1 00:00:05,080 --> 00:00:10,400 >>WELCOME. I'M WIN ARIAS 2 00:00:10,400 --> 00:00:13,520 SCIENTIST EMERITUS AT THE 3 00:00:13,520 --> 00:00:17,160 NATIONAL INSTITUTES OF HEALTH. 4 00:00:17,160 --> 00:00:20,000 THIS PROGRAM IS WORLDWIDE 5 00:00:20,000 --> 00:00:21,200 DISTRIBUTED NOW IN 38 DIFFERENT 6 00:00:21,200 --> 00:00:25,560 COUNTRIES. SO WE WELCOME ALL OF 7 00:00:25,560 --> 00:00:29,840 YOU TO WHAT IS THE 11TH SESSION 8 00:00:29,840 --> 00:00:35,160 AND 23RD YEAR OF DEMYSTIFYING 9 00:00:35,160 --> 00:00:37,760 MEDICINE THIS IS REALLY A COURSE 10 00:00:37,760 --> 00:00:39,200 IN BRIDGE BUILDING AND THE LOGO 11 00:00:39,200 --> 00:00:42,080 IN THE UPPER RIGHT OF MY 12 00:00:42,080 --> 00:00:44,040 POWERPOINT IS TO THOSE OF US IN 13 00:00:44,040 --> 00:00:45,800 THE EASTERN PART OF THE UNITED 14 00:00:45,800 --> 00:00:47,600 STATES, THE MOST FAMOUS BRIDGE 15 00:00:47,600 --> 00:00:50,200 IN THE WORLD. BROOKLYN BRIDGE. 16 00:00:50,200 --> 00:00:53,040 HERE IT IS UNDER CONSTRUCTION, 17 00:00:53,040 --> 00:00:54,760 AND YES LIKE THE TWO INDIVIDUALS 18 00:00:54,760 --> 00:00:58,280 ON THE CAT WALK EXCHANGING 19 00:00:58,280 --> 00:01:01,040 VIEWS, EXCHANGING KNOWLEDGE, AND 20 00:01:01,040 --> 00:01:03,520 SEEKING NEW COLLABORATIONS AND 21 00:01:03,520 --> 00:01:06,520 EXPANSION OF OUR UNDERSTANDING 22 00:01:06,520 --> 00:01:09,560 OF MAJOR HEALTH AND MEDICAL 23 00:01:09,560 --> 00:01:12,200 PROBLEMS. KEEP IN MIND ONCE YOU 24 00:01:12,200 --> 00:01:14,160 BUILD A BRIDGE LIFE IS NEVER THE 25 00:01:14,160 --> 00:01:16,920 SAME ON EITHER SIDE. SO 26 00:01:16,920 --> 00:01:18,280 DEMYSTIFYING MEDICINE IS A 27 00:01:18,280 --> 00:01:20,800 COURSE IN BRIDGE BUILDING, IT 28 00:01:20,800 --> 00:01:23,400 BRIDGES EXCITING DEVELOPMENTS IN 29 00:01:23,400 --> 00:01:25,320 BIOLOGY AND ENGINEERING WITH 30 00:01:25,320 --> 00:01:26,200 MEDICINE. 31 00:01:26,200 --> 00:01:33,320 TODAY WE ARE GOING TO 32 00:01:33,320 --> 00:01:35,000 HAVE A DISCUSSION OF A TOPIC 33 00:01:35,000 --> 00:01:36,720 THAT WE ARE A ALL CONCERNED 34 00:01:36,720 --> 00:01:39,160 WITH. THOSE OF US AT ANY AGE 35 00:01:39,160 --> 00:01:40,760 PARTICULARLY THOSE WHO ARE 36 00:01:40,760 --> 00:01:43,680 SLIGHTLY OLDER THAN YOUNGER. AND 37 00:01:43,680 --> 00:01:47,640 THAT IS, WHAT IS AGING? IS AGING 38 00:01:47,640 --> 00:01:50,880 A DISTINCT PROCESS, SOMETHING 39 00:01:50,880 --> 00:01:53,200 THAT IS UNRELATED TO WHAT YOU 40 00:01:53,200 --> 00:01:57,280 MIGHT CALL FRAILTY? OR ALL OF 41 00:01:57,280 --> 00:02:01,160 THOSE CO-MORBID DISEASES 42 00:02:01,160 --> 00:02:03,360 NEURODEGENERATIVE DISEASE, HEART 43 00:02:03,360 --> 00:02:06,600 DISEASE, CANCER, ARE THEY PART 44 00:02:06,600 --> 00:02:08,720 OF AGING? AND SPECIFICALLY 45 00:02:08,720 --> 00:02:13,160 REGARDING NEURODEGENERATION, HOW 46 00:02:13,160 --> 00:02:17,120 IS AGING RELATED THAT PROCESS? 47 00:02:17,120 --> 00:02:18,760 WE WONDER WHETHER THERE'S 48 00:02:18,760 --> 00:02:20,320 DISEASES OF PREMATURE AGING AND 49 00:02:20,320 --> 00:02:23,320 IF SO CAN GENETIC STUDIES HELP 50 00:02:23,320 --> 00:02:24,440 TO UNDERSTAND SOMETHING OF THE 51 00:02:24,440 --> 00:02:31,320 BASIC PRONESS A TOPIC TO BE 52 00:02:31,320 --> 00:02:33,280 DISCUSSED TODAY IS CAN AGING BE 53 00:02:33,280 --> 00:02:35,320 DELAYED? CAN IT BE REVERSED? CAN 54 00:02:35,320 --> 00:02:39,320 IT BE REGULATED? AND IF SO, HOW 55 00:02:39,320 --> 00:02:43,320 THIS IS ONE OF THE BIG EXCITING 56 00:02:43,320 --> 00:02:48,320 ASPECTS OF PANDORA'S BOX WHICH 57 00:02:48,320 --> 00:02:50,360 HAS BEEN OPENED THE LAST SEVERAL 58 00:02:50,360 --> 00:02:52,480 YEARS CREATING NEW IDEAS AND 59 00:02:52,480 --> 00:02:53,600 SCIENTIFIC APPROACHES TO 60 00:02:53,600 --> 00:02:58,400 UNDERSTANDING THE AGING PROCESS. 61 00:02:58,400 --> 00:03:01,480 DOES THE AGING PROCESS ITSELF 62 00:03:01,480 --> 00:03:04,280 AFFECT NEURODEGENERATION? HOW 63 00:03:04,280 --> 00:03:06,880 ARE THESE RELATED? WHERE ARE WE 64 00:03:06,880 --> 00:03:09,080 GOING TO BE THREE, FOUR, FIVE 65 00:03:09,080 --> 00:03:11,640 YEARS FROM NOW? NEXT SLIDE 66 00:03:11,640 --> 00:03:14,680 PLEASE. AGING HAS BEEN 67 00:03:14,680 --> 00:03:17,320 CONSIDERED BY MANY PEOPLE ONE OF 68 00:03:17,320 --> 00:03:19,120 MY FAVORITE THING IS A QUOTE 69 00:03:19,120 --> 00:03:23,400 FROM THE FAMOUS AMERICAN 70 00:03:23,400 --> 00:03:24,760 HUMORIST WILL ROGERS. YOU CAN 71 00:03:24,760 --> 00:03:26,320 CERTAINLY SLOW THE AGING PROCESS 72 00:03:26,320 --> 00:03:28,400 DOWN IF IT HAD TO WORK ITS WAY 73 00:03:28,400 --> 00:03:34,320 THROUGH CONGRESS. SO TODAY, NEXT 74 00:03:34,320 --> 00:03:36,800 SLIDE PLEASE, TODAY WE ARE 75 00:03:36,800 --> 00:03:40,160 EXTREMELY FORTUNATE TO HAVE TWO 76 00:03:40,160 --> 00:03:41,440 GLOBAL AUTHORITY IN THIS 77 00:03:41,440 --> 00:03:44,960 EXCITING AREA OF AGING RESEARCH 78 00:03:44,960 --> 00:03:48,360 AND ITS RELATIONSHIP TO 79 00:03:48,360 --> 00:03:50,600 NEURODEGENERATION IN PARTICULAR. 80 00:03:50,600 --> 00:04:00,200 OUR FIRST SPEAKER, LUIGI PHRYGIA 81 00:04:00,200 --> 00:04:02,400 IS A EPIDEMIOLOGIST AND RESEARCH 82 00:04:02,400 --> 00:04:04,240 SCIENTIST WHO IS CURRENTLY 83 00:04:04,240 --> 00:04:04,840 SCIENTIFIC DIRECTOR AT THE 84 00:04:04,840 --> 00:04:06,720 NATIONAL INSTITUTE OF AGING. AT 85 00:04:06,720 --> 00:04:10,640 THE NIH. LUIGI, FERRUCCI. PRIOR 86 00:04:10,640 --> 00:04:12,480 TO COMING HERE HE WAS AT THE 87 00:04:12,480 --> 00:04:14,600 UNIVERSITY OF FLORENCE ITALY, 88 00:04:14,600 --> 00:04:17,480 WHERE HE RECEIVED BOTH M.D. AND 89 00:04:17,480 --> 00:04:20,720 Ph.D. DEGREES, STUDYING AGING. 90 00:04:20,720 --> 00:04:22,720 WHERE HE WAS ASSOCIATE PROFESSOR 91 00:04:22,720 --> 00:04:26,240 OF BIOLOGY, HUMAN PHYSIOLOGY AND 92 00:04:26,240 --> 00:04:28,680 AGING. AND CHIEF OF THE 93 00:04:28,680 --> 00:04:31,000 GERIATRIC REHABILITATION AND 94 00:04:31,000 --> 00:04:33,000 DIRECTOR OF THE LABORATORY OF 95 00:04:33,000 --> 00:04:38,200 CLINICAL EPIDEMIOLOGY.LY YES 96 00:04:38,200 --> 00:04:39,600 CAME TO THE NIH IN THE 97 00:04:39,600 --> 00:04:43,120 LABORATORY OF -- LUIGI CAME TO 98 00:04:43,120 --> 00:04:46,760 THE NIH IN THE LABORATORY OF 99 00:04:46,760 --> 00:04:49,160 EPIDEMIOLOGY AND BIOLOGY AND 100 00:04:49,160 --> 00:04:50,280 2011 BECAME SCIENTIFIC DIRECTOR 101 00:04:50,280 --> 00:04:51,280 OF THE NATIONAL INSTITUTE OF 102 00:04:51,280 --> 00:04:56,120 AGING. HIS WELL KNOWN FOR 103 00:04:56,120 --> 00:04:57,160 EXTRAORDINARY LONGITUDINAL 104 00:04:57,160 --> 00:05:01,160 STUDIES OF THE RISK FACTORS FOR 105 00:05:01,160 --> 00:05:02,680 MOBILITY DISABILITY AGE 106 00:05:02,680 --> 00:05:03,800 ASSOCIATED FRAILTY AND 107 00:05:03,800 --> 00:05:08,400 MORBIDITY. HE FOCUSES ON THE 108 00:05:08,400 --> 00:05:13,040 HALLMARKS OF AGING. WHAT CAUSES 109 00:05:13,040 --> 00:05:15,080 DECREASE REGENERATIVE ABILITY 110 00:05:15,080 --> 00:05:17,720 AND IMPAIRED SYNAPTIC 111 00:05:17,720 --> 00:05:20,360 PLASTICITY? AND THE ROLE OF 112 00:05:20,360 --> 00:05:25,080 INCREASE NEUROINFLAMMATION? 113 00:05:25,080 --> 00:05:26,920 LUIGI WILL BE THE FIRST SPEAKER 114 00:05:26,920 --> 00:05:30,760 AND FOLLOWING HIS TALK OUR 115 00:05:30,760 --> 00:05:34,880 SECOND SPEAKER, NEXT SLIDE 116 00:05:34,880 --> 00:05:37,560 PLEASE, WILL BE SAUL VILLEDA, 117 00:05:37,560 --> 00:05:39,400 ASSOCIATE PROFESSOR OF ANATOMY 118 00:05:39,400 --> 00:05:40,680 AT THE UNIVERSITY OF CALIFORNIA 119 00:05:40,680 --> 00:05:44,120 AT SAN FRANCISCO. HE RECEIVED 120 00:05:44,120 --> 00:05:46,440 HIS Ph.D. DEGREE AT STANFORD 121 00:05:46,440 --> 00:05:50,120 IN NEUROSCIENCES. HIS RESEARCH 122 00:05:50,120 --> 00:05:55,000 FOCUSES ON THE REVERSAL OF AGING 123 00:05:55,000 --> 00:05:57,440 PARTICULARLY SYNAPTIC NEURAL 124 00:05:57,440 --> 00:06:00,960 PLASTICITY AS WELL AS COGNITIVE 125 00:06:00,960 --> 00:06:02,720 FUNCTION, PRIMARILY IN ANIMALS 126 00:06:02,720 --> 00:06:07,280 WHICH ARE INFUSED WITH YOUTHFUL 127 00:06:07,280 --> 00:06:10,600 FACTORS IN YOUNG BLOOD OR BLOOD 128 00:06:10,600 --> 00:06:13,160 AFTER EXERCISE AND PRO AGING 129 00:06:13,160 --> 00:06:14,800 FACTORS IN OLD BLOOD WHICH 130 00:06:14,800 --> 00:06:18,960 APPEAR TO DRIVE PRE-MATURE 131 00:06:18,960 --> 00:06:23,240 AGING. AT PRESENT HE HAS AN 132 00:06:23,240 --> 00:06:27,520 ENDOWED CHAIR AT UCSF AND 133 00:06:27,520 --> 00:06:31,800 RECEIVED A KECK AND GLENN AWARDS 134 00:06:31,800 --> 00:06:34,440 FOR BIOLOGICAL MECHANISMS OF 135 00:06:34,440 --> 00:06:36,760 AGING AS WELL AS NIH EARLY 136 00:06:36,760 --> 00:06:39,680 INDEPENDENCE AWARDS. SAUL IS THE 137 00:06:39,680 --> 00:06:43,280 ORGANIZER OF THE 2023 KEYSTONE 138 00:06:43,280 --> 00:06:45,600 CONFERENCE SHORTLY COMING UP ON 139 00:06:45,600 --> 00:06:48,200 THE MOLECULAR BASIS OF HEALTHY 140 00:06:48,200 --> 00:06:53,280 AGING. SO WE ARE APPRECIATIVE TO 141 00:06:53,280 --> 00:06:56,240 BOTH OF YOU AND LOOK FORWARD TO 142 00:06:56,240 --> 00:06:59,680 AN EXCITING AFTERNOON OF YOUR 143 00:06:59,680 --> 00:07:00,880 PRESENTATIONS AND OF DISCUSSION 144 00:07:00,880 --> 00:07:02,880 OF THE QUESTIONS AT THE END OF 145 00:07:02,880 --> 00:07:03,200 YOUR TALK. DR. FERRUCCI, WOULD 146 00:07:03,200 --> 00:07:04,760 YOU PLEASE BEGIN. 147 00:07:04,760 --> 00:07:08,040 >> SO FIRST OF ALL, 148 00:07:08,040 --> 00:07:11,120 LET ME THANK THE ORGANIZERS AND 149 00:07:11,120 --> 00:07:14,640 ESPECIALLY DR. ARIAS TO -- FOR 150 00:07:14,640 --> 00:07:18,080 INVITING ME THIS REALLY 151 00:07:18,080 --> 00:07:20,080 IMPORTANT CONVERSATION THAT IS 152 00:07:20,080 --> 00:07:22,040 FOCUSED ON WHAT I THINK IS NOT 153 00:07:22,040 --> 00:07:24,240 ONLY ONE VERY, VERY IMPORTANT 154 00:07:24,240 --> 00:07:28,320 ISSUE FOR SOCIETY BUT MY PASSION 155 00:07:28,320 --> 00:07:31,240 FOREVER. I WANTED TO STUDY AGING 156 00:07:31,240 --> 00:07:33,680 SINCE I WAS A TEENAGER AND I'M 157 00:07:33,680 --> 00:07:35,680 NO LONGER A TEENAGER YOU CAN SEE 158 00:07:35,680 --> 00:07:38,800 FROM THE COLOR OF MY HAIRS BUT 159 00:07:38,800 --> 00:07:42,760 IT IS ABSOLUTELY STILL THERE. I 160 00:07:42,760 --> 00:07:45,520 WILL START BY SAYING THAT I HAVE 161 00:07:45,520 --> 00:07:48,600 NO FINANCIAL CONFLICT TO 162 00:07:48,600 --> 00:07:51,040 DISCLOSE OF ANY TYPE. THEN I'M 163 00:07:51,040 --> 00:07:52,400 GOING TO TELL YOU WHAT I THINK 164 00:07:52,400 --> 00:07:54,760 IS OUR LEARNING OBJECTIVE FOR MY 165 00:07:54,760 --> 00:07:57,280 PRESENTATION TODAY. I WANT TO 166 00:07:57,280 --> 00:07:59,920 SHOW YOU SLOWING DOWN OF THE 167 00:07:59,920 --> 00:08:03,560 AGING HAS POTENTIAL TO IMPROVE 168 00:08:03,560 --> 00:08:05,360 GLOBAL HEALTH EXPECTANCY. THAT 169 00:08:05,360 --> 00:08:08,960 IS VERY IMPORTANT IN THIS WAR, 170 00:08:08,960 --> 00:08:12,000 WHERE AGES IS PROBABLY THE MOST 171 00:08:12,000 --> 00:08:14,080 IMPORTANT FORCE THAT IS CHANGING 172 00:08:14,080 --> 00:08:16,120 OUR ENTIRE SOCIETY FROM FAMILY 173 00:08:16,120 --> 00:08:18,440 TO ECONOMY TO HEALTHCARE AND 174 00:08:18,440 --> 00:08:22,720 OTHER CHARACTERISTICS. SO THIS 175 00:08:22,720 --> 00:08:25,160 IS AN INTRODUCTORY SLIDE FROM MY 176 00:08:25,160 --> 00:08:26,600 TALK TO THAT TELL US WHERE WE 177 00:08:26,600 --> 00:08:30,760 ARE. THIS IS A SLIDE THAT COME 178 00:08:30,760 --> 00:08:34,080 FROM PAPER THAT WAS WRITTEN BY 179 00:08:34,080 --> 00:08:36,440 JIM LAPEL AND HIS GROUP, HE'S 180 00:08:36,440 --> 00:08:38,920 BEEN CERTAINLY THE MOST 181 00:08:38,920 --> 00:08:41,280 IMPORTANT AGING DEMOGRAPHER IN 182 00:08:41,280 --> 00:08:43,360 THE WORLD, FOR VERY LONG TIME, 183 00:08:43,360 --> 00:08:46,400 HE JUST DIED VERY RECENTLY 184 00:08:46,400 --> 00:08:55,040 DURING THE PANDEMIC IN 2020. AND 185 00:08:55,040 --> 00:08:57,040 WHAT IS THE BIG TAKE HERE IN 186 00:08:57,040 --> 00:09:00,320 THIS LITTLE BALL OF DIFFERENT 187 00:09:00,320 --> 00:09:03,440 COLORS? THE NATURE WITH THE 188 00:09:03,440 --> 00:09:07,120 LONGEST LIFE EXPECTANCY. OVER 189 00:09:07,120 --> 00:09:10,720 TIME JIM SELECTED THOSE 190 00:09:10,720 --> 00:09:15,680 COUNTRIES THAT HAD THE LARGEST 191 00:09:15,680 --> 00:09:16,320 LIFE EXPECT STAIN, STARTED FROM 192 00:09:16,320 --> 00:09:18,920 YOU SEE THE BLUE THAT WAS 193 00:09:18,920 --> 00:09:22,640 AUSTRALIA, THEN NORWAY THEN NEW 194 00:09:22,640 --> 00:09:25,560 ZEALAND THEN SWEDEN THEN YOU CAN 195 00:09:25,560 --> 00:09:28,800 SEE THAT ICELAND CAME UP, THEN 196 00:09:28,800 --> 00:09:34,760 FOR LONG TIME THE OLD AGE NATION 197 00:09:34,760 --> 00:09:36,840 HAVE BEEN JAPAN. WHAT IS REALLY 198 00:09:36,840 --> 00:09:39,920 AMAZING TO ME IN THIS SLIDE IS 199 00:09:39,920 --> 00:09:42,840 THAT IF YOU LOOK AT OVER TIME 200 00:09:42,840 --> 00:09:46,000 THEY INCREASE IN LIFE 201 00:09:46,000 --> 00:09:47,800 EXPECTANCY, ALMOST LINEAR 202 00:09:47,800 --> 00:09:51,200 INCREASE WITH AGE. AND WHEN 203 00:09:51,200 --> 00:09:56,920 PEOPLE LOOK AT THIS SLIDE IN 204 00:09:56,920 --> 00:09:58,920 2000 WHEN THE FIRST SUBMISSION 205 00:09:58,920 --> 00:10:00,520 OF THIS PAPER, EVERYBODY SAID IN 206 00:10:00,520 --> 00:10:03,080 IS A PHENOMENON THAT HAS TO SLOW 207 00:10:03,080 --> 00:10:07,840 DOWN AT CERTAIN POINT. IN FACT, 208 00:10:07,840 --> 00:10:09,480 DIFFERENT ORGANIZATION INCLUDES 209 00:10:09,480 --> 00:10:10,720 UNITED NATION AND MILLION 210 00:10:10,720 --> 00:10:13,560 INDUSTRIAL STENOGRAPHERS AND 211 00:10:13,560 --> 00:10:14,720 EPIDEMIOLOGISTS MADE A NUMBER OF 212 00:10:14,720 --> 00:10:17,120 PROJECTION. THE PROJECTION ARE 213 00:10:17,120 --> 00:10:20,680 ILLUSTRATED HERE BY THIS DASHED 214 00:10:20,680 --> 00:10:24,120 LINE. OF COURSE NATURE HAS A WAY 215 00:10:24,120 --> 00:10:25,640 TO BE MUCH STRONGER AND MUCH 216 00:10:25,640 --> 00:10:28,400 MORE CONVINCING THAN ANY 217 00:10:28,400 --> 00:10:31,920 DEMOGRAPHER OR EPIDEMIOLOGIST. 218 00:10:31,920 --> 00:10:35,040 IN SPITE OF THE PRODUCTION, LIFE 219 00:10:35,040 --> 00:10:36,040 EXPECTANCY TEND TO INCREASE 220 00:10:36,040 --> 00:10:39,160 LINEARLY OVER TIME. AND DOESN'T 221 00:10:39,160 --> 00:10:43,120 REALLY HAVE SHOWN, AT LEAST SO 222 00:10:43,120 --> 00:10:45,520 FAR HAVE REALLY SHOWN NO SLOWING 223 00:10:45,520 --> 00:10:49,720 DOWN, NO MODIFICATION OVER TIME 224 00:10:49,720 --> 00:10:51,640 WHY THIS IS IMPORTANT? BECAUSE 225 00:10:51,640 --> 00:10:54,080 WHY WE NEED TO CELEBRATE THE 226 00:10:54,080 --> 00:10:56,360 INCREASING LIFE EXPECTANCY, WE 227 00:10:56,360 --> 00:10:58,160 NEED TO -- WE ARE ABLE TO LIVE 228 00:10:58,160 --> 00:11:01,600 LONGER. THIS IS SUCCESS OF 229 00:11:01,600 --> 00:11:04,560 HUMANS AND THE SAME TIME THE 230 00:11:04,560 --> 00:11:06,120 INCREASE IN LIFE IS NOT 231 00:11:06,120 --> 00:11:07,680 OCCURRING ON THE LEVEL OF THE 232 00:11:07,680 --> 00:11:10,320 GOOD LIFE, THE LIFE THAT IS 233 00:11:10,320 --> 00:11:13,000 CHARACTERIZED BY HEALTH AND JOY 234 00:11:13,000 --> 00:11:14,320 AND EVERYTHING THAT LIFE HAS TO 235 00:11:14,320 --> 00:11:16,920 OFFER BUT ALSO FROM THE LAST 236 00:11:16,920 --> 00:11:20,040 POINT OF LIFE, LIFE THAT IS 237 00:11:20,040 --> 00:11:21,400 CHARACTERIZED BY MULTI-MORBIDITY 238 00:11:21,400 --> 00:11:24,920 AND DISABILITY. AND INTERESTING 239 00:11:24,920 --> 00:11:26,960 PART YOU PROBABLY NEVER REALLY 240 00:11:26,960 --> 00:11:29,720 THOUGHT ABOUT, FEWER PEOPLE MAY 241 00:11:29,720 --> 00:11:32,880 HAVE IS THAT THE MOST SPENT IN 242 00:11:32,880 --> 00:11:37,960 HEALTHCARE, THE LONGEST IS 243 00:11:37,960 --> 00:11:40,040 (INAUDIBLE) OF LIFE EXPECTANCY. 244 00:11:40,040 --> 00:11:43,920 ISN'T THAT -- THE MORE 245 00:11:43,920 --> 00:11:45,800 HEALTHCARE WE TAUGHT INTO GRACE 246 00:11:45,800 --> 00:11:48,360 THE LONGER THE DISABLED LIFE 247 00:11:48,360 --> 00:11:51,920 EXPECTANCY. THAT IS AN IMPORTANT 248 00:11:51,920 --> 00:11:53,520 PART OF OUR CONVERSATION TODAY. 249 00:11:53,520 --> 00:11:57,920 IN FACT, WE SHOULD NOT BE 250 00:11:57,920 --> 00:11:59,680 DISADVISED. IF YOU LOOK AT 251 00:11:59,680 --> 00:12:01,240 EPIDEMIOLOGY OF MAJOR DISEASE, I 252 00:12:01,240 --> 00:12:03,280 THINK MOST OF THE AGING OF THE 253 00:12:03,280 --> 00:12:05,480 POPULATION ESPECIALLY IN THE 254 00:12:05,480 --> 00:12:06,800 DEVELOPED COUNTRY IS DUE TO 255 00:12:06,800 --> 00:12:09,000 DECLINE IN HEART DISEASE. 256 00:12:09,000 --> 00:12:11,000 DECLINE IN HEART DISEASE IS DUE 257 00:12:11,000 --> 00:12:14,600 TO REDUCTION OF THE MODIFICATION 258 00:12:14,600 --> 00:12:17,360 OF RISK FACTORS SUCH AS 259 00:12:17,360 --> 00:12:20,680 HYPERTENSION AND DISLIPIDEMIA. 260 00:12:20,680 --> 00:12:23,680 ALSO CANCER MORTALITY TEND TO 261 00:12:23,680 --> 00:12:26,320 DECLINE OVER TIME THOUGH LESS 262 00:12:26,320 --> 00:12:30,080 STEEPER THAN HEART DISEASE, 263 00:12:30,080 --> 00:12:31,760 THOUGH HERE THE DATA ARE MUCH 264 00:12:31,760 --> 00:12:34,480 MORE PROMISING ESPECIALLY WITH 265 00:12:34,480 --> 00:12:38,040 THE NEW TREATMENT DEVELOPED IN 266 00:12:38,040 --> 00:12:39,800 PARTICULAR WITH NEW TREATMENT 267 00:12:39,800 --> 00:12:41,440 FOR CANCER. STROKE IS DECLINING. 268 00:12:41,440 --> 00:12:45,240 WHAT IS NOW DECLINING AT ALL, 269 00:12:45,240 --> 00:12:48,120 THE DISEASE, THAT CHARACTERIZE 270 00:12:48,120 --> 00:12:53,000 BY MULTI-MORBID COMPLEX 271 00:12:53,000 --> 00:12:54,360 MULTI-MORE BUILDTY AND 272 00:12:54,360 --> 00:12:57,040 DISABILITY. ALZHEIMER'S DISEASE 273 00:12:57,040 --> 00:12:59,000 IS NOT E DECLINING IT IS 274 00:12:59,000 --> 00:13:02,560 INCREASING. INFLUENZA, COPD, 275 00:13:02,560 --> 00:13:06,320 DON'T SHOW ANY SIGN OF DECLINE 276 00:13:06,320 --> 00:13:07,520 AND IN FACT WHAT IS INCREASING 277 00:13:07,520 --> 00:13:11,880 IN TERMS OF CAUSE OF DEATH IS 278 00:13:11,880 --> 00:13:13,120 THE MULTI-(INAUDIBLE) OF DEATH. 279 00:13:13,120 --> 00:13:17,120 PEOPLE TEND TO HAVE -- DIE OF 280 00:13:17,120 --> 00:13:21,840 MULTIPLE DISEASES, PHENOMENON OF 281 00:13:21,840 --> 00:13:32,400 MULTI-MORBIDITY. LIFE THE AMOUNT 282 00:13:37,120 --> 00:13:39,960 OF TIME WE HAVE GAIN IS 283 00:13:39,960 --> 00:13:42,920 DETERMINED -- ESPECIALLY IN 284 00:13:42,920 --> 00:13:44,120 PERCENTAGE, IN THE BAD PART OF 285 00:13:44,120 --> 00:13:46,320 LIFE. THE LIFE CHARACTERIZED BY 286 00:13:46,320 --> 00:13:49,960 DISEASE AND DISABILITY. AS A 287 00:13:49,960 --> 00:13:53,680 PATIENT OF MINE TOLD ME ONCE, 288 00:13:53,680 --> 00:13:57,440 THE ISSUE IS THAT WHEN LIFE IS 289 00:13:57,440 --> 00:14:00,560 GOOD, IT GO REALLY FAS FAST. WHI 290 00:14:00,560 --> 00:14:02,040 HAVE DISEASE AND DISABILITY THE 291 00:14:02,040 --> 00:14:03,680 LIFE SEEM TO GO SLOWER AND 292 00:14:03,680 --> 00:14:07,880 SLOWER AN SLOWER. SO THAT IS ONE 293 00:14:07,880 --> 00:14:09,120 ISSUE WE SNEAD TO ADDRESS IN OUR 294 00:14:09,120 --> 00:14:12,760 SOCIETY. SO THE WAY I THINK 295 00:14:12,760 --> 00:14:16,600 ABOUT IT, IS THAT WE WANT THE 296 00:14:16,600 --> 00:14:17,880 HEALTHY LIFE THAT WE HAVE LOST 297 00:14:17,880 --> 00:14:20,080 OVER THE YEARS. THE ISSUES THAT 298 00:14:20,080 --> 00:14:22,640 HOW DO WE DO THAT, HOW DO WE 299 00:14:22,640 --> 00:14:26,920 ACCOMPLISH THAT? TO GO BACK TO 300 00:14:26,920 --> 00:14:29,840 UNDERSTANDING WHY THIS IS 301 00:14:29,840 --> 00:14:33,800 HAPPENING, IS THAT WE DISCOVERED 302 00:14:33,800 --> 00:14:36,240 IN EPIDEMIOLOGICAL STUDY, THIS 303 00:14:36,240 --> 00:14:40,400 HAS COME IN CLUSTERS. WHAT DO I 304 00:14:40,400 --> 00:14:43,040 MEAN? WHEN YOU DEVELOP ONE 305 00:14:43,040 --> 00:14:44,320 DISEASE THE PROBABILITY YOU 306 00:14:44,320 --> 00:14:46,520 DEVELOP A SECOND ONE IS MUCH 307 00:14:46,520 --> 00:14:49,400 HIGHER AT THE SAME AGE THAN IF 308 00:14:49,400 --> 00:14:50,960 WE DIDN'T HAVE THAT FIRST 309 00:14:50,960 --> 00:14:53,680 DISEASE. THIS IS TRUE 310 00:14:53,680 --> 00:14:54,600 INDEPENDENT OF WHAT DISEASE YOU 311 00:14:54,600 --> 00:15:01,000 ARE TALKING ABOUT. SO WHEN I 312 00:15:01,000 --> 00:15:03,000 START EPIDEMIOLOGIST WE USED TO 313 00:15:03,000 --> 00:15:06,040 SAY WELL, I THINK THAT WE WANT 314 00:15:06,040 --> 00:15:08,280 TO KNOW WHAT HAPPEN IF WE 315 00:15:08,280 --> 00:15:10,080 ELIMINATE CARDIOVASCULAR 316 00:15:10,080 --> 00:15:13,120 DISEASE. THAT WAS REALLY THE 317 00:15:13,120 --> 00:15:15,560 WRONG QUESTION BECAUSE 318 00:15:15,560 --> 00:15:16,680 CARDIOVASCULAR DISEASE ONLY 319 00:15:16,680 --> 00:15:18,360 MEANS ANOTHER DISEASE THAT IS 320 00:15:18,360 --> 00:15:20,560 CLUSTER WITH THE FIRST ONE WILL 321 00:15:20,560 --> 00:15:24,760 COME SHORTLY LATER. SO IF YOU 322 00:15:24,760 --> 00:15:28,920 THINK ABOUT THE PERSON THAT IS 323 00:15:28,920 --> 00:15:33,800 AN ARCH LIFE EXPECTANCY IS THE 324 00:15:33,800 --> 00:15:35,240 PEAK BY THIS GRAPH. YOU CAN SEE 325 00:15:35,240 --> 00:15:38,120 IN THE BLUE SHAPE PART OF THE 326 00:15:38,120 --> 00:15:40,680 GRAPH YOU HAVE PERIOD WHERE 327 00:15:40,680 --> 00:15:42,240 DISEASE EPIDEALOLOGY ACCUMULATE 328 00:15:42,240 --> 00:15:45,160 BUT IS NOT EVIDENT BECAUSE IT IS 329 00:15:45,160 --> 00:15:48,520 NOT EMERGE CLINICALLY AS SYMPTOM 330 00:15:48,520 --> 00:15:49,760 OF FUNCTIONAL LIMITATIONS. 331 00:15:49,760 --> 00:15:53,120 ANOTHER PERSON THAT HAS A LIFE 332 00:15:53,120 --> 00:15:56,720 EXPECTANCY THAT IS LONGER YOU 333 00:15:56,720 --> 00:15:59,200 WILL HAVE THIS BRIEF PATHOLOGY 334 00:15:59,200 --> 00:16:00,600 WILL BE LONGER BUT YOU WILL 335 00:16:00,600 --> 00:16:01,800 STILL SEE THE DISEASE THAT OCCUR 336 00:16:01,800 --> 00:16:04,720 AS A CLUSTER. THEREFORE, 337 00:16:04,720 --> 00:16:07,040 SOMEBODY WITH A SHORTER LIFE 338 00:16:07,040 --> 00:16:08,920 EXPECTANCY YOU WILL SEE A 339 00:16:08,920 --> 00:16:11,280 SHORTER PERIOD OF CLINICAL 340 00:16:11,280 --> 00:16:13,120 PATHOLOGY BUT THEN THE SAME 341 00:16:13,120 --> 00:16:16,320 CLUSTER OF DISEASE THAT OCCUR 342 00:16:16,320 --> 00:16:18,120 RECENTLY THEREAFTER. REMEMBER 343 00:16:18,120 --> 00:16:21,120 THIS SLIDE BECAUSE THIS IS THE 344 00:16:21,120 --> 00:16:24,960 KEY TO UNDERSTAND WHAT I WILL BE 345 00:16:24,960 --> 00:16:28,160 TALKING TODAY. THE REAL PROBLEM 346 00:16:28,160 --> 00:16:30,040 IS WE HAVE A HEALTHCARE SYSTEM 347 00:16:30,040 --> 00:16:32,520 THAT ONLY INTERVENE AT THE TIME 348 00:16:32,520 --> 00:16:34,520 WHEN DISEASE BECOME CLINICALLY 349 00:16:34,520 --> 00:16:35,960 RELEVANT. THAT IS THE TIME YOU 350 00:16:35,960 --> 00:16:37,400 INTERVENE. BECAUSE YOU INTERVENE 351 00:16:37,400 --> 00:16:40,280 AT THAT POINT, THE ONLY THING 352 00:16:40,280 --> 00:16:42,240 THAT YOU CAN INFLUENCE IS WHAT 353 00:16:42,240 --> 00:16:47,480 COME LATER. SO THE U.S. SPENT 354 00:16:47,480 --> 00:16:49,800 LESS THAN 3% OF THE ENTIRE 355 00:16:49,800 --> 00:16:52,360 BUDGET ON HEALTHCARE, 356 00:16:52,360 --> 00:16:54,800 PREVENTION, SO ON THIS PERIOD IN 357 00:16:54,800 --> 00:16:56,400 97% IN THIS PERIOD. THERE IS NO 358 00:16:56,400 --> 00:16:59,920 DOUBT THAT ONLY THING WE CAN 359 00:16:59,920 --> 00:17:01,840 ACCOMPLISH IS TO PROLONG THIS 360 00:17:01,840 --> 00:17:04,160 LIFE EXPECTANCY ESPECIALLY THOSE 361 00:17:04,160 --> 00:17:06,800 INCREASING LIFE EXPECTANCY 362 00:17:06,800 --> 00:17:09,440 RELATED TO HEALTHCARE. 