENTIONS IN GREEN ARE 4568 03:30:35,280 --> 03:30:40,760 PHENOTYPES WHERE THERE WAS NOT A 4569 03:30:40,760 --> 03:30:41,680 SIGNIFICANT DIFFERENCE BETWEEN 4570 03:30:41,680 --> 03:30:44,920 YOUNG AND OLD AND PHENOTYPES AND 4571 03:30:44,920 --> 03:30:47,280 AGING EFFECTS THAT COUNT ERRED 4572 03:30:47,280 --> 03:30:49,480 VIA INDEPENDENT EFFECTS THAT IS 4573 03:30:49,480 --> 03:30:50,360 SOMETHING REALLY IMPORTANT THAT 4574 03:30:50,360 --> 03:30:54,040 WE HAVE TO KEEP IN MIND FOR 4575 03:30:54,040 --> 03:31:01,120 FUTURE STUDIES FROM THIS STUDY 4576 03:31:01,120 --> 03:31:02,560 CONCLUDING THREE LONGEVITY 4577 03:31:02,560 --> 03:31:05,680 INTERVENTIONS WE EXAMINED HERE 4578 03:31:05,680 --> 03:31:07,280 FREQUENTLY HAVE PHENOTYPIC 4579 03:31:07,280 --> 03:31:09,360 EFFECTS COUNTERING AGE EFFECTS 4580 03:31:09,360 --> 03:31:12,200 SEEN IN YOUNG ANIMALS BEFORE AGE 4581 03:31:12,200 --> 03:31:14,880 DEPENDENT PHENOTYPIC CHANGE AND 4582 03:31:14,880 --> 03:31:17,000 ARGUING WITH TREATMENTS WITH 4583 03:31:17,000 --> 03:31:17,760 RESPECT TO PHENOTYPES ARE OFTEN 4584 03:31:17,760 --> 03:31:22,640 NOT TARGETING CAUSES OF AGE 4585 03:31:22,640 --> 03:31:23,600 DEPENDENT PHENOTYPIC CHANGE THAT 4586 03:31:23,600 --> 03:31:27,640 I THINK OF AS AGING AND WE 4587 03:31:27,640 --> 03:31:31,240 HAVING SYMPTOMATIC TREATMENT 4588 03:31:31,240 --> 03:31:32,400 EFFECTS THAT I THINK IS 4589 03:31:32,400 --> 03:31:37,320 IMPORTANT AND SHOULD TELL US TO 4590 03:31:37,320 --> 03:31:38,520 CLOSELY RE-EVALUATE SOME 4591 03:31:38,520 --> 03:31:41,840 MECHANISMS OF AGING THAT WE ARE 4592 03:31:41,840 --> 03:31:44,040 PRIMARILY INFORMED BY LIFESPAN 4593 03:31:44,040 --> 03:31:46,440 STUDIES TO SEE WHAT EXTENT 4594 03:31:46,440 --> 03:31:49,360 ACTUALLY PROCESSES ARE INVOLVED 4595 03:31:49,360 --> 03:31:52,840 IN SHAPING ORGANIZE MAL 4596 03:31:52,840 --> 03:31:54,200 PHENOTYPIC CHANGE OR NOT AND 4597 03:31:54,200 --> 03:31:55,720 WITH THIS WOULD LIKE TO CLOSE 4598 03:31:55,720 --> 03:31:57,800 AND THANK PEOPLE INVOLVED IN 4599 03:31:57,800 --> 03:32:00,000 THIS WORK AND MY LAB 4600 03:32:00,000 --> 03:32:01,360 HIGHLIGHTING CONTRIBUTION AND 4601 03:32:01,360 --> 03:32:07,280 BIG THANKS TO COLLABORATORS AT 4602 03:32:07,280 --> 03:32:12,480 [INDISCERN 4603 03:32:12,480 --> 03:32:12,880 [INDISCERNIBLE]. 4604 03:32:12,880 --> 03:32:14,560 THANK YOU FOR YOUR ATTENTION. 4605 03:32:14,560 --> 03:32:17,920 >>HI, EVERYBODY. I'M ALEX AND 4606 03:32:17,920 --> 03:32:23,080 FOUNDER AND CEO OF A COMPANY 4607 03:32:23,080 --> 03:32:28,560 INSILICO MEDICINE AND WISH I 4608 03:32:28,560 --> 03:32:30,280 COULD BE THERE IN PERSON WE ARE 4609 03:32:30,280 --> 03:32:32,520 WORKING ON A MEGA EXPERIMENT AND 4610 03:32:32,520 --> 03:32:34,320 HAVE TO MAKE SURE MY LAB IS 4611 03:32:34,320 --> 03:32:36,400 PROPERLY OPERATIONAL AND HAVE TO 4612 03:32:36,400 --> 03:32:39,560 SLEEP AND LIVE HERE FOR THE NEXT 4613 03:32:39,560 --> 03:32:42,880 WEEK. WITHOUT FURTHER ADO I 4614 03:32:42,880 --> 03:32:48,280 WILL SHARE MY SLIDES PRESENTING 4615 03:32:48,280 --> 03:32:54,800 TO YOU SOME NEW CONCEPTS FOR 4616 03:32:54,800 --> 03:32:57,480 AGING RESEARCH AND HOPE THEY CAN 4617 03:32:57,480 --> 03:32:59,880 SEE MY SCREEN AND TITLE OF TALK 4618 03:32:59,880 --> 03:33:02,680 TODAY IS USING AGING CLOCKS FOR 4619 03:33:02,680 --> 03:33:07,600 DRUG DISCOVERY AND EXTRACTING 4620 03:33:07,600 --> 03:33:12,120 TARGETS FROM RESEARCH AND TOPICS 4621 03:33:12,120 --> 03:33:16,160 PUBLISHED ABUNDANTLY IN 2015 AND 4622 03:33:16,160 --> 03:33:18,760 16 USING ARTIFICIAL INTELLIGENCE 4623 03:33:18,760 --> 03:33:20,800 TO TRAIN PREDICTORS FROM ANY 4624 03:33:20,800 --> 03:33:23,200 DATA TYPE AND REALIZED OVER THE 4625 03:33:23,200 --> 03:33:30,880 YEARS MANY AGING CLOCKS HAVE 4626 03:33:30,880 --> 03:33:32,480 LIMITED PRACTICAL UTILITY. 4627 03:33:32,480 --> 03:33:34,840 EASY TO PREDICT AGE AND HOWEVER 4628 03:33:34,840 --> 03:33:37,520 IS DIFFICULT TO TURN AGE 4629 03:33:37,520 --> 03:33:39,040 PREDICTORS INTO PRACTICAL 4630 03:33:39,040 --> 03:33:40,720 THERAPEUTIC APPLICATIONS UNLESS 4631 03:33:40,720 --> 03:33:43,320 YOU KNOW HOW TO DISCOVER PROTEIN 4632 03:33:43,320 --> 03:33:45,960 TARGETS TO FIT AGING CLOCK INTO 4633 03:33:45,960 --> 03:33:48,320 CLASSICAL TRADITIONAL 4634 03:33:48,320 --> 03:33:50,200 PHARMACEUTICAL DISCOVERY 4635 03:33:50,200 --> 03:33:51,800 BUSINESS MODEL FOR THIS PURPOSE 4636 03:33:51,800 --> 03:33:58,840 WE STARTED IN SILICON MEDICINE 4637 03:33:58,840 --> 03:34:00,120 TO ENSURE DISEASE AND AGING OAF 4638 03:34:00,120 --> 03:34:02,760 TIME AND TELLING YOU ABOUT 4639 03:34:02,760 --> 03:34:05,880 COMPANIES AND PLATFORM CONSISTS 4640 03:34:05,880 --> 03:34:08,080 OF THREE ELEMENTS AND THOSE 4641 03:34:08,080 --> 03:34:09,720 TOOLS ALLOW YOU TO IDENTIFY 4642 03:34:09,720 --> 03:34:11,320 TARGETS AND GENERATE CHEMISTRY 4643 03:34:11,320 --> 03:34:14,320 AND PREDICT OUTCOMES OF CLINICAL 4644 03:34:14,320 --> 03:34:18,120 TRIALS AND HOWEVER WE USE THIS 4645 03:34:18,120 --> 03:34:20,800 PLATFORM NOT ONLY TO PROVIDE 4646 03:34:20,800 --> 03:34:23,000 SOFTWARE AND AI SOLUTIONS FOR 4647 03:34:23,000 --> 03:34:24,480 OTHERS AND CURRENTLY 4648 03:34:24,480 --> 03:34:27,600 PHARMACEUTICAL COMPANIES USING 4649 03:34:27,600 --> 03:34:31,760 IT IN ONE OR ANOTHER WE USE TO 4650 03:34:31,760 --> 03:34:35,160 DEVELOP PIPELINE OF INTERNALLY 4651 03:34:35,160 --> 03:34:37,440 DERIVED THERAPEUTIC PROGRAMS 4652 03:34:37,440 --> 03:34:40,160 SOME FOCUSING ON AGE ASSOCIATED 4653 03:34:40,160 --> 03:34:45,760 DISEASES AND SOME FOCUSED ON 4654 03:34:45,760 --> 03:34:47,320 CANCER IMMUNOLOGY AND INFECTIOUS 4655 03:34:47,320 --> 03:34:49,080 DISEASES AND GLOBAL WE SPAN ALL 4656 03:34:49,080 --> 03:34:52,880 TIME ZONES AND HAVE TWO REGIONAL 4657 03:34:52,880 --> 03:34:54,360 HEADQUARTERS IN HONG KONG AND 4658 03:34:54,360 --> 03:34:55,920 NEW YORK AND LAB I'M IN RIGHT 4659 03:34:55,920 --> 03:34:59,680 NOW IS IN CHINA AND IT IS A FULL 4660 03:34:59,680 --> 03:35:03,520 ROBOTICS LAB AND WE HAVE DRUG 4661 03:35:03,520 --> 03:35:07,520 DISCOVERY SITES IN SHANGHAI AND 4662 03:35:07,520 --> 03:35:10,560 TYPEPAY AND AI RESEARCH IS DONE 4663 03:35:10,560 --> 03:35:14,880 IN MONTREAL AND UAE. MANY KNOW 4664 03:35:14,880 --> 03:35:16,960 THAT ARDD CONFERENCES AND WOULD 4665 03:35:16,960 --> 03:35:19,680 REALLY LIKE TO INVITE YOU TO 4666 03:35:19,680 --> 03:35:20,640 AGING RESEARCH AND DRUG 4667 03:35:20,640 --> 03:35:23,000 DISCOVERY MEETING 29TH OF AUGUST 4668 03:35:23,000 --> 03:35:25,880 AND 2ND OF SEPTEMBER THIS YEAR 4669 03:35:25,880 --> 03:35:28,160 AND WONDERFUL CONFERENCE AND 4670 03:35:28,160 --> 03:35:31,440 DISCUSS HOW AGING RESEARCH COULD 4671 03:35:31,440 --> 03:35:36,440 HAVE PHARMA-AND VICE VERSA AGING 4672 03:35:36,440 --> 03:35:39,520 PHARMA-ARG AND A BIT ABOUT THE 4673 03:35:39,520 --> 03:35:41,640 COMPANY WE ARE ONE OF LARGEST IN 4674 03:35:41,640 --> 03:35:45,440 OUR FIELD SINCE 2013 AND 4675 03:35:45,440 --> 03:35:48,080 EMPLOYEES AND DEEPLY COMMIT 4676 03:35:48,080 --> 03:35:51,040 TODAY AGING RESEARCH AND PUBLISH 4677 03:35:51,040 --> 03:35:53,960 PROBABLY 1 TO 2 RESEARCH PAPERS 4678 03:35:53,960 --> 03:35:57,760 A MONTH RAISED OVER $400 MILLION 4679 03:35:57,760 --> 03:36:02,840 AND HAVE OVER 30 THERAPEUTIC 4680 03:36:02,840 --> 03:36:06,400 PROGRAMS AND AS YOU KNOW DRUG 4681 03:36:06,400 --> 03:36:09,080 DISCOVERIES ARE COMPLEX AND 4682 03:36:09,080 --> 03:36:17,160 TEDIOUS INEFFICIENT PROCESS AND 4683 03:36:17,160 --> 03:36:23,480 LONGEVITY MIGHT BE LONGER TO 4684 03:36:23,480 --> 03:36:25,040 REPURPOSE ENSURING DRUG PREVENTS 4685 03:36:25,040 --> 03:36:27,360 DISEASES AND SLOWS DOWN 4686 03:36:27,360 --> 03:36:29,360 HOPEFULLY AGING AND WE HAVEN'T 4687 03:36:29,360 --> 03:36:31,520 SEEN LONGEVITY THERAPEUTICS ON 4688 03:36:31,520 --> 03:36:33,960 THE MARKET YET AND PROCESS 4689 03:36:33,960 --> 03:36:35,920 WITHIN TRADITIONAL 4690 03:36:35,920 --> 03:36:38,720 PHARMACEUTICAL APPROACH STARTS 4691 03:36:38,720 --> 03:36:40,600 WITH TARGET DISCOVERY AND 4692 03:36:40,600 --> 03:36:43,720 TARGETS DONE WITHIN ACADEMIC 4693 03:36:43,720 --> 03:36:46,240 INSTITUTIONS AND USUALLY IS 4694 03:36:46,240 --> 03:36:51,160 GOVERNMENT FUNDED AND NIH SPANS 4695 03:36:51,160 --> 03:36:53,040 ANNUALLY RESEARCH AND TARGETED 4696 03:36:53,040 --> 03:36:57,320 DISCOVERY COMES FROM SCIENTIFIC 4697 03:36:57,320 --> 03:37:00,680 SERENDIPITY FROM BASIC RESEARCH 4698 03:37:00,680 --> 03:37:03,080 AND INTELLIGENTLY SEARCHING FOR 4699 03:37:03,080 --> 03:37:04,680 TARGETS AND WE SEE PROBABILITY 4700 03:37:04,680 --> 03:37:15,040 OF SUCCESS AT EVERY STAGE BOTTOM 4701 03:37:15,040 --> 03:37:18,000 LINE IS NUMBERS OF MILLIONS OF 4702 03:37:18,000 --> 03:37:20,080 DOLLARS IT TAKES FOR AVERAGE 4703 03:37:20,080 --> 03:37:21,600 FROM BIG PHARMACEUTICAL COMPANY 4704 03:37:21,600 --> 03:37:24,280 AND COMPANY MANAGED TO GO FROM 0 4705 03:37:24,280 --> 03:37:28,760 TO PHASE 1 COMPLETE IN UNDER 4 4706 03:37:28,760 --> 03:37:32,320 YEARS AND FOR A DRUG THAT IS 4707 03:37:32,320 --> 03:37:34,200 TARGETING INTERASSOCIATED 4708 03:37:34,200 --> 03:37:37,160 DISEASE AND AGING AS WELL. AS I 4709 03:37:37,160 --> 03:37:39,160 MENTIONED, WE HAVE THREE 4710 03:37:39,160 --> 03:37:41,920 PLATFORM AND CHEMISTRY 2 AND 4711 03:37:41,920 --> 03:37:44,240 CLINICAL AND PAN DAYOMICS IS 4712 03:37:44,240 --> 03:37:48,560 USED FOR EUROPEAN LEADERS AND 4713 03:37:48,560 --> 03:37:50,480 FOCUSING ON THAT TODAY AND 4714 03:37:50,480 --> 03:37:52,280 DESIRED MOLECULES AND DESIRED 4715 03:37:52,280 --> 03:37:53,680 PROPERTIES AND EXPLORING 4716 03:37:53,680 --> 03:37:55,880 CHEMICAL SPACE THAT IS NOT 4717 03:37:55,880 --> 03:37:58,120 REPRESENTATIVE OF CHEMICAL 4718 03:37:58,120 --> 03:37:59,360 LIBRARIES AND YOU DESIGN SMALL 4719 03:37:59,360 --> 03:38:01,240 MOLECULES DESIGNING PROPERTIES 4720 03:38:01,240 --> 03:38:04,280 FROM SCRATCH THINKING OF DEEP 4721 03:38:04,280 --> 03:38:05,800 FAKES FROM CHEMISTRY AND 4722 03:38:05,800 --> 03:38:07,920 THINKING OF SINCE 2016 AND 4723 03:38:07,920 --> 03:38:09,440 CLINICAL PREDICTING OUTCOMES 4724 03:38:09,440 --> 03:38:12,960 PHASE 2 AND 3 TRANSITIONS 4725 03:38:12,960 --> 03:38:15,160 LOOKING AT PREDOMINANT SUCCESS 4726 03:38:15,160 --> 03:38:17,360 AND EFFICACY AND IMPLICATED 4727 03:38:17,360 --> 03:38:20,080 TARGET IS DISEASE AND 4728 03:38:20,080 --> 03:38:22,360 HETEROGENOUS POPULATION 4729 03:38:22,360 --> 03:38:27,840 FOUNDATION IS AND UTILIZES 4730 03:38:27,840 --> 03:38:28,440 PREDOMINANTLY METHYLATION AND 4731 03:38:28,440 --> 03:38:30,960 WHOLE GENOME SEQUENCING DATA 4732 03:38:30,960 --> 03:38:32,320 WHERE NOVELTY COMES FROM 4733 03:38:32,320 --> 03:38:34,600 CURRENTLY INTEGRATE PROBABLY 5 4734 03:38:34,600 --> 03:38:36,680 TO 10 MILLION SAMPLES DEPENDING 4735 03:38:36,680 --> 03:38:38,960 ON HOW IT COUNTS AND QUITE A BIT 4736 03:38:38,960 --> 03:38:41,600 OF ANIMAL DATA AND WE HAVE A LOT 4737 03:38:41,600 --> 03:38:44,320 OF TEXT THAT ALSO PROVIDES YOU 4738 03:38:44,320 --> 03:38:47,240 WITH CONFIDENCE. IF THEY TARGET 4739 03:38:47,240 --> 03:38:51,720 THAT HAVE BEEN ANNOTATED AND 4740 03:38:51,720 --> 03:38:52,400 LITERATURED SUBSTANTIALLY AND 4741 03:38:52,400 --> 03:38:54,840 ARE PRESENT IN MULTIPLE CLINICAL 4742 03:38:54,840 --> 03:38:57,160 STUDIES AND YOU HAVE MUCH HIGHER 4743 03:38:57,160 --> 03:38:59,280 LEVELS OF CONFIDENCE IN A 4744 03:38:59,280 --> 03:39:01,560 TARGET. YOU ALSO HAVE SAFETY 4745 03:39:01,560 --> 03:39:02,960 INFORMATION AND MANY OTHER DATA 4746 03:39:02,960 --> 03:39:06,080 POINTS THAT ARE VERY USEFUL. WE 4747 03:39:06,080 --> 03:39:06,960 INTEGRATE APPROXIMATELY 2 4748 03:39:06,960 --> 03:39:08,840 TRILLION DOLLARS WORTH OF DATA 4749 03:39:08,840 --> 03:39:15,320 IN THE SYSTEM AND FOLLOW BIOMED 4750 03:39:15,320 --> 03:39:17,960 GRANTS OVER PAST 50 YEARS AND 4751 03:39:17,960 --> 03:39:21,920 PATENTS AND CLINICAL TRIALS AND 4752 03:39:21,920 --> 03:39:23,040 PARTS FROM BIOMEDICAL COMPANIES 4753 03:39:23,040 --> 03:39:25,000 INTEGRATED IN THE SYSTEM THAT 4754 03:39:25,000 --> 03:39:29,240 ALLOWS YOU TO RAPIDLY IDENTIFY 4755 03:39:29,240 --> 03:39:34,040 LIST OF TARGETS WITH DESIRED 4756 03:39:34,040 --> 03:39:35,080 CONFIDENCE NOVELTY THAT GOES 4757 03:39:35,080 --> 03:39:40,480 HAND IN HAND AND LOADING MORE 4758 03:39:40,480 --> 03:39:42,400 NOVELTY YOU NEED TO VALIDATE 4759 03:39:42,400 --> 03:39:44,280 LONGER AND RISKIER AND 4760 03:39:44,280 --> 03:39:46,400 CONFIDENCE AND COMMERCIAL 4761 03:39:46,400 --> 03:39:47,800 [INDISCERNIBLE] IS LOWER BECAUSE 4762 03:39:47,800 --> 03:39:49,960 SOMEBODY ELSE IS TRYING ALREADY 4763 03:39:49,960 --> 03:39:52,320 AND SYSTEM ALLOWS YOU TO 4764 03:39:52,320 --> 03:39:54,960 PRIORITIZE TARGETS EFFICIENTLY 4765 03:39:54,960 --> 03:40:00,320 AND VALIDATED USING PUBLICATIONS 4766 03:40:00,320 --> 03:40:04,280 PUBLISHING AROUND 70 PAPERS ON 4767 03:40:04,280 --> 03:40:05,640 USING DIFFERENT APPROACHES 4768 03:40:05,640 --> 03:40:08,280 PATHWAY ANALYSIS TO DEEP 4769 03:40:08,280 --> 03:40:12,280 LEARNING AND TO TRANSFORMER ERA 4770 03:40:12,280 --> 03:40:14,480 TALKING ABOUT PAPERS HERE WHAT 4771 03:40:14,480 --> 03:40:17,200 WE ARE LOOKING FOR TALKING ABOUT 4772 03:40:17,200 --> 03:40:19,920 AGING IS LOOKING FOR TO IDENTIFY 4773 03:40:19,920 --> 03:40:23,200 DUAL PURPOSE THERAPEUTICS 4774 03:40:23,200 --> 03:40:25,960 IMPLICATED ON AGING AND DISEASE 4775 03:40:25,960 --> 03:40:28,840 AT SAME TIME FOCUSING ON AGING 4776 03:40:28,840 --> 03:40:32,320 IS DIFFICULT TO DEVELOP 4777 03:40:32,320 --> 03:40:34,800 COMMERCIALLY TRACTABLE PROGRAMS 4778 03:40:34,800 --> 03:40:38,480 INVESTORS WANT YOU TO FOCUS ON 4779 03:40:38,480 --> 03:40:42,120 DISEASES AND IN LICIENCE 4780 03:40:42,120 --> 03:40:44,200 MOLECULES DRUG DISCOVERY IS 4781 03:40:44,200 --> 03:40:46,440 EXPENSIVE TEDIOUS PROCESS AND 4782 03:40:46,440 --> 03:40:48,280 PRESENT VIABLE BUSINESS MODEL 4783 03:40:48,280 --> 03:40:50,600 WITH REASONABLE NOVELTY AND 4784 03:40:50,600 --> 03:40:52,760 CONFIDENCE TO INVESTOR COMMUNITY 4785 03:40:52,760 --> 03:40:54,400 IT IS DIFFICULT TO FUNDRAISE FOR 4786 03:40:54,400 --> 03:40:58,600 AGING AND SEE A LOT OF EFFORTS 4787 03:40:58,600 --> 03:41:00,320 AROUND THE WORLD WHERE 4788 03:41:00,320 --> 03:41:03,760 NON-PROFIT INSTITUTIONS AND 4789 03:41:03,760 --> 03:41:05,080 GOVERNMENTS ARE PROVIDING 4790 03:41:05,080 --> 03:41:06,760 SUBSTANTIAL RESEARCH DOLLARS TO 4791 03:41:06,760 --> 03:41:09,400 GO AND DISCOVER TARGETS PURELY 4792 03:41:09,400 --> 03:41:12,160 FOCUSED ON AGING AND REPURPOSE 4793 03:41:12,160 --> 03:41:13,480 TO DISEASE IT WILL NOT BE ENOUGH 4794 03:41:13,480 --> 03:41:15,440 AND YOU HAVE TO DEVELOP 4795 03:41:15,440 --> 03:41:18,160 SUSTAINABLE BUSINESS MODEL TO 4796 03:41:18,160 --> 03:41:20,160 RESEARCH AGING AT SCALE IN MY 4797 03:41:20,160 --> 03:41:22,160 OPINION AND FOCUSED ON DUAL 4798 03:41:22,160 --> 03:41:24,280 THERAPIUTE IBLGS AND PUBLISHED 4799 03:41:24,280 --> 03:41:25,600 PAPER DEMONSTRATING HOW TO 4800 03:41:25,600 --> 03:41:30,200 IDENTIFY TARGETS USING PANDOMICS 4801 03:41:30,200 --> 03:41:33,320 TARGETED DISCOVERY ENGINE AND WE 4802 03:41:33,320 --> 03:41:35,200 UTILIZE MANY DIFFERENT 4803 03:41:35,200 --> 03:41:37,000 PHILOSOPHIES FOR TARGET 4804 03:41:37,000 --> 03:41:37,840 DISCOVERY PHARMACEUTICAL 4805 03:41:37,840 --> 03:41:39,480 COMPANIES USE TO PRIORITIZE 4806 03:41:39,480 --> 03:41:42,280 TARGETS IMPLICATED IN AGE 4807 03:41:42,280 --> 03:41:43,920 ASSOCIATED DISEASES AND IN 4808 03:41:43,920 --> 03:41:46,120 NORMAL AGING AND CLASSIFY THEM 4809 03:41:46,120 --> 03:41:48,680 INTO HALLMARKS OF AGING AND IN 4810 03:41:48,680 --> 03:41:51,040 THIS PARTICULAR STUDY WE USED 4811 03:41:51,040 --> 03:41:53,960 MULTIPLE DATA SETS COMING FROM 4812 03:41:53,960 --> 03:41:56,480 AGE ASSOCIATED DISEASES TO 4813 03:41:56,480 --> 03:41:59,760 SEPARATE THEM AND SEPARATE 4814 03:41:59,760 --> 03:42:03,880 TARGETS THAT ARE PRESENT IN 4815 03:42:03,880 --> 03:42:04,960 NONASSOCIATED DISEASES AND 4816 03:42:04,960 --> 03:42:07,040 LOOKING AT THOSE THAT ARE 4817 03:42:07,040 --> 03:42:10,680 FOCUSED ON AGE ASSOCIATED 4818 03:42:10,680 --> 03:42:12,040 DISEASES INTEGRATING NORMAL 4819 03:42:12,040 --> 03:42:15,120 AGING AND PROCESSED DATA THROUGH 4820 03:42:15,120 --> 03:42:18,200 PAN DOMIC AND WENT THROUGH 4821 03:42:18,200 --> 03:42:20,000 MULTIPLE FILTERS AND DEVELOPMENT 4822 03:42:20,000 --> 03:42:24,280 LEVEL ASSESSMENT AND COMMERCIAL 4823 03:42:24,280 --> 03:42:27,280 TRIPT ABILITY AND STRUCTURED 4824 03:42:27,280 --> 03:42:30,440 POSSIBLE TARGETS IN THIS CASE A 4825 03:42:30,440 --> 03:42:36,280 LIST INTO DIFFERENT HALLMARKS OF 4826 03:42:36,280 --> 03:42:39,720 AGING USINGOMICS AND TEXT-BASED 4827 03:42:39,720 --> 03:42:42,320 SCORES AND CREATED THIS AND CAN 4828 03:42:42,320 --> 03:42:44,560 USE AS A DARTS BOARD IF YOU LIKE 4829 03:42:44,560 --> 03:42:47,520 AND PLAY DARTS WITH IT. 4830 03:42:47,520 --> 03:42:51,160 WE STRUCTURED TARGETS INTO HIGH 4831 03:42:51,160 --> 03:42:56,040 CONFIDENCE AND MEDIUM 4832 03:42:56,040 --> 03:42:56,520 NOVELTIABILITY AND 4833 03:42:56,520 --> 03:42:58,080 [INDISCERNIBLE] BY HALLMARKS AND 4834 03:42:58,080 --> 03:43:00,880 SOME OF THOSE TARGETS ARE VERY 4835 03:43:00,880 --> 03:43:02,440 WELL KNOWN AND ESTABLISHED 4836 03:43:02,440 --> 03:43:06,520 ALREADY IN AGING ASSOCIATIVE 4837 03:43:06,520 --> 03:43:10,920 DISEASES AND SOME ARE NORMAL 4838 03:43:10,920 --> 03:43:13,040 REQUIRING RESEARCH AND 4839 03:43:13,040 --> 03:43:17,320 SCIENTIFIC BASIS AND ANALYSIS 4840 03:43:17,320 --> 03:43:18,640 BEHIND TARGETS ALLOWING FOR 4841 03:43:18,640 --> 03:43:21,680 FURTHER VALIDATION AND APPLIED 4842 03:43:21,680 --> 03:43:23,800 SAME METHODOLOGY TO AGE 4843 03:43:23,800 --> 03:43:26,880 ASSOCIATED DISEASE ALS AND FIND 4844 03:43:26,880 --> 03:43:31,680 STUDY AT WWWALSPAI AND PROVIDE 4845 03:43:31,680 --> 03:43:35,920 SCREEN CAST OF PAN DOMICS AND 4846 03:43:35,920 --> 03:43:38,560 TOOLS IN STUDY AND STUDY UTILIZE 4847 03:43:38,560 --> 03:43:42,200 DATA FROM ALS CONSORTIUM AND 4848 03:43:42,200 --> 03:43:45,360 PROBABLY LARGEST CONSORTIUM ON 4849 03:43:45,360 --> 03:43:49,040 ALS DATA SETS IN WORLD AND RUN 4850 03:43:49,040 --> 03:43:59,600 BY [INDISCERNIBLE] WHO DEVELOPED 4851 03:44:03,680 --> 03:44:11,080 A FLY MODEL OF ALS AND WE HAVE 4852 03:44:11,080 --> 03:44:15,800 HUMAN LS PATIENT CELLS AND WE 4853 03:44:15,800 --> 03:44:17,520 PROGRAMMED BACK INTO NEURONS AND 4854 03:44:17,520 --> 03:44:20,360 HAVE GENETIC BACKGROUND IN THERE 4855 03:44:20,360 --> 03:44:22,600 LOST EPIGENETICS AND HAVE A BIT 4856 03:44:22,600 --> 03:44:26,080 OF SAMPLES THAT ARE COMING FROM 4857 03:44:26,080 --> 03:44:29,160 ALS PATIENT SAMPLES AND UTILIZE 4858 03:44:29,160 --> 03:44:31,640 PUBLIC ALS DATA INCLUDING TEXT 4859 03:44:31,640 --> 03:44:34,680 AND WE RUN DATA SETS THROUGH 4860 03:44:34,680 --> 03:44:37,240 PANDOMICS QUICKLY IN A MATTER OF 4861 03:44:37,240 --> 03:44:39,200 DAY AND IDENTIFIED LIST OF 4862 03:44:39,200 --> 03:44:42,040 TARGETS AND DRUGS TO REPURPOSE 4863 03:44:42,040 --> 03:44:46,560 AND UTILIZE VERY ESTABLISHED ALS 4864 03:44:46,560 --> 03:44:50,520 MODEL OUT OF MAYO CLINIC FLY 4865 03:44:50,520 --> 03:44:53,960 MODEL ALS NO GOOD MODEL ASIDE 4866 03:44:53,960 --> 03:44:55,640 FROM PATIENTS AND LOTS THAT IS 4867 03:44:55,640 --> 03:44:59,400 VERY IDIOPATHIC TO IDENTIFY WHAT 4868 03:44:59,400 --> 03:45:01,000 WILL WORK OR NOT. 4869 03:45:01,000 --> 03:45:05,280 WE VALIDATED HYPOTHESIS IN A FLY 4870 03:45:05,280 --> 03:45:08,320 MODEL AND UTILIZING RNRI AND 4871 03:45:08,320 --> 03:45:10,640 REAL COMPOUNDS ALSO. WE TESTED 4872 03:45:10,640 --> 03:45:13,240 1 IN 6 PROPOSED TARGETS OUT OF 4873 03:45:13,240 --> 03:45:17,960 PAN DOMICS AND MOST WORK AND 21 4874 03:45:17,960 --> 03:45:20,320 WORK MILDLY. 4875 03:45:20,320 --> 03:45:24,200 WE VERIFIED ALSO 8 PREVIOUSLY 4876 03:45:24,200 --> 03:45:27,600 UNREPORTED GENOMES AND 4877 03:45:27,600 --> 03:45:29,240 PERTURBATIONS RESCUE 4878 03:45:29,240 --> 03:45:30,800 NEURODEGENERATION AND FIND 4879 03:45:30,800 --> 03:45:35,600 DETAILS STUDY OF ALS.AI AND 4880 03:45:35,600 --> 03:45:38,280 PUBLISH AGING NEUROSCIENCE QUICK 4881 03:45:38,280 --> 03:45:41,000 PUBLICATION BECAUSE THERE IS 4882 03:45:41,000 --> 03:45:42,200 ADDITIONAL COOL AND INTERESTING 4883 03:45:42,200 --> 03:45:43,680 DATA POINT I WILL TELL YOU 4884 03:45:43,680 --> 03:45:45,680 ABOUT. HERE ARE SOME TARGETS 4885 03:45:45,680 --> 03:45:52,680 THAT GOT VALIDATED USING RNAI 4886 03:45:52,680 --> 03:45:55,040 AND SEE IN FIGURE B HERE NUMBER 4887 03:45:55,040 --> 03:45:59,240 OF GENES PREDICTED TO WORK THAT 4888 03:45:59,240 --> 03:46:05,800 SHOWED A STRONG M- RESCUE 4889 03:46:05,800 --> 03:46:07,040 INTERMEDIATE RESCUE AND GENES 4890 03:46:07,040 --> 03:46:09,440 DIDN'T DEMONSTRATE FACTS OR MILD 4891 03:46:09,440 --> 03:46:13,200 OR MODERATE ENHANCEMENT OF THIS 4892 03:46:13,200 --> 03:46:16,080 ALS PHENOTYPE AND 4893 03:46:16,080 --> 03:46:18,160 NEURODEGENERATIVE PHENOTYPE AND 4894 03:46:18,160 --> 03:46:20,320 SHOWS YOU THE SYSTEM IS PRETTY 4895 03:46:20,320 --> 03:46:24,280 GOOD AT PICKING UP PROMISING 4896 03:46:24,280 --> 03:46:27,520 TARGETS AND PROFESSOR AT 4897 03:46:27,520 --> 03:46:29,760 UNIVERSITY ONE OF LEADING 4898 03:46:29,760 --> 03:46:31,040 NEUROSCIENTISTS IN ASIA AND 4899 03:46:31,040 --> 03:46:34,320 GLOBALLY AND HE IS A CO-FOUNDER 4900 03:46:34,320 --> 03:46:38,080 OF TECHNOLOGIES AND THEY MANAGE 4901 03:46:38,080 --> 03:46:41,280 TO ENROLL PATIENTS IN A CLINICAL 4902 03:46:41,280 --> 03:46:42,640 STUDY IN A VERY SHORT PERIOD OF 4903 03:46:42,640 --> 03:46:45,080 TIME AND THEY ACTUALLY PICKED 4904 03:46:45,080 --> 03:46:47,640 SOME TARGETS FROM DECLARATION 4905 03:46:47,640 --> 03:46:50,160 AND NOW ARE DOING REPURPOSING 4906 03:46:50,160 --> 03:46:52,280 STUDIES AND FINGERS CROSSED AND 4907 03:46:52,280 --> 03:46:55,040 SHOWS YOU CAN GO FROM DISCOVERY 4908 03:46:55,040 --> 03:46:56,760 TO PATIENTS IN UNDER ONE YEAR 4909 03:46:56,760 --> 03:47:00,080 AND CONDUCT ADDITIONAL BIOMARKER 4910 03:47:00,080 --> 03:47:02,720 STUDIES TO DEMONSTRATE HOW 4911 03:47:02,720 --> 03:47:04,400 POSSIBLE REPURPOSING CANDIDATES 4912 03:47:04,400 --> 03:47:07,040 WORK AND MENTION I GOT FREE 4913 03:47:07,040 --> 03:47:08,280 SYSTEMS CHEMISTRY 2 AND 4914 03:47:08,280 --> 03:47:10,360 PRECLINICAL THAT ALLOW US TO GO 4915 03:47:10,360 --> 03:47:13,000 AFTER OUR OWN PIPELINE AND IN 4916 03:47:13,000 --> 03:47:14,720 2019 WHERE WE HAVE IDENTIFIED 4917 03:47:14,720 --> 03:47:17,200 SOME PROMISING TARGETS IN 4918 03:47:17,200 --> 03:47:19,640 FIBROSIS AND DECIDED TO GO AFTER 4919 03:47:19,640 --> 03:47:22,200 FIBROSIS AS BIOLOGICAL PROCESS 4920 03:47:22,200 --> 03:47:26,280 DRIVING MULTIPLE AGE ASSOCIATED 4921 03:47:26,280 --> 03:47:30,080 DISEASES IDENTIFYING 20 NOVEL 4922 03:47:30,080 --> 03:47:32,320 TARGETS BECAUSE OF FINANCIAL 4923 03:47:32,320 --> 03:47:34,640 CONSTRAINTS GENERATING NOVEL 4924 03:47:34,640 --> 03:47:36,320 CHEMISTRY DON'T EXIST IN 4925 03:47:36,320 --> 03:47:39,880 LIBRARIES USING CHEMISTRY 2 AND 4926 03:47:39,880 --> 03:47:43,040 CONDUCTED 20 CLINICAL 4927 03:47:43,040 --> 03:47:44,280 EXPERIMENTS AND MANY DIFFERENT 4928 03:47:44,280 --> 03:47:46,600 MICE EXPERIMENTS AND MODELS AND 4929 03:47:46,600 --> 03:47:49,280 PHASE 0 HUMAN STUDIES HEALTHY 4930 03:47:49,280 --> 03:47:51,520 VOLUNTEERS IN AUSTRALIA AND 4931 03:47:51,520 --> 03:47:54,000 PROPER PHASE 1 STUDY MORE THAN 4932 03:47:54,000 --> 03:47:57,960 80 PATIENTS IN NEW ZEALAND AND 4933 03:47:57,960 --> 03:48:00,280 BRANCH OF 43 PATIENTS IN CHINA 4934 03:48:00,280 --> 03:48:02,280 AND HEALTHY VOLUNTEERS 4935 03:48:02,280 --> 03:48:03,160 ESTABLISHING SAFETY AND 4936 03:48:03,160 --> 03:48:04,920 PREPARING FOR PHASE 2. IT IS 4937 03:48:04,920 --> 03:48:07,440 PRETTY COOL. THIS IS THE 4938 03:48:07,440 --> 03:48:09,280 PIPELINE OF THERAPEUTIC ASSETS 4939 03:48:09,280 --> 03:48:11,160 THAT WE CURRENTLY HAVE THAT WE 4940 03:48:11,160 --> 03:48:13,120 COULDN'T TALK ABOUT AND WE HAVE 4941 03:48:13,120 --> 03:48:19,080 ASSETS WE COULD NOT TALK ABOUT 4942 03:48:19,080 --> 03:48:20,080 NOT PROGRESSING BEYOND LEAD 4943 03:48:20,080 --> 03:48:21,800 STAGE AND TARGETS BEYOND THIS 4944 03:48:21,800 --> 03:48:27,360 AND ACCESS ON CLOSE AND PURPOSE 4945 03:48:27,360 --> 03:48:30,640 FOR KINNE FIBROSIS AND WE 4946 03:48:30,640 --> 03:48:34,400 DECIDED TO GO AFTER NO MOLECULE 4947 03:48:34,400 --> 03:48:35,240 FOR PRETTY ESTABLISHED TARGET 4948 03:48:35,240 --> 03:48:40,160 AND IS GOING AFTER THAT AND 4949 03:48:40,160 --> 03:48:42,680 WORKING TOWARDS GUT RESTRICTED 4950 03:48:42,680 --> 03:48:45,080 MOLECULE AND INTERESTING TARGET 4951 03:48:45,080 --> 03:48:47,760 GOLGI COMPLEX IDENTIFYING USING 4952 03:48:47,760 --> 03:48:49,760 AGING RESEARCH AND PURPOSING 4953 03:48:49,760 --> 03:48:53,120 TOWARDS ONCOLAND PARTNERING WITH 4954 03:48:53,120 --> 03:48:54,520 CO-DEVELOPMENT 50/50 AND 4955 03:48:54,520 --> 03:48:56,040 PROMISING TARGETS SHOWING THIS 4956 03:48:56,040 --> 03:48:58,040 APPROACH COULD BE USED TO 4957 03:48:58,040 --> 03:49:01,080 DEVELOP A PIPELINE OF VALUABLE 4958 03:49:01,080 --> 03:49:04,320 THERAPEUTICS AND NOW WANT TO 4959 03:49:04,320 --> 03:49:05,680 CONCLUDE BRIEFLY I'M ALMOST AT 4960 03:49:05,680 --> 03:49:08,880 TIME AND NOW WE ARE ALSO 4961 03:49:08,880 --> 03:49:13,440 DEVELOPING A FULLY AUTOMATED LAB 4962 03:49:13,440 --> 03:49:17,480 RATTORY TO ACCELERATE AGING 4963 03:49:17,480 --> 03:49:18,760 BIOMARKER STUDIES SHOWING 4964 03:49:18,760 --> 03:49:20,760 TYPICAL WORKFLOW OF THE LAB. 4965 03:49:20,760 --> 03:49:25,640 I'M IN THE LAB RIGHT NOW. 4966 03:49:25,640 --> 03:49:28,000 AND HERE IS THE REAL WORKFLOW OF 4967 03:49:28,000 --> 03:49:31,080 THE SLAB AND TAKING TISSUES OR 4968 03:49:31,080 --> 03:49:35,600 CELLS AND THROWING IT INTO THE 4969 03:49:35,600 --> 03:49:37,920 SAMPLE PROCESSING MODULE. 4970 03:49:37,920 --> 03:49:41,840 THE CELLS OR TISSUES ARE BEING 4971 03:49:41,840 --> 03:49:44,200 PICKED UP AND QUALITY CONTROL 4972 03:49:44,200 --> 03:49:46,360 AND USING AUTONOMOUS GUIDED 4973 03:49:46,360 --> 03:49:48,040 VEHICLES THAT ARE BEING PLACED 4974 03:49:48,040 --> 03:49:50,320 IN THE INCUBATOR AND SOME GET 4975 03:49:50,320 --> 03:49:55,560 INTO IMAGING MACHINES AND YOU 4976 03:49:55,560 --> 03:50:01,680 GET SALIGGOS AND TS7 IMAGING AND 4977 03:50:01,680 --> 03:50:04,600 YOU ALSO GET OTHER IMAGING DATA 4978 03:50:04,600 --> 03:50:05,000 TYPES. 4979 03:50:05,000 --> 03:50:09,720 PART OF THE SAMPLE GETS INTO THE 4980 03:50:09,720 --> 03:50:12,280 NGS WORKLOAD AND THERE WE 4981 03:50:12,280 --> 03:50:15,480 PREPARE THREE LIBRARIES AND 4982 03:50:15,480 --> 03:50:19,800 WHOLE GENOME SEQUENCING RNA SEEK 4983 03:50:19,800 --> 03:50:23,040 LIBRARY AND METHYLATION AND 4984 03:50:23,040 --> 03:50:25,120 TRANSCRIPTOMICS ARE POPULAR AND 4985 03:50:25,120 --> 03:50:26,920 GIVING TO ALUMINUM SEQUENCER 4986 03:50:26,920 --> 03:50:31,960 THAT SEQUENCES RNA SEEK 4987 03:50:31,960 --> 03:50:34,000 METHYLATION AND WHOLE GENOME 4988 03:50:34,000 --> 03:50:37,920 SEQUENCING GIVING TO PAN DOMICS 4989 03:50:37,920 --> 03:50:40,000 CLINICAL AND THIS WORKFLOW 4990 03:50:40,000 --> 03:50:42,120 COMPOUNDS ARE PICKED FROM 4991 03:50:42,120 --> 03:50:46,240 LIBRARIES UNCAPPED PLACED ON 4992 03:50:46,240 --> 03:50:48,720 LIQUID HANDLER FOR TRANSFER ON 4993 03:50:48,720 --> 03:50:53,360 TO CELLS THAT ARE USED IN THE 4994 03:50:53,360 --> 03:50:56,120 INCUBATOR. 4995 03:50:56,120 --> 03:51:04,960 AND THEN WE INCUBATE CELLS FROM 4996 03:51:04,960 --> 03:51:07,040 INCUBATOR FROM COMPOUND 4997 03:51:07,040 --> 03:51:08,400 PREDICTED TO WORK AND FROM 4998 03:51:08,400 --> 03:51:10,440 DIFFERENT CONCENTRATIONS PLACING 4999 03:51:10,440 --> 03:51:16,040 INTO INCUBATOR HERE 26 OR 48 OR 5000 03:51:16,040 --> 03:51:18,920 72 HOURS AND BROAD CONNECTIVITY 5001 03:51:18,920 --> 03:51:22,360 MAP AND LINKS AND OTHER DATA 5002 03:51:22,360 --> 03:51:25,000 SOURCES AND WE SEE IF THE 5003 03:51:25,000 --> 03:51:26,280 EXPERIMENTAL RESULTS THAT 5004 03:51:26,280 --> 03:51:28,080 CONFIRMED WHAT WE PREDICTED AND 5005 03:51:28,080 --> 03:51:31,680 AI LEARNS AND WE FIND VALUABLE 5006 03:51:31,680 --> 03:51:32,840 TARGETS VALIDATING THEM 5007 03:51:32,840 --> 03:51:33,600 EXPERIMENTALLY. 5008 03:51:33,600 --> 03:51:35,360 SO, THAT IS OUR CURRENT WORKFLOW 5009 03:51:35,360 --> 03:51:36,720 THAT IS ACTUALLY MY LAB. 5010 03:51:36,720 --> 03:51:43,440 THIS IS THE SAMPLE INTAKE ROOM. 5011 03:51:43,440 --> 03:51:47,440 THIS IS THE ACTUAL COMPOUND 5012 03:51:47,440 --> 03:51:48,920 MANAGEMENT SYSTEM. WE ARE 5013 03:51:48,920 --> 03:51:51,800 PREPARING FOR A BIG RUN RIGHT 5014 03:51:51,800 --> 03:51:52,000 NOW. 5015 03:51:52,000 --> 03:51:54,600 IT IS GOING TO TAKE US TWO WEEKS 5016 03:51:54,600 --> 03:51:57,320 AND THIS IS THE CULTURE MEDIUM 5017 03:51:57,320 --> 03:52:00,120 CHANGE THAT WE CAN WORK WITH 5018 03:52:00,120 --> 03:52:01,120 MULTIPLE DIFFERENT CELL AND 5019 03:52:01,120 --> 03:52:03,720 TISSUE TYPES AND IMAGING 5020 03:52:03,720 --> 03:52:06,160 STATIONS AND HERE WE HAVE 5021 03:52:06,160 --> 03:52:09,240 SEVERAL IMAGING MACHINES AND 5022 03:52:09,240 --> 03:52:11,920 HERE IS THE LIBRARY 5023 03:52:11,920 --> 03:52:13,080 [INDISCERNIBLE] TO PREPARE 5024 03:52:13,080 --> 03:52:14,880 DIFFERENT LIBRARIES AND SEE 5025 03:52:14,880 --> 03:52:17,920 THERE IS AGV THERE AND NGS ROOM 5026 03:52:17,920 --> 03:52:19,800 AND A FEW OTHER FACILITIES 5027 03:52:19,800 --> 03:52:21,440 ALLOWING YOU TO COLLECT OTHER 5028 03:52:21,440 --> 03:52:22,600 DATA TYPES AND VERY 5029 03:52:22,600 --> 03:52:24,280 COLLABORATIVE AND WOULD LOVE TO 5030 03:52:24,280 --> 03:52:26,480 WORK WITH YOU ON MULTIPLE 5031 03:52:26,480 --> 03:52:27,280 PROJECTS. IN THIS PARTICULAR 5032 03:52:27,280 --> 03:52:31,000 LAB WE CAN ACTUALLY PROCESS MANY 5033 03:52:31,000 --> 03:52:33,480 DIFFERENT DATA TYPES AND 5034 03:52:33,480 --> 03:52:34,920 CURRENTLY FOCUSED ON MOUSE AND 5035 03:52:34,920 --> 03:52:37,120 MONKEY DATA TYPES TO ESTABLISH 5036 03:52:37,120 --> 03:52:38,360 TRANSLATIONAL MODELS AND OF 5037 03:52:38,360 --> 03:52:41,360 COURSE WE ARE ALSO READY TO GO 5038 03:52:41,360 --> 03:52:41,600 HUMAN. 5039 03:52:41,600 --> 03:52:45,520 WE ARE -- MY DREAM IS TO MODIFY 5040 03:52:45,520 --> 03:52:47,400 THIS LAB OR MINIATURIZE IT TO 5041 03:52:47,400 --> 03:52:49,120 MAKE SURE IT IS SMALL ENOUGH TO 5042 03:52:49,120 --> 03:52:52,560 BE PLACED IN A HOSPITAL TO DO 5043 03:52:52,560 --> 03:52:54,640 HOSPITAL SIZE DISCOVERY AND 5044 03:52:54,640 --> 03:52:57,000 THANK YOU SO MUCH. LET'S 5045 03:52:57,000 --> 03:53:00,560 COLLABORATE. BYE, BYE. 5046 03:53:00,560 --> 03:53:03,080 >>THANKS SO 5047 03:53:03,080 --> 03:53:09,200 MUCH FOR ACCOMMODATING ME BY 5048 03:53:09,200 --> 03:53:15,320 ZOOM TITLE OF MY TALK WAS GIVEN 5049 03:53:15,320 --> 03:53:21,880 TO ME BY RON IT IS REJUVENATION 5050 03:53:21,880 --> 03:53:24,040 TO MODEL AGING. I LOVE IT. 5051 03:53:24,040 --> 03:53:26,920 THANK YOU, RON. USING AI MODEL 5052 03:53:26,920 --> 03:53:29,200 AND MACHINE LEARNING TO 5053 03:53:29,200 --> 03:53:30,920 FACILITATE DEVELOPMENT OF 5054 03:53:30,920 --> 03:53:33,160 HYPOTHESIS AND WONDERFUL TALKS 5055 03:53:33,160 --> 03:53:37,160 TODAY ON AI AND MACHINE LEARN 5056 03:53:37,160 --> 03:53:43,600 ING MODELS SAVING TIME BY 5057 03:53:43,600 --> 03:53:47,320 INTRODUCTION AND EFFICIENCY OF 5058 03:53:47,320 --> 03:53:51,000 REPAIR THAT IS FAIR RIT 5059 03:53:51,000 --> 03:54:01,520 COMPARISON OF [INDISCERNIBLE]. 5060 03:54:03,720 --> 03:54:08,880 THEN THE QUESTION IS IF 5061 03:54:08,880 --> 03:54:11,280 IMPROVING REPAIR IN INDIVIDUALS 5062 03:54:11,280 --> 03:54:13,880 UNDERSTAND TISSUES AND CELLS ND 5063 03:54:13,880 --> 03:54:24,440 ORGANELLES IS DEFICIENT AND -- 5064 03:54:25,280 --> 03:54:27,960 STEM CELLS AND DIFFERENTIATED 5065 03:54:27,960 --> 03:54:29,480 SOMATIC CELLS AND MANY THINGS OF 5066 03:54:29,480 --> 03:54:31,600 DAMAGE THAT ACCUMULATED IN THERE 5067 03:54:31,600 --> 03:54:36,040 AND INTERESTINGLY, DAMAGE WILL 5068 03:54:36,040 --> 03:54:39,040 BE RAPIDLY REDUCED AND TISSUES 5069 03:54:39,040 --> 03:54:40,960 YOUNGER IN OLD ANIMAL AND OLDER 5070 03:54:40,960 --> 03:54:44,320 IN YOUNG ANIMAL THROUGH WHAT WE 5071 03:54:44,320 --> 03:54:47,200 CALL BLOOD KRONISTY AND SEVERAL 5072 03:54:47,200 --> 03:54:53,200 EXPERIMENTAL MODELS THAT OLDEST 5073 03:54:53,200 --> 03:54:56,920 ONE IS HYDRO CHRONIC PARABIOSIS 5074 03:54:56,920 --> 03:54:58,920 AND ERIC WHO IS THE DIRECTOR 5075 03:54:58,920 --> 03:55:01,880 WITH SOME SLIDE AND THERE IS 5076 03:55:01,880 --> 03:55:04,640 HYDRO CHRONIC FORESIS AND THERE 5077 03:55:04,640 --> 03:55:06,040 IS DESIGNER FLUID EXCHANGE AND 5078 03:55:06,040 --> 03:55:08,880 THIS IS REALLY NOT JUST BLOOD 5079 03:55:08,880 --> 03:55:10,200 EXCHANGE BECAUSE ORGANS ARE 5080 03:55:10,200 --> 03:55:13,120 SHARED AND ENVIRONMENTS SHARED 5081 03:55:13,120 --> 03:55:14,840 AND ANIMALS BECOME PERHAPS 5082 03:55:14,840 --> 03:55:18,000 BETTER FROM EXERCISE AND BETTER 5083 03:55:18,000 --> 03:55:21,120 NUTRITION AND BETTER GI TRACT 5084 03:55:21,120 --> 03:55:26,840 AND BLOOD OXYGENATION AND HYDRO 5085 03:55:26,840 --> 03:55:29,760 CHRONIC FORESIS OLD CONTROL AND 5086 03:55:29,760 --> 03:55:32,840 NEWER DEVICE ALLOWS TO FOCUS ON 5087 03:55:32,840 --> 03:55:34,440 WHAT HAPPENS WITH EXCHANGED 5088 03:55:34,440 --> 03:55:36,440 BLOOD OR FLUIDS AND QUESTION IS 5089 03:55:36,440 --> 03:55:39,440 THIS, YOU KNOW, GLASS HALF EMPTY 5090 03:55:39,440 --> 03:55:44,240 AND HALF FULL IS YOUNG OR OLD 5091 03:55:44,240 --> 03:55:45,320 BLOOD THAT IS [INDISCERNIBLE] 5092 03:55:45,320 --> 03:55:48,840 AND REJUVENATION AND OLD 5093 03:55:48,840 --> 03:55:50,520 EXPERIMENTS THAT DID AND IT IS 5094 03:55:50,520 --> 03:55:56,240 IN EARLY 2000S AND SEEMS TO US 5095 03:55:56,240 --> 03:55:59,240 OLD BLOOD DOMINATES YOUNG AND 5096 03:55:59,240 --> 03:56:03,080 NEED TO REMOVE AGE ELEVATED 5097 03:56:03,080 --> 03:56:04,480 PROTEINS RATHER THAN ADD 5098 03:56:04,480 --> 03:56:07,880 PROTEINS ON TOP OF OLD BLOOD AND 5099 03:56:07,880 --> 03:56:10,120 FASCINATION AND THIS ROMANTIC 5100 03:56:10,120 --> 03:56:13,200 IDEA THAT YOUNG BLOOD COULD BE 5101 03:56:13,200 --> 03:56:14,520 HELPFUL ILLUSTRATED BY CARTOON 5102 03:56:14,520 --> 03:56:17,160 IN ECONOMIST OF ONE OF OUR 5103 03:56:17,160 --> 03:56:19,520 PAPERS AND AT SAME TIME THESE -- 5104 03:56:19,520 --> 03:56:23,960 THERE IS ALSO ACCUMULATING 5105 03:56:23,960 --> 03:56:26,760 EVIDENCE THAT [INDISCERNIBLE] OR 5106 03:56:26,760 --> 03:56:29,800 BLOOD EXCHANGE DON'T REJUVENATE 5107 03:56:29,800 --> 03:56:33,600 YOUNG ANIMALS BECAUSE OF OLD 5108 03:56:33,600 --> 03:56:35,560 BLOOD BUT THEY AGE YOUNG ANIMALS 5109 03:56:35,560 --> 03:56:37,160 BECAUSE OF OLD BLOOD AND THIS 5110 03:56:37,160 --> 03:56:39,800 GROUP THAT WAS PUBLISHED IN 5111 03:56:39,800 --> 03:56:45,160 REJUVENATION RESEARCH SHOWS IF 5112 03:56:45,160 --> 03:56:55,720 YOU HAVE -- SHARED IN BLOOD AND 5113 03:57:08,320 --> 03:57:13,080 ORGANS WITH YOUNG ANIMALS DON'T 5114 03:57:13,080 --> 03:57:14,720 LIVE LONGER YOUNG ANIMALS LIVE 5115 03:57:14,720 --> 03:57:17,680 SHORTER COMPARED TO ISOCHRONIC 5116 03:57:17,680 --> 03:57:19,160 YOUNG TO YOUNG PAIRS THAT IS ONE 5117 03:57:19,160 --> 03:57:22,240 PIECE OF EVIDENCE THAT IS 5118 03:57:22,240 --> 03:57:23,720 RECENTLY PUBLISHED IN 5119 03:57:23,720 --> 03:57:25,800 REJUVENATION RESEARCH AND EDITOR 5120 03:57:25,800 --> 03:57:28,760 REJUVENATION RESEARCH PLEASE, 5121 03:57:28,760 --> 03:57:31,800 PLEASE WITH SUGAR ON TOP SEND 5122 03:57:31,800 --> 03:57:34,240 GOOD PAPERS. ANOTHER PIECE OF 5123 03:57:34,240 --> 03:57:42,080 EVIDENCE THAT OLD BLOOD IS 5124 03:57:42,080 --> 03:57:45,200 DOMINATING OVER YOUNG AGING 5125 03:57:45,200 --> 03:57:46,920 REJUVENATION IS NOT BY OLD BUT 5126 03:57:46,920 --> 03:57:50,680 RATHER EXCESSIVE FACTORS COMES 5127 03:57:50,680 --> 03:57:54,920 FROM ALSO SOMEWHAT RECENT PAPER 5128 03:57:54,920 --> 03:57:56,520 PUBLISHED WITH GROUP THAT 5129 03:57:56,520 --> 03:57:57,920 [INDISCERNIBLE] WHO IS 5130 03:57:57,920 --> 03:57:59,720 [INDISCERNIBLE] POST DOC NOW WHO 5131 03:57:59,720 --> 03:58:01,760 HAS BEEN RUNNING OWN LABORATORY 5132 03:58:01,760 --> 03:58:05,040 AND CAREER. THIS PAPER SHOWS IF 5133 03:58:05,040 --> 03:58:07,200 YOU START WITH YOUNG ANIMALS 5134 03:58:07,200 --> 03:58:09,880 WITH ALL YOUNG ORGANS AND 5135 03:58:09,880 --> 03:58:12,600 TISSUES AND SHORTENED TELOMERES 5136 03:58:12,600 --> 03:58:16,840 AND EXCELLENT DNA AND EXCHANGE 5137 03:58:16,840 --> 03:58:19,920 WITH 50% OLD BLOOD THEY BECOME 5138 03:58:19,920 --> 03:58:30,760 OLD SEINE ES EXTNESCENT. 