363 00:17:09,440 --> 00:17:10,920 EXPERIENCE FOR ME, I GO TO THE 364 00:17:10,920 --> 00:17:13,640 DOCTOR EVERY YEAR, I ASK THE 365 00:17:13,640 --> 00:17:16,480 DOCTOR TO CHECK ME OUT, SEE WHAT 366 00:17:16,480 --> 00:17:21,200 I HAVE PROBLEM AND DO A SCOPE OF 367 00:17:21,200 --> 00:17:23,400 MY CHEST, PRETEND TO LOOK AT MY 368 00:17:23,400 --> 00:17:24,840 HEART, THEN THEY TELL ME THAT 369 00:17:24,840 --> 00:17:27,120 I'M GOOD. MY HEALTH IS GOOD, I 370 00:17:27,120 --> 00:17:29,040 EXERCISE, I EAT PROPERLY, MY 371 00:17:29,040 --> 00:17:31,360 WEIGHT IS NOT CHANGING, MY BLOOD 372 00:17:31,360 --> 00:17:32,960 PRESSURE IS OKAY, MY CHOLESTEROL 373 00:17:32,960 --> 00:17:36,040 IS OKAY. I GET FROM THERE UPSET 374 00:17:36,040 --> 00:17:38,280 BECAUSE I KNOW THERE IS 375 00:17:38,280 --> 00:17:40,000 PATHOLOGY, AQUME LATING IN MY 376 00:17:40,000 --> 00:17:42,000 BODY. I KNOW -- I WANT TO KNOW 377 00:17:42,000 --> 00:17:43,400 HOW MUCH AND I WANT TO KNOW WHY 378 00:17:43,400 --> 00:17:47,440 AND WHAT I CAN DO ABOUT IT. SO 379 00:17:47,440 --> 00:17:50,440 THE PROBLEM TO ME IS LIKE WE ARE 380 00:17:50,440 --> 00:17:51,960 HAVING AN EGG AND THE EGG IS IN 381 00:17:51,960 --> 00:17:54,920 THE MIDDLE OF THE AIR AND WE 382 00:17:54,920 --> 00:17:57,280 KNOW THAT IS IN A (INAUDIBLE) 383 00:17:57,280 --> 00:18:00,560 DOWN BECAUSE OF GRAVITY, WE 384 00:18:00,560 --> 00:18:01,480 DON'T DO ANYTHING OR THE EGG 385 00:18:01,480 --> 00:18:05,320 WILL BREAK. WHEN THE EGG BREAK, 386 00:18:05,320 --> 00:18:07,760 PUTTING BACK THE BROKEN EGG 387 00:18:07,760 --> 00:18:10,440 TOGETHER, IT IS GOING TO BE VERY 388 00:18:10,440 --> 00:18:12,800 PROBLEMATIC. SO WHAT YOU REALLY 389 00:18:12,800 --> 00:18:15,920 WANT TO DO IS TO CATCH THE EGG 390 00:18:15,920 --> 00:18:18,040 AND DO SOMETHING WHEN THE EGG IS 391 00:18:18,040 --> 00:18:21,760 STILL IN THE CHICKEN. WHEN IT IS 392 00:18:21,760 --> 00:18:23,240 STILL IN THE CHICKEN YOU CAN 393 00:18:23,240 --> 00:18:24,840 PREVENT THE EGG FROM BREAKING 394 00:18:24,840 --> 00:18:27,160 DOWN AND DROPPING AND MAYBE 395 00:18:27,160 --> 00:18:28,360 THERE'S SOMETHING THAT WE CAN DO 396 00:18:28,360 --> 00:18:31,560 ABOUT IT. HOW DO WE DO THAT? I 397 00:18:31,560 --> 00:18:35,360 THINK THAT WE HAVE TO GO BACK TO 398 00:18:35,360 --> 00:18:38,800 MY INITIAL SLIDE AND SAY LIFE 399 00:18:38,800 --> 00:18:40,760 EXPECTANCY DISEASE -- AS YOU CAN 400 00:18:40,760 --> 00:18:42,760 SEE THE ACCUMULATION OF 401 00:18:42,760 --> 00:18:46,000 PATHOLOGY THAT OCCUR PRETTY 402 00:18:46,000 --> 00:18:48,200 CLINICALLY IN THIS THREE 403 00:18:48,200 --> 00:18:50,200 INDIVIDUAL OCCUR ALSO AT 404 00:18:50,200 --> 00:18:52,320 (INAUDIBLE) SO IF I TRY TO 405 00:18:52,320 --> 00:18:56,720 AVERAGE THIS TRAJECTORY THAT ARE 406 00:18:56,720 --> 00:18:59,120 CLINICAL, I CAN SEE THIS PROJECT 407 00:18:59,120 --> 00:19:01,280 WILL HAVE DIFFERENT SLOPE IF I 408 00:19:01,280 --> 00:19:04,840 ONLY LOOK AT THE SLOPE Z THIS 409 00:19:04,840 --> 00:19:10,080 SLOPE TELL ME WHAT INCREASE 410 00:19:10,080 --> 00:19:11,800 SUSCEPTIBILITY TO THE MULTIPLE 411 00:19:11,800 --> 00:19:13,960 DISEASE. NEW SCIENCE IS 412 00:19:13,960 --> 00:19:19,880 EMERGING CALLED GEE ROW SCIENCE 413 00:19:19,880 --> 00:19:20,560 THEORIZE THE ONLY GENE OF 414 00:19:20,560 --> 00:19:22,520 DISEASE, ROOT TO DISEASE IS THE 415 00:19:22,520 --> 00:19:26,760 PACE OF AGING. GERO SCIENCE. THE 416 00:19:26,760 --> 00:19:29,320 SAME THAT CAUSED THE PHENOTYPIC 417 00:19:29,320 --> 00:19:30,600 MANIFESTATION OF AGING ARE THOSE 418 00:19:30,600 --> 00:19:32,160 THAT CREATE THE OPPORTUNITY FOR 419 00:19:32,160 --> 00:19:35,840 THE DEVELOPMENT OF CHRONIC 420 00:19:35,840 --> 00:19:39,040 DISEASE. SO IF I MENTION PACE OF 421 00:19:39,040 --> 00:19:42,320 AGING I CAN UNDERSTAND EARLY 422 00:19:42,320 --> 00:19:44,120 BEFORE THE CLINICAL AROUND 423 00:19:44,120 --> 00:19:45,040 REPRODUCIBILITY OF THE DISEASE 424 00:19:45,040 --> 00:19:46,640 WHO ARE THE INDIVIDUAL SHOWING 425 00:19:46,640 --> 00:19:49,000 RAPID AGING AN INTERVENE ON 426 00:19:49,000 --> 00:19:52,000 THEM. THEN I THINK THAT THIS IS 427 00:19:52,000 --> 00:19:56,840 OLD SLIDE BUT TO ME THE BEST 428 00:19:56,840 --> 00:19:59,440 PRESENTATION OVER GERO SCIENCE 429 00:19:59,440 --> 00:20:01,040 WANT TO DO. IF YOU SLOW DOWN 430 00:20:01,040 --> 00:20:03,320 AGING INSTEAD OF IN PARALLEL TO 431 00:20:03,320 --> 00:20:07,240 DO A SPECIFIC DISEASE 432 00:20:07,240 --> 00:20:08,400 PREVENTION, WE WILL NOT ADDRESS 433 00:20:08,400 --> 00:20:10,200 ONE SINGLE DISEASE BUT WILL 434 00:20:10,200 --> 00:20:13,760 ADDRESS MULTIPLE CHRONIC DISEASE 435 00:20:13,760 --> 00:20:15,720 OVER TIME AND INSTEAD OF 436 00:20:15,720 --> 00:20:16,760 SPECIFIC TREATMENT WE WILL SLOW 437 00:20:16,760 --> 00:20:20,080 DOWN AGING AND REDUCE THE 438 00:20:20,080 --> 00:20:21,640 EMERGENCE AND INCIDENCE OF 439 00:20:21,640 --> 00:20:26,720 MULTIPLE CHRONIC DISEASES. CAN 440 00:20:26,720 --> 00:20:31,600 WE SLOW DOWN AGING? I SAY 441 00:20:31,600 --> 00:20:33,480 SOMETHING LIKELY BUT IS THAT 442 00:20:33,480 --> 00:20:35,240 POSSIBLE. I THINK MY CALLING 443 00:20:35,240 --> 00:20:36,840 THAT WILL TALK AFTER ME WILL 444 00:20:36,840 --> 00:20:38,640 TALK MORE ABOUT THE MODEL 445 00:20:38,640 --> 00:20:41,560 ORGANISM SO I HAVE SOME SLIDES 446 00:20:41,560 --> 00:20:43,680 BUT U I REMOVE THEM AND PROBABLY 447 00:20:43,680 --> 00:20:45,520 MULTIPLE ORGANISM THERE IS SOME 448 00:20:45,520 --> 00:20:46,920 EVIDENCE THAT WE CAN SLOW DOWN 449 00:20:46,920 --> 00:20:51,560 AGING, I THINK THAT WHETHER WE 450 00:20:51,560 --> 00:20:53,320 CAN DO IT IN HUMAN IS 451 00:20:53,320 --> 00:20:54,920 QUESTIONABLE. BUT I HOPE WE CAN 452 00:20:54,920 --> 00:20:56,000 AND THERE IS SOME INDICATION 453 00:20:56,000 --> 00:20:59,080 THIS IS POSSIBLE. BUT THE SECOND 454 00:20:59,080 --> 00:21:00,600 QUESTION THAT TO ME IS MORE 455 00:21:00,600 --> 00:21:02,720 IMPORTANT, MORE URGENT IS TO SAY 456 00:21:02,720 --> 00:21:04,280 HOW DO YOU KNOW THAT YOU CAN 457 00:21:04,280 --> 00:21:08,440 SLOW OUR AGING IF YOU CANNOT 458 00:21:08,440 --> 00:21:10,920 MANAGE AGING? HOW DO I KNOW AN 459 00:21:10,920 --> 00:21:12,880 INTERVENTION WILL SLOW DOWN -- I 460 00:21:12,880 --> 00:21:13,680 CAN -- CLINICAL TRIAL IN A 461 00:21:13,680 --> 00:21:17,040 PERSON THAT IS BORN TODAY AND 462 00:21:17,040 --> 00:21:18,360 SEE WHETHER THAT WILL SLOW DOWN 463 00:21:18,360 --> 00:21:20,440 AGING REDUCE MORTALITY BUT 464 00:21:20,440 --> 00:21:23,800 RESULT OF THAT TRIAL WILL BE 465 00:21:23,800 --> 00:21:24,560 AVAILABLE IN (INAUDIBLE) SO IT 466 00:21:24,560 --> 00:21:27,280 IS A LITTLE BIT NOT PRACTICAL. A 467 00:21:27,280 --> 00:21:29,320 HUNDRED YEARS. SO NOT PRACTICAL. 468 00:21:29,320 --> 00:21:30,720 WHAT PEOPLE ARE WORKING ON IS A 469 00:21:30,720 --> 00:21:38,960 MODEL OF AGING THAT ALLOW US TO 470 00:21:38,960 --> 00:21:40,240 MEASURE AGING. THIS IS HOW IT 471 00:21:40,240 --> 00:21:41,680 PLAY OUT IN MY HEAD. THE WAY I 472 00:21:41,680 --> 00:21:46,600 THINK ABOUT AGING IS THAT DURING 473 00:21:46,600 --> 00:21:53,920 AFTER BIRTH WE ARE SUBJECT TO 474 00:21:53,920 --> 00:21:56,640 ENTROPIC STRES STRES STRESS. ENN 475 00:21:56,640 --> 00:21:58,680 PHYSICS CAN BE ELIMINATED. WE 476 00:21:58,680 --> 00:22:00,760 HAVE A NUMBER OF EVOLUTIONARILY 477 00:22:00,760 --> 00:22:02,000 SELECTED MECHANISMS THAT 478 00:22:02,000 --> 00:22:04,040 CONTRAST ACCUMULATION OF DAMAGE. 479 00:22:04,040 --> 00:22:08,080 AN EXAMPLE, YOU HAVE THE 480 00:22:08,080 --> 00:22:10,320 STOCHASTIC DNA DAMAGE, YOU CAN'T 481 00:22:10,320 --> 00:22:13,400 REPAIR THE DNA. YOU HAVE THE 482 00:22:13,400 --> 00:22:15,000 DETERIORATION OF MITOCHONDRIA 483 00:22:15,000 --> 00:22:18,480 AND YOU CAN ELIMINATE THEM BY 484 00:22:18,480 --> 00:22:23,240 MYTO HAVE GIVE AND BIOGENESIS. 485 00:22:23,240 --> 00:22:29,120 MY TO HA TO HAVE JUST. THEY ARE 486 00:22:29,120 --> 00:22:30,960 SUBJECT TO STOCHASTIC DAMAGE AS 487 00:22:30,960 --> 00:22:32,880 WELL SO OVER TIME RESILIENCE 488 00:22:32,880 --> 00:22:35,760 DECLINE, ENTROPY ACCUMULATE AND 489 00:22:35,760 --> 00:22:37,360 THEN YOU HAVE THAT IMBALANCE 490 00:22:37,360 --> 00:22:39,880 BETWEEN THE ENTROPY DAMAGE 491 00:22:39,880 --> 00:22:43,560 ACCUMULATION AND RESILIENCE. 492 00:22:43,560 --> 00:22:46,320 THEN WHEN YOU SAY TO ME THIS 493 00:22:46,320 --> 00:22:52,320 PART OF THE MANY DISCUSSION, 494 00:22:52,320 --> 00:22:54,160 (INAUDIBLE) IS -- FRAILTY IS THE 495 00:22:54,160 --> 00:22:55,400 CONDITION WHEN THE STRESS OF 496 00:22:55,400 --> 00:22:58,680 NORMAL LIFE CANNOT BE AFFORD AND 497 00:22:58,680 --> 00:22:59,560 LEAD TO FURTHER DAMAGE 498 00:22:59,560 --> 00:23:01,200 ACCUMULATION. SOME OF THE 499 00:23:01,200 --> 00:23:04,000 MECHANISM OF RESILIENCY HAS BEEN 500 00:23:04,000 --> 00:23:06,960 IDENTIFY AND I WILL NOT TALK 501 00:23:06,960 --> 00:23:09,240 ABOUT IT THOUGH I WILL PUT ONE 502 00:23:09,240 --> 00:23:10,680 MOMENT ABOUT MITOCHONDRIAL 503 00:23:10,680 --> 00:23:14,200 FUNCTION. THERE IS ALSO MANY 504 00:23:14,200 --> 00:23:17,400 MECHANISM EPIDEMIOLOGIST HAVE 505 00:23:17,400 --> 00:23:19,160 FOUND REALLY ACCELERATE AGING 506 00:23:19,160 --> 00:23:25,680 PROCESS. THERE IS SOME ENTROPY 507 00:23:25,680 --> 00:23:27,240 CAN KARMA STRESS, GENETICS ALL 508 00:23:27,240 --> 00:23:29,480 CAN ACCELERATE AGING. SO HOW 509 00:23:29,480 --> 00:23:33,000 DOES THIS HELP US? THINK ABOUT 510 00:23:33,000 --> 00:23:36,400 MODEL OF RATIO DAMAGE 511 00:23:36,400 --> 00:23:39,440 ACCUMULATION AND RESILIENCE 512 00:23:39,440 --> 00:23:42,880 STRATEGY, I WILL SKIP THIS, YOU 513 00:23:42,880 --> 00:23:48,000 CAN THINK ABOUT MEASURING 514 00:23:48,000 --> 00:23:49,960 RESILIENCY, MEASURING THIS 515 00:23:49,960 --> 00:23:51,840 MECHANISM OF RESILIENCY. IF I 516 00:23:51,840 --> 00:23:53,320 MEASURE THE MECHANISM OF 517 00:23:53,320 --> 00:23:55,440 RESILIENCY I WILL GO TO MY 518 00:23:55,440 --> 00:23:57,000 DOCTOR AND THEY WILL TELL ME, 519 00:23:57,000 --> 00:24:00,360 YOU ARE REALLY DOING WELL. WHEN 520 00:24:00,360 --> 00:24:02,680 I MEASURE RESILIENCE MECHANISM, 521 00:24:02,680 --> 00:24:03,920 YOUR RESILIENCE MECHANISM ARE 522 00:24:03,920 --> 00:24:06,480 NOT DOING VERY WELL. I WILL SKIP 523 00:24:06,480 --> 00:24:09,120 THIS SLIDE. SO THERE IS EVIDENCE 524 00:24:09,120 --> 00:24:12,360 THAT WE CAN REALLY SLOW DOWN 525 00:24:12,360 --> 00:24:15,800 AGING, IT IS REALLY INTRINSIC IN 526 00:24:15,800 --> 00:24:18,840 THE MODEL OF IONS.LY SHOW YOU 527 00:24:18,840 --> 00:24:22,000 ONE SLIDE ABOUT IT. SO THIS IS A 528 00:24:22,000 --> 00:24:23,760 FAMOUS PAPER THAT WAS PUBLISHED 529 00:24:23,760 --> 00:24:28,200 BY TOM PERTH IN THE LANSETT. WE 530 00:24:28,200 --> 00:24:31,440 CALCULATED THE PERCENTAGE OF 531 00:24:31,440 --> 00:24:32,360 CENTENARIANS THAT ARE 532 00:24:32,360 --> 00:24:34,080 FUNCTIONING OVER THE COURSE OF 533 00:24:34,080 --> 00:24:35,160 THE TEN PREVIOUS YEARS OF THEIR 534 00:24:35,160 --> 00:24:40,560 LIFE. ON AVERAGE TWO YEAR BEFORE 535 00:24:40,560 --> 00:24:43,560 THEY WERE STUDIES THERE WAS 536 00:24:43,560 --> 00:24:48,000 THEIR LEVEL OF INDEPENDENCE, 537 00:24:48,000 --> 00:24:50,840 90%, 75%, 60%. NOW, IF YOU LOOK 538 00:24:50,840 --> 00:24:52,760 AT THE GENERAL POPULATION, AND 539 00:24:52,760 --> 00:24:56,400 YOU LOOK AT THE PERCENTAGE OF 540 00:24:56,400 --> 00:24:59,840 THOSE 80 YEARS AND OLDER, 541 00:24:59,840 --> 00:25:01,640 INDEPENDENTLY FUNCTION IN 542 00:25:01,640 --> 00:25:03,160 DEGENERATIVE COGNITION AND YOU 543 00:25:03,160 --> 00:25:06,120 MAKE A COMPARISON, THIS PERSON 544 00:25:06,120 --> 00:25:08,680 THAT IS 97 YEARS OLD WILL BECOME 545 00:25:08,680 --> 00:25:12,840 A CENTENARIAN. AT THE AGE OF 97, 546 00:25:12,840 --> 00:25:17,480 IN 75% OF THE CASES INDEPENDENT. 547 00:25:17,480 --> 00:25:21,240 COMPARE TO ONLY 40% OF THOSE 80 548 00:25:21,240 --> 00:25:23,040 PLUS IN THE GENERAL POPULATION. 549 00:25:23,040 --> 00:25:25,960 SUGGESTING THAT THE PEOPLE THAT 550 00:25:25,960 --> 00:25:29,240 REACH VERY LONG, LONGEVITY, THEY 551 00:25:29,240 --> 00:25:31,840 ALSO HAVE A MUCH LONGER HEALTH 552 00:25:31,840 --> 00:25:34,680 EXPECTANCY. SO THAT IS 553 00:25:34,680 --> 00:25:36,160 INTRINSICALLY POSSIBLE IN OUR 554 00:25:36,160 --> 00:25:38,040 GENOME AND WE NEED TO FIND WAY 555 00:25:38,040 --> 00:25:44,240 TO ACCOMPLISH THIS POTENTIAL. 556 00:25:44,240 --> 00:25:47,520 HOW DO WE MEASURE AGE SOMETHING 557 00:25:47,520 --> 00:25:48,760 THIS IS A FRIEND OF MINE THAT I 558 00:25:48,760 --> 00:25:50,360 THINK IS A GENIUS THAT 559 00:25:50,360 --> 00:25:52,160 DISCOVERED THAT SPECIFIC 560 00:25:52,160 --> 00:25:53,200 MODIFICATION -- CHEMICAL 561 00:25:53,200 --> 00:25:58,040 MODIFICATION OF THE DNA CAN BE 562 00:25:58,040 --> 00:25:59,320 SUMMARIZE IN A SCORE THAT IS 563 00:25:59,320 --> 00:26:01,160 STRONGLY CORRELATED WITH AGING. 564 00:26:01,160 --> 00:26:05,120 YOU CAN SEE THAT THIS IS 565 00:26:05,120 --> 00:26:09,760 EPIGENETICS CLOCK. AND THIS IS 566 00:26:09,760 --> 00:26:12,560 DISCOVERY, I WILL DISPLAY YOU IN 567 00:26:12,560 --> 00:26:14,880 SIMPLE TERMS, IF YOU ARE IN THE 568 00:26:14,880 --> 00:26:16,880 CORRIDOR IN A BUILDING YOU SEE A 569 00:26:16,880 --> 00:26:20,040 DROP OF BLOOD ON THE GROUND, 570 00:26:20,040 --> 00:26:23,680 SOMEBODY ANALYZE (INAUDIBLE) IN 571 00:26:23,680 --> 00:26:25,040 THE DROP OF BLOOD THEY CAN TELL 572 00:26:25,040 --> 00:26:28,880 YOU EXACTLY HOW OLD THAT PERSON 573 00:26:28,880 --> 00:26:32,000 IS WITH TOLERANCE OF PLUS OR 574 00:26:32,000 --> 00:26:34,320 MINUS 1.5 YEARS. THAT HAS NEVER 575 00:26:34,320 --> 00:26:36,400 BEEN POSSIBLE BEFORE. WE ONLY 576 00:26:36,400 --> 00:26:38,320 USE THE CLOCK AND THE BIRTHDAY 577 00:26:38,320 --> 00:26:40,120 TO UNDERSTAND AGE OF PERSON AND 578 00:26:40,120 --> 00:26:42,720 WE NOW KNOW BETWEEN THE 579 00:26:42,720 --> 00:26:44,640 EPIGENETIC AGE AN CHRONOLOGICAL 580 00:26:44,640 --> 00:26:46,320 AGE THERE IS STRONG DISCREPANCY 581 00:26:46,320 --> 00:26:49,560 AND THIS DISCREPANCY PREDICT 582 00:26:49,560 --> 00:26:53,120 OUTCOME. THE DISCREPANCY BETWEEN 583 00:26:53,120 --> 00:26:55,480 CHRONOLOGICAL AGE AND EPIGENETIC 584 00:26:55,480 --> 00:26:58,360 AGE FOR EXAMPLE SLOWER 585 00:26:58,360 --> 00:27:00,440 EPIGENETIC AGE IS WITH FISH 586 00:27:00,440 --> 00:27:01,440 CONSUMPTION, CRUISABLE 587 00:27:01,440 --> 00:27:04,760 CONSUMPTION, EXERCISE AND FASTER 588 00:27:04,760 --> 00:27:06,360 EPIGENETIC AGING THAT WE THINK 589 00:27:06,360 --> 00:27:10,360 IS BIOLOGICAL AGING IS HIGH 590 00:27:10,360 --> 00:27:12,240 SYSTOLIC BLOOD PRESSURE AND 591 00:27:12,240 --> 00:27:14,440 INFLAMMATION. YOU CAN DO THIS 592 00:27:14,440 --> 00:27:17,080 SAME THING INSTEAD OF USING 593 00:27:17,080 --> 00:27:18,320 METHYLATION THAT IS A LITTLE 594 00:27:18,320 --> 00:27:20,080 OBSCURE BY LOOKING AT THE 595 00:27:20,080 --> 00:27:23,360 PROTEINS THAT WE MEASURE IN THE 596 00:27:23,360 --> 00:27:25,560 BLOOD. I GRADUATED AS A 597 00:27:25,560 --> 00:27:27,440 PHYSICIAN IN 1980. AT THAT TIME 598 00:27:27,440 --> 00:27:31,040 WE WERE MEASURING 30 PROTEIN 599 00:27:31,040 --> 00:27:33,960 ROUTINE FOR CLINICAL STUDIES. 600 00:27:33,960 --> 00:27:35,960 AND WE ARE MEASURING THE SAME 30 601 00:27:35,960 --> 00:27:39,000 PROTEIN, MANY, MANY YEARS LATER 602 00:27:39,000 --> 00:27:43,040 IN FACT EXPERIMENTALLY, WE CAN 603 00:27:43,040 --> 00:27:45,280 MEASURE 10,000 PROTEIN IN LESS 604 00:27:45,280 --> 00:27:48,480 THAN 1 MILLILITER OF BLOOD. THAT 605 00:27:48,480 --> 00:27:52,040 IS THE TECHNOLOGY WE WILL APPLY, 606 00:27:52,040 --> 00:27:53,360 CERTAIN CAN BE APPLIED TO 607 00:27:53,360 --> 00:27:55,480 MEASURE EPIGENETIC CLOCK, TO 608 00:27:55,480 --> 00:27:57,200 MEASURE THE SCORE THAT CORRELATE 609 00:27:57,200 --> 00:27:59,800 THE CHRONOLOGICAL AGE. THERE IS 610 00:27:59,800 --> 00:28:01,280 AN INTRINSIC PROBLEM WITH THIS, 611 00:28:01,280 --> 00:28:03,680 THE PROBLEM IS THAT THIS STUDY 612 00:28:03,680 --> 00:28:06,760 HAVE BEEN CROSS SECTIONAL. SO AS 613 00:28:06,760 --> 00:28:08,600 A PICTURE OF THE MOMENT IN TIME 614 00:28:08,600 --> 00:28:10,760 IN CROSS SECTIONAL STUDIES ARE 615 00:28:10,760 --> 00:28:12,840 PROBLEMATIC. WHY? I GIVE YOU 616 00:28:12,840 --> 00:28:15,560 ONLY ONE EXAMPLE TODAY. THAT IS 617 00:28:15,560 --> 00:28:19,040 VERY IMPORTANT. YOU THINK WHEN 618 00:28:19,040 --> 00:28:23,240 YOU STUDY IN EFFECT AGING OVER 619 00:28:23,240 --> 00:28:27,280 COMPARISON, 20, 50, 90 AND 105 620 00:28:27,280 --> 00:28:28,400 YOU LOOK AT THE DIFFERENCEIOUS 621 00:28:28,400 --> 00:28:29,880 THINK THEY ARE DIFFERENT BY AGE. 622 00:28:29,880 --> 00:28:34,640 YOU WILL BE WRONG. BECAUSE THESE 623 00:28:34,640 --> 00:28:36,400 105 YEARS OLD PERSON WAS AGE 20 624 00:28:36,400 --> 00:28:39,600 DURING WORLD WAR 1. SO HE WENT 625 00:28:39,600 --> 00:28:42,920 THROUGH WORLD WAR 1 AND AGE 90 626 00:28:42,920 --> 00:28:44,840 WAS DURING THE GREAT DEPRESSION. 627 00:28:44,840 --> 00:28:47,880 WHY THIS AGE OF 50 WAS AGE OF 20 628 00:28:47,880 --> 00:28:49,520 DURING THE REVOLUTION, THE FIRST 629 00:28:49,520 --> 00:28:52,760 TIME IN THEIR LIFE WHEN THERE IS 630 00:28:52,760 --> 00:28:54,200 ENOUGH FOOD FOR EVERYBODY. THAT 631 00:28:54,200 --> 00:28:56,720 REALLY MAKE THEM VERY, VERY 632 00:28:56,720 --> 00:28:57,760 DIFFICULT BECAUSE OF DIFFERENT 633 00:28:57,760 --> 00:29:00,480 EXPERIENCES. SO WE NEEDED TO 634 00:29:00,480 --> 00:29:03,080 FIND A WAY TO MEASURING AGING 635 00:29:03,080 --> 00:29:08,360 LONGITUDINALLY. THAT IS WHAT WE 636 00:29:08,360 --> 00:29:12,920 DID. IN THE LONGITUDINAL STUDY, 637 00:29:12,920 --> 00:29:15,200 IS REALLY UNBELIEVABLE STUDY, 638 00:29:15,200 --> 00:29:18,840 THEY WERE DESIGNED IN 1958 BY 639 00:29:18,840 --> 00:29:19,760 (INDISCERNIBLE) SO WE HAVE 640 00:29:19,760 --> 00:29:22,720 PEOPLE IN OUR STUDY THAT HAVE 641 00:29:22,720 --> 00:29:25,400 BEEN THERE FOR 50 OR 52 YEARS 642 00:29:25,400 --> 00:29:27,760 AND STILL COMING TO BE STUDIED 643 00:29:27,760 --> 00:29:31,080 IN OUR CLINIC. SO WHAT WE SAW IS 644 00:29:31,080 --> 00:29:33,520 THAT SOME OF THE PHENOTYPE OF 645 00:29:33,520 --> 00:29:35,680 AGING SUCH AS FAT MASS FOR 646 00:29:35,680 --> 00:29:38,760 EXAMPLE DO NOT CHANGE WITH AGE. 647 00:29:38,760 --> 00:29:41,000 FAT MASS TEND TO INCREASE WITH 648 00:29:41,000 --> 00:29:44,760 AGE, AND THEN DECLINE WITH AGE. 649 00:29:44,760 --> 00:29:48,320 IMAGINE THAT THOSE DASH LINE ARE 650 00:29:48,320 --> 00:29:50,560 TRAJECTORY OF SPECIFIC SINGLE 651 00:29:50,560 --> 00:29:51,920 INDIVIDUAL, WHY THOSE CONTINUOUS 652 00:29:51,920 --> 00:29:56,120 LINE FOR THE POPULATION. THAT'S 653 00:29:56,120 --> 00:30:00,840 TRUE, THIS GUY, THIS MAN, WILL 654 00:30:00,840 --> 00:30:02,480 BE SHOWING ACCELERATED AGING 655 00:30:02,480 --> 00:30:03,800 COMPARED TO THE GENERAL 656 00:30:03,800 --> 00:30:06,440 POPULATION. BUT IF I COMPARE 657 00:30:06,440 --> 00:30:08,600 THAT WITH SOMEBODY IN THIS AGE 658 00:30:08,600 --> 00:30:10,840 GROUP, IT WILL BE NOTABLE. SO 659 00:30:10,840 --> 00:30:12,400 THAT MEAN THAT IT CAN ONLY 660 00:30:12,400 --> 00:30:15,600 EVALUATE AGE OF A PERSON WITHIN 661 00:30:15,600 --> 00:30:19,960 A SPECIFIC AGE WINDOW WHEN YOU 662 00:30:19,960 --> 00:30:20,960 DO THAT YOU COME UP WITH 663 00:30:20,960 --> 00:30:24,880 SOMETHING EXTREMELY POWERFUL. SO 664 00:30:24,880 --> 00:30:27,840 THIS IS JUST TO SHOW YOU 665 00:30:27,840 --> 00:30:29,560 (INAUDIBLE) RESPIRATORY 666 00:30:29,560 --> 00:30:34,840 FUNCTION, SOME OF THE TERMS -- 667 00:30:34,840 --> 00:30:37,400 SOME OF THE BIOMARKERS LEAN MASS 668 00:30:37,400 --> 00:30:39,560 TIGHT AREA OR GRAY MATTER VOLUME 669 00:30:39,560 --> 00:30:42,640 THEY DO NOT CHANGE LINEARLY, 670 00:30:42,640 --> 00:30:44,200 THEY TEND TO HAVE CURVING 671 00:30:44,200 --> 00:30:45,440 CHANGES SO WE NEED TO USE THIS 672 00:30:45,440 --> 00:30:47,520 METHOD REALLY TO ADDRESS 673 00:30:47,520 --> 00:30:52,640 ACCELERATED AGING. WHEN YOU 674 00:30:52,640 --> 00:30:53,640 PULL THIS TOGETHER WHAT YOU CAN 675 00:30:53,640 --> 00:30:56,760 DO IS SAY WELL, IN EACH 676 00:30:56,760 --> 00:30:58,520 PHENOTYPE, I WILL LOOK AT THE 677 00:30:58,520 --> 00:31:02,200 POPULATION LEVEL, AND THEN THIS 678 00:31:02,200 --> 00:31:06,080 LINE OF EACH SPECIFIC 679 00:31:06,080 --> 00:31:08,120 INDIVIDUAL. THEN ON THE RIGHT 680 00:31:08,120 --> 00:31:12,200 SIDE, THIS IS A TRAJECTORY OF 681 00:31:12,200 --> 00:31:14,240 CHANGE IN THAT PHENOTYPE WITH 682 00:31:14,240 --> 00:31:17,920 AGING, THIS LINEAR ONE AND THIS 683 00:31:17,920 --> 00:31:20,440 LITTLE DOT, DEVIATION NORMAL 684 00:31:20,440 --> 00:31:22,320 (INAUDIBLE) SO I CAN DO THIS 685 00:31:22,320 --> 00:31:24,560 WITH MANY OF THE PHENOTYPE SHOWN 686 00:31:24,560 --> 00:31:29,160 BEFORE AND CREATE A SCORE. THIS 687 00:31:29,160 --> 00:31:31,400 SCORE IS AMAZING PREDICTOR. AND 688 00:31:31,400 --> 00:31:35,200 I WILL NOT GO HERE TO TELL -- 689 00:31:35,200 --> 00:31:38,840 BUT JUST TELL YOU THAT IF YOU 690 00:31:38,840 --> 00:31:42,160 HAVE ONE STANDARD DEVIATION 691 00:31:42,160 --> 00:31:45,120 HIGHER THIS LONGITUDINAL 692 00:31:45,120 --> 00:31:48,440 PHENOTYPIC SCORE YOUR MEMORY FOR 693 00:31:48,440 --> 00:31:51,880 EXAMPLE, VISUAL SPATIAL FUNCTION 694 00:31:51,880 --> 00:31:56,200 IS 5 TO 10 YEARS EQUIVALENT TO A 695 00:31:56,200 --> 00:31:58,960 PERSON THAT 10 TO 5 YEAR 15 696 00:31:58,960 --> 00:32:02,400 YEARS OLDER. SUGGESTING REALLY 697 00:32:02,400 --> 00:32:05,440 CHANGE OVER TIME IN THIS 698 00:32:05,440 --> 00:32:09,600 PARAMETER AFFECT AXONAL CHANGES. 699 00:32:09,600 --> 00:32:13,560 THE MOST IMPORTANT THING -- NOT 700 00:32:13,560 --> 00:32:15,360 ALL I'M MISSING A SLIDE. WITHOUT 701 00:32:15,360 --> 00:32:21,560 THIS SLIDE, THE NOT ONLY TRUE 702 00:32:21,560 --> 00:32:25,680 THAT AGE OF 80 OR 70 TO 60, THIS 703 00:32:25,680 --> 00:32:30,360 IS TRUE AT AGE 30. IF YOU 704 00:32:30,360 --> 00:32:32,080 MEASURE AT 30 YEARS OLD AND 705 00:32:32,080 --> 00:32:35,240 FOLLOW OVER TIME FOR FIVE YEARS, 706 00:32:35,240 --> 00:32:38,880 YOU CAN PREDICT STRONGLY WHAT IS 707 00:32:38,880 --> 00:32:42,040 HAPPENING WITH THEM VERY LATE IN 708 00:32:42,040 --> 00:32:48,120 LIFLIFE. SUGGESTING THE SEEDS 709 00:32:48,120 --> 00:32:49,600 ACCELERATED AGING ALREADY 710 00:32:49,600 --> 00:32:52,680 PRESENT EARLY IN LIFE AND WE 711 00:32:52,680 --> 00:32:54,520 COULD DETECT THEM AND USE THEM 712 00:32:54,520 --> 00:32:55,560 TO UNDERSTAND WHAT THE 713 00:32:55,560 --> 00:32:57,920 UNDERLYING MECHANISM AND ALSO TO 714 00:32:57,920 --> 00:33:02,880 DO EARLY DIAGNOSIS OF VIGOMAROR 715 00:33:02,880 --> 00:33:04,280 THAT NEED MORE ATTENTION. DO I 716 00:33:04,280 --> 00:33:08,720 HAVE FEW MORE MINUTES? I TALK TO 717 00:33:08,720 --> 00:33:12,160 YOU DIRECTLY BUT I WANT TO SHOW 718 00:33:12,160 --> 00:33:14,600 HOW DIFFERENT TO OLDER PEOPLE 719 00:33:14,600 --> 00:33:16,400 AND TO DO THAT I SELECT ONE OF 720 00:33:16,400 --> 00:33:21,520 THE THING THAT I'M STUDYING IN 721 00:33:21,520 --> 00:33:23,400 THE BIOLOGY OF NEURODEGENERATION 722 00:33:23,400 --> 00:33:27,040 AND AGING WHICH IS 723 00:33:27,040 --> 00:33:29,520 MITOCHONDRIAL. THE PASSION ABOUT 724 00:33:29,520 --> 00:33:32,000 MITOCHONDRIA, IT IS RELATESSED 725 00:33:32,000 --> 00:33:34,680 TO THE MODEL I PRESENT HERE 726 00:33:34,680 --> 00:33:38,440 BEFORE. I TOLD YOU AGING IS 727 00:33:38,440 --> 00:33:39,520 RATIO BETWEEN DAMAGE 728 00:33:39,520 --> 00:33:46,040 ACCUMULATION AN RESILIENCE. THAT 729 00:33:46,040 --> 00:33:48,760 IS IMPORTANT RESILIENCE TO WORK 730 00:33:48,760 --> 00:33:51,320 REQUIRE ENERGY. ANY SINGLE 731 00:33:51,320 --> 00:33:53,040 BIOLOGICAL INTERVENTION THAT 732 00:33:53,040 --> 00:33:55,040 NATURE HAS CREATED WORKS ONLY IF 733 00:33:55,040 --> 00:33:58,320 YOU CAN PROVIDE ENERGY AND MOST 734 00:33:58,320 --> 00:34:01,240 DAMAGE IN OUR BODY COME FROM 735 00:34:01,240 --> 00:34:02,880 THIS ORGANELLE, THE 736 00:34:02,880 --> 00:34:05,160 MITOCHONDRIA. I WILL GIVE AN 737 00:34:05,160 --> 00:34:07,880 EXAMPLE, IF YOU HAVE A MISFOLDED 738 00:34:07,880 --> 00:34:10,040 RECORD DAMAGED PROTEIN, YOU CAN 739 00:34:10,040 --> 00:34:13,600 REFOLD IT PROTEIN BY OTHER 740 00:34:13,600 --> 00:34:14,640 PROTEIN (INAUDIBLE) THAT MOST OF 741 00:34:14,640 --> 00:34:17,400 THE TIME WOULD REQUIRE ENERGY. 742 00:34:17,400 --> 00:34:20,480 IF YOU HAVE A MITOCHONDRIA THAT 743 00:34:20,480 --> 00:34:23,000 IS DAMAGE, THEIR MITOCHONDRIA 744 00:34:23,000 --> 00:34:25,960 CAN BE REPAIR, RECYCLE OR 745 00:34:25,960 --> 00:34:27,400 REPLACE BUT THESE REQUIRE 746 00:34:27,400 --> 00:34:28,560 ENORMOUS AMOUNT, REMEMBER ANY 747 00:34:28,560 --> 00:34:30,840 TIME WE SEE TO SYNTHESIZE 748 00:34:30,840 --> 00:34:33,080 PROTEIN, PROTEIN SYNTHESIS IS 749 00:34:33,080 --> 00:34:35,920 ONE OF THE MOST TELOMERE 750 00:34:35,920 --> 00:34:37,200 BIOCHEMICAL PROCESS WE KNOW 751 00:34:37,200 --> 00:34:42,240 AROUND SO YOU NEED ENERGY: WHAT 752 00:34:42,240 --> 00:34:43,720 HAPPENED TO MITOCHONDRIA WITH 753 00:34:43,720 --> 00:34:46,160 AGING? INTO SHOW YOU HOW WE 754 00:34:46,160 --> 00:34:48,200 STUDY MITOCHONDRIA. THIS IS IN 755 00:34:48,200 --> 00:34:51,800 MOVIE THAT WILL GO THROUGH THE 756 00:34:51,800 --> 00:34:53,320 (INAUDIBLE) MITOCHONDRIA ARE 757 00:34:53,320 --> 00:34:54,800 VERY IMPORTANT AND I WILL 758 00:34:54,800 --> 00:34:56,720 INDICATE TO YOU THE STRUCTURE 759 00:34:56,720 --> 00:35:00,480 THAT YOU SEE HERE. SO THIS IS A 760 00:35:00,480 --> 00:35:02,520 NUCLEI AND THEN YOU SEE THIS 761 00:35:02,520 --> 00:35:04,920 LITTLE STRUCTURE OF THE 762 00:35:04,920 --> 00:35:07,880 MITOCHONDRIA, THAT CLUSTER THE 763 00:35:07,880 --> 00:35:10,480 NUCLEI IS BLACK SPACE 764 00:35:10,480 --> 00:35:12,080 INTRACELLULAR MATRIX AND THIS IS 765 00:35:12,080 --> 00:35:14,880 THE FIBER OF COLLAGEN YOU SEE 766 00:35:14,880 --> 00:35:18,080 HERE. THIS IS A -- AND WHAT YOU 767 00:35:18,080 --> 00:35:23,240 CAN SEE WITHIN THE COPY OF RED 768 00:35:23,240 --> 00:35:26,400 BLOOD CELLS IS HEPATOCYTES THEN 769 00:35:26,400 --> 00:35:31,600 YOU SEE THE SARCO MERE, IT WILL 770 00:35:31,600 --> 00:35:32,840 -- THE SACK WILL APPEAR. THE 771 00:35:32,840 --> 00:35:37,200 SACK WILL APPEAR IN THE MUSCLE 772 00:35:37,200 --> 00:35:39,840 AND BETWEEN THIS SARCO MERE VERY 773 00:35:39,840 --> 00:35:41,280 CLOSE TO WHERE ENERGY IS 774 00:35:41,280 --> 00:35:43,600 REQUIRED YOU CAN SEE A LITTLE 775 00:35:43,600 --> 00:35:47,880 GLOBULE OF SHAPES THAT YOU HAVE, 776 00:35:47,880 --> 00:35:49,600 OF THE INTERMITOCHONDRIAIA. 777 00:35:49,600 --> 00:35:52,840 WHAT IS IMPORTANT IS THAT THIS 778 00:35:52,840 --> 00:35:55,600 MITOCHONDRIA, WHEN YOU LOOK AT 779 00:35:55,600 --> 00:35:57,000 THEM IN THREE DIMENSIONAL SPACE, 780 00:35:57,000 --> 00:36:02,480 I WILL SHOW YOU, THEY ARE A 781 00:36:02,480 --> 00:36:05,600 NETWORK THAT IS INVOLVED WITH 782 00:36:05,600 --> 00:36:07,040 FIBER SO THE FIBER CAN RECEIVE 783 00:36:07,040 --> 00:36:07,880 THE ENERGY THEY NEED TO 784 00:36:07,880 --> 00:36:13,840 FUNCTION. THIS IS A THREE KY 785 00:36:13,840 --> 00:36:14,600 MENTION PAL RECONSTRUCTION OF 786 00:36:14,600 --> 00:36:16,360 THE MITOCHONDRIA, YOU CAN SEE 787 00:36:16,360 --> 00:36:18,480 THERE IS -- AND YOU CAN SEE THAT 788 00:36:18,480 --> 00:36:20,640 THERE IS A HOLE THERE. I DON'T 789 00:36:20,640 --> 00:36:22,400 KNOW IF YOU CAN SEE THE HOLE 790 00:36:22,400 --> 00:36:26,520 HERE, THIS IS WHERE THE 791 00:36:26,520 --> 00:36:28,000 (INAUDIBLE) ARE. THIS IS A VERY 792 00:36:28,000 --> 00:36:29,360 HEALTHY MUSCLE. YOU CAN SEE A 793 00:36:29,360 --> 00:36:30,600 MUSCLE THAT IS A LITTLE BIT 794 00:36:30,600 --> 00:36:34,680 HEALTHY. LESS HEALTHY, WITH THE 795 00:36:34,680 --> 00:36:36,440 CONNECTION BUT STILL PRETTY 796 00:36:36,440 --> 00:36:40,840 GOOD. THEN YOU GO TO THIS LAST 797 00:36:40,840 --> 00:36:44,080 ONENA IS AN 80 YEARS OLD PERSON 798 00:36:44,080 --> 00:36:46,720 AND YOU CAN SEE THAT THOSE 799 00:36:46,720 --> 00:36:48,760 MITOCHONDRIA ARE NO LONGER 800 00:36:48,760 --> 00:36:51,120 CONNECTED. THE FRAGMENTATION OF 801 00:36:51,120 --> 00:36:53,960 THE NETWORK IS EXTREMELY 802 00:36:53,960 --> 00:36:54,800 IMPORTANT BECAUSE THE 803 00:36:54,800 --> 00:36:58,120 FUNCTIONING OF THE NETWORK OF 804 00:36:58,120 --> 00:37:00,280 MITOCHONDRIA REQUIRE ELECTRICAL 805 00:37:00,280 --> 00:37:01,560 TRANSMISSION, BETWEEN ONE 806 00:37:01,560 --> 00:37:03,280 MITOCHONDRIA AND THE OTHER. WHEN 807 00:37:03,280 --> 00:37:04,960 THIS ELECTRICAL TRANSMISSION, 808 00:37:04,960 --> 00:37:07,000 DOES NOT OCCUR, THAT MEAN THAT 809 00:37:07,000 --> 00:37:10,080 THE CENTER OF THE FIBER YOU 810 00:37:10,080 --> 00:37:14,240 DON'T HAVE ENOUGH ENERGY. SO THE 811 00:37:14,240 --> 00:37:16,600 CONTRACTION OF THE FIBER OCCUR 812 00:37:16,600 --> 00:37:22,480 IN A SEQUENCE WAY. YOU CAN 813 00:37:22,480 --> 00:37:23,720 MECHANICALLY DAMAGE, WE KNOW AT 814 00:37:23,720 --> 00:37:25,280 LEAST IN ANIMAL MODEL WE CAN 815 00:37:25,280 --> 00:37:26,560 KIND OF FIX THIS, WHETHER WE CAN 816 00:37:26,560 --> 00:37:30,000 DO THIS IN HUMANS, IS STILL THE 817 00:37:30,000 --> 00:37:32,760 QUESTION BUT I HOPE THAT THAT IS 818 00:37:32,760 --> 00:37:36,760 WHAT THE FUTURE WILL BRING US AT 819 00:37:36,760 --> 00:37:40,880 LEAST SOME ASPECTS OF THE HUMAN 820 00:37:40,880 --> 00:37:42,840 AGING BIOLOGY WE WILL BE ABLE TO 821 00:37:42,840 --> 00:37:44,320 ADDRESS. ONE OF THE FEW WE CAN 822 00:37:44,320 --> 00:37:46,840 DO NOW JUST TO FINISH, IF YOU 823 00:37:46,840 --> 00:37:50,280 EXERCISE, THOSE MITOCHONDRIA 824 00:37:50,280 --> 00:37:53,320 RETURN CONNECTED AS THEY WERE 825 00:37:53,320 --> 00:37:55,480 BEFORE THE AGING PROCESS. SO CAN 826 00:37:55,480 --> 00:37:57,800 WE SLOW DOWN AGING? I REALLY 827 00:37:57,800 --> 00:38:00,000 DON'T KNOW, CAN WE IMPROVE 828 00:38:00,000 --> 00:38:00,880 MITOCHONDRIAL FUNCTION, ONE OF 829 00:38:00,880 --> 00:38:02,360 THE HALLMARKS OF AGE SOMETHING 830 00:38:02,360 --> 00:38:05,840 CERTAINLY WE CAN. THANK YOU 831 00:38:05,840 --> 00:38:08,360 VERY MUCH. SO MY QUESTION IS, 832 00:38:08,360 --> 00:38:11,240 CAN WE SLOW DOWN AGING? THERE IS 833 00:38:11,240 --> 00:38:14,520 A LOT WE CAN DO, TO THIS PART OF 834 00:38:14,520 --> 00:38:15,840 THE POPULATION BUT WE ALSO NEED 835 00:38:15,840 --> 00:38:18,320 TO STUDY AGING IN THE LIFE 836 00:38:18,320 --> 00:38:20,240 COURSE PERSPECTIVE. WE NEED TO 837 00:38:20,240 --> 00:38:24,800 STUDY AGING IN THIS INDIVIDUAL. 838 00:38:24,800 --> 00:38:26,160 BECAUSE IF THERE WHEN WE HAVE 839 00:38:26,160 --> 00:38:28,960 THE CHANCE TO SLOW DOWN THE 840 00:38:28,960 --> 00:38:31,440 PROCESS EVENTUALLY WILL CREATE 841 00:38:31,440 --> 00:38:34,360 DISEASE AND DISABILITY. THANK 842 00:38:34,360 --> 00:38:36,160 YOU FOR YOUR ATTENTION, LOOKING 843 00:38:36,160 --> 00:38:37,000 FORWARD TO THE NEXT 844 00:38:37,000 --> 00:38:40,560 PRESENTATION. 845 00:38:40,560 --> 00:38:42,640 >>THANK YOU VERY MUCH, LUIGI. 846 00:38:42,640 --> 00:38:44,240 THAT WAS REALLY EXCITING 847 00:38:44,240 --> 00:38:45,640 PRESENTATION. NOW WE MOVE ON TO 848 00:38:45,640 --> 00:38:48,720 SAUL VILLEDA. PLEASE GO AHEAD, SAUL. 849 00:38:48,720 --> 00:38:51,160 >>THANK YOU TO DR. 850 00:38:51,160 --> 00:38:52,760 ARIAS FOR THE INVITATION IN 851 00:38:52,760 --> 00:38:54,000 GETTING A CHANCE TO SHARE OUR 852 00:38:54,000 --> 00:38:56,240 WORK WITH EVERYONE. REALLY 853 00:38:56,240 --> 00:38:58,960 QUICKLY, NO FINANCIAL 854 00:38:58,960 --> 00:39:00,320 DISCLOSURES. . IN TERMS OF 855 00:39:00,320 --> 00:39:01,640 LONG-TERM OBJECTIVE, I WOULD 856 00:39:01,640 --> 00:39:03,840 LOVE TO EVALUATE SOME OF THE 857 00:39:03,840 --> 00:39:05,160 MOLECULAR MECHANISMS THAT WE 858 00:39:05,160 --> 00:39:06,720 HAVE IDENTIFIED IN ANIMAL 859 00:39:06,720 --> 00:39:09,080 STUDIES WITH THE POTENTIAL WE 860 00:39:09,080 --> 00:39:11,400 THINK TO RESCUE COGNITIVE 861 00:39:11,400 --> 00:39:15,080 FUNCTION LATE IN LIFE. SO 862 00:39:15,080 --> 00:39:16,000 BROADLY WHAT MY LAB IS 863 00:39:16,000 --> 00:39:18,680 INTERESTED IN UNDERSTANDING AND 864 00:39:18,680 --> 00:39:20,000 INVESTIGATING IS THIS IDEA OF 865 00:39:20,000 --> 00:39:21,760 CAN THE EFFECT OF AGING ON THE 866 00:39:21,760 --> 00:39:24,640 BRAIN BE REVERSED? WE JUST HEARD 867 00:39:24,640 --> 00:39:26,840 ABOUT THE IDEA OF SLOWING DOWN 868 00:39:26,840 --> 00:39:29,240 AGING AND FOR ME I'M FOCUS ON 869 00:39:29,240 --> 00:39:31,800 INDIVIDUAL TISSUE WHICH WOULD BE 870 00:39:31,800 --> 00:39:34,240 THE BRAIN. TACKLING ON ONE 871 00:39:34,240 --> 00:39:37,160 TISSUE ONE FUNCTION AT A TIME 872 00:39:37,160 --> 00:39:40,040 MAY ALLOW US TO IDENTIFY 873 00:39:40,040 --> 00:39:41,120 MECHANISMS THAT MAYBE WE ARE 874 00:39:41,120 --> 00:39:43,120 ABLE TO APPLY MORE BROADLY TO 875 00:39:43,120 --> 00:39:45,360 OTHER TISSUES AS WELL. I LIKE 876 00:39:45,360 --> 00:39:48,280 THIS IMAGE, WE ARE TRYING TO 877 00:39:48,280 --> 00:39:50,880 START AT OLDER AGE AND TRYING TO 878 00:39:50,880 --> 00:39:55,760 UNDERSTAND HOW MUCH FUNCTION CAN 879 00:39:55,760 --> 00:39:57,480 YOU RESTORE? THINKING 880 00:39:57,480 --> 00:39:58,520 REVERSIBILITY IS NOT ENGAGING 881 00:39:58,520 --> 00:40:00,120 THE SAME MECHANISMS THERE WHEN 882 00:40:00,120 --> 00:40:01,800 WE ARE YOUNG BUT ENGAGING 883 00:40:01,800 --> 00:40:04,080 MECHANISMS THAT BRING BACK THE 884 00:40:04,080 --> 00:40:04,800 FUNCTION THAT WAS THERE DURING 885 00:40:04,800 --> 00:40:08,480 THE YOUTH. THAT IS WHAT WE THINK 886 00:40:08,480 --> 00:40:10,320 OF AS TERMS LIKE REJUVENATION OR 887 00:40:10,320 --> 00:40:11,680 DISABILITY. SO MY LAB WE ARE 888 00:40:11,680 --> 00:40:13,240 INTERESTED IN FUNCTION. WHY DO I 889 00:40:13,240 --> 00:40:17,480 THINK THAT THIS IS IMPORTANT? IN 890 00:40:17,480 --> 00:40:19,120 THE BRAIN THERE IS INTIMATE 891 00:40:19,120 --> 00:40:20,040 RELATIONSHIP BETWEEN AGING THE 892 00:40:20,040 --> 00:40:23,480 OLDER YOU GET AND THIS DECLINE 893 00:40:23,480 --> 00:40:26,080 YOU SEE IN BRAIN FUNCTION. THE 894 00:40:26,080 --> 00:40:27,640 VULNERABILITY AN SUSCEPTIBILITY 895 00:40:27,640 --> 00:40:29,520 TO NEURODEGENERATIVE DISEASES 896 00:40:29,520 --> 00:40:31,600 THAT WE OFTEN THINK ABOUT AS 897 00:40:31,600 --> 00:40:33,800 SOMETHING LIKE ALZHEIMER'S. 898 00:40:33,800 --> 00:40:37,040 EVEN SOMEONE WITH GENETIC 899 00:40:37,040 --> 00:40:38,480 PRE-DISPOSITION, IS NOT GOING TO 900 00:40:38,480 --> 00:40:42,440 EXHIBIT OVERT PATHOLOGY 901 00:40:42,440 --> 00:40:45,760 SOMETHING LIKE SAY 20 YEARS OLD. 902 00:40:45,760 --> 00:40:47,320 IF YOU LOOK LATER IN LIFE YOU 903 00:40:47,320 --> 00:40:50,120 WILL SEE THAT OVERT PATHOLOGY SO 904 00:40:50,120 --> 00:40:51,480 THERE IS A CONNECTION BETWEEN 905 00:40:51,480 --> 00:40:53,040 AGING AND DISEASE. WHAT WE WANT 906 00:40:53,040 --> 00:40:54,560 TO KNOW, LIKE I MENTION, SOMEONE 907 00:40:54,560 --> 00:40:57,440 IN THEIR 20s IS NOT GOING TO 908 00:40:57,440 --> 00:41:00,280 NECESSARILY HAVE THAT OVERT 909 00:41:00,280 --> 00:41:03,000 PATHOLOGY, SO NATURALLY DURING 910 00:41:03,000 --> 00:41:04,800 YOUTH YOUR BODY STAVES OFF THIS 911 00:41:04,800 --> 00:41:06,400 INSULT SO NATURALLY HAS 912 00:41:06,400 --> 00:41:09,480 MECHANISMS THAT ARE PROTECT. HOW 913 00:41:09,480 --> 00:41:11,040 DO WE UNDERSTAND WHAT THOSE 914 00:41:11,040 --> 00:41:12,400 MECHANISMS ARE? WHAT HAPPENS IF 915 00:41:12,400 --> 00:41:13,840 WE RESTORE THOSE MECHANISMS 916 00:41:13,840 --> 00:41:16,680 LATER IN LIFE? CAN WE THEN 917 00:41:16,680 --> 00:41:18,480 PREVENTS THIS ONSET OR INCREASE 918 00:41:18,480 --> 00:41:21,120 IN NEURODEGENERATIVE DISEASE. WE 919 00:41:21,120 --> 00:41:23,720 ARE NOT MANY MY LAB FOCUSING ON 920 00:41:23,720 --> 00:41:25,800 LIFE SPAN OR EXPANDING LIFE 921 00:41:25,800 --> 00:41:27,640 SPAN, WE ARE FOCUSING ON TACKLE 922 00:41:27,640 --> 00:41:29,960 THIS FUNCTIONAL DECLINE THAT 923 00:41:29,960 --> 00:41:33,080 COMES WITH AGE. I THINK ABOUT 924 00:41:33,080 --> 00:41:35,280 THIS A LOT WITH THIS IS JUST A 925 00:41:35,280 --> 00:41:37,960 GRAPHIC FROM THE UNITED NATIONS. 926 00:41:37,960 --> 00:41:39,600 WHEN MY PARENTS WERE BORN, THEY 927 00:41:39,600 --> 00:41:41,320 WERE BORN IN 1951. WHEN THEY 928 00:41:41,320 --> 00:41:43,240 WERE BORN, ABOUT 8% OF THE 929 00:41:43,240 --> 00:41:44,240 POPULATION AT LEAST IN THE U.S. 930 00:41:44,240 --> 00:41:46,640 WAS OVER THE AGE OF 65 65. SO WT 931 00:41:46,640 --> 00:41:49,720 WE THINK OF AS RETIREMENT AGE. 932 00:41:49,720 --> 00:41:54,080 BY THE TIME I RETIRE AROUND 933 00:41:54,080 --> 00:41:55,720 2050ISH, DURING THE PANDEMIC I 934 00:41:55,720 --> 00:41:57,560 TURNED 40. SO WHEN I THINK ABOUT 935 00:41:57,560 --> 00:41:59,960 IT BY THE TIME I RETIRE IT WILL 936 00:41:59,960 --> 00:42:02,840 BE OVER 21%, CLOSE TO 22% OF THE 937 00:42:02,840 --> 00:42:04,000 POPULATION WILL BE OLDER THAN 938 00:42:04,000 --> 00:42:06,560 RETIREMENT AGE. AND I JUST SAID, 939 00:42:06,560 --> 00:42:08,240 THERE IS THIS INTIMATE 940 00:42:08,240 --> 00:42:10,840 RELATIONSHIP BETWEEN AGING AND 941 00:42:10,840 --> 00:42:12,000 SUSCEPTIBILITY VULNERABILITY AND 942 00:42:12,000 --> 00:42:13,600 ONSET OF THINGS LIKE 943 00:42:13,600 --> 00:42:15,200 NEURODEGENERATIVE DISEASE. SO 944 00:42:15,200 --> 00:42:17,720 THEN THIS GRAPH TAKES ON NEW 945 00:42:17,720 --> 00:42:19,240 URGENCY IN THAT NOT ONLY DO WE 946 00:42:19,240 --> 00:42:20,600 KNOW THAT THIS IS COMING IN 947 00:42:20,600 --> 00:42:22,160 TERMS OF THE ONSET OF THESE 948 00:42:22,160 --> 00:42:23,520 DISEASES, NOW WE KNOW IT WILL 949 00:42:23,520 --> 00:42:24,880 HAPPEN IN A MUCH LARGER 950 00:42:24,880 --> 00:42:26,640 POPULATION. SO WHAT CAN WE DO 951 00:42:26,640 --> 00:42:30,120 ABOUT IT? JUST TO GIVE AN IDEA, 952 00:42:30,120 --> 00:42:31,800 A LITTLE BIT WHAT WE THINK OF IN 953 00:42:31,800 --> 00:42:33,880 MY LAB AS AGE RELATED COGNITIVE 954 00:42:33,880 --> 00:42:35,200 DECLINE WHICH IS WHAT WE WILL 955 00:42:35,200 --> 00:42:37,760 FOCUS ON, WE ARE GOING TO FOCUS 956 00:42:37,760 --> 00:42:39,880 ON PRIOR TO OVERT SIGNS OF THAT 957 00:42:39,880 --> 00:42:41,440 DISEASE. I WILL GIVE AN EXAMPLE 958 00:42:41,440 --> 00:42:42,800 OF AGE RELATED COGNITIVE 959 00:42:42,800 --> 00:42:44,520 DECLINE. I'M IN SAN FRANCISCO, 960 00:42:44,520 --> 00:42:45,960 UNIVERSITY OF CALIFORNIA SAN 961 00:42:45,960 --> 00:42:48,400 FRANCISCO. SO THERE ARE A 962 00:42:48,400 --> 00:42:50,280 RIDICULOUS NUMBER OF TESLAS IN 963 00:42:50,280 --> 00:42:52,760 THE ROAD. SO PRETEND I'M GOING 964 00:42:52,760 --> 00:42:56,960 TO DRIVE MY TESLA, I DON'T OWN 965 00:42:56,960 --> 00:42:58,640 ONE BUT HOPEFULLY ONE DAY, 966 00:42:58,640 --> 00:43:00,680 PRETEND I AM DRIVING IT INTO THE 967 00:43:00,680 --> 00:43:02,160 PARKING LOT AND THERE'S A BUNCH 968 00:43:02,160 --> 00:43:04,400 OF OTHER TESLA'S THERE. I'M 969 00:43:04,400 --> 00:43:06,280 GOING TO NEED TO BE ABLE TO FIND 970 00:43:06,280 --> 00:43:07,320 MY ELECTRIC CAR AT THE END OF 971 00:43:07,320 --> 00:43:09,600 THE DAY. SO MY BRAIN IS 972 00:43:09,600 --> 00:43:11,160 NATURALLY GOING TO LOOK AT 973 00:43:11,160 --> 00:43:12,560 QUEUES THAT ARE AROUND WHERE I 974 00:43:12,560 --> 00:43:17,320 PARKED THE CAR. ON A NICE SUNNY 975 00:43:17,320 --> 00:43:19,400 DATE, I MIGHT HAVE IT ON A HILL, 976 00:43:19,400 --> 00:43:21,440 DURING THE SUM ME RAINBOW FLAG 977 00:43:21,440 --> 00:43:23,280 DURING PRIDE OR MAYBE A FOOD 978 00:43:23,280 --> 00:43:25,240 TRUCK NEARBY. I GO TO WORK COME 979 00:43:25,240 --> 00:43:26,840 BACK AND MY BRAIN NATURALLY SEES 980 00:43:26,840 --> 00:43:28,920 THAT AND SAYS YOU PARKED CLOSER 981 00:43:28,920 --> 00:43:31,480 TO THE VIEW OF THE GOLDEN GATE 982 00:43:31,480 --> 00:43:32,480 BRIDGE AND FURTHER FROM THE FOOD 983 00:43:32,480 --> 00:43:33,680 TRUCK. WHEN YOU ARE YOUNG YOU 984 00:43:33,680 --> 00:43:35,720 HAVE NO ISSUES WITH THIS. BUT 985 00:43:35,720 --> 00:43:36,760 PERHAPS YOU HAVE BEEN IN A 986 00:43:36,760 --> 00:43:37,760 PARKING LOT WHERE YOU START 987 00:43:37,760 --> 00:43:39,400 SEEING MAYBE AN ELDERLY PERSON 988 00:43:39,400 --> 00:43:42,320 USING THEIR CAR ALARM, THAT IS 989 00:43:42,320 --> 00:43:44,160 SORT OF ONE SIGN OF THIS AGE 990 00:43:44,160 --> 00:43:46,160 RELATED COGNITIVE DECLINE, FULL 991 00:43:46,160 --> 00:43:47,160 DISCLOSURE BECAUSE KNOW THERE 992 00:43:47,160 --> 00:43:48,960 ARE STUDENTS OUT THERE THAT 993 00:43:48,960 --> 00:43:50,360 ALWAYS FREAK OUT A LITTLE BIT, 994 00:43:50,360 --> 00:43:52,000 IT MAY BE HAPPENING AS WELL 995 00:43:52,000 --> 00:43:53,680 CHRONIC STRESS IS ANOTHER REASON 996 00:43:53,680 --> 00:43:55,320 YOU WOULD SEE THIS TYPE OF 997 00:43:55,320 --> 00:43:56,800 COGNITIVE DECLINE SO AGING AS 998 00:43:56,800 --> 00:44:01,440 WELL AS CHRONIC STRESS. 999 00:44:01,440 --> 00:44:02,800 UNIVERSITY STUDENTS NEAR FINALS 1000 00:44:02,800 --> 00:44:04,880 THAT ARE WORRIED. SO THIS IS 1001 00:44:04,880 --> 00:44:06,240 TYPES OF FUNCTION WE ARE LOOKING 1002 00:44:06,240 --> 00:44:08,240 AT WHEN WE ARE THINKING ABOUT 1003 00:44:08,240 --> 00:44:11,440 AGE RELATED COGNITIVE DECLINE. 1004 00:44:11,440 --> 00:44:13,320 HOWEVER WE STUDY THINGS IN THE 1005 00:44:13,320 --> 00:44:14,720 HUMAN CONTEXT TO FIND 1006 00:44:14,720 --> 00:44:15,520 APPLICATIONS AND OF COURSE 1007 00:44:15,520 --> 00:44:17,080 TRYING TO TRANSLATE WHAT WE DO 1008 00:44:17,080 --> 00:44:18,640 BUT WE DO USE ANIMAL MODELS AND 1009 00:44:18,640 --> 00:44:20,240 WHAT IS INTERESTING IS THIS SAME 1010 00:44:20,240 --> 00:44:22,680 TYPE OF COGNITIVE DECLINE IS 1011 00:44:22,680 --> 00:44:24,120 CONSERVED ACROSS SPECIES 1012 00:44:24,120 --> 00:44:25,920 INCLUDING ANIMAL MODEL. SO OUR 1013 00:44:25,920 --> 00:44:27,600 MODEL OF CHOICE IS THE MOUSE. 1014 00:44:27,600 --> 00:44:29,400 AND THE REASON WE USE THIS IS 1015 00:44:29,400 --> 00:44:31,440 REALLY THERE IS A LOT OF POWER 1016 00:44:31,440 --> 00:44:32,760 WITH RESPECT TO MOLECULAR 1017 00:44:32,760 --> 00:44:34,960 BIOLOGY AND GENETICS AND JUST 1018 00:44:34,960 --> 00:44:36,440 DIFFERENT INTERVENTIONS AND 1019 00:44:36,440 --> 00:44:37,280 MANIPULATIONS WE CAN DO IN 1020 00:44:37,280 --> 00:44:39,560 THESE. HERE I'M SHOWING YOU A 1021 00:44:39,560 --> 00:44:41,360 YOUNG MOUSE AND OLDER MOUSE UX 1022 00:44:41,360 --> 00:44:42,920 SEE A LOT OF PHENOTYPES ARE 1023 00:44:42,920 --> 00:44:45,680 STILL THERE. THERE IS CHANGE IN 1024 00:44:45,680 --> 00:44:47,880 WEIGHT, YOU CAN SEE GRAIN AT THE 1025 00:44:47,880 --> 00:44:49,760 FUR SO THERE IS REAL 1026 00:44:49,760 --> 00:44:51,640 DIFFERENCES. IF YOU WERE TO ZOOM 1027 00:44:51,640 --> 00:44:53,760 IN THEIR ICE START DEVELOPING AT 1028 00:44:53,760 --> 00:44:55,440 SOME POINTS CATARACTS SO YOU CAN 1029 00:44:55,440 --> 00:44:58,360 START SEEING AGING APPROACH JUST 1030 00:44:58,360 --> 00:44:59,800 TO ORIENT EVERYONE A LITTLE BIT, 1031 00:44:59,800 --> 00:45:03,120 THIS IS FROM THE JACKSON 1032 00:45:03,120 --> 00:45:04,560 LABORATORIES WHICH IS A HUGE 1033 00:45:04,560 --> 00:45:08,200 ENTITY THAT PROHAVE SLIDES PLUS 1034 00:45:08,200 --> 00:45:08,720 MODELS TO THE SCIENTIFIC 1035 00:45:08,720 --> 00:45:10,360 COMMUNITY. IF YOU WERE TO 1036 00:45:10,360 --> 00:45:12,680 EXTRAPOLATE LOOSELY THE MOUSE 1037 00:45:12,680 --> 00:45:14,760 AGES TO HUMAN AGE, WE HAVE THESE 1038 00:45:14,760 --> 00:45:18,360 MORE MATURE ANIMALS, 3 TO 6 1039 00:45:18,360 --> 00:45:20,920 MONTHS, FROM 21 TO 30, MORE 1040 00:45:20,920 --> 00:45:23,360 MIDDLE AGE MOUSE ABOUT A YEAR. 1041 00:45:23,360 --> 00:45:25,600 THERE'S MORE MY AGE AND WE ALSO 1042 00:45:25,600 --> 00:45:27,880 HAVE THE OLDER ANIMAL MODELS 1043 00:45:27,880 --> 00:45:30,080 AROUND HERE, THEY WOULD BE 1044 00:45:30,080 --> 00:45:32,600 CLOSER GOING UP TO THE LATE 1045 00:45:32,600 --> 00:45:34,400 '60s OR SO, THOSE ARE THE AGE 1046 00:45:34,400 --> 00:45:38,320 CHANGES WE USE. SIMILAR TO WHAT 1047 00:45:38,320 --> 00:45:39,680 I MENTION ABOUT FINDING MY 1048 00:45:39,680 --> 00:45:41,040 ELECTRIC CAR IN THE MIDDLE OF A 1049 00:45:41,040 --> 00:45:43,280 PARKING LOT, WE CAN TRAIN 1050 00:45:43,280 --> 00:45:44,760 ANIMALS TO FIND A HIDDEN 1051 00:45:44,760 --> 00:45:47,240 PLATFORM IN A POOL OF WATER. 1052 00:45:47,240 --> 00:45:49,440 MICE ARE GREAT SWIMMERS BUT THEY 1053 00:45:49,440 --> 00:45:52,880 HATE COLD WATER SO THEY WILL DO 1054 00:45:52,880 --> 00:45:55,000 WHAT THEY CAN TO GET OUT OF THAT 1055 00:45:55,000 --> 00:45:57,560 POOL OF WATER FAST. SO THEY 1056 00:45:57,560 --> 00:45:59,880 REALLY GOOD FINDING THIS HIDDEN 1057 00:45:59,880 --> 00:46:00,880 WATER WITH RELATION TO QUEUES 1058 00:46:00,880 --> 00:46:03,920 AROUND THE ROOM SIMILAR TO THE 1059 00:46:03,920 --> 00:46:06,240 GOLDEN GATE BRIDGE, MAYBE A TRY 1060 00:46:06,240 --> 00:46:07,880 YANGING SIMILAR TO RAINBOW FLAG, 1061 00:46:07,880 --> 00:46:10,000 MAYBE STRIPES AND GO MY PLATFORM 1062 00:46:10,000 --> 00:46:11,600 IS CLOSER TO TRIANGLE THAN TO 1063 00:46:11,600 --> 00:46:14,160 THE STRIPES OR THE RECTANGLE. 