5139 03:58:35,600 --> 03:58:39,040 SOLELY FROM EXCHANGE OF OLD 5140 03:58:39,040 --> 03:58:41,000 BLOOD AND PAPER IS PUBLISHED YOU 5141 03:58:41,000 --> 03:58:43,160 CAN OBSERVE PHENOMENA OR 5142 03:58:43,160 --> 03:58:45,320 PARATIME BY CULTURING CELLS WITH 5143 03:58:45,320 --> 03:58:48,080 YOUNG VERSUS OLD SERUM THAT 5144 03:58:48,080 --> 03:58:49,200 COULD BE HUMAN OR 5145 03:58:49,200 --> 03:58:51,240 [INDISCERNIBLE] AND ADAP TAF 5146 03:58:51,240 --> 03:58:55,360 TRANSFER TO SENESCENCE TO CELLS 5147 03:58:55,360 --> 03:59:00,720 WHICH IS VERY RAPID IF YOU 5148 03:59:00,720 --> 03:59:06,760 COMPARE YOUNG SERUM YOU SEE OLD 5149 03:59:06,760 --> 03:59:09,440 SERUM IS INDUCING SENESCENCE IN 5150 03:59:09,440 --> 03:59:12,040 CELLS AND IF YOU LOOK AT CELL 5151 03:59:12,040 --> 03:59:13,480 PROTURATION AND ASSAY AND IF 5152 03:59:13,480 --> 03:59:18,080 LEUK AT HUMAN CELLS OR MOUSE 5153 03:59:18,080 --> 03:59:26,480 CELLS MOUSE CELLS AND HUMAN 5154 03:59:26,480 --> 03:59:28,360 CELLS WHEN MIXED KIND OF 5155 03:59:28,360 --> 03:59:31,080 PROVIDES A THOUGHT FOR CAN YOU 5156 03:59:31,080 --> 03:59:33,400 MAKE OLD PERSON HELP THERE AND 5157 03:59:33,400 --> 03:59:35,920 YOUNGER BY AGING YOUNG FACTORS 5158 03:59:35,920 --> 03:59:39,240 ON TOP OF OLD FACTORS AND AS I 5159 03:59:39,240 --> 03:59:41,640 MENTIONED MY CELL YOU SAW IN OLD 5160 03:59:41,640 --> 03:59:45,080 EXPERIMENTS LIKE 20 YEARS AGO 5161 03:59:45,080 --> 03:59:48,080 AND HERE WE HAVE OKG REPEATED 5162 03:59:48,080 --> 03:59:49,680 THEM IN NEW LABORATORY AND 5163 03:59:49,680 --> 03:59:51,440 RESULT IS THE SAME. 5164 03:59:51,440 --> 03:59:55,920 AGAIN, LOOKING AT 16 TO 21 AND 5165 03:59:55,920 --> 03:59:59,360 I'LL 6 AMONG P3 AND COMPARED TO 5166 03:59:59,360 --> 04:00:01,520 SERUM OLD SERUM AND YOUNG PLUS 5167 04:00:01,520 --> 04:00:05,920 OLD THAT IS KIND OF LIKE OLD AND 5168 04:00:05,920 --> 04:00:08,280 YOUNG PLUS OLD IS EXACTLY LIKE 5169 04:00:08,280 --> 04:00:10,520 OLD AND EXACTLY LIKE OLD AND 5170 04:00:10,520 --> 04:00:13,880 EXACTLY LIKE OLD AND KIND OF 5171 04:00:13,880 --> 04:00:24,400 LIKE OLD. IT MEANS REJUVENATED 5172 04:00:26,080 --> 04:00:28,240 FOR OLD BLOOD MANNED REASONS 5173 04:00:28,240 --> 04:00:30,080 THAT PROTEINS ARE PERHAPS 5174 04:00:30,080 --> 04:00:32,400 FILTERED OUT REMOVED BY YOUNG 5175 04:00:32,400 --> 04:00:36,080 PARTNER AND ALL STATUS THERE IS 5176 04:00:36,080 --> 04:00:39,680 NOTICEABLE PREMATURE AGING OF 5177 04:00:39,680 --> 04:00:41,400 YOUNG ANIMAL. 5178 04:00:41,400 --> 04:00:49,160 SAME WAS SHOWN NOW ANOTHER POINT 5179 04:00:49,160 --> 04:00:53,600 OF TRA FROM NATURE METABOLISM 5180 04:00:53,600 --> 04:00:58,760 PAPER USING THIS AND ANALYZING 5181 04:00:58,760 --> 04:01:01,400 MUSCLE REPAIRS AFTER SENESCENCE 5182 04:01:01,400 --> 04:01:05,000 CELLS ARE ELIMINATED SEE CONTROL 5183 04:01:05,000 --> 04:01:07,880 STATUS ON TOP IS DIMINIMOUS AS 5184 04:01:07,880 --> 04:01:10,480 ONE WOULD EXPECT AND LEVEL OF 5185 04:01:10,480 --> 04:01:13,200 CYTOKINES AND PROTEINS ARE 5186 04:01:13,200 --> 04:01:15,000 DIMINISHED IN BLOOD OF MICE AND 5187 04:01:15,000 --> 04:01:17,120 GENERATION IS NOT IMPROVED AND 5188 04:01:17,120 --> 04:01:21,160 FORMATION OF NEW MUSCLE FIBERS 5189 04:01:21,160 --> 04:01:23,960 AND INDEX AND MINIMAL ROBUSTNESS 5190 04:01:23,960 --> 04:01:29,480 OF NEW FIBERS AND MEANS THAT 5191 04:01:29,480 --> 04:01:32,000 REMOVAL OF SENESCENCE CELLS 5192 04:01:32,000 --> 04:01:33,480 ALONE DOESN'T SUFFICE AND THEN I 5193 04:01:33,480 --> 04:01:36,080 MENTIONED THAT WE DON'T HAVE TO 5194 04:01:36,080 --> 04:01:37,160 JUST EXCHANGE YOUNG WITH OLD 5195 04:01:37,160 --> 04:01:40,520 BLOOD ANYMORE WE CAN EXCHANGE 5196 04:01:40,520 --> 04:01:42,080 YOUNG BLOOD WITH SOLUTION AND 5197 04:01:42,080 --> 04:01:43,400 FIRST CONTROL EXPERIMENT IS 5198 04:01:43,400 --> 04:01:48,040 SIMPLY TO USE SALINE WITH 5199 04:01:48,040 --> 04:01:50,120 ALBUMIN AS SOLUTION AND SEE WHAT 5200 04:01:50,120 --> 04:01:54,000 EFFECTS ARE PLASMA PROTEINS ARE 5201 04:01:54,000 --> 04:01:56,400 PHYSICALLY DILUTING PLASMA 5202 04:01:56,400 --> 04:01:58,760 PROTEINS BY 50% WHAT HAPPENS? 5203 04:01:58,760 --> 04:02:00,000 DISCOVERING MANY GOOD THINGS 5204 04:02:00,000 --> 04:02:03,080 HAPPEN THAT IS REALLY AT 5205 04:02:03,080 --> 04:02:05,440 MAGNITUDE OF THOSE SHOWN IN 5206 04:02:05,440 --> 04:02:07,800 HYDRO CHRONIC PARABIOSIS AND 5207 04:02:07,800 --> 04:02:10,840 THREE LAYERS BECOMING 5208 04:02:10,840 --> 04:02:13,720 REJUVENATED AND COGNITION 5209 04:02:13,720 --> 04:02:15,920 IMPROVES INFLAMMATION IS 5210 04:02:15,920 --> 04:02:18,480 ACONTINUATED AND THESE SIMPLE 5211 04:02:18,480 --> 04:02:20,920 PROCEDURES THAT IS PERFORMED 5212 04:02:20,920 --> 04:02:22,640 ONCE MAKES TISSUES THE SAME AS 5213 04:02:22,640 --> 04:02:24,160 YOUNG AND NEVER SEEN APPROACHES 5214 04:02:24,160 --> 04:02:26,680 TO COLLEAGUES AND OUR OWN 5215 04:02:26,680 --> 04:02:27,320 RESEARCH BEFORE. 5216 04:02:27,320 --> 04:02:30,160 THEN, YOU KNOW, PAPERS HAVE BEEN 5217 04:02:30,160 --> 04:02:31,400 PUBLISHED ALMOST THREE YEARS AGO 5218 04:02:31,400 --> 04:02:33,760 AND GOING TO REPEAT A LOT OF 5219 04:02:33,760 --> 04:02:34,880 THAT. JUST SOME SUMMARY HERE 5220 04:02:34,880 --> 04:02:36,760 AND WHAT I WOULD LIKE TO MENTION 5221 04:02:36,760 --> 04:02:38,640 IS THAT SOME PEOPLE ARE STILL 5222 04:02:38,640 --> 04:02:41,200 KIND OF CLINGING TO THIS IDEA 5223 04:02:41,200 --> 04:02:43,640 THAT IT IS ALBUMIN DOING TRICK 5224 04:02:43,640 --> 04:02:45,360 AND REGENERATING SOMETHING AND 5225 04:02:45,360 --> 04:02:48,560 NO NET ADDITIONAL ALBUMIN THAT 5226 04:02:48,560 --> 04:02:50,640 POWDER THAT IS SHAPED AND STORED 5227 04:02:50,640 --> 04:02:54,000 AT ROOM TEMPERATURE THAT IS 99% 5228 04:02:54,000 --> 04:02:56,440 PURE ALBUMIN PROTEIN AND WITH 5229 04:02:56,440 --> 04:02:58,360 PROTEINS THERE ARE OTHER 5230 04:02:58,360 --> 04:03:01,120 PROTEINS MIGHT INADVERTIENTLY 5231 04:03:01,120 --> 04:03:02,760 CONTAMINATED AND SOME BEING 5232 04:03:02,760 --> 04:03:03,760 DENATURED ARE PRESENT AND ABOUT 5233 04:03:03,760 --> 04:03:07,480 WHAT YOU CALCULATED 10,000 TO 5234 04:03:07,480 --> 04:03:09,080 200 TIMES LESS CONCENTRATION 5235 04:03:09,080 --> 04:03:12,160 THAT THEY NEED TO ACT. IF 5236 04:03:12,160 --> 04:03:14,200 SOMEBODY WOULD LIKE TO TRY 5237 04:03:14,200 --> 04:03:17,200 ISOLATE SOMETHING REJUVENATING 5238 04:03:17,200 --> 04:03:19,240 FROM ALBUMIN POWDER INJECTED 5239 04:03:19,240 --> 04:03:22,720 INTO OLD ANIMAL ONCE AND 5240 04:03:22,720 --> 04:03:25,200 OBSERVED STATISTICALLY 5241 04:03:25,200 --> 04:03:27,120 SIGNIFICANT REJUVENATION OF GERM 5242 04:03:27,120 --> 04:03:28,720 LAYERS IS GREAT DISCOVERY AND IS 5243 04:03:28,720 --> 04:03:32,240 NOT REALISTIC. 5244 04:03:32,240 --> 04:03:35,080 SO, NOW HOW DOES PLASMA DILUTION 5245 04:03:35,080 --> 04:03:37,560 WORK COMING FROM OLDER STUDY IN 5246 04:03:37,560 --> 04:03:38,920 MICE AND PEOPLE AND BEFORE AND 5247 04:03:38,920 --> 04:03:41,680 AFTER EXCHANGES AND IN THIS HEAT 5248 04:03:41,680 --> 04:03:45,200 MAP YOU SEE THAT MANY PROTEINS 5249 04:03:45,200 --> 04:03:47,080 BECOME INTERESTINGLY UPREGULATED 5250 04:03:47,080 --> 04:03:50,440 AT SOME TIME AND ONE WEEK IN 5251 04:03:50,440 --> 04:03:53,360 MYOSIN AND 1 MONTH IN HUMANS 5252 04:03:53,360 --> 04:03:55,080 AFTER BLOOD DILATION AND WHAT IS 5253 04:03:55,080 --> 04:03:57,760 JUST ILLUSTRATION AND WHAT YOU 5254 04:03:57,760 --> 04:03:59,520 BELIEVE IS IF INHIBITIVE PROTEIN 5255 04:03:59,520 --> 04:04:02,560 THAT IS ELEVATED AND ONE THAT IS 5256 04:04:02,560 --> 04:04:04,320 DILUTION AND LEVEL DROPS DOWN IT 5257 04:04:04,320 --> 04:04:07,440 GOES DOWN MORE BECAUSE IT IS 5258 04:04:07,440 --> 04:04:08,960 INDUCING ITSELF AND NOW WE HAVE 5259 04:04:08,960 --> 04:04:11,440 POSTED FEEDBACK AND DOES NOT 5260 04:04:11,440 --> 04:04:12,560 REPRESS POSITIVE PROTEIN HOOER 5261 04:04:12,560 --> 04:04:14,600 AND THERE IS SOME OTHER INTERNAL 5262 04:04:14,600 --> 04:04:16,560 LINKS IN THE PATHWAY OF THE 5263 04:04:16,560 --> 04:04:18,600 MODEL HERE THAT IS VERY, VERY 5264 04:04:18,600 --> 04:04:20,560 SIMPLE SIMPLISTICALLY AND WHAT 5265 04:04:20,560 --> 04:04:22,040 HAPPENS IS YOU HAVE SLIGHTLY 5266 04:04:22,040 --> 04:04:24,880 LOWER OVERALL LEVEL OF THE 5267 04:04:24,880 --> 04:04:26,120 INHIBITORY PROTEIN THAT IS 5268 04:04:26,120 --> 04:04:28,280 CLOSER TO YOUNG LEVELS AND 5269 04:04:28,280 --> 04:04:30,440 SLIGHTLY HIGHER LEVELS OF USEFUL 5270 04:04:30,440 --> 04:04:35,560 PROTEIN THAT IS NOW NOT 5271 04:04:35,560 --> 04:04:37,440 REPRESSED AND CLOSER TO YOUNG 5272 04:04:37,440 --> 04:04:38,600 LEVELS AND ILLUSTRATION AND WHAT 5273 04:04:38,600 --> 04:04:42,160 YOU PLAN AND HOPE TO DO AND 5274 04:04:42,160 --> 04:04:44,360 ILLUSTRATION WITH ACTUAL DATA 5275 04:04:44,360 --> 04:04:46,560 FOUR DIMENSIONAL DATA AND 5276 04:04:46,560 --> 04:04:49,520 PROGRESSION AFTER PLASMA FORESIS 5277 04:04:49,520 --> 04:04:51,600 NEUTRAL BLOOD EXCHANGE AND 5278 04:04:51,600 --> 04:04:53,320 SYNONYMS AND WHAT HAPPENS WHICH 5279 04:04:53,320 --> 04:04:55,720 ARE KEY DETERMINANT PROTEINS 5280 04:04:55,720 --> 04:04:57,200 INHIBITORS DROPPED DOWN AT WHAT 5281 04:04:57,200 --> 04:04:59,360 TIME AND WHAT ARE PROTEINS THAT 5282 04:04:59,360 --> 04:05:02,720 ARE USEFUL NOW ARE REPRESSED AND 5283 04:05:02,720 --> 04:05:05,160 ELEVATED AND HOW WHOLE 5284 04:05:05,160 --> 04:05:07,840 TRANSDUCTION NETWORKS REGULATED 5285 04:05:07,840 --> 04:05:08,520 SYSTEMICALLY IS NOW 5286 04:05:08,520 --> 04:05:10,840 [INDISCERNIBLE] THAT IS A BIG 5287 04:05:10,840 --> 04:05:12,960 ENDEAVOR AND IS AN IMPORTANT PO 5288 04:05:12,960 --> 04:05:16,160 INT THAT TELLS THAT PLASMA 5289 04:05:16,160 --> 04:05:18,200 FORESIS OR NEUTRAL BLOOD 5290 04:05:18,200 --> 04:05:20,000 EXCHANGE OR PLASMA DILUTION 5291 04:05:20,000 --> 04:05:21,720 SHOULD SUFFICE BY THEMSELVES AND 5292 04:05:21,720 --> 04:05:24,400 WE DON'T NEED TO IN THEORY ADD 5293 04:05:24,400 --> 04:05:26,600 USEFUL FACTORS THEY DID NOT 5294 04:05:26,600 --> 04:05:29,840 DISAPPEAR FROM OUR GENOME AND 5295 04:05:29,840 --> 04:05:32,400 THEY ARE SIMPLY REPRESSED AND 5296 04:05:32,400 --> 04:05:34,440 COME BACK AND GIVING A QUICK 5297 04:05:34,440 --> 04:05:35,640 OVERVIEW OF DATA THAT I 5298 04:05:35,640 --> 04:05:38,680 MENTIONED AND HAVING WHAT IS 5299 04:05:38,680 --> 04:05:41,160 NEUTRAL BLOOD EXCHANGE COMPARED 5300 04:05:41,160 --> 04:05:43,200 TO ISOCHRONIC YOUNG YOUNG OLD 5301 04:05:43,200 --> 04:05:47,480 OLD EXCHANGES SEEING IMPROVED 5302 04:05:47,480 --> 04:05:48,360 COGNITION OR NEW OBJECT 5303 04:05:48,360 --> 04:05:50,240 RECOGNITION TESTS WHERE 5304 04:05:50,240 --> 04:05:52,680 TYPICALLY YOUNG MICE ARE MUCH 5305 04:05:52,680 --> 04:05:54,040 MORE INQUISITIVE AND KNOW WHICH 5306 04:05:54,040 --> 04:05:56,120 ONE AND WHICH ONE IS NEW AND OLD 5307 04:05:56,120 --> 04:05:59,640 AND OLD MICE ARE OLD AND ARE IN 5308 04:05:59,640 --> 04:06:01,200 CORNER OF [INDISCERNIBLE] AND 5309 04:06:01,200 --> 04:06:02,960 AFTER BLOOD OF MICE COGNITIVELY 5310 04:06:02,960 --> 04:06:05,400 BECOMES STATISTICALLY THE SAME 5311 04:06:05,400 --> 04:06:07,800 AS YOUNG. THOSE SHOW REDUCTION 5312 04:06:07,800 --> 04:06:10,240 OF BRAIN SENESCENCE OF NEUTRAL 5313 04:06:10,240 --> 04:06:13,240 BLOOD EXCHANGE THAT IS SIMILAR 5314 04:06:13,240 --> 04:06:14,920 TO THAT. 5315 04:06:14,920 --> 04:06:18,080 WE SHOW REDUCTION OF 5316 04:06:18,080 --> 04:06:20,800 NEUROINFLAMMATION THAT IS 5317 04:06:20,800 --> 04:06:22,560 ISOCHRONIC EXCHANGE NEUTRAL 5318 04:06:22,560 --> 04:06:25,160 BLOOD EXCHANGE MAKING ALL THESE 5319 04:06:25,160 --> 04:06:26,720 STATISTICALLY SAME AS YOUNG AND 5320 04:06:26,720 --> 04:06:28,200 WHAT IS INTERESTING IS THAT 5321 04:06:28,200 --> 04:06:29,760 COMPARED TO NEUTRAL BLOOD 5322 04:06:29,760 --> 04:06:33,800 EXCHANGE THAT IS ANALYTIC IS NOT 5323 04:06:33,800 --> 04:06:38,960 CAPABLE OF OTHER HIPPOCAMLE POE 5324 04:06:38,960 --> 04:06:40,280 NEUROGENESIS AND INFLAMMATION 5325 04:06:40,280 --> 04:06:44,000 SEEN HERE AND PUBLISHED IT AND 5326 04:06:44,000 --> 04:06:45,680 CURRENTLY MENTIONING TO ME THAT 5327 04:06:45,680 --> 04:06:47,360 THESE DO NOT CROSS BLOOD BRAIN 5328 04:06:47,360 --> 04:06:49,880 BARRIER AND INTERESTINGLY, EVEN 5329 04:06:49,880 --> 04:06:53,160 THOUGH IT DOESN'T IT REDUCES 5330 04:06:53,160 --> 04:06:56,520 NUMBER OF BRAIN SENESCENCE CELLS 5331 04:06:56,520 --> 04:06:58,480 CONNECTION BETWEEN CELLS IN 5332 04:06:58,480 --> 04:07:00,200 PERIPHERY AND IMPROVING THINGS 5333 04:07:00,200 --> 04:07:02,880 IN THE BRAIN AND NEUTRAL BLOOD 5334 04:07:02,880 --> 04:07:06,680 EXCHANGE AND DILUTION OF PLASMA 5335 04:07:06,680 --> 04:07:09,680 DOESN'T CROSS BLOOD BRAIN 5336 04:07:09,680 --> 04:07:13,240 BARRIER EITHER ELIMINATE 5337 04:07:13,240 --> 04:07:15,240 SENESCENCE IN BRAIN 5338 04:07:15,240 --> 04:07:20,680 [INDISCERNIBLE] AND ALSO 5339 04:07:20,680 --> 04:07:21,720 INDUCTION AND INFLAMMATION AND 5340 04:07:21,720 --> 04:07:26,360 HOW DOES IT HAPPEN? WE DON'T 5341 04:07:26,360 --> 04:07:34,400 KNOW YET PUBLISHED BRAIN ORGAN 5342 04:07:34,400 --> 04:07:37,600 CHIPS THAT IS WE CAN START 5343 04:07:37,600 --> 04:07:38,600 INTERACTION BETWEEN BRAIN AND 5344 04:07:38,600 --> 04:07:41,920 BLOOD AND OPENS MANY 5345 04:07:41,920 --> 04:07:45,480 OPPORTUNITIES FOR RESEARCH AND 5346 04:07:45,480 --> 04:07:47,360 LAST COUPLE SLIDES RELEVANCE FOR 5347 04:07:47,360 --> 04:07:50,440 HUMANS AND WORK DONE BY POST 5348 04:07:50,440 --> 04:07:54,080 DOCTORAL FELLOW SENIOR SCIENTIST 5349 04:07:54,080 --> 04:08:00,800 IN LAB HE RUNS HIS OWN CLINIC 5350 04:08:00,800 --> 04:08:03,200 AND IS DIRECTOR OF BRAIN AGING 5351 04:08:03,200 --> 04:08:09,200 CORRECTOR AT UCSF AND WHAT WE 5352 04:08:09,200 --> 04:08:11,720 DID THERE IS START 5353 04:08:11,720 --> 04:08:12,320 LONGITUDINALLY RESPONSES OF 5354 04:08:12,320 --> 04:08:19,040 PEOPLE THAT ARE MIDDLE AGE AND 5355 04:08:19,040 --> 04:08:21,440 PLASMA FORESIS AND 8 PEOPLE 5356 04:08:21,440 --> 04:08:25,400 STUDYING MANY PARAMETERS AND 5357 04:08:25,400 --> 04:08:31,280 PROETEE OHMO PROTEINS STARTING 5358 04:08:31,280 --> 04:08:34,560 TRANSCRIPTOMICS AND FIND IN 5359 04:08:34,560 --> 04:08:38,600 THESE SAMPLE DATA SETS USING DIG 5360 04:08:38,600 --> 04:08:43,240 DATA AND EXPERIMENTAL APPROACH 5361 04:08:43,240 --> 04:08:48,960 FOEKUSING ON ROBUST CHANGES I 5362 04:08:48,960 --> 04:08:51,240 THINK DISCOVERIES ARE POSSIBLE 5363 04:08:51,240 --> 04:08:54,880 PURCHASED IN COHORT A AND B AND 5364 04:08:54,880 --> 04:08:57,480 LONGITUDINALLY AND IN PEOPLE 5365 04:08:57,480 --> 04:09:01,160 BECOMING GRADUALLY YOUNGER IN 5366 04:09:01,160 --> 04:09:03,720 PROCEDURE AND LOOKING AT PBMC WE 5367 04:09:03,720 --> 04:09:06,720 SEE DECLINES AND EACH LINE HERE 5368 04:09:06,720 --> 04:09:09,960 IS INDIVIDUAL AND EEP IS ROUND 5369 04:09:09,960 --> 04:09:12,840 OF PLASMA FORESIS THAT IS 0 IS 5370 04:09:12,840 --> 04:09:15,800 WHEN STARTED AND SENESCENCE OF 5371 04:09:15,800 --> 04:09:17,560 CLIENTS AS WELL AND PLASMA 5372 04:09:17,560 --> 04:09:18,680 FORESIS AND IS DIFFERENT IN 5373 04:09:18,680 --> 04:09:21,440 PERSON TO PERSON AND OVERALL 5374 04:09:21,440 --> 04:09:24,680 TREND IS AMBIGUOUS AND 5375 04:09:24,680 --> 04:09:25,600 STATISTICALLY SIGNIFICANT AND 5376 04:09:25,600 --> 04:09:32,680 ONE PROFOUND EFFECT OF AGING IN 5377 04:09:32,680 --> 04:09:36,240 PBMC IS [INDISCERNIBLE] AND 5378 04:09:36,240 --> 04:09:39,960 INFLAMMATORY CELLS AND SHIFT IS 5379 04:09:39,960 --> 04:09:42,760 YOURS USING SEVERAL MARKERS AND 5380 04:09:42,760 --> 04:09:51,880 RECEPTORS CD4CDA CORECEPTORS AND 5381 04:09:51,880 --> 04:09:56,160 KILLER CELL MARKERS AND METRICS 5382 04:09:56,160 --> 04:09:58,040 AGAIN AVAILABILITY BETWEEN 5383 04:09:58,040 --> 04:10:00,560 SUBJECTS FOR CLEAR TREND AND 5384 04:10:00,560 --> 04:10:03,400 MOST SUBJECTS AT SOME POINT FOR 5385 04:10:03,400 --> 04:10:05,880 FORESIS THIS IS STATISTICALLY 5386 04:10:05,880 --> 04:10:08,200 SIGNIFICANT AND CAN OBSERVE SAME 5387 04:10:08,200 --> 04:10:11,720 TREND LOOKING AT RATIOS AND SO 5388 04:10:11,720 --> 04:10:16,560 FORTH. SEEMS THAT VERY QUICKLY 5389 04:10:16,560 --> 04:10:20,000 THAT PROFILE OF PBMCS IS 5390 04:10:20,000 --> 04:10:21,200 RESTORED AND COMPARTMENT OF 5391 04:10:21,200 --> 04:10:23,520 BLOOD IS RESTORED TO THAT OF THE 5392 04:10:23,520 --> 04:10:24,840 YOUNG PERSON. 5393 04:10:24,840 --> 04:10:26,600 ALSO, I WAS VERY WORRIED THAT 5394 04:10:26,600 --> 04:10:30,440 WHILE IT WAS RESTORED WE ARE 5395 04:10:30,440 --> 04:10:34,160 REDUCING ONCO GENESIS AND EITHER 5396 04:10:34,160 --> 04:10:37,360 WE DID NOT SEE EXCHANGE OR IN 5397 04:10:37,360 --> 04:10:39,440 FACT TUMOR SUPPRESSORS ARE 5398 04:10:39,440 --> 04:10:41,320 INCREASED IN SUBJECTS THAT IS A 5399 04:10:41,320 --> 04:10:43,440 GOOD SIGN AND IF YOU LIKE TO 5400 04:10:43,440 --> 04:10:47,760 LOOK AT INDIVIDUAL MARKERS AND 5401 04:10:47,760 --> 04:10:50,080 INFLAMMATORY CELLS MACROPHAGES 5402 04:10:50,080 --> 04:10:53,200 ARE DECLINED IN OR NOT IN ALL OF 5403 04:10:53,200 --> 04:10:56,800 THE SUBJECTS AND SHIFTING GEARS 5404 04:10:56,800 --> 04:11:01,840 TO PARTS OF SYSTEMIC MILIEU 5405 04:11:01,840 --> 04:11:04,320 ANALYZE 160 PROTEINS AND 5406 04:11:04,320 --> 04:11:06,840 THOUSANDS AND THOUSANDS OF DATA 5407 04:11:06,840 --> 04:11:09,280 POINTS AND THE -- EVENTUALLY 5408 04:11:09,280 --> 04:11:12,160 DISCOVERED 73 BIOMARKERS THAT 5409 04:11:12,160 --> 04:11:15,520 SHOW PRETTY MUCH IN COLOR CODED 5410 04:11:15,520 --> 04:11:17,920 SCHEMATIC OF THIS HEAT MAPPING 5411 04:11:17,920 --> 04:11:18,760 HOW AGING AND MORE 5412 04:11:18,760 --> 04:11:21,680 [INDISCERNIBLE] IS DILUTING THE 5413 04:11:21,680 --> 04:11:24,200 BLUE. THIS IS OLD SAMPLES AND 5414 04:11:24,200 --> 04:11:27,560 YOUNG SAMPLES AND PEOPLE 5415 04:11:27,560 --> 04:11:29,320 UNDERGOING ROUND OF PLASMA 5416 04:11:29,320 --> 04:11:32,200 FORESIS AND MEETINGS CALLING IT 5417 04:11:32,200 --> 04:11:35,120 THESE. HE DISCOVERED THOSE AND 5418 04:11:35,120 --> 04:11:36,520 VERY INTERESTINGLY SAME PATHWAY 5419 04:11:36,520 --> 04:11:45,160 ANALYSIS SHOWS SINGLE PROTEIN 5420 04:11:45,160 --> 04:11:48,160 THAT IS CROSSROADS OF 5421 04:11:48,160 --> 04:11:49,320 TRANSDUCTION PATHWAYS AND 5422 04:11:49,320 --> 04:11:51,400 INCREASED WITH AGING AND BECOMES 5423 04:11:51,400 --> 04:11:58,160 NOISY WITH AGING AND ANOTHER WAY 5424 04:11:58,160 --> 04:12:04,640 USING DAY 173 IS MAPPING THESE 5425 04:12:04,640 --> 04:12:06,360 INDIVIDUALS AND MAPPING BLOOD 5426 04:12:06,360 --> 04:12:09,640 PROETEE OHM OF VARIOUS PEOPLE 5427 04:12:09,640 --> 04:12:10,920 AND DISTINCTION BETWEEN PEOPLE 5428 04:12:10,920 --> 04:12:13,240 WITH NEUROCOGNITIVE DISEASE 5429 04:12:13,240 --> 04:12:16,200 VERSUS PEOPLE WHO ARE YOUNG 5430 04:12:16,200 --> 04:12:18,040 VERSUS OLD AND TWO DIFFERENT OLD 5431 04:12:18,040 --> 04:12:20,800 POPULATIONS FROM INDEPENDENT 5432 04:12:20,800 --> 04:12:23,120 STATUS OR PEOPLE UNDERWENT 5433 04:12:23,120 --> 04:12:25,200 PLASMA FORESIS ROUNDS OR THOSE 5434 04:12:25,200 --> 04:12:28,560 THAT ARE MIDDLE AGED AND DAY 173 5435 04:12:28,560 --> 04:12:30,640 ALLOWS TO VISUALIZE WITHOUT 5436 04:12:30,640 --> 04:12:32,600 PREDICTIONS AND LEARNING MODELS 5437 04:12:32,600 --> 04:12:34,560 BY USING THEM AND CLUSTERING AND 5438 04:12:34,560 --> 04:12:36,600 DIFFERENT GROUPS OF PEOPLE WHO 5439 04:12:36,600 --> 04:12:40,240 ARE YOUNG OR OLD OR HAVE OR 5440 04:12:40,240 --> 04:12:42,800 DON'T HAVE DISEASE. 5441 04:12:42,800 --> 04:12:47,120 LAST PART WILL BE ON KIND OF 5442 04:12:47,120 --> 04:12:48,200 COMPARISON BETWEEN PREDICTION 5443 04:12:48,200 --> 04:12:52,280 AND MEASUREMENT AND LAST SLIDE 5444 04:12:52,280 --> 04:12:57,840 AND THIS IS THAT WE CAN PREDICT 5445 04:12:57,840 --> 04:13:00,720 PEOPLES WEIGHT AND GUESS THEIR 5446 04:13:00,720 --> 04:13:03,360 WEIGHT AND POPULATION STATISTICS 5447 04:13:03,360 --> 04:13:05,880 METHOD SHOULD BE SUCCESSFUL 5448 04:13:05,880 --> 04:13:07,080 BASING IT ON SIZE AND COLONIALS 5449 04:13:07,080 --> 04:13:08,640 THAT PEOPLE ARE WEARING OR FOOD 5450 04:13:08,640 --> 04:13:10,880 THEY ARE EATING AND ALL THESE 5451 04:13:10,880 --> 04:13:12,880 SITUATIONS IT WILL BE RELATIVELY 5452 04:13:12,880 --> 04:13:14,520 ACCURATE PREDICTION AND MORE 5453 04:13:14,520 --> 04:13:16,440 PEOPLE THAT WE USE, BETTER 5454 04:13:16,440 --> 04:13:17,880 PREDICTION WILL BECOME. OF 5455 04:13:17,880 --> 04:13:20,680 COURSE, IT IS NOT ABSOLUTE. 5456 04:13:20,680 --> 04:13:25,240 SOMETIMES PEOPLE ARE WEARING 5457 04:13:25,240 --> 04:13:26,360 BAGGILY CLOTHES OR EAT FOOD AND 5458 04:13:26,360 --> 04:13:29,560 HAVE GREAT METABOLISM SO IT 5459 04:13:29,560 --> 04:13:32,040 DOESN'T REALLY HIT AND ON OTHER 5460 04:13:32,040 --> 04:13:33,960 HAND IF YOU SIMPLY HAVE A SCALE 5461 04:13:33,960 --> 04:13:37,160 AND KNOW WHAT TO MEASURE AND 5462 04:13:37,160 --> 04:13:40,680 MEASURING PARAMETER WE CAN DO IN 5463 04:13:40,680 --> 04:13:43,200 BLINDED FASHION AND IN RESILIENT 5464 04:13:43,200 --> 04:13:46,840 WAY REPRODUCIBLY AND DO NOT JUST 5465 04:13:46,840 --> 04:13:49,960 FOR PEOPLE BUT INANIMATE OBJECT 5466 04:13:49,960 --> 04:13:51,400 AND ELVANTS AND SO ON AND WHAT 5467 04:13:51,400 --> 04:13:56,000 YOU DO IN LAB COULD BE IN 5468 04:13:56,000 --> 04:13:59,440 MEASUREMENT AND BE USED OUR 5469 04:13:59,440 --> 04:14:01,200 BLOOD PROTEOMIC STUDY TO 5470 04:14:01,200 --> 04:14:03,600 IDENTIFY PROTEINS BECOMING 5471 04:14:03,600 --> 04:14:06,200 DYSREGULATED AND NOISY WITH AGE 5472 04:14:06,200 --> 04:14:09,760 AND HYPOTHESIZE PROTEINS WOULD 5473 04:14:09,760 --> 04:14:14,080 BE TOO MUCH FOR WEIGHING PEOPLE 5474 04:14:14,080 --> 04:14:17,200 AND WILL TELL US WHAT HAPPENS 5475 04:14:17,200 --> 04:14:20,560 WITH GOING THROUGH DISEASE OR 5476 04:14:20,560 --> 04:14:23,800 CHRONOLOGICAL AGE AND THIS IS 5477 04:14:23,800 --> 04:14:34,280 EXAMPLE OF PROTEIN -- NOISE 5478 04:14:36,320 --> 04:14:39,920 DECREASES AND THIS IS HERE IS 5479 04:14:39,920 --> 04:14:42,200 MIDDLE AGE AND APPLYING 5480 04:14:42,200 --> 04:14:44,800 PARAMETER TO LARGE DATA 5481 04:14:44,800 --> 04:14:47,120 IDENTIFIES DETECTORS OF 5482 04:14:47,120 --> 04:14:48,160 BIOLOGICAL AGE FROM BLOOD 5483 04:14:48,160 --> 04:14:50,680 PROETEE OHM AND COMPARING YOUNG 5484 04:14:50,680 --> 04:14:52,920 AND OLD AND OLD MIDDLE AGED OLD 5485 04:14:52,920 --> 04:14:55,520 AND OLD WITH DISEASE AND OLD 5486 04:14:55,520 --> 04:14:59,520 REJUVENATED BY ROUNDS OF TP AND 5487 04:14:59,520 --> 04:15:02,000 TAKING LEVELS OF YOUNG 5488 04:15:02,000 --> 04:15:03,680 ARBITRARILY TO 1 SEE AGE RELATED 5489 04:15:03,680 --> 04:15:06,880 INCREASE TO PROTEINS THAT IS 5490 04:15:06,880 --> 04:15:07,720 STATISTICALLY SIGNIFICANT AND IT 5491 04:15:07,720 --> 04:15:11,760 IS FASHIONABLE TO CALL 5492 04:15:11,760 --> 04:15:13,560 BIOLOGICAL OR WE CAN TRANSFORM 5493 04:15:13,560 --> 04:15:17,000 IT TO RELATIVE YEARS OR 5494 04:15:17,000 --> 04:15:19,400 BIOLOGICAL AGE AND SEE THAT WHEN 5495 04:15:19,400 --> 04:15:24,200 PEOPLE ARE YOUNG THEY ARE VERY 5496 04:15:24,200 --> 04:15:34,720 CLOSE TO THESE LINES OF WHEN 5497 04:15:37,280 --> 04:15:39,080 PEOPLE ARE MIDDLE AGE THERE IS 5498 04:15:39,080 --> 04:15:43,520 EFFECT THAT IS MORE AND IS 5499 04:15:43,520 --> 04:15:45,800 PERFECT PEOPLE MIDDLE AGE OR 5500 04:15:45,800 --> 04:15:46,840 ORDER DEVELOP VARIOUS CONDITIONS 5501 04:15:46,840 --> 04:15:49,120 AND DISEASES AND IF YOU DON'T 5502 04:15:49,120 --> 04:15:52,000 KNOW WHAT THOSE ARE YET YOU SEE 5503 04:15:52,000 --> 04:15:54,800 BIOLOGICAL AGE NOW IS NOT NEATLY 5504 04:15:54,800 --> 04:15:56,400 ALIGNED TO THIS ONE LINEAR MODEL 5505 04:15:56,400 --> 04:16:01,200 THAT IN MY OPINION IS HOW IT 5506 04:16:01,200 --> 04:16:05,160 REFLECTS REALITY AND PATIENTS 5507 04:16:05,160 --> 04:16:07,400 WITH BIOCOGNITIVE IMPAIRMENT 5508 04:16:07,400 --> 04:16:09,080 MOST ARE OLDER THAN BIOLOGICAL 5509 04:16:09,080 --> 04:16:11,440 AGE AND PEOPLE THAT HAVE BEFORE 5510 04:16:11,440 --> 04:16:13,880 VERSUS AFTER TP ASSESSMENT OF 5511 04:16:13,880 --> 04:16:16,200 BIOLOGICAL AGE IS MIRROR IMAGE 5512 04:16:16,200 --> 04:16:19,720 SUCH AS THIS ABOVE AND THIS 5513 04:16:19,720 --> 04:16:22,320 BELOW AND SO FORTH AND EXCHANGE 5514 04:16:22,320 --> 04:16:24,760 REDUCES BIOLOGICAL AGE BASED ON 5515 04:16:24,760 --> 04:16:27,360 WHAT YOU CALL DAY 1 OR 10 5516 04:16:27,360 --> 04:16:29,760 BIOMARKERS AND PROTEINS AND 5517 04:16:29,760 --> 04:16:31,760 EMPHASIZE YOU DON'T NEED PROTEIN 5518 04:16:31,760 --> 04:16:36,200 LEVELS HIGH OR LOW OR SAME CARE 5519 04:16:36,200 --> 04:16:41,160 ABOUT PROTEIN LEVELS BECOME 5520 04:16:41,160 --> 04:16:43,480 DYSREGULATED 20 PEOPLE IN SAME 5521 04:16:43,480 --> 04:16:45,160 AGE STANDARD DEVIATION INCREASE 5522 04:16:45,160 --> 04:16:48,360 WHEN GROWING OLDER OR HAVING 5523 04:16:48,360 --> 04:16:51,560 DISEASES AND AGAIN EMPHASIZING 5524 04:16:51,560 --> 04:16:55,360 LOOKING AT ROBUST PHENOMENA ALL 5525 04:16:55,360 --> 04:17:00,440 OF THE PEOPLE ARE 50S AND 60S 5526 04:17:00,440 --> 04:17:04,440 AND 70S AND PLASMA FORESIS YOU 5527 04:17:04,440 --> 04:17:06,200 HAVE 8 PEOPLE AND SEE REDUCTION 5528 04:17:06,200 --> 04:17:10,080 OF BIOLOGICAL NOISE OR AGE RIGHT 5529 04:17:10,080 --> 04:17:15,080 AWAY THIS IS KIND OF PROMISING 5530 04:17:15,080 --> 04:17:16,040 PHENOMENA IDENTIFYING THOSE YOU 5531 04:17:16,040 --> 04:17:17,640 DON'T HAVE TO USE PREDICTIONS 5532 04:17:17,640 --> 04:17:21,200 ABOUT YOU COULD FOCUS ON 5533 04:17:21,200 --> 04:17:22,680 MEASUREMENTS AND NOT THROWING 5534 04:17:22,680 --> 04:17:24,240 SHADE AND THINK THIS IS AWESOME 5535 04:17:24,240 --> 04:17:26,720 AND SO MANY WONDERFUL GROUPS DO 5536 04:17:26,720 --> 04:17:27,960 THIS RESEARCH AND IN OUR GROUP 5537 04:17:27,960 --> 04:17:30,160 WE ARE USING ACTUALLY ALL DATA 5538 04:17:30,160 --> 04:17:33,920 SETS AND MODELS TO GIVE OUR OWN 5539 04:17:33,920 --> 04:17:35,200 HUMAN INTELLIGENT BRAIN IDEAS 5540 04:17:35,200 --> 04:17:37,920 WHAT WE CAN MEASURE AND ONE MORE 5541 04:17:37,920 --> 04:17:39,760 LAST POINT HERE IF YOU LOOK AT 5542 04:17:39,760 --> 04:17:42,480 PEOPLE IN THEIR 40S AND 50S 5543 04:17:42,480 --> 04:17:45,200 BEFORE AND AFTER PLASMA FORESIS 5544 04:17:45,200 --> 04:17:49,480 DROP DOWN IN NOISE IS NOT MUCH 5545 04:17:49,480 --> 04:17:53,320 LOOKING AT OLDER PEOPLE THEY ARE 5546 04:17:53,320 --> 04:17:54,920 SIGNIFICANTLY REJUVENATED AND 5547 04:17:54,920 --> 04:17:59,000 DID BEFORE AND AGING IS YOU ARE 5548 04:17:59,000 --> 04:18:01,760 ON PRESS POWS OF SUCCESS AND ALL 5549 04:18:01,760 --> 04:18:06,240 ADAPTATIONS NOT VISIBLE BOOST 5550 04:18:06,240 --> 04:18:08,400 ADDITIONALLY HEALTH AND CONTRIB 5551 04:18:08,400 --> 04:18:10,320 AUTO AUTO UT TO REJUVENATION AND 5552 04:18:10,320 --> 04:18:11,960 MENTIONING AGE HERE IS 250 YEARS 5553 04:18:11,960 --> 04:18:14,440 AND DOES NO THE MEAN THAT THIS 5554 04:18:14,440 --> 04:18:16,520 PERSON WITH MIOCOGNITIVE 5555 04:18:16,520 --> 04:18:19,240 IMPAIRMENT THAT IS 70 OR 75 IS 5556 04:18:19,240 --> 04:18:23,320 250 ACTUALLY. WHAT IT MEANS IS 5557 04:18:23,320 --> 04:18:26,800 IF YOU DO MUCH AND REMAIN 5558 04:18:26,800 --> 04:18:29,200 ACCURATELY YES IN BIOLOGICAL 5559 04:18:29,200 --> 04:18:32,240 PEERS IS EQUIVALENT TO BLOOD PRO 5560 04:18:32,240 --> 04:18:34,160 TEE OHM TO SOMEBODY THAT COULD 5561 04:18:34,160 --> 04:18:36,200 BE 150 AND ANOTHER POINT I WANT 5562 04:18:36,200 --> 04:18:39,160 TO BRING UP HERE IS WHEN YOU 5563 04:18:39,160 --> 04:18:41,680 MEASURE BIOLOGICAL AGE IT STBT 5564 04:18:41,680 --> 04:18:44,720 HAVE TO BE ANALOGOUS OR PARALLEL 5565 04:18:44,720 --> 04:18:50,440 TO CHRONOLOGICAL AGE IT IS BLOOD 5566 04:18:50,440 --> 04:18:53,680 PROET EE 5567 04:18:53,680 --> 04:18:57,200 PROETEE OHM IT IS AGGREGATE OF 5568 04:18:57,200 --> 04:18:58,520 DIFFERENCES THAT FORM BIOLOGICAL 5569 04:18:58,520 --> 04:19:02,280 AGE AND IS THIS WEIGHT HEALTHY 5570 04:19:02,280 --> 04:19:06,120 IS NEXT ONE HERE CONCLUSIONS 5571 04:19:06,120 --> 04:19:09,160 [INDISCERNIBLE] PROTEINS AND 5572 04:19:09,160 --> 04:19:12,600 THEY ARE VITAL AT YOUNG LEVELS 5573 04:19:12,600 --> 04:19:15,920 CAN'T TURN OFF NEED TO CALIBRATE 5574 04:19:15,920 --> 04:19:18,400 THEM AND BLOOD DILUTION DOESN'T 5575 04:19:18,400 --> 04:19:21,040 ACT SIMPLY BY [INDISCERNIBLE] 5576 04:19:21,040 --> 04:19:24,240 AND SIN ALYTICS AND 5577 04:19:24,240 --> 04:19:25,680 [INDISCERNIBLE] IS DIFFERENT 5578 04:19:25,680 --> 04:19:29,480 FROM EACH OTHER AND IT IS NOT 5579 04:19:29,480 --> 04:19:31,320 SYNONYMOUS AND DEPENDENT ON TIME 5580 04:19:31,320 --> 04:19:33,680 AND YOUNG MICE AND BLOOD CELLS 5581 04:19:33,680 --> 04:19:35,520 THAT ARE YOUNG AND BLOOD THAT IS 5582 04:19:35,520 --> 04:19:37,160 YOUNG AND BASICALLY EVERYTHING 5583 04:19:37,160 --> 04:19:41,400 IS YOUNG. WE EXCHANGE 50% OF 5584 04:19:41,400 --> 04:19:43,640 ADULT BLOOD BEGS QUESTION HOW 5585 04:19:43,640 --> 04:19:47,200 BLOOD FACTORS HELP ENTIRELY OLD 5586 04:19:47,200 --> 04:19:47,440 ORGANISM. 5587 04:19:47,440 --> 04:19:49,040 I'M NOT DOUBTING IT CAN. IT 5588 04:19:49,040 --> 04:19:53,040 WOULD BE VERY INTERESTING 5589 04:19:53,040 --> 04:19:53,440 MECHANISM. 5590 04:19:53,440 --> 04:19:55,640 NOT PREDICTING BIOLOGICAL AGE IS 5591 04:19:55,640 --> 04:20:00,040 BASED ON DETECTORS OF BIOLOGICAL 5592 04:20:00,040 --> 04:20:03,320 NOISE CALLING DAY 10 AND PUT IN 5593 04:20:03,320 --> 04:20:04,760 PAPER AND THAT IS LABORATORY 5594 04:20:04,760 --> 04:20:06,880 THANKS TO PEOPLE AND BEFORE 5595 04:20:06,880 --> 04:20:08,720 PANDEMIC THAT IS BEFORE PANDEMIC 5596 04:20:08,720 --> 04:20:10,600 DURING AND AFTER PANDEMIC AND 5597 04:20:10,600 --> 04:20:13,360 MANY THINGS TO DEFINING SOURCES. 5598 04:20:13,360 --> 04:20:23,920 THANK YOU FOR YOUR ATTENTION. 5599 04:20:24,400 --> 04:20:27,920 >>WE ARE RUNNING OUT OF TIME 5600 04:20:27,920 --> 04:20:30,120 AND LET'S QUICKLY WRAP UP THE 5601 04:20:30,120 --> 04:20:31,640 SECTION AT THE END THREE 5602 04:20:31,640 --> 04:20:32,920 PANELISTS INCLUDING ME WOULD 5603 04:20:32,920 --> 04:20:37,160 LIKE TO GIVE OVERVIEW TO SHARE 5604 04:20:37,160 --> 04:20:42,480 OUR VIEWS ABOUT BIOLOGICAL AGING 5605 04:20:42,480 --> 04:20:46,400 MAJORS AND AS YOU CAN TELL 5606 04:20:46,400 --> 04:20:51,640 DIFFERENT PRESENTATIONS ARE 5607 04:20:51,640 --> 04:20:53,480 DIFFERENT AND HOPE YOU FIND WAY 5608 04:20:53,480 --> 04:21:04,000 TO RELATE TO EACH OTHER BRAVE 5609 04:21:13,120 --> 04:21:16,680 OKAY. GOING FIRST AND BRIAN 5610 04:21:16,680 --> 04:21:18,800 FROM FOXO TECHNOLOGIES AND 5611 04:21:18,800 --> 04:21:21,160 [INDISCERNIBLE] FROM COLUMBIA 5612 04:21:21,160 --> 04:21:31,640 UNIVERSITY WILL FOLLOW ME. 5613 04:21:33,240 --> 04:21:37,640 PEOPLE HAVE DIFFERENT MOLECULAR 5614 04:21:37,640 --> 04:21:41,840 DATA FROM SYSTEMS TO ESTIMATE 5615 04:21:41,840 --> 04:21:43,880 BIOLOGICAL AGE. 5616 04:21:43,880 --> 04:21:47,400 OR TO PREDICT TRAJECTORY OF 5617 04:21:47,400 --> 04:21:49,320 BIOLOGICAL AGING THAT YOU SEE IN 5618 04:21:49,320 --> 04:21:53,160 DATA FROM SINGLE TIME POINT OR 5619 04:21:53,160 --> 04:21:56,560 FROM TIME FORCE. 5620 04:21:56,560 --> 04:22:00,040 BUT, LET'S THINK ABOUT THIS. WE 5621 04:22:00,040 --> 04:22:02,160 CANNOT EXACTLY YOU KNOW MAJOR 5622 04:22:02,160 --> 04:22:05,160 BIOLOGICAL AGING AND NEED TO DO 5623 04:22:05,160 --> 04:22:07,480 IT THROUGH CERTIFIGATE. PEOPLE 5624 04:22:07,480 --> 04:22:14,720 SURE THEY USE CHRONOLOGICAL AGE. 5625 04:22:14,720 --> 04:22:16,680 BUT IS THAT ENOUGH? PERHAPS WE 5626 04:22:16,680 --> 04:22:18,880 NEED OUTCOME TOWARDS SCIENCE 5627 04:22:18,880 --> 04:22:22,640 INDICATION THAT IS SUCH LIKE A 5628 04:22:22,640 --> 04:22:24,040 DISEASE FREE OUTCOMES AND 5629 04:22:24,040 --> 04:22:27,240 COMPOSITE OUTCOMES THAT ARE 5630 04:22:27,240 --> 04:22:32,280 INCLUDING SEVERAL AGE SENSITIVE 5631 04:22:32,280 --> 04:22:33,160 PHENOTYPES. 5632 04:22:33,160 --> 04:22:34,920 VALIDATION OF CLOCK, LET ME PUT 5633 04:22:34,920 --> 04:22:36,680 IT CLOCK. 5634 04:22:36,680 --> 04:22:39,880 IT IS ESTABLISHED BY COMPARING 5635 04:22:39,880 --> 04:22:41,160 TO CHRONOLOGICAL AGE THAT IS FOR 5636 04:22:41,160 --> 04:22:44,520 STRONGER ASSOCIATIONS WITH A 5637 04:22:44,520 --> 04:22:48,280 NUMBER OF AGE RELATED OUTCOMES 5638 04:22:48,280 --> 04:22:50,000 THAT MAJOR CHRONIC DISEASE 5639 04:22:50,000 --> 04:22:53,200 OUTCOMES THAT YOU CAN THINK OF. 5640 04:22:53,200 --> 04:22:56,000 AND PERHAPS TYPICAL AGING 5641 04:22:56,000 --> 04:23:00,120 OUTCOMES THAT ARE SUCH AS 5642 04:23:00,120 --> 04:23:01,480 FRAILTY THAT GET SPEED AND 5643 04:23:01,480 --> 04:23:02,360 STRENGTH. 5644 04:23:02,360 --> 04:23:06,920 THERE IS A THEORY. ALSO, 5645 04:23:06,920 --> 04:23:12,200 EVIDENCE THAT SHOWS THAT 5646 04:23:12,200 --> 04:23:12,720 DIFFERENT BIOLOGICAL AGE 5647 04:23:12,720 --> 04:23:13,760 PREDICPRED 5648 04:23:13,760 --> 04:23:15,880 PREDICTORS CAPTURE DIFFERENT 5649 04:23:15,880 --> 04:23:18,920 ASPECTS OF BIOLOGICAL AGING AND 5650 04:23:18,920 --> 04:23:21,120 RESEARCH SHOWS THAT DIFFERENT 5651 04:23:21,120 --> 04:23:21,800 BIOLOGICAL AGE PREDICTORS ARE 5652 04:23:21,800 --> 04:23:23,680 NOT SO CORRELATED AND HAVE 5653 04:23:23,680 --> 04:23:26,520 DIFFERENT ASSOCIATIONS WITH 5654 04:23:26,520 --> 04:23:30,720 DIFFERENT AGING RELATED 5655 04:23:30,720 --> 04:23:31,280 OUTCOMES. 5656 04:23:31,280 --> 04:23:35,840 SO, TO GAIN BIOLOGICAL INSIGHTS, 5657 04:23:35,840 --> 04:23:37,160 WE COULD USE [INDISCERNIBLE] 5658 04:23:37,160 --> 04:23:39,520 DATA TO ASSOCIATE WITH DIFFERENT 5659 04:23:39,520 --> 04:23:43,120 BIOLOGICAL AGE PREDICTORS TO GET 5660 04:23:43,120 --> 04:23:48,280 TO KNOW UNDERLYING PATHWAYS, FOR 5661 04:23:48,280 --> 04:23:48,560 EXAMPLE. 5662 04:23:48,560 --> 04:23:51,000 IN FIRST TALK, TREY ALSO 5663 04:23:51,000 --> 04:23:56,760 SUGGESTS THREE DOMAINS TO LOOK 5664 04:23:56,760 --> 04:24:01,080 AT FOR EXAMPLE DNA DAMAGE 5665 04:24:01,080 --> 04:24:06,320 MUTATION OR DUE TO CHANGE IN 5666 04:24:06,320 --> 04:24:08,800 CELL TYPE COMPOSITION. 