1064 00:46:14,160 --> 00:46:16,480 WITH AGE THIS IS SIMILAR TO WHAT 1065 00:46:16,480 --> 00:46:20,400 WE SEE, WE SEE IMPAIRMENT. SO 1066 00:46:20,400 --> 00:46:22,080 NATURALLY OVER TIME AND TRAINING 1067 00:46:22,080 --> 00:46:24,640 A YOUNG ANIMAL CAN GET GOOD, 1068 00:46:24,640 --> 00:46:27,360 DOESN'T MAKE MISTAKES MANY. BUT 1069 00:46:27,360 --> 00:46:29,720 OTHER ANIMAL MIGHT GO A 1070 00:46:29,720 --> 00:46:30,600 DIFFERENT DIRECTION, IN THE END 1071 00:46:30,600 --> 00:46:31,960 THEY WILL FIND THE PLATFORM THEY 1072 00:46:31,960 --> 00:46:33,160 JUST HAVE MISTAKES ON THEIR WAY 1073 00:46:33,160 --> 00:46:36,840 THERE. SO WE CAN ASK A FEW 1074 00:46:36,840 --> 00:46:38,480 QUESTIONS WITH REALLY BASIC 1075 00:46:38,480 --> 00:46:41,280 BEHAVIORAL ASSAYS. NUMBER ONE, 1076 00:46:41,280 --> 00:46:43,600 WHAT IS DRIVING THIS IMPAIRMENT? 1077 00:46:43,600 --> 00:46:45,400 ARE THERE MECHANISMS WE CAN FIND 1078 00:46:45,400 --> 00:46:46,640 THAT INCREASE OR EMERGE WITH AGE 1079 00:46:46,640 --> 00:46:50,280 THAT CAN MIMIC THIS IMPAIRMENT. 1080 00:46:50,280 --> 00:46:51,840 ALTERNATIVELY, CAN WE RESTORE 1081 00:46:51,840 --> 00:46:54,080 IDENTIFY AND RESTORE POTENTIALLY 1082 00:46:54,080 --> 00:46:58,280 BENEFICIAL MECHANISMS TO BRING 1083 00:46:58,280 --> 00:46:59,840 OLDER MECHANISM TO MORE YOUTHFUL 1084 00:46:59,840 --> 00:47:01,160 FUNCTIONAL STATE. CAN WE IMPROVE 1085 00:47:01,160 --> 00:47:02,080 THESE TYPES OF LEARNING AND 1086 00:47:02,080 --> 00:47:06,760 MEMORY. WE FOCUS ON PARTS OF 1087 00:47:06,760 --> 00:47:08,000 THE BRAIN THAT REGULATES ASPECT 1088 00:47:08,000 --> 00:47:10,040 OF LEARNING AND MEMORY KNOWN AS 1089 00:47:10,040 --> 00:47:12,160 HIPPOCAMPUS. HERE IS IN SALMON 1090 00:47:12,160 --> 00:47:16,440 COLOR AND THIS IS BEFORE DISEASE 1091 00:47:16,440 --> 00:47:20,720 ONSET. SAY LIKE ALZHEIMER WE 1092 00:47:20,720 --> 00:47:21,920 DON'T HAVE GROSS 1093 00:47:21,920 --> 00:47:23,080 NEURODEGENERATION SO NOT A LOT 1094 00:47:23,080 --> 00:47:24,440 OF CELL DEATH BUT WE HAVE SERIES 1095 00:47:24,440 --> 00:47:26,560 OF CELLULAR CHANGES THAT ARE 1096 00:47:26,560 --> 00:47:28,760 HAPPENING. WE FOCUS ON 1097 00:47:28,760 --> 00:47:30,000 HIPPOCAMPUS ONE BECAUSE IT IS A 1098 00:47:30,000 --> 00:47:31,280 MOUSE REGULATOR OF LEARN AND 1099 00:47:31,280 --> 00:47:34,600 MEMORY AND TWO, IT IS VULNERABLE 1100 00:47:34,600 --> 00:47:35,840 REGION TO EFFECT AND AGING ONE 1101 00:47:35,840 --> 00:47:37,560 OF THE FIRST POINTS OF CONTACT 1102 00:47:37,560 --> 00:47:38,880 BETWEEN BRAIN AND AGING. SO 1103 00:47:38,880 --> 00:47:41,200 WHAT IS AGING LOOK LIKE IN IF WE 1104 00:47:41,200 --> 00:47:42,960 LOOK AT THE NEURONS WHAT CHANGES 1105 00:47:42,960 --> 00:47:45,400 IS NOT REALLY NECESSARILY THEY 1106 00:47:45,400 --> 00:47:49,240 ARE DYING BUT RATHER CONNECTION 1107 00:47:49,240 --> 00:47:50,760 BETWEEN NEURONS BECOME FAULTY SO 1108 00:47:50,760 --> 00:47:53,080 NO LONGER STABLE. NORMALLY YOU 1109 00:47:53,080 --> 00:47:54,320 HAVE THESE STABLE CONNECTIONS, 1110 00:47:54,320 --> 00:47:56,560 IT KIND OF LOOKS LIKE A ROSE 1111 00:47:56,560 --> 00:47:58,760 STEM AND YOU CAN SEE LITTLE 1112 00:47:58,760 --> 00:47:59,760 THORNS, JUST CALLED SYNAPTIC 1113 00:47:59,760 --> 00:48:01,320 SPINES. THAT IS THE PHYSICAL 1114 00:48:01,320 --> 00:48:02,200 CONTACT WHERE THE SYNAPSES 1115 00:48:02,200 --> 00:48:04,360 OCCUR. HOW THE NEURONS 1116 00:48:04,360 --> 00:48:06,040 COMMUNICATE WITH ONE ANOTHER. 1117 00:48:06,040 --> 00:48:08,400 NOSE BECOME UNSTABLE FAULTY, WE 1118 00:48:08,400 --> 00:48:09,760 LOSE SOME OF THEM. ADDITION 1119 00:48:09,760 --> 00:48:13,560 A.M.LY WE ALSO HAVE CHANGES IN 1120 00:48:13,560 --> 00:48:15,200 REGENERATIVE CAPACITY SO NEURAL 1121 00:48:15,200 --> 00:48:17,560 STEM CELLS THAT GIVE RISE TO 1122 00:48:17,560 --> 00:48:18,880 NEURONS, WE HAVE OTHER 1123 00:48:18,880 --> 00:48:20,920 PROGENITORS THAT MYELINATE AND 1124 00:48:20,920 --> 00:48:23,200 GIVE RISE TO MYELINATI MYELINATE 1125 00:48:23,200 --> 00:48:26,200 HAVE DYSFUNCTION. THIS IS 1126 00:48:26,200 --> 00:48:28,440 CONTROVERSIAL IN HUMANS SOME 1127 00:48:28,440 --> 00:48:30,680 REPORTS SAY THIS DISAPPEARS BY 1128 00:48:30,680 --> 00:48:31,880 PUBERTY, OTHER REPORTS SHOWING 1129 00:48:31,880 --> 00:48:33,720 NO, YOU HAVE THESE STEMS UNTIL 1130 00:48:33,720 --> 00:48:34,960 LATE IN LIFE AND THEY ARE 1131 00:48:34,960 --> 00:48:37,520 DECLINE ACTUALLY CORRELATES WITH 1132 00:48:37,520 --> 00:48:38,680 COGNITIVE IMPAIRMENT. RIGHT NOW 1133 00:48:38,680 --> 00:48:40,800 THERE IS LARGER NUMBER OF PAPERS 1134 00:48:40,800 --> 00:48:41,240 THAT ARE. 1135 00:48:41,240 --> 00:48:44,640 COMING IN SUPPORT OF THAT SORT 1136 00:48:44,640 --> 00:48:46,000 OF POOL BEGIN INTO OLD AGE BUT 1137 00:48:46,000 --> 00:48:48,240 THAT IS ONGOING RESEARCH. IN OUR 1138 00:48:48,240 --> 00:48:51,520 ANIMAL MODEL IT IS QUITE CLEAR 1139 00:48:51,520 --> 00:48:57,040 THIS PERSISTENT. WE HAVE 1140 00:48:57,040 --> 00:48:58,040 INFLAMMATION BECOMING MORE 1141 00:48:58,040 --> 00:49:00,040 RELEVANT IN CONTEXT OF AGE. WE 1142 00:49:00,040 --> 00:49:02,600 KNOW IT HAS A HUGE ROLE IN 1143 00:49:02,600 --> 00:49:04,840 PROMOTING THESE AGING PHENOTYPES 1144 00:49:04,840 --> 00:49:06,280 BOTH IN THE PERIPHERY AS WELL AS 1145 00:49:06,280 --> 00:49:11,000 IN THE BRAIN. LASTLY, THE 1146 00:49:11,000 --> 00:49:11,840 COMMUNICATION BETWEEN WHAT IS IN 1147 00:49:11,840 --> 00:49:14,360 THE BRAIN AND OUT OF THE BRAIN, 1148 00:49:14,360 --> 00:49:16,280 GETS FALLY AS WE GO OVER TO 1149 00:49:16,280 --> 00:49:18,680 BLOOD -- FAULTY AS WE GO OVER 1150 00:49:18,680 --> 00:49:20,640 BLOOD BRAIN BARRIER AND 1151 00:49:20,640 --> 00:49:22,120 VASCULATURE IS EMERGING AS 1152 00:49:22,120 --> 00:49:23,960 ANOTHER HALLMARK OF AGING AND IT 1153 00:49:23,960 --> 00:49:25,600 IS NOT THAT THE BARRIER BREAKS 1154 00:49:25,600 --> 00:49:27,360 AND EVERYTHING GETS INTO THE 1155 00:49:27,360 --> 00:49:28,800 BRAIN BUT SELECTIVITY OF WHAT 1156 00:49:28,800 --> 00:49:30,600 GETS IN AND DOESN'T GET IN IS 1157 00:49:30,600 --> 00:49:31,880 CHANGING WITH AGE SO SIGNALS 1158 00:49:31,880 --> 00:49:33,480 THAT ARE GETTING TO YOUR BRAIN 1159 00:49:33,480 --> 00:49:34,840 ARE SHIFTING BETWEEN WHEN YOU 1160 00:49:34,840 --> 00:49:41,640 ARE YOUNG AND WHEN YOU ARE OLD. 1161 00:49:41,640 --> 00:49:43,720 WORK FIRST AS GRADUATE STUDENT 1162 00:49:43,720 --> 00:49:46,920 AT STANFORD WORKING WITH DR. TOM 1163 00:49:46,920 --> 00:49:48,760 (INAUDIBLE) WAS USING THIS VERY 1164 00:49:48,760 --> 00:49:51,720 OLD MODEL FIRST DESCRIBED IN THE 1165 00:49:51,720 --> 00:49:53,320 LATE 1700S WHERE YOU PHYSICALLY 1166 00:49:53,320 --> 00:49:56,960 CONNECT A YOUNG AND OLD -- ADD 1167 00:49:56,960 --> 00:49:58,200 THEM TOGETHER IN THIS PARTICULAR 1168 00:49:58,200 --> 00:50:01,080 CASE MICE, TWO HEARTS PUMP ONE 1169 00:50:01,080 --> 00:50:02,000 BLOODSTREAM SO TWO QUESTIONS. 1170 00:50:02,000 --> 00:50:03,600 NUMBER ONE, WHAT IS IMPACT OF 1171 00:50:03,600 --> 00:50:05,240 OLD BLOOD AND OLD BLOOD SIGNALS 1172 00:50:05,240 --> 00:50:07,040 ON TO THE YOUNG ANIMAL? AND WHAT 1173 00:50:07,040 --> 00:50:09,480 ARE THE IMPACT OF THOSE YOUNG 1174 00:50:09,480 --> 00:50:11,080 FACTORS OR YOUNG BLOOD TO OLD 1175 00:50:11,080 --> 00:50:14,120 ANIMAL? AND WORK BY DR. TOM 1176 00:50:14,120 --> 00:50:16,720 RANDO AND AMY WAGER IS STARTED 1177 00:50:16,720 --> 00:50:19,040 SHOWING THAT THERE ARE SIGNALS, 1178 00:50:19,040 --> 00:50:20,520 THAT ARE -- THAT HAVE 1179 00:50:20,520 --> 00:50:22,760 INFORMATION THAT CAN REALLY 1180 00:50:22,760 --> 00:50:24,200 REJUVENATE OR RESTORE FUNCTION 1181 00:50:24,200 --> 00:50:25,760 IN THAT OLDER ANIMAL 1182 00:50:25,760 --> 00:50:27,760 PARTICULARLY IN THE CONTEXT OF 1183 00:50:27,760 --> 00:50:31,640 STEM CELL BIOLOGY. TOGETHER WITH 1184 00:50:31,640 --> 00:50:33,200 TONY AND NUMBER OF DIFFERENT 1185 00:50:33,200 --> 00:50:36,320 LIVES AROUND THE WORLD, WE 1186 00:50:36,320 --> 00:50:38,440 DEMONSTRATED THAT THESE AGE 1187 00:50:38,440 --> 00:50:43,080 FACTORS CAN PROMOTE AGENING THE 1188 00:50:43,080 --> 00:50:50,680 BRAIN A LOT A AGING IN NATURE. T 1189 00:50:50,680 --> 00:50:51,920 FACTORS IMPROVE FUNCTION IN THE 1190 00:50:51,920 --> 00:50:53,000 BRAIN INCLUDING LEARNING AND 1191 00:50:53,000 --> 00:50:54,120 MEMORY. WHAT IS INTERESTING AT 1192 00:50:54,120 --> 00:50:55,120 THE BEGINNING WHEN I STARTED 1193 00:50:55,120 --> 00:50:56,720 RESEARCH I THOUGHT THERE WAS 1194 00:50:56,720 --> 00:50:59,160 SOMETHING UNIQUE ABOUT YOUNG 1195 00:50:59,160 --> 00:51:00,560 BLOOD. THERE MUST BE SOMETHING 1196 00:51:00,560 --> 00:51:02,800 THAT IS UNIQUE TO THIS ONE 1197 00:51:02,800 --> 00:51:04,920 CONDITION. IT TURNS OUT IF YOU 1198 00:51:04,920 --> 00:51:07,440 LOOK AT A LONG, LONG HISTORY, 1199 00:51:07,440 --> 00:51:10,080 LONG HISTORY OF RESEARCH, IT IS 1200 00:51:10,080 --> 00:51:12,560 NOT JUST ABOUT A MODEL OF 1201 00:51:12,560 --> 00:51:14,360 PARABAYOUSIS I CONSIDER A 1202 00:51:14,360 --> 00:51:15,120 SYSTEMIC INTERVENTION BUT THERE 1203 00:51:15,120 --> 00:51:17,320 IS A NUMBER OF LIFESTYLE 1204 00:51:17,320 --> 00:51:18,440 INTERVENTIONS THAT CAN ALSO 1205 00:51:18,440 --> 00:51:20,600 IMPACT AND RESTORE FUNCTION OR 1206 00:51:20,600 --> 00:51:23,000 REJUVENATE TISSUE. FOR EXAMPLE 1207 00:51:23,000 --> 00:51:24,920 EXERCISE, WE JUST HER EXERCISE 1208 00:51:24,920 --> 00:51:26,120 IMPACT MITOCHONDRIA WHICH IS A 1209 00:51:26,120 --> 00:51:28,240 HALLMARK OF AGING, EXERCISE ALSO 1210 00:51:28,240 --> 00:51:30,520 IMPROVE LEARN AND MEMORY. WE 1211 00:51:30,520 --> 00:51:32,160 KNOW THERE SHAH CORE 1212 00:51:32,160 --> 00:51:34,520 RESTRICTION. THROUGH PRIMATE, IT 1213 00:51:34,520 --> 00:51:36,600 SEEMED TO IMPROVE HEALTH IN 1214 00:51:36,600 --> 00:51:39,080 ANIMAL MODELS, IMPROVE LIFE SPAN 1215 00:51:39,080 --> 00:51:41,480 IN CERTAIN CASES AS WELL ALSO 1216 00:51:41,480 --> 00:51:44,560 LESS STUDIED ALSO HAS IMPACT ON 1217 00:51:44,560 --> 00:51:45,680 COGNITIVE FUNCTION DURING OLD 1218 00:51:45,680 --> 00:51:47,600 AGE. SO WE KNEW THERE WAS ALL 1219 00:51:47,600 --> 00:51:48,880 THESE DIFFERENT TYPES OF 1220 00:51:48,880 --> 00:51:51,400 INTERVENTIONS. WHEN WE STARTED 1221 00:51:51,400 --> 00:51:53,760 DOING THE WORK IN PARABIOSIS WE 1222 00:51:53,760 --> 00:51:55,920 WERE ASKED ABOUT THE 1223 00:51:55,920 --> 00:51:56,760 TRANSLATABILITY OF THIS 1224 00:51:56,760 --> 00:51:59,840 APPROACH. YOU CAN'T SEW 1225 00:51:59,840 --> 00:52:01,440 INDIVIDUALS TOGETHER. WE DID IS 1226 00:52:01,440 --> 00:52:03,360 WE CAME UP WITH AN ALTERNATIVE 1227 00:52:03,360 --> 00:52:07,960 WHERE WE FOUND THE VOLUME OF 1228 00:52:07,960 --> 00:52:10,880 PLASMA IN THIS CASE, MOSTLY 1229 00:52:10,880 --> 00:52:12,640 FACTORS IN BLOOD AND WE INJECTED 1230 00:52:12,640 --> 00:52:14,880 THEM INTO THESE OLDER ANIMALS 1231 00:52:14,880 --> 00:52:19,200 AND WE JUST ASKED CAN WE MIMIC 1232 00:52:19,200 --> 00:52:20,080 OR TRANSFER SOME OF THE BENEFITS 1233 00:52:20,080 --> 00:52:23,520 OF THIS SURGERY THROUGH 1234 00:52:23,520 --> 00:52:24,760 ADMINISTRATION OF YOUNG BLOOD 1235 00:52:24,760 --> 00:52:26,960 FACTORS. THIS IS WHERE I STARTED 1236 00:52:26,960 --> 00:52:29,720 MY LAB AND STARTED DOING WORK 1237 00:52:29,720 --> 00:52:31,880 HERE AT UCSF AND I WILL SHOW YOU 1238 00:52:31,880 --> 00:52:34,880 ONE PIECE OF DATA, AGAIN, I WILL 1239 00:52:34,880 --> 00:52:35,960 UTILIZE THAT WATER MAZE I TALKED 1240 00:52:35,960 --> 00:52:38,000 TO YOU ABOUT TO TRY TO FIND THAT 1241 00:52:38,000 --> 00:52:39,480 PLATFORM WITH RESPECT TO QUEUES. 1242 00:52:39,480 --> 00:52:41,640 WHAT WE ARE GOING TO DO IS COUNT 1243 00:52:41,640 --> 00:52:43,480 HOW MANY ERRORS WE DIVIDE THIS 1244 00:52:43,480 --> 00:52:44,600 POOL TO SERIES OF ARMS, THEY 1245 00:52:44,600 --> 00:52:46,240 HAVE TO GET HERE, SO IN THIS 1246 00:52:46,240 --> 00:52:47,400 PARTICULAR CASE THEY MADE THREE 1247 00:52:47,400 --> 00:52:49,600 ERRORS AND WE CAN QUANTIFY 1248 00:52:49,600 --> 00:52:51,000 ERRORS, THIS IS GREAT BECAUSE IT 1249 00:52:51,000 --> 00:52:52,600 GETS AROUND A YOUNG OR OLDER 1250 00:52:52,600 --> 00:52:54,240 ANIMAL SWIMMING AT DIFFERENT 1251 00:52:54,240 --> 00:52:55,640 SPEEDS, THIS WILL FORCE THEM TO 1252 00:52:55,640 --> 00:52:58,960 JUST MAKE A SERIES OF DECISIONS 1253 00:52:58,960 --> 00:53:02,920 WE INJECT 5% VOLUME OF BLOOD IN 1254 00:53:02,920 --> 00:53:04,920 OLDER ANIMAL WITH YOUNG PLASMA. 1255 00:53:04,920 --> 00:53:07,440 AND WE JUST DO THESE EXPERIMENTS 1256 00:53:07,440 --> 00:53:09,360 ABOUT A MONTH LATER. I WANT TO 1257 00:53:09,360 --> 00:53:10,960 POINT OUT THESE ARE NATURALLY 1258 00:53:10,960 --> 00:53:12,680 NORMALLY AGED ANIMALS. THEY ARE 1259 00:53:12,680 --> 00:53:14,280 NOT GENETIC MODELS THEE ARE JUST 1260 00:53:14,280 --> 00:53:17,200 NORMAL ANIMALS, WHENEVER 1261 00:53:17,200 --> 00:53:18,760 POSSIBLE, EVEN LITTER MATES A 1262 00:53:18,760 --> 00:53:20,200 LOT BORN TOGETHER. WHAT WE KNOW 1263 00:53:20,200 --> 00:53:21,800 IS THAT AT THIS AGE THERE ARE 1264 00:53:21,800 --> 00:53:24,040 ABOUT A LITTLE UNDER TWO YEARS 1265 00:53:24,040 --> 00:53:28,520 OLD. SO EQUIVALENT TO 60s IN A 1266 00:53:28,520 --> 00:53:32,160 HUMAN. WE SEE WHEN YOU GIVE THIS 1267 00:53:32,160 --> 00:53:34,200 NORMAL OLD BLOOD IN GRAY YOU 1268 00:53:34,200 --> 00:53:36,120 CONTINUE TO MAKE ERRORS THEY 1269 00:53:36,120 --> 00:53:37,520 START ABOUT FOUR AND THEY GO 1270 00:53:37,520 --> 00:53:41,120 DOWN TO TWO, BUT OLD ANIMALS IN 1271 00:53:41,120 --> 00:53:42,600 RED THAT RECEIVED THAT YOUNG 1272 00:53:42,600 --> 00:53:44,040 PLASMA WENT DOWN CLOSE TO ONE 1273 00:53:44,040 --> 00:53:45,560 ERROR SO YOU CAN RESTORE 1274 00:53:45,560 --> 00:53:47,080 FUNCTION. THIS IS EXCITING FOR A 1275 00:53:47,080 --> 00:53:49,200 FEW REASONS. NUMBER ONE, YOUR 1276 00:53:49,200 --> 00:53:51,120 BRAIN IS CAPABLE OF BEING 1277 00:53:51,120 --> 00:53:55,440 RESTORED. THERE IS ENOUGH 1278 00:53:55,440 --> 00:53:56,280 PLASTICITY LEFT IN THOSE THAT 1279 00:53:56,280 --> 00:53:57,840 YOU CAN BRING BACK FUNCTION. 1280 00:53:57,840 --> 00:53:59,480 THAT MEANS WE JUST NEED TO CRACK 1281 00:53:59,480 --> 00:54:01,840 THE CODE. WHAT ARE THE CHANGES, 1282 00:54:01,840 --> 00:54:03,280 WHICH CELL TYPES ARE THE MOST 1283 00:54:03,280 --> 00:54:04,840 IMPORTANT TO HAVE THIS 1284 00:54:04,840 --> 00:54:06,240 RESTORATION. WHAT ARE THE 1285 00:54:06,240 --> 00:54:08,080 MOLECULES POTENTIALLY THAT 1286 00:54:08,080 --> 00:54:10,320 HAPPEN, BUT IT DID GIVE US AN 1287 00:54:10,320 --> 00:54:14,480 IDEA THAT THERE IS THE ABILITY 1288 00:54:14,480 --> 00:54:16,320 TO RESTORE FUNCTION. IN MANY MY 1289 00:54:16,320 --> 00:54:20,120 LAB WE HAVE ONGOING WORK GOING 1290 00:54:20,120 --> 00:54:22,520 ON FOCUSING ON HALLMARK OF 1291 00:54:22,520 --> 00:54:24,080 CHANGING, DO YOU HAVE TO RESTORE 1292 00:54:24,080 --> 00:54:25,560 EVERY FUNCTION TO GET THAT 1293 00:54:25,560 --> 00:54:26,920 COGNITIVE RESTORATION OR 1294 00:54:26,920 --> 00:54:29,480 REJUVENATION OR MAYBE IT IS A 1295 00:54:29,480 --> 00:54:30,800 COMBINATION, MAYBE IF WE 1296 00:54:30,800 --> 00:54:32,920 DECREASE INFLAMMATION GNAT BRAIN 1297 00:54:32,920 --> 00:54:34,240 THAT ENOUGH AND ALLOWING NEURONS 1298 00:54:34,240 --> 00:54:36,080 THERE TO COMMUNICATE. IF YOU 1299 00:54:36,080 --> 00:54:37,520 TALK ABOUT SAY REGENERATION AND 1300 00:54:37,520 --> 00:54:38,560 NEURONAL COMMUNICATION MAYBE 1301 00:54:38,560 --> 00:54:40,480 THAT IS ENOUGH TO REJUVENATE. SO 1302 00:54:40,480 --> 00:54:42,240 WE ARE FOCUSING ON THE 1303 00:54:42,240 --> 00:54:43,320 CONTRIBUTION OF DIFFERENT 1304 00:54:43,320 --> 00:54:45,320 HALLMARKS AS WELL AS WHAT YOU 1305 00:54:45,320 --> 00:54:46,680 HAVE TO TARGET. THE OTHER THING, 1306 00:54:46,680 --> 00:54:48,040 WE ARE STARTING TO LOOK AT THE 1307 00:54:48,040 --> 00:54:50,360 DIFFERENT INTERVENTIONS. NOT 1308 00:54:50,360 --> 00:54:52,280 JUST YOUNG BLOOD BUT WHAT ABOUT 1309 00:54:52,280 --> 00:54:54,040 EXERCISE OR CAN CALORIC 1310 00:54:54,040 --> 00:54:56,240 RESTRICTION. ONE PROBLEM WE HAVE 1311 00:54:56,240 --> 00:54:57,520 ESPECIALLY IN THE ELDERLY 1312 00:54:57,520 --> 00:55:01,520 POPULATION OR THOSE WITH 1313 00:55:01,520 --> 00:55:02,720 ALZHEIMERS OFTEN TIMES COMPANY 1314 00:55:02,720 --> 00:55:04,520 WITH FRAILTY, THEY ARE NOT ABLE 1315 00:55:04,520 --> 00:55:07,440 TO ADHERE OR PHYSICALLY DO THE 1316 00:55:07,440 --> 00:55:09,280 ACTIVITY ITSELF, THEY CAN'T 1317 00:55:09,280 --> 00:55:12,080 ACTUALLY EXERCISE THOUGH WE KNOW 1318 00:55:12,080 --> 00:55:13,280 BENEFICIAL IN THE HUMAN 1319 00:55:13,280 --> 00:55:16,440 CONDITION. SO THEN WHAT MY LAB, 1320 00:55:16,440 --> 00:55:18,120 ESPECIALLY A POST DOC GRADUATE 1321 00:55:18,120 --> 00:55:19,840 STUDENT IN MY LAB GOT EXCITED, 1322 00:55:19,840 --> 00:55:22,320 THEY WERE LIKE WELL, WE KNOW 1323 00:55:22,320 --> 00:55:24,920 EXERCISE IS ACCOMPANIED WITH 1324 00:55:24,920 --> 00:55:25,840 IMPROVED HEALTH SPAN AND 1325 00:55:25,840 --> 00:55:27,080 BENEFITS AND I LOVE THIS IMAGE 1326 00:55:27,080 --> 00:55:28,800 I'M SHOWING YOU THE THIS 1327 00:55:28,800 --> 00:55:31,120 PICTURE, THIS GENTLEMAN, 1328 00:55:31,120 --> 00:55:35,320 MR. SING PREPARING FOR THE 1329 00:55:35,320 --> 00:55:37,560 MARATHON. HE IS A HUNDRED YEARS 1330 00:55:37,560 --> 00:55:40,320 OLD AND JUST HEALTH SPAN IS 1331 00:55:40,320 --> 00:55:41,920 INCREDIBLE. HE'S BOTH A 1332 00:55:41,920 --> 00:55:43,560 CENTENARIAN BUT ALSO A HISTORY 1333 00:55:43,560 --> 00:55:45,120 OF EXERCISE SO REALLY 1334 00:55:45,120 --> 00:55:45,880 UNDERSCORES THIS BENEFIT THAT 1335 00:55:45,880 --> 00:55:50,040 CAN HAPPEN. WHEN MY STUDENTS 1336 00:55:50,040 --> 00:55:51,520 SAID WHEN THEY WERE THINKING 1337 00:55:51,520 --> 00:55:52,720 EXERCISE THEY WERE LIKE EXERCISE 1338 00:55:52,720 --> 00:55:54,320 HAS A LOT OF THE SAME BENEFITS 1339 00:55:54,320 --> 00:55:56,960 WE SEE IN PARABIOSIS. 1340 00:55:56,960 --> 00:55:58,360 REGENERATION, NEURONAL 1341 00:55:58,360 --> 00:55:59,440 COMMUNICATION, INFLAMMATION, 1342 00:55:59,440 --> 00:56:00,720 IMPROVED COGNITION. SO THEY WERE 1343 00:56:00,720 --> 00:56:02,360 REALLY INTERESTED IN ASKING IF 1344 00:56:02,360 --> 00:56:05,760 YOU CAN TRANSFER THE EFFECT OF 1345 00:56:05,760 --> 00:56:07,000 PARABIOSIS THROUGH BLOOD 1346 00:56:07,000 --> 00:56:08,000 ADMINISTRATION CAN YOU DO THE 1347 00:56:08,000 --> 00:56:09,280 SAME WITH EXERCISE? CAN WE 1348 00:56:09,280 --> 00:56:10,760 IDENTIFY FACTORS? SO THAT IS 1349 00:56:10,760 --> 00:56:12,080 WHAT THEY DID. THEY ASKED THAT 1350 00:56:12,080 --> 00:56:13,520 QUESTION, CAN THE BENEFITS OF 1351 00:56:13,520 --> 00:56:15,000 EXERCISE JUST BE TRANSFERRED 1352 00:56:15,000 --> 00:56:19,440 THROUGH BLOOD AND THIS IS 1353 00:56:19,440 --> 00:56:22,440 SHELLEY, TALENTED. THEY WENT OFF 1354 00:56:22,440 --> 00:56:25,120 AND SET UP AN EXERCISE PARADIGM, 1355 00:56:25,120 --> 00:56:26,920 WELL REPORTED MANY LABS FOR A 1356 00:56:26,920 --> 00:56:28,120 LONG TIME HAVE SEEN THE BENEFITS 1357 00:56:28,120 --> 00:56:29,760 YOU GIVE A LITTLE VOLUNTARY 1358 00:56:29,760 --> 00:56:33,680 WHEEL RUNNING, WE DID IT FOR 1359 00:56:33,680 --> 00:56:36,200 ABOUT SIX WEEKS THEN WE DID 1360 00:56:36,200 --> 00:56:38,400 BEHAVIORAL ANALYSIS. WE DID 1361 00:56:38,400 --> 00:56:39,640 CELLULAR PREDOMINANTLY ON 1362 00:56:39,640 --> 00:56:41,080 BEHAVIOR. SO USING THAT SAME 1363 00:56:41,080 --> 00:56:43,200 MODEL, YOU STARTED AROUND 4 AND 1364 00:56:43,200 --> 00:56:44,440 YOU END UP MAKING HERE ABOUT TWO 1365 00:56:44,440 --> 00:56:47,560 AND A HALF ERRORS IN THE 1366 00:56:47,560 --> 00:56:49,240 NORMALLY OLD ANALYSIS BUT PUT IN 1367 00:56:49,240 --> 00:56:50,280 RUNNING WHEEL IT GETS DOWN TO 1368 00:56:50,280 --> 00:56:52,960 ONE. ONE OF THE STRONGEST 1369 00:56:52,960 --> 00:56:53,680 INTERVENTIONS THAT WE HAVE SEEN 1370 00:56:53,680 --> 00:56:55,040 TO RESTORE FUNCTION. SO 1371 00:56:55,040 --> 00:56:57,880 EXERCISE, REALLY IS GOOD EVEN AT 1372 00:56:57,880 --> 00:57:04,800 OLD AGE IN THIS MOUSE MODEL. 1373 00:57:04,800 --> 00:57:06,680 NEXT THEY RAN OLD MICE AND USED 1374 00:57:06,680 --> 00:57:08,960 IT TO TEASE APART THE BENEFIT OF 1375 00:57:08,960 --> 00:57:10,000 YOUNG BLOOD FROM BENEFIT OF 1376 00:57:10,000 --> 00:57:11,920 EXERCISE FACTORS. SO EXERCISE 1377 00:57:11,920 --> 00:57:13,200 OLD MICE THAT COULD EXERCISE, 1378 00:57:13,200 --> 00:57:14,840 THEY TOOK PLASMA, INJECTED INTO 1379 00:57:14,840 --> 00:57:16,920 OLD MICE AND THEN AGAIN LOOKED 1380 00:57:16,920 --> 00:57:20,600 AT BEHAVIOR AGAIN WE SAW A 1381 00:57:20,600 --> 00:57:21,840 FRACTION OF THAT BENEFIT THAT WE 1382 00:57:21,840 --> 00:57:24,440 SEE WITH EXERCISE CAN ACTUALLY 1383 00:57:24,440 --> 00:57:28,600 BE TRANSFERRED THROUGH JUST 1384 00:57:28,600 --> 00:57:30,120 ADMINISTRATION OF THOSE BLOOD 1385 00:57:30,120 --> 00:57:31,400 FACTORS SO THAT WAS REALLY 1386 00:57:31,400 --> 00:57:33,400 EXCITING TO US. SO OF COURSE WE 1387 00:57:33,400 --> 00:57:34,760 WANTS TO KNOW WHAT ARE THE 1388 00:57:34,760 --> 00:57:35,960 MOLECULAR MECHANISM? 1389 00:57:35,960 --> 00:57:38,400 I WILL USE THIS OPPORTUNITY JUST 1390 00:57:38,400 --> 00:57:40,960 TO SAY THE IDEA OF 1391 00:57:40,960 --> 00:57:42,480 ADMINISTRATING BLOOD CAPTURED 1392 00:57:42,480 --> 00:57:45,000 THE ATTENTION OF THE PUBLIC BUT 1393 00:57:45,000 --> 00:57:47,200 I WILL SAY AND THE FDA SAID, YOU 1394 00:57:47,200 --> 00:57:49,200 CANNOT JUST INJECT BLOOD WHETHER 1395 00:57:49,200 --> 00:57:51,040 YOUNG BLOOD OR EXERCISE BLOOD 1396 00:57:51,040 --> 00:57:53,400 INTO HUMANS THAT IS NOT A TENIAL 1397 00:57:53,400 --> 00:57:55,040 SOLUTION OR THERAPEUTIC. 1398 00:57:55,040 --> 00:57:56,440 LIMITATIONS IN TERMS OF AMOUNT 1399 00:57:56,440 --> 00:57:59,480 OF BLOOD, THERE IS NOT ENOUGH TO 1400 00:57:59,480 --> 00:58:01,400 TREAT THE ALZHEIMER'S PATIENTS 1401 00:58:01,400 --> 00:58:03,400 TODAY LET ALONE ONES COMING AND 1402 00:58:03,400 --> 00:58:05,280 NUMBER TWO, REAL DANGERS TO IT 1403 00:58:05,280 --> 00:58:06,640 IN TERMS OF PRESSURE IN YOUR 1404 00:58:06,640 --> 00:58:08,720 LUNG AND OTHER POTENTIALS SORT 1405 00:58:08,720 --> 00:58:10,960 OF CONTAMINATION FROM THE BLOOD. 1406 00:58:10,960 --> 00:58:12,520 SO THE ALTERNATIVE WHAT WE ARE 1407 00:58:12,520 --> 00:58:15,200 TRYING TO ACHIEVE IS TRYING TO 1408 00:58:15,200 --> 00:58:16,200 UNDERSTAND WHAT ARE THE 1409 00:58:16,200 --> 00:58:19,080 MOLECULAR MECHANISMS, WHAT IS IT 1410 00:58:19,080 --> 00:58:21,040 IN THE BLOOD THAT CAN CONFER 1411 00:58:21,040 --> 00:58:22,920 THIS BENEFIT, WHAT ARE THE CELL 1412 00:58:22,920 --> 00:58:25,000 TARGETS WHETHER THEY BE OUTSIDE 1413 00:58:25,000 --> 00:58:26,280 OF THE BRAIN OR IN THE BRAIN. 