5667 04:24:08,800 --> 04:24:12,280 OVERALL PICTURE IS TAKING INPUT 5668 04:24:12,280 --> 04:24:18,240 AND DATA TO APPLY MSH LEARNING 5669 04:24:18,240 --> 04:24:21,000 METHOD AND PEOPLE USE PENALIZED 5670 04:24:21,000 --> 04:24:24,280 REGRESSION MODEL WITHOUT 5671 04:24:24,280 --> 04:24:26,240 PRESELECTING FEATURES. 5672 04:24:26,240 --> 04:24:28,160 SO, IN THE END WHAT INCLUDED IN 5673 04:24:28,160 --> 04:24:32,960 A PREDICTOR ARE NO LONGER THE 5674 04:24:32,960 --> 04:24:33,920 MEANINGFUL. 5675 04:24:33,920 --> 04:24:37,160 SO, TO UNDERSTAND DIFFERENT 5676 04:24:37,160 --> 04:24:40,440 BIOLOGICAL AGE PREDICTORS YOU 5677 04:24:40,440 --> 04:24:43,840 HAVE TO TREAT AS WHOLE TO 5678 04:24:43,840 --> 04:24:44,680 ASSOCIATE WITH DIFFERENT AGE 5679 04:24:44,680 --> 04:24:50,120 SENSITIVE PHENOTYPES OR MAYBE 5680 04:24:50,120 --> 04:24:54,320 DIFFERENTOMIC DATA TO HAVE 5681 04:24:54,320 --> 04:24:56,720 BETTER UNDERSTANDING AND OF 5682 04:24:56,720 --> 04:24:58,960 COURSE TO HAVE GOOD BIOLOGICAL 5683 04:24:58,960 --> 04:25:03,320 AGE PREDICTOR TO BE STRONGLY 5684 04:25:03,320 --> 04:25:05,160 ASSOCIATED WITH AGE RELATED 5685 04:25:05,160 --> 04:25:05,760 OUTCOMES IN GENERAL. 5686 04:25:05,760 --> 04:25:09,760 IN THE END, WE WILL HAVE A 5687 04:25:09,760 --> 04:25:13,680 CLOCK, BIOLOGICAL AGE PREDICTOR 5688 04:25:13,680 --> 04:25:18,160 THAT IS TO MONITOR THE 5689 04:25:18,160 --> 04:25:20,800 BIOLOGICAL AGING PROCESS FOR 5690 04:25:20,800 --> 04:25:23,320 INDIVIDUALS WITH AND WITHOUT 5691 04:25:23,320 --> 04:25:24,800 INTERVENTION THAT COULD BE VERY 5692 04:25:24,800 --> 04:25:27,720 USEFUL TOOL IN RANDOMIZED 5693 04:25:27,720 --> 04:25:30,280 CONTROL TRIALS TO MONITOR 5694 04:25:30,280 --> 04:25:32,720 TREATMENT EFFECTS FOR EXAMPLE. 5695 04:25:32,720 --> 04:25:37,560 NOW, I WILL PASS IT TO BRIAN. 5696 04:25:37,560 --> 04:25:40,160 >>BEFORE I GET INTO MY NEXT 5697 04:25:40,160 --> 04:25:42,760 SLIDE, I WANT TO PREFACE A 5698 04:25:42,760 --> 04:25:45,160 DECLARATION AND WARNING THAT WE 5699 04:25:45,160 --> 04:25:47,520 KNOW ARTIFICIAL INTELLIGENCE IS 5700 04:25:47,520 --> 04:25:48,800 MATURING VERY RAPID WILL I TO 5701 04:25:48,800 --> 04:25:52,080 THE POINT WHERE I THINK IT WILL 5702 04:25:52,080 --> 04:25:53,480 BE ACCESSIBLE TO A LOT MORE 5703 04:25:53,480 --> 04:25:57,200 PEOPLE AND THAT PART OF THE 5704 04:25:57,200 --> 04:25:59,960 BUILDING CLOCKS OR MATHEMATICAL 5705 04:25:59,960 --> 04:26:01,840 MODELING WON'T BE THE CHALLENGE 5706 04:26:01,840 --> 04:26:03,600 ANYMORE AND IT WILL BE DATA 5707 04:26:03,600 --> 04:26:05,440 QUALITY AND QUANTITY AND WHAT I 5708 04:26:05,440 --> 04:26:07,360 WOULD CALL HUMAN INTELLIGENCE 5709 04:26:07,360 --> 04:26:11,960 THAT IS WHAT MY NEXT SLIDE IS 5710 04:26:11,960 --> 04:26:14,760 DESCRIBING BASED OFF EXAMPLES 5711 04:26:14,760 --> 04:26:17,160 WHERE HUMAN INTELLIGENCE IS 5712 04:26:17,160 --> 04:26:19,320 NEEDED IN ARTIFICIAL 5713 04:26:19,320 --> 04:26:20,360 INTELLIGENCE CAN'T SOLVE FOR AND 5714 04:26:20,360 --> 04:26:23,840 ARE BASICALLY THE STUDY DESIGNS. 5715 04:26:23,840 --> 04:26:25,200 WHAT IS THE QUESTION THAT YOU 5716 04:26:25,200 --> 04:26:26,200 ARE ASKING? 5717 04:26:26,200 --> 04:26:28,120 WHAT IS INPUT DATA YOU ARE 5718 04:26:28,120 --> 04:26:31,280 PUTTING IN THERE? 5719 04:26:31,280 --> 04:26:37,160 THINKING THROUGH WHAT USE CASE 5720 04:26:37,160 --> 04:26:42,440 CLINICAL PREDICTOR FRAMING HAM 5721 04:26:42,440 --> 04:26:43,360 RISK SCORE WHAT IT IS MEANT TO 5722 04:26:43,360 --> 04:26:45,160 DO AND WAY I WOULD DESIGN THAT 5723 04:26:45,160 --> 04:26:48,080 STUDY IF TRYING TO GET 5724 04:26:48,080 --> 04:26:49,120 BIOLOGICAL MECHANISMS I WOULD 5725 04:26:49,120 --> 04:26:53,120 DESIGN STUDY DIFFERENTLY AND 5726 04:26:53,120 --> 04:26:55,440 ANOTHER EXAMPLE IS ON MACHINE 5727 04:26:55,440 --> 04:26:56,960 LEARNING PART AND I SPEND MY 5728 04:26:56,960 --> 04:26:58,880 TIME THINKING WHAT IS TARGET 5729 04:26:58,880 --> 04:27:01,720 VARIABLE IS IT MECHANISM AND IS 5730 04:27:01,720 --> 04:27:06,440 IT A PHENOTYPE IF A PHENOTYPE AT 5731 04:27:06,440 --> 04:27:10,320 WHAT AGE WHAT ARE OTHER 5732 04:27:10,320 --> 04:27:11,800 COMPETING OUTCOMES AND 5733 04:27:11,800 --> 04:27:13,200 PHENOTYPES I'M LOOKING AT AND 5734 04:27:13,200 --> 04:27:15,280 YOU DON'T HAVE TO LOOK AT TARGET 5735 04:27:15,280 --> 04:27:20,520 BUT ON PERIPHERAL AND BIGGER 5736 04:27:20,520 --> 04:27:24,200 PICTURE AND HOW PRECISE TO BE ON 5737 04:27:24,200 --> 04:27:27,720 TARGET VARIABLE AND USE A LOOSE 5738 04:27:27,720 --> 04:27:30,320 TERM AND BIOLOGICAL AREA WE TALK 5739 04:27:30,320 --> 04:27:31,600 ABOUT FRAILTY AND THERE IS 5740 04:27:31,600 --> 04:27:32,960 MULTIPLE DEFINITIONS OF FRAILTY 5741 04:27:32,960 --> 04:27:35,800 AND TO ME IS MULTIPLE 5742 04:27:35,800 --> 04:27:36,960 DEFINITIONS THAT IS NOT PRECISE 5743 04:27:36,960 --> 04:27:39,440 ENOUGH OFTEN TIMES CAN WE GO 5744 04:27:39,440 --> 04:27:41,160 MORE PRECISE WHAT ARE SOME 5745 04:27:41,160 --> 04:27:42,240 ASPECTS OF FRAILTY YOU ARE 5746 04:27:42,240 --> 04:27:43,280 TRYING TO LOOK AT? 5747 04:27:43,280 --> 04:27:45,680 I THINK THAT GENERALLY SHOULD 5748 04:27:45,680 --> 04:27:48,400 YOU EXPECT A SUMMARY SCORE TO BE 5749 04:27:48,400 --> 04:27:50,280 ABLE TO CAPTURE EVERYTHING THAT 5750 04:27:50,280 --> 04:27:51,480 IS ABOUT BIOLOGY. 5751 04:27:51,480 --> 04:27:54,080 BUT, THERE IS A UTILITY FOR 5752 04:27:54,080 --> 04:27:55,320 SINGLE SCORES OFTEN TIMES AND WE 5753 04:27:55,320 --> 04:27:58,640 CAN TALK ABOUT THAT LATER. ALSO 5754 04:27:58,640 --> 04:28:01,080 IN THE VALUATION, THERE NEEDS TO 5755 04:28:01,080 --> 04:28:03,600 BE HUMAN INTELLIGENCE IN 5756 04:28:03,600 --> 04:28:04,960 SELECTING HOW YOU WILL VALIDATE. 5757 04:28:04,960 --> 04:28:07,360 THERE IS A LOT OF WAYS TO FOOL 5758 04:28:07,360 --> 04:28:08,600 YOURSELF INTO THINKING YOU 5759 04:28:08,600 --> 04:28:10,520 VALIDATED A MODEL AND IT IS 5760 04:28:10,520 --> 04:28:12,600 ACTUALLY AN ARTIFACT HOW YOU 5761 04:28:12,600 --> 04:28:17,200 DESIGN VALIDATION AND OFTEN TIME 5762 04:28:17,440 --> 04:28:27,320 TIMES I THINK NONREPLICATION 5763 04:28:27,320 --> 04:28:28,760 BIOLOGICAL CLOCK IN ONE 5764 04:28:28,760 --> 04:28:29,920 POPULATION AND TRY ANOTHER IT 5765 04:28:29,920 --> 04:28:31,880 DOESN'T WORK IN ONE OF THOSE AND 5766 04:28:31,880 --> 04:28:34,160 TRY TO DISSECT WHAT ASPECTS OF 5767 04:28:34,160 --> 04:28:36,960 ONE OF THE COHORTS AND STUDIES 5768 04:28:36,960 --> 04:28:38,280 ARE AND TRY TO UNDERSTAND WHY 5769 04:28:38,280 --> 04:28:39,960 ARE THERE DIFFERENCES THAT MIGHT 5770 04:28:39,960 --> 04:28:44,640 INFORM ME TO GO BACK TO REDEFINE 5771 04:28:44,640 --> 04:28:45,840 WHAT TARGET VARIABLE IS AND IT 5772 04:28:45,840 --> 04:28:48,800 IS AN ITERATIVE PROCESS. 5773 04:28:48,800 --> 04:28:50,880 SO, TO GIVE YOU ONE EXAMPLE, I 5774 04:28:50,880 --> 04:28:54,360 SEE DATA SETS WHERE YOU MIGHT 5775 04:28:54,360 --> 04:28:57,280 HAVE MULTIPLE OMICS THAT ARE 5776 04:28:57,280 --> 04:28:58,920 MEASURED SLIGHTLY DIFFERENT 5777 04:28:58,920 --> 04:28:59,960 TIMES THAT COULD BE DIFFERENT BY 5778 04:28:59,960 --> 04:29:01,720 A YEAR OR BY AN HOUR AND WHEN 5779 04:29:01,720 --> 04:29:05,280 YOU ARE TALKING ABOUT SOME OF 5780 04:29:05,280 --> 04:29:12,360 THE OMICS RNA GENE EXPRESSION 5781 04:29:12,360 --> 04:29:17,080 AND PROTEOMICS COULD FOOL YOU. 5782 04:29:17,080 --> 04:29:19,800 IF THEY ARE AN HOUR DIFFERENCE 5783 04:29:19,800 --> 04:29:22,200 OR SOMETHING IS THAT TRULY A 5784 04:29:22,200 --> 04:29:25,880 VALIDATION IS THE QUESTION. 5785 04:29:25,880 --> 04:29:28,280 THE OTHER QUESTION THAT I ELUDED 5786 04:29:28,280 --> 04:29:30,840 TO ARE SUMMARY SCORES VERSUS 5787 04:29:30,840 --> 04:29:33,200 COMPONENTS AND THERE ARE SCORES 5788 04:29:33,200 --> 04:29:35,480 WE USE IN GERIATRICS AND AGING 5789 04:29:35,480 --> 04:29:37,720 AND ARE USEFUL AND WE ARE 5790 04:29:37,720 --> 04:29:38,960 COMFORTABLE WITH THOSE AND WE 5791 04:29:38,960 --> 04:29:41,560 KNOW HOW THEY ARE BUILT AND THEY 5792 04:29:41,560 --> 04:29:43,360 ARE MEANT TO BE AVERAGE AND 5793 04:29:43,360 --> 04:29:46,080 SUMMARY SCORE AND TALKING ABOUT 5794 04:29:46,080 --> 04:29:48,120 EPIGENETIC CLOGS AND AGE 5795 04:29:48,120 --> 04:29:49,200 MEASURES WITH MATHEMATICAL 5796 04:29:49,200 --> 04:29:51,160 MODELS WE ARE NOT BUILDING IT 5797 04:29:51,160 --> 04:29:52,560 FROM GROUND UP WE ARE STARTING 5798 04:29:52,560 --> 04:29:55,440 FROM TOP DOWN. IT IS A BLACK 5799 04:29:55,440 --> 04:29:57,800 BOX. WE DON'T KNOW WHAT ITS 5800 04:29:57,800 --> 04:29:59,720 MEANING OR WHAT IT IS MEASURING 5801 04:29:59,720 --> 04:30:02,560 AND KNOW THAT MAKES US 5802 04:30:02,560 --> 04:30:04,160 UNCOMFORTABLE AS SCIENTISTS AND 5803 04:30:04,160 --> 04:30:05,200 THINK WITH MACHINE LEARNING 5804 04:30:05,200 --> 04:30:07,160 OFTEN TIMES IT IS A BLACK BOX 5805 04:30:07,160 --> 04:30:09,920 THAT IS HARD TO TRY TO UNPACKING 5806 04:30:09,920 --> 04:30:12,320 MECHANISMS BEHIND THAT AND AS 5807 04:30:12,320 --> 04:30:14,560 LONG AS WE VIEW THESE AS 5808 04:30:14,560 --> 04:30:17,400 PREDICTION AND CLASSIFICATION 5809 04:30:17,400 --> 04:30:19,160 PURPOSES, WE MIGHT SLEEP BETTER 5810 04:30:19,160 --> 04:30:21,240 AT NIGHT. I THINK THAT EARLIER 5811 04:30:21,240 --> 04:30:29,200 WE SAW THIS EXAMPLE WHERE YOU Z 5812 04:30:29,200 --> 04:30:30,320 A SYMPTOMATIC EFFECT OR 5813 04:30:30,320 --> 04:30:32,480 CAUSALITY THAT IS IMPORTANT TO 5814 04:30:32,480 --> 04:30:34,440 TEASE OUT TALKING ABOUT 5815 04:30:34,440 --> 04:30:36,280 PREDICTION CLASSIFICATION IT 5816 04:30:36,280 --> 04:30:38,240 DOESN'T MATTER GRAY HAIR IS A 5817 04:30:38,240 --> 04:30:40,320 SIGN OF AGING AS IMPERFECT AS IT 5818 04:30:40,320 --> 04:30:42,640 IS AND THIS IS A EXAMPLE WHERE 5819 04:30:42,640 --> 04:30:44,760 USE CASE MIGHT MATTER AND MY 5820 04:30:44,760 --> 04:30:46,840 LAST SLIDE HERE I WILL LET ALLAN 5821 04:30:46,840 --> 04:30:49,160 TAKE OVER. THEY ARE ALL TOOLS 5822 04:30:49,160 --> 04:30:51,840 AND NOT ALL TOOLS ARE PERFECT 5823 04:30:51,840 --> 04:30:53,560 AND YOU WOULDN'T USE A WRENCH TO 5824 04:30:53,560 --> 04:30:58,480 DRIVE A NAIL THROUGH A 2 x 4 OR 5825 04:30:58,480 --> 04:31:00,200 HAMMER TO SCREW A LUG NUT. WE 5826 04:31:00,200 --> 04:31:03,960 HAVE TO THINK THROUGH REALLY 5827 04:31:03,960 --> 04:31:14,320 TOOLS YOU ARE USING. 5828 04:31:17,320 --> 04:31:21,760 >>HI. THANK YOU TO THE FOUR 5829 04:31:21,760 --> 04:31:23,400 SPEAKERS FOR FOUR GREAT 5830 04:31:23,400 --> 04:31:24,880 PRESENTATIONS AND I PREPARED 5831 04:31:24,880 --> 04:31:28,560 SLIDES AND I WILL GO BACK AND 5832 04:31:28,560 --> 04:31:39,040 NOT USE SLIDES I HAD -- IF WE 5833 04:31:43,880 --> 04:31:47,240 THINK ABOUT OUR SELVES THAT WAY, 5834 04:31:47,240 --> 04:31:48,360 CHANGES QUESTIONS WE ASK AND HOW 5835 04:31:48,360 --> 04:31:49,760 WE THINK ABOUT THINGS AND IN 5836 04:31:49,760 --> 04:31:51,160 PARTICULAR I WOULD LIKE TO GIVE 5837 04:31:51,160 --> 04:31:52,920 YOU THE IDEA THAT MAYBE WE ARE A 5838 04:31:52,920 --> 04:31:56,240 TYPE OF COMPUTER OR INFORMATION 5839 04:31:56,240 --> 04:32:03,160 SYSTEM AND TO KEEP OURSELVES 5840 04:32:03,160 --> 04:32:06,360 GOING WE NEED INTERNAL 5841 04:32:06,360 --> 04:32:07,480 [INDISCERNIBLE] SIMULTANEOUSLY 5842 04:32:07,480 --> 04:32:10,840 TO KEEP PHYSIOLOGY AND BIOLOGY 5843 04:32:10,840 --> 04:32:11,840 IN RIGHT STATE. 5844 04:32:11,840 --> 04:32:14,000 MOST BIOLOGICAL MOLECULES ARE AT 5845 04:32:14,000 --> 04:32:16,880 SAME TIME DOING SOMETHING AND 5846 04:32:16,880 --> 04:32:18,360 GIVING INFORMATION ABOUT SYSTEM 5847 04:32:18,360 --> 04:32:22,360 ATP IS ENERGY AND TELLING YOU 5848 04:32:22,360 --> 04:32:25,200 ENERGY YOU HAVE. IN THAT 5849 04:32:25,200 --> 04:32:26,520 CONTEXT WITH THAT AS A 5850 04:32:26,520 --> 04:32:28,160 BACKGROUND I WOULD LIKE TO MAKE 5851 04:32:28,160 --> 04:32:29,840 A FEW COMMENTS ON THE 5852 04:32:29,840 --> 04:32:30,760 PRESENTATIONS AND ONE THING THAT 5853 04:32:30,760 --> 04:32:33,200 I THINK CUTS ACROSS ALL FOUR OF 5854 04:32:33,200 --> 04:32:36,400 THEM IS REALLY A CHALLENGE AND 5855 04:32:36,400 --> 04:32:38,800 IS A NOTION THAT YOUNGER STATES 5856 04:32:38,800 --> 04:32:40,560 ARE BETTER STATES AND I THINK 5857 04:32:40,560 --> 04:32:42,400 THAT THERE IS A LOT OF CASES 5858 04:32:42,400 --> 04:32:45,000 WHERE CHANGES THAT ARE 5859 04:32:45,000 --> 04:32:47,600 AGE-RELATED ARE PATHOLOGICAL AND 5860 04:32:47,600 --> 04:32:49,200 DON'T THINK ANYBODY WOULD DOUBT 5861 04:32:49,200 --> 04:32:52,880 THAT AND CHAFKS WITH AGE ARE 5862 04:32:52,880 --> 04:32:54,720 ADAPTIVE AND FOR EXAMPLE 5863 04:32:54,720 --> 04:32:57,320 ADOPTIVE IMMUNE SYSTEM HAS 5864 04:32:57,320 --> 04:32:58,560 DECREASED FUNCTION WITH AGE 5865 04:32:58,560 --> 04:33:00,360 WHICH IS A GOOD THING PROBABLY 5866 04:33:00,360 --> 04:33:02,880 IN CONTEXT OF ANCESTRAL 5867 04:33:02,880 --> 04:33:04,560 CONDITION EXPOSED TO PASSAGES 5868 04:33:04,560 --> 04:33:06,800 THAT WE WILL SEE EARLY IN LIFE 5869 04:33:06,800 --> 04:33:09,200 AND SO DOES THAT MEAN THAT ALL 5870 04:33:09,200 --> 04:33:11,560 ASPECTS OF CHANGE HAVE ACTIVE 5871 04:33:11,560 --> 04:33:13,520 IMMUNE SYSTEM ARE ADAPTIVE? 5872 04:33:13,520 --> 04:33:14,840 NOT NECESSARILY AND CHALLENGE IS 5873 04:33:14,840 --> 04:33:16,480 WE DON'T HAVE GOOD WAY TO FIGURE 5874 04:33:16,480 --> 04:33:19,480 OUT WHAT AGE RELATED CHANGES WE 5875 04:33:19,480 --> 04:33:21,560 ARE SEEING THAT ARE PATHOLOGICAL 5876 04:33:21,560 --> 04:33:23,880 ADAPTIVE NEUTRAL CORRELATED IS 5877 04:33:23,880 --> 04:33:25,880 IT ADAPTIVE IN SENSE THAT IT IS 5878 04:33:25,880 --> 04:33:27,040 ALL INDIVIDUALS WILL DO THAT AND 5879 04:33:27,040 --> 04:33:30,360 IT IS RELATIVELY ADAPTIVE OR ONE 5880 04:33:30,360 --> 04:33:32,040 INDIVIDUAL ADAPTING TO HIS OR 5881 04:33:32,040 --> 04:33:33,840 HER PARTICULAR CIRCUMSTANCES AND 5882 04:33:33,840 --> 04:33:36,120 THESE ARE VERY DIFFICULT THINGS 5883 04:33:36,120 --> 04:33:37,400 TO TEASE OUT. 5884 04:33:37,400 --> 04:33:41,240 SO, I FEEL THERE IS OFTEN AN 5885 04:33:41,240 --> 04:33:42,080 UNDERLYING ASSUMPTION THAT YOUNG 5886 04:33:42,080 --> 04:33:44,920 IS GOOD. I THINK THAT DOES 5887 04:33:44,920 --> 04:33:46,800 REFLECT A CULTURAL BIAS WHERE WE 5888 04:33:46,800 --> 04:33:49,200 HAVE LOTS OF INHERENT AGEISM 5889 04:33:49,200 --> 04:33:50,880 THAT IS NOT TRUE IN ALL CULTURES 5890 04:33:50,880 --> 04:33:53,160 ALL THE TIME AND WE HAVE TO BE 5891 04:33:53,160 --> 04:33:55,480 AWARE OF MOST CULTURAL BIAS IN 5892 04:33:55,480 --> 04:33:57,080 THINKING THE YOUNGER STATE IS 5893 04:33:57,080 --> 04:33:59,120 BETTER STATE AND TRYING TO TEASE 5894 04:33:59,120 --> 04:34:02,920 THAT OUT AND A FEW COMMENTS TO 5895 04:34:02,920 --> 04:34:06,360 MORE SPECIFICALLY IN TALKS THAT 5896 04:34:06,360 --> 04:34:09,080 I CAN'T WORK WITH. GENETIC 5897 04:34:09,080 --> 04:34:11,440 AGING AND CURVE WE HAVE THERE 5898 04:34:11,440 --> 04:34:12,960 AND ONE THOUGHT FOR FUTURE WORK 5899 04:34:12,960 --> 04:34:14,800 IN THAT DIRECTION IS DOING THAT 5900 04:34:14,800 --> 04:34:17,040 FOR MORE SPECIES WE MIGHT BE 5901 04:34:17,040 --> 04:34:20,480 ABLE TO PARAMETERIZE THAT SHAPE 5902 04:34:20,480 --> 04:34:22,760 IN DIFFERENT SPECIES IN HOW IT 5903 04:34:22,760 --> 04:34:24,240 VARIES ACROSS SPECIES AND 5904 04:34:24,240 --> 04:34:26,480 LOOKING FOR GENES THAT ARE 5905 04:34:26,480 --> 04:34:27,560 CONTROLLING EVOLUTION OF SHAPE 5906 04:34:27,560 --> 04:34:31,080 OF THAT CURVE THAT MIGHT REFLECT 5907 04:34:31,080 --> 04:34:31,480 DEVELOPMENT. 5908 04:34:31,480 --> 04:34:33,880 THAT IS AN INTERESTING DIRECTION 5909 04:34:33,880 --> 04:34:35,960 TO GO. 5910 04:34:35,960 --> 04:34:38,920 IN TERMS OF DAN'S TALK, R I 5911 04:34:38,920 --> 04:34:40,120 THINK IT IS VERY INTERESTING 5912 04:34:40,120 --> 04:34:43,000 THAT YOU ARE FINDING WITH CANON 5913 04:34:43,000 --> 04:34:45,760 CAL AGING PATHWAYS THAT YOU ARE 5914 04:34:45,760 --> 04:34:47,800 GETTING A MIX OF EFFECTS THAT 5915 04:34:47,800 --> 04:34:51,320 ARE QUOTE ON QUOTE PROAGING AND 5916 04:34:51,320 --> 04:34:53,680 ANTIAGING FROM THE SAME 5917 04:34:53,680 --> 04:34:55,320 INTERVENTION; RIGHT? 5918 04:34:55,320 --> 04:34:57,600 THIS REFLECTS IN MY OPINION THAT 5919 04:34:57,600 --> 04:34:59,400 WE OVERSIMPLIFY THINGS THINKING 5920 04:34:59,400 --> 04:35:02,680 THERE IS A SINGLE AGING 5921 04:35:02,680 --> 04:35:05,560 PHENOMENON. REALLY EACH OF THE 5922 04:35:05,560 --> 04:35:07,080 PATHWAYS IS REGULATING SOME 5923 04:35:07,080 --> 04:35:10,520 THINGS THAT ARE PROAGING OR 5924 04:35:10,520 --> 04:35:12,360 ANTIAGING THINGS WE CAN SAY 5925 04:35:12,360 --> 04:35:14,280 THOSE THAT WILL BE VERY MIXED 5926 04:35:14,280 --> 04:35:16,760 AND EXPECT THAT AND PATHWAYS ARE 5927 04:35:16,760 --> 04:35:19,760 DOING INTEGRATING ABOUT ORGANIZE 5928 04:35:19,760 --> 04:35:22,880 SITUATION AND USING THAT TO 5929 04:35:22,880 --> 04:35:25,200 GENERATE DOWNSTREAM BEST 5930 04:35:25,200 --> 04:35:25,960 CONDITIONS FOR ORGANISM AND 5931 04:35:25,960 --> 04:35:29,200 GIVEN ALL THAT AND DIDN'T HAVE 5932 04:35:29,200 --> 04:35:31,640 ANYTHING SPECIFIC TO ALEX'S TALK 5933 04:35:31,640 --> 04:35:35,000 AND FOR IRINA'S TALK I THOUGHT 5934 04:35:35,000 --> 04:35:38,080 IT WAS INTERESTING OLD FACTORS 5935 04:35:38,080 --> 04:35:39,720 DOMINATE AND THINKING WHAT IT 5936 04:35:39,720 --> 04:35:42,400 MEANS IN ADAPTIVE VERSUS PANEL 5937 04:35:42,400 --> 04:35:44,520 LOGICAL ASPECTS OF AGING AND 5938 04:35:44,520 --> 04:35:46,200 WHAT WE ARE THINKING ABOUT AND I 5939 04:35:46,200 --> 04:35:49,160 REALLY LIKE THE IDEA OF USING 5940 04:35:49,160 --> 04:35:51,360 INCREASING HETEROGENEITY AS 5941 04:35:51,360 --> 04:35:52,920 MEASURE OF BIOLOGICAL AGING AND 5942 04:35:52,920 --> 04:35:54,920 THERE IS A LOT TO BE DONE WITH 5943 04:35:54,920 --> 04:35:56,440 THAT AND IT IS EXCITING TO SEE 5944 04:35:56,440 --> 04:35:58,400 THAT WORK AND STOPPING THERE IF 5945 04:35:58,400 --> 04:36:05,200 WE HAVE TIME FOR QUESTIONS. 5946 04:36:05,200 --> 04:36:09,200 >>[APPLAUSE]. 5947 04:36:09,200 --> 04:36:19,720 >>SO, ANY QUESTIONS FOR US? 5948 04:36:32,120 --> 04:36:36,400 >>HI. I'M FROM UNIVERSITY OF 5949 04:36:36,400 --> 04:36:39,520 CONNECTICUT. I HAVE QUESTIONS 5950 04:36:39,520 --> 04:36:44,080 FOR DR. EHNINGER AND WHAT YOU 5951 04:36:44,080 --> 04:36:46,440 SHOWED, I LOVE THAT YOU DID 3 TO 5952 04:36:46,440 --> 04:36:49,720 5 MONTH THAT WE DO THAT TO LOOK 5953 04:36:49,720 --> 04:36:52,680 AT MATURATION VERSUS AGING AND I 5954 04:36:52,680 --> 04:36:55,160 STUDIED BLADDERS WHEN I COMPARE 5955 04:36:55,160 --> 04:36:57,640 A MOUSE THAT IS 2 TO 4 MONTHS TO 5956 04:36:57,640 --> 04:37:00,240 A MOUSE THAT IS 8 TO 10 MONTHS I 5957 04:37:00,240 --> 04:37:02,400 CONSIDER WHATEVER HAPPENS THERE 5958 04:37:02,400 --> 04:37:04,200 TO BE MATURATION CHANGE AND WHEN 5959 04:37:04,200 --> 04:37:06,400 I COMPARE 8 TO 10 MONTH OLD 5960 04:37:06,400 --> 04:37:08,920 MONTH US TO MY 22 AND HIGHER I 5961 04:37:08,920 --> 04:37:15,120 CONSIDER IT TO BE AN AGIING 5962 04:37:15,120 --> 04:37:18,400 CHANGE AND WHEN YOU DID STUDIES 5963 04:37:18,400 --> 04:37:22,120 DID YOU PICK WHAT WAS CHANGING 5964 04:37:22,120 --> 04:37:24,320 FROM MIDDLE AGE/MATURE AGING TO 5965 04:37:24,320 --> 04:37:26,280 INCLUDE IN FUTURE STUDIES OR 5966 04:37:26,280 --> 04:37:28,680 CONTINUE TO USE ALL ASPS FOR 5967 04:37:28,680 --> 04:37:38,880 THOSE FINAL GENETIC AND DIETARY 5968 04:37:38,880 --> 04:37:40,000 INTERVENTION STUDIES? 5969 04:37:40,000 --> 04:37:41,240 >>CAN YOU HEAR ME? 5970 04:37:41,240 --> 04:37:45,680 >>WE DESIGNED STUDIES SUCH THAT 5971 04:37:45,680 --> 04:37:49,200 ARE YOUNG GROUP THAT IS YOUNG 5972 04:37:49,200 --> 04:37:50,920 ADULT AND COUPLE GROUPS THAT ARE 5973 04:37:50,920 --> 04:37:54,400 CLOSE BY TO SEE WHETHER OR NOT 5974 04:37:54,400 --> 04:37:57,960 MOST PHENOTYPES ARE STABLE 5975 04:37:57,960 --> 04:38:00,400 DURING PERIOD OF YOUNG ADULTHOOD 5976 04:38:00,400 --> 04:38:04,280 AND COVERED UP TO AGE OF 20 5977 04:38:04,280 --> 04:38:11,000 MONTHS THAT IS BEFORE SURVIVAL 5978 04:38:11,000 --> 04:38:12,400 CURVE GOES DOWN AND LOST 5979 04:38:12,400 --> 04:38:15,440 POPULATION AND THERE IS 5980 04:38:15,440 --> 04:38:18,400 SURVIVORSHIP BIAS IN OLDEST 5981 04:38:18,400 --> 04:38:20,240 GROUP AND FUTURE STUDIES WE ARE 5982 04:38:20,240 --> 04:38:23,800 NOT -- THIS IS PART OF 5983 04:38:23,800 --> 04:38:25,880 PHENOTYPING PIPELINE APPROACH 5984 04:38:25,880 --> 04:38:29,160 WHERE YOU OFTEN GET A NUMBER OF 5985 04:38:29,160 --> 04:38:31,960 PHENOTYPES FROM SAME KIND OF 5986 04:38:31,960 --> 04:38:35,040 MEASUREMENT OR FROM THE SAME 5987 04:38:35,040 --> 04:38:38,640 KIND OF EXPERIMENTAL APPROACH 5988 04:38:38,640 --> 04:38:41,200 NOT MEANINGFUL TO RESTRICT TO 5989 04:38:41,200 --> 04:38:43,360 SUBSETS OF PHENOTYPES THAT THERE 5990 04:38:43,360 --> 04:38:46,680 MIGHT BE WITHIN ONE EXPERIMENTAL 5991 04:38:46,680 --> 04:38:48,840 DOMAIN MIGHT BE AGE SENSITIVE 5992 04:38:48,840 --> 04:38:50,040 PHENOTYPES AND OTHERS THAT ARE 5993 04:38:50,040 --> 04:38:51,800 NOT AGE SENSITIVE AND CONTINUE 5994 04:38:51,800 --> 04:38:55,320 TO MEASURE THEM ALL BASICALLY 5995 04:38:55,320 --> 04:39:00,480 AND WE DIDN'T REALLY THEY ARE 5996 04:39:00,480 --> 04:39:02,560 ALL AND ONES THAT CHANGE EARLY 5997 04:39:02,560 --> 04:39:05,120 ON AS I SHOWED AN EXAMPLE AT 5998 04:39:05,120 --> 04:39:06,240 HEARING LOSS; RIGHT? 5999 04:39:06,240 --> 04:39:09,800 THIS IS SOMETHING THAT IS VERY 6000 04:39:09,800 --> 04:39:10,760 SPECIFIC TO THAT PARTICULAR 6001 04:39:10,760 --> 04:39:16,000 MOUSE STRAIN; RIGHT? THERE ARE 6002 04:39:16,000 --> 04:39:20,800 OTHER ONES THAT YOU DO SEE EARLY 6003 04:39:20,800 --> 04:39:23,040 CHANGE CONTINUING TO PROGRESS 6004 04:39:23,040 --> 04:39:26,240 EARLY AGE TO REFLECT SOMETHING 6005 04:39:26,240 --> 04:39:33,800 YOU CONSIDER AGING AND REDUCTION 6006 04:39:33,800 --> 04:39:38,360 OF CD4 T-CELLS AND PHENOTYPES IN 6007 04:39:38,360 --> 04:39:39,120 PATHOLOGIES IN PARTICULAR YOU 6008 04:39:39,120 --> 04:39:42,400 SEE THOSE EMERGING IN OLDER AGE 6009 04:39:42,400 --> 04:39:44,320 GROUPS THAT MIGHT BE WHAT WE 6010 04:39:44,320 --> 04:39:48,720 CLASSICALLY THINK OF AS AGING 6011 04:39:48,720 --> 04:39:49,160 PHENOTYPES. 6012 04:39:49,160 --> 04:39:52,120 >>THANK YOU. 6013 04:39:52,120 --> 04:39:54,200 ANOTHER QUESTION FOR YOU. FOR 6014 04:39:54,200 --> 04:39:56,240 JEANETTE KALILY TWO MODELS YOU 6015 04:39:56,240 --> 04:39:58,640 SHOWED WITH GENETIC TREATMENTS 6016 04:39:58,640 --> 04:40:02,440 WERE THEY UNUSABLE OR WERE THEY 6017 04:40:02,440 --> 04:40:06,280 I MISSED THAT PART WERE THEY 6018 04:40:06,280 --> 04:40:07,880 MUTATED? 6019 04:40:07,880 --> 04:40:18,400 >>[INDISCERNIBLE] -- IT IS NOT 6020 04:40:20,680 --> 04:40:23,720 KNOWN SPECIFIC STRAINS 6021 04:40:23,720 --> 04:40:24,960 GENETICALLY MODIFIED ONES WE 6022 04:40:24,960 --> 04:40:26,440 DON'T KNOW HOW THEY AGED 6023 04:40:26,440 --> 04:40:28,840 DIFFERENTLY TO CONTROL IF USED 6024 04:40:28,840 --> 04:40:30,400 OUT OF MIDDLE AGE I GUESS YOU 6025 04:40:30,400 --> 04:40:32,400 WOULD BE ABLE TO TELL IF I 6026 04:40:32,400 --> 04:40:36,760 WONDER ABOUT HAVING COMPARED 6027 04:40:36,760 --> 04:40:40,080 THEM WILD TYPE C57 CAN YOU 6028 04:40:40,080 --> 04:40:41,160 COMMENT ON THAT? 6029 04:40:41,160 --> 04:40:44,360 >>GROUPS WE HAVE FOR GENETIC 6030 04:40:44,360 --> 04:40:46,840 LINES AND YOUNG ADULTHOOD AND 6031 04:40:46,840 --> 04:40:49,160 COMPARISON OF 20 MONTHS OF AGE 6032 04:40:49,160 --> 04:40:51,840 AND WE HAVE TWO SNAPSHOTS THAT 6033 04:40:51,840 --> 04:40:53,440 ARE CROSS-SECTION ALLEY ACROSS 6034 04:40:53,440 --> 04:40:56,360 LIFESPAN OF THESE WHERE WE CAN 6035 04:40:56,360 --> 04:40:58,440 ESTIMATE INTERVENTION EFFECTS IN 6036 04:40:58,440 --> 04:41:00,720 THAT PARTICULAR CASE GENOTYPE 6037 04:41:00,720 --> 04:41:02,840 EFFECTS AND COMPARE THEM TO 6038 04:41:02,840 --> 04:41:05,800 GENOTYPE EFFECTS YOU SEE IN AGE 6039 04:41:05,800 --> 04:41:06,360 ALMOST RIGHT. 6040 04:41:06,360 --> 04:41:07,640 >>FOR SAME STREAM. 6041 04:41:07,640 --> 04:41:09,080 >>FOR SAME STREAM? 6042 04:41:09,080 --> 04:41:11,800 >>THAT IS ALL SAME STREAM. 6043 04:41:11,800 --> 04:41:13,080 THIS IS ALL EXCHANGE. 6044 04:41:13,080 --> 04:41:15,920 >>THANK YOU. 6045 04:41:15,920 --> 04:41:16,280 >>WELCOME. 6046 04:41:16,280 --> 04:41:18,320 >>GENERAL QUESTION ABOUT 6047 04:41:18,320 --> 04:41:19,800 PHENOTYPE WE SEE IN MULTIPLE 6048 04:41:19,800 --> 04:41:22,120 AGING SYSTEMS THAT IS UP 6049 04:41:22,120 --> 04:41:24,080 REGULATION OF PROCESSES AND 6050 04:41:24,080 --> 04:41:26,320 PROTEINS AND GENES AT MOLECULAR 6051 04:41:26,320 --> 04:41:28,120 LEVEL THAT IS WHAT SEEMED LIKE 6052 04:41:28,120 --> 04:41:31,440 GAIN OF FUNCTION IN TERMS OF 6053 04:41:31,440 --> 04:41:33,880 SIGNALING OR SENESCENCE PROFILE 6054 04:41:33,880 --> 04:41:38,000 AND GENES INDUCED WITH EACH AND 6055 04:41:38,000 --> 04:41:39,880 PHENOTYPIC LEVEL WE SEE LOSS OF 6056 04:41:39,880 --> 04:41:43,240 FUNCTION AND DECLINE IN SENSORY 6057 04:41:43,240 --> 04:41:44,560 CAPABILITIES AND LOCOMOTION AND 6058 04:41:44,560 --> 04:41:46,760 THINGS AND SEEMS LIKE 6059 04:41:46,760 --> 04:41:48,360 INTERESTING PARADOX AND WONDER 6060 04:41:48,360 --> 04:41:51,840 NOT SURE IF IRINA IS STILL THERE 6061 04:41:51,840 --> 04:41:53,960 AND HER EXPERIMENTS DILUTING 6062 04:41:53,960 --> 04:41:56,680 BLOOD OF OLD ANIMALS AND 6063 04:41:56,680 --> 04:41:58,120 RESCUING THIS GAIN OF FUNCTION 6064 04:41:58,120 --> 04:42:00,760 AND MORE SIGNALING PROTEINS AND 6065 04:42:00,760 --> 04:42:01,920 CIRCULATION AND SOMEHOW THIS 6066 04:42:01,920 --> 04:42:06,280 ENDS UP IMPROVING AGING RELATED 6067 04:42:06,280 --> 04:42:07,200 PHENOTYPES AND ONE POSSIBILITY 6068 04:42:07,200 --> 04:42:09,160 THERE COULD BE THAT HAVING A LOT 6069 04:42:09,160 --> 04:42:11,880 OF SIGNALING FACTORS AND 6070 04:42:11,880 --> 04:42:13,040 CIRCULATION COSTS A LOT TO 6071 04:42:13,040 --> 04:42:14,440 ORGANISM AND IF WE THINK THERE 6072 04:42:14,440 --> 04:42:18,400 IS A FINITE AMOUNT OF ENERGY 6073 04:42:18,400 --> 04:42:20,320 THAT AGING ORGANISM HAS ACCESS 6074 04:42:20,320 --> 04:42:23,520 TO AND ENERGY IS MONOPOLIZED BY 6075 04:42:23,520 --> 04:42:25,920 PRODUCING FACTORS AND HAVING TO 6076 04:42:25,920 --> 04:42:28,760 FOR TARGET ORGANS TO EXPERIENCE 6077 04:42:28,760 --> 04:42:31,920 SIGNALING EFFECTS OF THIS AND 6078 04:42:31,920 --> 04:42:34,520 ALL THESE DIFFERENT STEPS OF 6079 04:42:34,520 --> 04:42:36,480 THESE COST ENERGY RELIEVING 6080 04:42:36,480 --> 04:42:39,280 THAT, THAT MAYBE FREES UP ENERGY 6081 04:42:39,280 --> 04:42:43,360 BUDGET THAT ALLOWS HIGHER LEVEL 6082 04:42:43,360 --> 04:42:45,600 FUNCTIONS AND NEEDING TO OPERATE 6083 04:42:45,600 --> 04:42:47,800 MORE EFFECTIVELY. 6084 04:42:47,800 --> 04:42:51,280 IF SOMEONE CAN COMMENT ON THIS. 6085 04:42:51,280 --> 04:42:54,480 >>I WILL TURN TO DR. FARUCHI TO 6086 04:42:54,480 --> 04:42:56,760 COMMENT ON THEORY OF ADAPTATION 6087 04:42:56,760 --> 04:42:59,800 AND HOW THAT IS BEHIND SCENES 6088 04:42:59,800 --> 04:43:01,280 HOUSEKEEPING THAT IS HAPPENING. 6089 04:43:01,280 --> 04:43:03,600 >>MY QUESTION IS RELATED VERY 6090 04:43:03,600 --> 04:43:05,600 MUCH AND PUTTING IN PERSPECTIVE 6091 04:43:05,600 --> 04:43:07,320 AND THINK THAT FOR THE MOMENT 6092 04:43:07,320 --> 04:43:12,440 THAT WE BELIEVE THAT AGING IS 6093 04:43:12,440 --> 04:43:13,840 RATIO BETWEEN SKOE CASTIC DAMAGE 6094 04:43:13,840 --> 04:43:15,560 OF AACCUMULATE LAITION AND 6095 04:43:15,560 --> 04:43:19,120 STRATEGIES PREVENTING AND 6096 04:43:19,120 --> 04:43:21,280 REPAIRING THAT DAMAGE AND MY 6097 04:43:21,280 --> 04:43:23,320 IDEA IS THAT HAS TO BE DIFFERENT 6098 04:43:23,320 --> 04:43:26,200 RATE OF AGING AND COST DIFFERENT 6099 04:43:26,200 --> 04:43:28,680 TISSUES BECAUSE DEMAND OF ENERGY 6100 04:43:28,680 --> 04:43:30,440 IN DIFFERENT TISSUE IS 6101 04:43:30,440 --> 04:43:30,760 DIFFERENT. 6102 04:43:30,760 --> 04:43:34,120 YOU KNOW, MUSCLE AND BRAIN AND 6103 04:43:34,120 --> 04:43:36,440 HEART WILL HAVE ENORMOUS AMOUNT 6104 04:43:36,440 --> 04:43:42,200 OF DEMAND. THERE WILL BE ENERGY 6105 04:43:42,200 --> 04:43:45,200 MUCH SOONER AND SISTER WILL BE 6106 04:43:45,200 --> 04:43:47,040 CRITICALLY IMPACTED FASTER THAN 6107 04:43:47,040 --> 04:43:49,040 ANOTHER TISSUE THAT IS 6108 04:43:49,040 --> 04:43:50,640 ACQUIESCIENT OR CALLED INTO 6109 04:43:50,640 --> 04:43:52,840 ACTION AND YOU KNOW MUCH, MUCH 6110 04:43:52,840 --> 04:43:53,040 LESS. 6111 04:43:53,040 --> 04:43:55,040 SO, I THINK THAT, YOU KNOW, WHEN 6112 04:43:55,040 --> 04:43:57,680 WE SAY WE NEED TO BE CAREFUL 6113 04:43:57,680 --> 04:44:00,240 ABOUT FINDING -- IT IS USEFUL 6114 04:44:00,240 --> 04:44:02,200 FOR CLINICALLY TO FIND A 6115 04:44:02,200 --> 04:44:05,200 BIOMARKER OF AGING THAT IS 6116 04:44:05,200 --> 04:44:06,560 UNIQUE AND THERE IS AVERAGE AGE 6117 04:44:06,560 --> 04:44:08,360 ON [INDISCERNIBLE] AND I HAVE 6118 04:44:08,360 --> 04:44:09,680 ANOTHER QUESTION. CAN I ASK 6119 04:44:09,680 --> 04:44:11,840 ANOTHER QUESTION THAT I THINK IS 6120 04:44:11,840 --> 04:44:14,160 RELATED. OTHER RELATED QUESTION 6121 04:44:14,160 --> 04:44:16,480 IS THAT IN ALL THESE 6122 04:44:16,480 --> 04:44:18,440 DISCUSSIONS, I HAVE NOT HEARD 6123 04:44:18,440 --> 04:44:20,240 SOMETHING THAT TO ME IS 6124 04:44:20,240 --> 04:44:21,920 EXTREMELY IMPORTANT THAT IS 6125 04:44:21,920 --> 04:44:24,480 EPIGENETIC THAT IS REALLY THE 6126 04:44:24,480 --> 04:44:29,200 WAY THAT THE SYSTEM CHANGES AND 6127 04:44:29,200 --> 04:44:30,080 TRANSCRIPTIONAL PROGRAM WITHIN 6128 04:44:30,080 --> 04:44:32,880 ONE LIFE IS NOT -- YOU KNOW, 6129 04:44:32,880 --> 04:44:35,320 INDEPENDENT BY EVOLUTION IN A 6130 04:44:35,320 --> 04:44:37,560 WAY. IF YOU CAN CHANGE THAT 6131 04:44:37,560 --> 04:44:38,960 WITHIN ONE LIFE COURSE. 6132 04:44:38,960 --> 04:44:42,240 SO, TO ME, EPIGENETICS IS 6133 04:44:42,240 --> 04:44:45,160 ADAPTIVE AND WHY WE ARE LOOKING 6134 04:44:45,160 --> 04:44:46,720 AT EPIGENETIC AS A CAUSE OF 6135 04:44:46,720 --> 04:44:48,160 DISEASE AND WE ARE NOT LOOKING 6136 04:44:48,160 --> 04:44:52,280 AT EPIGENETIC AS, YOU KNOW, 6137 04:44:52,280 --> 04:44:53,200 ADAPTIVE STRATEGY THAT WE FOUND 6138 04:44:53,200 --> 04:44:55,360 THAT IS RELATED TO AGING BECAUSE 6139 04:44:55,360 --> 04:44:57,840 WITH AGING AND ACCUMULATION OF 6140 04:44:57,840 --> 04:45:00,440 DAMAGE, YOU HAVE TO READJUST 6141 04:45:00,440 --> 04:45:03,480 YOUR GENETIC AND GENOMIC PROGRAM 6142 04:45:03,480 --> 04:45:05,880 TO ADAPT TO THESE LOSS OF 6143 04:45:05,880 --> 04:45:09,160 FUNCTION AND YOU NEED COMPLEXITY 6144 04:45:09,160 --> 04:45:11,360 AND BECAUSE PROBABLY NATURAL 6145 04:45:11,360 --> 04:45:13,120 FUNCTION IS SIMPLE AND DIRECT. 6146 04:45:13,120 --> 04:45:16,360 YOU NEED TO FIND ALTERNATIVE 6147 04:45:16,360 --> 04:45:17,240 STRATEGIES AND THOSE NEED MUCH 6148 04:45:17,240 --> 04:45:21,000 MORE COMPLEXITY OF ACTION FROM 6149 04:45:21,000 --> 04:45:21,880 THE GENOME. 6150 04:45:21,880 --> 04:45:26,000 >>SOMEWHAT RELATED. 6151 04:45:26,000 --> 04:45:28,480 >>I WILL SAY THAT I COMPLETELY 6152 04:45:28,480 --> 04:45:31,800 AGREE WITH THAT AND THAT IS AN 6153 04:45:31,800 --> 04:45:33,320 EXCELLENT EXAMPLE OF WHERE 6154 04:45:33,320 --> 04:45:34,640 ADAPTATION MIGHT BE COMING IN 6155 04:45:34,640 --> 04:45:37,360 AND WE HAVE WORK IT DO TO TRY TO 6156 04:45:37,360 --> 04:45:40,080 FIGURE OUT HOW TO DISTINGUISH 6157 04:45:40,080 --> 04:45:41,200 ASPECTS THAT ARE PANEL LOGICAL 6158 04:45:41,200 --> 04:45:42,840 OR ADAPTIVE THERE. 6159 04:45:42,840 --> 04:45:46,080 >>I WILL STICK UP FOR 6160 04:45:46,080 --> 04:45:47,080 EPIGENETICS AND I THINK THERE IS 6161 04:45:47,080 --> 04:45:49,120 SOMETHING THAT IS UNIQUE WITH 6162 04:45:49,120 --> 04:45:52,200 AGING AND IN PARTICULAR WITH 6163 04:45:52,200 --> 04:45:54,320 EPIGENETICS HEARING OF ORIGIN 6164 04:45:54,320 --> 04:45:58,160 STORIES OF EPIGENETIC CLOCKS 6165 04:45:58,160 --> 04:45:59,560 THEY ARE ALWAYS LOOKING FOR 6166 04:45:59,560 --> 04:46:01,640 SOMETHING ELSE AND SIGNAL FROM 6167 04:46:01,640 --> 04:46:04,040 AGING IS ABSURDLY LOUD AND THEY 6168 04:46:04,040 --> 04:46:05,040 COULDN'T DROWN IT OUT AND 6169 04:46:05,040 --> 04:46:06,840 SHIFTED TO LOOKING AT THAT. 6170 04:46:06,840 --> 04:46:07,880 THERE IS SOMETHING UNIQUE THERE. 6171 04:46:07,880 --> 04:46:11,360 WE ARE ASKING TOO MUCH OUT OF 6172 04:46:11,360 --> 04:46:12,600 EPIGENETICS TO TRY TO EXPLAIN 6173 04:46:12,600 --> 04:46:14,680 ALL OF BIOLOGY FOR US AND AGREE 6174 04:46:14,680 --> 04:46:16,320 WE HAVE TO LOOK DEEPER. 6175 04:46:16,320 --> 04:46:21,960 >>DO YOU THINK WE NEED MORE 6176 04:46:21,960 --> 04:46:26,080 CLOCKS, MORE SPECIFIC CLOCKS AND 6177 04:46:26,080 --> 04:46:28,080 TISSUE SPECIFIC CLOCKS FOR MAYBE 6178 04:46:28,080 --> 04:46:29,200 DIFFERENT POPULATIONS? 6179 04:46:29,200 --> 04:46:31,960 WE HAVE ALREADY MANY, MANY. 6180 04:46:31,960 --> 04:46:34,480 >>YEAH. I THINK. 6181 04:46:34,480 --> 04:46:37,080 >>THIS IS AN OPEN QUESTION TO 6182 04:46:37,080 --> 04:46:39,720 MYSELF AND PROBABLY TO YOU TOO. 6183 04:46:39,720 --> 04:46:40,840 >>SUCH AN IMPORTANT QUESTION 6184 04:46:40,840 --> 04:46:43,040 AND THINK THAT WE HAVE TO DREAM 6185 04:46:43,040 --> 04:46:43,720 BIG. 6186 04:46:43,720 --> 04:46:47,000 WHEN WE DREAM BIG WE NEED TO 6187 04:46:47,000 --> 04:46:50,280 HAVE AN EPIGENETIC CLOCK THAT 6188 04:46:50,280 --> 04:46:53,160 APPLIES TO A PATIENT AND COMES 6189 04:46:53,160 --> 04:46:55,360 TO YOU BECAUSE THEY HAVE 6190 04:46:55,360 --> 04:46:57,120 [INDISCERNIBLE] IN LEFT 6191 04:46:57,120 --> 04:47:00,160 SHOULDER. YOU CAN DO EPIGENETIC 6192 04:47:00,160 --> 04:47:02,000 CLOCK AND SAY THIS PERSON HAS 6193 04:47:02,000 --> 04:47:06,800 THAT AND IS BRINGING THIS PERSON 6194 04:47:07,280 --> 04:47:09,320 OBSERVATION AND HAS IMPENDING 6195 04:47:09,320 --> 04:47:13,200 PROBLEM THAT IS RTERY AND 6196 04:47:13,200 --> 04:47:17,160 IMPENDING CARCINOMA INSITU THAT 6197 04:47:17,160 --> 04:47:19,200 IS SOMEWHERE ELSE AND IS TYPES 6198 04:47:19,200 --> 04:47:20,680 OF DETAIL WE DREAM TO HAVE. 6199 04:47:20,680 --> 04:47:24,320 THAT MEANS THAT WHY IT IS USEFUL 6200 04:47:24,320 --> 04:47:27,720 TO START WITH SOMETHING THAT IS 6201 04:47:27,720 --> 04:47:28,040 AVERAGE. 6202 04:47:28,040 --> 04:47:31,520 WE NEED TO BE ABLE TO GRAB A LOT 6203 04:47:31,520 --> 04:47:33,760 MORE INFORMATION. THERE IS 6204 04:47:33,760 --> 04:47:35,360 EVIDENCE THAT IS DOABLE, 6205 04:47:35,360 --> 04:47:38,480 ACTUALLY. I THINK THAT SOME 6206 04:47:38,480 --> 04:47:40,600 WORK THAT IS INDELIVERABLE SHOWS 6207 04:47:40,600 --> 04:47:43,960 THAT THERE IS SOME SPECIFICITY 6208 04:47:43,960 --> 04:47:48,320 OF DIFFERENCE OF APGS FOR 6209 04:47:48,320 --> 04:47:49,720 PREDICTION OF SPECIFIC DISEASE. 6210 04:47:49,720 --> 04:47:52,160 >>IF I CAN RIFF ON THAT, I 6211 04:47:52,160 --> 04:47:53,280 THINK THERE IS INFORMATION 6212 04:47:53,280 --> 04:47:56,640 COMING OUT THAT WE CAN 6213 04:47:56,640 --> 04:48:00,480 DECONVOLUTE CELL TYPES WITH 6214 04:48:00,480 --> 04:48:02,080 EPIGENETICS AND MENL ILL OHM AND 6215 04:48:02,080 --> 04:48:04,920 BEING PRECISE IN WHAT WE PREDICT 6216 04:48:04,920 --> 04:48:06,760 AND TRAIN AND GETTING CLOCKS NOT 6217 04:48:06,760 --> 04:48:09,200 JUST CLOCKS BUT PREDICTORS OF 6218 04:48:09,200 --> 04:48:11,920 MANY DIFFERENT THINGS AND DOG 6219 04:48:11,920 --> 04:48:13,240 HOMEWORK UPSTREAM TO BE PRECISE 6220 04:48:13,240 --> 04:48:22,400 ABOUT WHAT WE WANT TO PREDICT. 