1414 00:58:26,280 --> 00:58:28,640 WHAT IS IT ELICITING INSIDE THE 1415 00:58:28,640 --> 00:58:31,720 CELLS? IS IT GENE, IS IT 1416 00:58:31,720 --> 00:58:33,440 EPIGENETICS, PROTEINS? SO WE ARE 1417 00:58:33,440 --> 00:58:36,320 TRYING TO TACKLE ALL THAT. AS WE 1418 00:58:36,320 --> 00:58:38,120 IDENTIFY THESE FACTORS THAT CAN 1419 00:58:38,120 --> 00:58:40,320 NOW BE PRODUCED, THEY CAN THEN 1420 00:58:40,320 --> 00:58:43,200 BE DOSED AND WE CAN GO THROUGH 1421 00:58:43,200 --> 00:58:45,080 TRADITIONAL CLINICAL TRIALS IN A 1422 00:58:45,080 --> 00:58:46,200 CONTROLLED SETTING TOWARDS 1423 00:58:46,200 --> 00:58:47,040 SOMETHING THAT CAN BE APPLIED SO 1424 00:58:47,040 --> 00:58:49,960 I WANT TO STRESS THAT IS THE 1425 00:58:49,960 --> 00:58:51,720 REASON THE FIELD IS REALLY AFTER 1426 00:58:51,720 --> 00:58:53,600 THE MOLECULAR MECHANISMS, WHAT 1427 00:58:53,600 --> 00:58:55,600 IS IT THAT IS DOING. WHAT WE 1428 00:58:55,600 --> 00:58:57,480 ENDED UP TRYING IS WE DID WHAT 1429 00:58:57,480 --> 00:58:59,880 IS CALLED PROTEOMICS. WE TOOK 1430 00:58:59,880 --> 00:59:02,440 THE BLOOD OF THOSE EXERCISE OR 1431 00:59:02,440 --> 00:59:03,800 NON-EXERCISE ANIMALS AND WE JUST 1432 00:59:03,800 --> 00:59:04,920 SAID WHAT ARE THE DIFFERENCES? 1433 00:59:04,920 --> 00:59:07,160 ARE THERE ANY PROTEINS THAT ARE 1434 00:59:07,160 --> 00:59:08,480 DIFFERENT IN ONE CONDITION 1435 00:59:08,480 --> 00:59:10,120 VERSUS OTHER? WE CAME UP WITH A 1436 00:59:10,120 --> 00:59:11,880 HANDFUL OF FACTORS THAT DID 1437 00:59:11,880 --> 00:59:14,200 CHANGE BETWEEN THE TWO 1438 00:59:14,200 --> 00:59:15,200 CONDITIONS. WE LOOK AT WHERE 1439 00:59:15,200 --> 00:59:18,200 THEY GENERALLY COMING FROM, AND 1440 00:59:18,200 --> 00:59:19,440 EXPRESSED AND WE WERE SURPRISED 1441 00:59:19,440 --> 00:59:20,880 BECAUSE WE EXPECTED TO SEE 1442 00:59:20,880 --> 00:59:24,320 MOSTLY MUSCLE FACTORS BUT WE SAW 1443 00:59:24,320 --> 00:59:25,840 TWO-THIRDS BEGIN LIVER FACTOR, 1444 00:59:25,840 --> 00:59:27,280 DIDN'T MATTER OLD MICE OR 1445 00:59:27,280 --> 00:59:29,480 SLIGHTLY YOUNGER MICE. IT WAS 1446 00:59:29,480 --> 00:59:30,840 PREDOMINANTLY LIVER FACTORS. SO 1447 00:59:30,840 --> 00:59:32,880 THEN WE LOOK AT ALL FACTORS AND 1448 00:59:32,880 --> 00:59:34,200 SAID ARE THEY INVOLVED IN 1449 00:59:34,200 --> 00:59:35,760 PARTICULAR PROCESSES IN THE 1450 00:59:35,760 --> 00:59:39,200 BRAIN? AND IF SO, DO ANY FACTORS 1451 00:59:39,200 --> 00:59:41,520 LIKE JUMP OUT AT US? WHAT WE DID 1452 00:59:41,520 --> 00:59:44,600 IS WE JUST TOOK THOSE FACTORS 1453 00:59:44,600 --> 00:59:46,080 AND JUST BIOINFORMATICS ASKED 1454 00:59:46,080 --> 00:59:47,640 ARE YOU INVOLVED IN ANY 1455 00:59:47,640 --> 00:59:48,440 PARTICULAR PROCESSES? AND IT WAS 1456 00:59:48,440 --> 00:59:50,200 A LOT OF METABOLIC PROCESSES 1457 00:59:50,200 --> 00:59:52,000 THAT CAME OUT. THAT MAKES SENSE 1458 00:59:52,000 --> 00:59:53,160 BECAUSE IT IS LIVER PROTEINS. 1459 00:59:53,160 --> 00:59:54,680 BUT ONE FACTOR, ACTUALLY TWO, 1460 00:59:54,680 --> 00:59:56,040 CAME UP A LOT. ONE OF THEM I 1461 00:59:56,040 --> 00:59:58,200 WILL TALK ABOUT TODAY, IT IS AN 1462 00:59:58,200 --> 01:00:01,640 ENZYME CALLED GPLT 1, ONE IS 1463 01:00:01,640 --> 01:00:03,040 RIVER FACTOR CALLED POL 1 THAT 1464 01:00:03,040 --> 01:00:05,600 DID NOTHING WHEN WE TESTED SO 1465 01:00:05,600 --> 01:00:06,280 NEGATIVE DAS, IT ISN'T A 1466 01:00:06,280 --> 01:00:07,840 SUPPLEMENT OF THE PAPER, IT IS 1467 01:00:07,840 --> 01:00:11,600 LIKE FIGURE 17. BUT WE DID TEST 1468 01:00:11,600 --> 01:00:12,160 BOTH AND THERE WAS ONE THAT 1469 01:00:12,160 --> 01:00:13,320 SHOWED PROMISING EFFECTS AND 1470 01:00:13,320 --> 01:00:14,800 THAT IS WHAT I WILL FOCUS ON 1471 01:00:14,800 --> 01:00:21,760 TODAY WHICH IS GPLD 1. IT ACTS 1472 01:00:21,760 --> 01:00:24,040 AS A SCISSOR SO ON A CELL 1473 01:00:24,040 --> 01:00:25,840 SURFACE WE HAVE PROTEINS STUCK 1474 01:00:25,840 --> 01:00:27,960 THE SURFACE, THEY ARE ANCHORED 1475 01:00:27,960 --> 01:00:31,240 BY THE LITTLE TAGS AND ALL THIS 1476 01:00:31,240 --> 01:00:32,600 ENZYME DOES IT COMES AN CLEAVES 1477 01:00:32,600 --> 01:00:34,680 AND THE PROTEIN CAN GO AND IT 1478 01:00:34,680 --> 01:00:36,720 CAN ACTIVATE PATHWAYS, INHIBIT 1479 01:00:36,720 --> 01:00:38,240 PATHWAYS OR THE PROTEINS JUST 1480 01:00:38,240 --> 01:00:39,600 GET DEGRADED SO IT CAN HAVE A 1481 01:00:39,600 --> 01:00:40,640 NUMBER OF DIFFERENT FUNCTIONS. 1482 01:00:40,640 --> 01:00:42,080 WE LIKE THAT BECAUSE THAT MEANS 1483 01:00:42,080 --> 01:00:45,080 IT WILL HAVE BROAD EFFECTS. SO 1484 01:00:45,080 --> 01:00:47,560 FOCUS ON THIS ONE LIVER DERIVED 1485 01:00:47,560 --> 01:00:49,800 FACTOR, YOU EXERCISE, IT GOES 1486 01:00:49,800 --> 01:00:51,000 UP, IT'S COMING FROM THE LIVER 1487 01:00:51,000 --> 01:00:53,320 AND WE WANTED TO KNOW IS IT 1488 01:00:53,320 --> 01:00:54,520 ASSOCIATED WITH THAT BENEFIT. 1489 01:00:54,520 --> 01:00:56,680 HERE I'M SHOWING YOU IN ANOTHER 1490 01:00:56,680 --> 01:00:58,760 GROUP OF OLD MICE WE EXERCISE, 1491 01:00:58,760 --> 01:01:02,200 IT IS HIGHER, THIS IS JUST 1492 01:01:02,200 --> 01:01:03,120 MEASUREMENT WESTERN BLOT IT IS 1493 01:01:03,120 --> 01:01:06,320 HIGHER IN ANIMALS THAT RUN. WE 1494 01:01:06,320 --> 01:01:08,000 CORRELATED IT SO THAT HIGHER 1495 01:01:08,000 --> 01:01:09,600 LEVELS IN THE BLOOD OF THIS 1496 01:01:09,600 --> 01:01:12,640 FACTOR CORRELATE WITH LESS ROARS 1497 01:01:12,640 --> 01:01:14,320 IN THAT WATER SO NICE 1498 01:01:14,320 --> 01:01:16,000 ASSOCIATION. WE HAD ACCESS TO 1499 01:01:16,000 --> 01:01:18,040 BLOOD FROM ELDERLY INDIVIDUALS, 1500 01:01:18,040 --> 01:01:20,880 OTHER AGE 70 THAT HAD FIT BITS 1501 01:01:20,880 --> 01:01:22,080 FOR A MONTH AND LOOKED AT THEIR 1502 01:01:22,080 --> 01:01:24,720 ACTIVITY. WE ALSO SAW THAT THE 1503 01:01:24,720 --> 01:01:25,960 MORE ACTIVE INDIVIDUALS, WE USE 1504 01:01:25,960 --> 01:01:27,520 SPORTS MEDICINE CUT OFFS FOR 1505 01:01:27,520 --> 01:01:28,920 THIS, THE MORE ACTIVE THE 1506 01:01:28,920 --> 01:01:30,320 ELDERLY INDIVIDUAL, THE HIGHER 1507 01:01:30,320 --> 01:01:34,080 THE LEVEL OF GPLD 1. IN MY LAB 1508 01:01:34,080 --> 01:01:38,960 WE USED HUMAN DATA AS SORT OF 1509 01:01:38,960 --> 01:01:40,960 LIKE FILTERS FOR WHICH FACTORS 1510 01:01:40,960 --> 01:01:43,240 WE PURSUE. ONLY PURSUING ONES WE 1511 01:01:43,240 --> 01:01:44,600 IDENTIFY FROM ANIMAL MODELS THAT 1512 01:01:44,600 --> 01:01:45,960 WE ALSO SEE CORRESPONDING 1513 01:01:45,960 --> 01:01:50,000 CHANGES IN THE HUMANS AS WELL. 1514 01:01:50,000 --> 01:01:51,680 WE GOT EXCITED. THERE'S NICE 1515 01:01:51,680 --> 01:01:52,680 ASSOCIATIONS BETWEEN LIVER 1516 01:01:52,680 --> 01:01:54,280 FACTOR AND SORT OF FUNCTION AND 1517 01:01:54,280 --> 01:01:56,080 SEEMS RELEVANT IN HUMANSS. SO 1518 01:01:56,080 --> 01:01:57,720 WHAT ABOUT IT? CAN WE INCREASE 1519 01:01:57,720 --> 01:02:00,360 IT THEN? CAN YOU CONFER SOME 1520 01:02:00,360 --> 01:02:01,240 BENEFIT THROUGH INDIVIDUAL 1521 01:02:01,240 --> 01:02:02,800 FACTORS THAT ARE INDUCED BY 1522 01:02:02,800 --> 01:02:04,160 EXERCISE? THE FIRST THING WE 1523 01:02:04,160 --> 01:02:05,400 WANTED TO KNOW IS WHERE IS THIS 1524 01:02:05,400 --> 01:02:08,160 FACTOR COMING FROM, AND IS IT 1525 01:02:08,160 --> 01:02:11,400 GOING UP IN ANY PARTICULAR 1526 01:02:11,400 --> 01:02:14,440 TISSUE? WE KNEW IT WAS 1527 01:02:14,440 --> 01:02:16,800 PREDOMINANTLY LIVER DRIVE, WE 1528 01:02:16,800 --> 01:02:17,880 LOOKED ACROSS HE CAN 1529 01:02:17,880 --> 01:02:19,120 PRESENTATION LUNG FAT SPLEEN 1530 01:02:19,120 --> 01:02:20,800 BRAIN HEART AND SAW HIGHEST 1531 01:02:20,800 --> 01:02:22,440 EXPRESSION IN LIVER. WHEN WE 1532 01:02:22,440 --> 01:02:24,760 LOOK AT AFTER EXERCISE, ONLY 1533 01:02:24,760 --> 01:02:25,880 WENT UP IN THE LIVER. SO IT 1534 01:02:25,880 --> 01:02:28,640 REALLY IS COMING FROM THE LIVER. 1535 01:02:28,640 --> 01:02:30,320 SO REMEMBER I SAID THAT WE USE 1536 01:02:30,320 --> 01:02:31,720 THESE MOUSE MODELS BECAUSE WE 1537 01:02:31,720 --> 01:02:33,680 ARE ABLE TO MANIPULATE AND USE 1538 01:02:33,680 --> 01:02:35,920 GENE EDITING AND MOLECULAR 1539 01:02:35,920 --> 01:02:38,920 BIOLOGY TO DO THEM. SO WE USED A 1540 01:02:38,920 --> 01:02:40,360 TRICK THAT IMMUNOLOGISTS USE. 1541 01:02:40,360 --> 01:02:43,160 WHAT WE DID IS MAKE A LITTLE 1542 01:02:43,160 --> 01:02:47,000 JUST CIRCULAR DNA THAT ENCODES 1543 01:02:47,000 --> 01:02:47,600 YOUR SOMEWHERE GENE OF INTEREST 1544 01:02:47,600 --> 01:02:48,840 IN THIS PARTICULAR CASE OR 1545 01:02:48,840 --> 01:02:51,520 ENZYME, GPLD 1. WHAT YOU CAN DO 1546 01:02:51,520 --> 01:02:53,200 WITH A LARGE VOLUME, JUST INJECT 1547 01:02:53,200 --> 01:02:55,040 THIS INTO THE BLOODSTREAM OF A 1548 01:02:55,040 --> 01:02:56,400 MOUSE AND BECAUSE IT IS A LARGE 1549 01:02:56,400 --> 01:02:58,200 VOLUME IT GETS TAKEN UP INTO THE 1550 01:02:58,200 --> 01:02:59,880 LIVER. AND THEN THE LIVER STARTS 1551 01:02:59,880 --> 01:03:02,760 MAKING THE PROTEIN FOR YOU. AND 1552 01:03:02,760 --> 01:03:04,320 IT STARTS SPITTING OUT INTO THE 1553 01:03:04,320 --> 01:03:05,760 BLOOD SO WE ARE ABLE TO MIMIC 1554 01:03:05,760 --> 01:03:08,720 THAT EXERCISE EFFECT BY USING IN 1555 01:03:08,720 --> 01:03:11,160 A WAY THIS GENE EDITING APPROACH 1556 01:03:11,160 --> 01:03:13,880 OR OVEREXPRESSION APPROACH. O SO 1557 01:03:13,880 --> 01:03:15,680 THREE THINGS, CONTROL, SEPARATE 1558 01:03:15,680 --> 01:03:17,320 PROTEIN NORMALLY NOT IN A MOUSE, 1559 01:03:17,320 --> 01:03:19,760 COMES FROM A JELLY FISH. WE THEN 1560 01:03:19,760 --> 01:03:23,000 PUT PROTEIN OF INTEREST GPLD 1. 1561 01:03:23,000 --> 01:03:26,400 I TOLD YOU IT ACTS AS A SCISSOR 1562 01:03:26,400 --> 01:03:27,640 SO WHAT WE ENDED UP DOING IS 1563 01:03:27,640 --> 01:03:29,120 COMPLETELY TOOK AWAY ITS ABILITY 1564 01:03:29,120 --> 01:03:31,400 TO CUT. WE MADE A MUTATIONS 1565 01:03:31,400 --> 01:03:32,720 FORM ONE LITTLE POINT MUTATION 1566 01:03:32,720 --> 01:03:34,280 AND IT CAN NO LONGER CUT THOSE 1567 01:03:34,280 --> 01:03:36,920 PROTEINS ANY MORE. THEN WE SAID 1568 01:03:36,920 --> 01:03:38,760 WHAT ABOUT BEHAVIOR? SO HERE I'M 1569 01:03:38,760 --> 01:03:40,560 SHOWING YOU THAT CONTROL, AND 1570 01:03:40,560 --> 01:03:42,520 THESE OLDER ANIMALS WERE SMARTER 1571 01:03:42,520 --> 01:03:44,040 TO BEGIN WITH, BUT THEN WHEN WE 1572 01:03:44,040 --> 01:03:45,680 JUST LOOKED AT THESE INDIVIDUAL 1573 01:03:45,680 --> 01:03:48,760 OLDER ANIMALS COMPARED TO GPLD 1574 01:03:48,760 --> 01:03:51,960 1, THE GPLD 1 WAS BETTER. SO IT 1575 01:03:51,960 --> 01:03:53,280 IMPROVED BEHAVIOR A LOT. WHEN 1576 01:03:53,280 --> 01:03:55,400 WE LOOK AT THE ONE THAT CAN NO 1577 01:03:55,400 --> 01:03:57,640 LONGER CUT THE EFFECT WENT AWAY. 1578 01:03:57,640 --> 01:03:59,120 SO ALL WE KNOW IS IT HAS TO BE 1579 01:03:59,120 --> 01:04:00,240 SOME OF THOSE PROTEINS THAT ARE 1580 01:04:00,240 --> 01:04:01,680 COMING. THAT'S ONE PARTS THAT MY 1581 01:04:01,680 --> 01:04:03,040 LAB IS DOING, WE ARE TRYING TO 1582 01:04:03,040 --> 01:04:04,480 FIGURE OUT WHAT THE TARGET CELLS 1583 01:04:04,480 --> 01:04:05,960 ARE, WHAT ARE THE FACTORS THAT 1584 01:04:05,960 --> 01:04:07,560 THEY ARE TARGETING, DO WE WANT 1585 01:04:07,560 --> 01:04:09,480 TO HAVE AS MANY POTENTIAL 1586 01:04:09,480 --> 01:04:11,920 MOLECULAR TARGETS AS POSSIBLE TO 1587 01:04:11,920 --> 01:04:14,160 SEE WHICH MAY BE APPLICABLE AND 1588 01:04:14,160 --> 01:04:15,840 TRANSLATABLE TO HUMAN. I WILL 1589 01:04:15,840 --> 01:04:17,840 END QUICKLY WITH JUST ONE LAST 1590 01:04:17,840 --> 01:04:19,760 THING. ONE THING I GET ASKED A 1591 01:04:19,760 --> 01:04:22,960 LOT IS WE FOCUS ALMOST EXCLUE 1592 01:04:22,960 --> 01:04:24,520 SUVLY ON BIOLOGY OF AGING AND 1593 01:04:24,520 --> 01:04:27,160 THE AGING CONTEXT. WE DON'T GO 1594 01:04:27,160 --> 01:04:28,800 MUCH INTO THE DISEASE. I'M 1595 01:04:28,800 --> 01:04:30,240 ALWAYS ASKED, WELL YOU ARE 1596 01:04:30,240 --> 01:04:32,400 FINDING THESE MOLECULES, DO WE 1597 01:04:32,400 --> 01:04:34,280 HAVE TO TREAT ONLY THE ELDERLY 1598 01:04:34,280 --> 01:04:36,200 OR IS IT POSSIBLE THEY MIGHT 1599 01:04:36,200 --> 01:04:38,080 HAVE SOME BENEFIT EVEN IN THE 1600 01:04:38,080 --> 01:04:39,760 CONTEXT OF DISEASE? SO I HEAR 1601 01:04:39,760 --> 01:04:42,800 THAT A LOT AND A FOURTH QUARTER 1602 01:04:42,800 --> 01:04:43,720 WAS INTERESTED IN ADDRESSING 1603 01:04:43,720 --> 01:04:46,000 THIS. WE USED THIS EXERCISE 1604 01:04:46,000 --> 01:04:48,240 EXAMPLE, THIS MOLECULE, TO ASK, 1605 01:04:48,240 --> 01:04:51,960 WELL, COULD THEN THESE AGING 1606 01:04:51,960 --> 01:04:53,360 FUNDINGS APPLY TO DISEASE 1607 01:04:53,360 --> 01:04:55,160 CONTEXT? WHAT HE DID IS USED AN 1608 01:04:55,160 --> 01:04:56,840 ANIMAL MODEL OF ALZHEIMERS 1609 01:04:56,840 --> 01:04:58,320 DISEASE PATHOLOGY. NOW, THIS 1610 01:04:58,320 --> 01:04:59,680 PATHOLOGY IS VERY AGGRESSIVE AND 1611 01:04:59,680 --> 01:05:02,160 IT HAPPENS WHEN MUCH YOUNGER. IT 1612 01:05:02,160 --> 01:05:04,320 HAPPENS BY THE TIME THEY ARE 1613 01:05:04,320 --> 01:05:05,640 MATURE MAX MIDDLE AGE BEFORE 1614 01:05:05,640 --> 01:05:07,880 THEY EVER HAVE IMPAIRMENTS FOR 1615 01:05:07,880 --> 01:05:11,080 BEING OLD. HE EXERCISED THEM IN 1616 01:05:11,080 --> 01:05:12,000 BEHAVIOR, IN THIS PARTICULAR 1617 01:05:12,000 --> 01:05:13,640 CASE WE USE A DIFFERENT BEHAVIOR 1618 01:05:13,640 --> 01:05:14,880 BUT STILL HIPPOCAMPUS. THESE 1619 01:05:14,880 --> 01:05:16,880 ANIMALS ARE SUPER CURIOUS SO IF 1620 01:05:16,880 --> 01:05:18,560 YOU PUT TWO IDENTICAL OBJECTS 1621 01:05:18,560 --> 01:05:19,760 THEY WILL EXPLORE BOTH. IF YOU 1622 01:05:19,760 --> 01:05:21,680 COME BACK THE NEXT DAY, AND YOU 1623 01:05:21,680 --> 01:05:23,640 JUST PUT A DIFFERENT OBJECT, IF 1624 01:05:23,640 --> 01:05:25,000 THEY REMEMBER THIS ONE THEY WILL 1625 01:05:25,000 --> 01:05:26,160 EXPLORE THE NOVEL ONE MORE SO 1626 01:05:26,160 --> 01:05:27,480 CALL IT A NOVEL OBJECT 1627 01:05:27,480 --> 01:05:29,360 RECOGNITION. THE MORE TIME WITH 1628 01:05:29,360 --> 01:05:31,160 A NOVEL OBJECT THE MORE YOU 1629 01:05:31,160 --> 01:05:32,280 REMEMBER THE OLD OBJECT SO 1630 01:05:32,280 --> 01:05:34,640 METRIC OF MEMORY. WE JUST LOOKED 1631 01:05:34,640 --> 01:05:37,440 AFTER EXERCISE, THESE 1632 01:05:37,440 --> 01:05:38,800 ALZHEIMER'S DISEASE PATHOLOGY 1633 01:05:38,800 --> 01:05:40,040 MODEL THEY SPEND MORE TIME WITH 1634 01:05:40,040 --> 01:05:43,040 THE OBJECT SO BETTER AT MEMORY 1635 01:05:43,040 --> 01:05:45,720 OLD. WE LOOK AT GPLD 1 1636 01:05:45,720 --> 01:05:47,080 EXPRESSION IT WENT UP AND IT 1637 01:05:47,080 --> 01:05:47,960 CORRELATED IN THIS MODEL OF 1638 01:05:47,960 --> 01:05:49,520 DISEASE SO WE ARE LIKE OKAY THE 1639 01:05:49,520 --> 01:05:51,720 SAME MECHANISMS BY EXERCISE ARE 1640 01:05:51,720 --> 01:05:53,440 BEING ENGAGED WHICH IS GOOD. WE 1641 01:05:53,440 --> 01:05:57,400 THEN USED AGAIN OUR MOLECULAR 1642 01:05:57,400 --> 01:06:00,160 CHECK WE OVEREXPRESS FACTOR ONLY 1643 01:06:00,160 --> 01:06:02,160 IN LIVER IN YOUNGER BUT 1644 01:06:02,160 --> 01:06:03,160 ALZHEIMER'S DISEASE PATHOLOGY 1645 01:06:03,160 --> 01:06:05,080 MODELS. WE LOOK AT PATHOLOGIES 1646 01:06:05,080 --> 01:06:06,440 SO THESE ARE PLAQUES WE 1647 01:06:06,440 --> 01:06:07,840 TRADITIONALLY THINK OF IN 1648 01:06:07,840 --> 01:06:09,280 ALZHEIMERS SO WE SEE LESS OF 1649 01:06:09,280 --> 01:06:10,960 THESE AND YOU SEE THEY ARE 1650 01:06:10,960 --> 01:06:12,240 SMALLER SO WE HAVE LESS OF THAT 1651 01:06:12,240 --> 01:06:14,840 A BETA WITHIN THEIR BRAIN. WE 1652 01:06:14,840 --> 01:06:16,200 DID BEHAVIOR, THE FIRST THING IS 1653 01:06:16,200 --> 01:06:18,400 THESE -- THIS ANIMAL MODEL GETS 1654 01:06:18,400 --> 01:06:19,920 SICK SO WE CAN USE THESE WELL 1655 01:06:19,920 --> 01:06:21,320 BEING METRICS AND NORMAL MOUSE 1656 01:06:21,320 --> 01:06:24,840 LIKES TO MAKE THESE CUTE LITTLE 1657 01:06:24,840 --> 01:06:27,120 NESTLETS. BUT ALWAYS MYERS 1658 01:06:27,120 --> 01:06:29,720 MODELS ARE NOT GOOD, ALZHEIMERS 1659 01:06:29,720 --> 01:06:32,160 ARE NOT GOOD ATE. THE ONES 1660 01:06:32,160 --> 01:06:33,760 EXPRESSED IN BLOOD WERE BETTER 1661 01:06:33,760 --> 01:06:35,160 AT MAKING THE LITTLE NESTS. 1662 01:06:35,160 --> 01:06:36,840 WHEN WE LOOK AT NOVEL OBJECT 1663 01:06:36,840 --> 01:06:37,680 LIKE BEFORE THEY ARE IMPAIRED 1664 01:06:37,680 --> 01:06:40,240 THIS MODEL IS IMPAIRED YOU CAN 1665 01:06:40,240 --> 01:06:42,240 MAKE THEM A BIT BETTER, BY JUST 1666 01:06:42,240 --> 01:06:44,600 EXPRESSING THIS LIVER FACTOR. SO 1667 01:06:44,600 --> 01:06:46,240 JUST TO WRAP THIS UP, WE THINK 1668 01:06:46,240 --> 01:06:47,920 THAT WE CAN TRANSFER SOME OF THE 1669 01:06:47,920 --> 01:06:49,480 BENEFIT OF EXERCISE, THIS IS 1670 01:06:49,480 --> 01:06:51,440 REALLY EXCITING FOR THOSE THAT 1671 01:06:51,440 --> 01:06:52,680 CAN'T ACTUALLY EXERCISE. WE 1672 01:06:52,680 --> 01:06:54,120 THINK THE LIVER IS SECRETING 1673 01:06:54,120 --> 01:06:55,280 CERTAIN PROTEINS THAT GO IN. AND 1674 01:06:55,280 --> 01:06:56,840 WE ARE ALSO FINDING THE 1675 01:06:56,840 --> 01:06:58,080 MECHANISMS IN THE BRAIN. WE 1676 01:06:58,080 --> 01:06:59,200 DON'T THINK IT GOES INTO THE 1677 01:06:59,200 --> 01:07:00,720 BRAIN, WE THINK IT MIGHT BE 1678 01:07:00,720 --> 01:07:02,000 WORKING THROUGH THE IMMUNE 1679 01:07:02,000 --> 01:07:03,720 SYSTEM AND VASCULATURE BUT PLACE 1680 01:07:03,720 --> 01:07:04,920 IT IS LIVER IN AN INTERESTING 1681 01:07:04,920 --> 01:07:09,640 POT.POSITION. CAN AFFECTS OF AGG 1682 01:07:09,640 --> 01:07:12,400 BE REVERSEDD? IN ANIMAL MODELS 1683 01:07:12,400 --> 01:07:13,840 ITS CAN. THERE'S CERTAIN 1684 01:07:13,840 --> 01:07:14,880 MANIPULATIONS THAT INVOLVE THE 1685 01:07:14,880 --> 01:07:17,520 BLOOD CAN HAVE A BENEFIT EVEN ON 1686 01:07:17,520 --> 01:07:19,440 -- IN INDIVIDUALS WITH 1687 01:07:19,440 --> 01:07:21,160 ALZHEIMER'S. THERE IS A GROUP 1688 01:07:21,160 --> 01:07:22,960 IN SOUTH KOREA AS WELL AS 1689 01:07:22,960 --> 01:07:24,000 BARCELONA AND SPAIN THAT HAVE 1690 01:07:24,000 --> 01:07:25,360 NICE EVIDENCE. SO WE FIND THIS 1691 01:07:25,360 --> 01:07:27,400 REALLY PROMISING. THAT IS WHERE 1692 01:07:27,400 --> 01:07:29,280 MY LAB IS GOING. WITH THAT, I 1693 01:07:29,280 --> 01:07:30,560 WANT TO THANK NUMBER OF MY LAB, 1694 01:07:30,560 --> 01:07:31,720 THESE ARE THE HAPPY PEOPLE THAT 1695 01:07:31,720 --> 01:07:34,400 ARE THERE. WITH THAT, I THINK WE 1696 01:07:34,400 --> 01:07:40,080 ARE GOING TO TAKE QUESTIONS. 1697 01:07:40,080 --> 01:07:41,760 >>THANK YOU VERY MUCH. THIS IS 1698 01:07:41,760 --> 01:07:47,400 REALLY VERY EXCITING. LET ME 1699 01:07:47,400 --> 01:07:48,440 LOOK THROUGH THE QUESTIONS HERE 1700 01:07:48,440 --> 01:07:54,800 AND PUT THEM IN SOME GROUP SO WE 1701 01:07:54,800 --> 01:08:05,320 CAN GET IT TOGETHER. SO WE HAVE 1702 01:08:09,320 --> 01:08:11,720 A QUESTION ABOUT -- THERE WE 1703 01:08:11,720 --> 01:08:21,000 ARE. SO IS THERE A ROLE FOR THES 1704 01:08:21,000 --> 01:08:25,680 ARE VEER TROLL AND SERTUIN 1705 01:08:25,680 --> 01:08:28,240 DEACETYLATION PATHWAY? THAT IN 1706 01:08:28,240 --> 01:08:32,040 YEAST SEEMS TO HAVE ROSE VEER 1707 01:08:32,040 --> 01:08:33,840 TROLL SEEMS TO HAVE SUBSTANTIAL 1708 01:08:33,840 --> 01:08:36,080 FUNCTION IN TERMS OF AGING. WHAT 1709 01:08:36,080 --> 01:08:38,960 IS THE CURRENT VIEW ABOUT THAT 1710 01:08:38,960 --> 01:08:43,160 WITH REGARD TO THE AN MALL 1711 01:08:43,160 --> 01:08:46,320 STUDIES OR HUMAN AGE -- ANIMAL 1712 01:08:46,320 --> 01:08:46,960 STUDIES ANDOR OR HUMAN AGE 1713 01:08:46,960 --> 01:08:47,200 SOMETHING 1714 01:08:47,200 --> 01:08:51,800 >>I CAN TRY AND THEN SAUL CAN. 1715 01:08:51,800 --> 01:08:55,320 I THINK THAT BEING THE 1716 01:08:55,320 --> 01:08:57,520 ENTHUSIAST ABOUT THE METHYLATION 1717 01:08:57,520 --> 01:09:01,040 OF (INAUDIBLE) RESVERTROL AS YOU 1718 01:09:01,040 --> 01:09:03,080 KNOW IT WAS CONSIDERED THE 1719 01:09:03,080 --> 01:09:04,720 REASON WHY THE FRENCH PEOPLE CAN 1720 01:09:04,720 --> 01:09:08,200 EAT, DRINK SO MUCH WINE AND NOT 1721 01:09:08,200 --> 01:09:10,080 GETTING CARDIOVASCULAR DISEASE. 1722 01:09:10,080 --> 01:09:15,160 THE STUDY IN MICE SHOW THAT 1723 01:09:15,160 --> 01:09:16,560 STRONG STRONG EFFECT IN -- WHEN 1724 01:09:16,560 --> 01:09:21,120 THE MICE WERE FED WITH FAT, FAT 1725 01:09:21,120 --> 01:09:23,760 RICH DIET, THERE WAS INCREMENTAL 1726 01:09:23,760 --> 01:09:29,680 LIFE EXPECTANCY ALSO IN 1727 01:09:29,680 --> 01:09:33,520 PATHOLOGY THAT WITH BASICALLY NO 1728 01:09:33,520 --> 01:09:34,640 EFFECT. THEY WERE FED A NORMAL 1729 01:09:34,640 --> 01:09:38,080 DIET. THEY WERE NOT -- VERY 1730 01:09:38,080 --> 01:09:41,680 LITTLE EFFECT. I HAVE TO TELL 1731 01:09:41,680 --> 01:09:45,520 YOU WE RECENTRY STUDIED THE 1732 01:09:45,520 --> 01:09:46,920 MUSCLE OF THE CALORIE STUDY, THE 1733 01:09:46,920 --> 01:09:48,680 CALORIE STUDY IS THE ONLY STUDY 1734 01:09:48,680 --> 01:09:53,600 IN HUMANS THAT LOOK AT THE FAT 1735 01:09:53,600 --> 01:09:54,960 OF CALORIE RESTRICTION. IN THE 1736 01:09:54,960 --> 01:09:57,280 MUSCLE OF PEOPLE THAT WERE 1737 01:09:57,280 --> 01:09:58,840 CALORIE RESTRICTION, WE SEE 1738 01:09:58,840 --> 01:10:00,840 IMPROVEMENT IN MUSCLE QUALITY 1739 01:10:00,840 --> 01:10:06,640 THAT IS PARALLEL BY 1740 01:10:06,640 --> 01:10:07,800 OVEREXPRESSION OF (INAUDIBLE) 1741 01:10:07,800 --> 01:10:14,480 PATHWAY. SO I THINK THAT WHILE 1742 01:10:14,480 --> 01:10:15,280 RESVERTROL I DON'T THINK IS 1743 01:10:15,280 --> 01:10:17,600 GOING TO WORK I THINK THE SIP 1 1744 01:10:17,600 --> 01:10:18,840 STUDY IS NOT CONCLUDED YET. 1745 01:10:18,840 --> 01:10:21,360 >>JUST TO FOLLOW-UP A LITTLE 1746 01:10:21,360 --> 01:10:23,280 BIT, AS THE LAB IS ENGAGING IN 1747 01:10:23,280 --> 01:10:24,840 MORE INTERVENTION WE WAS THE 1748 01:10:24,840 --> 01:10:26,360 YOUNG BLOOD, OLD BLOOD, 1749 01:10:26,360 --> 01:10:27,960 EXERCISE, CALORIC RESTRICTION, 1750 01:10:27,960 --> 01:10:29,360 THEY ALL ENGAGE DIFFERENT 1751 01:10:29,360 --> 01:10:30,800 MECHANISMS AT LEAST WHEN WE LOOK 1752 01:10:30,800 --> 01:10:34,640 INTO THE TISSUE. SO WHEN WE LOOK 1753 01:10:34,640 --> 01:10:36,760 AT THIS BROAD SEQUENCING OF 1754 01:10:36,760 --> 01:10:38,840 EXERCISE, SAY IN THE BRAIN, WE 1755 01:10:38,840 --> 01:10:43,760 SEE MITOCHONDRIA, WE SEE MPTOR 1756 01:10:43,760 --> 01:10:45,440 SIGNATURES. WHEN WE LOOK AT 1757 01:10:45,440 --> 01:10:49,480 YOUNG BLOOD WE SAW KREB AND KREB 1758 01:10:49,480 --> 01:10:50,080 ACTIVATION, DIFFERENT 1759 01:10:50,080 --> 01:10:51,920 TRANSCRIPTION FACTORS IN THAT 1760 01:10:51,920 --> 01:10:53,720 CONTEXT. SO HEARING WHAT LUIGI 1761 01:10:53,720 --> 01:10:55,080 SAID IN TERMS OF CALORIC 1762 01:10:55,080 --> 01:10:56,720 RESTRICTION AND ENGAGING THE 1763 01:10:56,720 --> 01:10:57,600 PATHWAYS, THAT P GOES WITH WHAT 1764 01:10:57,600 --> 01:10:59,760 WE ARE SEEING WHICH IS DIFFERENT 1765 01:10:59,760 --> 01:11:01,080 INTERVENTIONS AT LEAST AT THE 1766 01:11:01,080 --> 01:11:04,840 POINT OF TISSUE ENGAGE DIFFERENT 1767 01:11:04,840 --> 01:11:05,360 PATHWAYS. 