6221 04:48:22,400 --> 04:48:24,160 >>HI. I THINK IT HAS BEEN SAID 6222 04:48:24,160 --> 04:48:28,200 AT THIS POINT I HAVE BEEN 6223 04:48:28,200 --> 04:48:29,640 LISTENING IN. [INDISCERNIBLE] 6224 04:48:29,640 --> 04:48:31,520 QUESTION ABOUT WHY WE ARE 6225 04:48:31,520 --> 04:48:34,120 FOCUSING ON EPIGENETICS AND 6226 04:48:34,120 --> 04:48:35,720 COMPLETELY AGREE WITH THE 6227 04:48:35,720 --> 04:48:38,360 QUESTION AND BRIAN'S ANSWER AND 6228 04:48:38,360 --> 04:48:40,040 IT IS CERTAINLY QUITE 6229 04:48:40,040 --> 04:48:40,360 DIAGNOSTIC. 6230 04:48:40,360 --> 04:48:42,000 YOU KNOW, THERE HAS BEEN A LOT 6231 04:48:42,000 --> 04:48:45,200 OF WORK TO LOOK AT HOW MUCH 6232 04:48:45,200 --> 04:48:48,480 INFORMATION IS IN METHYLOME 6233 04:48:48,480 --> 04:48:50,040 VERSUS TRANSCRIPTOME AND 6234 04:48:50,040 --> 04:48:51,920 TELOMERES AND THINGS LIKE THAT 6235 04:48:51,920 --> 04:48:54,440 AND IS CERTAINLY VERY 6236 04:48:54,440 --> 04:48:56,560 QUANTITATIVE AND COMPLETELY 6237 04:48:56,560 --> 04:49:00,280 AGREE WITH EXTENSION TO WORK 6238 04:49:00,280 --> 04:49:10,760 TOWARDS CAUSAL -- YOU KNOW 6239 04:49:12,560 --> 04:49:15,160 INTERESTING QUESTION THAT IS NOT 6240 04:49:15,160 --> 04:49:17,000 ONLY QUESTION. 6241 04:49:17,000 --> 04:49:18,520 >>ROUND OF APPLAUSE FOR 6242 04:49:18,520 --> 04:49:22,760 SPEAKERS AND PANEL IFTS AND 6243 04:49:22,760 --> 04:49:24,200 RECONVENING AT 3:20. 6244 04:49:24,200 --> 04:49:28,040 >>IT IS 3:24. 6245 04:49:28,040 --> 04:49:29,720 WE SHOULD PROBABLY GET STARTED 6246 04:49:29,720 --> 04:49:31,640 AND LAST SESSION OF THE DAY. 6247 04:49:31,640 --> 04:49:33,720 ONLY THING THAT STANDS BETWEEN 6248 04:49:33,720 --> 04:49:36,080 YOU AND AFTER DINNER DRINKS OR 6249 04:49:36,080 --> 04:49:37,680 DINNER ITSELF IS US. THANKS 6250 04:49:37,680 --> 04:49:41,640 VERY MUCH. WE WILL TALK ABOUT 6251 04:49:41,640 --> 04:49:43,320 BIOMARKERS FOR GEROSCIENCE AND 6252 04:49:43,320 --> 04:49:45,280 HAVE A NICE LINEUP OF SPEAKERS 6253 04:49:45,280 --> 04:49:47,640 TO COVER THIS TOPIC. I'M REALLY 6254 04:49:47,640 --> 04:49:50,000 HAPPY FOR THOSE AND IT 6255 04:49:50,000 --> 04:49:51,720 DOVE-TAILS NICELY WITH SOME 6256 04:49:51,720 --> 04:49:55,880 OTHER TALKS THAT PRECEDED THIS. 6257 04:49:55,880 --> 04:50:02,320 WE WILL FIRST HEAR FROM STEVE 6258 04:50:02,320 --> 04:50:06,960 KRICH EF SKI AND ALICE KANE 6259 04:50:06,960 --> 04:50:08,960 FOLLOWED BY A PANEL DISCUSSION 6260 04:50:08,960 --> 04:50:10,840 WRAP-UP AND BRINGING STEVE UP 6261 04:50:10,840 --> 04:50:13,360 FOR THE FIRST TALK. HE IS MY 6262 04:50:13,360 --> 04:50:15,600 MENTOR AT WAKE FOREST SCHOOL OF 6263 04:50:15,600 --> 04:50:18,440 MEDICINE AND PROFESSOR OF 6264 04:50:18,440 --> 04:50:22,040 GEROSCIENCE AND INTERNAL 6265 04:50:22,040 --> 04:50:32,120 MEDICINE AT WAKE FOR EEST STEVE 6266 04:50:32,120 --> 04:50:35,600 RESEARCH FOCUSES ON NUTRITIONAL 6267 04:50:35,600 --> 04:50:39,040 INFLUENCES IN OLDER ADULTS AND 6268 04:50:39,040 --> 04:50:43,640 ESTABLISHING FRAMEWORKS FOR 6269 04:50:43,640 --> 04:50:45,080 CLINICAL SCIENCE AND EXTENSIVE 6270 04:50:45,080 --> 04:50:47,240 WORK IN BIOMARKERS. 6271 04:50:47,240 --> 04:50:51,040 >>I HAVE ENJOYED THIS 6272 04:50:51,040 --> 04:50:53,200 CONFERENCE SO FAR AND GUESSING I 6273 04:50:53,200 --> 04:50:56,760 DON'T HAVE TO PUSH ANYTHING. 6274 04:50:56,760 --> 04:51:07,000 THERE WE GO. 6275 04:51:07,720 --> 04:51:11,120 SO, I WANT TO REALLY LEVEL SET 6276 04:51:11,120 --> 04:51:16,720 IN THIS TALK. BIOMARKERS IS A 6277 04:51:16,720 --> 04:51:18,680 FRAUGHT AREA AND LOTS OF TIMES 6278 04:51:18,680 --> 04:51:20,800 ALL PEOPLE USING WORD THAT IS 6279 04:51:20,800 --> 04:51:21,960 SOMETHING DIFFERENT AND TALKING 6280 04:51:21,960 --> 04:51:23,240 ABOUT HOW TO MAKE SENSE OUT OF 6281 04:51:23,240 --> 04:51:26,280 ALL OF THE WAYS THAT PEOPLE USE 6282 04:51:26,280 --> 04:51:29,160 WORD BIOMARKERS AND TALKING 6283 04:51:29,160 --> 04:51:32,240 ABOUT THEIR VALIDATION AND IN 6284 04:51:32,240 --> 04:51:35,520 PARTICULAR WITH REFERENCE TO 6285 04:51:35,520 --> 04:51:37,040 BIOMARKERS OF AGE AND TALKING 6286 04:51:37,040 --> 04:51:39,880 ABOUT A HOLY GRAIL FOR THE FIELD 6287 04:51:39,880 --> 04:51:42,840 THAT IS DEVELOPMENT OF VALIDATED 6288 04:51:42,840 --> 04:51:45,160 SURROGATE BIOMARKERS SO WE HAVE 6289 04:51:45,160 --> 04:51:47,640 THINGS WE CAN TRACK SO THAT IF 6290 04:51:47,640 --> 04:51:49,320 WE INTERVENE ON SOMEBODY AND 6291 04:51:49,320 --> 04:51:53,160 THAT BIOMARKER CHANGES, WE ARE 6292 04:51:53,160 --> 04:51:54,720 CONFIDENT WE HAVE HAD SOME 6293 04:51:54,720 --> 04:51:57,600 IMPORTANT BENEFIT FOR THEIR 6294 04:51:57,600 --> 04:52:00,240 LIFESPAN OR HEALTH SPAN. 6295 04:52:00,240 --> 04:52:03,040 THIS IS TOWER OF BABEL AND OFTEN 6296 04:52:03,040 --> 04:52:05,440 I FEEL THIS WAY IN THIS FIELD. 6297 04:52:05,440 --> 04:52:10,960 PEOPLE ARE ALL USING THE WORD 6298 04:52:10,960 --> 04:52:17,680 BIOMARKER IN DIFFERENT WAYS AND 6299 04:52:17,680 --> 04:52:19,640 FDNC ACT -- MOST PEOPLE IN THIS 6300 04:52:19,640 --> 04:52:20,920 ROOM PROBABLY MEAN SOMETHING 6301 04:52:20,920 --> 04:52:23,440 THAT YOU MEASURE IN A TISSUE AND 6302 04:52:23,440 --> 04:52:25,400 IN BLOOD AND DON'T HAVE TO BE 6303 04:52:25,400 --> 04:52:27,600 AND COULD BE ANYTHING AND 6304 04:52:27,600 --> 04:52:29,080 BIOMARKER COULD BE AN INDIVIDUAL 6305 04:52:29,080 --> 04:52:30,200 MEASURE OR PANEL AND DOESN'T 6306 04:52:30,200 --> 04:52:36,120 HAVE TO BE A SINGLE ENTITY. 6307 04:52:36,120 --> 04:52:40,320 FDA IN THE GUIDEBOOK IN THE 6308 04:52:40,320 --> 04:52:41,960 FOOTNOTE THERE DISTINGUISHES 7 6309 04:52:41,960 --> 04:52:45,960 APPLICATIONS OF BIOMARKERS AND 6310 04:52:45,960 --> 04:52:47,840 PEOPLE USE THE WORD AND MEAN 6311 04:52:47,840 --> 04:52:50,480 SOME WORD OR SET OF THESE AND 6312 04:52:50,480 --> 04:52:52,080 OTHERS VARIOUSLY AND IS UP TO 6313 04:52:52,080 --> 04:52:55,600 YOU USUALLY TO FIGURE OUT WHICH 6314 04:52:55,600 --> 04:53:00,200 ONE RUNNING THROUGH THEM IS 6315 04:53:00,200 --> 04:53:01,960 SUSCEPTIBILITY OF RISK MARKER 6316 04:53:01,960 --> 04:53:03,000 FOR DEVELOPING DISEASE OR 6317 04:53:03,000 --> 04:53:05,120 CONDITION AND DIAGNOSTIC 6318 04:53:05,120 --> 04:53:07,600 BIOMARKER THAT TELLS YOU A 6319 04:53:07,600 --> 04:53:09,760 PERSON HAS A DISEASE OR 6320 04:53:09,760 --> 04:53:11,640 CONDITION AND PROGNOSTIC 6321 04:53:11,640 --> 04:53:13,680 BIOMARKER THAT IDENTIFIED A 6322 04:53:13,680 --> 04:53:18,000 LIKELIHOOD OF CLINICAL EVENT 6323 04:53:18,000 --> 04:53:19,240 DISEASE REOCCURRENCE OR 6324 04:53:19,240 --> 04:53:22,720 PROGRESSION AND A PREDICTIVE 6325 04:53:22,720 --> 04:53:24,560 BIOMARKER IF A PERSON IS LIKELY 6326 04:53:24,560 --> 04:53:26,480 TO HAVE A RESPONSE THAT IS BASED 6327 04:53:26,480 --> 04:53:28,680 ON AN INTERVENTION AND OF 6328 04:53:28,680 --> 04:53:30,800 MONITORING BIOMARKER THAT IS 6329 04:53:30,800 --> 04:53:34,400 SOMETHING THAT WOULD MEASURE 6330 04:53:34,400 --> 04:53:37,200 REPEATEDLY TO LOOK FOR EVIDENCE 6331 04:53:37,200 --> 04:53:40,640 OF EXPOSURE OR EFFECT OF AN 6332 04:53:40,640 --> 04:53:45,080 AGENT. SAFETY BIOMARKERS 6333 04:53:45,080 --> 04:53:47,520 INDICATING LIKELIHOOD OF 6334 04:53:47,520 --> 04:53:49,640 PRESENCE OF TOXICITY AND 6335 04:53:49,640 --> 04:53:52,000 RESPONSE TO BIOMARKER AND ARE 6336 04:53:52,000 --> 04:53:55,760 HERE TWO FLAVORS FARMICO DYNAMIC 6337 04:53:55,760 --> 04:53:58,000 THAT INDICATES BILOGIC ACTIVITY 6338 04:53:58,000 --> 04:54:01,520 OF AGENT THAT YOU ARE GIVING 6339 04:54:01,520 --> 04:54:02,920 SOMEBODY AND A SUR ENDPOINT THAT 6340 04:54:02,920 --> 04:54:05,560 I WILL TALK ABOUT LATER THAT IS 6341 04:54:05,560 --> 04:54:08,840 A SUBSTITUTE FOR A DIRECT 6342 04:54:08,840 --> 04:54:11,640 MEASURE OF HOW A PATIENT FEELS 6343 04:54:11,640 --> 04:54:14,840 THAT FUNCTIONS SURVIVE AND A 6344 04:54:14,840 --> 04:54:16,520 BIOMARKER COULD SERVE MANY ROLES 6345 04:54:16,520 --> 04:54:18,640 AND BLOOD PRESSURE IS A GOOD 6346 04:54:18,640 --> 04:54:20,640 EXAMPLE IF IN CONTINUOUS FORM 6347 04:54:20,640 --> 04:54:24,760 AND IS A RISK BIOMARKER AND IN 6348 04:54:24,760 --> 04:54:27,680 DICHOTOMOUS FORM THERE IS A 6349 04:54:27,680 --> 04:54:31,600 DISEASE DIAGNOSTIC BIOMARKER AND 6350 04:54:31,600 --> 04:54:33,960 PROGNOSTIC BIOMARKER AND 6351 04:54:33,960 --> 04:54:35,720 MONITORING BIOMARKER. SORRY IT 6352 04:54:35,720 --> 04:54:38,000 IS ALSO A RESPONSE BIOMARKER AND 6353 04:54:38,000 --> 04:54:41,280 IN FACT IS INDEED A SURROGATE 6354 04:54:41,280 --> 04:54:43,120 ENDPOINT AND CALLING YOUR 6355 04:54:43,120 --> 04:54:45,200 ATTENTION THIS IS AN FDA 6356 04:54:45,200 --> 04:54:46,360 APPROACH. 6357 04:54:46,360 --> 04:54:49,760 FDA APPROACH IS PREDICATED ON 6358 04:54:49,760 --> 04:54:52,480 THEIR BEING A SPECIFIC DISEASE 6359 04:54:52,480 --> 04:54:54,480 OR HEALTH CONDITION OF INTEREST. 6360 04:54:54,480 --> 04:54:58,320 TALKING ABOUT AGING BROADLY 6361 04:54:58,320 --> 04:54:58,560 DEFINED. 6362 04:54:58,560 --> 04:55:00,800 IT IS A LITTLE TRICKY TO APPLY 6363 04:55:00,800 --> 04:55:03,200 THIS EXACTLY TO THAT AND CALLING 6364 04:55:03,200 --> 04:55:05,080 AN AGING AND DISEASE WILL NOT 6365 04:55:05,080 --> 04:55:06,560 HELP THIS PROBLEM. 6366 04:55:06,560 --> 04:55:12,120 IF WE WANT TO DEVELOP AN 6367 04:55:12,120 --> 04:55:15,000 INTERVENTION THAT COULD BE 6368 04:55:15,000 --> 04:55:17,720 MARKETED UNDER FDA RULES NEEDS 6369 04:55:17,720 --> 04:55:21,040 TO BE CLEAR CUT RULES TO SAY WHO 6370 04:55:21,040 --> 04:55:22,880 HAS CONDITIONS AND WE ARE NOT 6371 04:55:22,880 --> 04:55:25,400 THERE YET. 6372 04:55:25,400 --> 04:55:26,800 FUNDAMENTAL EVALUATION 6373 04:55:26,800 --> 04:55:29,120 CONSIDERATIONS WITH A CANDIDATE 6374 04:55:29,120 --> 04:55:30,520 BIOMARKER NEEDS TO KNOW WHY -- 6375 04:55:30,520 --> 04:55:32,920 WHAT MAKES IT VARY FROM -- AT 6376 04:55:32,920 --> 04:55:33,360 ALL? 6377 04:55:33,360 --> 04:55:36,120 WHAT ARE SOURCES OF VARIANTS AND 6378 04:55:36,120 --> 04:55:39,720 THERE ARE SOURCES IN THE ASSAYS 6379 04:55:39,720 --> 04:55:41,080 THEMSELVES AND HOW THEIR PROCESS 6380 04:55:41,080 --> 04:55:43,440 AND LABORATORY PROBLEMS OR 6381 04:55:43,440 --> 04:55:45,360 PROBLEMS OF SOURCES AND VARIANCE 6382 04:55:45,360 --> 04:55:47,640 IN POST PROCESSING IN THE 6383 04:55:47,640 --> 04:55:49,400 INFORMATION THAT COMES OFF 6384 04:55:49,400 --> 04:55:51,720 CERTAINLY WITH PLATE READERS AND 6385 04:55:51,720 --> 04:55:54,360 THAT SORT OF THING AND WITHIN 6386 04:55:54,360 --> 04:55:56,240 PERSON ARE SOURCES OF 6387 04:55:56,240 --> 04:55:58,880 VARIABILITY AND DIURNAL AND 6388 04:55:58,880 --> 04:56:00,560 DAY-TO-DAY AND SEASONAL 6389 04:56:00,560 --> 04:56:03,640 VARIATION AND MOST PEOPLE DON'T 6390 04:56:03,640 --> 04:56:06,480 REALIZE THAT SERUM CHOLESTEROL 6391 04:56:06,480 --> 04:56:09,120 COULD EAT 15 POINTS PLUS OR 6392 04:56:09,120 --> 04:56:11,360 MINUS DEPENDING WHAT SEASON OF 6393 04:56:11,360 --> 04:56:14,040 THE YEAR IS MEASURED AND 6394 04:56:14,040 --> 04:56:15,640 BIOMARKERS WE WANT IT TO SAY 6395 04:56:15,640 --> 04:56:16,880 SOMETHING ABOUT THE TRUE FEATURE 6396 04:56:16,880 --> 04:56:18,960 OF THE THING IN WHOM WE MEASURED 6397 04:56:18,960 --> 04:56:21,760 IT. IF THERE IS A LOT OF 6398 04:56:21,760 --> 04:56:23,680 VARIABILITY WE ARE NEVER QUITE 6399 04:56:23,680 --> 04:56:25,920 SURE THAT THE MEASUREMENT WE 6400 04:56:25,920 --> 04:56:27,080 HAVE REFLECTS THE THING WE WANT 6401 04:56:27,080 --> 04:56:30,160 TO SAY ABOUT THAT PERSON. 6402 04:56:30,160 --> 04:56:32,720 THEN THE EPIDEMIOLOGISTS IN ME 6403 04:56:32,720 --> 04:56:34,840 THINKS ABOUT SCALABILITY AND HOW 6404 04:56:34,840 --> 04:56:36,840 MUCH DOES IT COST AND IS IT 6405 04:56:36,840 --> 04:56:38,320 TRICKY TO COLLECT THE SAMPLE. 6406 04:56:38,320 --> 04:56:41,600 SO, THINGS THAT COULD BE DRAWN 6407 04:56:41,600 --> 04:56:44,320 INTO EDTA PLASMA TUBE AND LEFT 6408 04:56:44,320 --> 04:56:47,040 OUT, GREAT. OTHER THINGS WE 6409 04:56:47,040 --> 04:56:49,320 FINISHED THE STUDY WITH 850 6410 04:56:49,320 --> 04:56:53,280 MUSCLE BIOPSIES IN ORDER TO LOOK 6411 04:56:53,280 --> 04:56:57,040 AT MITOCHONDRIAL ENERGETICS AND 6412 04:56:57,040 --> 04:57:01,320 IN MUSCLE BUNDLES AND THAT TOOK 6413 04:57:01,320 --> 04:57:04,040 EACH ONE TAKES ABOUT FOUR HOURS 6414 04:57:04,040 --> 04:57:07,560 BETWEEN COLLECTION AND 6415 04:57:07,560 --> 04:57:08,840 PROCESSING IN THESE AND ABOUT 6416 04:57:08,840 --> 04:57:11,640 THREE OR FOUR PEOPLE IN IT. 6417 04:57:11,640 --> 04:57:13,200 THAT IS NOT SCALEABLE. 6418 04:57:13,200 --> 04:57:14,920 CAN THE -- HOW -- IS THERE 6419 04:57:14,920 --> 04:57:16,760 SOMETHING THAT IS FANCY ABOUT 6420 04:57:16,760 --> 04:57:18,000 THE STORAGE? 6421 04:57:18,000 --> 04:57:20,160 WHAT DO WE TELL PARTICIPANTS IN 6422 04:57:20,160 --> 04:57:21,520 WHOM WE ARE DRAWING THIS MEASURE 6423 04:57:21,520 --> 04:57:23,720 AND DO THEY HAVE TO BE FASTED 6424 04:57:23,720 --> 04:57:26,000 AND SHOULD THEY EXERCISE AND CAN 6425 04:57:26,000 --> 04:57:27,200 THEY EXERCISE AND ARE THERE 6426 04:57:27,200 --> 04:57:29,600 MEDICATIONS TO WORRY ABOUT AND 6427 04:57:29,600 --> 04:57:30,800 DOES DIETS HAVE TO BE 6428 04:57:30,800 --> 04:57:32,000 STANDARDIZE THE? 6429 04:57:32,000 --> 04:57:34,240 DO YOU FINALLY NEED OTHER 6430 04:57:34,240 --> 04:57:36,080 MEASURES TO FULLY INTERPRET. IN 6431 04:57:36,080 --> 04:57:38,280 SOME CASES IT IS IMPORTANT TO 6432 04:57:38,280 --> 04:57:41,080 KNOW BODY SIZE OR BINDING 6433 04:57:41,080 --> 04:57:43,240 PROTEIN CONCENTRATIONS THAT 6434 04:57:43,240 --> 04:57:46,360 WOULD TELL YOU THE FREE AMOUNT 6435 04:57:46,360 --> 04:57:48,960 AVAILABLE TO INTERACT AND A LOT 6436 04:57:48,960 --> 04:57:52,880 OF THE MEASURES OF BIOMARKERS OF 6437 04:57:52,880 --> 04:57:55,600 NEURODEGENERATION THAT ARE 6438 04:57:55,600 --> 04:57:56,640 HIGHLY DEPENDENT ON KIDNEY 6439 04:57:56,640 --> 04:57:58,800 FUNCTION AND IS IMPORTANT TO 6440 04:57:58,800 --> 04:58:01,640 KNOW WHAT KIDNEY FUNCTION 6441 04:58:01,640 --> 04:58:02,520 INTERPRETS CIRCULATING LEVELS. 6442 04:58:02,520 --> 04:58:06,040 THIS IS A EXAMPLE OF A 6443 04:58:06,040 --> 04:58:06,840 VALIDATION OF MEASURE. 6444 04:58:06,840 --> 04:58:09,400 IT IS OF A KIND OF VALIDATION. 6445 04:58:09,400 --> 04:58:11,640 THAT IS ANOTHER WORD THAT HAS A 6446 04:58:11,640 --> 04:58:13,960 TOWER OF BABEL AROUND IT AND 6447 04:58:13,960 --> 04:58:15,040 PEOPLE USING VALIDATION THEY 6448 04:58:15,040 --> 04:58:16,600 MEAN A LOT OF DIFFERENT THINGS 6449 04:58:16,600 --> 04:58:17,840 AND USE IT IN LOTS OF DIFFERENT 6450 04:58:17,840 --> 04:58:20,480 WAYS AND THIS IS AN EXERCISE 6451 04:58:20,480 --> 04:58:23,600 THAT WE UNDERTOOK THAT JUST GOT 6452 04:58:23,600 --> 04:58:26,240 PUBLISHED RECENTLY AND WORKING 6453 04:58:26,240 --> 04:58:30,520 WITH A MACHINE LEARNING 6454 04:58:30,520 --> 04:58:32,480 STATISTICIAN DR. RAMON KAS ANOVA 6455 04:58:32,480 --> 04:58:36,000 THAT HAD USED MACHINE LEARNING 6456 04:58:36,000 --> 04:58:38,320 TO COME UP WITH AN ALZHEIMER'S 6457 04:58:38,320 --> 04:58:40,240 DISEASE AND PATTERN SIMILARITY 6458 04:58:40,240 --> 04:58:43,240 SCORE BY APPLYING MRI DATA AND I 6459 04:58:43,240 --> 04:58:47,480 MEAN THESE ALGORITHMS TO MRI 6460 04:58:47,480 --> 04:58:50,880 DATA FROM ADMI COHORT AND OTHER 6461 04:58:50,880 --> 04:58:52,920 COHORTS LOOKING AT DATA SHOWING 6462 04:58:52,920 --> 04:58:55,640 IT TO OUR GROUP. IT OCCURRED TO 6463 04:58:55,640 --> 04:58:56,920 US THAT THERE WAS NOTHING REALLY 6464 04:58:56,920 --> 04:59:00,200 IN THE IMAGES THAT IT WAS 6465 04:59:00,200 --> 04:59:02,200 ACTUALLY SPECIFIC TO ALZHEIMER'S 6466 04:59:02,200 --> 04:59:03,600 DISEASE THERE IS NO 6467 04:59:03,600 --> 04:59:05,320 [INDISCERNIBLE] THAT IS JUST 6468 04:59:05,320 --> 04:59:08,520 ANATOMICAL FEATURES AND AGE IS A 6469 04:59:08,520 --> 04:59:11,000 STRONG RISK FACTOR FOR 6470 04:59:11,000 --> 04:59:12,360 ALZHEIMER'S DISEASE RISK MAY BE 6471 04:59:12,360 --> 04:59:14,120 THIS IS ACTUALLY COULD BE 6472 04:59:14,120 --> 04:59:17,920 CONSIDERED A MEASURE OF BIOLOGIC 6473 04:59:17,920 --> 04:59:19,120 BRAIN AGE. 6474 04:59:19,120 --> 04:59:22,320 SO HOW DO YOU VALIDATE THAT 6475 04:59:22,320 --> 04:59:23,880 THOUGHT AND TAKE THAT AND 6476 04:59:23,880 --> 04:59:24,600 VALIDATE IT? 6477 04:59:24,600 --> 04:59:27,520 YOU ASK YOURSELF IF THIS WERE A 6478 04:59:27,520 --> 04:59:29,280 MEASURE OF BRAIN AGE, WHAT WE 6479 04:59:29,280 --> 04:59:32,120 WOULD EXPECT TO SEE, WE WOULD 6480 04:59:32,120 --> 04:59:33,760 EXPECT IT TO CORRELATE WITH 6481 04:59:33,760 --> 04:59:36,040 OTHER AGE RELATED MEASURES THAT 6482 04:59:36,040 --> 04:59:39,800 ARE NOT BRAIN RELATED. THIS IS 6483 04:59:39,800 --> 04:59:41,800 SOMETIMES ON THIS CONVERGENT 6484 04:59:41,800 --> 04:59:43,880 VALIDITY THAT CONVERGES ON 6485 04:59:43,880 --> 04:59:46,320 THINGS ALL MEANT TO MEASURE THE 6486 04:59:46,320 --> 04:59:49,400 SAME THING THAT SHOULD HANG 6487 04:59:49,400 --> 04:59:49,640 TOGETHER. 6488 04:59:49,640 --> 04:59:51,960 IT SHOULD PREDICT AGING OUTCOMES 6489 04:59:51,960 --> 04:59:54,280 AND OTHER THAN ONES THAT ARE 6490 04:59:54,280 --> 04:59:56,520 RELATED TO BRAIN HEALTH IF IT IS 6491 04:59:56,520 --> 04:59:59,280 A MEASURE OF OVERALL AGING THAT 6492 04:59:59,280 --> 05:00:01,720 IS PREDICTIVE VALIDITY AND 6493 05:00:01,720 --> 05:00:03,920 ASSOCIATIONS SHOULD BE 6494 05:00:03,920 --> 05:00:06,760 INDEPENDENT OF CONLOGIC AGE THAT 6495 05:00:06,760 --> 05:00:09,440 IS DISCRIMINATIVE OF VALIDITY 6496 05:00:09,440 --> 05:00:11,600 AND ALL KINDS TLOOEND WE PICK TO 6497 05:00:11,600 --> 05:00:17,200 PURSUE AND WE LOOKED AT THIS IN 6498 05:00:17,200 --> 05:00:19,080 ATHLOW SCLEROSIS COMMUNITIES 6499 05:00:19,080 --> 05:00:22,960 COHORT AND HAD MRI IMAGES AT 6500 05:00:22,960 --> 05:00:24,640 VISIT 5 FROM THAT SAME VISIT WE 6501 05:00:24,640 --> 05:00:27,200 WERE ABLE TO CALCULATE A FRAILTY 6502 05:00:27,200 --> 05:00:29,880 INDEX FROM 38 MEASUREMENTS 6503 05:00:29,880 --> 05:00:31,880 AVAILABLE IN THE DATA SET AT 6504 05:00:31,880 --> 05:00:32,520 THAT TIME. 6505 05:00:32,520 --> 05:00:39,360 WE ALSO HAD AVAILABLESOMO LOGIC 6506 05:00:39,360 --> 05:00:41,480 APTIMER-BASED SCAN OF THOUSANDS 6507 05:00:41,480 --> 05:00:47,120 OF APTIMERS SOME ARE AGE RELATED 6508 05:00:47,120 --> 05:00:49,200 AND PREDICTIVE VALIDITY COULD 6509 05:00:49,200 --> 05:00:54,400 THIS PREDICT ALL CAUSE NON-CNS 6510 05:00:54,400 --> 05:00:56,720 RELATED MORTALITY? FRAILTY 6511 05:00:56,720 --> 05:00:58,680 INDEX THIS IS WHAT IT LOOKS 6512 05:00:58,680 --> 05:01:01,800 LIKE. IT IS A DEFINITION OR 6513 05:01:01,800 --> 05:01:03,080 DEFICIT ACCUMULATION INDEX. 6514 05:01:03,080 --> 05:01:05,600 IT IS INDEX THAT LOOKS -- THIS 6515 05:01:05,600 --> 05:01:07,200 LOOKS LIKE A FRAILISH 6516 05:01:07,200 --> 05:01:09,440 POPULATION. IT IS. THIS IS 6517 05:01:09,440 --> 05:01:11,640 PRETTY -- THIS COHORT WAS PRETTY 6518 05:01:11,640 --> 05:01:14,960 AGED AT THIS POINT. 6519 05:01:14,960 --> 05:01:20,360 THERE WAS A -- A SIGNIFICANT 6520 05:01:20,360 --> 05:01:23,600 ASSOCIATION BETWEEN THIS EDPS 6521 05:01:23,600 --> 05:01:26,000 SCORE AND FRAILTY INDEX AND WAS 6522 05:01:26,000 --> 05:01:29,200 TRUE EVEN AFTER ADMITTING 6523 05:01:29,200 --> 05:01:32,800 COGNITIVELY IMPAIRED FROM THE 6524 05:01:32,800 --> 05:01:34,240 ASSOCIATION. 6525 05:01:34,240 --> 05:01:37,400 FOR THE AGE-RELATED APTO MERS WE 6526 05:01:37,400 --> 05:01:40,320 REFERRED TO PAPERS BY JOHNSON 6527 05:01:40,320 --> 05:01:41,920 AND COLLEAGUES AND LOOKED AT ALL 6528 05:01:41,920 --> 05:01:43,880 ONES THAT THEY IDENTIFIED AS 6529 05:01:43,880 --> 05:01:47,360 BEING CONSISTENTLY RELATED WITH 6530 05:01:47,360 --> 05:01:51,160 KRON LOGIC AGE ACROSS A NUMBER 6531 05:01:51,160 --> 05:01:53,880 OF POPULATIONS AND AFTER 6532 05:01:53,880 --> 05:01:56,000 ADJUSTING FOR MULTIPLE 6533 05:01:56,000 --> 05:01:59,240 COMPARISONS, TWO THAT REMAINED 6534 05:01:59,240 --> 05:02:05,600 WERE PLEOTROPHEN THAT ARE 6535 05:02:05,600 --> 05:02:07,720 ASSOCIATED WITH MEASURE OF 6536 05:02:07,720 --> 05:02:10,120 ANATOMICAL BRAIN AGING AND 6537 05:02:10,120 --> 05:02:13,600 FINALLY FOR MORTALITY RISKS, 6538 05:02:13,600 --> 05:02:15,120 FIRST -- THE FIRST SET OF 6539 05:02:15,120 --> 05:02:17,720 NUMBERS SHOWS THAT THE LOWEST 6540 05:02:17,720 --> 05:02:19,520 QUARTILE ARE PEOPLE THAT ARE 6541 05:02:19,520 --> 05:02:22,720 BEST BRAINS WHEN WE OBSERVE 6542 05:02:22,720 --> 05:02:23,040 THEM. 6543 05:02:23,040 --> 05:02:26,360 AND WE HAD HALF OF THE RISK OF 6544 05:02:26,360 --> 05:02:28,240 ALL CAUSE MORTALITY. THAT WAS 6545 05:02:28,240 --> 05:02:31,640 STILL TRUE AFTER WE OMITTED 6546 05:02:31,640 --> 05:02:37,080 PEOPLE WITH COGNITIVE IMPAIRMENT 6547 05:02:37,080 --> 05:02:38,720 AT BASELINE THAT IS STILL TRUE 6548 05:02:38,720 --> 05:02:40,960 LOOKING AT COGNITIVELY NORMAL 6549 05:02:40,960 --> 05:02:44,120 REMOVING CNS-RELATED CAUSES OF 6550 05:02:44,120 --> 05:02:46,360 DEATH FROM OUTCOME TREATING IT 6551 05:02:46,360 --> 05:02:49,520 AS COMPETING CAUSE OF DEATH. 6552 05:02:49,520 --> 05:02:56,360 ABOUT 40% REDISCUSSUCTION IN 6553 05:02:56,360 --> 05:02:57,800 PREDICTION OF MORTALITY IN THIS 6554 05:02:57,800 --> 05:02:59,040 WAY SOMETHING LOOKING AT BRAIN 6555 05:02:59,040 --> 05:03:01,000 IS CONNECTING TO SOMETHING WITH 6556 05:03:01,000 --> 05:03:02,560 OVERALL AGING AND WHAT IT MIGHT 6557 05:03:02,560 --> 05:03:04,240 BE IS A GREAT QUESTION. WE 6558 05:03:04,240 --> 05:03:09,120 WOULD LIKE TO KNOW MORE ABOUT 6559 05:03:09,120 --> 05:03:10,040 THAT. 6560 05:03:10,040 --> 05:03:14,920 A LOT OF PEOPLE VALIDATE 6561 05:03:14,920 --> 05:03:17,000 MEASURES BY AGING WITH 6562 05:03:17,000 --> 05:03:18,320 CORRELATIONS WITH KRON LOGIC AGE 6563 05:03:18,320 --> 05:03:21,120 THAT IS DONE IN SINGLE VISIT IN 6564 05:03:21,120 --> 05:03:26,800 A STUDY WITH POPULATION AND MANY 6565 05:03:26,800 --> 05:03:31,400 PEOPLE IN IT AND AGES TO SPAN 6566 05:03:31,400 --> 05:03:32,440 AND WARNING EVERYONE IF YOU 6567 05:03:32,440 --> 05:03:34,560 HADN'T THOUGHT OF THIS AND 6568 05:03:34,560 --> 05:03:36,400 BIOMARKERS ARE VALIDATED BASED 6569 05:03:36,400 --> 05:03:39,640 ONLY ON ASSOCIATION WITH NORTH 6570 05:03:39,640 --> 05:03:43,240 CHRONOLOGIC AGE SAMPLE SINGLE 6571 05:03:43,240 --> 05:03:46,360 POINT OFTEN BIASED AND OFTEN 6572 05:03:46,360 --> 05:03:47,840 SEVERELY BIASES AND MANY REASONS 6573 05:03:47,840 --> 05:03:50,400 FOR THIS AND THREE TO KEEP IN 6574 05:03:50,400 --> 05:03:53,240 MIND IS COHORT HE EFFECTS AND 30 6575 05:03:53,240 --> 05:03:55,600 YEAR OLD IN 2020 HAS DIFFERENT 6576 05:03:55,600 --> 05:03:59,840 LIFE HISTORY THAN 30 YEAR OLD IN 6577 05:03:59,840 --> 05:04:02,080 1980. YOU HAVE A 70 YEAR OLD IN 6578 05:04:02,080 --> 05:04:04,640 SAME POPULATION AND YOU ARE 6579 05:04:04,640 --> 05:04:05,800 CLAIMING ANY BIOMARKER 6580 05:04:05,800 --> 05:04:09,160 DIFFERENCE YOU SEE IS BECAUSE OF 6581 05:04:09,160 --> 05:04:12,040 40 YEARS AGE LAPSE MAY OR MAY 6582 05:04:12,040 --> 05:04:13,920 NOT BE TRUE AND KNOW FOR EXAMPLE 6583 05:04:13,920 --> 05:04:18,280 THAT PEOPLE THAT ARE 30 IN 2020 6584 05:04:18,280 --> 05:04:20,920 THAT WHOLE BIRTH COHORT IS 6585 05:04:20,920 --> 05:04:22,640 HEAVIER AND MORE OBESE THAN 6586 05:04:22,640 --> 05:04:26,320 BIRTH COHORT FROM THE PERSON WHO 6587 05:04:26,320 --> 05:04:34,640 IS NOW 70 WHEN THEY WERE BORN IN 6588 05:04:34,640 --> 05:04:35,280 1950. 6589 05:04:35,280 --> 05:04:37,520 ANOTHER IMPORTANT CAVEAT IS 6590 05:04:37,520 --> 05:04:38,840 SELECTIVE SURVIVAL. 6591 05:04:38,840 --> 05:04:41,720 IF YOU HAVE A VERY BENEFICIAL 6592 05:04:41,720 --> 05:04:44,200 CHARACTERISTIC, SAY IT MAKES YOU 6593 05:04:44,200 --> 05:04:45,120 IMMORTAL. 6594 05:04:45,120 --> 05:04:47,480 THAT CHARACTERISTIC WILL BECOME 6595 05:04:47,480 --> 05:04:49,400 MORE COMMON AT OLDER AGES AND 6596 05:04:49,400 --> 05:04:51,400 ALL PEOPLE WITHOUT IT CAN DIE 6597 05:04:51,400 --> 05:04:53,840 AND PEOPLE WITH IT CAN'T. 6598 05:04:53,840 --> 05:04:55,320 NOW, THAT IS THE MOST EXTREME 6599 05:04:55,320 --> 05:04:57,560 VIEW AND WORKS BOTH WAYS IF YOU 6600 05:04:57,560 --> 05:04:59,480 HAVE A DELETERIOUS EFFECT IT 6601 05:04:59,480 --> 05:05:01,880 WILL LOOK TO GO DOWN WITH AGE. 6602 05:05:01,880 --> 05:05:05,360 PEOPLE WITH IT ARE REMOVED. 6603 05:05:05,360 --> 05:05:08,200 AND THEN ALSO REALIZING THAT 6604 05:05:08,200 --> 05:05:11,600 WHATEVER YOU MEASURE AND 6605 05:05:11,600 --> 05:05:13,520 WHATEVER CORRELATION, IT CAN 6606 05:05:13,520 --> 05:05:15,600 INDEX THE CUMULATIVE AGING 6607 05:05:15,600 --> 05:05:17,480 EFFECTS AND DOESN'T NECESSARILY 6608 05:05:17,480 --> 05:05:19,360 REFLECT CURRENT STATE. 6609 05:05:19,360 --> 05:05:21,280 SO, IF YOU HAVE A 6610 05:05:21,280 --> 05:05:24,840 CROSS-SECTIONAL ASSOCIATION AND 6611 05:05:24,840 --> 05:05:27,240 RELATE THIS TO ANY OTHER MEASURE 6612 05:05:27,240 --> 05:05:30,560 AND WE WILL, I THINK WE WILL 6613 05:05:30,560 --> 05:05:33,720 HEAR ABOUT EPIGENETICS A LITTLE 6614 05:05:33,720 --> 05:05:35,360 BIT LATER. YOU MIGHT SAY THAT 6615 05:05:35,360 --> 05:05:38,000 PEOPLE ARE OLDER BECAUSE OF 6616 05:05:38,000 --> 05:05:39,240 THEIR EPIGENETICS AND THAT AGING 6617 05:05:39,240 --> 05:05:43,600 IF IT IS AGING, IT COULD HAVE 6618 05:05:43,600 --> 05:05:44,800 OCCURRED ANY TIME DURING THEIR 6619 05:05:44,800 --> 05:05:46,000 LIFE COURSE AND DOESN'T TELL YOU 6620 05:05:46,000 --> 05:05:48,080 THEY ARE AGING FASTER RIGHT THEN 6621 05:05:48,080 --> 05:05:50,280 BUT AT SOME POINT IN LIFE 6622 05:05:50,280 --> 05:05:54,640 HISTORY UP TO THAT POINT THEY 6623 05:05:54,640 --> 05:06:03,440 MAY HAVE AGED OR QUICK LY THIS S 6624 05:06:03,440 --> 05:06:07,640 DATA FROM LONGITUDINAL AGING AND 6625 05:06:07,640 --> 05:06:08,840 TRACKING LONGITUDINALLY 20 6626 05:06:08,840 --> 05:06:10,680 DIFFERENT AGE RELATED PHENOTYPES 6627 05:06:10,680 --> 05:06:12,520 AND MEASUREMENTS TO REPRESENT 6628 05:06:12,520 --> 05:06:17,360 FOUR PHENOTYPIC DOMAINS BODY 6629 05:06:17,360 --> 05:06:19,640 COMPOSITION ENERGY HOMEOSTASIS 6630 05:06:19,640 --> 05:06:21,520 AND NEURODEGENERATION AND EACH 6631 05:06:21,520 --> 05:06:25,280 OF THE LINES REPRESENTS A PERSON 6632 05:06:25,280 --> 05:06:33,160 IN BLSA AND LOOKS AT TRAJECTORY 6633 05:06:33,160 --> 05:06:36,080 OF MEASURE OVER TIME AND ENERGY 6634 05:06:36,080 --> 05:06:38,840 USE WITH SLOW WALKING AND ENERGY 6635 05:06:38,840 --> 05:06:42,200 USE OF SLOW WALKING RATIO OF 6636 05:06:42,200 --> 05:06:43,840 PEAK ENERGY CONSUMPTION THAT YOU 6637 05:06:43,840 --> 05:06:48,160 SEE GOES UP WITH AGE AT ALL TIME 6638 05:06:48,160 --> 05:06:53,440 POINTS FITTING AS A 6639 05:06:53,440 --> 05:06:55,080 CROSS-SECTIONAL STUDY AND TAKING 6640 05:06:55,080 --> 05:06:56,600 MIDPOINTS OF BLUE LINES 6641 05:06:56,600 --> 05:06:57,800 CONNECTING THEM YOU WOULD HAVE 6642 05:06:57,800 --> 05:06:59,640 SEEN IT IN A CROSS-SECTIONAL 6643 05:06:59,640 --> 05:07:01,840 STUDY AND LOOKED LIKE NO CHANGE 6644 05:07:01,840 --> 05:07:03,360 IN MEASUREMENT BETWEEN AGES OF 6645 05:07:03,360 --> 05:07:05,840 25 AND 50 AND THEN WOULD RISE 6646 05:07:05,840 --> 05:07:07,200 THEREAFTER. THIS IS A EXAMPLE 6647 05:07:07,200 --> 05:07:11,000 OF BIAS THAT YOU WOULD ATTRIBUTE 6648 05:07:11,000 --> 05:07:13,920 OR BIAS YOU WOULD MAKE LOOKING 6649 05:07:13,920 --> 05:07:15,120 AT CROSS-SECTIONAL DATA RATHER 6650 05:07:15,120 --> 05:07:19,640 THAN HAVING ACTUAL LONGITUDINAL 6651 05:07:19,640 --> 05:07:22,760 MEASU 6652 05:07:22,760 --> 05:07:23,000 MEASURES. 6653 05:07:23,000 --> 05:07:25,680 LET'S TALK P MORE ABOUT 6654 05:07:25,680 --> 05:07:26,800 SURROGATE ENDPOINTS THAT ARE 6655 05:07:26,800 --> 05:07:30,120 THINGS PEOPLE WOULD REALLY WISH 6656 05:07:30,120 --> 05:07:32,840 THEY HAD AND SO A SURROGATE 6657 05:07:32,840 --> 05:07:35,640 ENDPOINT IS AN ENDPOINT IN A 6658 05:07:35,640 --> 05:07:39,160 CLINICAL TRIAL AND SUBSTITUTE 6659 05:07:39,160 --> 05:07:43,200 FOR DIRECT MEASURE OF PERSON AND 6660 05:07:43,200 --> 05:07:45,600 HOW THEY FEEL FUNCTIONS AND 6661 05:07:45,600 --> 05:07:46,560 SURVIVES THAT COULD BE 6662 05:07:46,560 --> 05:07:48,920 REASONABLY LIKELY AND VALIDATED 6663 05:07:48,920 --> 05:07:53,040 AND SO DR. JUSTICE WITH PEOPLE 6664 05:07:53,040 --> 05:07:55,320 WORKING WITH TAME WENT THROUGH 6665 05:07:55,320 --> 05:07:57,200 EXERCISE TO IDENTIFY POTENTIAL 6666 05:07:57,200 --> 05:08:00,400 THINGS THAT WE ALREADY KNEW THAT 6667 05:08:00,400 --> 05:08:02,280 COULD BE CONSIDERED AS 6668 05:08:02,280 --> 05:08:03,720 REASONABLE ONES AND REASONABLY 6669 05:08:03,720 --> 05:08:08,320 LIKELY ONES AND CAME UP WITH A 6670 05:08:08,320 --> 05:08:11,320 LIST OF THE FOUR OR FIVE 6671 05:08:11,320 --> 05:08:14,360 BIOMARKERS THAT ARE INCLUDING 6672 05:08:14,360 --> 05:08:17,600 TNF ALPHA SOIL RECEPTORS AND 6673 05:08:17,600 --> 05:08:24,480 STATUS C AND PROBIANP AND NT 6674 05:08:24,480 --> 05:08:28,400 PROBIAN NP BRINGING UP FEATURING 6675 05:08:28,400 --> 05:08:31,080 IN DR. KRIMON'S TALK EARLIER AND 6676 05:08:31,080 --> 05:08:33,800 TO FULLY VALIDATE MARKER, YOU 6677 05:08:33,800 --> 05:08:36,200 HAVE TO HAVE DATA SHOWING 6678 05:08:36,200 --> 05:08:38,400 CLINICAL BENEFIT OF THE 6679 05:08:38,400 --> 05:08:39,920 INTERVENTION THAT YOU ARE 6680 05:08:39,920 --> 05:08:41,040 CONSIDERING. 6681 05:08:41,040 --> 05:08:43,880 WE HAVE A GOOD REFLECTION OF 6682 05:08:43,880 --> 05:08:46,480 THIS. IT IS IN BONE MINERAL 6683 05:08:46,480 --> 05:08:48,880 DENSITY WHERE IT TOOK 12 OR 13 6684 05:08:48,880 --> 05:08:52,520 TRIALS OF 7 TO 20,000 PEOPLE FOR 6685 05:08:52,520 --> 05:08:55,160 THREE OR MORE YEARS TO GENERATE 6686 05:08:55,160 --> 05:08:57,320 DATA TO SHOW THAT EXTENT OF 6687 05:08:57,320 --> 05:08:59,360 REDUCTION IN BONE DENSITY IS 6688 05:08:59,360 --> 05:09:01,360 RELATED TO EXTENT OF REDUCTION 6689 05:09:01,360 --> 05:09:04,320 IN RISK OF FRACTURE THAT ALLOWED 6690 05:09:04,320 --> 05:09:07,600 VALIDATION OF BONE DENSITY IN 6691 05:09:07,600 --> 05:09:11,000 THIS REGARD. 6692 05:09:11,000 --> 05:09:13,120 THESE ARE SUCCESSFUL SURROGATES 6693 05:09:13,120 --> 05:09:15,400 AND FAILED ONES AND WON'T 6694 05:09:15,400 --> 05:09:19,600 BELABOR THIS. YOU CANNOT 6695 05:09:19,600 --> 05:09:20,920 VALIDATE SURROGATE WITHOUT TRIAL 6696 05:09:20,920 --> 05:09:22,760 SHOWING EFFICACY AND I WILL 6697 05:09:22,760 --> 05:09:24,480 LEAVE YOU WITH THIS THOUGHT. IF 6698 05:09:24,480 --> 05:09:27,400 WE HAVE A VALID SURROGATE 6699 05:09:27,400 --> 05:09:28,920 BIOMARKER, WHAT IS ENDPOINT THAT 6700 05:09:28,920 --> 05:09:34,120 WE WANT THE SURROGATE FOR? THAT 6701 05:09:34,120 --> 05:09:36,360 IS A GEROSCIENCE CHALLENGE 6702 05:09:36,360 --> 05:09:38,960 COMING UP WITH DEFINITIONS OF 6703 05:09:38,960 --> 05:09:42,720 PHENOTYPIC AGING THAT WE CAN 6704 05:09:42,720 --> 05:09:44,440 APPLY IN A TRIAL. 6705 05:09:44,440 --> 05:09:47,000 WE CAN FIND BIOMARKERS RELATING 6706 05:09:47,000 --> 05:09:49,320 TO IT. WE DON'T HAVE IT YET. 6707 05:09:49,320 --> 05:09:52,320 WE DON'T OR HAVEN'T HAD A TRIAL 6708 05:09:52,320 --> 05:09:54,640 LARGE ENOUGH WITH INTERVENTIONS 6709 05:09:54,640 --> 05:10:01,920 TO SHOW EFFICACY ON THIS NOW 6710 05:10:01,920 --> 05:10:05,000 HYPOTHETICAL ENDPOINT WE HAVE TO 6711 05:10:05,000 --> 05:10:15,400 DEVELOP. THANK YOU. 6712 05:10:20,520 --> 05:10:22,800 >>THANK YOU, STEVE. NEXT IS 6713 05:10:22,800 --> 05:10:25,600 DAN AND I WILL GIVE A TALK HE IS 6714 05:10:25,600 --> 05:10:29,520 A PROFESSOR AT EPIDEMIOLOGY 6715 05:10:29,520 --> 05:10:31,920 COLUMBIA SCHOOL OF MAILMAN 6716 05:10:31,920 --> 05:10:34,320 HEALTH. DAN'S WORK IS AT 6717 05:10:34,320 --> 05:10:35,000 INTERSECTION OF SOCIAL SCIENCE 6718 05:10:35,000 --> 05:10:38,960 AND GENOMICS AND PUBLIC HEALTH 6719 05:10:38,960 --> 05:10:42,680 AND RECENT WORK EVALUATED 6720 05:10:42,680 --> 05:10:48,120 METHODS QUANTIFY IING -- 6721 05:10:48,120 --> 05:10:50,960 APPLICATION OF THESE LIFE 6722 05:10:50,960 --> 05:10:52,640 HISTORY AND SOCIAL FACTORS AND 6723 05:10:52,640 --> 05:10:57,280 AGING PROCESS AND HOW TO BE 6724 05:10:57,280 --> 05:11:02,480 MODIFIED WITH INTERVENTION AND 6725 05:11:02,480 --> 05:11:11,880 ORIGINATING METHOD -- DAN TAKE 6726 05:11:11,880 --> 05:11:13,160 IT AWAY. 6727 05:11:13,160 --> 05:11:15,080 >>OKAY. THANK YOU VERY MUCH. 6728 05:11:15,080 --> 05:11:20,000 SEEING IF I CAN DO THIS STANDING 6729 05:11:20,000 --> 05:11:26,720 STILL AND NOT PREFERRED MODE OF 6730 05:11:26,720 --> 05:11:29,000 OPERATION AND DISCLOSURE KEEP IN 6731 05:11:29,000 --> 05:11:30,640 MIND IN TALK AND REMIND US WHERE 6732 05:11:30,640 --> 05:11:32,640 WE CAME FROM. WE HAVE NOT SEEN 6733 05:11:32,640 --> 05:11:34,600 THIS KIND OF CARTOON I FEEL LIKE 6734 05:11:34,600 --> 05:11:39,400 SO FAR IN LAST COUPLE OF DAYS OR 6735 05:11:39,400 --> 05:11:42,480 I HAVEN'T AND WITH AGING 6736 05:11:42,480 --> 05:11:44,120 ACCUMULATING CELLULAR LEVEL 6737 05:11:44,120 --> 05:11:47,640 CHANGES FEEDING FORWARD TO 6738 05:11:47,640 --> 05:11:52,040 UNDERMINE CAPACITY AND ORGANS -- 6739 05:11:52,040 --> 05:11:55,600 ULTIMATELY DISABLE AND KILL US. 6740 05:11:55,600 --> 05:11:59,640 BY INTERVENTION ON THESE 6741 05:11:59,640 --> 05:12:03,360 MOLECULAR CHANGES WE CAN DELAY 6742 05:12:03,360 --> 05:12:09,080 OR SLOW PROCESS FOR CHANGE AND 6743 05:12:09,080 --> 05:12:11,560 PRESERVING HEALTHY LIFESPAN AND 6744 05:12:11,560 --> 05:12:15,120 FRAMING FOCUSING ON MEASUREMENTS 6745 05:12:15,120 --> 05:12:20,800 TO MAKE WITH INTEGRITY CHANGE 6746 05:12:20,800 --> 05:12:23,760 AND PACE AND PROJECTS ULTIMATELY 6747 05:12:23,760 --> 05:12:26,600 SOURCE OF CHANGE AND CARTOON IS 6748 05:12:26,600 --> 05:12:29,120 WHERE PROGRAM OF RESEARCH THAT I 6749 05:12:29,120 --> 05:12:32,960 HAVE BEEN AFTER SINCE ABOUT 2014 6750 05:12:32,960 --> 05:12:36,680 BEGAN WITH TERRY AND 6751 05:12:36,680 --> 05:12:38,920 IDENTIFICATION OF THE MIDLIFE 6752 05:12:38,920 --> 05:12:44,320 AND HEALTHY PERIOD OF LIFE WITH 6753 05:12:44,320 --> 05:12:47,640 OPTIMAL POINT FOR THERAPEUTICS 6754 05:12:47,640 --> 05:12:50,520 AND DIVERGENT TRAJECTORIES OF 6755 05:12:50,520 --> 05:12:53,560 AGING WHEN POSSIBLE TO INTERVENE 6756 05:12:53,560 --> 05:12:58,280 AND PRESERVE SYSTEM INTEGRITY 6757 05:12:58,280 --> 05:13:01,680 AND DECLINE AND CHALLENGES 6758 05:13:01,680 --> 05:13:05,280 MANLING ONE OF STEVE'S TRIAL AND 6759 05:13:05,280 --> 05:13:07,640 LATENCY TO ONSET OF DISABLING 6760 05:13:07,640 --> 05:13:11,600 CONDITIONS AIMING TO PREVENT IS 6761 05:13:11,600 --> 05:13:14,480 STREAMLY LONG NOBODY HAS TIME OR 6762 05:13:14,480 --> 05:13:19,280 MONEY TO RUN A CLINICAL TRIAL 6763 05:13:19,280 --> 05:13:22,560 AND SUROGATES WE HAVE IN MIND 6764 05:13:22,560 --> 05:13:26,880 ARE CALLED PACE OF AGING AND 6765 05:13:26,880 --> 05:13:28,440 MEASUREMENTS TAKEN OUT OVER 6766 05:13:28,440 --> 05:13:30,960 YEARS OR MONTHS AND READING OUT 6767 05:13:30,960 --> 05:13:35,200 SLOWING DOWN ACCUMULATION OF 6768 05:13:35,200 --> 05:13:37,120 BIOLOGICAL CHANGE IN TREATMENT 6769 05:13:37,120 --> 05:13:38,960 RATHER THAN CONTROL GROUP AND 6770 05:13:38,960 --> 05:13:40,680 WENT ABOUT DOING THAT IN FIRST 6771 05:13:40,680 --> 05:13:44,360 CASE THAT IS FAIRLY OLD WORK 6772 05:13:44,360 --> 05:13:53,120 FROM 2015 COMPILING RECORDS 6773 05:13:53,120 --> 05:13:56,840 FUNDED IN NIA AND -- ACROSS A 6774 05:13:56,840 --> 05:13:59,360 HALF CENTURY. 