1768 01:11:05,360 --> 01:11:07,200 >>HERE IS A QUESTION, YOU THINK 1769 01:11:07,200 --> 01:11:12,640 THERE IS A LINK IN SOME WAY 1770 01:11:12,640 --> 01:11:17,640 BETWEEN THE PROPOSE SIRTUIN 1771 01:11:17,640 --> 01:11:21,360 MECHANISM AND SEE ONE ALPHA 1772 01:11:21,360 --> 01:11:23,480 LEADING THE MITOCHONDRIAL 1773 01:11:23,480 --> 01:11:25,120 BIOGENESIS, IS THERE A LINK 1774 01:11:25,120 --> 01:11:28,120 BETWEEN THAT AND WHAT YOU ARE 1775 01:11:28,120 --> 01:11:30,480 OBSERVING WITH THE 1776 01:11:30,480 --> 01:11:33,120 >>ABSOLUTELY. WELL, I DON'T 1777 01:11:33,120 --> 01:11:36,760 KNOW ABOUT EXPERIMENTAL, SAUL 1778 01:11:36,760 --> 01:11:39,160 WILL ADDRESS THAT BUT ABSOLUTELY 1779 01:11:39,160 --> 01:11:42,160 WE SEE A IN THE STUDY THAT WAS 1780 01:11:42,160 --> 01:11:45,560 MENTION BEFORE, WHAT WE SEE IS 1781 01:11:45,560 --> 01:11:47,440 AN INCREMENT IN MITOCHONDRIAL 1782 01:11:47,440 --> 01:11:50,560 BIOGENESIS THAT IS DRIVEN BY PDC 1783 01:11:50,560 --> 01:11:53,440 1 ALPHA IN INCREMENTING IN 1784 01:11:53,440 --> 01:11:55,800 TRANSCRIPTION FACTOR THAT ACT AT 1785 01:11:55,800 --> 01:11:58,920 LEVEL OF MITOCHONDRIAL DNA. SO 1786 01:11:58,920 --> 01:12:02,040 WE THINK THAT MITOCHONDRIA 1787 01:12:02,040 --> 01:12:04,520 REALLY PLAY IMPORTANT ROLE IN 1788 01:12:04,520 --> 01:12:07,200 THE POSSIBLE BENEFICIAL EFFECT 1789 01:12:07,200 --> 01:12:09,880 OF SERTU ISHN ACTIVATORS. 1790 01:12:09,880 --> 01:12:12,200 >>I GUESS BROADRY IN THE 1791 01:12:12,200 --> 01:12:15,640 INTERVENTION WE ARE SEEING, 1792 01:12:15,640 --> 01:12:19,080 ABSOLUTELY MITOCHONDRIA 1793 01:12:19,080 --> 01:12:21,360 SIGNATURES COME UP AUTOPHAGY 1794 01:12:21,360 --> 01:12:22,440 SIGNATURES COME UP, ONCE YOU GET 1795 01:12:22,440 --> 01:12:23,920 TO LEVEL OF CELLULAR MECHANISMS 1796 01:12:23,920 --> 01:12:24,880 YOU ARE ABSOLUTELY ENGAGING 1797 01:12:24,880 --> 01:12:27,200 THEM. WHAT WE SEE FOR EXAMPLE, 1798 01:12:27,200 --> 01:12:29,960 IN SOMETHING LIKE EXERCISE LOT 1799 01:12:29,960 --> 01:12:32,600 OF PEOPLE ALSO SEEN MUSCLE 1800 01:12:32,600 --> 01:12:34,400 DERIVED FACTORS, LIVE DERIVED 1801 01:12:34,400 --> 01:12:35,400 FACTORS IN THOSE CONTEXT 1802 01:12:35,400 --> 01:12:37,360 ABSOLUTELY. TRYING TO IDENTIFY 1803 01:12:37,360 --> 01:12:39,720 MASTER REGULATORS WHAT REGULATES 1804 01:12:39,720 --> 01:12:41,800 THE FACT YOU ARE SPINNING OUT SO 1805 01:12:41,800 --> 01:12:43,480 MANY LIVER FACTORS AND A LOT OF 1806 01:12:43,480 --> 01:12:46,680 THINGS LIKE P BGC ALPHA A LOT OF 1807 01:12:46,680 --> 01:12:47,480 REGULATORS ARE COMING UP AS 1808 01:12:47,480 --> 01:12:50,800 WELL. 1809 01:12:50,800 --> 01:12:59,840 >>HERE IS ANOTHER SEEMS AS IF 1810 01:12:59,840 --> 01:13:03,400 THE GENERAL VIEW ABOUT AGING, IT 1811 01:13:03,400 --> 01:13:08,920 IS PROBABLY A GOOD THING, TO EAT 1812 01:13:08,920 --> 01:13:13,320 LESS, EXERCISE MORE, PROBABLY 1813 01:13:13,320 --> 01:13:18,040 EAT LESS RED MEAT THAN FISH AND 1814 01:13:18,040 --> 01:13:21,120 VEGETABLES AND DON'T TAKE DRUGS 1815 01:13:21,120 --> 01:13:22,680 DON'T SMOKE. DON'T DRINK TOO 1816 01:13:22,680 --> 01:13:23,960 MUCH AND BE EXPOSED TO THE COLD 1817 01:13:23,960 --> 01:13:27,960 A LITTLE BIT BIT. MORE THAN ONE 1818 01:13:27,960 --> 01:13:31,960 MIGHT NORMALLY DO. IF THOSE HAVE 1819 01:13:31,960 --> 01:13:34,640 THOSE ASPECTS BEEN EXPLORED IN 1820 01:13:34,640 --> 01:13:39,160 EITHER OF YOUR WORKS? LUIGI, 1821 01:13:39,160 --> 01:13:40,640 FROM THE STANDPOINT OF 1822 01:13:40,640 --> 01:13:40,960 EPIDEMIOLOGY? 1823 01:13:40,960 --> 01:13:43,600 >>WE WILL STUDY ALL OF THE 1824 01:13:43,600 --> 01:13:53,880 ABOVE. OF COURSE. I THINK THAT 1825 01:13:53,880 --> 01:13:55,440 STARTING WITH DIET, DIET IS 1826 01:13:55,440 --> 01:13:56,200 PROBABLY THE MOST IMPORTANT 1827 01:13:56,200 --> 01:13:59,600 INTERVENTION WE CAN DO. IF YOU 1828 01:13:59,600 --> 01:14:02,040 CAN IDENTIFY WHAT ARE THE FACTOR 1829 01:14:02,040 --> 01:14:03,720 ACESORBIATED WITH THE BENEFICIAL 1830 01:14:03,720 --> 01:14:05,160 EFFECT OF GOOD DIET, THE PROBLEM 1831 01:14:05,160 --> 01:14:07,120 IS THAT WE DON'T KNOW VERY WELL 1832 01:14:07,120 --> 01:14:16,040 HOW TO MEASURE DIET IN HUMANS. 1833 01:14:16,040 --> 01:14:18,360 CHANGING THE DIET OF PEOPLE IS 1834 01:14:18,360 --> 01:14:21,360 CHALLENGCHALLENGING. THE CALORIY 1835 01:14:21,360 --> 01:14:23,440 REDUCE THE CALORIC INTAKE WE ARE 1836 01:14:23,440 --> 01:14:25,920 CALLING PEOPLE TWICE A WEEK. SO 1837 01:14:25,920 --> 01:14:27,880 THAT WAS PRETTY INTENSE AND THEY 1838 01:14:27,880 --> 01:14:32,840 WERE NOT ABLE TO REACH THE LEVEL 1839 01:14:32,840 --> 01:14:34,360 OF WHAT THEY WANTED. I THINK WE 1840 01:14:34,360 --> 01:14:39,640 SEE CERTAINLY BENEFICIAL EFFECT 1841 01:14:39,640 --> 01:14:40,600 OF THE (INAUDIBLE) DIET 1842 01:14:40,600 --> 01:14:44,280 ASSOCIATED WITH REDUCE RISK OF 1843 01:14:44,280 --> 01:14:45,520 CARDIOVASCULAR DISEASE, SUCH AS 1844 01:14:45,520 --> 01:14:47,080 BASIC MORTALITY, RECENTLY A 1845 01:14:47,080 --> 01:14:48,960 PAPER SHOWING ALSO THAT THERE IS 1846 01:14:48,960 --> 01:14:51,680 AN EFFECT ON PREVENTION OF 1847 01:14:51,680 --> 01:14:54,520 CANCER. WE KNOW THAT PHYSICAL 1848 01:14:54,520 --> 01:14:57,760 ACTIVITY NOT ONLY INCREASE 1849 01:14:57,760 --> 01:15:00,520 LONGEVITY BUT INCREASE ACTIVE 1850 01:15:00,520 --> 01:15:03,960 LIFE EXPECTANCY. IT IS REALLY 1851 01:15:03,960 --> 01:15:06,440 EXPAND THE PORTION OF LIFE THAT 1852 01:15:06,440 --> 01:15:07,840 IS WITHOUT DISEASE AND 1853 01:15:07,840 --> 01:15:09,960 DISABILITY. SO EXERCISE I ALWAYS 1854 01:15:09,960 --> 01:15:13,440 SAY IS A JEWEL, I LIKE TO GIVE 1855 01:15:13,440 --> 01:15:15,240 TO EVERYBODY BECAUSE IT IS GOING 1856 01:15:15,240 --> 01:15:18,400 TO GIVE SO MUCH BENCH THERE IS 1857 01:15:18,400 --> 01:15:19,520 OTHER RESPECT COMPARED TO WHAT 1858 01:15:19,520 --> 01:15:22,120 THE ONE YOU WERE TALKING ABOUT, 1859 01:15:22,120 --> 01:15:26,320 PEOPLE DON'T THINK ABOUT, ONE IS 1860 01:15:26,320 --> 01:15:27,560 SLEEP. THE IMPORTANCE OF SLEEP 1861 01:15:27,560 --> 01:15:30,680 IS COMING OUT INCREDIBLY STRONG. 1862 01:15:30,680 --> 01:15:33,560 BOTH IN THE TERMS OF OUR 1863 01:15:33,560 --> 01:15:36,240 INTERNAL CLOCK, THE CLOCK THAT 1864 01:15:36,240 --> 01:15:38,120 IS IN OUR ORGANISM BUT ALSO IN 1865 01:15:38,120 --> 01:15:42,480 TERMS OF THE RECOVERY, THE 1866 01:15:42,480 --> 01:15:44,280 ORGANISM GO THROUGH. WE DO KNOW 1867 01:15:44,280 --> 01:15:48,840 FOR EXAMPLE THAT PEOPLE THAT 1868 01:15:48,840 --> 01:15:51,920 SLEEP CONTINUOUSLY LESS THAN 7 1869 01:15:51,920 --> 01:15:53,920 HOURS A DAY, TEND TO HAVE 1870 01:15:53,920 --> 01:15:56,120 ACCELERATED ACCUMULATION OF BETA 1871 01:15:56,120 --> 01:15:59,000 AMYLOID AND PERHAPS EVEN TAU AND 1872 01:15:59,000 --> 01:16:03,360 THE REASON ACCELERATED COGNITIVE 1873 01:16:03,360 --> 01:16:09,000 DECLINE. I SAY THERE ARE PEOPLE 1874 01:16:09,000 --> 01:16:12,800 PEOPLE CAN DO TO SLOW DOWN THEIR 1875 01:16:12,800 --> 01:16:15,120 AGING NOW. ONE IMPORTANT THING, 1876 01:16:15,120 --> 01:16:16,320 I TALKED EXERCISE BEFORE, IT IS 1877 01:16:16,320 --> 01:16:18,960 NOT THAT YOU NEED TO GO OUT AND 1878 01:16:18,960 --> 01:16:21,280 JOG FOR THREE HOURS. THE REAL 1879 01:16:21,280 --> 01:16:23,480 DIFFERENCE IS BETWEEN SEDENTARY 1880 01:16:23,480 --> 01:16:24,720 STATE AND WALKING TEN MINUTE. 1881 01:16:24,720 --> 01:16:27,280 THAT DIFFERENCE IS HUGE. IF YOU 1882 01:16:27,280 --> 01:16:30,040 EXERCISE MORE IT IS BETTER BUT I 1883 01:16:30,040 --> 01:16:31,960 THINK THE PUBLIC MESSAGE IS 1884 01:16:31,960 --> 01:16:34,920 DON'T STAY IN FRONT OF THE 1885 01:16:34,920 --> 01:16:37,600 TELEVISION OR THE -- GET OUT 1886 01:16:37,600 --> 01:16:42,000 ROUND THE BLOCK AND THAT WILL 1887 01:16:42,000 --> 01:16:43,880 IMPROVE INCREDIBLE BENEFIT TRUE 1888 01:16:43,880 --> 01:16:45,760 IN ANIMAL MODEL AS WELL AS 1889 01:16:45,760 --> 01:16:46,040 HUMANS. 1890 01:16:46,040 --> 01:16:49,880 >>FOLLOWING UP ON THE ANIMAL 1891 01:16:49,880 --> 01:16:51,240 MODEL, MY STUDENTS AND POST-DOCS 1892 01:16:51,240 --> 01:16:52,400 GOT TO ME BECAUSE WHEN WE THINK 1893 01:16:52,400 --> 01:16:56,120 ABOUT THE ELDERLY POPULATION, 1894 01:16:56,120 --> 01:16:57,280 OFTENTIMES THEY CAN'T EXERCISE 1895 01:16:57,280 --> 01:16:58,680 AND YOU ARE NOT GOING TO PUT 1896 01:16:58,680 --> 01:17:00,600 THEM ON CALORIC RESTRICTION. SO 1897 01:17:00,600 --> 01:17:03,400 HOW DO WE START CONFERRING THAT? 1898 01:17:03,400 --> 01:17:04,880 THAT IS ONE OF THE ASPECTS WE 1899 01:17:04,880 --> 01:17:06,200 HAVE BEEN DOING AND I SHARE THE 1900 01:17:06,200 --> 01:17:08,680 EXERCISE STORY. IF WE TAKE BLOOD 1901 01:17:08,680 --> 01:17:10,160 FROM SHORT TERM CALORIC 1902 01:17:10,160 --> 01:17:11,240 RESTRICTION OLD IN LIFE AND 1903 01:17:11,240 --> 01:17:13,080 INJECT IT, YES, THERE'S 1904 01:17:13,080 --> 01:17:14,600 BENEFITS. AND IT IS JUST 1905 01:17:14,600 --> 01:17:16,400 ENGAGING SOMETHING DIFFERENT. 1906 01:17:16,400 --> 01:17:18,040 THE FACTORS ARE COMING FROM 1907 01:17:18,040 --> 01:17:19,200 DIFFERENT PLACES. I THINK ABOUT 1908 01:17:19,200 --> 01:17:20,000 OTHER THINGS, I HAVE BEEN 1909 01:17:20,000 --> 01:17:22,120 THINKING A LOT ABOUT THE HUMAN 1910 01:17:22,120 --> 01:17:23,440 CONDITION LATE IN LIFE. IT IS 1911 01:17:23,440 --> 01:17:25,640 NOT JUST ABOUT EXERCISE CALORIC 1912 01:17:25,640 --> 01:17:27,000 RESTRICTION, THERE'S SLEEP AN 1913 01:17:27,000 --> 01:17:29,280 WHAT ABOUT LIKE SOCIAL 1914 01:17:29,280 --> 01:17:30,080 ISOLATION, VERSUS SOCIAL 1915 01:17:30,080 --> 01:17:31,560 INTERACTION. WE KNOW THAT THAT 1916 01:17:31,560 --> 01:17:33,520 IS ALSO ASSOCIATED AND 1917 01:17:33,520 --> 01:17:34,920 CORRELATED WITH HEALTH SPAN AND 1918 01:17:34,920 --> 01:17:37,400 AGE. SO ANYTHING THAT IMPACTS AN 1919 01:17:37,400 --> 01:17:39,680 ORGANISM, I THINK WILL HAVE SOME 1920 01:17:39,680 --> 01:17:40,560 MECHANISMS THAT I THINK WE CAN 1921 01:17:40,560 --> 01:17:48,560 LEVERAGE. 1922 01:17:48,560 --> 01:17:50,960 >>I MISSED THE POINT. WHAT 1923 01:17:50,960 --> 01:17:53,040 ABOUT THE QUESTION OF COLD AND 1924 01:17:53,040 --> 01:17:57,040 BROWN FAT, HAVE YOU INVESTIGATED 1925 01:17:57,040 --> 01:17:57,200 THAT 1926 01:17:57,200 --> 01:17:58,440 >>IT WAS A BEAUTIFUL QUESTION 1927 01:17:58,440 --> 01:18:00,640 BUT WE HAVE NOT INVESTIGATED 1928 01:18:00,640 --> 01:18:03,200 THAT. I THINK SLIGHT UNCOUPLING 1929 01:18:03,200 --> 01:18:10,720 SHOULD BE REALLY GOOD BECAUSE 1930 01:18:10,720 --> 01:18:12,760 THE OXYGEN RADICALS BUT WE HAVE 1931 01:18:12,760 --> 01:18:14,240 NOT DONE THAT. I THINK THAT WHAT 1932 01:18:14,240 --> 01:18:16,160 I CAN TELL YOU IS PEOPLE THAT 1933 01:18:16,160 --> 01:18:17,720 LIVE LONGER TEND TO BE A LITTLE 1934 01:18:17,720 --> 01:18:21,920 BIT COLDER. I THINK YOU LOOK AT 1935 01:18:21,920 --> 01:18:23,040 INTERNAL INNER TEMPERATURE IN 1936 01:18:23,040 --> 01:18:26,760 THE BLSA PARTICIPANT, THOSE THAT 1937 01:18:26,760 --> 01:18:28,480 HAVE LOWER INNER TEMPERATURE 1938 01:18:28,480 --> 01:18:31,280 HAVE LOWER MORTALITY AND TEND TO 1939 01:18:31,280 --> 01:18:33,400 HAVE BETTER PHYSICAL FUNCTION. 1940 01:18:33,400 --> 01:18:35,080 IT COULD BE SOMETHING THERE, BUT 1941 01:18:35,080 --> 01:18:40,560 I'M NOT SURE THERE THIS HAHN 1942 01:18:40,560 --> 01:18:48,360 STUDY. REGENERATION AND STEM 1943 01:18:48,360 --> 01:18:50,040 CELL FUNCTION IN TERMS OF ACUTE 1944 01:18:50,040 --> 01:18:51,840 COLD, TIMING HAS TO DO WITH IT 1945 01:18:51,840 --> 01:18:53,560 SO IT CAN'T BE CHRONIC, THAT 1946 01:18:53,560 --> 01:18:54,800 BECOMES DETRIMENTAL, THE AMOUNT 1947 01:18:54,800 --> 01:18:56,720 OF COLD YOU GIVE THESE 1948 01:18:56,720 --> 01:18:58,200 ANIMALLINGS HAS A HUGE EFFEC EF 1949 01:18:58,200 --> 01:18:59,680 NOT SURE IF IT TRANSLATES TO ALL 1950 01:18:59,680 --> 01:19:01,840 TISSUE OR NOT, THERE'S SOME 1951 01:19:01,840 --> 01:19:03,640 EVIDENCE WHERE IN SORT OF HUMAN 1952 01:19:03,640 --> 01:19:05,000 CONDITIONS, IF THEY DO IT IN THE 1953 01:19:05,000 --> 01:19:07,120 WRONG WAY CAN BE DETRIMENTAL FOR 1954 01:19:07,120 --> 01:19:07,760 COGNITIVE FUNCTION AT LEAST IN 1955 01:19:07,760 --> 01:19:09,360 THE SHORT TERM. SO I THINK THIS 1956 01:19:09,360 --> 01:19:11,520 ONE WILL BE A LITTLE MORE 1957 01:19:11,520 --> 01:19:12,520 NUANCED BUT THERE ARE GROUPS IN 1958 01:19:12,520 --> 01:19:13,920 THE ANIMAL DOING ANIMAL 1959 01:19:13,920 --> 01:19:15,840 EXPERIMENTS IN THE CONTEXT OF 1960 01:19:15,840 --> 01:19:17,240 REGENERATION. THERE'S PROMISING 1961 01:19:17,240 --> 01:19:19,560 STUFF THERE. 1962 01:19:19,560 --> 01:19:29,000 >>HERE ARE SOME QUESTIONS ABOUT 1963 01:19:29,000 --> 01:19:29,280 GPD 1. 1964 01:19:29,280 --> 01:19:30,800 >>THE ENZYME. 1965 01:19:30,800 --> 01:19:32,760 [LAUGHTER] 1966 01:19:32,760 --> 01:19:34,840 >>IS THE LIVER THE ONLY SOURCE 1967 01:19:34,840 --> 01:19:35,760 OF IT? 1968 01:19:35,760 --> 01:19:37,960 >>SO NO, IT IS -- THE 1969 01:19:37,960 --> 01:19:39,080 PREDOMINANT SOURCE OF IT BUT IT 1970 01:19:39,080 --> 01:19:41,120 IS EXPRESSED IN P OTHER TISSUES 1971 01:19:41,120 --> 01:19:42,720 AND KRILLS. IT IS JUST THAT 1972 01:19:42,720 --> 01:19:44,720 WHEN WE LOOKED AT EXERCISE IT 1973 01:19:44,720 --> 01:19:47,520 WAS THE ONLY TISSUE THAT 1974 01:19:47,520 --> 01:19:49,240 ACTUALLY GOT INDUCED. THE 1975 01:19:49,240 --> 01:19:50,880 HIGHEST EXPRESSION PREDOMINANTLY 1976 01:19:50,880 --> 01:19:52,240 IN THE LIVER AND AFTER EXERCISE 1977 01:19:52,240 --> 01:19:54,400 IT WAS THE ONLY ONE ELEVATED AND 1978 01:19:54,400 --> 01:19:55,360 THAT ONE IS SECRETED TO THE 1979 01:19:55,360 --> 01:19:56,920 BLOOD. 1980 01:19:56,920 --> 01:20:03,560 >>SO DO YOU THINK PEOPLE WHO 1981 01:20:03,560 --> 01:20:07,240 HAVE CHRONIC LIVER DISEASE WHO 1982 01:20:07,240 --> 01:20:12,440 DON'T EXERCISE TOO MUCH, COULD 1983 01:20:12,440 --> 01:20:14,320 GPD 1 BE A FACTOR CONTRIBUTING 1984 01:20:14,320 --> 01:20:16,680 TO THEIR COGNITIVE DECLINE? 1985 01:20:16,680 --> 01:20:20,000 >>YES. I SHOULD MENTION, THIS 1986 01:20:20,000 --> 01:20:21,600 FACTOR ACTUALLY DOESN'T CHANGE 1987 01:20:21,600 --> 01:20:23,040 WITH AGE. SO WE ARE NOT LOSING 1988 01:20:23,040 --> 01:20:24,720 IT AS WE ARE GETTING OLDER. SO 1989 01:20:24,720 --> 01:20:26,720 WE DON'T REALLY THINK IT IS 1990 01:20:26,720 --> 01:20:31,000 ENGAGING NECESSARILY LIKE 1991 01:20:31,000 --> 01:20:32,400 PROJERONIC MECHANISMS. THIS IS 1992 01:20:32,400 --> 01:20:34,280 JUST INDUCED BY EXERCISE. AND IT 1993 01:20:34,280 --> 01:20:37,880 IS REALLY ACROSS AGES, WHY IT 1994 01:20:37,880 --> 01:20:38,960 CAN WORK IN SOME OF THESE 1995 01:20:38,960 --> 01:20:40,720 DISEASE MODELS. SO I'M NOT SURE 1996 01:20:40,720 --> 01:20:42,640 WHETHER IT WOULD -- I DON'T HAVE 1997 01:20:42,640 --> 01:20:45,600 IF IT IS CONTRIBUTING TO THAT 1998 01:20:45,600 --> 01:20:46,920 DECLINE BECAUSE ITS LEVELS ARE 1999 01:20:46,920 --> 01:20:48,160 STEADY STATE THROUGH AGING, IT 2000 01:20:48,160 --> 01:20:49,720 IS REALLY A BOOST WE ARE SEEING. 2001 01:20:49,720 --> 01:20:50,560 THAT IS A LITTLE BIT DIFFERENT 2002 01:20:50,560 --> 01:20:52,920 OF THE MECHANISM THAN LIKE YOUNG 2003 01:20:52,920 --> 01:20:53,120 BLOOD. 2004 01:20:53,120 --> 01:20:56,080 >>LEVEL OF THE STUDY STATE -- 2005 01:20:56,080 --> 01:20:58,120 >>SO LIKE WHETHER YOU ARE YOUNG 2006 01:20:58,120 --> 01:21:00,240 OR OLD YOUR LEVEL IS NOT 2007 01:21:00,240 --> 01:21:01,800 CHANGING, JUST WHEN YOU ENGAGE 2008 01:21:01,800 --> 01:21:03,840 IN EXERCISE IT GOES UP AND THAT 2009 01:21:03,840 --> 01:21:05,400 INCREASE IS WHAT IS CAUSING SOME 2010 01:21:05,400 --> 01:21:06,640 OF THESE BENEFITS WE SEE. 2011 01:21:06,640 --> 01:21:09,680 >>AND IT IS UNAFFECTED BY 2012 01:21:09,680 --> 01:21:11,000 CHRONIC LIVER DISEASE. 2013 01:21:11,000 --> 01:21:12,520 >>THAT I DON'T KNOW, THAT IS A 2014 01:21:12,520 --> 01:21:13,840 GREAT QUESTION. I DO KNOW IT IS 2015 01:21:13,840 --> 01:21:16,200 IMPACTED BY THINGS LIKE DIABETES 2016 01:21:16,200 --> 01:21:17,520 AND ANYTHING THAT HAS TO DO SORT 2017 01:21:17,520 --> 01:21:19,280 OF WITH THAT INSULIN PATHWAY, WE 2018 01:21:19,280 --> 01:21:20,720 HAVE TO FIGURE OUT LIKE HOW DOES 2019 01:21:20,720 --> 01:21:22,040 IT WORK IN THAT CONTEXT. BECAUSE 2020 01:21:22,040 --> 01:21:23,160 THAT IS VERY DIFFERENT. 2021 01:21:23,160 --> 01:21:24,240 ABSOLUTELY. THAT IS A VERY GOOD 2022 01:21:24,240 --> 01:21:31,240 POINT. SOUNDS LIKE MUCH OF THE 2023 01:21:31,240 --> 01:21:33,760 WORK BOTH OF YOU PRESENTED BUT 2024 01:21:33,760 --> 01:21:39,360 PERHAPS MORE SO HAVE ENORMOUS 2025 01:21:39,360 --> 01:21:42,920 OPPORTUNITIES FOR HEPATOLOGISTS, 2026 01:21:42,920 --> 01:21:44,440 CLINICAL INVESTIGATORS, ARE THEY 2027 01:21:44,440 --> 01:21:45,440 INTERESTED AND AWARE OF YOUR 2028 01:21:45,440 --> 01:21:48,080 WORK? 2029 01:21:48,080 --> 01:21:49,800 >>SO I WAS INVITED TO GIVE A 2030 01:21:49,800 --> 01:21:52,080 TALK I THINK LATER THIS YEAR TO 2031 01:21:52,080 --> 01:21:54,360 A GROUP ACTUALLY, PHYSICIANS 2032 01:21:54,360 --> 01:21:56,120 INTERESTED IN LIVER BIOLOGY. I 2033 01:21:56,120 --> 01:21:57,880 ALWAYS COME WITH A BIG 2034 01:21:57,880 --> 01:21:59,720 DISCLAIMER WHICH IS I'M 2035 01:21:59,720 --> 01:22:01,600 TECHNICALLY A NEUROSCIENTIST, I 2036 01:22:01,600 --> 01:22:03,560 APPARENTLY DON'T STUDY THE 2037 01:22:03,560 --> 01:22:04,760 BRAINNA MUCH ANY MORE. I FOLLOW 2038 01:22:04,760 --> 01:22:07,560 THE BIOLOGY, SO ANY TISSUE OR 2039 01:22:07,560 --> 01:22:09,360 THINGS WE SEE THE BIOLOGY 2040 01:22:09,360 --> 01:22:10,760 TAKING, IT MEANS I WILL LEARN A 2041 01:22:10,760 --> 01:22:13,400 LOT ABOUT IT. IT IS AN 2042 01:22:13,400 --> 01:22:16,640 INTERESTING ROLE FOR IF THE 2043 01:22:16,640 --> 01:22:17,920 LIVER, BUT I DIDN'T THINK I 2044 01:22:17,920 --> 01:22:18,720 WOULD END UP WITH HERE. 2045 01:22:18,720 --> 01:22:21,360 >>SO IN HUMANS, THE STUDY THAT 2046 01:22:21,360 --> 01:22:23,800 HAVE BEEN DONE ON GENE 2047 01:22:23,800 --> 01:22:26,240 EXPRESSION METABOLOMICS SHOWED 2048 01:22:26,240 --> 01:22:29,880 MOST OF THE TIME SIGNAL 2049 01:22:29,880 --> 01:22:31,360 (INAUDIBLE) SO THERE IS RELATED 2050 01:22:31,360 --> 01:22:35,280 TO PATHOLOGY. AND ONE PAPER THAT 2051 01:22:35,280 --> 01:22:40,120 WAS PUBLISHED LONG AGO BY GEORGE 2052 01:22:40,120 --> 01:22:41,960 (INAUDIBLE) A CITY IN ITALY 2053 01:22:41,960 --> 01:22:44,160 WHERE EVERYBODY GETS AN AUTOPSY, 2054 01:22:44,160 --> 01:22:46,160 THIS OBSERVATION WAS THAT ALL 2055 01:22:46,160 --> 01:22:48,800 THE SENNARYIANS HAVE GOOD LIVER 2056 01:22:48,800 --> 01:22:52,040 -- CENTENARIANS HAVE GOOD LIVER, 2057 01:22:52,040 --> 01:22:54,040 THAT WHAT DISTINGUISH FROM MY 2058 01:22:54,040 --> 01:22:56,840 AUTOPSY, WHETHER THIS IS TRUE, I 2059 01:22:56,840 --> 01:22:58,880 THINK YOUR PRESENTATION REALLY 2060 01:22:58,880 --> 01:23:00,320 PROMPTED MY CURIOSITY. AND I'M 2061 01:23:00,320 --> 01:23:01,720 GOING TO LOOK INTO THAT. 2062 01:23:01,720 --> 01:23:07,600 >>PLEASE DO. KEEP ME POSTED. 2063 01:23:07,600 --> 01:23:11,760 >>SO ONE OF MY HATS IS I'M A 2064 01:23:11,760 --> 01:23:13,160 LIVER DOCTOR AND I CAN TELL YOU 2065 01:23:13,160 --> 01:23:16,280 THAT A LOT OF VERY GOOD ONES AT 2066 01:23:16,280 --> 01:23:18,320 UCSF, I WOULD THINK THEY WOULD 2067 01:23:18,320 --> 01:23:20,440 WANT TO COLLABORATE WITH. 2068 01:23:20,440 --> 01:23:22,120 >>CHATTING WITH THE WHOLE LIVER 2069 01:23:22,120 --> 01:23:24,200 CENTER. YES. 2070 01:23:24,200 --> 01:23:26,360 >>SO HAVE YOU OR ANYONE ELSE 2071 01:23:26,360 --> 01:23:34,280 BEEN SUCCESSFUL IN KNOCKING OUT 2072 01:23:34,280 --> 01:23:34,480 GPD 1? 2073 01:23:34,480 --> 01:23:36,240 >>GOOD QUESTION. WHAT WE HAVE 2074 01:23:36,240 --> 01:23:40,320 BEEN DOING IS WE MADE ANTISENSE 2075 01:23:40,320 --> 01:23:42,160 OLIGONUCLEOTIDES TARGETING GPLD 2076 01:23:42,160 --> 01:23:44,480 1 SPECIFICALLY IN LIVER AND THEN 2077 01:23:44,480 --> 01:23:45,400 EXERCISING MICE AND WANT TO SEE 2078 01:23:45,400 --> 01:23:47,280 WHAT IS THE RELATIVE 2079 01:23:47,280 --> 01:23:49,400 CONTRIBUTION OF THIS INCREASE. 2080 01:23:49,400 --> 01:23:51,400 AGAIN, IT GETS AT NECESSITY 2081 01:23:51,400 --> 01:23:54,400 VERSUS SUFFICIENCY, SO SOMETHING 2082 01:23:54,400 --> 01:23:56,000 CAN BE REALLY GOOD BUT DOESN'T 2083 01:23:56,000 --> 01:23:56,800 HAVE TO BE THE ONLY THING 2084 01:23:56,800 --> 01:23:58,160 INVOLVED IN BENEFIT. THE IDEA 2085 01:23:58,160 --> 01:24:00,200 THAT THERE IS ONLY ONE FACTOR, 2086 01:24:00,200 --> 01:24:01,800 WE KNOW THERE IS ADDITIVE 2087 01:24:01,800 --> 01:24:02,840 MECHANISMS AND IT IS IMPORTANT 2088 01:24:02,840 --> 01:24:04,200 THAT THERE IS MORE THAN ONE. WE 2089 01:24:04,200 --> 01:24:05,360 ARE ALL AGEING A LITTLE BIT 2090 01:24:05,360 --> 01:24:09,160 DIFFERENTLY. 2091 01:24:09,160 --> 01:24:12,160 >>WHAT MIGHT PHENOTYPE BE IN A 2092 01:24:12,160 --> 01:24:13,120 SPECIES LIKE THIS PROTEIN? 2093 01:24:13,120 --> 01:24:15,360 >>I THINK WE GET -- IT WOULD BE 2094 01:24:15,360 --> 01:24:17,640 -- I THINK LIKE THE SERT 2095 01:24:17,640 --> 01:24:18,760 CONDITION WHERE IF THEY ARE FAT 2096 01:24:18,760 --> 01:24:20,320 AND OBESE YOU SIGH IT, IF THEY 2097 01:24:20,320 --> 01:24:22,000 ARE NOT MAYBE NOT NECESSARILY. 2098 01:24:22,000 --> 01:24:23,560 SO BECAUSE IT DOESN'T CHANGE 2099 01:24:23,560 --> 01:24:25,800 WITH AGE WE HAVE TO PERTURB THE 2100 01:24:25,800 --> 01:24:27,680 SYSTEM SOMEHOW. WE ALSO THINK IT 2101 01:24:27,680 --> 01:24:29,040 IS INVOLVED WITH THE IMMUNE 2102 01:24:29,040 --> 01:24:32,400 SYSTEM SO IN THE CONTEXT OF 2103 01:24:32,400 --> 01:24:32,960 INFLAMMATION IT WOULD HAVE 2104 01:24:32,960 --> 01:24:34,920 SOMETHING. WHAT WE ARE SEEING 2105 01:24:34,920 --> 01:24:38,240 OVEREXPRESS IS IT IS GOOD AT 2106 01:24:38,240 --> 01:24:39,200 (INAUDIBLE) FUNCTION, IF YOU 2107 01:24:39,200 --> 01:24:40,880 GIVE INFLAMMATION TO A YOUNG 2108 01:24:40,880 --> 01:24:42,680 ANIMAL, IT HAS A CHANGE IN THE 2109 01:24:42,680 --> 01:24:44,000 BRAIN YOU CAN BLOCK THAT WITH 2110 01:24:44,000 --> 01:24:45,960 THIS FACTOR. BUT WHEN EVERYTHING 2111 01:24:45,960 --> 01:24:48,000 IS NORMAL, IT DOESN'T SEEM TO DO 2112 01:24:48,000 --> 01:24:49,240 ANYTHING. SO IT DOESN'T SEEM TO 2113 01:24:49,240 --> 01:24:51,800 BE A BOOSTER, IT REALLY JUST 2114 01:24:51,800 --> 01:24:52,960 SEEMS TO BE SUPPRESSING 2115 01:24:52,960 --> 01:24:55,040 IMPAIRMENT. 2116 01:24:55,040 --> 01:24:57,640 >>SO WE HAVE SOME MORE 2117 01:24:57,640 --> 01:25:02,400 QUESTIONS ABOUT THIS PROTEIN: 2118 01:25:02,400 --> 01:25:05,160 HEPATOCYTE, THE CELL OF ORIGIN, 2119 01:25:05,160 --> 01:25:08,800 AND WHAT IS KNOWN AT THE MOMENT 2120 01:25:08,800 --> 01:25:10,640 ABOUT THE CELL BIOLOGY OF IT? 2121 01:25:10,640 --> 01:25:15,600 HOW DOES IT GET OUT OF THE CELL? 2122 01:25:15,600 --> 01:25:16,800 YOU HAVE NEWS ABOUT WHAT IT IS 2123 01:25:16,800 --> 01:25:20,120 DOING ONCE IT GETS OUT, HOW DOES 2124 01:25:20,120 --> 01:25:21,040 IT INTERACT? 2125 01:25:21,040 --> 01:25:23,040 >>WE HAVE A WHOLE -- WE HAVE 2126 01:25:23,040 --> 01:25:24,320 TWO POST DOCS THAT ARE CURRENTLY 2127 01:25:24,320 --> 01:25:25,680 LOOKING INTO NUMBER ONE IN THE 2128 01:25:25,680 --> 01:25:29,120 BRAIN, YES, IT IS EXPRESS BY 2129 01:25:29,120 --> 01:25:30,040 HEPATOCYTES RIGHT NOW WHAT WE 2130 01:25:30,040 --> 01:25:32,120 ARE TRYING TO DO IS IDENTIFY THE 2131 01:25:32,120 --> 01:25:34,080 TRANSCRIPTION FACTORS THAT ARE 2132 01:25:34,080 --> 01:25:36,080 INDUCED BY EXERCISE THAT ALLOW 2133 01:25:36,080 --> 01:25:38,840 IT TO COME OUT. UNDER NORMAL 2134 01:25:38,840 --> 01:25:41,080 CONDITIONS IT IS JUST SECRETED 2135 01:25:41,080 --> 01:25:42,880 BY HEMATOCYTES THEN IT GOES INTO 2136 01:25:42,880 --> 01:25:44,320 CIRCULATION. THE WAY IT WORKS 2137 01:25:44,320 --> 01:25:45,800 IS BY CLEAVING THOSE PROTEINS ON 2138 01:25:45,800 --> 01:25:47,680 THE CELL SURFACE AND THEN IT 2139 01:25:47,680 --> 01:25:49,400 IMPACTS PROCESSES LIKE 2140 01:25:49,400 --> 01:25:50,880 COMPLIMENT IN THE IMMUNE SYSTEM. 2141 01:25:50,880 --> 01:25:53,760 MOST OF THE CELLS THAT HAVE 2142 01:25:53,760 --> 01:25:55,320 THOSE ANCHOR PROTEINS ARE IMMUNE 2143 01:25:55,320 --> 01:25:57,840 CELLS OR VASCULATURE. THOSE ARE 2144 01:25:57,840 --> 01:26:00,360 ENRICHED FOR MOST OF THESE 2145 01:26:00,360 --> 01:26:01,360 PROTEINS WE CLEAVE SO IT 2146 01:26:01,360 --> 01:26:02,760 SUGGESTS THEN AN INVOLVEMENT IN 2147 01:26:02,760 --> 01:26:04,560 THE IMMUNE SYSTEM, PROBABLY SOME 2148 01:26:04,560 --> 01:26:06,000 SORT OF INFLAMMATION. WE ARE 2149 01:26:06,000 --> 01:26:08,520 ALSO LOOKING AT VASCULATURE, 2150 01:26:08,520 --> 01:26:10,120 THINGS LIKE BLOOD BRAIN BARRIER. 2151 01:26:10,120 --> 01:26:11,480 THAT IS AS FAR AS WE HAVE GONE. 2152 01:26:11,480 --> 01:26:13,520 >>ANOTHER QUESTION FOR YOU TO 2153 01:26:13,520 --> 01:26:16,440 SOLVE. SO SOME STUDIES HAVE BEEN 2154 01:26:16,440 --> 01:26:19,960 DONE LIKE WITH THE PARABIOTIC, 2155 01:26:19,960 --> 01:26:25,120 TALKING ABOUT CELLS. AND STUDIES 2156 01:26:25,120 --> 01:26:27,080 WITH STEM CELLS AND OTHER KINDS 2157 01:26:27,080 --> 01:26:29,200 OF CELLS IN THE PROCESS. THEN 2158 01:26:29,200 --> 01:26:33,200 YOU HAVE STUDIES WITH PLASMA. 2159 01:26:33,200 --> 01:26:35,720 PRESUMABLY COMPLETELY CELL FREE. 2160 01:26:35,720 --> 01:26:38,400 SO DOES THAT SUGGEST THAT THERE 2161 01:26:38,400 --> 01:26:43,400 ARE MULTIPLE FACTORS RESIDING IN 2162 01:26:43,400 --> 01:26:46,920 DIFFERENT SOURCES, IN SOME SENSE 2163 01:26:46,920 --> 01:26:49,680 RELATED TO THE CELLS, STEM CELL 2164 01:26:49,680 --> 01:26:52,880 OR OTHER? AND OTHERS RELATING TO 2165 01:26:52,880 --> 01:26:54,880 CIRCULATING COMPONENTS; IS THAT 2166 01:26:54,880 --> 01:26:56,480 WHAT THE THINKING IS AT THE 2167 01:26:56,480 --> 01:26:56,680 MOMENT? 2168 01:26:56,680 --> 01:26:58,720 >>YES. I THINK THAT THE FIELD, 2169 01:26:58,720 --> 01:27:00,400 IF YOU TALK TO SOME OF THE 2170 01:27:00,400 --> 01:27:02,200 FACULTY THAT ARE IN THIS FIELD, 2171 01:27:02,200 --> 01:27:07,720 I THINK THE IDEA IS IN AD ACTIVE 2172 01:27:07,720 --> 01:27:13,000 MECHANISMS I THINK -- -- EVEN IF 2173 01:27:13,000 --> 01:27:14,440 YOU THINK ABOUT ONE FACTOR LIKE 2174 01:27:14,440 --> 01:27:16,440 A CYTOKINE TO A RECEPTOR, IF IT 2175 01:27:16,440 --> 01:27:18,240 HAS TWO OR THREE RECEPTORS YOU 2176 01:27:18,240 --> 01:27:21,680 SIGNAL TO MORE THINGS. SO IDEA 2177 01:27:21,680 --> 01:27:24,040 IS YES, EVEN IN YOUNG BLOOD 2178 01:27:24,040 --> 01:27:25,880 THERE COULD BE YOUNG FACTORS YOU 2179 01:27:25,880 --> 01:27:27,320 CANNOT FORGET YOU CAN TARGET OR 2180 01:27:27,320 --> 01:27:32,000 BLOCK AGING FACTORS OR PRO 2181 01:27:32,000 --> 01:27:33,440 GERONIC FACTORS. T THAT HAS 2182 01:27:33,440 --> 01:27:35,320 BENEFIT. PEOPLE EXCHANGED AND 2183 01:27:35,320 --> 01:27:36,720 DILUTED THE OLD FACTORS THAT CAN 2184 01:27:36,720 --> 01:27:38,080 CAUSE A BENEFIT. SO I THIS I IT 2185 01:27:38,080 --> 01:27:44,040 REALLY SUGGESTS TO THIS HUGE 2186 01:27:44,040 --> 01:27:45,520 INNER PLAY BETWEEN ORGANS AND 2187 01:27:45,520 --> 01:27:49,120 BLOOD AND AGING. ANYTHING THAT 2188 01:27:49,120 --> 01:27:51,200 CHANGES THAT COMPOSITION HAS 2189 01:27:51,200 --> 01:27:52,840 POTENTIAL TO HAVE IT BUT 2190 01:27:52,840 --> 01:27:53,840 ABSOLUTELY THERE ARE ADDITIVE 2191 01:27:53,840 --> 01:27:55,320 MECHANISMS DEPENDING ON THE 2192 01:27:55,320 --> 01:27:56,120 CELLULAR SOURCE AND THE 2193 01:27:56,120 --> 01:27:59,480 INTERVENTION. 2194 01:27:59,480 --> 01:28:01,920 >>LUIGI, YOU HAVE THIS 2195 01:28:01,920 --> 01:28:04,520 WONDERFUL STATEMENT WE WANT THE 2196 01:28:04,520 --> 01:28:08,880 HEALTHY LIFE WE HAVE LOST. WHEN 2197 01:28:08,880 --> 01:28:11,760 DID WE EVER HAVE A HEALTHY LIFE? 2198 01:28:11,760 --> 01:28:18,520 AND IN ORDER TO ACHIEVE IT, 2199 01:28:18,520 --> 01:28:22,040 DOESN'T IT REQUIRE HUGE CHANGES 2200 01:28:22,040 --> 01:28:25,320 IN OUR SOCIOECONOMIC AND 2201 01:28:25,320 --> 01:28:26,280 POLITICAL WAY OF LIFE? 2202 01:28:26,280 --> 01:28:30,920 >>YEAH. THAT IS ABSOLUTELY. WE 2203 01:28:30,920 --> 01:28:35,560 NEED TO CHANGE THE WAY WE USE 2204 01:28:35,560 --> 01:28:41,280 OUR HEALTHCARE. I THINK WE USE 2205 01:28:41,280 --> 01:28:42,920 GRADUAL AM OF MONEY TO CURE 2206 01:28:42,920 --> 01:28:45,560 PEOPLE WHEN THEY HAVE DEVELOPED 2207 01:28:45,560 --> 01:28:49,320 DISEASE, WHILE IDENTIFYING THE 2208 01:28:49,320 --> 01:28:51,640 EARLY, WOULD BE MUCH MORE 2209 01:28:51,640 --> 01:28:55,200 EFFECTIVE. MUCH LESS EXPENSIVE 2210 01:28:55,200 --> 01:28:58,000 AND WILL ALLOW US TO EXPAND THE 2211 01:28:58,000 --> 01:29:00,440 GOOD PART OF LIFE. WHEN I WAS 2212 01:29:00,440 --> 01:29:03,560 SAYING THE LIFE WE HAVE LOST, I 2213 01:29:03,560 --> 01:29:05,960 THINK THAT IS REALLY THE IDEA 2214 01:29:05,960 --> 01:29:08,080 THAT WITH INCREASE LIFE 2215 01:29:08,080 --> 01:29:11,080 EXPECTANCY, WHICH AS I SAY 2216 01:29:11,080 --> 01:29:13,440 SOMETHING PEOPLE (INAUDIBLE) 2217 01:29:13,440 --> 01:29:16,320 MOST OF WHAT WE GAIN IS DISEASE 2218 01:29:16,320 --> 01:29:18,960 AND DISABILITY LIFE EXPECTANCY 2219 01:29:18,960 --> 01:29:22,360 OF THE LIFE WHERE YOU ARE SICK. 2220 01:29:22,360 --> 01:29:25,600 SO IT IS NOT A GOOD LIFE. WHAT I 2221 01:29:25,600 --> 01:29:27,680 WANT TO KNOW IS WHETHER WE CAN 2222 01:29:27,680 --> 01:29:29,120 COMPRESS THE PERIOD OF DISEASE 2223 01:29:29,120 --> 01:29:30,680 AND DISABILITY LATER IN LIFE. I 2224 01:29:30,680 --> 01:29:32,360 THINK THAT THERE IS EVIDENCE 2225 01:29:32,360 --> 01:29:37,280 THAT CAN BE DONE. ANIMAL MODEL 2226 01:29:37,280 --> 01:29:41,480 FOR EXAMPLE STUDIES ON REMOVAL 2227 01:29:41,480 --> 01:29:43,520 OF SENESCENCE CELLS HAVE SHOWN 2228 01:29:43,520 --> 01:29:47,720 YOU HAVE A VERY LITTLE EFFECT ON 2229 01:29:47,720 --> 01:29:49,960 LIFE EXPECTANCY THAT YOU HAVE 2230 01:29:49,960 --> 01:29:51,320 DELAY SOME OF THE MAJOR 2231 01:29:51,320 --> 01:29:53,000 CONDITION THAT CHARACTERIZE 2232 01:29:53,000 --> 01:29:54,840 AGING, FOR EXAMPLE HEARING LOSS. 2233 01:29:54,840 --> 01:29:58,800 YOU HAVE A DECLINE IN THE 2234 01:29:58,800 --> 01:30:02,400 DEVELOPMENT OF (INAUDIBLE) A 2235 01:30:02,400 --> 01:30:04,760 DECLINE A A REDUCTION OF 2236 01:30:04,760 --> 01:30:07,200 SARCOPENIA, DELAYED SARCOPENIA. 2237 01:30:07,200 --> 01:30:11,920 SO THIS CAN BE DONE BUT WE HAVE 2238 01:30:11,920 --> 01:30:13,800 A MODEL OF MEDICINE THAT IS ONLY 2239 01:30:13,800 --> 01:30:17,120 CENTERED ON DAMAGE. WE WANT TO 2240 01:30:17,120 --> 01:30:20,760 SEE THE SYMPTOM, WE WANT THE SEE 2241 01:30:20,760 --> 01:30:23,440 PATHOLOGY, WHAT IS GOING ON, WE 2242 01:30:23,440 --> 01:30:26,760 NEVER MEASURE WHAT IS DEFENDING 2243 01:30:26,760 --> 01:30:29,520 US FROM OUR ORGANISM BEFORE 2244 01:30:29,520 --> 01:30:32,040 FALLING APART. WE DON'T HAVE 2245 01:30:32,040 --> 01:30:34,480 THAT SIDE OF THE STUDY. 2246 01:30:34,480 --> 01:30:37,200 DEVELOPING THAT SIDE OF THE 2247 01:30:37,200 --> 01:30:40,640 STUDY IS IMPORTANT, IF WE HAVE A 2248 01:30:40,640 --> 01:30:41,880 FACTOR THAT PROMOTE HEALTHY 2249 01:30:41,880 --> 01:30:43,440 AGING WE WANT TO KNOW HOW THAT 2250 01:30:43,440 --> 01:30:46,520 FACTOR WORKS. BECAUSE THAT CAN 2251 01:30:46,520 --> 01:30:49,560 BE APPLY NOT WHEN SOMEBODY SHAH 2252 01:30:49,560 --> 01:30:51,440 ALREADY DEVELOPED DEMENTIA BUT 2253 01:30:51,440 --> 01:30:54,640 FOR SOMEBODY THAT WE SAW ALREADY 2254 01:30:54,640 --> 01:30:57,440 THAT HAS A PATHWAY GOING THAT 2255 01:30:57,440 --> 01:31:00,560 DIRECTION, MAYBE WE CAN 2256 01:31:00,560 --> 01:31:01,800 INTERVENE EARLY AND AVOID THAT 2257 01:31:01,800 --> 01:31:04,120 PERSON TO DEVELOP ACCELERATED 2258 01:31:04,120 --> 01:31:08,800 COGNITIVE DECLINE. I THINK THE 2259 01:31:08,800 --> 01:31:11,160 RATIONALE IS THERE. WE HAVE NOT 2260 01:31:11,160 --> 01:31:14,680 LOST HEALTH. WE HAVE (INAUDIBLE) 2261 01:31:14,680 --> 01:31:16,040 TO BE THE HEALTH WE THOUGHT WE 2262 01:31:16,040 --> 01:31:18,080 WERE GETTING. AND -- FAILED TO 2263 01:31:18,080 --> 01:31:19,640 GET THE HEALTH WE THOUGHT 2264 01:31:19,640 --> 01:31:20,960 THOUGHT WE WERE GETTING. I WANT 2265 01:31:20,960 --> 01:31:22,240 THAT BACK. THERE IS STRATEGY 2266 01:31:22,240 --> 01:31:23,040 THAT CAN BE ACCOMPLISHED. SOME 2267 01:31:23,040 --> 01:31:30,440 OF THAT IS NOW, YOU KNOW WHAT IS 2268 01:31:30,440 --> 01:31:31,760 SECRET OF HEALTHY LIFE. I CAN 2269 01:31:31,760 --> 01:31:34,120 TELL YOU, YOU SAID THAT. DO NOT 2270 01:31:34,120 --> 01:31:37,680 SMOKE, EXERCISE, TRY TO MAINTAIN 2271 01:31:37,680 --> 01:31:40,600 YOUR WEIGHT, SLEEP, DO 2272 01:31:40,600 --> 01:31:44,640 SCREENING. PEOPLE HAVE SHOWN 2273 01:31:44,640 --> 01:31:46,720 THAT YOU CAN GAIN GOOD DEAL OF 2274 01:31:46,720 --> 01:31:51,040 LIFE BY JUST DOING THAT. BUT THE 2275 01:31:51,040 --> 01:31:52,680 PROBLEM IS PEOPLE DON'T DO IT 2276 01:31:52,680 --> 01:31:55,080 BUT YOU COULD. SO ONCE I DO NEW 2277 01:31:55,080 --> 01:31:58,240 DISCOVERY, ONE SIDE WILL NEED TO 2278 01:31:58,240 --> 01:32:01,440 IMPLEMENT THE COOPERATION, THE 2279 01:32:01,440 --> 01:32:02,920 DISCOVERY THAT WE ALREADY HAVE 2280 01:32:02,920 --> 01:32:05,480 MADE. THE KNOWLEDGE WE ALREADY 2281 01:32:05,480 --> 01:32:08,000 HAVE. THOSE ARE TWO 2282 01:32:08,000 --> 01:32:08,840 COMPLIMENTARY BY BUT REALLY 2283 01:32:08,840 --> 01:32:15,400 IMPORTANT GOALS. 2284 01:32:15,400 --> 01:32:17,520 WE HAVE MORE QUESTIONS PRIMARILY 2285 01:32:17,520 --> 01:32:19,440 FOR YOU. I'M GOING TO BUNCH THEM 2286 01:32:19,440 --> 01:32:20,640 TOGETHER. SAUL. WHAT HAPPENS TO 2287 01:32:20,640 --> 01:32:25,080 A MOUSE THAT OVEREXPRESSES GPLD 2288 01:32:25,080 --> 01:32:26,560 1 FROM BIRTH AND HOW LONG DOES 2289 01:32:26,560 --> 01:32:31,680 IT LIVE, DO YOU KNOW? 2290 01:32:31,680 --> 01:32:33,440 >>WE HAVE NOT DONE THAT. ONE 2291 01:32:33,440 --> 01:32:34,560 THING TO KEEP IN MIND IS 2292 01:32:34,560 --> 01:32:37,120 EXERCISE IS OPPOSED TO CALORIC 2293 01:32:37,120 --> 01:32:39,480 RESTRICTION IN TERMS OF LIFE 2294 01:32:39,480 --> 01:32:41,480 SPAN STUDIES IN MICE, IT IS NOT 2295 01:32:41,480 --> 01:32:43,840 AS CLEAR CUT, CALORIC 2296 01:32:43,840 --> 01:32:45,280 RESTRICTION IT IS VERY YES AND 2297 01:32:45,280 --> 01:32:47,000 NO SO I WOULDN'T EXPECT FACTORS 2298 01:32:47,000 --> 01:32:49,200 THAT ARE MORE EXERCISE 2299 01:32:49,200 --> 01:32:51,720 ASSOCIATED TO IMPACT -- AND I'M 2300 01:32:51,720 --> 01:32:54,280 REALLY INTERESTED IN EXACTLY 2301 01:32:54,280 --> 01:32:56,160 WHAT LUIGI SAID WHICH IS 2302 01:32:56,160 --> 01:32:58,240 SHORTENING THE TIME OF THAT 2303 01:32:58,240 --> 01:33:00,000 DECLINE NOT NECESSARILY JUST 2304 01:33:00,000 --> 01:33:01,320 EXTENDING LIFE SPAN. THE WORST 2305 01:33:01,320 --> 01:33:04,640 THING I CAN THINK OF IS LIVING 2306 01:33:04,640 --> 01:33:06,920 150 YEARS AND LITERALLY 75 BEING 2307 01:33:06,920 --> 01:33:09,480 WITH DEMENTIA BECAUSE I -- THAT 2308 01:33:09,480 --> 01:33:11,280 TO ME IS NOT WHAT WE ARE TRYING. 2309 01:33:11,280 --> 01:33:12,920 SO WE DON'T FOCUS OR THAT IS NOT 2310 01:33:12,920 --> 01:33:15,280 ONE OF OUR CONSIDERATIONS WOULD 2311 01:33:15,280 --> 01:33:16,560 BE KIND OF LIFE SPAN EXTENSION. 2312 01:33:16,560 --> 01:33:19,480 BUT BECAUSE THIS IS AN EXERCISE 2313 01:33:19,480 --> 01:33:21,560 FACTOR, I WOULD IN MY HYPOTHESIS 2314 01:33:21,560 --> 01:33:26,440 NOT BE ABLE TO EXTEND LIFE SPAN 2315 01:33:26,440 --> 01:33:28,200 >>ANOTHER QUESTION, DO YOU KNOW 2316 01:33:28,200 --> 01:33:31,200 ANYTHING ABOUT THE REGULATION OF 2317 01:33:31,200 --> 01:33:35,160 THE EXPRESSION OF GPLD 1? 2318 01:33:35,160 --> 01:33:36,280 >>THAT IS WHAT I MENTION. WE 2319 01:33:36,280 --> 01:33:39,640 HAVE BEEN DOING SOME RNA 2320 01:33:39,640 --> 01:33:41,360 SEQUENCING WE HAVE DONE 2321 01:33:41,360 --> 01:33:44,920 PROTEOMICS, NOT SURE WHETHER WE 2322 01:33:44,920 --> 01:33:48,840 DID AWE TACK SEQ OR NOT, WE 2323 01:33:48,840 --> 01:33:50,160 TRYING WHAT ARE THE 2324 01:33:50,160 --> 01:33:54,200 TRANSCRIPTION FACTOR UPSTREAM OR 2325 01:33:54,200 --> 01:33:57,600 PROPROMOTER REGIONS, INCREASE 2326 01:33:57,600 --> 01:33:59,520 GENE WITH EXERCISE. EXERCISE IS 2327 01:33:59,520 --> 01:34:02,040 ALL SORT OF CHROMATIN HYDROXY 2328 01:34:02,040 --> 01:34:03,160 METHYLATION. SO WE ARE 2329 01:34:03,160 --> 01:34:04,320 INTERESTED IN UNDERSTANDING WHAT 2330 01:34:04,320 --> 01:34:06,240 IS IT ABOUT EXERCISE THAT ENAGES 2331 01:34:06,240 --> 01:34:08,480 THAT TO BE EXPRESSED. IT IS 2332 01:34:08,480 --> 01:34:10,600 USUALLY THESE AN OFF SWITCHES OR 2333 01:34:10,600 --> 01:34:12,000 USUALLY THINGS THAT TITRATE 2334 01:34:12,000 --> 01:34:13,640 ACCESSIBILITY. WE KNOW THAT IS 2335 01:34:13,640 --> 01:34:14,800 VERY LINKED TO AGING. SO IT IS 2336 01:34:14,800 --> 01:34:24,440 KIND OF THE ROUTES WE ARE GOING 2337 01:34:24,440 --> 01:34:26,280 >>LUIGI, ARE BENEFITS O 2338 01:34:26,280 --> 01:34:29,960 EXERCISE ACHIEVED WITH EPISODIC 2339 01:34:29,960 --> 01:34:33,480 WHETHER THAN CHRONIC EXERCISE? 2340 01:34:33,480 --> 01:34:37,440 >>THERE IS MANUSCRIPT RECENTLY 2341 01:34:37,440 --> 01:34:39,520 PUBLISHED SHOWING THAT PEOPLE 2342 01:34:39,520 --> 01:34:43,440 THAT EXERCISE ONLY ONCE A WEEK 2343 01:34:43,440 --> 01:34:46,760 ON SUNDAY ALREADY HAVE BENEFIT 2344 01:34:46,760 --> 01:34:48,240 IN TERMS OF HEALTH EXPECTANCY 2345 01:34:48,240 --> 01:34:53,160 AND LIFE EXPECTANCY. I THINK 2346 01:34:53,160 --> 01:34:57,760 THAT EXERCISE, IS A VERY STRANGE 2347 01:34:57,760 --> 01:34:59,240 INTERVENTION BECAUSE IF YOU HAVE 2348 01:34:59,240 --> 01:35:01,240 NEVER BEEN EXERCISING AND YOU 2349 01:35:01,240 --> 01:35:05,520 EXERCISE THE FIRST TIME, YOU THE 2350 01:35:05,520 --> 01:35:08,640 EFFECT YOUR SEE BIOCHEMICALLY 2351 01:35:08,640 --> 01:35:09,800 BIOLOGICALLY, YOU SEE 2352 01:35:09,800 --> 01:35:13,400 INCREMENTING OX DATING STRESS, 2353 01:35:13,400 --> 01:35:15,480 YOU SEE INFLAMMATION THROUGHOUT 2354 01:35:15,480 --> 01:35:18,680 THE BODY, PEOPLE FEEL THAT HAVE 2355 01:35:18,680 --> 01:35:20,320 PAIN AND ACHE EVERYWHERE. BUT 2356 01:35:20,320 --> 01:35:25,720 THE ISSUE THAT HAS (INAUDIBLE) 2357 01:35:25,720 --> 01:35:32,000 SO IS RESPONDED, VERY ROBUST 2358 01:35:32,000 --> 01:35:35,600 RESILIENCE OF RESPONSE, WITH 2359 01:35:35,600 --> 01:35:37,800 STRONG -- ANTI-INFLAMMATORY 2360 01:35:37,800 --> 01:35:39,880 PATHWAY, SO THAT OVER TIME, AS 2361 01:35:39,880 --> 01:35:44,040 YOU BUILD ON THAT, THE EFFECT 2362 01:35:44,040 --> 01:35:45,960 BECOME BETTER AND BETTER. I 2363 01:35:45,960 --> 01:35:50,360 THINK THAT WE SEE THIS IN OUR 2364 01:35:50,360 --> 01:35:52,960 STUDIES, WE HAVE DONE FOR 2365 01:35:52,960 --> 01:35:55,000 EXAMPLE, VERY RECENTLY A STUDY 2366 01:35:55,000 --> 01:35:58,080 ON CHANGE IN ACUTE METABOLOMICS 2367 01:35:58,080 --> 01:36:01,480 AND YOUR PRESENTATION MADE ME 2368 01:36:01,480 --> 01:36:02,760 THINK WE SHOULD TAKE THOSE 2369 01:36:02,760 --> 01:36:05,320 SERUM. BEFORE WE PUT YOU ON THE 2370 01:36:05,320 --> 01:36:10,520 TREADMILL AND WE DO SERIAL ZERO, 2371 01:36:10,520 --> 01:36:14,400 10, 15, 20, 30, ONE HOUR, 2 2372 01:36:14,400 --> 01:36:16,400 HOUR, 12 HOURS TO SEE WHAT THE 2373 01:36:16,400 --> 01:36:20,680 METABOLOMIC CHANGES AND WHAT WAY 2374 01:36:20,680 --> 01:36:22,680 THEY -- THOSE CHANGES ARE 2375 01:36:22,680 --> 01:36:27,840 ACUTELY EFFECT METABOLISM AND 2376 01:36:27,840 --> 01:36:34,560 HOW THEY CHANGE CHRONICALLY 2377 01:36:34,560 --> 01:36:35,840 BECAUSE WE LOOK AT THE WAY THEY 2378 01:36:35,840 --> 01:36:38,160 ARE. WE STUDY MITOCHONDRIAL 2379 01:36:38,160 --> 01:36:41,000 FUNCTION WITH MRI. THE NEGATIVE 2380 01:36:41,000 --> 01:36:43,800 OR POSITIVE RESPONSE WITHIN 2381 01:36:43,800 --> 01:36:45,200 METABOLOMICS THE RELATED TO THE 2382 01:36:45,200 --> 01:36:47,440 BASIC MITOCHONDRIAL FUNCTI FUNCF 2383 01:36:47,440 --> 01:36:49,040 YOU HAVE GOOD MITOCHONDRIAL 2384 01:36:49,040 --> 01:36:50,280 FUNCTION THE BENEFIT OF EXERCISE 2385 01:36:50,280 --> 01:36:52,040 ARE BETTER. THAT IS ACUTE 2386 01:36:52,040 --> 01:36:59,000 EXERCISE. SO IN A WAY, TRAIN 2387 01:36:59,000 --> 01:37:00,520 MITOCHONDRIA AND ALLOW THE 2388 01:37:00,520 --> 01:37:02,320 EXERCISE TO EXERT MUCH BETTER 2389 01:37:02,320 --> 01:37:03,680 BENEFIT THAN IF YOU ARE NOT 2390 01:37:03,680 --> 01:37:06,960 TRAINING. SO I THINK THAT 2391 01:37:06,960 --> 01:37:09,880 EXERCISE IS GOOD IN ANY FORM, 2392 01:37:09,880 --> 01:37:11,880 CONTINUOUS EXERCISE IS PROBABLY 2393 01:37:11,880 --> 01:37:15,960 BETTER. BUT AS I SAY, AND I HAVE 2394 01:37:15,960 --> 01:37:17,760 ALWAYS SAID THAT, BECAUSE IT IS 2395 01:37:17,760 --> 01:37:19,760 IMPORTANT, DON'T STAY ON THE 2396 01:37:19,760 --> 01:37:22,560 COUCH. TEN MINUTES AROUND YOUR 2397 01:37:22,560 --> 01:37:23,880 HOUSE, SO MUCH BETTER THAN DOING 2398 01:37:23,880 --> 01:37:29,600 NOTHING. SO MUCH BETTER. 2399 01:37:29,600 --> 01:37:32,320 >>THERE IS A QUESTION I GUESS, 2400 01:37:32,320 --> 01:37:35,800 IS THERE ANY INFORMATION, AN 2401 01:37:35,800 --> 01:37:40,160 UPDATE ON THE PLASMA FACTOR TEMP 2402 01:37:40,160 --> 01:37:41,720 2 DEMONSTRATED BY ANOTHER GROUP 2403 01:37:41,720 --> 01:37:44,800 EARLIER I THINK THIS YEAR? 2404 01:37:44,800 --> 01:37:47,200 >>YES. THE ORIGINAL FINDING 2405 01:37:47,200 --> 01:37:49,960 WHERE I DID MY Ph.D., IT WAS 2406 01:37:49,960 --> 01:37:52,280 DONE BY DR. JOSEPH 2407 01:37:52,280 --> 01:37:53,320 (INDISCERNIBLE) HE NOW HAS A 2408 01:37:53,320 --> 01:37:56,040 GROUP AT THE ICAN MEDICAL SCHOOL 2409 01:37:56,040 --> 01:37:58,320 NEW YORK AND ME HAS AN ENTIRE 2410 01:37:58,320 --> 01:37:59,880 RESEARCH PROGRAM, ON IT, I 2411 01:37:59,880 --> 01:38:01,680 BELIEVE HE'S LOOKING AT HIS 2412 01:38:01,680 --> 01:38:03,800 ROLES IN ALZHEIMER'S AND MODELS 2413 01:38:03,800 --> 01:38:07,240 AND POTENTIAL INTERACTIONS WITH 2414 01:38:07,240 --> 01:38:11,400 SOME GENETIC RISK FACTORS SO 2415 01:38:11,400 --> 01:38:13,760 HE'S DEFINITELY CHAMPIONING THAT 2416 01:38:13,760 --> 01:38:15,440 AND HE'S GOING IN THE ROUTE OF 2417 01:38:15,440 --> 01:38:19,240 SOME DISEASES AS WELL. 2418 01:38:19,240 --> 01:38:24,800 >>LUIGI, THERE IS INQUIRY ABO 2419 01:38:24,800 --> 01:38:26,520 ABOUT, HAS COVID, THE PANDEMIC 2420 01:38:26,520 --> 01:38:27,440 ILLUMINATED ANYTHING ABOUT THE 2421 01:38:27,440 --> 01:38:31,280 AGING PROCESS? DO WE HAVE ANY 2422 01:38:31,280 --> 01:38:34,080 THOUGHTS ABOUT THAT? 2423 01:38:34,080 --> 01:38:38,960 >>THE SHORT ANSWER IS YES, WE 2424 01:38:38,960 --> 01:38:42,160 DO KNOW THAT OLD AGE HAS BEEN 2425 01:38:42,160 --> 01:38:46,280 ASSOCIATED WITH ACTIVITY TO BE 2426 01:38:46,280 --> 01:38:49,600 AFFECTED, ESPECIALLY TO HAVE 2427 01:38:49,600 --> 01:38:50,960 DISASTROUS EFFECT FROM THE 2428 01:38:50,960 --> 01:38:54,400 DISEASE, THE SO CALLED CYTOKINE 2429 01:38:54,400 --> 01:38:59,400 STORM, THAT LEAD TO RAPID 2430 01:38:59,400 --> 01:39:01,000 RESPIRATORY FAILURE AN 2431 01:39:01,000 --> 01:39:03,480 ASSOCIATES WITH HIGH MORTALITY. 2432 01:39:03,480 --> 01:39:07,040 MANY STUDIES SHOWING THE 2433 01:39:07,040 --> 01:39:10,320 INTERACTION BETWEEN AGE AND 2434 01:39:10,320 --> 01:39:12,120 FATALITY. FATALITY NUMBER OF 2435 01:39:12,120 --> 01:39:14,320 PEOPLE THAT GET INFECTION AND 2436 01:39:14,320 --> 01:39:16,520 THEY DIE BECAUSE OF INFECTION 2437 01:39:16,520 --> 01:39:20,960 COMPARED TO ALL THOSE THAT ARE 2438 01:39:20,960 --> 01:39:22,160 INFECTED. SO ACTIVITY TO AGING 2439 01:39:22,160 --> 01:39:24,560 AND THERE IS ALSO AREAS THAT IS 2440 01:39:24,560 --> 01:39:27,840 JUST NOT CHRONOLOGICAL AGE, 2441 01:39:27,840 --> 01:39:33,240 PEOPLE THAT HAVE ACCELERATED 2442 01:39:33,240 --> 01:39:35,040 EPIGENETIC AGE THEY TEND TO HAVE 2443 01:39:35,040 --> 01:39:36,560 HIGHER FATALITY RATE COMPARED TO 2444 01:39:36,560 --> 01:39:40,760 THOSE THAT HAVE -- NORMAL 2445 01:39:40,760 --> 01:39:45,840 EPIGENETIC AGE. SO WHEN I SAY 2446 01:39:45,840 --> 01:39:46,840 RESILIENT, HOW MUCH RESILIENCE 2447 01:39:46,840 --> 01:39:48,680 DO YOU HAVE, THAT IS GOING TO 2448 01:39:48,680 --> 01:39:51,440 AFFECT ALSO WHAT WOULD BE THE 2449 01:39:51,440 --> 01:39:53,480 FACTOR OF INFECTION. CAN YOU 2450 01:39:53,480 --> 01:39:54,920 OVERCOME THE INFECTION OR NOT. 2451 01:39:54,920 --> 01:39:55,960 WE DON'T KNOW HOW TO MEASURE 2452 01:39:55,960 --> 01:40:04,280 THAT. THERE IS PRELIMINARY 2453 01:40:04,280 --> 01:40:07,400 EVIDENCE THAT ALSO THE LUNG 2454 01:40:07,400 --> 01:40:08,640 COVID IS A LITTLE MORE FREQUENT 2455 01:40:08,640 --> 01:40:11,520 IN OLDER PEOPLE. ONE OF MY 2456 01:40:11,520 --> 01:40:19,520 SCIENTISTS, HAVE LOOKED AT THE 2457 01:40:19,520 --> 01:40:21,320 WHETHER THERE IS VIRUS IN THE 2458 01:40:21,320 --> 01:40:23,400 MICROVESICLE IN THE BLOOD. THEY 2459 01:40:23,400 --> 01:40:25,400 FOUND (INDISCERNIBLE) IS THE 2460 01:40:25,400 --> 01:40:26,280 NAME, WHO I DON'T KNOW WHETHER 2461 01:40:26,280 --> 01:40:31,360 IT IS LISTED OR NOT AND THEY 2462 01:40:31,360 --> 01:40:34,920 HAVE ENVIRONMENT PARTICLE IS 2463 01:40:34,920 --> 01:40:38,440 TRANSPORTED IN MICROVESICLE IN 2464 01:40:38,440 --> 01:40:41,640 (INAUDIBLE) PEOPLE BUT NOT ONLY 2465 01:40:41,640 --> 01:40:48,080 IN THOSE THAT DEVELOP LUNG COVID 2466 01:40:48,080 --> 01:40:49,920 AND IN THOSE THAT DON'T DEVELOP 2467 01:40:49,920 --> 01:40:51,840 LUNG COVID. SO LONG STORY IS WE 2468 01:40:51,840 --> 01:40:54,080 DON'T KNOW WHAT THE EFFECT OF 2469 01:40:54,080 --> 01:40:56,160 LONG COVID LONG TERM. I THINK WE 2470 01:40:56,160 --> 01:40:57,320 ARE LIVING THE SITUATION AND WE 2471 01:40:57,320 --> 01:41:04,160 WILL SEE, I WI WILL WILL BE AN R 2472 01:41:04,160 --> 01:41:06,240 IN THE NEXT YEAR NEXT TEN YEARS 2473 01:41:06,240 --> 01:41:08,800 THE EPIDEMIOLOGICAL DATA THE 2474 01:41:08,800 --> 01:41:12,920 MIGHTY STUDIED NIH IS DOING, 2475 01:41:12,920 --> 01:41:14,040 ESPECIALLY NIAID, WILL PUBLISH 2476 01:41:14,040 --> 01:41:18,320 THE RESULTS. 