6775 05:13:59,360 --> 05:14:00,920 WITH ALMOST PERFECT RETENTION 6776 05:14:00,920 --> 05:14:03,800 AND 95% AS RECENT FOLLOW UP AND 6777 05:14:03,800 --> 05:14:07,120 FROM AGE OF 26, PARTICIPANTS 6778 05:14:07,120 --> 05:14:08,720 WERE BROUGHT INTO CLINIC 6779 05:14:08,720 --> 05:14:11,040 UNIVERSITY AND RECEIVED A 6780 05:14:11,040 --> 05:14:13,280 COMPREHENSIVE CLINICAL EXAM AND 6781 05:14:13,280 --> 05:14:14,760 RECEIVED MEASUREMENTS TAKEN IN 6782 05:14:14,760 --> 05:14:16,640 PARALLEL WITH TIME POINTS 6783 05:14:16,640 --> 05:14:18,680 PARTICIPANTS WERE 26 AND 32 AND 6784 05:14:18,680 --> 05:14:21,480 38 YEARS OF AGE ON FIGURE ON 6785 05:14:21,480 --> 05:14:23,200 YOUR LEFT AND READ OUT ON 6786 05:14:23,200 --> 05:14:25,400 VARIOUS ORGAN SYSTEMS THROUGHOUT 6787 05:14:25,400 --> 05:14:27,120 BODIES OF INDIVIDUALS HEART AND 6788 05:14:27,120 --> 05:14:30,480 LUNGS AND KIDNEYS AND LIVERS AND 6789 05:14:30,480 --> 05:14:34,000 ALIGNING THAT DATA AND TRACKING 6790 05:14:34,000 --> 05:14:35,520 INDIVIDUALS CHANGE ACROSS 20 6791 05:14:35,520 --> 05:14:38,920 YEARS OF FOLLOW UP AND SAW WITH 6792 05:14:38,920 --> 05:14:43,200 YOUNG PEOPLE BODIES EVIDENCED 6793 05:14:43,200 --> 05:14:46,320 DECLINE IN INTEGRITY OVER THE 6794 05:14:46,320 --> 05:14:50,040 COURSE OF A LIFETIME AND WITH 18 6795 05:14:50,040 --> 05:14:50,960 BIOMARKERS COMPOSITING 6796 05:14:50,960 --> 05:14:53,160 INDIVIDUAL DIFFERENCES TO FORM A 6797 05:14:53,160 --> 05:14:56,720 SINGLE INDEX WE SEE VARIATION 6798 05:14:56,720 --> 05:15:02,680 AND HOW FAST PEOPLE'S BODIES ARE 6799 05:15:02,680 --> 05:15:05,520 CHANGING AND METRIC MEAN AVERAGE 6800 05:15:05,520 --> 05:15:07,360 BIOLOGICAL CHANGE PER YEAR IN 6801 05:15:07,360 --> 05:15:09,960 INDIVIDUAL IN LONGITUDINAL STUDY 6802 05:15:09,960 --> 05:15:11,200 POPULATION REPRESENTATIVE BIRTH 6803 05:15:11,200 --> 05:15:14,200 COHORT AND ONE ADMITTEDLY 6804 05:15:14,200 --> 05:15:16,240 ENTIRELY WHITE AND SOURCED FROM 6805 05:15:16,240 --> 05:15:18,400 SINGLE CITY AT BOTTOM OF THE 6806 05:15:18,400 --> 05:15:20,120 WORLD AND SOME PEOPLE'S BODIES 6807 05:15:20,120 --> 05:15:22,440 ARE NOT CHANGING AT ALL AND 6808 05:15:22,440 --> 05:15:25,240 OTHERS THAT BODIES ARE CHANGING 6809 05:15:25,240 --> 05:15:28,200 NEARLY TWICE AS FAST AND 30-A AT 6810 05:15:28,200 --> 05:15:30,480 TIME WE CONDUCT STUDY THERE IS 6811 05:15:30,480 --> 05:15:32,320 NO FOLLOW UP FOR DISEASE OR 6812 05:15:32,320 --> 05:15:33,840 MORTALITY AND OBSERVE THAT 6813 05:15:33,840 --> 05:15:37,200 INDIVIDUALS BODIES CHANGING MORE 6814 05:15:37,200 --> 05:15:38,840 SLOWLY SHOW SUPERIOR PHYSICAL 6815 05:15:38,840 --> 05:15:41,040 FUNCTIONING AND COGNITIVE 6816 05:15:41,040 --> 05:15:42,120 FUNCTIONING REDUCING COGNITIVE 6817 05:15:42,120 --> 05:15:45,320 DECLINE LOOKING YOUNGER SHOWING 6818 05:15:45,320 --> 05:15:48,080 PICTURES OF GRADUATE FACES AND 6819 05:15:48,080 --> 05:15:49,520 SUBSEQUENT WORK MAX ELLIOT 6820 05:15:49,520 --> 05:15:51,200 SHOWED THEY HAVE YOUNGER LOOKING 6821 05:15:51,200 --> 05:15:53,000 BRAINS AND IN ADDITION LOOKING 6822 05:15:53,000 --> 05:15:55,680 BACKWARDS IN LIVES WE SEE THOSE 6823 05:15:55,680 --> 05:15:58,040 AGING FASTER HAVE LIFE HISTORIES 6824 05:15:58,040 --> 05:15:59,280 CHARACTERISTIC OF PEOPLE TENDING 6825 05:15:59,280 --> 05:16:02,400 TO HAVE SICKER SHORTER LIVED 6826 05:16:02,400 --> 05:16:04,080 LIVES AND GROWING UP IN POVERTY 6827 05:16:04,080 --> 05:16:07,640 AND GREAT EAR ACCUMULATIONS OF 6828 05:16:07,640 --> 05:16:08,800 ADVERSE CHILDHOOD EXPERIENCES 6829 05:16:08,800 --> 05:16:10,840 AND YOUNG PEOPLE SHOW SIGNS OF 6830 05:16:10,840 --> 05:16:13,080 RISK FOR LATER AGE-RELATED 6831 05:16:13,080 --> 05:16:15,240 DISEASE AND IS NOT A MEASURE 6832 05:16:15,240 --> 05:16:16,560 PUTTING INTO CLINICAL TRIAL 6833 05:16:16,560 --> 05:16:19,840 REQUIRING 12 YEARS FOLLOW UP AND 6834 05:16:19,840 --> 05:16:20,840 GREAT DEAL OF COMPLEX 6835 05:16:20,840 --> 05:16:22,000 EXAMINATION AND GOAL FROM HERE 6836 05:16:22,000 --> 05:16:24,400 IS TO TRY TO BOTTLE THIS PACE OF 6837 05:16:24,400 --> 05:16:26,240 AGING INTO A BLOOD TEST THAT 6838 05:16:26,240 --> 05:16:27,840 COULD BE DELIVERED OVER COURSE 6839 05:16:27,840 --> 05:16:30,160 OF REPEATED MEASUREMENTS IN 6840 05:16:30,160 --> 05:16:32,640 CONTEXT OF RCT AND TO DO THAT WE 6841 05:16:32,640 --> 05:16:35,160 TURNED TO THIS MOLECULE THAT WE 6842 05:16:35,160 --> 05:16:36,920 HEARD SOMETHING ABOUT AND 6843 05:16:36,920 --> 05:16:38,400 EPIGENETIC CLOCKS THAT PAVE THE 6844 05:16:38,400 --> 05:16:42,240 WAY AND DNA METHYLATION AND MENL 6845 05:16:42,240 --> 05:16:48,840 ILL GROUPS BONDED TO CG DIO 6846 05:16:48,840 --> 05:16:50,840 NUCLEOTIDES AND TURNING GENES ON 6847 05:16:50,840 --> 05:16:55,520 AND OFF AND NOT HOW WE ARE 6848 05:16:55,520 --> 05:16:56,920 STUDYING THEM HERE AND TINY 6849 05:16:56,920 --> 05:16:59,120 BLACK BOXES RECORDING 6850 05:16:59,120 --> 05:17:00,520 INFORMATION INDIVIDUALS BIOLOGY 6851 05:17:00,520 --> 05:17:02,240 AND POTENTIALLY ENVIRONMENT TO 6852 05:17:02,240 --> 05:17:05,240 DATA MINE AND TRY TO UNDERSTAND 6853 05:17:05,240 --> 05:17:06,080 DERIVING MEASUREMENT OF 6854 05:17:06,080 --> 05:17:09,200 PHENOTYPE IN THIS CASE THAT IS 6855 05:17:09,200 --> 05:17:13,240 THE AGE OF PACING AGING AND CAME 6856 05:17:13,240 --> 05:17:16,440 TO WORK CONDUCTED BY LAB AND 6857 05:17:16,440 --> 05:17:17,520 [INDISCERNIBLE] AND COLLEAGUES 6858 05:17:17,520 --> 05:17:21,960 AND FIRST CASE SHOWED METHO LOAM 6859 05:17:21,960 --> 05:17:23,600 WAS EXTRAORDINARY TIME KEEPER 6860 05:17:23,600 --> 05:17:25,600 GOOD AT RECORDING HOW OLD PEOPLE 6861 05:17:25,600 --> 05:17:29,800 WERE AND THEORY DERIVING 6862 05:17:29,800 --> 05:17:31,120 PREDICTIONS PREDICTING THOSE 6863 05:17:31,120 --> 05:17:35,760 FROM METHYL OHM AND EPIGENOMIC 6864 05:17:35,760 --> 05:17:38,200 AGE AND FAST OR RANGING SLOW AND 6865 05:17:38,200 --> 05:17:40,680 DIDN'T TURN OUT TO BE TRUE 6866 05:17:40,680 --> 05:17:41,360 CONSISTENTLY AND FIRST 6867 05:17:41,360 --> 05:17:47,640 GENERATION OF EPIGENETIC CLOCKS 6868 05:17:47,640 --> 05:17:50,320 UNRELIABLE PREDICTORS LIKE PACE 6869 05:17:50,320 --> 05:17:54,320 OF AGING IN PART BECAUSE OF 6870 05:17:54,320 --> 05:17:57,160 LIMITATIONS THAT STEVE NOTED 6871 05:17:57,160 --> 05:18:00,000 SURVIVAL BIAS COHORTS MOST OF 6872 05:18:00,000 --> 05:18:02,760 ALL AND COULD BE SIGNS OF 6873 05:18:02,760 --> 05:18:06,640 RESILIENCE AND OF SURVIVABLE OR 6874 05:18:06,640 --> 05:18:09,240 TRIVIAL BILOGICAL CHANGE NOT 6875 05:18:09,240 --> 05:18:10,960 SUBSTANTIVE BILOGICAL DAMAGE WE 6876 05:18:10,960 --> 05:18:12,400 ARE AIMING TO PREVENT AND 6877 05:18:12,400 --> 05:18:15,240 BECAUSE OR MOTIVATED BY OVENGSS 6878 05:18:15,240 --> 05:18:18,360 SECOND GENERATION OF EPIGENETIC 6879 05:18:18,360 --> 05:18:21,240 CLOCKS WAS DEVELOPED BY MORGAN 6880 05:18:21,240 --> 05:18:24,800 LEVINE DESIGNED TO PREDICT 6881 05:18:24,800 --> 05:18:35,320 BACKWARD TO TIME OF BIRTH -- 6882 05:19:00,240 --> 05:19:02,000 CAUSES OF DEATH IN OLDER PEOPLE 6883 05:19:02,000 --> 05:19:04,560 AND CHANGES ACCUMULATIVE AND 6884 05:19:04,560 --> 05:19:06,360 GREAT DEAL OF LIFE COURSE NOT 6885 05:19:06,360 --> 05:19:07,240 NECESSARILY CHANGE THAT IS 6886 05:19:07,240 --> 05:19:09,600 HAPPENING RIGHT NOW AND 6887 05:19:09,600 --> 05:19:10,960 CRITICALLY IMPORTANT DELIVERING 6888 05:19:10,960 --> 05:19:12,600 CLINICAL TRIAL THINKING OF 6889 05:19:12,600 --> 05:19:14,400 SLOWING DOWN PACE OF AGING TODAY 6890 05:19:14,400 --> 05:19:17,840 AND NOT REVERSING LIFETIME WORTH 6891 05:19:17,840 --> 05:19:19,640 OF BIOLOGICAL DAMAGE AND IN 6892 05:19:19,640 --> 05:19:21,640 RESPONSE TO LIMITATIONS WE 6893 05:19:21,640 --> 05:19:24,480 SOUGHT TO DEVELOP ALTERNATIVE 6894 05:19:24,480 --> 05:19:25,960 EPIGENETIC CLOCK AND THIS ONE 6895 05:19:25,960 --> 05:19:28,160 DESIGNED TO PREDICT PACE OF 6896 05:19:28,160 --> 05:19:32,720 AGING AND WE HAVE DONE 6897 05:19:32,720 --> 05:19:33,720 SUBSTITUTING COMPOSITE PACE OF 6898 05:19:33,720 --> 05:19:35,560 AGING MARKER FOR CHRONOLOGICAL 6899 05:19:35,560 --> 05:19:38,560 AGE OF MORTALITY IN MACHINE 6900 05:19:38,560 --> 05:19:41,360 LEARNING PARADIGM ATTEMPTING TO 6901 05:19:41,360 --> 05:19:42,240 DERIVE EPIGENETIC PREDICTION OF 6902 05:19:42,240 --> 05:19:45,200 PACE OF AGING AND WHAT COMES OUT 6903 05:19:45,200 --> 05:19:47,640 IS UNLIKE PREVIOUS CLOCK. YOU 6904 05:19:47,640 --> 05:19:50,960 CAN THINK OF ORIGINAL EPIGENETIC 6905 05:19:50,960 --> 05:19:53,200 CLOCK OR ODOMETER MEASURES 6906 05:19:53,200 --> 05:19:56,400 TELLING BUT MILES TRAVELED AND 6907 05:19:56,400 --> 05:20:00,240 WE ARE DOING A SPEED OM TER OR 6908 05:20:00,240 --> 05:20:01,560 RADAR GUN AND BLOOD TEST TELLING 6909 05:20:01,560 --> 05:20:12,120 YOU HOW FAST YOU ARE GOING NOW 6910 05:20:47,320 --> 05:20:49,400 -- FORMING PHENOTYPE IN MACHINE 6911 05:20:49,400 --> 05:20:52,640 LEARNING THAT DELIVERS THE FINAL 6912 05:20:52,640 --> 05:20:54,800 EPIGENETIC CLOCK ALGORITHM IN 6913 05:20:54,800 --> 05:20:57,040 PACE AND TIME POINTS BIOLOGICAL 6914 05:20:57,040 --> 05:20:58,440 MEASUREMENT FOUND TO BE 6915 05:20:58,440 --> 05:21:01,720 IMPORTANT REFINING GREAT DEAL OF 6916 05:21:01,720 --> 05:21:04,280 SIGNAL THAN 3 TIME POINT SLOPE 6917 05:21:04,280 --> 05:21:05,280 MEASUREMENT IS ABLE TO AND 6918 05:21:05,280 --> 05:21:07,200 POINTING OUT BECAUSE WE ARE 6919 05:21:07,200 --> 05:21:09,360 INITIATING FOLLOW UP IN YOUNG 6920 05:21:09,360 --> 05:21:11,280 ADULTHOOD IS A CLOCK DEVELOPED 6921 05:21:11,280 --> 05:21:13,360 FREE OF CONTAMINATION OF 6922 05:21:13,360 --> 05:21:15,640 SURVIVAL BIAS THAT IS DEVELOPED 6923 05:21:15,640 --> 05:21:17,560 IN A SINGLE YEAR BIRTH COHORT 6924 05:21:17,560 --> 05:21:20,720 AND WE KNOW THERE IS NO COHORT 6925 05:21:20,720 --> 05:21:22,040 EFFECTS CONTAMINATING THE SIGNAL 6926 05:21:22,040 --> 05:21:25,440 AND BECAUSE WE ARE CONDUCTING 6927 05:21:25,440 --> 05:21:27,240 REPEATED MEASUREMENTS TO 6928 05:21:27,240 --> 05:21:29,520 PHENOTYPE LONGITUDINAL CHANGE 6929 05:21:29,520 --> 05:21:32,040 CRITERIA MEASURE IS DATA MINING 6930 05:21:32,040 --> 05:21:34,080 PHENOTYPE AND KNOW WHEN IT IS 6931 05:21:34,080 --> 05:21:39,680 OCCURRING WITHIN HUMAN LIVES 6932 05:21:39,680 --> 05:21:42,800 ADDITIONALLY COULD SUGGEST DONE 6933 05:21:42,800 --> 05:21:44,480 A NUMBER OF TIMES BECAUSE PEOPLE 6934 05:21:44,480 --> 05:21:53,920 ARE IN MID LIFE MEASURING THEM 6935 05:21:53,920 --> 05:21:57,000 THAT MIGHT BE A TO BE DETERMINED 6936 05:21:57,000 --> 05:21:59,640 THING AND FEW WORDS WHAT IT IS 6937 05:21:59,640 --> 05:22:03,200 FIRST IS A TECHNICAL PROPERTY 6938 05:22:03,200 --> 05:22:05,760 AND STEVE HELPED PUT KAREN'S 6939 05:22:05,760 --> 05:22:07,640 PAPER UP EARLIER AND WILL 6940 05:22:07,640 --> 05:22:11,480 MENTION AGAIN OBSERVED IN 2020 6941 05:22:11,480 --> 05:22:13,240 PAPER SITES ON ALUM IN AN EPIC 6942 05:22:13,240 --> 05:22:16,080 RELAY HAVE LO HE RELIABILITY 6943 05:22:16,080 --> 05:22:17,360 IMPLEMENTED IN BLOOD RUNNING 6944 05:22:17,360 --> 05:22:21,880 SAME DNA TWO DIFFERENT ARRAYS 6945 05:22:21,880 --> 05:22:24,160 COMPARING CPG SITE BETWEEN THEM 6946 05:22:24,160 --> 05:22:25,960 YOU HAVE DIFFERENT ANSWERS 6947 05:22:25,960 --> 05:22:27,200 STUDYING CHANGE RESPONSE TO 6948 05:22:27,200 --> 05:22:29,480 TRIAL AND DEVELOPED EVEN PACE 6949 05:22:29,480 --> 05:22:31,600 TRAINING ALGORITHM ON SUBSET OF 6950 05:22:31,600 --> 05:22:32,640 PROBES OF ARRAY SHOWING BEST 6951 05:22:32,640 --> 05:22:36,960 TEST AND RETEST RELIABILITY YOU 6952 05:22:36,960 --> 05:22:39,640 SEE CONSEQUENCES OF EFFORT IN 6953 05:22:39,640 --> 05:22:43,880 BLOT AND Y AXIS COEFFICIENTS 6954 05:22:43,880 --> 05:22:45,640 REPEATABILITY OF MEASURE SAME 6955 05:22:45,640 --> 05:22:49,120 DNA TWO ARRAYS HOW SIMILAR ARE 6956 05:22:49,120 --> 05:22:50,600 MEASUREMENTS PACE AND GOLD AND 6957 05:22:50,600 --> 05:22:52,960 GENERATION IN ORANGE AND 6958 05:22:52,960 --> 05:22:55,640 EPIGENETIC CLOCKS IN BLUES AND 6959 05:22:55,640 --> 05:22:58,080 PURPLES AND SEE THAT IT PAYS IN 6960 05:22:58,080 --> 05:23:01,000 FACT REPRODUCIBLE AND FINAL 6961 05:23:01,000 --> 05:23:03,200 FARNLEST RIGHT GRAPH IS SHOWING 6962 05:23:03,200 --> 05:23:05,000 COMPARISON OF TWO DIFFERENT 6963 05:23:05,000 --> 05:23:06,480 FLAVORS ALUM IN AN ARRAY AND 6964 05:23:06,480 --> 05:23:09,240 THESE ARE GOING DOWN AND IS 6965 05:23:09,240 --> 05:23:11,320 WORTH NOTING ALBERT SPEAKING 6966 05:23:11,320 --> 05:23:13,880 NEXT SOLVING IN A PROBLEM IN A 6967 05:23:13,880 --> 05:23:16,240 GENERAL WAY OFFERING ELEGANTLY 6968 05:23:16,240 --> 05:23:18,040 FOR OTHER CLOCKS AND SPEAKING 6969 05:23:18,040 --> 05:23:21,960 BRIEFLY ABOUT THAT CHECKING OUT 6970 05:23:21,960 --> 05:23:23,480 HIGGINS JEN PAPER AND WE HAVE 6971 05:23:23,480 --> 05:23:25,080 THIS THING AND WHAT DOES IT DO 6972 05:23:25,080 --> 05:23:26,640 AND ONE THING IT DOES THAT IS 6973 05:23:26,640 --> 05:23:29,040 INTERESTING TO US IS SHOWING 6974 05:23:29,040 --> 05:23:30,440 HIGHER VALUES FASTER PACE OF 6975 05:23:30,440 --> 05:23:32,040 AGING IN OLDER PEOPLE AND THIS 6976 05:23:32,040 --> 05:23:34,920 IS A CLOCK THAT IS TRAINED IN 6977 05:23:34,920 --> 05:23:37,200 1,000 PEOPLE THAT ARE ALL SAME 6978 05:23:37,200 --> 05:23:39,240 CHRONOLOGICAL AGE AND BORN IN 6979 05:23:39,240 --> 05:23:41,480 SAME YEARS AND NO CHRONOLOGICAL 6980 05:23:41,480 --> 05:23:42,960 AGE VARIATION IN SOURCE MATERIAL 6981 05:23:42,960 --> 05:23:45,640 AND THERE IS WITH CHRONOLOGICAL 6982 05:23:45,640 --> 05:23:47,840 AGE IN MIXED POPULATIONS AND 6983 05:23:47,840 --> 05:23:52,360 1200 ADULTS IN UK AND RANGING IN 6984 05:23:52,360 --> 05:24:02,920 AGE 30 TO 90 -- MORTALITY RISK 6985 05:24:03,280 --> 05:24:05,680 WITH ADVANCING AGE AND WHAT WE 6986 05:24:05,680 --> 05:24:07,600 KNOW ABOUT DECLINING 6987 05:24:07,600 --> 05:24:09,280 PHYSIOLOGICAL INTEGRITY IN 6988 05:24:09,280 --> 05:24:11,120 PEOPLE'S BODIES GROWING OLDER 6989 05:24:11,120 --> 05:24:14,760 FOR EXAMPLE WITH LONGITUDINAL 6990 05:24:14,760 --> 05:24:16,200 STUDY OKAY IT DOES THE THING 6991 05:24:16,200 --> 05:24:18,920 THAT IT IS MAINLY SUPPOSED TO DO 6992 05:24:18,920 --> 05:24:21,280 PREDICTING WHEN TO GET SICK AND 6993 05:24:21,280 --> 05:24:27,280 HOW LONG TO LIVE NOT PERFECTLY 6994 05:24:27,280 --> 05:24:31,120 OF -- CARDIOVASCULAR DISEASE AND 6995 05:24:31,120 --> 05:24:37,600 STROKE AND DEMENTIA AND HEART 6996 05:24:37,600 --> 05:24:38,840 STUDY AND RIGHT SIGH DATA 6997 05:24:38,840 --> 05:24:42,440 SURVIVAL HEALTH ADMINISTRATION 6998 05:24:42,440 --> 05:24:45,240 AND FRAMING HAM HEART STUDY 6999 05:24:45,240 --> 05:24:48,040 OFFSPRING COHORT AND EFFECT 7000 05:24:48,040 --> 05:24:50,200 SIZES ARE COMPARABLE AND 7001 05:24:50,200 --> 05:24:51,640 REFERRING TO EARLIER WITH EFFECT 7002 05:24:51,640 --> 05:24:54,560 SIZES WE SEE FOR WHAT WE THINK 7003 05:24:54,560 --> 05:24:58,880 IS AS BEST IN CLASS BIOMARKER 7004 05:24:58,880 --> 05:25:08,800 PREDICTION IN MORTALITY -- WE 7005 05:25:08,800 --> 05:25:15,280 ALSO CARE ABOUT AGING AND THAT 7006 05:25:15,280 --> 05:25:17,400 IS SOMETHING I BROUGHT UP ON THE 7007 05:25:17,400 --> 05:25:20,240 FIRST DAY IN FIRST HALF AS WELL 7008 05:25:20,240 --> 05:25:21,240 CRITICALLY IMPORTANT SOMETHING 7009 05:25:21,240 --> 05:25:23,600 LOOKING TO INVALIDATING 7010 05:25:23,600 --> 05:25:27,520 BIOMARKERS AND DATA ON SCREEN 7011 05:25:27,520 --> 05:25:30,080 FROM ERISK LONGITUDINAL STUDY 7012 05:25:30,080 --> 05:25:33,280 CHILDREN BORN IN BRITAIN 1994 7013 05:25:33,280 --> 05:25:35,880 AND 1995 BLOOD SAMPLES TAKEN 7014 05:25:35,880 --> 05:25:38,520 WHEN 18 YEARS OLD AND SEEING 7015 05:25:38,520 --> 05:25:40,840 DIFFERENCE IN PACE BY CHILDHOOD 7016 05:25:40,840 --> 05:25:43,000 FAMILY SOCIAL CLASS MEASUREMENT 7017 05:25:43,000 --> 05:25:47,600 TAKEN IN AGE 5 AND HISTORY OF 7018 05:25:47,600 --> 05:25:51,160 VICTIMIZATION ACCUMULATED THESE 7019 05:25:51,160 --> 05:25:52,840 BETWEEN HAVING HARD CHILDHOOD 7020 05:25:52,840 --> 05:25:55,320 EVIDENCING FAST AGING ON DAWN OF 7021 05:25:55,320 --> 05:25:58,640 ADULTHOOD AND BOTTOM OF THE 7022 05:25:58,640 --> 05:26:00,000 SCREEN HIGHLIGHTING ON PREVIOUS 7023 05:26:00,000 --> 05:26:02,720 SLIDE AS WELL AND HANDFUL OF 7024 05:26:02,720 --> 05:26:04,880 COHORTS MIXED ANCESTRY AND RACE 7025 05:26:04,880 --> 05:26:07,640 ETHNICITY AND DIFFERENT 7026 05:26:07,640 --> 05:26:08,720 COUNTRIES REPLICATING BROAD 7027 05:26:08,720 --> 05:26:11,640 PATTERNS DRAWING ATTENTION TO 7028 05:26:11,640 --> 05:26:15,760 PAPER THAT WAS IN PARTICULARLY 7029 05:26:15,760 --> 05:26:20,320 IN GERONTOLOGY SHOWING 7030 05:26:20,320 --> 05:26:24,560 PATTERNING OF PACE BY 7031 05:26:24,560 --> 05:26:30,520 EDUCATIONAL ATTAINMENT AND TA 7032 05:26:30,520 --> 05:26:33,680 PAPER BY LAUREN SMITH AND FASTER 7033 05:26:33,680 --> 05:26:36,560 PACE OF AGING IN LATE LIFE AND 7034 05:26:36,560 --> 05:26:38,080 RETIREMENT STUDY AND AT END OF 7035 05:26:38,080 --> 05:26:41,520 THE DAY WE WANT TO KNOW HOW DOES 7036 05:26:41,520 --> 05:26:44,720 THIS MEASURE PERFORM IN CONTEXT 7037 05:26:44,720 --> 05:26:49,200 OF RTC AND HAD A CHANCE TO TEST 7038 05:26:49,200 --> 05:26:51,720 HYPOTHESIS AND CALORIE TRIAL 7039 05:26:51,720 --> 05:26:54,960 RANDOMIZED TRIAL OF LONG TERM 7040 05:26:54,960 --> 05:26:57,160 CALORIC RESTRICTION IN ADULTS 7041 05:26:57,160 --> 05:26:59,640 AND CONTROL FOR TWO YEARS 7042 05:26:59,640 --> 05:27:03,280 FAMOUSLY INTERVENTION ACHIEVED 7043 05:27:03,280 --> 05:27:06,720 HALF PRESCRIBED DOSE ON AVERAGE 7044 05:27:06,720 --> 05:27:10,160 PRODUCED SUBSTANTIAL WEIGHT LOSS 7045 05:27:10,160 --> 05:27:13,480 KILOGRAMS AND PUBLISHED BY KRAUS 7046 05:27:13,480 --> 05:27:15,360 AND COLLEAGUES AND ALSO IN OUR 7047 05:27:15,360 --> 05:27:18,320 HANDS SHOWS A SLOWING OF 7048 05:27:18,320 --> 05:27:20,280 INCREASE IN BLOOD CHEMISTRY 7049 05:27:20,280 --> 05:27:23,160 MEASURES OF BIOLOGICAL AGEING 7050 05:27:23,160 --> 05:27:25,920 THAT ARE ALSO COOL MOLECULAR 7051 05:27:25,920 --> 05:27:27,360 SCIENCE ANALYSIS PAPER FROM LAB 7052 05:27:27,360 --> 05:27:29,480 A COUPLE YEARS AGO SHOWING IT 7053 05:27:29,480 --> 05:27:31,200 MAY HAVE SLOWED IMMUNE AGING AND 7054 05:27:31,200 --> 05:27:35,320 YOU CAN SEE HERE EPIGENETIC 7055 05:27:35,320 --> 05:27:37,680 CLOCKS SECOND GENERATION DON'T 7056 05:27:37,680 --> 05:27:41,400 RESPOND TO INTERVENTION RATE OF 7057 05:27:41,400 --> 05:27:44,880 INCREASE IN ALBERT'S HIGH 7058 05:27:44,880 --> 05:27:46,400 TECHNICAL RELIABILITY OF 7059 05:27:46,400 --> 05:27:49,320 VERSIONS OF THESE ARE IDENTICAL 7060 05:27:49,320 --> 05:27:51,560 BETWEEN AD-LIB AND CONTROL AND 7061 05:27:51,560 --> 05:27:54,200 CONTRACT AND PAYS SHOWING 7062 05:27:54,200 --> 05:27:56,560 REDUCTION IN PACE OF AGING 7063 05:27:56,560 --> 05:27:57,240 RESPONSE INTERVENTION OVER FIRST 7064 05:27:57,240 --> 05:28:01,480 12 MONTHS OF FOLLOW UP AND 7065 05:28:01,480 --> 05:28:02,960 MAINTENANCE OF SLOWED RATE OF 7066 05:28:02,960 --> 05:28:04,360 AGING IN SECOND MONTHS OF FOLLOW 7067 05:28:04,360 --> 05:28:06,440 UP AND RUNNING OUT OF TIME WON'T 7068 05:28:06,440 --> 05:28:09,280 TELL YOU WHY THAT HAPPENED AND 7069 05:28:09,280 --> 05:28:11,440 SAVING FOR Q & A, PERHAPS. I 7070 05:28:11,440 --> 05:28:13,360 WILL LEAVE YOU WITH BROAD 7071 05:28:13,360 --> 05:28:15,280 CONCLUSION THAT WE THINK PACE OF 7072 05:28:15,280 --> 05:28:18,280 AGING IN GENERAL AND PACE IN 7073 05:28:18,280 --> 05:28:20,920 PARTICULAR MAY BE USEFUL 7074 05:28:20,920 --> 05:28:23,680 BIOMARKERS FOR SCIENCE AND MAY 7075 05:28:23,680 --> 05:28:27,680 IN PARTICULAR OFFER BENEFIT OF 7076 05:28:27,680 --> 05:28:30,200 INCREASED SENSITIVITY TO SHORT 7077 05:28:30,200 --> 05:28:31,600 TERM INTERVENTIONS AND FORGET 7078 05:28:31,600 --> 05:28:34,320 WHO BROUGHT THIS UP YESTERDAY. 7079 05:28:34,320 --> 05:28:35,480 MORAL IMPERATIVE EXPANDING 7080 05:28:35,480 --> 05:28:37,760 RESEARCH TO OTHER POPULATIONS IS 7081 05:28:37,760 --> 05:28:41,040 A CLEARLY CRITICAL FRONTIER 7082 05:28:41,040 --> 05:28:43,640 ACKNOWLEDGING NIA FUNDED DATA 7083 05:28:43,640 --> 05:28:45,360 GENERATION IN COHORTS NO THE 7084 05:28:45,360 --> 05:28:47,560 WELL WHITE EDUCATED -- AND 7085 05:28:47,560 --> 05:28:50,240 SEEING VALIDATION OF METRICS IN 7086 05:28:50,240 --> 05:28:52,120 COHORTS THAT IS TREMENDOUSLY 7087 05:28:52,120 --> 05:28:53,760 IMPORTANT AND CODE THAW WANT 7088 05:28:53,760 --> 05:28:57,000 PACE IS AVAILABLE WRITTEN BY 7089 05:28:57,000 --> 05:29:00,160 DAVID AND MAINTAINED BY KALIN 7090 05:29:00,160 --> 05:29:02,800 AND THANKS TO FUNDERS AND 7091 05:29:02,800 --> 05:29:05,880 COLLABORATORS AND TEAM AT 7092 05:29:05,880 --> 05:29:07,600 COLUMBIA. SO -- 7093 05:29:07,600 --> 05:29:11,600 >>>>ALL RIGHT. THANKS TO DAN, 7094 05:29:11,600 --> 05:29:14,000 NEXT SPEAKER IS ALBERT HIGGINS 7095 05:29:14,000 --> 05:29:15,920 CHEN WHO IS ASSISTANT PROFESSOR 7096 05:29:15,920 --> 05:29:18,120 IN DEPARTMENT OF PSYCHIATRY AND 7097 05:29:18,120 --> 05:29:20,080 DEPARTMENT OF PANELOLOGY AT YALE 7098 05:29:20,080 --> 05:29:24,760 UNIVERSITY DURING TRAINING AT 7099 05:29:24,760 --> 05:29:25,440 UNIVERSITY OF MICHIGAN WORKED 7100 05:29:25,440 --> 05:29:27,920 WITH -- AGING AND LONGEVITY AND 7101 05:29:27,920 --> 05:29:31,600 DURING CLINICAL PSYCHIATRY 7102 05:29:31,600 --> 05:29:35,560 RESIDENCE AT YALE UNIVERSITY 7103 05:29:35,560 --> 05:29:38,840 WORKED WITH DR. MORGAN LEFIN AND 7104 05:29:38,840 --> 05:29:42,200 STUDIED HOW BIOMARKERS ALTERED 7105 05:29:42,200 --> 05:29:44,200 IN HUMAN HEALTH AND TREATMENT 7106 05:29:44,200 --> 05:29:45,960 AND CONSTRUCTING AGING 7107 05:29:45,960 --> 05:29:48,280 BIOMARKERS FOR SPECIFICALLY 7108 05:29:48,280 --> 05:29:50,520 LONGITUDINAL INTERVENTION 7109 05:29:50,520 --> 05:29:52,440 STUDIES AND THOSE COMPLEMENTING 7110 05:29:52,440 --> 05:29:54,200 CLINICAL KNOWLEDGE AND DATA. 7111 05:29:54,200 --> 05:29:55,280 ALBERT, THANK YOU. 7112 05:29:55,280 --> 05:30:01,120 >>THANK YOU, JAICHLEE. 7113 05:30:01,120 --> 05:30:03,600 SO, ONE BIOLOGICAL AGE VERSUS 7114 05:30:03,600 --> 05:30:06,760 MANY BIOLOGICAL AGES AND LOTS OF 7115 05:30:06,760 --> 05:30:11,600 DISCUSSION AT SUMMIT ABOUT THE 7116 05:30:11,600 --> 05:30:14,120 QUEST 7117 05:30:14,120 --> 05:30:14,400 QUESTION. 7118 05:30:14,400 --> 05:30:16,040 MY TALK WILL BUILD OFF TALKS 7119 05:30:16,040 --> 05:30:19,800 BEFORE. IN PARTICULAR, THERE IS 7120 05:30:19,800 --> 05:30:24,000 SERENDIPITOUS COMPLEMENTIARITY 7121 05:30:24,000 --> 05:30:28,400 WITH EILEEN'S TALK AND AGING IN 7122 05:30:28,400 --> 05:30:30,160 HRS AND SHE WENT DEEP INTO ONE 7123 05:30:30,160 --> 05:30:34,560 STUDY AND I WANT TO GO BROAD AND 7124 05:30:34,560 --> 05:30:38,920 ASK BIGGER PICTURE QUESTIONS AND 7125 05:30:38,920 --> 05:30:41,320 COMPARISONS AND WHY AND WHAT IS 7126 05:30:41,320 --> 05:30:43,240 MOTIVATION FOR SYSTEMS 7127 05:30:43,240 --> 05:30:47,240 SPECIFICITY AND THIS IS A VERY 7128 05:30:47,240 --> 05:30:49,000 NEW TREND IN LITERATURE THOUGHT 7129 05:30:49,000 --> 05:30:51,720 IT WOULD BE USEFUL TO GO THROUGH 7130 05:30:51,720 --> 05:30:53,320 COMPARISON OF RECENT APPROACHES 7131 05:30:53,320 --> 05:30:57,280 AND ONE OF WHICH I'M PART OF 7132 05:30:57,280 --> 05:31:00,360 THAT WILL BE SPECIFIC 7133 05:31:00,360 --> 05:31:01,320 [INDISCERNIBLE] AND WILL END 7134 05:31:01,320 --> 05:31:02,880 WITH OUTSTANDING QUESTIONS ABOUT 7135 05:31:02,880 --> 05:31:06,680 THIS APPROACH AND AGING UNFOLDS 7136 05:31:06,680 --> 05:31:09,320 OVER TIME. 7137 05:31:09,320 --> 05:31:11,760 AGING WILL INVOLVE ACCUMULATION 7138 05:31:11,760 --> 05:31:14,040 OF BIOLOGICAL CHANGES OVER TIME 7139 05:31:14,040 --> 05:31:16,960 LEADING TO INCREASING RISK OF 7140 05:31:16,960 --> 05:31:18,920 DISFUNCTION AND DEATH AND 7141 05:31:18,920 --> 05:31:20,480 BIOMARKERS WE HAVE ARE ANCHORED 7142 05:31:20,480 --> 05:31:23,320 TO SINGLE TIMELINE AND WE HAVE 7143 05:31:23,320 --> 05:31:26,360 THOSE THAT PREDICT CHRONOLOGICAL 7144 05:31:26,360 --> 05:31:28,640 AGE TIME VERSUS BIRTH AND 7145 05:31:28,640 --> 05:31:30,640 PREDICTING MORTALITY AND DEATH 7146 05:31:30,640 --> 05:31:33,080 AND PREDICTIVE PACE OF AGING AND 7147 05:31:33,080 --> 05:31:36,280 AS SPEAKERS BEFORE ME DISCUSSED 7148 05:31:36,280 --> 05:31:38,480 LOTS OF CAVEATS TO MEASURES AND 7149 05:31:38,480 --> 05:31:41,080 ONE I WANT TO POINT OUT IN 7150 05:31:41,080 --> 05:31:43,480 PARTICULAR IS A MAJOR CONCEPTUAL 7151 05:31:43,480 --> 05:31:46,120 ONE THAT IS ASSUMING THAT AGING 7152 05:31:46,120 --> 05:31:49,360 IS A SINGLE STRAIGHT TIMELINE. 7153 05:31:49,360 --> 05:31:51,360 EACH OF THEM REPORTS OUT A 7154 05:31:51,360 --> 05:31:53,800 SINGLE NUMBER AND WHEN YOU USE 7155 05:31:53,800 --> 05:31:55,600 THEM TOGETHER, YOU ARE TREATING 7156 05:31:55,600 --> 05:31:58,400 AGING AS SINGLE UNIT DIMENSIONAL 7157 05:31:58,400 --> 05:32:03,000 PROCESS AND SINGLE BILOGICAL 7158 05:32:03,000 --> 05:32:05,120 AGE. COULD AGING BE LOTS MOR 7159 05:32:05,120 --> 05:32:07,920 LIKE THIS WHERE THERE COULD BE 7160 05:32:07,920 --> 05:32:10,880 MANY DIFFERENT TRAJECTORIES OF 7161 05:32:10,880 --> 05:32:11,880 AGING? CAPTURING SOMETHING LIKE 7162 05:32:11,880 --> 05:32:15,120 THIS, YOU NEED OR CAN'T JUST 7163 05:32:15,120 --> 05:32:18,000 HAVE A SINGLE NUMBER AND HAVE A 7164 05:32:18,000 --> 05:32:23,040 LOT MORE RICH DATA. 7165 05:32:23,040 --> 05:32:25,760 ONE TREND HAS BEEN TO LOOK AT 7166 05:32:25,760 --> 05:32:27,160 BIOLOGICAL AGES FOR DIFFERENT 7167 05:32:27,160 --> 05:32:29,200 ORGAN SYSTEMS THAT IS A PRETTY 7168 05:32:29,200 --> 05:32:32,000 NATURAL LEVEL AT WHICH TO DEFINE 7169 05:32:32,000 --> 05:32:36,120 MANY BIOLOGICAL AGES AND EACH 7170 05:32:36,120 --> 05:32:38,560 ORGAN SYSTEM IS DEFINED BY 7171 05:32:38,560 --> 05:32:41,040 COMMON FUNCTIONS AND RESPIRATORY 7172 05:32:41,040 --> 05:32:44,040 SYSTEM IS GETTING OXYGEN AND C02 7173 05:32:44,040 --> 05:32:50,200 OUT AND PROTECTING FROM 7174 05:32:50,200 --> 05:32:54,440 EXPOSURES AND IT IS ILLUMINATING 7175 05:32:54,440 --> 05:32:56,120 URINE AND THERE IS A SET NUMBER 7176 05:32:56,120 --> 05:32:59,080 OF SYSTEMS ABOUT A DOZEN 7177 05:32:59,080 --> 05:33:00,360 DEPENDING HOW YOU ARE FINDING 7178 05:33:00,360 --> 05:33:05,320 THEM AND GET A NUMBER OF 7179 05:33:05,320 --> 05:33:06,640 BIOLOGICAL AGES THAN SAY 7180 05:33:06,640 --> 05:33:08,640 DIFFERENT NUMBER FOR EVERY CELL 7181 05:33:08,640 --> 05:33:11,240 OF THE BODY AND DISEASES LINKED 7182 05:33:11,240 --> 05:33:13,600 TO ORGAN SYSTEMS AND MANY 7183 05:33:13,600 --> 05:33:14,960 DISEASES INVOLVE MULTIPLE 7184 05:33:14,960 --> 05:33:16,680 SYSTEMS YOU CAN STILL POINT TO 7185 05:33:16,680 --> 05:33:19,920 ONE OR TWO THAT ARE TYPICALLY 7186 05:33:19,920 --> 05:33:21,640 INVOLVED IN PANELOLOGY AND 7187 05:33:21,640 --> 05:33:23,640 OTHERS ARE SECONDARILY EFFECTED 7188 05:33:23,640 --> 05:33:27,360 AND RECENT TRENDS HAVE BEEN TO 7189 05:33:27,360 --> 05:33:29,200 MODIFY THE EXISTING PIPELINE FOR 7190 05:33:29,200 --> 05:33:31,600 DEVELOPING AGING BIOMARKERS TO 7191 05:33:31,600 --> 05:33:33,480 MAKE THEM MORE ORGAN SPECIFIC 7192 05:33:33,480 --> 05:33:35,920 AND RIGHT NOW YOU CAN USE A WIDE 7193 05:33:35,920 --> 05:33:39,360 VARIETY OF DATA AND FOR EXAMPLE 7194 05:33:39,360 --> 05:33:41,360 CLINICAL MARKERS AND CLINICAL 7195 05:33:41,360 --> 05:33:44,400 LABS AND VITAL SIGNS AND MEDICAL 7196 05:33:44,400 --> 05:33:48,280 TESTS AND MEDICAL HISTORY AND 7197 05:33:48,280 --> 05:33:48,920 SELF-REPORT, ET CETERA, ET 7198 05:33:48,920 --> 05:33:51,280 CETERA. THESE ARE COLLECTED BY 7199 05:33:51,280 --> 05:33:53,320 CLINICIANS AND RESEARCH STUDIES 7200 05:33:53,320 --> 05:33:54,960 AND CLINICIANS KNOW ALREADY HOW 7201 05:33:54,960 --> 05:33:57,760 TO ACT UPON THIS INFORMATION TO 7202 05:33:57,760 --> 05:33:59,960 MAKE AN AGING BOMBER YOU HAVE TO 7203 05:33:59,960 --> 05:34:04,680 AFRNGSOR ONE OF THREE OUTCOMES 7204 05:34:04,680 --> 05:34:05,320 CHRONOLOGICAL MORTALITY AGE OF 7205 05:34:05,320 --> 05:34:06,840 [INDISCERNIBLE] AND DATA YOU 7206 05:34:06,840 --> 05:34:09,880 HAVE CLINICAL LABS MORTALITY 7207 05:34:09,880 --> 05:34:11,520 BUILDING MORTALITY PROJECTOR 7208 05:34:11,520 --> 05:34:16,000 FROM THIS AND YOU HAVOMICS DATA 7209 05:34:16,000 --> 05:34:18,840 MENLO LOAM AND TRANSCRIPTOME, ET 7210 05:34:18,840 --> 05:34:20,440 CETERA AND ADVANTAGE IS 7211 05:34:20,440 --> 05:34:23,640 DISCOVERING NEW MARKERS NOT 7212 05:34:23,640 --> 05:34:24,680 CURREN 7213 05:34:24,680 --> 05:34:27,480 CURRENTLY USED CLINICALLY AND 7214 05:34:27,480 --> 05:34:29,240 DISADVANTAGED YOU DON'T 7215 05:34:29,240 --> 05:34:30,240 NECESSARILY KNOW WHAT CLINICAL 7216 05:34:30,240 --> 05:34:32,240 REFERENCE IS. THEREFORE, IT IS 7217 05:34:32,240 --> 05:34:35,600 COMMON FOR EXAMPLE WITH PACE 7218 05:34:35,600 --> 05:34:38,920 MEASURE OR PHENOAGE MEASURE TO 7219 05:34:38,920 --> 05:34:40,960 PREDICT CLINICAL THOUGHT 7220 05:34:40,960 --> 05:34:43,960 FROMOMICS DATA. 7221 05:34:43,960 --> 05:34:45,720 SO, THE -- THERE HAVE BEEN A 7222 05:34:45,720 --> 05:34:47,800 SLEW OF PAPERS OVER THE LAST 7223 05:34:47,800 --> 05:34:51,320 COUPLE YEARS TRYING TO MODIFY 7224 05:34:51,320 --> 05:34:54,920 THIS MOST COMMON STRATEGY IS 7225 05:34:54,920 --> 05:34:56,440 ORGANIZING MARKERS FIRST BY 7226 05:34:56,440 --> 05:34:59,240 SYSTEM THAT IS A PAPER THAT CAME 7227 05:34:59,240 --> 05:35:04,040 OUT LAST EARLIER THIS MONTH. IT 7228 05:35:04,040 --> 05:35:06,000 IS IN NATURE MEDICINE AND THEY 7229 05:35:06,000 --> 05:35:10,080 LOOKED AT SO MANY DIFFERENT BODY 7230 05:35:10,080 --> 05:35:12,160 PHENOTYPES AND 29 COGNITIVE 7231 05:35:12,160 --> 05:35:16,600 MEASURE AND MRI DERIVED BRAIN 7232 05:35:16,600 --> 05:35:18,200 MEASURES AND SIMPLY ORGANIZED 7233 05:35:18,200 --> 05:35:20,840 ALL THESE BIOMARKERS INTO 7234 05:35:20,840 --> 05:35:25,320 SYSTEMS BY MANUAL ANNOTATION AND 7235 05:35:25,320 --> 05:35:27,640 EXPERTS WOULD SAY THAT THESE 7236 05:35:27,640 --> 05:35:28,920 MARKERS OR WHAT SYSTEM EXPERTS 7237 05:35:28,920 --> 05:35:32,920 WOULD SAY THESE BELONG TO. 7238 05:35:32,920 --> 05:35:36,760 SO, THEY GENERATED TOOK 7239 05:35:36,760 --> 05:35:39,600 PHENOTYPES IN PULMONARY CLOCK 7240 05:35:39,600 --> 05:35:41,400 TRAINING PREDICTOR IN 7241 05:35:41,400 --> 05:35:43,600 CHRONOLOGICAL AGE AND PREDICTOR 7242 05:35:43,600 --> 05:35:45,760 OF CHRONOLOGICAL AGE, ET CETERA, 7243 05:35:45,760 --> 05:35:47,200 ET CETERA TO AVOID HAVING LOTS 7244 05:35:47,200 --> 05:35:49,800 OF ERRORS ON MY SLIDESLY DENOTE 7245 05:35:49,800 --> 05:35:52,000 THIS WITH A SINGLE BRACKET AND 7246 05:35:52,000 --> 05:35:54,160 KNOW THAT, THAT MEANS THAT EACH 7247 05:35:54,160 --> 05:35:59,640 OF THE CLOCKS WERE TRAINED 7248 05:35:59,640 --> 05:36:04,480 SEPARAT 7249 05:36:04,480 --> 05:36:06,400 SEPARATELY ADVANTAGE HERE IS 7250 05:36:06,400 --> 05:36:08,480 USING THIS IN SYSTEM AND WHAT TO 7251 05:36:08,480 --> 05:36:10,120 DO WITH THEM AND ADVANTAGE IS 7252 05:36:10,120 --> 05:36:12,040 DATA TO COLLECT ON LARGE NUMBER 7253 05:36:12,040 --> 05:36:14,640 OF PEOPLE IN A STANDARDIZED 7254 05:36:14,640 --> 05:36:16,360 FASHION AND ANOTHER PAPER THAT 7255 05:36:16,360 --> 05:36:21,400 IS FROM 2022 USED NOT JUST 7256 05:36:21,400 --> 05:36:27,000 CLINICAL DATA AND ALSO INCLU 7257 05:36:27,000 --> 05:36:29,680 INCLUDEDOMICS DATA AND 7258 05:36:29,680 --> 05:36:31,160 METABOLOMICS AND MYCOBIOME THAT 7259 05:36:31,160 --> 05:36:33,680 IS NOT IN THE CLINIC AND 7260 05:36:33,680 --> 05:36:38,000 DISCOVERING NEW BIOLOGY BY DOG 7261 05:36:38,000 --> 05:36:39,480 THIS THEY -- ISSUES THEY ARE 7262 05:36:39,480 --> 05:36:42,720 STILL ASSIGNING BIOMARKER 7263 05:36:42,720 --> 05:36:44,480 SYSTEMS BY MANUAL ORIENTATION 7264 05:36:44,480 --> 05:36:46,480 AND JUST LOOKING AT WHAT IS 7265 05:36:46,480 --> 05:36:48,160 KNOWN AND SEEING WHICH SYSTEM 7266 05:36:48,160 --> 05:36:51,040 THEY THINK THEY BELONG TO. 7267 05:36:51,040 --> 05:36:54,200 THEY PREDICTED CHRONOLOGICAL 7268 05:36:54,200 --> 05:36:54,600 AGE. 7269 05:36:54,600 --> 05:36:58,280 THIS IS A PAPER FROM -- THERE IS 7270 05:36:58,280 --> 05:37:02,200 AT TERNTIVE METHODS AND PAPER 7271 05:37:02,200 --> 05:37:05,280 FROM 2020 THAT TOOK BLOOD, 7272 05:37:05,280 --> 05:37:09,360 STOOL, AND NASAL SAMPLES 7273 05:37:09,360 --> 05:37:12,320 PERFORMNESS OMICS ANALYSIS AND 7274 05:37:12,320 --> 05:37:14,120 CLINICAL BLOOD TEST THANDZ IS 7275 05:37:14,120 --> 05:37:15,520 INTERESTING DIDN'T DO MANUAL 7276 05:37:15,520 --> 05:37:18,480 ORIENTATION AND WERE STILL 7277 05:37:18,480 --> 05:37:21,160 PREASSIGNING DOING ITERATIVE 7278 05:37:21,160 --> 05:37:25,200 PATHWAY ANALYSIS AND THEY HAVE 7279 05:37:25,200 --> 05:37:27,400 FOUR PATHWAYS TO DELIVER 7280 05:37:27,400 --> 05:37:30,160 METABOLISM AND INFORMATION AND 7281 05:37:30,160 --> 05:37:32,800 RICH LONGITUDINAL DATA SET FOR 7282 05:37:32,800 --> 05:37:33,840 INDIVIDUALS AND WERE ABLE TO 7283 05:37:33,840 --> 05:37:44,360 HAVE PACE OF AGING MEASURE ONE 7284 05:37:45,400 --> 05:37:46,480 ADVANTAGE HERE MAKING 7285 05:37:46,480 --> 05:37:48,680 ASSUMPTIONS WHAT BIOMARKERS 7286 05:37:48,680 --> 05:37:50,080 BELONG TO AND WHAT IS 7287 05:37:50,080 --> 05:37:52,720 SIGNIFICANT SEEING FROM VENN 7288 05:37:52,720 --> 05:37:55,160 DIAGRAM SIGNIFICANT OVERLAP 7289 05:37:55,160 --> 05:38:01,120 BETWEEN PATHWAYS ANOTHER WAY 7290 05:38:01,120 --> 05:38:03,000 QUITE INTERESTING FROM PAPER 7291 05:38:03,000 --> 05:38:04,480 INTERESTING EXPLAINABLE AI WORK 7292 05:38:04,480 --> 05:38:07,640 AND TRAINING WORK IS THEY DIDN'T 7293 05:38:07,640 --> 05:38:09,480 PREASSIGN BIOMARKERS TO ANY 7294 05:38:09,480 --> 05:38:13,440 SYSTEM AT ALL AND THEY TOOK 250 7295 05:38:13,440 --> 05:38:16,880 FEATURES FROM DATA TYPES AND 7296 05:38:16,880 --> 05:38:19,280 DEFINITION OF SPECIFICITY COMES 7297 05:38:19,280 --> 05:38:20,880 AT OUTCOME LEVEL AND THEY USE 7298 05:38:20,880 --> 05:38:24,200 DIFFERENT FEATURES FIRST TRAIN 7299 05:38:24,200 --> 05:38:29,000 OF THOUGHT FOR MORTALITY DUE TO 7300 05:38:29,000 --> 05:38:30,640 CANCER HEART DISEASE AND 7301 05:38:30,640 --> 05:38:31,760 DIGESTIVE DISEASE AND OTHER 7302 05:38:31,760 --> 05:38:32,880 CAUSES THAT IS A VERY 7303 05:38:32,880 --> 05:38:34,800 INTERESTING WAY. YOU ARE NOT 7304 05:38:34,800 --> 05:38:37,000 MAKING ANY PREASSUMPTIONS ABOUT 7305 05:38:37,000 --> 05:38:40,880 WHAT BELONGS TO WHAT. YOU CAN 7306 05:38:40,880 --> 05:38:43,440 DISCOVER NEW RELATIONSHIPS 7307 05:38:43,440 --> 05:38:46,320 ALTHOUGH ARGUABLY THIS WILL LEAD 7308 05:38:46,320 --> 05:38:48,440 TO A LOT MORE RELATIONSHIPS DOO 7309 05:38:48,440 --> 05:38:52,080 YOU TO CORRELATION NOT 7310 05:38:52,080 --> 05:38:54,040 CAUSATION. 7311 05:38:54,040 --> 05:38:56,080 ALL THESE GROUPS DID AN 7312 05:38:56,080 --> 05:38:57,800 INCREDIBLE AMOUNT OF WORK AND I 7313 05:38:57,800 --> 05:38:59,480 CAN'T DO JUSTICE TO ALL OF THEM. 7314 05:38:59,480 --> 05:39:02,080 I WANT TO POINT OUT THAT THE 7315 05:39:02,080 --> 05:39:05,360 GENERAL CONSENSUS IS THAT 7316 05:39:05,360 --> 05:39:08,120 RESULTS FROM MULTIPLE STUDIES 7317 05:39:08,120 --> 05:39:10,680 SUGGEST THAT SPECIFICITY IS 7318 05:39:10,680 --> 05:39:12,360 USEFUL AND ORGANIZATIONS VARY IN 7319 05:39:12,360 --> 05:39:15,160 WHICH SYSTEMS AGE AND MOST 7320 05:39:15,160 --> 05:39:18,200 SYSTEMS CONTRIBUTE TO PREDICTION 7321 05:39:18,200 --> 05:39:20,920 OF MORTALITY AND MUTUALLY 7322 05:39:20,920 --> 05:39:22,480 SUBJECTIVE MODELS YOU ARE 7323 05:39:22,480 --> 05:39:25,280 GETTING MORE INFORMATION BY 7324 05:39:25,280 --> 05:39:27,120 USING MULTIPLE BILOGICAL AGES 7325 05:39:27,120 --> 05:39:29,520 AND IN ONE SYSTEM COULD EFFECT 7326 05:39:29,520 --> 05:39:32,760 AGING RACE IN OTHER SYSTEMS THAT 7327 05:39:32,760 --> 05:39:37,800 LARGELY SHOW ASSOCIATIONS MAKING 7328 05:39:37,800 --> 05:39:38,160 SENSE. 7329 05:39:38,160 --> 05:39:41,880 SO, THIS IS GETTING THE IDEA OF 7330 05:39:41,880 --> 05:39:43,400 SYSTEM SPECIFICITY. 7331 05:39:43,400 --> 05:39:46,200 SO, I WANT TO TALK A LITTLE 7332 05:39:46,200 --> 05:39:47,600 ABOUT SOMETHING WE DID WE WERE 7333 05:39:47,600 --> 05:39:49,920 ASKING HOW FAR WE CAN ACTUALLY 7334 05:39:49,920 --> 05:39:51,320 TAKE THIS CONCEPT. 7335 05:39:51,320 --> 05:39:56,400 SO, THIS IS WORK DONE BY RAGO 7336 05:39:56,400 --> 05:39:59,040 SEGAL FIRST AUTHOR IN AUDIENCE 7337 05:39:59,040 --> 05:40:03,800 AND PROJECT LED BY MORGAN LEVINE 7338 05:40:03,800 --> 05:40:08,120 AND BROUGHT ON AFTER RAJ JOINED 7339 05:40:08,120 --> 05:40:10,280 MY LAB AT YALE AND HELPING TO 7340 05:40:10,280 --> 05:40:11,800 CONSIDER CLINICAL IMPLICATIONS 7341 05:40:11,800 --> 05:40:13,120 OF THE MEASURE. 7342 05:40:13,120 --> 05:40:15,960 BUT, ESSENTIALLY, ALSO IN THE 7343 05:40:15,960 --> 05:40:19,800 HEALTH AND RETIREMENT STUDY AND 7344 05:40:19,800 --> 05:40:22,840 EILEEN'S STUDY LOOKING AT AGING 7345 05:40:22,840 --> 05:40:26,120 BIOMARKERS 11 SYSTEMS IN 7346 05:40:26,120 --> 05:40:26,840 BIOMANUAL [INDISCERNIBLE] AND 7347 05:40:26,840 --> 05:40:28,280 WHEN WE THOUGHT ABOUT THIS FACT 7348 05:40:28,280 --> 05:40:32,040 THAT THERE IS A LOT OF 7349 05:40:32,040 --> 05:40:33,240 BIOMARKERS TO COLLECT. 7350 05:40:33,240 --> 05:40:35,200 THERE IS A LOT OF FUNCTIONAL 7351 05:40:35,200 --> 05:40:39,240 MEASURES YOU NEED TO HAVE 7352 05:40:39,240 --> 05:40:40,560 TRAINED RATERS AND TRAINED 7353 05:40:40,560 --> 05:40:42,400 CLINICIANS AND WHAT NOT AND WE 7354 05:40:42,400 --> 05:40:45,080 ASKED WHETHER OR NOT YOU COULD 7355 05:40:45,080 --> 05:40:45,600 ACTUALLY JUST COMPRESS 7356 05:40:45,600 --> 05:40:47,640 INFORMATION INTO BLOOD DNA 7357 05:40:47,640 --> 05:40:48,800 METHYLATION AND BLOOD BECAUSE IT 7358 05:40:48,800 --> 05:40:55,680 IS A HIGHLY ACCESSIBLE TISSUE 7359 05:40:55,680 --> 05:40:56,800 AND WE 7360 05:40:56,800 --> 05:40:58,440 USED PAIRED -- CLINICAL MARKER 7361 05:40:58,440 --> 05:41:00,520 TO TRAIN A CLOCK AND PREDICTORS 7362 05:41:00,520 --> 05:41:03,400 OF VARIOUS ASPECTS OF KIDNEY 7363 05:41:03,400 --> 05:41:04,840 AGING AND HERE SINCE I MENTIONED 7364 05:41:04,840 --> 05:41:10,640 IT WE ARE USING THE HIGH 7365 05:41:10,640 --> 05:41:14,160 RELIABILITY CLOCK APPROACH AND 7366 05:41:14,160 --> 05:41:19,960 METHYLATION AND ALSO FOR KIDNEY 7367 05:41:19,960 --> 05:41:22,120 BIOMARKERS AND METHYLATION DATA 7368 05:41:22,120 --> 05:41:25,960 IS IN OTHER COHORTS YOU CAN 7369 05:41:25,960 --> 05:41:27,720 EASILY RECALCULATION METHYLATION 7370 05:41:27,720 --> 05:41:30,200 MARKERS IN ONE DATA SET AND 7371 05:41:30,200 --> 05:41:32,440 IMPORT TO ANOTHER AND 7372 05:41:32,440 --> 05:41:33,840 METHYLATION MORTALITY DATA FROM 7373 05:41:33,840 --> 05:41:36,760 FRAMING HART STUDY TO TRAIN 7374 05:41:36,760 --> 05:41:38,480 MORTALITY PREDICTOR AND GET A 7375 05:41:38,480 --> 05:41:41,320 LONGER FOLLOW UP TIME FOR 7376 05:41:41,320 --> 05:41:42,000 MORTALITY AND SAME THING FOR 7377 05:41:42,000 --> 05:41:44,520 HEART AND DOING THE SAME FOR 7378 05:41:44,520 --> 05:41:47,920 OTHER 11 SYSTEMS THAT PROVIDES 7379 05:41:47,920 --> 05:41:48,760 11 DIFFERENT [INDISCERNIBLE] AND 7380 05:41:48,760 --> 05:41:51,520 WHAT IS INTERESTING IS THAT YOU 7381 05:41:51,520 --> 05:41:55,400 DON'T NEED INITIAL 130 DIFFERENT 7382 05:41:55,400 --> 05:41:58,960 BIOMARKERS THAN CALCULATING 7383 05:41:58,960 --> 05:42:01,120 DIFFERENT 11 EPIGENETIC CLOCKS 7384 05:42:01,120 --> 05:42:06,240 AND GETTING FROM SINGLE DNA 7385 05:42:06,240 --> 05:42:08,040 METHYLATION ASSAY AND RAGA WAS 7386 05:42:08,040 --> 05:42:09,880 ABLE TO CALCULATE THIS AND THESE 7387 05:42:09,880 --> 05:42:12,920 IN WOMEN'S HEALTH INITIATIVE AND 7388 05:42:12,920 --> 05:42:17,320 HAS 20 YEARS OF FOLLOWUP AND SO 7389 05:42:17,320 --> 05:42:27,960 HE FORMED METAANALYSIS SYSTEMS 7390 05:42:27,960 --> 05:42:38,480 OUTCOMES AND SO FOR BREVITY WE 7391 05:42:41,280 --> 05:42:42,680 SUMMARIZED AND TOOK Z SCORE 7392 05:42:42,680 --> 05:42:46,760 PLOTTED ON BODY PLOT AND TEXT 7393 05:42:46,760 --> 05:42:57,320 SIDE IS PROPORTIONAL TO Z SCORE 7394 05:43:00,680 --> 05:43:05,520 AND THERE IS -- MUSCULOSKELETAL 7395 05:43:05,520 --> 05:43:09,600 INFORMATION AND HEART AND 7396 05:43:09,600 --> 05:43:13,320 COMORBIDITIES BASELINE 7397 05:43:13,320 --> 05:43:14,520 MUSCULOSKELETAL WITH DIABETES 7398 05:43:14,520 --> 05:43:18,280 AND DISEASES HORMONE AND HEART 7399 05:43:18,280 --> 05:43:19,240 AND SKELETAL INFORMATION AND 7400 05:43:19,240 --> 05:43:22,680 CATARACT MULTIPLE SYSTEMS AND 7401 05:43:22,680 --> 05:43:25,320 TIED TO DISEASE EVENTS AND 7402 05:43:25,320 --> 05:43:26,840 PEOPLE WITHOUT DISEASE AND 7403 05:43:26,840 --> 05:43:30,360 DEVELOP DISEASE AND LUNG CANCERS 7404 05:43:30,360 --> 05:43:35,600 PREDICTED BY LUNG AND HEART AND 7405 05:43:35,600 --> 05:43:43,640 -- CORONARY HEART DISEASE AND 7406 05:43:43,640 --> 05:43:47,480 INFLAMMATION GETTING TO SYSTEM 7407 05:43:47,480 --> 05:43:49,840 MORTALITIES AND IT IS NOT 7408 05:43:49,840 --> 05:43:50,520 RANDOMLY ASSOCIATED WITH LOTS OF 7409 05:43:50,520 --> 05:43:54,240 DIFFERENT OUTCOMES AND WE ALSO 7410 05:43:54,240 --> 05:43:55,920 COMBINE THEM IN SINGLE SYSTEMS 7411 05:43:55,920 --> 05:43:58,800 AGE SCORE AND DUE TO TIME I 7412 05:43:58,800 --> 05:44:01,480 WON'T GO -- I WILL PREEFLY SAY 7413 05:44:01,480 --> 05:44:03,400 WE COMPARE THESE OTHER CLOCKS 7414 05:44:03,400 --> 05:44:05,920 FOR VARIETY OF CONDITIONS AND 7415 05:44:05,920 --> 05:44:07,680 SYSTEMS AGE FIRST PREDICTS EACH 7416 05:44:07,680 --> 05:44:11,000 SYSTEM INDIVIDUALLY AND WON'T BE 7417 05:44:11,000 --> 05:44:13,880 BIASED AND ALL SYSTEMS ALLOWED 7418 05:44:13,880 --> 05:44:15,400 TO CONTRIBUTE TO FULL MEASURE 7419 05:44:15,400 --> 05:44:17,240 NOT BIASED TOWARDS ANY 7420 05:44:17,240 --> 05:44:19,640 PARTICULAR OUTCOME AND TRAINED 7421 05:44:19,640 --> 05:44:20,840 PREDICTOR OF MORTALITY STRAIGHT 7422 05:44:20,840 --> 05:44:25,000 OFF GETTING THINGS LIKE HEART 7423 05:44:25,000 --> 05:44:26,560 DISEASE OR CANCER. 7424 05:44:26,560 --> 05:44:30,120 SAME QUESTIONS, SO, SHALL 7425 05:44:30,120 --> 05:44:32,640 SYSTEM SPECIFIC IS BASED ON 7426 05:44:32,640 --> 05:44:34,560 PRE-EXISTING NOTIONS WHAT 7427 05:44:34,560 --> 05:44:36,120 BIOMARKERS AND OUTCOMES BELONGS 7428 05:44:36,120 --> 05:44:39,400 TO EACH SYSTEM RAISING A 7429 05:44:39,400 --> 05:44:41,240 PHILOSOPHICAL QUESTION AND 7430 05:44:41,240 --> 05:44:42,800 ULTIMATELY FROM PRACTICAL 7431 05:44:42,800 --> 05:44:45,400 STANDPOINT WE ARE SIMPLY 7432 05:44:45,400 --> 05:44:47,640 LEVERAGING CLINICAL WIS COME 7433 05:44:47,640 --> 05:44:51,400 THAT WE ALREADY ACCUMULATED IN 7434 05:44:51,400 --> 05:44:54,440 TRYING TO MAKE THESE JUDGMENTS. 7435 05:44:54,440 --> 05:45:04,960 SOME SUBJECTIVE IS ACTUALLY OKAY 7436 05:45:05,960 --> 05:45:07,600 ONE IMPORTANT THING WE HAVE 7437 05:45:07,600 --> 05:45:09,160 CLINICAL JUDGMENTS TAKING INTO 7438 05:45:09,160 --> 05:45:11,600 ACCOUNT WIDE VARIETY OF 7439 05:45:11,600 --> 05:45:14,000 INFORMATION FAMILY HISTORY AND 7440 05:45:14,000 --> 05:45:15,400 SOCIAL DETERMINANTS OF HEALTH, 7441 05:45:15,400 --> 05:45:18,000 ET CETERA AND ARE BIOMARKERS 7442 05:45:18,000 --> 05:45:18,720 ADDING PREDICTIVE INFORMATION? 7443 05:45:18,720 --> 05:45:21,640 I WILL SAY IT IS IMPORTANT GIVEN 7444 05:45:21,640 --> 05:45:23,640 RELATIVE INTERPRETABILITY OF 7445 05:45:23,640 --> 05:45:25,280 MEASURES YOU KNOW WHAT 7446 05:45:25,280 --> 05:45:27,400 BIOMARKERS GOES INTO SYSTEMS AND 7447 05:45:27,400 --> 05:45:31,440 IS BEST TO ASK CLIN IKSS ABOUT 7448 05:45:31,440 --> 05:45:33,280 ANY GIVEN RESULT AND PEOPLE KNOW 7449 05:45:33,280 --> 05:45:42,360 ABOUT THESE BIOMARKERS WHEN WE 7450 05:45:42,360 --> 05:45:45,360 HAVE THESE SPECIFIC BIOMARKERS 7451 05:45:45,360 --> 05:45:46,400 ENOUGH TO PARTITION THEM INTO 7452 05:45:46,400 --> 05:45:48,040 DIFFERENT SYSTEMS AND IF YOU 7453 05:45:48,040 --> 05:45:50,360 WILL BE HAVING HUNDREDS OF 7454 05:45:50,360 --> 05:45:53,360 MEASUREMENTS OF DIFFERENT TYPES 7455 05:45:53,360 --> 05:45:59,240 IT WILL BE CHALLENGING TO 7456 05:45:59,240 --> 05:45:59,840 OPTIMIZE THEM AND CONSIDERING 7457 05:45:59,840 --> 05:46:03,440 PREDICTIVE INFORMATION AND 7458 05:46:03,440 --> 05:46:06,920 MISSING VALUES AND BETWEEN 7459 05:46:06,920 --> 05:46:08,880 CLINICIANS AND LABS, ET CETERA. 7460 05:46:08,880 --> 05:46:10,960 MOVING TOWARDS COMPRESSING 7461 05:46:10,960 --> 05:46:12,160 RELEVANT INFORMATION AND FEWER 7462 05:46:12,160 --> 05:46:15,160 TESTS COULD BE PROMISING 7463 05:46:15,160 --> 05:46:16,280 STRATEGY. 7464 05:46:16,280 --> 05:46:17,840 FINALLY, QUESTIONS THAT OTHERS 7465 05:46:17,840 --> 05:46:20,920 HAVE MENTIONED THAT APPLY TO 7466 05:46:20,920 --> 05:46:22,960 GENERAL BIOMARKERS APPLY HERE 7467 05:46:22,960 --> 05:46:25,840 AND WE NEED TO THINK MORE ABOUT 7468 05:46:25,840 --> 05:46:27,040 EXPLAINABILITY AND UNDERLYING 7469 05:46:27,040 --> 05:46:28,280 MECHANISMS AND WHETHER OR NOT IN 7470 05:46:28,280 --> 05:46:33,440 COULD BE USED AS SURROGATE 7471 05:46:33,440 --> 05:46:36,960 BIOMAR 7472 05:46:36,960 --> 05:46:37,280 BIOMARKERS. 7473 05:46:37,280 --> 05:46:38,720 SINGLE NUMBER IF ANY THIS IS 7474 05:46:38,720 --> 05:46:39,440 SOMETHING WE SHOULD BE 7475 05:46:39,440 --> 05:46:43,280 CONSIDERING AND HERE ARE ALL OF 7476 05:46:43,280 --> 05:46:43,760 THE REFERENCES. 7477 05:46:43,760 --> 05:46:54,040 >>[APPLAUSE]. 7478 05:47:10,960 --> 05:47:14,080 >>NEXT SPEAKER IS MARTIN AND HE 7479 05:47:14,080 --> 05:47:15,960 HAD SP [INDISCERNIBLE] AND 7480 05:47:15,960 --> 05:47:19,640 COMPLETED POST DOCTORAL 7481 05:47:19,640 --> 05:47:23,000 FELLOWSHIP WITH DOUG WALLACE AT 7482 05:47:23,000 --> 05:47:24,400 UNIVERSITY OF PENNSYLVANIA 7483 05:47:24,400 --> 05:47:26,720 ASSOCIATE PROFESSOR OF 7484 05:47:26,720 --> 05:47:30,040 BEHAVIORAL MEDICINE IN 7485 05:47:30,040 --> 05:47:33,440 PSYCHIATRY AND NEUR OL AND 7486 05:47:33,440 --> 05:47:37,160 DIRECTS MITOCHONDRIAL 7487 05:47:37,160 --> 05:47:39,160 PSYCHOBIOLOGY GROUP. 7488 05:47:39,160 --> 05:47:42,600 RESEARCH PROGRAM FOCUSES ON 7489 05:47:42,600 --> 05:47:45,480 IDENTIFYING ORGANELLE TO 7490 05:47:45,480 --> 05:47:48,520 ORGANISM PROCESSES AND SMALL 7491 05:47:48,520 --> 05:47:50,520 INTRACELLULAR ORGANELLES 7492 05:47:50,520 --> 05:47:51,640 SUSTAINING LIFE AND RESILIENCE 7493 05:47:51,640 --> 05:47:53,640 AND ARE LOOKING FORWARD TO 7494 05:47:53,640 --> 05:47:55,320 HEARING ABOUT COLLABORATIVE WORK 7495 05:47:55,320 --> 05:47:57,720 FROM CLINICAL AND CELLULAR 7496 05:47:57,720 --> 05:47:59,640 COMPUTATIONAL APPROACHES FROM 7497 05:47:59,640 --> 05:48:08,600 PROCESSES IN BRAIN BODY UNITS. 7498 05:48:08,600 --> 05:48:12,440 >>THANK YOU. HAPPY TO BE HERE. 7499 05:48:12,440 --> 05:48:19,120 I AM HAPPY TO BE HERE TO TALK TO 7500 05:48:19,120 --> 05:48:22,480 YOU. BEFORE I DIVE INTO 7501 05:48:22,480 --> 05:48:29,000 MITOCHONDRIA SHOWING SOMETHING 7502 05:48:29,000 --> 05:48:31,160 WE CAME ACROSS MICROSCOPY OF 7503 05:48:31,160 --> 05:48:33,080 HUMAGE HAIR AND TRAVELING ALONG 7504 05:48:33,080 --> 05:48:35,600 TIP OF HAIR AND TRAVELING DOWN 7505 05:48:35,600 --> 05:48:36,840 AND SEEING YOUNG DARK HAIR 7506 05:48:36,840 --> 05:48:39,640 TURNING WHITE AND NOW WE ARE IN 7507 05:48:39,640 --> 05:48:43,240 OLD PART OF THE HAIR LOST 7508 05:48:43,240 --> 05:48:45,960 PIGMENTATION UNDENIABLE HALLMARK 7509 05:48:45,960 --> 05:48:48,280 OF HAIR AGING HAIR GRAIN AND 7510 05:48:48,280 --> 05:48:51,200 OBSERVING IN SINGLE HAIR YOU SEE 7511 05:48:51,200 --> 05:48:52,680 PIGMENT COMING BACK AND BROWN IS 7512 05:48:52,680 --> 05:48:56,760 SOMEHOW RETURNING AND ALL OF A 7513 05:48:56,760 --> 05:48:59,120 SUDDEN HAIR IS DARK AGAIN 7514 05:48:59,120 --> 05:49:00,720 REVERSAL OF HAIR GRAIN IN HUMAN 7515 05:49:00,720 --> 05:49:03,240 HAIR DEVELOPING APPROACH TO MAP 7516 05:49:03,240 --> 05:49:06,240 THIS AND TAKING SINGLE HAIR AND 7517 05:49:06,240 --> 05:49:09,480 PUTTING ON HIGH RES SCANNER AND 7518 05:49:09,480 --> 05:49:12,000 PROFILE IS ORIGINALLY ON GRAPH 7519 05:49:12,000 --> 05:49:15,440 AND LOSING PIGMENTATION AND 7520 05:49:15,440 --> 05:49:16,720 RECOVERS PIGMENTATION AND FOUND 7521 05:49:16,720 --> 05:49:18,200 IN PARTICULAR PARTICIPANT AND 7522 05:49:18,200 --> 05:49:20,400 OTHER PEOPLE CORRELATED ARE 7523 05:49:20,400 --> 05:49:24,080 LEVELS OF REPORTED LIFE STRESS 7524 05:49:24,080 --> 05:49:26,440 AND THAT PARTICULAR PERSON 7525 05:49:26,440 --> 05:49:27,560 EXPERIENCED SAYING IN WORDS MOST 7526 05:49:27,560 --> 05:49:30,120 STRESSFUL TWO MONTHS OF HER LIFE 7527 05:49:30,120 --> 05:49:32,720 AND MATCHED STRESS GRAPH HERE. 7528 05:49:32,720 --> 05:49:35,080 FINISHED PHD AND SHE WAS GOING 7529 05:49:35,080 --> 05:49:36,240 THROUGH DIFFICULT LIFE STRESS 7530 05:49:36,240 --> 05:49:38,280 WITH RELATIONSHIP ISSUES AND 7531 05:49:38,280 --> 05:49:40,080 BROKE UP WITH PARTNER AND MOVED 7532 05:49:40,080 --> 05:49:42,240 ACROSS COUNTRY AND LIFE WAS GOOD 7533 05:49:42,240 --> 05:49:46,400 AGAIN AND HAIR RECOVERED COLOR 7534 05:49:46,400 --> 05:49:51,640 AND ILLUSTRATES PLASTICITY AND 7535 05:49:51,640 --> 05:49:54,080 HUMAN IMAGING IN QUANTITATIVE 7536 05:49:54,080 --> 05:49:56,880 WAY AND PSYCHOLOGICAL STATES AND 7537 05:49:56,880 --> 05:49:58,480 STRESS IN HUMANS. 7538 05:49:58,480 --> 05:50:01,640 WE DID SINGLE HAIR PROTEOMICS 7539 05:50:01,640 --> 05:50:03,480 HELL OF A CHALLENGE BUT 7540 05:50:03,480 --> 05:50:04,640 INTERESTING WHAT CHANGES IN HAIR 7541 05:50:04,640 --> 05:50:06,360 WHEN GOES OLD AND LOSES COLOR 7542 05:50:06,360 --> 05:50:08,880 AND RECOVERS COLOR AND TURNS OUT 7543 05:50:08,880 --> 05:50:11,640 YOU SEE VOLCANO PLOT HERE 7544 05:50:11,640 --> 05:50:13,200 PROTEINS DOWNREGULATED ON LEFT 7545 05:50:13,200 --> 05:50:15,120 OR UPREGULATED ON RIGHT AND 7546 05:50:15,120 --> 05:50:21,440 MAJORITY OF PRO E- TEENS ARE UP 7547 05:50:21,440 --> 05:50:32,000 REGULATED WHY CARE ABOUT ENERGY 7548 05:50:33,640 --> 05:50:37,480 AND MITOCHONDRIA PAINTING A 7549 05:50:37,480 --> 05:50:40,440 BRIEF PICTURE LOU EVENI DID GOOD 7550 05:50:40,440 --> 05:50:44,200 WITH THIS YESTERDAY AND GIVING A 7551 05:50:44,200 --> 05:50:46,760 BRIEF SUMMARY FROM MY 7552 05:50:46,760 --> 05:50:48,880 PERSPECTIVE WE CARE ABOUT THESE 7553 05:50:48,880 --> 05:50:51,800 AND PRESERVING PERSON AND 7554 05:50:51,800 --> 05:50:53,920 BIOLOGY AND FIZZ YOL AND 7555 05:50:53,920 --> 05:50:56,960 COGNITION AND HUMAN 7556 05:50:56,960 --> 05:50:58,400 CONSCIOUSNESS RELIES ON HUMAN 7557 05:50:58,400 --> 05:51:00,600 FIZZ YOL AND DEVELOPMENT AND 7558 05:51:00,600 --> 05:51:03,320 AGING PROCESSES AND THAT ENERGY 7559 05:51:03,320 --> 05:51:05,480 COMES FROM MITOCHONDRIA AND 7560 05:51:05,480 --> 05:51:09,560 WON'T GO INTO DETAILS THERE BUT 7561 05:51:09,560 --> 05:51:11,080 MITOCHONDRIA'S JOB IS TAKING 7562 05:51:11,080 --> 05:51:14,200 ENERGY IN FORM OF CHEMICAL FORM 7563 05:51:14,200 --> 05:51:15,560 TRANSFORMING INTO ELECTRICAL 7564 05:51:15,560 --> 05:51:18,240 FORM AND ELECTRICITY USING 7565 05:51:18,240 --> 05:51:21,400 BATTERIES TO POWER CELLS TO CARS 7566 05:51:21,400 --> 05:51:24,960 ORGANISM USES MITOCHONDRIAL 7567 05:51:24,960 --> 05:51:26,560 BATTERIES TO POWER EVERYTHING 7568 05:51:26,560 --> 05:51:29,520 ELSE AND COMES FROM WHERE? FOOD 7569 05:51:29,520 --> 05:51:32,920 WE EAT AND OXYGEN WE BREENL AND 7570 05:51:32,920 --> 05:51:34,040 MITOCHONDRIA TRANSFORMING 7571 05:51:34,040 --> 05:51:36,520 CHEMICAL TO ELECTRICAL ENERGY 7572 05:51:36,520 --> 05:51:38,800 PRODUCES C02 AND WATER CLOSING 7573 05:51:38,800 --> 05:51:40,640 LIFE CYCLE IN INTERESTING WAY 7574 05:51:40,640 --> 05:51:44,400 AND THAT COMES ULTIMATELY FROM 7575 05:51:44,400 --> 05:51:48,440 SUN POWERED BY NUCLEAR REACTOR 7576 05:51:48,440 --> 05:51:50,600 IN SPACE AND MITOCHONDRIA PORTAL 7577 05:51:50,600 --> 05:51:53,920 FORM OF ENERGY COMING THROUGH 7578 05:51:53,920 --> 05:51:57,000 IMMATERIAL RADIATION THAT IS 7579 05:51:57,000 --> 05:52:02,720 TURNED INTO LIFE INTERESTING TO 7580 05:52:02,720 --> 05:52:04,360 CONSIDER LIFE STARTED WITH 7581 05:52:04,360 --> 05:52:05,920 METABOLISM BEFORE GENES AND 7582 05:52:05,920 --> 05:52:07,680 CELLS EXIST TD WAS METABOLISM 7583 05:52:07,680 --> 05:52:10,480 AND TRANSFORMATION OF SOME 7584 05:52:10,480 --> 05:52:12,560 ENERGY TO ANOTHER FORM AND 7585 05:52:12,560 --> 05:52:14,160 METABOLISM FOUND WAY TO BECOME 7586 05:52:14,160 --> 05:52:16,840 ENGRAINED AND SUSTAIN ITSELF 7587 05:52:16,840 --> 05:52:20,880 THROUGH GENES. WE ARE 7588 05:52:20,880 --> 05:52:25,200 UNINTERRUPTED CLAIM OF ENERGY 7589 05:52:25,200 --> 05:52:27,080 BEFORE IMPACT OF GENES. 7590 05:52:27,080 --> 05:52:29,480 THIS IS LIVING CELL IF FORTUNATE 7591 05:52:29,480 --> 05:52:35,560 TO WORK IN A LAB AND SEE 7592 05:52:35,560 --> 05:52:36,240 MITOCHONDRIA FLUORESCENT THESE 7593 05:52:36,240 --> 05:52:38,800 ARE WHAT YOU SEE AND MIDDLE HERE 7594 05:52:38,800 --> 05:52:42,280 ARE BELOVED GENES AND EPIGENOME 7595 05:52:42,280 --> 05:52:45,960 AND TELOMERES APD SO ON AND 7596 05:52:45,960 --> 05:52:48,320 OUTSIDE ARE ENVIRONMENTAL THINGS 7597 05:52:48,320 --> 05:52:50,760 CARING ABOUT UNDERSTANDING HOW 7598 05:52:50,760 --> 05:52:51,520 THOSE ACTUALLY IMPACT WHAT 7599 05:52:51,520 --> 05:52:54,880 HAPPEN INSIDE AND EPIGENETIC 7600 05:52:54,880 --> 05:52:59,000 CLOCKS THAT REFLECT THAT AND X 7601 05:52:59,000 --> 05:53:00,080 FACTOR CONNECTING THESE AND 7602 05:53:00,080 --> 05:53:03,480 SEVERAL ARGUMENTS ILLUSTRATING 7603 05:53:03,480 --> 05:53:06,280 TYPICALLY MITOCHONDRIA 7604 05:53:06,280 --> 05:53:08,800 INTERPHASE THAT LIE BETWEEN 7605 05:53:08,800 --> 05:53:11,640 OUTSIDE AND INSIDE WORLD AND 7606 05:53:11,640 --> 05:53:15,080 CELL OF EPIGENOME MAKING 7607 05:53:15,080 --> 05:53:16,880 POTENTIAL IN PROCESS AND 7608 05:53:16,880 --> 05:53:19,240 INTERACTION EMERGES PROCESS AND 7609 05:53:19,240 --> 05:53:21,720 HEALTH AND AGING AND HOW WE 7610 05:53:21,720 --> 05:53:24,000 STUDY THIS QUESTION THAT WE CARE 7611 05:53:24,000 --> 05:53:25,720 ABOUT WE WANT TO APPROACH THIS 7612 05:53:25,720 --> 05:53:29,840 IN WAY TO ALLOW US TO TEST ROLE 7613 05:53:29,840 --> 05:53:31,800 OF MITOCHONDRIA IN REGULATING 7614 05:53:31,800 --> 05:53:33,680 HALLMARKS OF AGING AND HUMAN 7615 05:53:33,680 --> 05:53:37,200 AGING THAT IS CHALLENGING TO DO 7616 05:53:37,200 --> 05:53:39,400 FOR MANY REASONS AND TRACKING 7617 05:53:39,400 --> 05:53:40,920 PEOPLE OVER LONG PERIODS OF TIME 7618 05:53:40,920 --> 05:53:42,520 AND COLLECTING SAMPLES IS 7619 05:53:42,520 --> 05:53:44,120 DIFFICULT AND WORK THAT HAD BEEN 7620 05:53:44,120 --> 05:53:46,320 DONE BEFORE CAN SHOW YOU CAN AGE 7621 05:53:46,320 --> 05:53:48,440 CELLS IN A DISH AND WE TRIED TO 7622 05:53:48,440 --> 05:53:51,960 DO THIS IN A SIMPLE WAY AND 7623 05:53:51,960 --> 05:53:54,520 WHERE YOU PASS PRIMARY 7624 05:53:54,520 --> 05:53:56,160 NONTRANSFORMTIVE HUMAN CELLS IN 7625 05:53:56,160 --> 05:54:00,520 ADDITION AND ALLOWS YOU TO STUDY 7626 05:54:00,520 --> 05:54:03,480 MITONUCLEAR SYSTEM AND YOU SEE 7627 05:54:03,480 --> 05:54:06,560 NUCLEUS IS IN BLUE AND CYTOPLASM 7628 05:54:06,560 --> 05:54:09,480 AND PAIL GREEN IS OUTSIDE WORLD 7629 05:54:09,480 --> 05:54:13,080 AND MITOCHONDRION IS A RIBBON 7630 05:54:13,080 --> 05:54:16,800 AND STRUCTURES IN BETWEEN AND 7631 05:54:16,800 --> 05:54:23,280 PICTURE ON RIGHT ARE -- IT IS A 7632 05:54:23,280 --> 05:54:26,480 ZOOMED IN VERSION OF MITONUKE 7633 05:54:26,480 --> 05:54:30,400 LEEACE THAT IS THERE FEW HUNDRED 7634 05:54:30,400 --> 05:54:32,320 NANOMETERS AWAY FROM CHROMATIN 7635 05:54:32,320 --> 05:54:33,840 AND GENES THERE BEING REGULATED 7636 05:54:33,840 --> 05:54:36,680 AND YOU CAN DEPLOY SAME TOOLS WE 7637 05:54:36,680 --> 05:54:40,440 HEARD ABOUT THAT ARE EPIC 7638 05:54:40,440 --> 05:54:44,800 DEMETHYLATION ARRAY AND DID THIS 7639 05:54:44,800 --> 05:54:48,440 WITH 500 PERSON/TIMEPOINTS 7640 05:54:48,440 --> 05:54:53,400 TRACKING SAME THINGS AND -- AND 7641 05:54:53,400 --> 05:54:56,280 ALSO HAVING THE ABILITY IN VITRO 7642 05:54:56,280 --> 05:54:58,320 AND EVERYTHING IS CONTROLLED 7643 05:54:58,320 --> 05:55:03,440 EXCEPT ONE THING EXPERIMENTALLY 7644 05:55:03,440 --> 05:55:04,760 MANIPULATING EXPOSURE AND ASKING 7645 05:55:04,760 --> 05:55:06,400 CAUSAL QUESTIONS AND EXAMPLE 7646 05:55:06,400 --> 05:55:08,880 WHAT WE FOUND EARLIER ON THAT 7647 05:55:08,880 --> 05:55:10,280 CONVINCED ME THAT THERE WAS 7648 05:55:10,280 --> 05:55:15,200 SOMETHING TO THIS THAT IS L2 AND 7649 05:55:15,200 --> 05:55:25,000 LOCI THAT COMES -- OUT IN SWEDEN 7650 05:55:25,000 --> 05:55:27,120 I BELIEVE AND THEN YOU CAN SEE 7651 05:55:27,120 --> 05:55:29,240 THAT YOUNGER INDIVIDUALS ARE 7652 05:55:29,240 --> 05:55:31,880 OLDER INDIVIDUALS ARE BLUE AND 7653 05:55:31,880 --> 05:55:34,200 PURPLE AND SEE AT THIS SITE HERE 7654 05:55:34,200 --> 05:55:36,520 THAT IS I HAVE A POINTER AND 7655 05:55:36,520 --> 05:55:38,560 SITE WHERE THERE IS A SPIKE 7656 05:55:38,560 --> 05:55:40,360 THERE WITH CPG HIGHLIGHTED IN 7657 05:55:40,360 --> 05:55:42,760 COLOR AND LOCI THAT COMES UP IN 7658 05:55:42,760 --> 05:55:45,360 ASSOCIATION STUDIES AND YOU CAN 7659 05:55:45,360 --> 05:55:47,600 SEE IN VITRO SYSTEM WE HAVE 7660 05:55:47,600 --> 05:55:49,600 CELLS THAT ARE ADVANCING IN AGE 7661 05:55:49,600 --> 05:55:51,480 AS WE CULTURE THEM AND IN THE 7662 05:55:51,480 --> 05:55:53,440 LAB AND YOU CAN SEE SAME KIND OF 7663 05:55:53,440 --> 05:55:55,560 PATTERN AND ON THE RIGHT IS 7664 05:55:55,560 --> 05:55:57,200 ACTUALLY THE CHANGE OVER TIME IN 7665 05:55:57,200 --> 05:56:00,680 THE METHYLATION LEVEL IN BETA 7666 05:56:00,680 --> 05:56:03,280 VALUE FOR CBG AND CONCORDANCE 7667 05:56:03,280 --> 05:56:06,560 BETWEEN IN VITRO DATA AND 7668 05:56:06,560 --> 05:56:08,960 DEPLOYING FIRST CONVENIENTATION 7669 05:56:08,960 --> 05:56:10,720 CLOCKS AND SKIN AND BLOOD CLOCK 7670 05:56:10,720 --> 05:56:12,760 AND CLOCKS WORK IN A DISH TAKING 7671 05:56:12,760 --> 05:56:16,000 CELLS FROM SOMEONE'S SKIN AND 7672 05:56:16,000 --> 05:56:18,560 PUT IN A DISH PASSAGE OVER TIME 7673 05:56:18,560 --> 05:56:20,880 AND AGE CELLS AND YOU SEE SAME 7674 05:56:20,880 --> 05:56:24,280 PATTERNS THAT IS INTERESTING AND 7675 05:56:24,280 --> 05:56:25,360 REMARKABLE IS COMPARE TODAY RATE 7676 05:56:25,360 --> 05:56:28,520 OF AGING IN HUMAN BODY CLOCKS 7677 05:56:28,520 --> 05:56:32,840 ARE RETURNED TO ON ONE YEAR 7678 05:56:32,840 --> 05:56:34,240 PREDICT AGE ONE YEAR 7679 05:56:34,240 --> 05:56:35,480 CHRONOLOGICAL TIME AND RATES 50 7680 05:56:35,480 --> 05:56:38,440 TO 100 TIMES FASTER AND 7681 05:56:38,440 --> 05:56:39,800 EVERYTHING SEEMS TO HAPPEN 7682 05:56:39,800 --> 05:56:41,760 FASTER AND THINK WE KNOW WHY 7683 05:56:41,760 --> 05:56:45,520 THAT HAPPENS AND MIGHT RELATE TO 7684 05:56:45,520 --> 05:56:46,640 ENERGETICS AND DATA SET THAT 7685 05:56:46,640 --> 05:56:48,680 THOSE THAT MIGHT BE INTERESTED 7686 05:56:48,680 --> 05:56:51,520 IS GABRIEL A WONDERFUL STUDENT 7687 05:56:51,520 --> 05:56:54,760 IN LAB CREATED THIS APP TO GO ON 7688 05:56:54,760 --> 05:56:57,800 TO THERE AND TRACK DEMETHYLATION 7689 05:56:57,800 --> 05:57:03,520 AND RNA SEQUENCING DATA SEEK 7690 05:57:03,520 --> 05:57:05,240 CRETETIVE FACTORS AND GENETICS 7691 05:57:05,240 --> 05:57:06,560 AND OTHER THINGS. THAT IS THE 7692 05:57:06,560 --> 05:57:07,040 APPLICATION. 7693 05:57:07,040 --> 05:57:08,680 SO, LET'S SEE WHAT THIS LOOKS 7694 05:57:08,680 --> 05:57:13,240 LIKE AND HOW TO MANIPULATE 7695 05:57:13,240 --> 05:57:14,520 MITOCHONDRIA AND BASIC DESIGN TO 7696 05:57:14,520 --> 05:57:18,200 COLLECT UP TO 42 TIME POINTS AND 7697 05:57:18,200 --> 05:57:20,120 EVERY REGULAR INTERVALS 7698 05:57:20,120 --> 05:57:20,840 COLLECTING INFORMATION ABOUT 7699 05:57:20,840 --> 05:57:22,960 WHAT CELLS LOOK LIKE AND HOW BIG 7700 05:57:22,960 --> 05:57:25,040 THEY ARE AND HOW MANY THERE ARE 7701 05:57:25,040 --> 05:57:27,480 AND YOU CAN COLLECT CELLULAR 7702 05:57:27,480 --> 05:57:29,080 ENERGETICS AND METABOLIC RATE 7703 05:57:29,080 --> 05:57:32,400 AND ENERGY CONSUMPTION PROXY 7704 05:57:32,400 --> 05:57:35,760 GLYCOLYSIS COLLECTING DNA AND 7705 05:57:35,760 --> 05:57:39,440 TELOMERE LENGTH AND 7706 05:57:39,440 --> 05:57:40,040 MITOCHONDRIAL DELETIONS AND 7707 05:57:40,040 --> 05:57:41,240 GENOME STABILITY COLLECTING TO 7708 05:57:41,240 --> 05:57:44,040 DO RNA SEQUENCING AND MEDIA 7709 05:57:44,040 --> 05:57:47,000 COLLECTING FOR PROXY TO BLOOD 7710 05:57:47,000 --> 05:57:49,720 LOOKING AT SECRETIVE FACTORS AND 7711 05:57:49,720 --> 05:57:52,360 CELL DNA FOR EXAMPLE DOING IN 7712 05:57:52,360 --> 05:57:55,160 THREE HEALTHY DONORS AND THREE 7713 05:57:55,160 --> 05:57:58,160 PATIENT DERIVED FIBRO BLASTS 7714 05:57:58,160 --> 05:57:59,880 WITH KNOWN MITOCONDREEAL TOOE 7715 05:57:59,880 --> 05:58:03,840 FEKTS THAT IS WAY TO HAVE 7716 05:58:03,840 --> 05:58:06,840 MITOCHONDRIA AND ORTHOGONAL 7717 05:58:06,840 --> 05:58:09,400 METHOD WE HAVE THIS FOR ENERGY 7718 05:58:09,400 --> 05:58:10,440 TRANSFORMATION WITHOUT KILLING 7719 05:58:10,440 --> 05:58:12,840 CELLS AND ASKING WHAT 7720 05:58:12,840 --> 05:58:14,600 CONVERGENCE IS AND CONVERGING 7721 05:58:14,600 --> 05:58:17,200 FINDINGS BETWEEN GENETIC AND 7722 05:58:17,200 --> 05:58:19,880 FARM COLONL CAL MODEL THAT MIGHT 7723 05:58:19,880 --> 05:58:22,640 HAVE OWN DRAWBACK AND WHAT WAS 7724 05:58:22,640 --> 05:58:24,760 ASTONISHING DOING THIS GENETIC 7725 05:58:24,760 --> 05:58:27,720 AND FARM COLONL CAL MODEL 7726 05:58:27,720 --> 05:58:30,320 MITOCHONDRIA CELLS ARE NOT HAPPY 7727 05:58:30,320 --> 05:58:32,240 SLOWING DOWN DIVISION 7728 05:58:32,240 --> 05:58:33,520 CONSIDERABLY AND MOVING SLOWLY 7729 05:58:33,520 --> 05:58:36,040 AND MEASURING ENERGETICS AND 7730 05:58:36,040 --> 05:58:37,680 THIS IS COMBINED AMOUNT OF 7731 05:58:37,680 --> 05:58:40,480 ENERGY THAT CELLS ARE CONSUMING 7732 05:58:40,480 --> 05:58:42,440 EVERY HOUR AND DAY TO STAY ALIVE 7733 05:58:42,440 --> 05:58:44,640 AND SEE IN THREE DONORS WITH 7734 05:58:44,640 --> 05:58:48,880 THIS ONE THIS IS GENETIC 7735 05:58:48,880 --> 05:58:50,160 MITOCONDREEAL PERTUBATION AND 7736 05:58:50,160 --> 05:58:52,600 DOUBLING ENERGY INCREASE ENERGY 7737 05:58:52,600 --> 05:58:55,640 CONSUMED PER TIME AND UNIT PER 7738 05:58:55,640 --> 05:58:59,520 CELL VOLUME AND THIS IS FARM 7739 05:58:59,520 --> 05:59:01,440 COLONL CAL MODEL AND COSTS CELLS 7740 05:59:01,440 --> 05:59:04,160 TWICE AS MUCH ENERGY TO STAY 7741 05:59:04,160 --> 05:59:06,880 ALIVE AND CELLS WITH HEALTHY 7742 05:59:06,880 --> 05:59:08,480 MITOCHONDRIA AND LOOKING BACK AT 7743 05:59:08,480 --> 05:59:14,720 THIS PROXIMITY AND MITOCHONDRIA 7744 05:59:14,720 --> 05:59:16,040 PERTURBED MITOCHONDRIA CHANGING 7745 05:59:16,040 --> 05:59:18,800 CELL RATE AS WHICH THEY ARE 7746 05:59:18,800 --> 05:59:21,520 DIVIDING AND CAN ASK WHAT IS 7747 05:59:21,520 --> 05:59:22,600 HAPPENING THERE THIS WAS 7748 05:59:22,600 --> 05:59:24,880 PUBLISHED RECENTLY AND SUMMARY 7749 05:59:24,880 --> 05:59:27,680 WHAT WE FOUND ON TOP HERE IS 7750 05:59:27,680 --> 05:59:29,920 CONTRASTING CELLS WITH HEALTHY 7751 05:59:29,920 --> 05:59:32,560 MITOCON DREE AYOU ON LEFT AND -- 7752 05:59:32,560 --> 05:59:35,640 ON RIGHT AND FIND CELLS SLOW 7753 05:59:35,640 --> 05:59:41,640 DOWN DIVISION RATE AND HAVE 7754 05:59:41,640 --> 05:59:43,600 MITOCONDREEAL DNA AND PROTEINS 7755 05:59:43,600 --> 05:59:48,240 RELEASING DNA INTO THE MEDIA AND 7756 05:59:48,240 --> 05:59:50,520 THEY ILLUSTRATE HYPERSECRETARY 7757 05:59:50,520 --> 05:59:52,400 PHENOTYPE RECAPITULATING WHAT WE 7758 05:59:52,400 --> 05:59:55,760 SEE IN HUMAN AGING AND PLASMA 7759 05:59:55,760 --> 05:59:59,680 PRO TEUMS ASSOCIATED WITH 7760 05:59:59,680 --> 06:00:01,920 INTEGRATED STRESS RESPONSE 7761 06:00:01,920 --> 06:00:02,880 ACTIVATION WITH GENE EXPRESSION 7762 06:00:02,880 --> 06:00:05,520 AND INCREASE IN AMOUNT OF 7763 06:00:05,520 --> 06:00:07,080 TRANSCRIPTION AND TRANSLATION 7764 06:00:07,080 --> 06:00:09,960 ACTIVITY AND CELLS DOING MORE 7765 06:00:09,960 --> 06:00:12,720 UPREGULATING PATHWAYS AND CELL 7766 06:00:12,720 --> 06:00:15,040 SIGNALING AS WAY TO COMPENSATE 7767 06:00:15,040 --> 06:00:16,800 OR TRY TO COOPERATE IN WAY THAT 7768 06:00:16,800 --> 06:00:19,120 ORGANS AND CELLS IN HUMAN BODY 7769 06:00:19,120 --> 06:00:21,400 DO AND ATTRIBUTE PATHWAYS FOR 7770 06:00:21,400 --> 06:00:22,680 DEVELOPMENT AND DIFFERENTIATION 7771 06:00:22,680 --> 06:00:24,640 AND ALL THESE ARE ENERGY 7772 06:00:24,640 --> 06:00:27,880 EXPENSIVE AND WE SEE AT 7773 06:00:27,880 --> 06:00:30,280 ENERGETIC LEVEL THERE IS 7774 06:00:30,280 --> 06:00:32,800 HYPERMETABOLIC SIGNATURE 7775 06:00:32,800 --> 06:00:36,760 ASSOCIATED WITH TELOMERE 7776 06:00:36,760 --> 06:00:40,240 SHORTENING AND END OF 7777 06:00:40,240 --> 06:00:43,120 CHROMOSOMES AND IF YOU PERTURB 7778 06:00:43,120 --> 06:00:46,040 MITOCHONDRIA CELLS LOSE MORE 7779 06:00:46,040 --> 06:00:48,360 TELOMERES FOR EACH CELL DIVISION 7780 06:00:48,360 --> 06:00:51,200 AND UNCOUPLING OF THEM AND IN 7781 06:00:51,200 --> 06:00:54,600 CONTEXT OF MITOCHONDRIAL 7782 06:00:54,600 --> 06:00:56,360 PERTUBATION AND WHAT SETS PACE 7783 06:00:56,360 --> 06:01:00,400 OF AGING PERTURBING MITOCHONDRIA 7784 06:01:00,400 --> 06:01:03,560 ACCELERATE BIOMARKERS OF 7785 06:01:03,560 --> 06:01:05,080 ACCELERATED AGING AND TWO 7786 06:01:05,080 --> 06:01:06,680 BEAUTIFUL PAPERS COMING OUT IN 7787 06:01:06,680 --> 06:01:08,560 NATURE AND SCIENCE IN LAST FEW 7788 06:01:08,560 --> 06:01:11,640 MONTHS AND THEY CONVERGE ON THE 7789 06:01:11,640 --> 06:01:13,920 SAME FINDING WHERE MITOCHONDRIA 7790 06:01:13,920 --> 06:01:17,280 AND ACTIVITY OF ENL ERNL JI 7791 06:01:17,280 --> 06:01:19,880 TRANSFORMATION AND ELECTRON 7792 06:01:19,880 --> 06:01:22,480 TRANSPORT CHAIN ETC REGULATES 7793 06:01:22,480 --> 06:01:26,040 CHEMICALS AND REGULATES RATE OF 7794 06:01:26,040 --> 06:01:29,360 PROTEIN SYNTHESIS AND BY 7795 06:01:29,360 --> 06:01:30,440 MANIPULATING MITOCHONDRIA SHOW 7796 06:01:30,440 --> 06:01:32,880 REGULATION OF TIME PERCEPTION AT 7797 06:01:32,880 --> 06:01:35,320 CELLULAR LEVEL AND RATE OF 7798 06:01:35,320 --> 06:01:36,400 CELLULAR ENERGETICS AND I WILL 7799 06:01:36,400 --> 06:01:38,040 SUMMARIZE IT IN THIS WAY AND 7800 06:01:38,040 --> 06:01:40,480 THINKING ABOUT ENERGY FLOW. 7801 06:01:40,480 --> 06:01:43,320 IT CREATES ENTROPY AND MORE THAT 7802 06:01:43,320 --> 06:01:45,920 THERE IS FASTER THINGS DECAY AND 7803 06:01:45,920 --> 06:01:48,960 THERE IS FINITE LIFESPAN AND 7804 06:01:48,960 --> 06:01:52,520 MOST EPHEMERAL THINGS IN WORLD 7805 06:01:52,520 --> 06:01:54,160 RELATE TO FIRE COMBUSTION AND 7806 06:01:54,160 --> 06:01:55,440 FLAME LAST AS I SECOND AND IS 7807 06:01:55,440 --> 06:01:58,200 GONE AND THINGS WHERE ENERGY 7808 06:01:58,200 --> 06:02:00,600 FLOWS SLOWLY AND 1,000 YEAR OLD 7809 06:02:00,600 --> 06:02:03,920 LIVING TREE AND THEN THERE IS 7810 06:02:03,920 --> 06:02:06,800 LIVING CREATURES THAT LIE 7811 06:02:06,800 --> 06:02:09,280 IN-BETWEEN TWO EXTREMES AND 7812 06:02:09,280 --> 06:02:10,720 WONDERFUL ORGANISMS ENERGY FLOWS 7813 06:02:10,720 --> 06:02:14,480 AT REGULATED AND CONTROLLED PACE 7814 06:02:14,480 --> 06:02:17,000 UNLIKE A FLAME AND FLOW MORE 7815 06:02:17,000 --> 06:02:20,040 ENERGY THAN A ROCK OR TREE AND 7816 06:02:20,040 --> 06:02:21,400 HYPERMETABOLISM IS A NOTION THAT 7817 06:02:21,400 --> 06:02:23,760 RATE OF ENERGY EXPENDITURE CAN 7818 06:02:23,760 --> 06:02:25,760 ACTUALLY SPEED UP AND ARE 7819 06:02:25,760 --> 06:02:27,200 PREDICTIONS THAT COULD BE MADE 7820 06:02:27,200 --> 06:02:28,840 AROUND THIS AND WE HAVE TESTED 7821 06:02:28,840 --> 06:02:30,680 SOME OF THAT AND I WON'T TALK 7822 06:02:30,680 --> 06:02:33,560 ABOUT IT TODAY. WE CAN 7823 06:02:33,560 --> 06:02:35,600 ACCELERATE RATE OF ENERGY FLOW 7824 06:02:35,600 --> 06:02:39,160 AND RATE OF ENERGY FLOW AND 7825 06:02:39,160 --> 06:02:41,280 REGULATE PACE OF AGING AT 7826 06:02:41,280 --> 06:02:42,960 CELLULAR LEVEL AND A FEW WORDS 7827 06:02:42,960 --> 06:02:45,080 ABOUT MITOCHONDRIA AND HOW WE 7828 06:02:45,080 --> 06:02:46,640 SHOULD THINK ABOUT IT TALKING 7829 06:02:46,640 --> 06:02:50,840 ABOUT BIOMARKERS AND USE THAT 7830 06:02:50,840 --> 06:02:53,920 IMAGE TO ILLUSTRATE WHAT WE HAVE 7831 06:02:53,920 --> 06:02:57,560 DONE WITH AGING AND 7832 06:02:57,560 --> 06:02:59,040 MITOCHONDRIAL BIOLOGY AND BLIND 7833 06:02:59,040 --> 06:03:00,320 MEN AND SCIENTISTS THAT ARE 7834 06:03:00,320 --> 06:03:03,160 LOOKING AT AN OBJECT AND ARE 7835 06:03:03,160 --> 06:03:05,120 MAKING VALID OBSERVATIONS ABOUT 7836 06:03:05,120 --> 06:03:07,600 PARTS OF THE WHOLE THAT ARE 7837 06:03:07,600 --> 06:03:09,560 BLINDED AND CAN'T SEE THE HOLE. 7838 06:03:09,560 --> 06:03:11,080 MEASURING DIFFERENT PIECES 7839 06:03:11,080 --> 06:03:12,640 MAKING VALID OBSERVATIONS 7840 06:03:12,640 --> 06:03:14,520 DRAWING SPECIFIC CONCLUSIONS AND 7841 06:03:14,520 --> 06:03:16,080 MISSING THE WHOLE POINT AND WHAT 7842 06:03:16,080 --> 06:03:20,800 WE HAVE DONE WITH MITOCHONDRIAL 7843 06:03:20,800 --> 06:03:22,520 BIOLOGY AND POWERHOUSE MAKING 7844 06:03:22,520 --> 06:03:26,680 ATP THAT IS 1957 FROM AN ARTICLE 7845 06:03:26,680 --> 06:03:29,160 IN AMERICAN SCIENTISTS AND IF 7846 06:03:29,160 --> 06:03:32,720 YOU LOOK AT MITOCHONDRIA FROM 7847 06:03:32,720 --> 06:03:34,560 DIFFERENT ANGLES CONCLUSIONS 7848 06:03:34,560 --> 06:03:38,560 THEY DO THIS KILL CELL AND 7849 06:03:38,560 --> 06:03:39,360 TRIGGER DIFFERENTIATION AND 7850 06:03:39,360 --> 06:03:42,480 REGULATE EPIGENOME AND 7851 06:03:42,480 --> 06:03:45,240 PERSPECTIVE WE HAVE TO ADOPT AND 7852 06:03:45,240 --> 06:03:46,440 PIECE COMING OUT TOMORROW WE ARE 7853 06:03:46,440 --> 06:03:50,520 VERY EXCITED ABOUT LAYING OUT 7854 06:03:50,520 --> 06:03:51,720 IDEA MITOCHONDRIA COMPLEX AND 7855 06:03:51,720 --> 06:03:54,120 DYNAMIC AND MODEL THAT IS 7856 06:03:54,120 --> 06:03:56,920 EMERGING IS ONE THAT INVOLVES 7857 06:03:56,920 --> 06:03:57,960 MITOCHONDRIAL SIGNAL 7858 06:03:57,960 --> 06:03:59,640 TRANSDUCTION AND DO MORE THAN 7859 06:03:59,640 --> 06:04:01,400 TRANSFORMING ENERGY AND 7860 06:04:01,400 --> 06:04:02,560 COMMUNICATE INFORMATION AND 7861 06:04:02,560 --> 06:04:04,040 RECEIVE INFORMATION AND 7862 06:04:04,040 --> 06:04:10,240 TRANSFORM INFORMATION PROOND AND 7863 06:04:10,240 --> 06:04:12,400 PRODUCE -- THESE ARE THINGS 7864 06:04:12,400 --> 06:04:15,560 ALONG WHEEL I WON'T GO INTO THAT 7865 06:04:15,560 --> 06:04:17,680 MITOCHONDRIA ARE SENSITIVE TO 7866 06:04:17,680 --> 06:04:19,640 RECEPTORS ON SURFACE AND 7867 06:04:19,640 --> 06:04:21,240 TRANSPORTER AS LOUING TO SEND 7868 06:04:21,240 --> 06:04:23,480 FACTORS AND PRODUCE AS SIGNALS 7869 06:04:23,480 --> 06:04:26,600 AND EXAMPLE MITOCHONDRIA ARE 7870 06:04:26,600 --> 06:04:37,160 SOURCE OF STEROID HORMONES THAT 7871 06:04:40,520 --> 06:04:42,720 ALLOW NEW LIFE AND THESE ARE 7872 06:04:42,720 --> 06:04:45,760 MADE INSIDE OF THE MITOCHONDRIA 7873 06:04:45,760 --> 06:04:47,080 FOR EVOLUTIONARY REASONS THAT 7874 06:04:47,080 --> 06:04:50,920 ARE QUITE INTERESTING AND I WILL 7875 06:04:50,920 --> 06:04:55,440 FINISH WITH THIS MITOCHONDRIA 7876 06:04:55,440 --> 06:04:58,600 PRODUCE SIGNALS AND INFORMATION 7877 06:04:58,600 --> 06:05:00,120 PROCESSING SYSTEM PROVIDING 7878 06:05:00,120 --> 06:05:00,880 STRUCKTIVE INFORMATION FOR 7879 06:05:00,880 --> 06:05:03,120 NUMBER OF SYSTEMS RELEVANT TO 7880 06:05:03,120 --> 06:05:04,680 AGING AND WE NEED TO BRING MIND 7881 06:05:04,680 --> 06:05:08,560 INTO THE PICTURE. ALL OF THE 7882 06:05:08,560 --> 06:05:11,560 ASPECTS OF METABOLISM AND ENERGY 7883 06:05:11,560 --> 06:05:16,800 METABOLISM MITOCHONDRIA FOR 7884 06:05:16,800 --> 06:05:18,920 DESCENDING INPUTS REGULATING 7885 06:05:18,920 --> 06:05:22,560 METABOLISM IN MITOCHONDRIA THAT 7886 06:05:22,560 --> 06:05:23,320 REGULATES PROCESSES IN THE BRAIN 7887 06:05:23,320 --> 06:05:25,640 AND IN SUMMARY I TOLD YOU WHERE 7888 06:05:25,640 --> 06:05:27,240 ENERGY COMES FROM AND WHY IT IS 7889 06:05:27,240 --> 06:05:29,840 CRITICAL SUGGESTING THAT 7890 06:05:29,840 --> 06:05:33,560 MITOCHONDRIA MIGHT BE DYNAMIC 7891 06:05:33,560 --> 06:05:35,120 ENERGETIC INTERFACE BETWEEN 7892 06:05:35,120 --> 06:05:38,320 OUTSIDE AND INSIDE WORLD AND 7893 06:05:38,320 --> 06:05:39,640 STUDYING THINGS IN VITRO 7894 06:05:39,640 --> 06:05:41,520 STUDYING RATE OF AGING AND 7895 06:05:41,520 --> 06:05:45,040 THINKING OF MITOCHONDRIA AGING 7896 06:05:45,040 --> 06:05:50,000 BIOLOGY IN INTEGRATED WAY AND 7897 06:05:50,000 --> 06:05:52,400 MITOCHONDRIAL SIGNAL TRANSLATION 7898 06:05:52,400 --> 06:05:55,280 AND THIS WORK AND IN TOP RIGHT 7899 06:05:55,280 --> 06:05:57,040 AND DOING CELLULAR LIFESPAN WORK 7900 06:05:57,040 --> 06:06:01,760 IN COLLABORATION WITH MANY 7901 06:06:01,760 --> 06:06:03,080 OTHERS AND [INDISCERNIBLE] DID 7902 06:06:03,080 --> 06:06:06,960 WORK ON HAIR I MENTIONED IN 7903 06:06:06,960 --> 06:06:07,680 BEGINNING AND POST DOCS IN 7904 06:06:07,680 --> 06:06:09,600 LABORATORY DEVELOPING THIS AND 7905 06:06:09,600 --> 06:06:11,920 AMAZING COLLABORATE YRS AND 7906 06:06:11,920 --> 06:06:15,440 FUNDING WORK THAT MADE THIS 7907 06:06:15,440 --> 06:06:16,120 POSSIBLE. THANK YOU. 7908 06:06:16,120 --> 06:06:19,640 >>[APPLAUSE]. 7909 06:06:19,640 --> 06:06:24,600 >>>>WE ARE HERE FOR THE LAST 7910 06:06:24,600 --> 06:06:27,600 TALK OF THE DAY. THIS IS ALICE 7911 06:06:27,600 --> 06:06:29,960 KANE STARTED AT INSTITUTE FOR 7912 06:06:29,960 --> 06:06:32,160 SYSTEMS BIOLOGY AND ASSISTANT 7913 06:06:32,160 --> 06:06:34,640 PROFESSOR IN THE FALL OF LAST 7914 06:06:34,640 --> 06:06:39,600 YEAR 2022 AND -- IN BOTH SEXES 7915 06:06:39,600 --> 06:06:41,840 USING INTEGRATIVE APPROACH. SHE 7916 06:06:41,840 --> 06:06:45,360 IS FOCUSED ON ASSOCIATION 7917 06:06:45,360 --> 06:06:52,760 BETWEEN FRAILTY AND EPIGENETIC 7918 06:06:52,760 --> 06:06:55,960 USES OF AGE AND BIOMARKERS OF 7919 06:06:55,960 --> 06:06:57,320 FRAILTY. ALICE. 7920 06:06:57,320 --> 06:06:58,840 >>THANK YOU TO ORGANIZERS FOR 7921 06:06:58,840 --> 06:07:01,880 OPPORTUNITY TO TELL YOU A LITTLE 7922 06:07:01,880 --> 06:07:04,760 BIT ABOUT SOME WORK TODAY AND 7923 06:07:04,760 --> 06:07:11,480 TALKING ABOUT BIOMARKERS FOR 7924 06:07:11,480 --> 06:07:13,120 SCIENCE AND COMING BACK TO MOUSE 7925 06:07:13,120 --> 06:07:14,040 PERSPECTIVE NOW AND LITTLE BIT 7926 06:07:14,040 --> 06:07:16,000 OF AN OVERVIEW I WILL TALK A 7927 06:07:16,000 --> 06:07:18,760 LITTLE ABOUT FIRST GENERATION 7928 06:07:18,760 --> 06:07:21,040 VERSUS SECOND GENERATION 7929 06:07:21,040 --> 06:07:21,720 EPIGENETIC [INDISCERNIBLE] THAT 7930 06:07:21,720 --> 06:07:24,840 WAS INTRODUCED NICELY IN THE 7931 06:07:24,840 --> 06:07:29,480 BEGINNING AND VANLS OF STUDYING 7932 06:07:29,480 --> 06:07:30,560 BIOMARKERS AND [INDISCERNIBLE] 7933 06:07:30,560 --> 06:07:32,960 IN MICE AND DEVELOPMENT OF 7934 06:07:32,960 --> 06:07:34,440 SECOND GENERATION CLOGS IN MICE 7935 06:07:34,440 --> 06:07:36,240 THAT WE CURRENTLY DON'T HAVE AND 7936 06:07:36,240 --> 06:07:38,800 A FEW OPEN QUESTIONS AND DAN 7937 06:07:38,800 --> 06:07:41,000 ALREADY COUGHED THIS NICELY. 7938 06:07:41,000 --> 06:07:44,840 THIS IS A EXAMPLE OF EPIGENETIC 7939 06:07:44,840 --> 06:07:47,640 CLOCK THAT I DID DEVELOPED WITH 7940 06:07:47,640 --> 06:07:50,520 A GRADUATE STUDENT IN DAVID 7941 06:07:50,520 --> 06:07:52,120 SINCLAIR'S LAB AND NEW TECHNIQUE 7942 06:07:52,120 --> 06:07:55,880 THAT IS SLIGHTLY DECREASING COST 7943 06:07:55,880 --> 06:07:59,480 OF GETTING THESE EPI GENETIC 7944 06:07:59,480 --> 06:08:01,640 CLOCKS AND EXAMPLE FROM MOUSE 7945 06:08:01,640 --> 06:08:03,880 CLOCK FROM BLOOD PREDICTIVE AGE 7946 06:08:03,880 --> 06:08:08,000 OF DEMETHYLATION ON X AXIS AND 7947 06:08:08,000 --> 06:08:10,640 AGE ON Y AXIS AND SEEN MANY 7948 06:08:10,640 --> 06:08:13,520 TIMES TODAY LOOKING AT 7949 06:08:13,520 --> 06:08:16,520 METHYLATION OF SPECIFIC CPGS 7950 06:08:16,520 --> 06:08:19,960 MODELING AGAINST AGE WE CAN 7951 06:08:19,960 --> 06:08:22,560 ACCURATELY PREDICT HOW OLD A 7952 06:08:22,560 --> 06:08:25,680 MOUSE OR HUMAN IS AND GET A NICE 7953 06:08:25,680 --> 06:08:27,600 CURVE AND ASSUMPTION DAN ELUDED 7954 06:08:27,600 --> 06:08:29,800 TO IS DIFFERENCE FROM ACTUAL 7955 06:08:29,800 --> 06:08:33,200 PREDICTED AGE TELLS SOMETHING 7956 06:08:33,200 --> 06:08:34,360 INTERESTING ABOUT YOUR BIOLOGY 7957 06:08:34,360 --> 06:08:36,240 OR YOUR HEALTH AND MOUSE HERE 7958 06:08:36,240 --> 06:08:38,840 THAT IS 25 MONTHS OF AGE IS 7959 06:08:38,840 --> 06:08:40,480 PREDICT TODAY BE 20 MONTHS OF 7960 06:08:40,480 --> 06:08:42,920 AGE AND POTENTIAL BIOLOGICAL AGE 7961 06:08:42,920 --> 06:08:45,720 THAT IS FIVE MONTHS YOUNGER THAN 7962 06:08:45,720 --> 06:08:49,680 ACTUAL AGE AND WOULD BE PRESUMED 7963 06:08:49,680 --> 06:08:52,480 TO BE HEALTHIER AND OPPOSITE OF 7964 06:08:52,480 --> 06:08:54,000 MICE ON OTHER SIDE OF THE CURVE 7965 06:08:54,000 --> 06:08:57,200 WE ASSUME TO BE BIOLOGICALLY 7966 06:08:57,200 --> 06:08:59,480 OLDER THAT IS ASSUMPTION THOUGH 7967 06:08:59,480 --> 06:09:02,040 AND NOT ALWAYS THE CASE AS THAT 7968 06:09:02,040 --> 06:09:04,400 WE HAVE HEARD. THERE IS 7969 06:09:04,400 --> 06:09:05,560 ASSOCIATION BETWEEN RESIDUALS 7970 06:09:05,560 --> 06:09:08,000 AND NUMBER OF HEALTH OUTCOMES IN 7971 06:09:08,000 --> 06:09:10,280 SPECIFIC DISEASES IN HUMANS AND 7972 06:09:10,280 --> 06:09:12,200 IN MICE WE NEVER LOOKED AT 7973 06:09:12,200 --> 06:09:14,400 WHETHER RESIDUALS AND 7974 06:09:14,400 --> 06:09:15,640 DIFFERENCES ARE CORRELATED ARE 7975 06:09:15,640 --> 06:09:18,720 HEALTH OUTCOMES AND THIS IS A 7976 06:09:18,720 --> 06:09:20,240 FIGURE FROM THE SAME PAPER I WAS 7977 06:09:20,240 --> 06:09:21,600 DISCUSSING WHERE WE HAVE A 7978 06:09:21,600 --> 06:09:24,040 DIFFERENCE OF PREDICTED VERSUS 7979 06:09:24,040 --> 06:09:27,600 ACTUAL AGE BASE ON EPIGENOME ON 7980 06:09:27,600 --> 06:09:29,080 Y AXIS AND LOOKING AT DIFFERENCE 7981 06:09:29,080 --> 06:09:32,320 FROM NORMALIZED FRAILTY ON X 7982 06:09:32,320 --> 06:09:34,200 AXIS AND EXPECTED MICE THAT ARE 7983 06:09:34,200 --> 06:09:36,360 MORE FRAIL TO HAVE HIGHER 7984 06:09:36,360 --> 06:09:38,000 BIOLOGICAL AGE AND VICE VERSA 7985 06:09:38,000 --> 06:09:42,200 AND WE SAW ABSOLUTELY NO 7986 06:09:42,200 --> 06:09:43,360 RELATIONSHIPS AND THESE ARE TWO 7987 06:09:43,360 --> 06:09:45,160 CLOCKS TELLING US DIFFERENT 7988 06:09:45,160 --> 06:09:46,400 THINGS PERHAPS GETTING AT 7989 06:09:46,400 --> 06:09:47,800 DIFFERENT MECHANISMS AND WE ARE 7990 06:09:47,800 --> 06:09:50,120 NOT SEEING SAME ASSOCIATION WE 7991 06:09:50,120 --> 06:09:53,320 MIGHT HAVE EXPECTED HERE. 7992 06:09:53,320 --> 06:09:56,440 SO, ALL THIS COMES TO SECOND 7993 06:09:56,440 --> 06:09:57,640 GENERATION CLOCKS AND FIRST 7994 06:09:57,640 --> 06:10:01,080 CLOCKS THAT ARE MODELED TO 7995 06:10:01,080 --> 06:10:02,280 PREDICT CHRONOLOGICAL AGE AND 7996 06:10:02,280 --> 06:10:05,680 ARE DEVELOPED ENTIRE WILL I TO 7997 06:10:05,680 --> 06:10:08,520 TELL US HOW OLD A SAMPLE IS. 7998 06:10:08,520 --> 06:10:11,720 SECOND GENERATION CLOCKS PREDICT 7999 06:10:11,720 --> 06:10:14,920 NOT CHRONOLOGICAL AGE BUT 8000 06:10:14,920 --> 06:10:16,200 SOMETHING USEFUL HEALTH OR 8001 06:10:16,200 --> 06:10:19,760 MORTALITY AND TRUE MEASURE OF 8002 06:10:19,760 --> 06:10:21,560 BIOLOGICAL AGE THAT INCLUDE GRIM 8003 06:10:21,560 --> 06:10:24,640 AGE AND PHENOAGE THAT WE HEARD 8004 06:10:24,640 --> 06:10:27,040 ABOUT THAT BASICALLY PREDICT AGE 8005 06:10:27,040 --> 06:10:30,480 FROM MORTALITY RISKS AND OTHER 8006 06:10:30,480 --> 06:10:32,120 CLINICALLY RELEVANT OUTCOMES 8007 06:10:32,120 --> 06:10:34,320 THAT WE HAERRED ABOUT AGING 8008 06:10:34,320 --> 06:10:36,600 CLOCK THAT LOOKS AT CHANGE RS IN 8009 06:10:36,600 --> 06:10:38,880 CLINICAL OUTCOMES AND THERE IS A 8010 06:10:38,880 --> 06:10:40,800 RECENT CLOCK DEVELOPED TO 8011 06:10:40,800 --> 06:10:43,160 SPECIFICALLY PREDICT FRAILTY 8012 06:10:43,160 --> 06:10:44,920 FROM EPIGENETIC MEASURES THAT 8013 06:10:44,920 --> 06:10:47,600 ARE ALL HUMAN CLOCKS PROVIDING 8014 06:10:47,600 --> 06:10:49,160 CLINICALLY RELEVANT OUTCOMES WE 8015 06:10:49,160 --> 06:10:51,200 ARE MORE INTERESTED IN AND 8016 06:10:51,200 --> 06:10:54,600 MODELING SPECIFIC DNA 8017 06:10:54,600 --> 06:10:56,080 METHYLATION TO PREDICT CLINICAL 8018 06:10:56,080 --> 06:10:58,040 OUTCOMES RATHER THAN ASSUMING 8019 06:10:58,040 --> 06:11:00,840 THAT FROM PREDICTION OF AGE AND 8020 06:11:00,840 --> 06:11:02,480 WE DON'T HAVE YET ANY SECOND 8021 06:11:02,480 --> 06:11:04,760 GENERATION CLOCKS OR CLOCKS TO 8022 06:11:04,760 --> 06:11:06,680 PREDICT COMPOSITION MEASURES IN 8023 06:11:06,680 --> 06:11:09,600 MICE STUDIES AND WANT TO TELL 8024 06:11:09,600 --> 06:11:11,360 YOU A LITTLE WHY I THINK GREAT 8025 06:11:11,360 --> 06:11:15,040 MODELS TO STUDY BIOMARKERS FOR 8026 06:11:15,040 --> 06:11:16,360 GEROSCIENCE AND HEARD ABOUT 8027 06:11:16,360 --> 06:11:20,040 LIMITATIONS OF HUMAN STUDIES OF 8028 06:11:20,040 --> 06:11:23,640 ACR AND -- FOLLOWED FOR ENTIRE 8029 06:11:23,640 --> 06:11:25,080 LIFESPAN LONGITUDINALLY AND 8030 06:11:25,080 --> 06:11:27,920 DEEPLY PHENOTYPED AND THERE IS A 8031 06:11:27,920 --> 06:11:30,080 LOT OF DISCUSSION OVER LAST FEW 8032 06:11:30,080 --> 06:11:31,760 DAYS ABOUT WHETHER WE WANT TO 8033 06:11:31,760 --> 06:11:33,760 MEASURE LIFESPAN AND HEALTH SPAN 8034 06:11:33,760 --> 06:11:35,680 AND HOW THEY ARE DIFFERENT AND 8035 06:11:35,680 --> 06:11:36,880 MICE PROVIDED OPPORTUNITY TO 8036 06:11:36,880 --> 06:11:40,160 MESH YOUR BOTH AND WE CAN DO 8037 06:11:40,160 --> 06:11:43,640 LIVE SCALE LIFESPAN STUDIES 8038 06:11:43,640 --> 06:11:46,080 HISTORICAL FOCUS OF RESEARCH AND 8039 06:11:46,080 --> 06:11:48,440 RANGE OF HEALTH SPAN WE CAN DO 8040 06:11:48,440 --> 06:11:50,080 IN THESE MICE AND PARTICULARLY 8041 06:11:50,080 --> 06:11:52,360 FRAILTY INDEX THAT SUSAN 8042 06:11:52,360 --> 06:11:54,200 BEAUTIFULLY INTRODUCED THIS 8043 06:11:54,200 --> 06:11:56,600 MORNING AND WE CAN QUICKLY AND I 8044 06:11:56,600 --> 06:11:59,560 PUT IN QUOTATIONS BECAUSE MOUSE 8045 06:11:59,560 --> 06:12:01,000 STUDIES TAKE SEVERAL YEARS AND 8046 06:12:01,000 --> 06:12:03,440 IF YOU HAVE DONE AGING STUDIES 8047 06:12:03,440 --> 06:12:05,960 AS POST DOC YOU KNOW THIS. 8048 06:12:05,960 --> 06:12:07,640 COMPARED TO HUMAN INTERVENTION 8049 06:12:07,640 --> 06:12:09,920 STUDIES WE CAN FAIRLY QUICKLY 8050 06:12:09,920 --> 06:12:11,680 ASSESS EFFECT OF INTERVENTIONS 8051 06:12:11,680 --> 06:12:14,760 ON AGING HOWEVER WE CHOOSE TO 8052 06:12:14,760 --> 06:12:15,720 DEFINE THAT. 8053 06:12:15,720 --> 06:12:18,760 AND THIS THEN PROVIDES 8054 06:12:18,760 --> 06:12:19,960 PRECLINICAL EVIDENCE IN WELL 8055 06:12:19,960 --> 06:12:21,400 CONTROLLED POPULATION TO DECIDE 8056 06:12:21,400 --> 06:12:24,360 WHAT TO TRANSLATE TO CLINICAL 8057 06:12:24,360 --> 06:12:24,720 POPULATIONS. 8058 06:12:24,720 --> 06:12:25,960 WHAT I AM PERHAPS MOST 8059 06:12:25,960 --> 06:12:29,560 INTERESTED IN AND WHY I THINK 8060 06:12:29,560 --> 06:12:36,720 THESE MOST INTERESTING MODELS TO 8061 06:12:36,720 --> 06:12:40,080 USE INVESTIGATE BIOMARKERS IN 8062 06:12:40,080 --> 06:12:42,920 MOST INVASIVE WAY WE CAN IN 8063 06:12:42,920 --> 06:12:45,720 CLINICAL STUDIES AND I USED SOME 8064 06:12:45,720 --> 06:12:48,120 STUDIES THAT ARE MICE AND 8065 06:12:48,120 --> 06:12:50,800 LONGITUDINAL ASSESSMENTS IN MICE 8066 06:12:50,800 --> 06:12:53,280 TO DEVELOP THESE IN STUDIES 8067 06:12:53,280 --> 06:12:54,520 DOING THIS HAVING MALE AND 8068 06:12:54,520 --> 06:12:56,800 FEMALE MICE AND STARTED WITH 8069 06:12:56,800 --> 06:12:58,760 LIFESPAN 13 MONTHS OF AGE ABOUT 8070 06:12:58,760 --> 06:13:00,360 MIDDLE AGE FOR HUMAN AND EVERY 8071 06:13:00,360 --> 06:13:03,520 COUPLE MONTHS WE DID FRAILTY 8072 06:13:03,520 --> 06:13:05,800 ASSESSMENT AND WE TOOK A BLOOD 8073 06:13:05,800 --> 06:13:09,760 SAMPLE FOLLOWING MICE THROUGH 8074 06:13:09,760 --> 06:13:11,640 LIFESPAN THROUGH NATURAL 8075 06:13:11,640 --> 06:13:14,040 MORTALITY BLOOD SAMPLES 8076 06:13:14,040 --> 06:13:15,880 COLLECTED THESE AND ISOLATED DNA 8077 06:13:15,880 --> 06:13:20,280 WE DID DNA METHYLATION TIPS ON 8078 06:13:20,280 --> 06:13:23,160 WITH BRIAN AT FOXO WHO WE HEARD 8079 06:13:23,160 --> 06:13:25,280 FROM EARLIER AND LOOK AD THE 8080 06:13:25,280 --> 06:13:29,040 WIGGLE METABOLOMICS IN PLASMA 8081 06:13:29,040 --> 06:13:32,040 WITH METABOLOME AND DID BLOOD 8082 06:13:32,040 --> 06:13:34,760 COUNTS USING DATA AND NUMBER OF 8083 06:13:34,760 --> 06:13:36,480 THINGS TO DO WITH THIS 8084 06:13:36,480 --> 06:13:37,920 LONGITUDINAL DATA SET AND WHAT 8085 06:13:37,920 --> 06:13:39,360 PARTICULARLY INTERESTED IN IS 8086 06:13:39,360 --> 06:13:41,800 USING DATA TO MAKE CLOCKS FOR 8087 06:13:41,800 --> 06:13:43,400 MICE PREDICTING NOT 8088 06:13:43,400 --> 06:13:47,680 CHRONOLOGICAL AGE BUT FRAILTY 8089 06:13:47,680 --> 06:13:50,360 INDEX AND -- MEASURE CLINICAL 8090 06:13:50,360 --> 06:13:53,680 MEASURE FROM MORGAN LEVINE AND 8091 06:13:53,680 --> 06:13:55,640 MADE CLOCKS TO PREDICT THAT AS 8092 06:13:55,640 --> 06:13:58,920 WELL AND QUICKLY I WILL 8093 06:13:58,920 --> 06:14:01,600 HIGHLIGHT MOUSE CLINICAL FRAILTY 8094 06:14:01,600 --> 06:14:04,560 INDEX MAIN OUTCOME PREDICTING 8095 06:14:04,560 --> 06:14:07,480 SUSAN TALKED ABOUT BRIEFLY 8096 06:14:07,480 --> 06:14:09,680 REVERSE FROM DEFICIT APPROACHING 8097 06:14:09,680 --> 06:14:13,680 HUMANS 31 HEALTH DEFICITS FAST 8098 06:14:13,680 --> 06:14:15,160 NOT INVASIVE TO MEASURE AND HAVE 8099 06:14:15,160 --> 06:14:19,640 A VIDEO THAT IS ALWAYS RISKY AND 8100 06:14:19,640 --> 06:14:22,120 ITEM TAIL STIFFENING AND MICE 8101 06:14:22,120 --> 06:14:24,160 THERE AND BEAUTIFUL CURVATURE 8102 06:14:24,160 --> 06:14:26,440 AROUND TAIL AND THIS MOUSE GETS 8103 06:14:26,440 --> 06:14:28,280 LOW SCORE AND OLD MOUSE NO 8104 06:14:28,280 --> 06:14:29,320 RESPONSE TO [INDISCERNIBLE] AND 8105 06:14:29,320 --> 06:14:31,520 MOUSE WOULD RECEIVE A HIGH SCORE 8106 06:14:31,520 --> 06:14:34,480 THIS IS A EXAMPLE OF ITEMS WE 8107 06:14:34,480 --> 06:14:37,160 ASSESS AND WE HAVE FRAILTY INDEX 8108 06:14:37,160 --> 06:14:40,360 DATA AND DNA METHYLATION DATA 8109 06:14:40,360 --> 06:14:42,800 USING ELASTIC APPROACH TO 8110 06:14:42,800 --> 06:14:45,600 DEVELOP A CLOCK TO PREDICT 8111 06:14:45,600 --> 06:14:46,200 FRAILTY AND YOU SEE HERE 8112 06:14:46,200 --> 06:14:50,360 PREDICTIVE FRAILTY INDEX ON Y 8113 06:14:50,360 --> 06:14:52,440 AND -- WE SEE A NICE CORRELATION 8114 06:14:52,440 --> 06:14:54,640 HERE THAT WE ARE PRETTY HAPPY 8115 06:14:54,640 --> 06:15:01,120 WITH TO PRETTY ACCURATELY 8116 06:15:01,120 --> 06:15:05,560 PREDICT THIS FROM MARKERS AND 8117 06:15:05,560 --> 06:15:07,600 METABOLOMICS DATA AND 8118 06:15:07,600 --> 06:15:11,120 INCORPORATING EPIGENETIC AND 8119 06:15:11,120 --> 06:15:13,960 METABOLOMICS DATA TO ACCURATELY 8120 06:15:13,960 --> 06:15:15,720 PREDICT FRAILTY INDEX AND 8121 06:15:15,720 --> 06:15:18,800 INPROVED IT SPLIETH WILL YOU BUT 8122 06:15:18,800 --> 06:15:21,400 NOT ENOUGH TO JUSTIFY COSTS OF 8123 06:15:21,400 --> 06:15:25,320 EXPENSIVE EXPERIMENTS AND 8124 06:15:25,320 --> 06:15:28,200 METABOLOMICS CLOCK ALONE WAS AS 8125 06:15:28,200 --> 06:15:30,480 PREDICTIVE AS EPIGENERAL EMIC 8126 06:15:30,480 --> 06:15:33,280 ALONE AND TO BE GAINED FROM 8127 06:15:33,280 --> 06:15:37,360 EVALUATION OF DATA SETS, YEAH. 8128 06:15:37,360 --> 06:15:39,480 WE THEN DEVELOPED PHENOAGE 8129 06:15:39,480 --> 06:15:40,920 CLOCKS THAT IS PREDICTING 8130 06:15:40,920 --> 06:15:43,520 FRAILTY INDEX AND WONDER WHETHER 8131 06:15:43,520 --> 06:15:48,000 A MORE COMPOSITE MEASURE OF 8132 06:15:48,000 --> 06:15:49,240 BIOLOGICAL AGE AND HOWEVER WE 8133 06:15:49,240 --> 06:15:50,920 WANT TO TERM THIS AGING PROCESS 8134 06:15:50,920 --> 06:15:53,280 MAY ENABLE US TO PREDICT BETTER 8135 06:15:53,280 --> 06:15:57,640 AND DEVELOPED MOUSE PHENOAGE 8136 06:15:57,640 --> 06:15:58,600 MODEL BASEDONTIRELY ON APPROACH 8137 06:15:58,600 --> 06:16:03,120 OF LIVING AND CLINICAL GROUP OF 8138 06:16:03,120 --> 06:16:04,960 PHENOAGE AND MEASURES IN 8139 06:16:04,960 --> 06:16:06,720 CLINICAL MARKERS NO THE IN MICE 8140 06:16:06,720 --> 06:16:10,440 AND WE HAD 31 FRAILTY MEASURES 8141 06:16:10,440 --> 06:16:12,880 AND WHOLE BLOOD COUNTS AND 8142 06:16:12,880 --> 06:16:14,080 INCORPORATED THEM INTO 8143 06:16:14,080 --> 06:16:16,800 REGRESSION TO BASICALLY MAKE A 8144 06:16:16,800 --> 06:16:18,840 MODEL OF MORTALITY RISK WITHIN 8145 06:16:18,840 --> 06:16:21,880 NEXT FOUR MONTHS AND SOLVED THIS 8146 06:16:21,880 --> 06:16:23,920 FOR A SIMILAR REGRESSION FOR AGE 8147 06:16:23,920 --> 06:16:27,120 THAT GIVES PHENOAGE MEASURE FOR 8148 06:16:27,120 --> 06:16:30,720 A MOUSE THAT IS BASICALLY A 8149 06:16:30,720 --> 06:16:32,640 CHRONOLOGICAL AGE AND ADJUSTED 8150 06:16:32,640 --> 06:16:34,960 FOR BOTH FRAILTY AND MORTALITY 8151 06:16:34,960 --> 06:16:36,520 AND BLOOD COUNTS THAT YOU CAN 8152 06:16:36,520 --> 06:16:40,120 SEE PHENO-ATR ON Y AXIS AND 8153 06:16:40,120 --> 06:16:44,200 ACTUAL AGE ON X AXIS AND NICE 8154 06:16:44,200 --> 06:16:51,120 CORRELATION THAT WE WOULD EX 8155 06:16:51,120 --> 06:16:51,480 EXPECT. 8156 06:16:51,480 --> 06:16:53,360 WE APPLIED SAME MODELING TO SEE 8157 06:16:53,360 --> 06:16:56,040 IF WE COULD PREDICT MODEL 8158 06:16:56,040 --> 06:16:58,000 PERHAPS BEST MEASURE OF 8159 06:16:58,000 --> 06:16:59,600 BIOLOGICAL AGING IN MOUSE MODELS 8160 06:16:59,600 --> 06:17:01,920 AND DID THE SAME PROCESS AND 8161 06:17:01,920 --> 06:17:05,400 ELASTIC APPROACH PREDICTIVE 8162 06:17:05,400 --> 06:17:12,280 PHENOAGE AXIS AND WE SEE A NICE 8163 06:17:12,280 --> 06:17:13,640 CORRELATION HERE AND 8164 06:17:13,640 --> 06:17:15,640 PREDICTABILITY OF EPIGENETIC 8165 06:17:15,640 --> 06:17:19,640 DATA TO PREDICT PHENOAGE 8166 06:17:19,640 --> 06:17:21,560 INCORPORATING MULTI OMIC DATA 8167 06:17:21,560 --> 06:17:25,280 AND NOT HUGE IMPROVEMENT WITH 8168 06:17:25,280 --> 06:17:27,360 COMBINED DATA SETS AND 8169 06:17:27,360 --> 06:17:30,880 METABOLOMICS WAS AS GOOD AS DNA 8170 06:17:30,880 --> 06:17:33,640 METHYLATION DATA BY ITSELF AND 8171 06:17:33,640 --> 06:17:35,000 PROVIDES TOOLS FOR ONGOING MOUSE 8172 06:17:35,000 --> 06:17:37,240 STUDIES TO MEASURE AND PREDICT 8173 06:17:37,240 --> 06:17:38,800 BIOLOGICAL AGE THAT IS A LOADED 8174 06:17:38,800 --> 06:17:40,560 TERM THAT I ASSUME IN THE PANEL 8175 06:17:40,560 --> 06:17:42,240 AFTER THIS WILL BE DISCUSS ABOUT 8176 06:17:42,240 --> 06:17:44,800 WHAT THAT MEANS AND PROVIDES 8177 06:17:44,800 --> 06:17:46,600 SOME COMPOSITE MEASURES THAT WE 8178 06:17:46,600 --> 06:17:48,480 CAN USE IN MOUSE STUDIES THAT WE 8179 06:17:48,480 --> 06:17:51,160 CAN PREDICT WITH OUR MULTI OMIC 8180 06:17:51,160 --> 06:17:52,520 DATA YOU THAT IS OFTEN COLLECTED 8181 06:17:52,520 --> 06:17:56,360 IN STUDIES AS WELL. 8182 06:17:56,360 --> 06:17:58,360 WHAT I'M INTERESTED IN AS I SAID 8183 06:17:58,360 --> 06:18:01,840 IS USING MODEL AND MEASURESES TO 8184 06:18:01,840 --> 06:18:04,560 UNDERSTAND MECHANISMS UNDERLYING 8185 06:18:04,560 --> 06:18:06,880 FRAILTY AND HETEROGENEITY IN 8186 06:18:06,880 --> 06:18:10,680 AGING LOOKING AT BASIC INITIAL 8187 06:18:10,680 --> 06:18:11,880 PRELIMINARY ANALYSIS CORRELATION 8188 06:18:11,880 --> 06:18:14,760 OF METHYLATION OF EACH OF THE 8189 06:18:14,760 --> 06:18:17,280 CPGS WITH FRAILTY INDEX AND HUGE 8190 06:18:17,280 --> 06:18:20,320 AMOUNT OF CPGS IT CORRELATED 8191 06:18:20,320 --> 06:18:22,640 WITH FRAILTY AND COUPLING THESE 8192 06:18:22,640 --> 06:18:25,520 WHICH WE KNOW IS A PROET TERROID 8193 06:18:25,520 --> 06:18:27,680 MOUSE MODEL AND [INDISCERNIBLE] 8194 06:18:27,680 --> 06:18:29,400 THAT WE HEARD ABOUT EARLIER 8195 06:18:29,400 --> 06:18:38,200 COMMONLY ASSOCIATED CPGS WITH 8196 06:18:38,200 --> 06:18:41,120 COMING UP WITH AGING IN HUMAN 8197 06:18:41,120 --> 06:18:42,480 STUDIES AND THERE IS 8198 06:18:42,480 --> 06:18:43,640 CROSS-CORRELATION HERE LOOKING 8199 06:18:43,640 --> 06:18:46,080 AT FRAILTY AND BREAKING DOWN 8200 06:18:46,080 --> 06:18:50,080 NUMBER OF CPGS OF VARIOUS 8201 06:18:50,080 --> 06:18:51,640 PHENOTYPES INTERESTED IN NUMBER 8202 06:18:51,640 --> 06:18:55,640 OF CPGS CORRELATED ACROSS FOUR 8203 06:18:55,640 --> 06:18:59,440 PHENOTYPES AND CPGS CORRELATING 8204 06:18:59,440 --> 06:19:01,280 WITH FRAILTY AND LONGEVITY AND 8205 06:19:01,280 --> 06:19:03,520 COMBINATION OF THESE AND 8206 06:19:03,520 --> 06:19:05,400 INTERESTING TO LOOK INTO SUBSETS 8207 06:19:05,400 --> 06:19:08,960 OF CPGS ASSOCIATED GENES 8208 06:19:08,960 --> 06:19:10,800 ASSOCIATED WITH FRAILTY AND 8209 06:19:10,800 --> 06:19:14,000 INDEPENDENT AGE AND THAT WORK IS 8210 06:19:14,000 --> 06:19:18,800 ONGOING AND ANALYSIS FOR 8211 06:19:18,800 --> 06:19:21,240 METABOLITES AND METABOLOMICS 8212 06:19:21,240 --> 06:19:23,640 DATA AND WE CAN MEASURE AND SEE 8213 06:19:23,640 --> 06:19:25,080 NUMBER OF SIGNIFICANT 8214 06:19:25,080 --> 06:19:27,680 CORRELATIONS HERE AND WHAT WE 8215 06:19:27,680 --> 06:19:33,280 ARE INVESTIGATING FURTHER AND 8216 06:19:33,280 --> 06:19:35,600 TAKEAWAYS USING -- TO PREDICT 8217 06:19:35,600 --> 06:19:38,520 COMPOSITE HEALTH OUTCOMES 8218 06:19:38,520 --> 06:19:40,160 CALLING PERHAPS BIOLOGIC AGES IN 8219 06:19:40,160 --> 06:19:41,920 HUMANS THAT WE HEARD A LOT ABOUT 8220 06:19:41,920 --> 06:19:45,640 AND NOW IN MOUSE MODELS AVEND 8221 06:19:45,640 --> 06:19:48,520 PROVIDE POTENTIAL BIOMARKERS FOR 8222 06:19:48,520 --> 06:19:50,520 PRECLINICAL INTERVENTION STUDIES 8223 06:19:50,520 --> 06:19:53,400 AND ANOTHER PLUG FOR MICE THERE 8224 06:19:53,400 --> 06:19:56,400 ARE VALUABLE MODELS TO STUDY 8225 06:19:56,400 --> 06:19:57,680 BIOMARKERS AND OPPORTUNITY TO 8226 06:19:57,680 --> 06:20:01,000 GIVE CLUES ABOUT MECHANISMS 8227 06:20:01,000 --> 06:20:03,040 UNDERLYING AGING AND HETDERRO 8228 06:20:03,040 --> 06:20:04,280 JENAETY AND CONSIDERATIONS THAT 8229 06:20:04,280 --> 06:20:06,680 I THINK THAT WE CAN DISCUSS MORE 8230 06:20:06,680 --> 06:20:09,080 IN THE PANEL OR MORE IDEAS OF 8231 06:20:09,080 --> 06:20:10,720 OTHER THINGS TO CONSIDER WE 8232 06:20:10,720 --> 06:20:12,120 HAVEN'T HEARD ALL THAT MUCH 8233 06:20:12,120 --> 06:20:13,360 ABOUT SEX DIFFERENCES TODAY THAT 8234 06:20:13,360 --> 06:20:17,240 IS REALLY IMPORTANT AND WE 8235 06:20:17,240 --> 06:20:20,680 GROUPED MALE AND MICE FULLY 8236 06:20:20,680 --> 06:20:22,280 ANALYSIS DIDN'T SEPARATE OUT AND 8237 06:20:22,280 --> 06:20:25,320 QUICK MAP THIS IS DNA 8238 06:20:25,320 --> 06:20:27,960 METHYLATION DATA AND DATA 8239 06:20:27,960 --> 06:20:30,160 ENTIRELY ALMOST SPLITS AND MALE 8240 06:20:30,160 --> 06:20:31,640 AND FEMALE CALLING IT 8241 06:20:31,640 --> 06:20:33,680 DIFFERENTLY HERE AND IS SEX 8242 06:20:33,680 --> 06:20:35,480 SPECIFIC CHANGES HAPPENING HERE 8243 06:20:35,480 --> 06:20:37,680 REQUIRING LOTS MORE 8244 06:20:37,680 --> 06:20:38,840 INVESTIGATION AND THERE IS ALSO 8245 06:20:38,840 --> 06:20:41,320 OTHER DATA THAT COULD BE 8246 06:20:41,320 --> 06:20:44,920 INCORPORATED IN MOUSE STUDIES 8247 06:20:44,920 --> 06:20:47,600 ESPECIALLY LOOKING AT MICROBIOME 8248 06:20:47,600 --> 06:20:50,840 AND PROTEOMICS AND LOTS IS 8249 06:20:50,840 --> 06:20:52,320 ONGOING AND IN THE SLAM STUDY 8250 06:20:52,320 --> 06:20:57,400 THAT RAFA IS UNDERTAKING AND 8251 06:20:57,400 --> 06:21:01,520 FINALLY I THINK AS I SAID MICE 8252 06:21:01,520 --> 06:21:02,680 PROVIDE EXCITING OPPORTUNITY TO 8253 06:21:02,680 --> 06:21:05,280 DELVE INTO MECHANISMS AND 8254 06:21:05,280 --> 06:21:07,280 DETERMINANTS OF FRAILTY AND 8255 06:21:07,280 --> 06:21:08,680 AVAILABILITY OF BIOLOGICAL AGE 8256 06:21:08,680 --> 06:21:10,200 AND FIGURING OUT STILL HOW BEST 8257 06:21:10,200 --> 06:21:13,920 TO DO THIS AND COMING BACK TO 8258 06:21:13,920 --> 06:21:15,160 CIRCULAR ARGUMENTS WHAT MEASURES 8259 06:21:15,160 --> 06:21:20,520 OF AGE ARE THAT WE ARE TRYING TO 8260 06:21:20,520 --> 06:21:21,040 UNDERSTAND. 8261 06:21:21,040 --> 06:21:22,320 WOULD LIKE TO THANK EVERYONE 8262 06:21:22,320 --> 06:21:25,960 INVOLVED IN THIS WORK AND DATA 8263 06:21:25,960 --> 06:21:28,480 COLLECTED IN DAVID SINCLAIR LAB 8264 06:21:28,480 --> 06:21:31,800 AND GRADUATE STUDENT PATRICK 8265 06:21:31,800 --> 06:21:33,680 GRIFFIN WAS A HUGE PART OF THIS 8266 06:21:33,680 --> 06:21:35,840 AND MY COLLABORATORS AND MY 8267 06:21:35,840 --> 06:21:38,800 FUNDING. THANK YOU. 8268 06:21:38,800 --> 06:21:39,640 >>[APPLAUSE]. 8269 06:21:39,640 --> 06:21:49,560 >>INTRODUCING DISCUSSANTS 8270 06:21:49,560 --> 06:21:52,960 BEFORE CALLING PANEL BACK UP. 8271 06:21:52,960 --> 06:21:56,200 FIRST IS NATE TENURE TRACK 8272 06:21:56,200 --> 06:21:59,480 INVESTIGATOR AT NIH AND HEAD OF 8273 06:21:59,480 --> 06:22:02,520 TRANSLATIONAL GEROPROTEOMICS 8274 06:22:02,520 --> 06:22:05,920 UNIT AT NIAAA. THINK I GOT THAT 8275 06:22:05,920 --> 06:22:11,040 RECEIVED PHD AT UNIVERSITY OF 8276 06:22:11,040 --> 06:22:14,800 WASHINGTON -- AND JUDY 8277 06:22:14,800 --> 06:22:15,200 [INDISCERNIBLE]. 8278 06:22:15,200 --> 06:22:20,240 >>THANK YOU, JAMIE. SO, YES. 8279 06:22:20,240 --> 06:22:22,640 I WOULD LIKE TO SPEND A SLIDE 8280 06:22:22,640 --> 06:22:24,120 REFLECTING ON THINGS WE HEARD IN 8281 06:22:24,120 --> 06:22:26,760 TALKS TODAY AND WOULD LIKE TO 8282 06:22:26,760 --> 06:22:27,920 GIVE PERSPECTIVE AS SOMEBODY 8283 06:22:27,920 --> 06:22:30,560 COMING IN AS A MORE BASIC 8284 06:22:30,560 --> 06:22:32,560 BIOLOGIST AND PROTEOMICS PERSON. 8285 06:22:32,560 --> 06:22:36,560 SO, YOU KNOW, I THINK THAT 8286 06:22:36,560 --> 06:22:38,120 TAKING A STEP BACK THINKING WHAT 8287 06:22:38,120 --> 06:22:40,480 WE WANT FROM A BIOMARKER THERE 8288 06:22:40,480 --> 06:22:42,640 IS A FEW YOU KNOW I THINK IT 8289 06:22:42,640 --> 06:22:45,200 BOILS DOWN ESSENTIALLY TO MAINLY 8290 06:22:45,200 --> 06:22:48,080 WE WANT TO MEASURE A CHANGE IN 8291 06:22:48,080 --> 06:22:51,640 RATE OF BIOLOGICAL AGING OR 8292 06:22:51,640 --> 06:22:53,520 AGING PHENOTYPE WITHIN A SHORT 8293 06:22:53,520 --> 06:22:56,080 PERIOD OF TIME AND TO MEASURE 8294 06:22:56,080 --> 06:22:58,440 SPAN WITHIN A CLINICAL TRIAL TO 8295 06:22:58,440 --> 06:23:00,000 TRANSLATE INTERVENTIONS INTO 8296 06:23:00,000 --> 06:23:03,200 PEOPLE; RIGHT? 8297 06:23:03,200 --> 06:23:06,200 SECONDLY AND PREFERABLY WE WOULD 8298 06:23:06,200 --> 06:23:08,880 LIKE TO MEASURE AGING CHANGES 8299 06:23:08,880 --> 06:23:11,440 AND AGING PHENOTYPES BEFORE 8300 06:23:11,440 --> 06:23:13,360 CLINICAL ONSET. WE WANT TO 8301 06:23:13,360 --> 06:23:15,320 MINIMIZE AMOUNT OF TIME THAT WE 8302 06:23:15,320 --> 06:23:23,520 SPENT WITH THAT AGING PHENOTYPE. 8303 06:23:23,520 --> 06:23:26,520 SO, AS WE HEARD FROM SPEAKERS 8304 06:23:26,520 --> 06:23:28,520 TODAY THERE IS A NUMBER OF WAYS 8305 06:23:28,520 --> 06:23:30,080 TO APPROACH THIS PROBLEM AND 8306 06:23:30,080 --> 06:23:33,000 THAT WE CAN BEGIN TO MEASURE 8307 06:23:33,000 --> 06:23:35,160 BIOLOGICAL AGING TO LOOK AT 8308 06:23:35,160 --> 06:23:39,240 CURRENT BIOLOGICAL AGE AND PAST 8309 06:23:39,240 --> 06:23:41,080 EXPOSURES LOOKING AT FUTURE 8310 06:23:41,080 --> 06:23:43,040 HEALTH AND MORTALITY AND LOOK AT 8311 06:23:43,040 --> 06:23:45,600 PACE OF AGING AND TRAJECTORIES 8312 06:23:45,600 --> 06:23:49,240 OF AGING AND VALUE ORGANIZING 8313 06:23:49,240 --> 06:23:52,160 THEM AT OR BEGANIS MAL LEVEL AND 8314 06:23:52,160 --> 06:23:55,240 OR BEGAN SPECIFIC LEVEL THINKING 8315 06:23:55,240 --> 06:23:59,120 OF TAILORING INTERVENTIONS TO 8316 06:23:59,120 --> 06:24:02,120 SPECIFIC DISEASES AND MYRIAD OF 8317 06:24:02,120 --> 06:24:04,080 HALLMARK APPROACH AND TWO TYPES 8318 06:24:04,080 --> 06:24:06,400 OF BIOMARKERS THAT WERE 8319 06:24:06,400 --> 06:24:09,680 DISCUSSED AND INTRODUCED NICELY 8320 06:24:09,680 --> 06:24:12,040 BY STEVE. FIRST IS 8321 06:24:12,040 --> 06:24:13,640 STRATIFICATION BIOMARKERS AND 8322 06:24:13,640 --> 06:24:16,320 THINK THEY WILL BE EXTREMELY 8323 06:24:16,320 --> 06:24:20,320 IMPORTANT IF WE WILL CARRY OUT A 8324 06:24:20,320 --> 06:24:21,560 SUCCESSFUL CLINICAL TRIAL AND 8325 06:24:21,560 --> 06:24:23,280 WANT TO IDENTIFY POPULATION OF 8326 06:24:23,280 --> 06:24:26,360 PEOPLE THAT GET MOST BENEFIT 8327 06:24:26,360 --> 06:24:29,360 FROM A POTENTIAL AGING 8328 06:24:29,360 --> 06:24:35,360 INTERVENTION AND FOR EXAMPLE IF 8329 06:24:35,360 --> 06:24:37,840 I WANT TO DO A SEINO WILLITYIC 8330 06:24:37,840 --> 06:24:41,720 TRIAL SENESCENCE BURDEN; RIGHT? 8331 06:24:41,720 --> 06:24:44,240 IDENTIFYING POPULATION WITH HIGH 8332 06:24:44,240 --> 06:24:51,240 SENESCENCE BURDEN TREATING WITH 8333 06:24:51,240 --> 06:24:52,200 SENOLYTIC REMOVAL TO MAXIMIZE 8334 06:24:52,200 --> 06:24:53,600 CHANCES OF HAVING A POSITIVE 8335 06:24:53,600 --> 06:24:55,240 RESULT IN THE CLINICAL TRIAL AND 8336 06:24:55,240 --> 06:24:57,360 NOT ONLY THAT BIOMARKER COULD BE 8337 06:24:57,360 --> 06:25:01,400 A BIOMARKER INDICATING THAT 8338 06:25:01,400 --> 06:25:03,480 INTERVENTION WHERE TRYING WAS 8339 06:25:03,480 --> 06:25:05,960 EFFECTIVE AND WAY THAT WE WERE 8340 06:25:05,960 --> 06:25:07,440 HOPING FOR THAT COULD INDICATE 8341 06:25:07,440 --> 06:25:13,600 THAT WE SUCCESSFULLY REMOVED 8342 06:25:13,600 --> 06:25:16,320 SENESCENCE CELLS. 8343 06:25:16,320 --> 06:25:19,840 MIGHT NOT NECESSARILY TELL US 8344 06:25:19,840 --> 06:25:22,240 THAT WE SUCCESSFULLY SLOWED 8345 06:25:22,240 --> 06:25:24,800 AGING THAT IS NEXT TYPE OF 8346 06:25:24,800 --> 06:25:26,640 BIOMARKER TO HIGHLIGHT AND IS AN 8347 06:25:26,640 --> 06:25:28,360 IMPORTANT ONE THAT WILL PROBABLY 8348 06:25:28,360 --> 06:25:30,880 BE TRICKIEST ONE FOR US TO 8349 06:25:30,880 --> 06:25:35,240 IMPLEMENT AND STEVE DID A GOOD 8350 06:25:35,240 --> 06:25:39,480 JOB INTRODUCING US LEAVING 8351 06:25:39,480 --> 06:25:40,680 QUESTION OPEN IN LAST SLIDE AND 8352 06:25:40,680 --> 06:25:45,000 WE NEED TO THINK REALLY CAREFUL 8353 06:25:45,000 --> 06:25:47,480 AND MAYBE DISCUSS WHAT WE EXPECT 8354 06:25:47,480 --> 06:25:49,200 AND IN AN INTERVENTION 8355 06:25:49,200 --> 06:25:51,400 RESPONSIVE BIOMARKER TO LOOK 8356 06:25:51,400 --> 06:25:54,360 LIKE AND MIGHT BE MORE STRAIGHT 8357 06:25:54,360 --> 06:25:55,600 FORWARD WITH CLINICAL AND 8358 06:25:55,600 --> 06:25:58,000 FUNCTIONAL MEASUREMENTS AND WHEN 8359 06:25:58,000 --> 06:26:00,360 TALKING ABOUT OTHER MOLECULAR 8360 06:26:00,360 --> 06:26:04,000 MEASUREMENTS WE NEED TO ASK WHAT 8361 06:26:04,000 --> 06:26:06,320 EXACTLY DO WE EXPECT IT OWE TO 8362 06:26:06,320 --> 06:26:09,160 LOOK LIKE CONSIDERING DIFFERENT 8363 06:26:09,160 --> 06:26:10,160 SCENARIOS AND PAST SESSION WE 8364 06:26:10,160 --> 06:26:14,040 SAW SOMETHING TALKING ABOUT 8365 06:26:14,040 --> 06:26:15,320 NONAGING SPECIFIC INTERVENTIONS 8366 06:26:15,320 --> 06:26:17,320 THAT HAVE NONAGING SPECIFIC 8367 06:26:17,320 --> 06:26:19,720 EFFECTS THAT MIGHT ACTUALLY 8368 06:26:19,720 --> 06:26:21,760 EXTEND LIFESPAN AND WOULD 8369 06:26:21,760 --> 06:26:23,120 INTERVENTION LIKE THAT, THAT WE 8370 06:26:23,120 --> 06:26:25,040 ARE STILL INTERESTED IN WOULD 8371 06:26:25,040 --> 06:26:27,680 THAT NECESSARILY REVERSE AN 8372 06:26:27,680 --> 06:26:29,040 AGING BIOLOGICAL AGING CLOCK WAY 8373 06:26:29,040 --> 06:26:33,440 WE EXPECT IT TO OR HAVE AGING 8374 06:26:33,440 --> 06:26:35,480 INDEPENDENT MECHANISM AND WITH 8375 06:26:35,480 --> 06:26:37,880 INTERVENTION RESPONSIVE 8376 06:26:37,880 --> 06:26:39,640 BIOMARKERS PARTICULARLY WITH 8377 06:26:39,640 --> 06:26:41,880 MOLECULAR ONES WE NEED TO 8378 06:26:41,880 --> 06:26:43,600 DISCUSS WHAT DATA WE NEED TO SEE 8379 06:26:43,600 --> 06:26:46,280 TO CONVINCE OURSELVES THAT THIS 8380 06:26:46,280 --> 06:26:50,160 IS A RELIABLE SURROGATE FOR 8381 06:26:50,160 --> 06:26:51,920 SOMETHING COMPLEX AS BIOLOGICAL 8382 06:26:51,920 --> 06:26:55,600 AGING AND CAN WE GET TO THAT 8383 06:26:55,600 --> 06:26:56,600 POINT? 8384 06:26:56,600 --> 06:26:58,920 SECONDLY, I WANT TO REITERATE 8385 06:26:58,920 --> 06:27:00,280 WHAT ALICE PRESENTED THAT IS 8386 06:27:00,280 --> 06:27:02,160 IMPORTANCE OF MODEL ORGANISMS 8387 06:27:02,160 --> 06:27:03,640 AND MICE WILL BE EXTREMELY 8388 06:27:03,640 --> 06:27:06,040 IMPORTANT FOR DEVELOPING AGING 8389 06:27:06,040 --> 06:27:07,680 BIOMARKERS AND FOR ALL REASONS 8390 06:27:07,680 --> 06:27:11,080 THAT ALICE SAID, WE CAN DEVELOP 8391 06:27:11,080 --> 06:27:12,320 PRECLINICAL BIOMARKER CANDIDATES 8392 06:27:12,320 --> 06:27:14,480 IN MICE AND GO INTO HUMANS TO 8393 06:27:14,480 --> 06:27:16,280 TEST WHETHER THEY ARE 8394 06:27:16,280 --> 06:27:16,600 TRANSLATABLE. 8395 06:27:16,600 --> 06:27:21,720 AND IT WILL BE REALLY IMPORTANT 8396 06:27:21,720 --> 06:27:23,200 TO DETERMINE WHICH ARE AND 8397 06:27:23,200 --> 06:27:25,000 ONGOING EFFORTS TO DO THIS AND 8398 06:27:25,000 --> 06:27:27,680 FOR EXAMPLE HEARING ABOUT BLSA 8399 06:27:27,680 --> 06:27:30,400 AND SLAM STUDIESALITY NIAAA THAT 8400 06:27:30,400 --> 06:27:32,440 ARE COLLECTING SIMILAR PHENOTYPE 8401 06:27:32,440 --> 06:27:35,240 DATA FROM BOTH MODELS GETTING AT 8402 06:27:35,240 --> 06:27:37,240 QUESTIONS WHAT ARE TRANSLATABLE 8403 06:27:37,240 --> 06:27:41,000 BETWEEN MICE AND HUMANS AND I 8404 06:27:41,000 --> 06:27:42,840 THINK THAT ANOTHER GREAT 8405 06:27:42,840 --> 06:27:43,640 OPPORTUNITY IS [INDISCERNIBLE] 8406 06:27:43,640 --> 06:27:46,280 AND CONSORTIUM OF RESEARCHERS 8407 06:27:46,280 --> 06:27:48,560 MAPPING SENESCENCE CELLS IN 8408 06:27:48,560 --> 06:27:50,200 TISSUES IN MICE AND HUMANS AND 8409 06:27:50,200 --> 06:27:52,200 GREAT OPPORTUNITY TO TELL US 8410 06:27:52,200 --> 06:27:54,520 WHAT SENESCENCE SPECIFIC MARKERS 8411 06:27:54,520 --> 06:27:56,800 THAT ARE TRANSLATABLE BETWEEN 8412 06:27:56,800 --> 06:27:58,080 INTERVENTIONS THAT I'M NOT EVEN 8413 06:27:58,080 --> 06:27:59,920 -- I DON'T NECESSARILY KNOW HOW 8414 06:27:59,920 --> 06:28:02,360 MANY SPECIFIC BIOMARKERS WILL 8415 06:28:02,360 --> 06:28:03,600 TRANSLATE BETWEEN MICE AND 8416 06:28:03,600 --> 06:28:06,000 HUMANS AND IF THERE ARE NO 8417 06:28:06,000 --> 06:28:07,960 BIOMARKERS TRANSLATING, I THINK 8418 06:28:07,960 --> 06:28:10,560 THAT, YOU KNOW, MICE ARE 8419 06:28:10,560 --> 06:28:12,040 INCREDIBLY USEFUL TOOLS FOR US 8420 06:28:12,040 --> 06:28:15,720 TO TEST BIOMARKER THEORY; RIGHT? 8421 06:28:15,720 --> 06:28:18,120 IN MICE AS ALICE POINTED OUT WE 8422 06:28:18,120 --> 06:28:21,080 CAN FOLLOW THEM INDIVIDUALLY AND 8423 06:28:21,080 --> 06:28:23,360 LONGITUDINALLY UNTIL END OF 8424 06:28:23,360 --> 06:28:25,680 LIFESPAN TESTING INTERVENTIONS 8425 06:28:25,680 --> 06:28:27,880 LOOKING AT INTERVENTIONS AND 8426 06:28:27,880 --> 06:28:34,760 RESPONSES AND SHOWING WE CAN 8427 06:28:34,760 --> 06:28:37,400 BUILD SAME CLOCKS WE DID FOR 8428 06:28:37,400 --> 06:28:38,680 HUMANS AND WITH MICE WE ASK 8429 06:28:38,680 --> 06:28:40,800 QUESTIONS WHICH CLOCKS HAVE MOST 8430 06:28:40,800 --> 06:28:42,200 UTILITY FOR PREDICTING OUTCOMES 8431 06:28:42,200 --> 06:28:44,440 THAT WE ARE INTERESTED IN AND 8432 06:28:44,440 --> 06:28:46,000 VERY LEAST MICE CAN GIVE US AND 8433 06:28:46,000 --> 06:28:48,640 LET US OR HELP US TO STRATEGIZE 8434 06:28:48,640 --> 06:28:57,880 HOW TO APPROACH BIO-MMARKERS - 8435 06:28:57,880 --> 06:28:59,160 BIOMARKERS. AND TECHNOLOGICALLY 8436 06:28:59,160 --> 06:29:01,760 THERE IS ROOM FOR DEVELOPMENT OF 8437 06:29:01,760 --> 06:29:03,560 SENSITIVE AND SPECIFIC 8438 06:29:03,560 --> 06:29:05,360 BIO-MACERS AND LEAVING THIS 8439 06:29:05,360 --> 06:29:08,760 EXAMPLE HERE THAT IS A PROTEOMIC 8440 06:29:08,760 --> 06:29:12,400 EXAMPLE AND APPLIES TO 8441 06:29:12,400 --> 06:29:14,240 TRANSCRIPTOMICS THAT IS MOST 8442 06:29:14,240 --> 06:29:16,560 LARGE SCALE DISCOVERY PROTEOMIC 8443 06:29:16,560 --> 06:29:20,280 PLATFORMS IS AGNOSTIC TO PROTEIN 8444 06:29:20,280 --> 06:29:23,000 VARIANCE OR PROET TEE OE FORMS 8445 06:29:23,000 --> 06:29:26,960 AND THINKING FOR APTO MER OR 8446 06:29:26,960 --> 06:29:28,320 ANTIBODY BINDING SPECIFIC REGION 8447 06:29:28,320 --> 06:29:30,480 OF PROTEIN THAT WILL HAVE PROET 8448 06:29:30,480 --> 06:29:33,320 TEE OE FORMS AND ASSAY IS DOG 8449 06:29:33,320 --> 06:29:34,920 AND AGGREGATING DIFFERENT FORMS 8450 06:29:34,920 --> 06:29:38,000 OF PROTEIN THAT IS INTO A SINGLE 8451 06:29:38,000 --> 06:29:40,200 READ OUT; RIGHT? 8452 06:29:40,200 --> 06:29:42,720 IF YOU -- SAY GLYCOSCILLATED 8453 06:29:42,720 --> 06:29:45,080 FORM OF PROTEIN IS BIOMARKER OF 8454 06:29:45,080 --> 06:29:47,440 AGING YOU ARE LOOKING FOR 8455 06:29:47,440 --> 06:29:49,360 AGGREGATING DATA INTO A SINGLE 8456 06:29:49,360 --> 06:29:51,360 MEASUREMENT YOU ARE DILUTING OUT 8457 06:29:51,360 --> 06:29:53,760 SENSITIVITY OF BIOMARKER THAT 8458 06:29:53,760 --> 06:29:55,120 INTERVENTIONS ARE GOING AND 8459 06:29:55,120 --> 06:29:56,360 TECHNOLOGIES ARE GOING FORWARD 8460 06:29:56,360 --> 06:29:59,120 THAT CAN PAY MORE ATTENTION TO 8461 06:29:59,120 --> 06:30:01,360 PROET TEE OE FORM AND GENE 8462 06:30:01,360 --> 06:30:03,600 VARIANCE WHEN WE MAKE 8463 06:30:03,600 --> 06:30:03,920 MEASUREMENTS. 8464 06:30:03,920 --> 06:30:05,400 THAT IS ALL FOR ME. I THINK 8465 06:30:05,400 --> 06:30:09,240 THAT I WOULD LIKE TO PASS IT ON 8466 06:30:09,240 --> 06:30:16,400 TO LAURA. 8467 06:30:16,400 --> 06:30:18,920 >>AS LAUREN IS COMING UP SHE IS 8468 06:30:18,920 --> 06:30:22,480 AN ASSISTANT PROFESSOR OF -- 8469 06:30:22,480 --> 06:30:24,400 POPULATION RESEARCH CENTER AND 8470 06:30:24,400 --> 06:30:25,200 FACULTY AFFILIATE IN CORRECTOR 8471 06:30:25,200 --> 06:30:27,200 OF AGING AND POPULATION SCIENCES 8472 06:30:27,200 --> 06:30:31,000 AT UNIVERSITY OF TEXAS AUSTIN. 8473 06:30:31,000 --> 06:30:33,720 >>THANK YOU. THANK YOU TO THE 8474 06:30:33,720 --> 06:30:35,240 ORGANIZERS FOR REALLY EXCITING 8475 06:30:35,240 --> 06:30:38,520 SESSION AND FOR INVITING ME TO 8476 06:30:38,520 --> 06:30:38,760 COMMENT. 8477 06:30:38,760 --> 06:30:41,520 I WAS ASKED TO PROVIDE 8478 06:30:41,520 --> 06:30:43,360 REFLECTIONS IN FIVE MINUTES 8479 06:30:43,360 --> 06:30:45,760 ENCOURAGE TODAY BE BOLD AND 8480 06:30:45,760 --> 06:30:47,000 CONTROVERSIAL MAKING PREDICTIONS 8481 06:30:47,000 --> 06:30:50,200 FOR THE FUTURE AND TALL ORDER I 8482 06:30:50,200 --> 06:30:51,600 CAN'T PROMISE FOR FIRST TWO. I 8483 06:30:51,600 --> 06:30:54,600 WILL STICK TO FIVE MINUTES AND 8484 06:30:54,600 --> 06:30:56,080 CONCENTRATING COMMENTS ON 8485 06:30:56,080 --> 06:30:57,240 RELEELATED POINTS REGARDING 8486 06:30:57,240 --> 06:30:59,520 DEVELOPMENT AND USE OF 8487 06:30:59,520 --> 06:31:01,120 BIOMARKERS FORMED BY MY POSITION 8488 06:31:01,120 --> 06:31:03,880 AS A DEMOGRAPHER AND DRAWN TO 8489 06:31:03,880 --> 06:31:05,920 POPULATION PERSPECTIVE AGING AS 8490 06:31:05,920 --> 06:31:09,680 LIFE COURSE PROMISE PROMISES AND 8491 06:31:09,680 --> 06:31:13,000 PITFALLS OF LONGITUDINAL DATA 8492 06:31:13,000 --> 06:31:14,600 AND THESE COMMENTS ARE MOTIVATED 8493 06:31:14,600 --> 06:31:16,440 BY WHAT ARE BIGGEST CHALLENGE RS 8494 06:31:16,440 --> 06:31:17,840 IN COLLECTION AND DEVELOPMENT 8495 06:31:17,840 --> 06:31:21,280 AND USE IN BIO-MACERS AND 8496 06:31:21,280 --> 06:31:23,520 SCIENCE REGARDING DATA AND 8497 06:31:23,520 --> 06:31:24,800 APPROACH AND HOPE TO CONSIDER 8498 06:31:24,800 --> 06:31:27,600 LOOKING TOWARDS FUTURE OF 8499 06:31:27,600 --> 06:31:30,320 GEROSCIENCE AND FIRST 8500 06:31:30,320 --> 06:31:31,280 GEROSCIENCE FRAMEWORK FOR 8501 06:31:31,280 --> 06:31:33,560 CONCEPTUAL AGING EXTENDS WELL TO 8502 06:31:33,560 --> 06:31:36,000 UNDERSTANDING OF AGING AS LIFE 8503 06:31:36,000 --> 06:31:37,240 COURSE PROCESS LATE LIFE AND 8504 06:31:37,240 --> 06:31:39,760 HEALTH DISEASE OUTCOMES WE 8505 06:31:39,760 --> 06:31:41,480 TYPICALLY OBSERVE IN OLD AGE ARE 8506 06:31:41,480 --> 06:31:43,800 ROOTED IN EXPOSURES AND 8507 06:31:43,800 --> 06:31:45,680 EXPERIENCES ACROSS ALL AGES AND 8508 06:31:45,680 --> 06:31:48,600 MEANS TO ADDRESS AGING OUTCOMES 8509 06:31:48,600 --> 06:31:50,960 WE HAVE TO ADDRESS ANTECEDENTS 8510 06:31:50,960 --> 06:31:53,760 OF ANTIAGING ACROSS THE LIFE 8511 06:31:53,760 --> 06:31:55,560 COURSE AND COULD BE DIFFICULT 8512 06:31:55,560 --> 06:31:57,200 STUDYING AGING AND DISEASE AND 8513 06:31:57,200 --> 06:32:00,720 YOUNG POPULATIONS ON SURFACE 8514 06:32:00,720 --> 06:32:03,320 APPEAL HEALTHY AND BIOMARKERS 8515 06:32:03,320 --> 06:32:05,240 COULD BE PARTICULARLY POWERFUL 8516 06:32:05,240 --> 06:32:07,120 AND WHERE WE FACE CHALLENGES 8517 06:32:07,120 --> 06:32:08,880 GIVEN WORK ON BIOMARKER 8518 06:32:08,880 --> 06:32:10,680 DEVELOPMENT AND VALIDATION IS 8519 06:32:10,680 --> 06:32:12,320 THAT OLDER INDIVIDUALS IS STILL 8520 06:32:12,320 --> 06:32:14,600 AN OPEN QUESTION EXTENT TO WHICH 8521 06:32:14,600 --> 06:32:16,240 MARKERS INDICATE RISK AT EARLIER 8522 06:32:16,240 --> 06:32:19,040 AGES AND WHAT DO BIOMARKERS OF 8523 06:32:19,040 --> 06:32:20,640 AGING MEAN IN YOUNG PEOPLE AND 8524 06:32:20,640 --> 06:32:22,560 IN PARTICULAR EARLY LIFE COURSE 8525 06:32:22,560 --> 06:32:25,160 STAGES HOW DO WE KNOW WHAT IS 8526 06:32:25,160 --> 06:32:28,320 ACCELERATED AGING VERSUS WHAT IS 8527 06:32:28,320 --> 06:32:30,520 ACCELERATED HEALTHY OR NORMAL 8528 06:32:30,520 --> 06:32:31,600 DEVELOPMENT AND ARE THESE 8529 06:32:31,600 --> 06:32:33,600 DISTINCTION OR REFLECTIVE OF 8530 06:32:33,600 --> 06:32:37,480 SHARED LIFE COURSE PROCESS OF 8531 06:32:37,480 --> 06:32:38,640 BIOLOGICAL ACCELERATION AND 8532 06:32:38,640 --> 06:32:40,200 BRINGING TO SECOND POINT 8533 06:32:40,200 --> 06:32:41,880 PROMISES AND PITFALLS OF 8534 06:32:41,880 --> 06:32:44,440 LONGITUDINAL DATA TALKING ABOUT 8535 06:32:44,440 --> 06:32:45,760 PERILS OF CROSS-SECTIONAL 8536 06:32:45,760 --> 06:32:47,080 STUDIES AND CONSIDERING 8537 06:32:47,080 --> 06:32:49,920 OPPORTUNITIES AND CHALLENGES OF 8538 06:32:49,920 --> 06:32:51,280 LONGITUDINAL STUDIES RELATED TO 8539 06:32:51,280 --> 06:32:53,280 LIFE COURSE PROCESS AND INSTEAD 8540 06:32:53,280 --> 06:32:54,800 OF THINKING ABOUT INDIVIDUALS AT 8541 06:32:54,800 --> 06:32:57,320 VARIED LIFE STAGES WE CONSIDER 8542 06:32:57,320 --> 06:32:59,240 SAME PERSON FOLLOWED OVER TIME 8543 06:32:59,240 --> 06:33:01,200 AND LONGITUDINAL DATA IS 8544 06:33:01,200 --> 06:33:03,640 VALUABLE AND CAN HELP TO PROVIDE 8545 06:33:03,640 --> 06:33:05,400 LEVERAGE ON SOME MOST PRESSING 8546 06:33:05,400 --> 06:33:07,840 QUESTIONS ABOUT CHANGE AND AGING 8547 06:33:07,840 --> 06:33:09,760 AND IT IS OFTEN CHALLENGING TO 8548 06:33:09,760 --> 06:33:12,840 KNOW WHAT IS TRUE CHANGE AND 8549 06:33:12,840 --> 06:33:14,320 MEASURED ERROR? DAN TALKED 8550 06:33:14,320 --> 06:33:16,320 ABOUT NICELY SELECTION OF PROBES 8551 06:33:16,320 --> 06:33:18,880 FOR PACE STUDY AND HOW MUCH 8552 06:33:18,880 --> 06:33:20,280 CHANGE SHOULD WE EXPECT OVER A 8553 06:33:20,280 --> 06:33:21,760 PARTICULAR PERIOD OF TIME? 8554 06:33:21,760 --> 06:33:23,800 DOES IT DEPEND ON WHEN IN THE 8555 06:33:23,800 --> 06:33:25,960 LIFE COURSE THAT WE ARE LOOKING? 8556 06:33:25,960 --> 06:33:28,880 THEN FINALLY, IMPROVEMENTS 8557 06:33:28,880 --> 06:33:29,960 CONSISTENT WITH 8558 06:33:29,960 --> 06:33:31,720 CONCEPTUALIZATION OF AGING THAT 8559 06:33:31,720 --> 06:33:33,760 FOCUSES ON DECLINE. 8560 06:33:33,760 --> 06:33:37,600 SO, FINALLY, IMPORTANCE OF 8561 06:33:37,600 --> 06:33:38,080 REPRESENTATIVENESS AND 8562 06:33:38,080 --> 06:33:39,040 REPRESENTATION AND MUCH DATA WE 8563 06:33:39,040 --> 06:33:42,480 USE IN BIOMARKER RESEARCH AND 8564 06:33:42,480 --> 06:33:44,240 GEROSCIENCE RELIES ON CLINICAL 8565 06:33:44,240 --> 06:33:45,360 SAMPLE VOLUNTEER SAMPLE 8566 06:33:45,360 --> 06:33:47,440 CONVENIENT SAMPLES OR PARTICULAR 8567 06:33:47,440 --> 06:33:49,160 GEOGRAPHIC POPULATIONS AND OWE 8568 06:33:49,160 --> 06:33:51,400 VEN TIMES SAMPLES ARE 8569 06:33:51,400 --> 06:33:54,120 PREDOMINANT WILL I FROM 8570 06:33:54,120 --> 06:33:55,280 INDIVIDUALS RACIALIZED AS WHITE 8571 06:33:55,280 --> 06:33:57,800 AND RELIANCE ON DATA SOURSS HAVE 8572 06:33:57,800 --> 06:34:00,080 EFFECT OF SUSTAINING REPRODUCING 8573 06:34:00,080 --> 06:34:02,520 HEALTH DISPARITIES AND BOOKENDS 8574 06:34:02,520 --> 06:34:04,080 US WITH WHERE WE STARTED 8575 06:34:04,080 --> 06:34:06,000 YESTERDAY AND LACK OF DIVERSITY 8576 06:34:06,000 --> 06:34:08,000 AND POPULATION REPRESENTATION IN 8577 06:34:08,000 --> 06:34:09,440 BIOMARKER RESEARCH THAT BOTH I 8578 06:34:09,440 --> 06:34:11,920 THINK IN PARTICIPANTS AND IN 8579 06:34:11,920 --> 06:34:14,280 SCIENTISTS THAT PRESENTS MAJOR 8580 06:34:14,280 --> 06:34:15,560 CHALLENGE TO PROGRESS AND 8581 06:34:15,560 --> 06:34:17,440 GEROSCIENCE AND WHAT I WANT TO 8582 06:34:17,440 --> 06:34:19,800 ENCOURAGE US TO THINK ABOUT IS 8583 06:34:19,800 --> 06:34:22,080 IMPROVING SCIENCE THROUGH 8584 06:34:22,080 --> 06:34:24,080 POPULATION REPRESENTATION AND WE 8585 06:34:24,080 --> 06:34:25,840 MUST BE SURE WE DON'T MOTIVATE 8586 06:34:25,840 --> 06:34:30,320 OR USE BIOMARKERS IN WAYS THAT 8587 06:34:30,320 --> 06:34:31,440 BIOLOGY JIEZ GROUP DIFFERENCES 8588 06:34:31,440 --> 06:34:33,240 AND PART OF ANSWER INCLUDES 8589 06:34:33,240 --> 06:34:35,120 RECOGNIZING AND RECKONING WITH 8590 06:34:35,120 --> 06:34:36,920 HARMS AND MALTREATMENT OF 8591 06:34:36,920 --> 06:34:38,280 MARGINALIZED GROUPS AND IN DOING 8592 06:34:38,280 --> 06:34:40,000 THIS WORK, INVITE US TO THINK 8593 06:34:40,000 --> 06:34:42,960 ABOUT HOW WE ENSURE USE AND 8594 06:34:42,960 --> 06:34:48,360 EMPHASIS ON BIOMARKERS DOESN'T 8595 06:34:48,360 --> 06:34:49,440 DESTRUCT FROM SOCIAL 8596 06:34:49,440 --> 06:34:51,160 DETERMINANTS OF HEALTHY AGING 8597 06:34:51,160 --> 06:34:56,080 USING BIOMARKERS -- AND 8598 06:34:56,080 --> 06:34:57,760 DISMANTLING SYSTEMS OF 8599 06:34:57,760 --> 06:34:59,280 OPPRESSION AND THANK YOU AND 8600 06:34:59,280 --> 06:35:02,480 LOOK FORWARD TO OUR DISCUSSION. 8601 06:35:02,480 --> 06:35:06,880 >>[APPLAUSE]. 8602 06:35:06,880 --> 06:35:10,120 >>OKAY. SO, LET'S SEE. I'M 8603 06:35:10,120 --> 06:35:11,840 JAMIE. I HAVE A COUPLE SLIDES 8604 06:35:11,840 --> 06:35:14,280 AND I'M RUNNING LATE AND IF 8605 06:35:14,280 --> 06:35:16,800 SLIDES DON'T POP UP, WELL, 8606 06:35:16,800 --> 06:35:19,000 EITHER WAY HOW ABOUT I CALL 8607 06:35:19,000 --> 06:35:20,480 EVERYBODY UP HERE. IF YOU SPOKE 8608 06:35:20,480 --> 06:35:23,160 THERE IS A NAME CARD FOR YOU. 8609 06:35:23,160 --> 06:35:25,480 WE WILL SEE IF SLIDES COME UP 8610 06:35:25,480 --> 06:35:26,440 AND MAYBE THEY WILL OR MAYBE 8611 06:35:26,440 --> 06:35:30,360 THEY WON'T AND IF NOT I WON'T 8612 06:35:30,360 --> 06:35:40,920 CRY ABOUT IT OKAY. I GUESS WE 8613 06:36:04,200 --> 06:36:06,160 ARE NOT HAVING SLIDES WE WILL GO 8614 06:36:06,160 --> 06:36:09,840 AHEAD AND JUMP INTO THE Q & A 8615 06:36:09,840 --> 06:36:12,120 AND I DID HAVE A COUPLE THINGS. 8616 06:36:12,120 --> 06:36:13,680 WE HAVE PEOPLE LINING UP AND I 8617 06:36:13,680 --> 06:36:17,840 WILL GO AHEAD AND ROLL IT OVER 8618 06:36:17,840 --> 06:36:28,160 TO THE AUDIENCE. 8619 06:37:02,000 --> 06:37:04,240 >>PLOTS. 8620 06:37:04,240 --> 06:37:06,840 >>SO, FOR THOSE SO WE ARE 8621 06:37:06,840 --> 06:37:08,640 SHOWING Z SCORES THAT IS RELATED 8622 06:37:08,640 --> 06:37:10,920 TO STATISTICAL SIGNIFICANCE AND 8623 06:37:10,920 --> 06:37:13,560 IS SOMETHING THAT IS GOING TO BE 8624 06:37:13,560 --> 06:37:15,560 GREATER THAN 2 IS GREATER OR 8625 06:37:15,560 --> 06:37:21,920 WILL BE STATISTICALLY 8626 06:37:21,920 --> 06:37:22,680 SIGNIFI. 8627 06:37:22,680 --> 06:37:27,480 >>COULD YOU HIT THE BUTTON ON 8628 06:37:27,480 --> 06:37:31,040 YOUR MIC? I CAN'T HEAR YOU. 8629 06:37:31,040 --> 06:37:34,400 >>YEAH. SO, I WAS SHOWING Z 8630 06:37:34,400 --> 06:37:36,200 SCORES THERE THAT IS, YOU KNOW, 8631 06:37:36,200 --> 06:37:38,640 WHICH YOU WILL DERIVE BEFORE 8632 06:37:38,640 --> 06:37:42,560 CALCULATING A P VALUE AND SO, 8633 06:37:42,560 --> 06:37:45,880 YOU KNOW, LOOKING AT P VALUE AND 8634 06:37:45,880 --> 06:37:48,560 LESS THAN .05 LOOKING FOR Z 8635 06:37:48,560 --> 06:37:51,920 SCORES DEPENDING ON 1 OR 2 TAIL 8636 06:37:51,920 --> 06:37:53,880 TESTS APPROXIMATELY GREATER THAN 8637 06:37:53,880 --> 06:37:55,520 2 THAT ARE ALL SIGNIFICANT. 8638 06:37:55,520 --> 06:38:00,960 SO, ONE THAT I SHOWED FOR 8639 06:38:00,960 --> 06:38:01,560 MUSCULOSKELETAL AND PHYSICAL 8640 06:38:01,560 --> 06:38:05,200 FUNCTION FIRST THAT IS 9 AND 8641 06:38:05,200 --> 06:38:09,000 ENDS UP BEING VERY SIGNIFICANT. 8642 06:38:09,000 --> 06:38:12,760 >>SO SH, PERHAPS TALKING TO SE 8643 06:38:12,760 --> 06:38:13,440 THE SLIDE? 8644 06:38:13,440 --> 06:38:14,400 >>YEAH. 8645 06:38:14,400 --> 06:38:18,120 >>WHEN YOU LOOK AT COMMENTS. 8646 06:38:18,120 --> 06:38:18,840 >>YEAH. 8647 06:38:18,840 --> 06:38:27,320 >>[INDISCERNIBLE]. 8648 06:38:27,320 --> 06:38:34,880 >>OKAY. JORNL CONNECTICUT AND 8649 06:38:34,880 --> 06:38:36,360 FOLLOW UP COMMENT FROM 8650 06:38:36,360 --> 06:38:38,040 [INDISCERNIBLE] AND SHOUTOUT FOR 8651 06:38:38,040 --> 06:38:42,040 WONDERFUL INVESTMENT TO DEFINE 8652 06:38:42,040 --> 06:38:43,840 SENESCENCE CELLS AND LINK TO 8653 06:38:43,840 --> 06:38:45,000 MICE AND SEVERAL WERE THERE 8654 06:38:45,000 --> 06:38:48,080 THURSDAY AND FRIDAY AND YOU AND 8655 06:38:48,080 --> 06:38:49,920 RAFI AND OTHERS AND THINK THERE 8656 06:38:49,920 --> 06:38:50,640 IS ANOTHER OPPORTUNITY THERE 8657 06:38:50,640 --> 06:38:54,080 THAT WE NEED TO TALK ABOUT THAT 8658 06:38:54,080 --> 06:38:56,280 IS WHAT WE HEAR ABOUT HERE IS 8659 06:38:56,280 --> 06:38:57,840 EXTENT TO WHAT ONE HAS TO DO 8660 06:38:57,840 --> 06:39:01,040 WORKING WITH HUMANS TO TRY TO 8661 06:39:01,040 --> 06:39:02,680 UNDERSTAND WHAT CHANGES IN 8662 06:39:02,680 --> 06:39:06,720 TISSUES CAN GET ACCESS TO LIKE 8663 06:39:06,720 --> 06:39:09,000 BLOOD MEAN IN SPECIFIC OCCURRING 8664 06:39:09,000 --> 06:39:13,760 IN SPECIFIC OR BEGANS SENDING 8665 06:39:13,760 --> 06:39:15,480 AMAZING OPPORTUNITY AND 18 8666 06:39:15,480 --> 06:39:16,880 TISSUES CHARACTERIZED AND 8667 06:39:16,880 --> 06:39:20,480 COLLECTED AND HUGE INVESTMENT 8668 06:39:20,480 --> 06:39:23,360 TERM TERMS LOOKING FOR HEALTHY 8669 06:39:23,360 --> 06:39:25,000 INDIVIDUALS IN ALL AGES 8670 06:39:25,000 --> 06:39:27,080 DESCRIBING WHOLE EFFORT AT 8671 06:39:27,080 --> 06:39:27,720 CONFERENCE TALKING ABOUT 8672 06:39:27,720 --> 06:39:31,400 DISCUSSION ACTUALLY OF DOING 8673 06:39:31,400 --> 06:39:32,920 EPIGENETIC CLOKZ IN INDIVIDUAL 8674 06:39:32,920 --> 06:39:35,160 TISSUES AS WAY OF GETTING SENSE 8675 06:39:35,160 --> 06:39:39,600 OF BIOLOGICAL AGE OF INDIVIDUAL 8676 06:39:39,600 --> 06:39:41,440 THAT IS COMING FROM AND 8677 06:39:41,440 --> 06:39:43,600 OPPORTUNITY TO LOOK AT 8678 06:39:43,600 --> 06:39:47,440 BIOLOGICAL PROCESSES IN BLOOD 8679 06:39:47,440 --> 06:39:49,200 AND 18 DIFFERENT TISSUES 8680 06:39:49,200 --> 06:39:50,000 INCREDIBLE OPPORTUNITY FOR 8681 06:39:50,000 --> 06:39:54,000 COMMUNITY AT LARGE TO LEVERAGE. 8682 06:39:54,000 --> 06:39:59,640 >>JOVRJ THANK YOU FOR THE 8683 06:39:59,640 --> 06:40:00,480 COMMENT. 8684 06:40:00,480 --> 06:40:03,280 AGREE AND IN FACT WITH THESE IN 8685 06:40:03,280 --> 06:40:04,560 PARTICULAR WE HAVE A GREAT 8686 06:40:04,560 --> 06:40:07,560 OPPORTUNITY TO NOW LOOK AT 8687 06:40:07,560 --> 06:40:09,520 CHANGES AND TISSUE SPECIFIC 8688 06:40:09,520 --> 06:40:10,960 CHANGES LONGITUDINALLY THAT IS 8689 06:40:10,960 --> 06:40:13,960 SOMETHING WE ARE DOING WITH RAFA 8690 06:40:13,960 --> 06:40:14,800 AND [INDISCERNIBLE] AND 8691 06:40:14,800 --> 06:40:18,000 BEGINNING TO QUANTIFY THINGS EPI 8692 06:40:18,000 --> 06:40:20,280 GENETIC CLOCKS OR SENESCENCE 8693 06:40:20,280 --> 06:40:23,840 CELL BURDEN BUT CAN GO BACK INTO 8694 06:40:23,840 --> 06:40:26,200 BIO FLUIDS AND BACK INTO THE 8695 06:40:26,200 --> 06:40:28,640 BLOOD AND TRACK LONGITUDINALLY 8696 06:40:28,640 --> 06:40:31,120 HOW MARKERS CHANGE R AS 8697 06:40:31,120 --> 06:40:32,480 SENESCENCE CELL BURDEN CHANGES 8698 06:40:32,480 --> 06:40:34,640 AND EVENTUALLY WOULD BE GREAT TO 8699 06:40:34,640 --> 06:40:36,880 UTILIZE MODELS TO KIND OF YOU 8700 06:40:36,880 --> 06:40:39,640 KNOW DO SOMETHING LIKE REMOVE 8701 06:40:39,640 --> 06:40:41,360 SENESCENCE CELLS OR ACCELERATE 8702 06:40:41,360 --> 06:40:44,240 THEM TO SHOW THESE ARE FOLLOWING 8703 06:40:44,240 --> 06:40:47,760 DOSE DEPENDENT EFFECTS WE EXPECT 8704 06:40:47,760 --> 06:40:50,840 THAT MAY HELP US GET INTO 8705 06:40:50,840 --> 06:40:53,160 IMPROVED PLASMA BIOMARKERS AND 8706 06:40:53,160 --> 06:40:55,800 THERE IS COOL STUFF WE CAN DO ON 8707 06:40:55,800 --> 06:40:59,000 THAT STUDY. 8708 06:40:59,000 --> 06:40:59,280 THANK YOU. 8709 06:40:59,280 --> 06:41:00,360 >>HI. 8710 06:41:00,360 --> 06:41:02,960 SO, ALICE, YOU KIND OF PREEMPTED 8711 06:41:02,960 --> 06:41:06,200 MY QUESTION BY SHOWING THAT 8712 06:41:06,200 --> 06:41:07,600 PROFOUND MALE/FEMALE DIFFERENCE 8713 06:41:07,600 --> 06:41:09,720 IN MARKERS AT VERY END OF THE 8714 06:41:09,720 --> 06:41:12,440 TALK. I WAS INTERESTED IN SEX 8715 06:41:12,440 --> 06:41:13,560 DIFFERENCE AND PERHAPS I WILL 8716 06:41:13,560 --> 06:41:15,800 ASK -- FIRST, I WILL ASK DAN. 8717 06:41:15,800 --> 06:41:19,600 HE SHOWED ONE SLIDE THAT WAS THE 8718 06:41:19,600 --> 06:41:21,840 PACE DATA AT PLOTTED IS A 8719 06:41:21,840 --> 06:41:25,000 FUNCTION OF AGE AND IS WHERE IT 8720 06:41:25,000 --> 06:41:27,480 WAS CROSS-SECTIONAL DATA IF NOT 8721 06:41:27,480 --> 06:41:29,680 MISTAKEN GOING TO 60 OR 70 YEARS 8722 06:41:29,680 --> 06:41:31,240 OLD AND TWO DIFFERENT CURVES 8723 06:41:31,240 --> 06:41:32,840 THROUGH OR LINES THROUGH MALE 8724 06:41:32,840 --> 06:41:36,480 AND FEMALE AND SHOWED ACTUALLY A 8725 06:41:36,480 --> 06:41:39,040 SLOWER RATE OF AGING IF NOT 8726 06:41:39,040 --> 06:41:40,480 MISTAKEN IN FEMALES COMMENTING 8727 06:41:40,480 --> 06:41:43,680 ON THAT AND IF YOU HAVE OLDER 8728 06:41:43,680 --> 06:41:45,200 DATA TO DRAW ON. 8729 06:41:45,200 --> 06:41:48,480 >>YES. THAT IS RIGHT. 8730 06:41:48,480 --> 06:41:49,640 CROSS-SECTIONAL DATA AND OLDEST 8731 06:41:49,640 --> 06:41:53,480 FOLKS IN SAMPLE WR A LITTLE 8732 06:41:53,480 --> 06:41:55,560 ABOVE 90 AND SLOPE IS STEEPER 8733 06:41:55,560 --> 06:41:56,840 FOR MEN THAN WOMEN AND WE SEE 8734 06:41:56,840 --> 06:41:59,400 THAT IN OTHER DATA SETS AND IT 8735 06:41:59,400 --> 06:42:00,680 IS POSSIBLE THAT, THAT 8736 06:42:00,680 --> 06:42:03,600 CORRESPONDS TO WHAT HAS BEEN 8737 06:42:03,600 --> 06:42:05,520 OBSERVED AS AN IN EARLIER 8738 06:42:05,520 --> 06:42:08,120 MORTALITY IN MEN AND THINK THAT 8739 06:42:08,120 --> 06:42:10,400 THERE IS A LOT WE DON'T KNOW 8740 06:42:10,400 --> 06:42:13,200 ABOUT WHY WE MIGHT SEE THAT 8741 06:42:13,200 --> 06:42:15,480 INCLUDING WHAT ARE LIFESTYLE 8742 06:42:15,480 --> 06:42:16,480 DIFFERENCES PARTICULARLY IN 8743 06:42:16,480 --> 06:42:18,200 COHORTS OF INDIVIDUALS IN 70S 8744 06:42:18,200 --> 06:42:21,320 AND 80S AND 90S IN DATA SETS WE 8745 06:42:21,320 --> 06:42:27,000 ARE LOOKING AT HIGHER RATES OF 8746 06:42:27,000 --> 06:42:28,640 SMOKING IN LIVES OF MEN IN THE 8747 06:42:28,640 --> 06:42:31,600 PAST AND WE HESITATE TO MAKE 8748 06:42:31,600 --> 06:42:33,000 ATTRIBUTION TO BIOLOGICAL SEX AT 8749 06:42:33,000 --> 06:42:35,120 THIS POINT AND IS SOMETHING TO 8750 06:42:35,120 --> 06:42:35,400 EXPLORE. 8751 06:42:35,400 --> 06:42:37,680 >>SURE. I MEAN, IF YOU THINK 8752 06:42:37,680 --> 06:42:39,360 ABOUT FRAILTY FOR EXAMPLE YOU 8753 06:42:39,360 --> 06:42:41,640 FIND FEMALES ARE FRAILER BUT 8754 06:42:41,640 --> 06:42:42,960 LIVE LONGER AND LOOKING AT RATE 8755 06:42:42,960 --> 06:42:45,840 OF AGING AND THOUGHT IT WAS AN 8756 06:42:45,840 --> 06:42:46,640 INTERESTING PIECE AND WANTED 8757 06:42:46,640 --> 06:42:48,720 COMMENT ON IT. ANYONE HAVE A 8758 06:42:48,720 --> 06:42:55,320 COMMENT ON MALE/FEMALE? NO? 8759 06:42:55,320 --> 06:42:58,040 OKAY MALE OR FEMALE ANY DATA YOU 8760 06:42:58,040 --> 06:42:58,920 MIGHT HAVE DONE. 8761 06:42:58,920 --> 06:43:01,360 >>SOMETHING I MIGHT OFFER ABOUT 8762 06:43:01,360 --> 06:43:02,560 SEX DIFFERENCES IN HOW WE 8763 06:43:02,560 --> 06:43:05,080 DEVELOP MEASURES OF BIOLOGICAL 8764 06:43:05,080 --> 06:43:07,440 AGING AND CASE OF PACE OF AGING 8765 06:43:07,440 --> 06:43:10,440 IT IS BUILT ON IS NORMALIZED 8766 06:43:10,440 --> 06:43:12,680 WITH INSECTS AND VALUE OF ONE 8767 06:43:12,680 --> 06:43:14,000 CORRESPONDS TO AVERAGE RATE FOR 8768 06:43:14,000 --> 06:43:16,440 A MAN AND IF MAN AVERAGE RATE 8769 06:43:16,440 --> 06:43:17,880 FOR A WOMAN AND IF WOMAN. 8770 06:43:17,880 --> 06:43:18,640 >>RIGHT. 8771 06:43:18,640 --> 06:43:24,040 >>AND IN THE DENEDON COHORT AND 8772 06:43:24,040 --> 06:43:26,360 SEE DIFFERENCES IN BIOLOGICAL 8773 06:43:26,360 --> 06:43:28,320 CHANGES ACROSS LIFESPAN IN MEN 8774 06:43:28,320 --> 06:43:31,080 AND WOMEN AND NOT YET A DECISION 8775 06:43:31,080 --> 06:43:33,480 IN FIELD ABOUT MODELING 8776 06:43:33,480 --> 06:43:35,640 SEPARATELY OR LUMPING TOGETHER 8777 06:43:35,640 --> 06:43:38,480 OR SEEKING TO ACCOMMODATE A 8778 06:43:38,480 --> 06:43:40,600 BROADER SPECTRUM OF BIOLOGICAL 8779 06:43:40,600 --> 06:43:43,600 SEX OR GENDER IDENTITIES AS WE 8780 06:43:43,600 --> 06:43:45,440 INCORPORATE DATA FROM NEWER 8781 06:43:45,440 --> 06:43:45,760 COHORTS. 8782 06:43:45,760 --> 06:43:46,240 >>RIGHT. 8783 06:43:46,240 --> 06:43:48,440 >>BUT THAT IS DIFFERENT FROM 8784 06:43:48,440 --> 06:43:50,760 THE WAY THAT FOR EXAMPLE 8785 06:43:50,760 --> 06:43:52,720 MORTALITY IS MODELS IN OTHER 8786 06:43:52,720 --> 06:43:54,240 SECOND GENERATION CLOCKS IN CASE 8787 06:43:54,240 --> 06:43:59,200 OF PHENOAGE IS SEX NAÏVE AND 8788 06:43:59,200 --> 06:44:00,520 GRIM AGE PARTICIPATE REPORTED 8789 06:44:00,520 --> 06:44:03,640 SEX IS ON RIGHT-HAND SIDE OF 8790 06:44:03,640 --> 06:44:06,480 EQUATION INDEPENDENT PREDICTOR 8791 06:44:06,480 --> 06:44:09,240 IN MODEL DEMETHYLATION PART OF 8792 06:44:09,240 --> 06:44:11,920 THE GRIM AGE IS SEX DEPENDENT 8793 06:44:11,920 --> 06:44:13,200 CONSTRUCT IN THAT WAY. 8794 06:44:13,200 --> 06:44:16,160 >>ENERGY METABOLISM TERMS THERE 8795 06:44:16,160 --> 06:44:17,840 IS KNOWN ESTABLISH THE 8796 06:44:17,840 --> 06:44:18,840 DIFFERENCES BETWEEN WOMEN AND 8797 06:44:18,840 --> 06:44:22,920 MEN AND THINK WE ARE AWAKENING 8798 06:44:22,920 --> 06:44:25,680 TO IDEA ALSO GENDER NOT 8799 06:44:25,680 --> 06:44:27,880 BIOLOGICAL SEX BUT GENDER MIGHT 8800 06:44:27,880 --> 06:44:30,080 PLAY ROLE IN SHAPING BEHAVIORS 8801 06:44:30,080 --> 06:44:34,800 AND THINGS ENDING UP SHAPING 8802 06:44:34,800 --> 06:44:36,560 MITOCHONDRIAL BIOLOGY AND 8803 06:44:36,560 --> 06:44:38,160 DOMAINS OF METABOLISM AND 8804 06:44:38,160 --> 06:44:39,480 IMPORTANT QUESTIONS THAT HAVE 8805 06:44:39,480 --> 06:44:41,160 NOT BEEN TACKLED DIRECTLY BUT 8806 06:44:41,160 --> 06:44:43,600 NEED TO. 8807 06:44:43,600 --> 06:44:46,560 >>RIGHT. OKAY. 8808 06:44:46,560 --> 06:44:49,800 >>I'M FROM UNIVERSITY OF 8809 06:44:49,800 --> 06:44:50,840 CONNECTICUT HEALTH AND FIRST 8810 06:44:50,840 --> 06:44:54,000 QUESTION IS TO DAN. 8811 06:44:54,000 --> 06:44:59,000 CAN WE NOT TRACK FIRST OR SECOND 8812 06:44:59,000 --> 06:45:04,320 GENERATION CLOCKS OVER TIME SO 8813 06:45:04,320 --> 06:45:09,040 CAPTURE CHANGE ACROSS TIME THAT 8814 06:45:09,040 --> 06:45:11,960 ARE ADVANTAGES OF USING CLOCKS 8815 06:45:11,960 --> 06:45:17,920 IN THE TEST OF AGING? 8816 06:45:17,920 --> 06:45:20,240 >>SO, THE QUESTION IS COULD WE 8817 06:45:20,240 --> 06:45:26,040 USE LONGITUDINAL DNA METHYLATION 8818 06:45:26,040 --> 06:45:26,480 DAT 8819 06:45:26,480 --> 06:45:26,680 DATA. 8820 06:45:26,680 --> 06:45:29,560 >>NO TRACKING FIRST OR SECOND 8821 06:45:29,560 --> 06:45:30,880 GENERATIONAL CLOCKS OVER TIME TO 8822 06:45:30,880 --> 06:45:33,040 CAPTURE CHANGE. 8823 06:45:33,040 --> 06:45:33,560 >>OKAY. 8824 06:45:33,560 --> 06:45:36,800 >>OVER TIME AND WHY DO WE NEED 8825 06:45:36,800 --> 06:45:38,840 CLOCKS IN THE PAST OF AGING? 8826 06:45:38,840 --> 06:45:39,920 >>GOOD QUESTION. WHY CAN'T WE 8827 06:45:39,920 --> 06:45:42,520 USE REPEATED MEASURES 8828 06:45:42,520 --> 06:45:44,520 DEMETHYLATION DATA TO PHENOTYPE 8829 06:45:44,520 --> 06:45:46,800 PACE OF AGING AND THERE I THINK 8830 06:45:46,800 --> 06:45:48,760 THAT THERE IS A FEW ANSWERS AND 8831 06:45:48,760 --> 06:45:51,840 ONE IS THAT THERE MAY BE 8832 06:45:51,840 --> 06:45:55,640 INTRINSIC VALUE IN SPEEDOMETER 8833 06:45:55,640 --> 06:45:58,400 MEASURES VERSUS ODOMETER 8834 06:45:58,400 --> 06:46:00,440 MEASURES AND TRUE BY CHA 8835 06:46:00,440 --> 06:46:02,920 TRACKING CHANGE OVER TIME IN 8836 06:46:02,920 --> 06:46:04,920 EPIGENETIC CLOCK YOU CAN DERIVE 8837 06:46:04,920 --> 06:46:06,880 PACE OF AGING AND MIGHT BE VALUE 8838 06:46:06,880 --> 06:46:08,720 IN SINGLE POINT TIME ASSESSMENT 8839 06:46:08,720 --> 06:46:11,560 HOW AGING IS OCCURRING AND RICH 8840 06:46:11,560 --> 06:46:13,200 MILLER HAS COMMENTARY ON THIS IN 8841 06:46:13,200 --> 06:46:14,760 AGING CELL THAT CAME OUT EARLIER 8842 06:46:14,760 --> 06:46:16,760 THIS YEAR OR END OF LAST YEAR HE 8843 06:46:16,760 --> 06:46:18,960 IS WORKING ON SPEEDOMETERS IN 8844 06:46:18,960 --> 06:46:21,960 MICE AND SO THE SECOND REASON IS 8845 06:46:21,960 --> 06:46:25,360 THAT DNA -- LONGITUDINAL DNA 8846 06:46:25,360 --> 06:46:26,800 METHYLATION DATA UP TO NOW HAS 8847 06:46:26,800 --> 06:46:29,120 BEEN RELATIVELY RARE AND 8848 06:46:29,120 --> 06:46:30,880 OPPORTUNITIES FOR PHENOTYPING 8849 06:46:30,880 --> 06:46:32,960 PACING AGING IN THAT FASHION ARE 8850 06:46:32,960 --> 06:46:34,000 LIMITED AND THIRD REASON, AS WE 8851 06:46:34,000 --> 06:46:37,760 HAVE LOOKED AT IT, CHANGES OVER 8852 06:46:37,760 --> 06:46:39,000 TIME IN FIRST GENERATION CLOCKS 8853 06:46:39,000 --> 06:46:41,640 ARE NOT SYSTEMATIC WITH OTHER 8854 06:46:41,640 --> 06:46:43,320 CHANGES THAT WOULD BE 8855 06:46:43,320 --> 06:46:44,680 COMMENSURATE WITH AN AGING 8856 06:46:44,680 --> 06:46:48,320 PROCESS AND IN OTHER WORDS AGE 8857 06:46:48,320 --> 06:46:49,600 ACCELERATION RESIDUAL INCREASING 8858 06:46:49,600 --> 06:46:51,160 OVER TIME DOES NOT CORRESPOND TO 8859 06:46:51,160 --> 06:46:52,960 OTHER SIGNS OF WHAT WE MIGHT 8860 06:46:52,960 --> 06:46:55,040 THINK OF AS ACCELERATED AGING 8861 06:46:55,040 --> 06:46:57,360 PROCESS IN DATA THAT WE HAVE 8862 06:46:57,360 --> 06:46:59,040 LOOKED AT AND AS YOU COULD SEE 8863 06:46:59,040 --> 06:47:01,520 IN THE CALORIE DATA AND SECOND 8864 06:47:01,520 --> 06:47:03,640 GENERATION CLOCKS MEASURED 8865 06:47:03,640 --> 06:47:05,440 REPEATEDLY OVER TIME DID NOT 8866 06:47:05,440 --> 06:47:07,640 DETECT THE BIOLOGICAL CHANGES 8867 06:47:07,640 --> 06:47:08,760 OCCURRING IN THE INDIVIDUALS 8868 06:47:08,760 --> 06:47:11,080 UNDER THE CALORIC RESTRICTION 8869 06:47:11,080 --> 06:47:13,560 REGIME THAT ARE OBSERVED IN 8870 06:47:13,560 --> 06:47:15,200 BLOOD CHEMISTRY ANALYSIS OF 8871 06:47:15,200 --> 06:47:17,320 INDIVIDUALS OR IN PACE OF AGING 8872 06:47:17,320 --> 06:47:19,520 MEASURE AND I GUESS TO CONCLUDE 8873 06:47:19,520 --> 06:47:20,960 IN PRINCIPLE, YES. AND IT WOULD 8874 06:47:20,960 --> 06:47:22,920 BE GOOD TO SEE MORE OF THAT KIND 8875 06:47:22,920 --> 06:47:24,800 OF WORK AS MORE LONGITUDINAL 8876 06:47:24,800 --> 06:47:26,040 DATA IS AVAILABLE. 8877 06:47:26,040 --> 06:47:28,600 >>THANK YOU. CAN I QUICKLY ASK 8878 06:47:28,600 --> 06:47:30,480 A QUESTION TO ALBERT? 8879 06:47:30,480 --> 06:47:32,920 HAVE YOU TRIED TO LOOK AT 8880 06:47:32,920 --> 06:47:35,400 CORRELATIONS THAT ARE BETWEEN 8881 06:47:35,400 --> 06:47:38,280 ORGAN SPECIFIC CLOCKS IF LAID 8882 06:47:38,280 --> 06:47:40,840 OUT LIKE HIGHLY CORRELATED AND 8883 06:47:40,840 --> 06:47:43,400 WE PROBABLY DON'T NEED SO MANY 8884 06:47:43,400 --> 06:47:44,880 ORGAN SPECIFIC CLOCKS. IT WOULD 8885 06:47:44,880 --> 06:47:47,800 BE INTERESTED TO LOOK AT 8886 06:47:47,800 --> 06:47:50,840 [INDISCERNIBLE] ACROSS ORGAN 8887 06:47:50,840 --> 06:47:52,080 SPECIFIC CLOCKS? 8888 06:47:52,080 --> 06:47:55,840 >>SO, THE QUESTION ABOUT 8889 06:47:55,840 --> 06:47:59,640 CORRELATION BETWEEN DIFFERENT 8890 06:47:59,640 --> 06:48:01,480 SYSTEMS SCORES. 8891 06:48:01,480 --> 06:48:04,640 SO, FOR THE RAW VALUES HIGHLY 8892 06:48:04,640 --> 06:48:06,440 CORRELATED BECAUSE THEY ARE ALL 8893 06:48:06,440 --> 06:48:07,600 ASSOCIATED WITH CHRONOLOGICAL 8894 06:48:07,600 --> 06:48:10,800 AGE AND IF YOU CAN RESIDUALIZE 8895 06:48:10,800 --> 06:48:14,640 OUT AGE LOOKING AT CORRELATIONS 8896 06:48:14,640 --> 06:48:19,800 MANY ARE SHOWING CORRELATIONS .5 8897 06:48:19,800 --> 06:48:22,080 AND .6 AND SOME ARE WEAKER AND 8898 06:48:22,080 --> 06:48:23,880 LESS CORRELATED WITH OTHERS AND 8899 06:48:23,880 --> 06:48:25,120 THINK THAT ACTUALLY I DIDN'T GET 8900 06:48:25,120 --> 06:48:27,520 A CHANCE TO SHOW THIS AND IN 8901 06:48:27,520 --> 06:48:31,120 MANY CASES SIMILAR TO WHAT WAS 8902 06:48:31,120 --> 06:48:34,400 SHOWN FOR CORRELATIONS BETWEEN 8903 06:48:34,400 --> 06:48:34,760 SYSTEMS. 8904 06:48:34,760 --> 06:48:36,040 >>I SEE. SECOND QUESTION WOULD 8905 06:48:36,040 --> 06:48:40,360 IT BE -- SORRY TO LOOK AT 8906 06:48:40,360 --> 06:48:41,240 PATIENTS ACROSS CLOCKS. 8907 06:48:41,240 --> 06:48:43,920 >>LOOKING AT WHAT? 8908 06:48:43,920 --> 06:48:47,160 >>PATIENTS ACROSS ORGAN 8909 06:48:47,160 --> 06:48:47,920 SPECIFIC CLOCKS. 8910 06:48:47,920 --> 06:48:49,760 >>ARE YOU TALKING ABOUT 8911 06:48:49,760 --> 06:48:51,440 POTENTIALLY CLUSTERING. 8912 06:48:51,440 --> 06:48:53,080 >>MAYBE CLUSTERING STUFF. 8913 06:48:53,080 --> 06:48:56,560 >>CLUSTERING INDIVIDUALS? 8914 06:48:56,560 --> 06:49:01,680 YEAH. RAGAF HAS DONE THAT IN 8915 06:49:01,680 --> 06:49:04,960 WOMEN HEALTH INITIATIVE COHORTS 8916 06:49:04,960 --> 06:49:07,120 HE WAS ABLE TO DERIVE 9 8917 06:49:07,120 --> 06:49:09,160 DIFFERENT CLUSTERS DIDN'T QUITE 8918 06:49:09,160 --> 06:49:11,240 SHOW IT THERE ARE IF YOU TAKE 8919 06:49:11,240 --> 06:49:13,920 THREE PEOPLE EXACT SAME AGE AND 8920 06:49:13,920 --> 06:49:17,200 SEX AND YOU KNOW EPIGENETIC AGE 8921 06:49:17,200 --> 06:49:19,360 YOU SEE SOME ARE HIGHLY 8922 06:49:19,360 --> 06:49:22,400 ACCELERATED IN SOME SYSTEMS 8923 06:49:22,400 --> 06:49:23,800 TOTALLY DIFFERENT PERSON MIGHT 8924 06:49:23,800 --> 06:49:25,240 ACCELERATE IN OTHER SYSTEMS 8925 06:49:25,240 --> 06:49:26,360 USING THAT TO CLUSTER 8926 06:49:26,360 --> 06:49:27,680 INDIVIDUALS AND WE ARE WORKING 8927 06:49:27,680 --> 06:49:31,840 NOW TO CLUSTER IN LONGITUDINAL 8928 06:49:31,840 --> 06:49:32,040 DATA. 8929 06:49:32,040 --> 06:49:32,920 >>THANK YOU. 8930 06:49:32,920 --> 06:49:36,480 >>FINAL QUESTION. 8931 06:49:36,480 --> 06:49:42,560 >>SCOTT FROM UCSF. I WANTED TO 8932 06:49:42,560 --> 06:49:45,000 ASK THE PANEL ABOUT STEVE YOUR 8933 06:49:45,000 --> 06:49:48,760 COMMENT ABOUT BIOMARKERS THAT 8934 06:49:48,760 --> 06:49:52,360 ARE -- BIOMARKERS USED AS 8935 06:49:52,360 --> 06:49:53,440 SURROGATE AND UNDERSTANDING IS 8936 06:49:53,440 --> 06:49:56,120 THEY HAVE TO BE ON CAUSAL 8937 06:49:56,120 --> 06:49:58,360 PATHWAY FROM INTERVENTION TO 8938 06:49:58,360 --> 06:49:59,280 OUTCOME AND WANT TO CONFIRM 8939 06:49:59,280 --> 06:50:04,880 THAT. IF SO, I WAS CURIOUS HOW 8940 06:50:04,880 --> 06:50:06,160 CONFIDENT ARE WE THAT THESE 8941 06:50:06,160 --> 06:50:08,400 CLOCKS ARE ON CAUSAL PATHWAY? 8942 06:50:08,400 --> 06:50:11,000 I KNOW THERE IS A FEW LIKE 8943 06:50:11,000 --> 06:50:13,160 CALORIE STUDY LOOKING AT 8944 06:50:13,160 --> 06:50:15,080 INTERVENTION AND WHAT WORK IS 8945 06:50:15,080 --> 06:50:19,200 BEING DONE TO PROVE CAUSALITY ON 8946 06:50:19,200 --> 06:50:21,880 PATHWAY? IF NOT, CAN THEY EVER 8947 06:50:21,880 --> 06:50:26,480 BECOME SURROGATE OUTCOMES? 8948 06:50:26,480 --> 06:50:27,640 THANKS. 8949 06:50:27,640 --> 06:50:29,320 >>THAT IS TO YOU. 8950 06:50:29,320 --> 06:50:31,800 >>WELL, I THINK THAT YOU CAN 8951 06:50:31,800 --> 06:50:35,240 MAKE AN EASY CASE FOR SURROGATE 8952 06:50:35,240 --> 06:50:36,880 OUTCOME WHEN YOU KNOW BIOMARKER 8953 06:50:36,880 --> 06:50:42,320 IS ON CAUSAL PATHWAY YOU CAN 8954 06:50:42,320 --> 06:50:44,040 IMAGINE THINGS HIGHLY CORRELATED 8955 06:50:44,040 --> 06:50:48,000 WITH THINGS ON CAUSAL PATHWAY 8956 06:50:48,000 --> 06:50:49,800 THAT MIGHT ALSO SERVE. 8957 06:50:49,800 --> 06:50:51,880 LOOKING BLOOD PRESSURE IS 8958 06:50:51,880 --> 06:50:55,400 SURROGATE OUTCOME FOR LOTS OF 8959 06:50:55,400 --> 06:51:00,480 THINGS AND SOME THAT ARE 8960 06:51:00,480 --> 06:51:02,520 CONSIDERED TO BE AGNOSTIC SORT 8961 06:51:02,520 --> 06:51:05,320 OF. FDA WILL ALLOW IT TO BE 8962 06:51:05,320 --> 06:51:08,680 USED ADS SURROGATE ON OWN NOW 8963 06:51:08,680 --> 06:51:11,960 BECAUSE IT IS RELATED TO SO MANY 8964 06:51:11,960 --> 06:51:14,160 DIFFERENT THINGS AND WE WILL 8965 06:51:14,160 --> 06:51:16,320 NEED TO HAVE STUDIES WHERE WE 8966 06:51:16,320 --> 06:51:19,480 ACTUALLY HAVE AN INTERVENTION 8967 06:51:19,480 --> 06:51:24,080 AND HAS AN EFFECT AND WORK IT 8968 06:51:24,080 --> 06:51:27,200 OUT I THINK AND LARGELY IS AN 8969 06:51:27,200 --> 06:51:29,000 EMPIRICAL QUESTION I THINK TO ME 8970 06:51:29,000 --> 06:51:29,360 ANYWAY. 8971 06:51:29,360 --> 06:51:30,360 >>THANK YOU TO EVERYBODY FOR 8972 06:51:30,360 --> 06:51:32,920 STAYING LATE. WE HAD A REALLY 8973 06:51:32,920 --> 06:51:34,280 DEEP BENCH HERE FOR THE LAST 8974 06:51:34,280 --> 06:51:36,520 SESSION OF THE DAY AND THANK YOU 8975 06:51:36,520 --> 06:51:38,200 TO EVERYONE FOR HANGING IN IF 8976 06:51:38,200 --> 06:51:39,640 YOU HAVE FURTHER QUESTIONS I 8977 06:51:39,640 --> 06:51:41,960 KNOW I DO FEEL FREE TO GRAB 8978 06:51:41,960 --> 06:51:45,280 FOLKS WHILE THEY ARE HERE FOR 8979 06:51:45,280 --> 06:51:45,920 THE MEETING. 8980 06:51:45,920 --> 06:51:56,200 >>[APPLAUSE] A