2477 01:41:18,320 --> 01:41:22,960 >>HERE IS A QUESTION THAT DEALS 2478 01:41:22,960 --> 01:41:27,120 ON THE ISSUE OF WHETHER THE 2479 01:41:27,120 --> 01:41:32,560 PARABIOTIC EXPERIMENTS OR PLASMA 2480 01:41:32,560 --> 01:41:37,640 EXPERIMENTS, YOU STUDY OR SAW 2481 01:41:37,640 --> 01:41:39,120 THE EFFECT ON THE HIPPOCAMPUS 2482 01:41:39,120 --> 01:41:41,040 AND THE BRAIN AND SO FORTH. SO 2483 01:41:41,040 --> 01:41:47,680 THE QUESTION REALLY IS, HOW 2484 01:41:47,680 --> 01:41:49,040 UNION VERSAL ARE THESE EFFECTS 2485 01:41:49,040 --> 01:41:51,640 ON DIFFERENT -- UNIVERSAL ON 2486 01:41:51,640 --> 01:41:53,240 DIFFERENT TISSUE SYSTEMS? AND 2487 01:41:53,240 --> 01:41:56,120 THIS UNDOUBTEDLY HAS SOME DEGREE 2488 01:41:56,120 --> 01:41:57,840 ON THE QUESTION WE RECEIVED ON 2489 01:41:57,840 --> 01:42:00,280 WHETHER THE INFUSIONS EFFECT 2490 01:42:00,280 --> 01:42:04,560 FERTILITY IN MALE OR FEMALE MICE 2491 01:42:04,560 --> 01:42:06,440 OR MEN OR WOMEN. 2492 01:42:06,440 --> 01:42:08,600 >>YES. T SO I THINK THE 2493 01:42:08,600 --> 01:42:10,800 EVIDENCE NOW IS THAT NO, THE -- 2494 01:42:10,800 --> 01:42:14,640 WHETHER IT BE PARABIOSIS, DO NOT 2495 01:42:14,640 --> 01:42:16,840 IMPACT ALL TISSUES, SOME OF THEM 2496 01:42:16,840 --> 01:42:18,120 DO SEEM TO BE THERE'S SOME 2497 01:42:18,120 --> 01:42:19,920 EVIDENCE THAT SOME DO SEEM TO BE 2498 01:42:19,920 --> 01:42:22,000 REFRACTORY TO SOME OF THESE 2499 01:42:22,000 --> 01:42:23,680 INTERVENTIONS. ALSO THE 2500 01:42:23,680 --> 01:42:26,320 MAGNITUDE IS DIFFERENT, THERE 2501 01:42:26,320 --> 01:42:28,560 WERE A FEW SEQUENCING PAPERS 2502 01:42:28,560 --> 01:42:30,240 THAT CAME OUT, STEM CELL AND 2503 01:42:30,240 --> 01:42:31,480 NATURE, THEY DID SINGLE CELL TO 2504 01:42:31,480 --> 01:42:32,720 SEE THE MAGNITUDE AND IT IS NOT 2505 01:42:32,720 --> 01:42:34,880 THE SAME. I THINK WE ARE STILL 2506 01:42:34,880 --> 01:42:37,440 WAITING ON SOME BROADER 2507 01:42:37,440 --> 01:42:39,080 EPIGENETIC SORT OF 2508 01:42:39,080 --> 01:42:40,840 CHARACTERIZATION AS WEL WELL. NT 2509 01:42:40,840 --> 01:42:42,760 ALL TISSUES RESPOND THE SAME 2510 01:42:42,760 --> 01:42:44,560 WAY. SOME HIGHER MAGNITUDE, SOME 2511 01:42:44,560 --> 01:42:45,840 LOWER, I THINK IT DEPENDS ALSO 2512 01:42:45,840 --> 01:42:47,720 ON THE LEVEL OF GENERATIVE 2513 01:42:47,720 --> 01:42:49,280 CAPACITY OF EACH INDIVIDUAL 2514 01:42:49,280 --> 01:42:52,640 TISSUE. IN TERMS OF 2515 01:42:52,640 --> 01:42:53,280 REPRODUCTION, I BELIEVE THERE 2516 01:42:53,280 --> 01:42:59,160 WAS ONE PARABIOSIS, PARABIOSIS 2517 01:42:59,160 --> 01:43:02,000 STUDY THAT CAME OUT, IT WAS NOT 2518 01:43:02,000 --> 01:43:03,000 NECESSARILY THOUGH LIKE THE 2519 01:43:03,000 --> 01:43:04,760 YOUNG AND THE OLD, I FORGOT WHAT 2520 01:43:04,760 --> 01:43:06,520 IT WAS THEY PUT TOGETHER BUT 2521 01:43:06,520 --> 01:43:07,360 THERE WERE HUMAN MORAL 2522 01:43:07,360 --> 01:43:08,640 COMPONENTS THAT HAD AN EFFECT. 2523 01:43:08,640 --> 01:43:11,320 THERE'S BEEN PAPERS THAT FOCUS 2524 01:43:11,320 --> 01:43:14,760 MORE ON THINGS LIKE NAD PLUS 2525 01:43:14,760 --> 01:43:18,920 NADH, THAT HAD IMPACT ON THE 2526 01:43:18,920 --> 01:43:21,800 FOCUNDITY AS WELL AS EQUALITY, 2527 01:43:21,800 --> 01:43:23,600 BUT NOT TOO MUCH, IT'S TOTALLY 2528 01:43:23,600 --> 01:43:24,000 UNDERSTUDIED. 2529 01:43:24,000 --> 01:43:25,800 >>HERE IS AN INTERESTING 2530 01:43:25,800 --> 01:43:29,280 QUESTION, THAT CAME IN. HAVE YOU 2531 01:43:29,280 --> 01:43:31,960 OR ANYONE REPEATED SOME OF YOUR 2532 01:43:31,960 --> 01:43:34,520 STUDIES IN TRANSGENIC MICE WHICH 2533 01:43:34,520 --> 01:43:39,160 HAVE A HUMANIZED LIVER? 2534 01:43:39,160 --> 01:43:45,120 >>NO. I DO KNOW THAT THERE ARE 2535 01:43:45,120 --> 01:43:49,520 STUDY BEING DONE WITH CHIMERIC 2536 01:43:49,520 --> 01:43:50,560 ANIMALS WHERE THEY HAVE BEEN 2537 01:43:50,560 --> 01:43:53,400 MIXING LIKE RAT AND MOUSE OR 2538 01:43:53,400 --> 01:43:55,720 OTHER SPECIES LONGER LIVED WITH 2539 01:43:55,720 --> 01:43:57,000 NOT. THAT MIGHT GET INTO THAT 2540 01:43:57,000 --> 01:43:57,840 TYPE OF QUESTION. I DON'T KNOW 2541 01:43:57,840 --> 01:44:00,440 IF THEY ARE DOING IT IN A TISSUE 2542 01:44:00,440 --> 01:44:03,040 SPECIFIC MANNER OR NOT. BUT 2543 01:44:03,040 --> 01:44:04,040 YEAH, I HAVE HEARD OF THOSE 2544 01:44:04,040 --> 01:44:07,640 TYPES OF EXPERIMENTS IN TERMS OF 2545 01:44:07,640 --> 01:44:10,280 INNER SPECIES. 2546 01:44:10,280 --> 01:44:13,080 >>HUMANIZED LIVER, I DIDN'T 2547 01:44:13,080 --> 01:44:16,120 KNOW THAT. 2548 01:44:16,120 --> 01:44:17,720 (OVERLAPPING SPEAKERS) 2549 01:44:17,720 --> 01:44:23,080 >>YOU DO IT NSG SO THE HUMAN 2550 01:44:23,080 --> 01:44:24,560 UMBILICAL CORD BLOOD WAS NSG AND 2551 01:44:24,560 --> 01:44:27,480 YOU CAN DO IT IN IMMUNE 2552 01:44:27,480 --> 01:44:28,960 COMPROMISED MICE. THEY SHOW 2553 01:44:28,960 --> 01:44:30,840 SOME ACCELERATED AGING 2554 01:44:30,840 --> 01:44:31,600 PHENOTYPES BUT THEN YOU ARE 2555 01:44:31,600 --> 01:44:34,160 TAKING AWAY THE IMMUNE 2556 01:44:34,160 --> 01:44:36,960 COMPONENT. SO YOU TAKE THE MODEL 2557 01:44:36,960 --> 01:44:39,440 BUT THERE ARE RESTRICTIONS. 2558 01:44:39,440 --> 01:44:43,480 >>SO WE HAVE -- HERE IS A 2559 01:44:43,480 --> 01:44:47,360 PROVOCATIVE QUESTION. IS AGING 2560 01:44:47,360 --> 01:44:52,720 OR -- IS AGING AND 2561 01:44:52,720 --> 01:44:55,040 NEURODEGENERATION, ARE THEY 2562 01:44:55,040 --> 01:44:56,480 CAUSALLY OR ARE THEY CAUSE OR 2563 01:44:56,480 --> 01:45:02,320 EFFECT? IS AGING THE CAUSE OF 2564 01:45:02,320 --> 01:45:05,680 NEURODEGENERATION OR IS 2565 01:45:05,680 --> 01:45:06,640 NEURODEGENERATION ACTUALLY CAUSE 2566 01:45:06,640 --> 01:45:16,480 OF AGING? 2567 01:45:16,480 --> 01:45:20,160 >>I THINK AGING IS FINALLY, 2568 01:45:20,160 --> 01:45:22,280 AGING IS MACRO MOLECULAR 2569 01:45:22,280 --> 01:45:23,440 ORGANELLE AND CELLULAR DAMAGE 2570 01:45:23,440 --> 01:45:25,520 AND THAT HAS AN EFFECT IN 2571 01:45:25,520 --> 01:45:30,200 MULTIPLE LEVEL. AND IN THE BRAIN 2572 01:45:30,200 --> 01:45:31,360 MORE THAN ANYWHERE ELSE BECAUSE 2573 01:45:31,360 --> 01:45:35,040 OF THE INTRINSIC COMPLEXITY OF 2574 01:45:35,040 --> 01:45:40,200 THIS STRUCTURE IS MORE SUSES 2575 01:45:40,200 --> 01:45:41,040 ACCEPTABLE TO DAMAGE 2576 01:45:41,040 --> 01:45:43,040 ACCUMULATION. ONCE THE BRAIN -- 2577 01:45:43,040 --> 01:45:44,040 SUSCEPTIBLE TO DAMAGE 2578 01:45:44,040 --> 01:45:46,000 ACCUMULATION. ONCE THE BRAIN IS 2579 01:45:46,000 --> 01:45:48,760 AFFECTED, THERE'S A MULTIPLE -- 2580 01:45:48,760 --> 01:45:50,080 OF THE EFFECT ON THE PHENOTYPE 2581 01:45:50,080 --> 01:45:51,640 BECAUSE THE BRAIN REALLY 2582 01:45:51,640 --> 01:45:53,600 CONTROLS SO MANY THINGS. THE 2583 01:45:53,600 --> 01:45:59,800 BRAIN IS AFFECTING THE INNER 2584 01:45:59,800 --> 01:46:00,760 CLOCK, IT IS AFFECTING HORMONE 2585 01:46:00,760 --> 01:46:03,360 PRODUCTION. WE KNOW THAT THE 2586 01:46:03,360 --> 01:46:06,360 BRAIN IS AFFECTING IMMUNOLOGY, 2587 01:46:06,360 --> 01:46:10,000 SYMPATHETIC AND PARASYMPATHETIC 2588 01:46:10,000 --> 01:46:11,680 SYSTEM. SO (INAUDIBLE) NOT 2589 01:46:11,680 --> 01:46:12,920 WORKING MOST REGULATORY 2590 01:46:12,920 --> 01:46:15,800 MECHANISM THAT MAINTAIN STABLE 2591 01:46:15,800 --> 01:46:18,160 HOMEOSTASIS IN THE BODY START 2592 01:46:18,160 --> 01:46:19,760 COLLAPSING. SO I THINK ONCE THE 2593 01:46:19,760 --> 01:46:22,200 BRAIN IS INVOLVED THERE IS 2594 01:46:22,200 --> 01:46:25,680 ACCELERATION OF THE PROCESS. WE 2595 01:46:25,680 --> 01:46:30,440 SEE PEOPLE, WE SEE CLEARLY 2596 01:46:30,440 --> 01:46:32,560 CLINICALLY THAT BRAIN PATHOLOGY 2597 01:46:32,560 --> 01:46:34,240 IS ACCELERATOR. THE OTHER THING 2598 01:46:34,240 --> 01:46:37,880 IS THAT WE CLEARLY SEE THAT 2599 01:46:37,880 --> 01:46:40,000 GENERAL HEALTH IS A STRONG 2600 01:46:40,000 --> 01:46:41,920 PREDICTOR OF COGNITIVE DECLINE 2601 01:46:41,920 --> 01:46:44,080 AND DEMENTIA. GENERAL HEALTH, 2602 01:46:44,080 --> 01:46:46,120 PEOPLE THAT MANY, MANY 2603 01:46:46,120 --> 01:46:48,040 MULTI-MORBIDITIES TEND TO HAVE 2604 01:46:48,040 --> 01:46:50,480 ACCELERATED COGNITIVE DECLINE. 2605 01:46:50,480 --> 01:46:53,160 SO TWO THINGS VERY CORRELATED. 2606 01:46:53,160 --> 01:46:54,600 >>VERY GOOD. DO YOU WANT TO 2607 01:46:54,600 --> 01:46:56,400 COMMENT ABOUT THAT, SAUL? 2608 01:46:56,400 --> 01:46:58,960 >>I GUESS I THINK ABOUT IT IN 2609 01:46:58,960 --> 01:47:00,960 TERMS OF TEMPORAL COMPONENT. 2610 01:47:00,960 --> 01:47:03,720 THERE IS A TEMPORAL COMPONENT, 2611 01:47:03,720 --> 01:47:06,240 TO NEURO-- AGE RELATED DEMENTIA 2612 01:47:06,240 --> 01:47:08,480 RELATED NEURODEGENERATION. YOU 2613 01:47:08,480 --> 01:47:11,760 CAN'T UNCOUPLE THE TIMING AND 2614 01:47:11,760 --> 01:47:13,080 PROGRESSION OF TIME WITH ONSET 2615 01:47:13,080 --> 01:47:14,800 AND SORT OF ACCUMULATION AND 2616 01:47:14,800 --> 01:47:18,880 EXACERBATION OF THAT DISEASE. I 2617 01:47:18,880 --> 01:47:19,920 DON'T KNOW ABOUT CAUSE 2618 01:47:19,920 --> 01:47:21,560 CONSEQUENCE BUT I DO KNOW ABOUT 2619 01:47:21,560 --> 01:47:23,640 ASSOCIATION. YOU CAN'T UNLINK 2620 01:47:23,640 --> 01:47:25,520 THE ONE FROM THE OTHER. SO I 2621 01:47:25,520 --> 01:47:27,080 THINK ABOUT THEM TOGETHER IN 2622 01:47:27,080 --> 01:47:28,680 THAT WAY. I DO THE SAME THING 2623 01:47:28,680 --> 01:47:31,520 WHEN TRYING TO PLAN EXPERIMENTS 2624 01:47:31,520 --> 01:47:33,680 AND DESIGN EXPERIMENTS. TEMPORAL 2625 01:47:33,680 --> 01:47:38,880 COMPONENT IS ALWAYS THERE. 2626 01:47:38,880 --> 01:47:40,800 >>INTERESTED, SEVERAL MONTHS 2627 01:47:40,800 --> 01:47:43,960 AGO I WAS READING ABOUT AGING IN 2628 01:47:43,960 --> 01:47:46,960 SPECIES OF DIFFERENT LIFE SPAN. 2629 01:47:46,960 --> 01:47:49,480 AND I WAS FASCINATED BY THE IDEA 2630 01:47:49,480 --> 01:47:52,440 THAT BIG ANIMALS, ELEPHANTS AND 2631 01:47:52,440 --> 01:47:56,120 ALL, WHEN THEY FINALLY DIE, AND 2632 01:47:56,120 --> 01:48:00,080 THEY ARE AUTOPSIED, THEY DON'T 2633 01:48:00,080 --> 01:48:02,800 FIND VERY MUCH, THEY DON'T DIE 2634 01:48:02,800 --> 01:48:06,120 OF DEGENERATIVE DISEASES LIKE WE 2635 01:48:06,120 --> 01:48:14,280 HAVE. THEY JUST SORT OF LIKE OLD 2636 01:48:14,280 --> 01:48:15,880 SOLDIERS THEY JUST FADE AWAY. IS 2637 01:48:15,880 --> 01:48:18,480 THAT THE AGING PROCESS? AS 2638 01:48:18,480 --> 01:48:20,040 COMPARED TO WHAT HAPPENS IN 2639 01:48:20,040 --> 01:48:24,400 ANIMALS HAVING A SHORT HALF 2640 01:48:24,400 --> 01:48:26,000 LIFE, OR IN HUMANS WHERE WE DO 2641 01:48:26,000 --> 01:48:27,320 ALL KINDS OF THINGS THAT AREN'T 2642 01:48:27,320 --> 01:48:32,440 GOOD FOR US. BUT IN A SHORT HALF 2643 01:48:32,440 --> 01:48:33,800 LIFE YOU CAN DO THINGS TO AFFECT 2644 01:48:33,800 --> 01:48:36,920 THE PROCESS THAT IS OPERATING 2645 01:48:36,920 --> 01:48:38,920 OVER A MUCH SHORTER TIME FRAME. 2646 01:48:38,920 --> 01:48:42,720 WHAT DO YOU THINK ABOUT THAT? 2647 01:48:42,720 --> 01:48:43,960 ANY TAKERS? 2648 01:48:43,960 --> 01:48:46,720 >>I HAVE NO IDEA. I THINK THAT 2649 01:48:46,720 --> 01:48:50,160 I HAVEN'T HAD THAT PARTICULAR -- 2650 01:48:50,160 --> 01:48:52,480 THAT SOUNDS QUITE INTERESTING. 2651 01:48:52,480 --> 01:48:54,600 WE DO KNOW VERY DIFFERENT BIC 2652 01:48:54,600 --> 01:48:56,080 DIFFERENCE BETWEEN SMALL ANIMAL 2653 01:48:56,080 --> 01:49:01,920 AND LARGE ANIMAL, THE THEORY 2654 01:49:01,920 --> 01:49:03,360 THAT I DON'T KNOW HOW MUCH IS 2655 01:49:03,360 --> 01:49:07,200 FOLLOW NOW THAT THERE IS THE IN 2656 01:49:07,200 --> 01:49:08,080 RELATIONSHIP BETWEEN THE SIZE 2657 01:49:08,080 --> 01:49:12,400 AND LONGEVITY. THE THEORY OF 2658 01:49:12,400 --> 01:49:16,080 ALLO STATIC LOAD, IT SEEM TO BE 2659 01:49:16,080 --> 01:49:18,280 THERE IS A CORRELATION, OF O 2660 01:49:18,280 --> 01:49:21,480 COURSE, THERE'S BEEN ARGUED THAT 2661 01:49:21,480 --> 01:49:27,560 THIS CORRELATION HAS EXCEPTIONS 2662 01:49:27,560 --> 01:49:30,000 THAT BREAK THE RULES. FOR 2663 01:49:30,000 --> 01:49:31,560 EXAMPLE BIG DOGS LIVE LESS THAN 2664 01:49:31,560 --> 01:49:33,640 SMALL DOGS AND PEOPLE HAVE BEEN 2665 01:49:33,640 --> 01:49:36,360 ARGUING THAT THIS IS BECAUSE 2666 01:49:36,360 --> 01:49:40,680 DOGS ARE NOT SELECTED BY NATURE 2667 01:49:40,680 --> 01:49:42,600 BUT BREED. SO THEY ARE NOT 2668 01:49:42,600 --> 01:49:44,840 SUBJECT TO SAME NATURAL 2669 01:49:44,840 --> 01:49:48,000 SELECTION. ALSO THERE IS 2670 01:49:48,000 --> 01:49:49,880 BIRDINGS SEEM TO VIE -- BIRDS 2671 01:49:49,880 --> 01:49:51,120 VIOLATE THIS RULE. BUT PEOPLE 2672 01:49:51,120 --> 01:49:54,880 SAY THAT IS BECAUSE THEIR 2673 01:49:54,880 --> 01:49:56,320 MITOCHONDRIA ARE SEALED BECAUSE 2674 01:49:56,320 --> 01:49:59,760 THEY HAVE SO MUCH NEED TORR 2675 01:49:59,760 --> 01:50:03,200 ENERGY DURING FLYING. SO 2676 01:50:03,200 --> 01:50:06,920 EVOLUTION SEALED THEM SO THEY 2677 01:50:06,920 --> 01:50:11,320 CANNOT PRODUCE AT ALL THAT GO 2678 01:50:11,320 --> 01:50:14,080 BEYOND BOUNDS OF MITOCHONDRIA. 2679 01:50:14,080 --> 01:50:15,880 IT IS ALL INTERESTING 2680 01:50:15,880 --> 01:50:16,920 SPECULATION, I'M ALWAYS 2681 01:50:16,920 --> 01:50:19,720 FASCINATED. THE LAST ONE I READ 2682 01:50:19,720 --> 01:50:22,680 IS REALLY BEAUTIFUL 2683 01:50:22,680 --> 01:50:23,760 DEMONSTRATION OF THE RATE OF 2684 01:50:23,760 --> 01:50:28,840 SOMATIC MUTATION. THE LEAST 2685 01:50:28,840 --> 01:50:30,400 SOMATIC MUTATION YOU HAVE THE 2686 01:50:30,400 --> 01:50:32,400 HIGHEST LONGEVITY SUGGESTING 2687 01:50:32,400 --> 01:50:34,200 THAT THE ONLY THING THAT 2688 01:50:34,200 --> 01:50:39,000 EVOLUTION HAS DONE IS IMPROVE 2689 01:50:39,000 --> 01:50:40,680 THE SURVEILLANCE AND REPAIR OF 2690 01:50:40,680 --> 01:50:42,240 SOMATIC MUTATION. WHETHER THIS 2691 01:50:42,240 --> 01:50:46,080 IS TRUE OR NOT, I DON'T REALLY 2692 01:50:46,080 --> 01:50:50,240 HAVE AUTHORITY TO SAY. 2693 01:50:50,240 --> 01:50:52,680 >>SO SAUL WE HAVE ANOTHER 2694 01:50:52,680 --> 01:50:56,320 QUESTION FOR YOU. DO FACTORS 2695 01:50:56,320 --> 01:50:58,640 LIKE ALCOHOL OR TOXINS OR SOME 2696 01:50:58,640 --> 01:51:01,840 STUFF THAT IS BAD FOR THE LIVER, 2697 01:51:01,840 --> 01:51:04,960 IS THERE ANY EVIDENCE THAT THAT 2698 01:51:04,960 --> 01:51:07,720 AFFECTS THE LEVEL OF THE 2699 01:51:07,720 --> 01:51:09,760 PROTEINS YOU'RE STUDYING OR THE 2700 01:51:09,760 --> 01:51:13,320 EFFECT OF PLASMA FROM SUCH 2701 01:51:13,320 --> 01:51:15,560 ANIMALS IN YOUR EXPERIMENTS? HAS 2702 01:51:15,560 --> 01:51:18,040 THAT BEEN INVESTIGATED? ANY WAY? 2703 01:51:18,040 --> 01:51:21,880 >>THERE VERY LITTLE KNOWN ABOUT 2704 01:51:21,880 --> 01:51:24,240 THE ENZYME WHICH MAKES IT EXCITE 2705 01:51:24,240 --> 01:51:25,360 BUG DIFFICULT BECAUSE YOU KIND 2706 01:51:25,360 --> 01:51:26,480 OF JUST EXPLORING SOMETHING. 2707 01:51:26,480 --> 01:51:28,240 WHAT I WILL SAY IS EVEN IN THE 2708 01:51:28,240 --> 01:51:30,160 ANIMAL MODEL FOR EXAMPLE IF YOU 2709 01:51:30,160 --> 01:51:31,680 WERE TO INCREASE INFLAMMATION IN 2710 01:51:31,680 --> 01:51:35,360 THE CONTEXT OF EXERCISE IT CAN 2711 01:51:35,360 --> 01:51:36,280 BLOUNT SOME OF THE EFFECTS, THE 2712 01:51:36,280 --> 01:51:37,560 SAME FOR YOUNG BLOOD IF YOU WERE 2713 01:51:37,560 --> 01:51:39,000 TO INCREASE INFLAMMATION SO 2714 01:51:39,000 --> 01:51:41,440 THERE IS AN IMMUNE COMPONENT. SO 2715 01:51:41,440 --> 01:51:44,120 JUST THE REACTION OF A TOXIN 2716 01:51:44,120 --> 01:51:45,400 THAT WOULD ELICIT THAT RESPONSE 2717 01:51:45,400 --> 01:51:48,400 IN THE IMMUNE SYSTEM, I WOULD 2718 01:51:48,400 --> 01:51:49,720 THINK IT WOULD HAVE SOME 2719 01:51:49,720 --> 01:51:52,240 DETRIMENTAL EFFECT THAT CAN 2720 01:51:52,240 --> 01:51:54,000 BLUNTED THAT FROM HAPPENING. WE 2721 01:51:54,000 --> 01:51:56,520 SEE THAT AS WELL THINGS LIKE 2722 01:51:56,520 --> 01:51:58,000 SAYS FROM SENESCENCE THERE IS SO 2723 01:51:58,000 --> 01:52:01,560 MUCH OVERLAP BETWEEN SAS AND PRO 2724 01:52:01,560 --> 01:52:04,760 JERONIC FACTORS A LOT IMMUNE IN 2725 01:52:04,760 --> 01:52:06,520 NATURE. SO THERE ARE THINGS THAT 2726 01:52:06,520 --> 01:52:08,120 PROMPT AGING MECHANISMS AS WELL, 2727 01:52:08,120 --> 01:52:10,160 THAT CAN'T JUST -- WE HAVE TO 2728 01:52:10,160 --> 01:52:11,720 REMEMBER IT GOES BOTH WAYS, IT 2729 01:52:11,720 --> 01:52:12,880 IS BIDIRECTIONAL. 2730 01:52:12,880 --> 01:52:15,040 >>SO WHAT THE TWO OF YOU 2731 01:52:15,040 --> 01:52:20,040 PRESENTED US WITH IS AN 2732 01:52:20,040 --> 01:52:24,480 INCREDIBLE POTPOURRI LIST OF 2733 01:52:24,480 --> 01:52:25,640 EXCITING DEVELOPMENTS IN ONE OF 2734 01:52:25,640 --> 01:52:29,880 THE MOST CHALLENGING AREAS OF 2735 01:52:29,880 --> 01:52:35,040 PUBLIC HEALTH MEDICINE AND BASIC 2736 01:52:35,040 --> 01:52:37,040 BIOLOGY. SO MAYBE EACH ONE OF 2737 01:52:37,040 --> 01:52:41,120 YOU WOULD LIKE TO TAKE A COUPLE 2738 01:52:41,120 --> 01:52:42,600 OF LAST MINUTES THAT WE HAVE AND 2739 01:52:42,600 --> 01:52:44,400 IF YOU FEEL LIKE IT, LOOK IN 2740 01:52:44,400 --> 01:52:47,240 YOUR CRYSTAL BALL AND TELL US 2741 01:52:47,240 --> 01:52:49,480 WHAT YOU WOULD LIKE DO SEE 2742 01:52:49,480 --> 01:52:52,240 HAPPEN OR WHAT YOU THINK IS 2743 01:52:52,240 --> 01:52:54,040 LIKELY TO HAPPEN AND BEHIND ALL 2744 01:52:54,040 --> 01:52:57,120 THIS OF COURSE IS THE ENORMOUS 2745 01:52:57,120 --> 01:53:00,480 OPPORTUNITY FOR YOUNG PEOPLE 2746 01:53:00,480 --> 01:53:03,960 INTERESTED IN SCIENCE TO BE 2747 01:53:03,960 --> 01:53:05,480 INTERESTED IN THIS PROBLEM AS 2748 01:53:05,480 --> 01:53:08,080 BOTH OF YOU HAVE REFLECTED BOTH 2749 01:53:08,080 --> 01:53:13,400 FROM THE STANDPOINT OF CLINICAL 2750 01:53:13,400 --> 01:53:15,320 INVESTIGATION AND FROM 2751 01:53:15,320 --> 01:53:20,160 STANDPOINT OF BASIC MECHANISMS. 2752 01:53:20,160 --> 01:53:20,720 YOU WANT TO BE -- 2753 01:53:20,720 --> 01:53:22,840 >>I WILL GO FOR IT. I REALLY 2754 01:53:22,840 --> 01:53:24,200 WANT TO HEAR WHAT LUIGI HAS TO 2755 01:53:24,200 --> 01:53:26,520 SAY. WE TALKED ABOUT THIS BEFORE 2756 01:53:26,520 --> 01:53:29,840 THE EVENT STARTED WITH YOU AS 2757 01:53:29,840 --> 01:53:32,920 WELL AS WITH LUIGI, FOR ME, THE 2758 01:53:32,920 --> 01:53:34,960 FACT WE ARE NOW SEEING DIFFERENT 2759 01:53:34,960 --> 01:53:35,680 INTERVENTIONS HAVE DIFFERENT 2760 01:53:35,680 --> 01:53:37,520 EFFECTS THERE'S MULTIPLE FACTORS 2761 01:53:37,520 --> 01:53:39,000 THAT'S ADDITIVE, COUPLE THAT 2762 01:53:39,000 --> 01:53:40,520 WITH THE FACT WE ARE ALL AGING 2763 01:53:40,520 --> 01:53:42,240 SLIGHTLY DIFFERENTLY OR 2764 01:53:42,240 --> 01:53:43,240 DIFFERENT SYSTEMS MIGHT BE GOING 2765 01:53:43,240 --> 01:53:46,240 FIRST OR SECOND OR THIRD. I LOVE 2766 01:53:46,240 --> 01:53:48,000 THIS IDEA OF A PERSONALIZED 2767 01:53:48,000 --> 01:53:49,800 APPROACH. I WOULD LOVE TO BE 2768 01:53:49,800 --> 01:53:51,720 ABLE TO GO TO THE PHYSICIAN, 2769 01:53:51,720 --> 01:53:53,520 GETTING A CHECK UP AND THEY TAKE 2770 01:53:53,520 --> 01:53:58,000 MY BLOOD, MEASURE MY PROGERONIC 2771 01:53:58,000 --> 01:54:00,040 FACTORS OR SAS FACTORS, TAKE MY 2772 01:54:00,040 --> 01:54:02,760 BLOOD AND THEN DO A EPIGENETIC 2773 01:54:02,760 --> 01:54:04,440 CLOCK AND THEY CAN GIVE ME AN 2774 01:54:04,440 --> 01:54:06,000 IDEA OF KIND OF WHAT IS 2775 01:54:06,000 --> 01:54:08,800 HAPPENING RIGHT NOW AT THIS 2776 01:54:08,800 --> 01:54:15,720 STAGE. EXERCISE EFFECTS THE 2777 01:54:15,720 --> 01:54:19,440 VASCULATURE BUT MAYBE THE 2778 01:54:19,440 --> 01:54:20,800 ANTI-GERONIC EFFECTS THE STEM 2779 01:54:20,800 --> 01:54:22,040 CELLS AND WE SEE YOUR 2780 01:54:22,040 --> 01:54:24,160 REGENERATION MARKERS ARE LOW. I 2781 01:54:24,160 --> 01:54:25,760 WOULD LOVE THAT. WHICH IS IN A 2782 01:54:25,760 --> 01:54:27,680 PERSONALIZED WAY, USING 2783 01:54:27,680 --> 01:54:28,800 BIOMARKERS AND USING SOME OF 2784 01:54:28,800 --> 01:54:32,000 THESE MECHANISMS ANALYTICS, 2785 01:54:32,000 --> 01:54:33,560 BLOOD, ALL THAT WE ARE 2786 01:54:33,560 --> 01:54:35,040 IDENTIFYING BE PERSONALIZE AND 2787 01:54:35,040 --> 01:54:35,840 TAILORED TO EACH INDIVIDUAL 2788 01:54:35,840 --> 01:54:37,920 PERSOPERSON. THAT'S WHAT I WANTI 2789 01:54:37,920 --> 01:54:39,280 WILL PUT LUIGI ON THE SPOT, 2790 01:54:39,280 --> 01:54:40,520 BECAUSE I ASKED EARLIER DO YOU 2791 01:54:40,520 --> 01:54:42,560 THINK WE ARE CLOSE AND DO YOU 2792 01:54:42,560 --> 01:54:46,120 THINK WE ARE FAR? I THINK I HAVE 2793 01:54:46,120 --> 01:54:47,720 MORE EXCITED TWO HOURS IN THAN I 2794 01:54:47,720 --> 01:54:49,600 WAS TWO HOURS AGO BECAUSE LUIGI, 2795 01:54:49,600 --> 01:54:51,960 HE'S LIKE YES, I THINK WE ARE 2796 01:54:51,960 --> 01:54:54,560 CLOSE. I'M AT THE BASIC WHYOLOGY 2797 01:54:54,560 --> 01:54:55,920 PERSPECTIVE AND IT IS NICE TO BE 2798 01:54:55,920 --> 01:54:58,040 -- BIOLOGY PERSPECTIVE, NICE TO 2799 01:54:58,040 --> 01:54:59,280 HAVE THOSE CONVERSATIONS WITH 2800 01:54:59,280 --> 01:55:00,840 CLINICIANS AND PEOPLE AT LEVEL 2801 01:55:00,840 --> 01:55:03,160 OF THE PATIENTS AND THE HUMAN 2802 01:55:03,160 --> 01:55:04,440 CONDITICONDITION. BECAUSE SOMETR 2803 01:55:04,440 --> 01:55:06,560 BASIC SCIENTISTS WE FORGET HOW 2804 01:55:06,560 --> 01:55:08,600 IS IT THAT WE ARE -- WHAT WE ARE 2805 01:55:08,600 --> 01:55:10,440 DOING CAN IMPACT IN THE NEXT 2806 01:55:10,440 --> 01:55:12,440 YEAR OR TWO, BUT WE HAVE SEEP IT 2807 01:55:12,440 --> 01:55:13,680 IN MY FELTED BETTER OR WORSE, I 2808 01:55:13,680 --> 01:55:15,360 SAW PEOPLE TRYING TO DO THINGS 2809 01:55:15,360 --> 01:55:17,280 THEY SHOULDN'T WITH YOUNG BLOOD 2810 01:55:17,280 --> 01:55:20,080 SO I KNOW BASIC CAN HAVE A HUGE 2811 01:55:20,080 --> 01:55:21,200 IMPACT ON THE HUMAN CONDITION. 2812 01:55:21,200 --> 01:55:22,720 NOW I HOPE THAT WE CAN COURSE 2813 01:55:22,720 --> 01:55:23,720 CORRECT AND DO IT IN THE 2814 01:55:23,720 --> 01:55:25,480 APPROPRIATE WAY. 2815 01:55:25,480 --> 01:55:29,040 >>RIGHT ON. 2816 01:55:29,040 --> 01:55:34,360 >>I THINK THAT WHAT I HAVE -- 2817 01:55:34,360 --> 01:55:36,680 FIRST OF ALL, I AM A DOCTOR. I'M 2818 01:55:36,680 --> 01:55:39,720 STILL A DOCTOR. I FEEL LIKE FOR 2819 01:55:39,720 --> 01:55:43,880 ME, EVERYTHING I DO HAS TO BE A 2820 01:55:43,880 --> 01:55:45,920 REFLECT IN HEALTH. SO I THINK IN 2821 01:55:45,920 --> 01:55:49,000 THIS TERM OF WHAT WOULD BE THE 2822 01:55:49,000 --> 01:55:51,440 IDEAL DREAM WHAT WE CAN 2823 01:55:51,440 --> 01:55:52,960 ACCOMPLISH. THIS IS SIMILAR TO 2824 01:55:52,960 --> 01:55:55,920 WHAT SAUL WAS SAYING. BUT LET ME 2825 01:55:55,920 --> 01:55:59,560 TRY TO ARTICULATE A DREAM. THE 2826 01:55:59,560 --> 01:56:00,480 DREAM WILL BE SOMEBODY GOES TO 2827 01:56:00,480 --> 01:56:04,960 THE DOCTOR, BECAUSE THEY HAVE 2828 01:56:04,960 --> 01:56:06,640 HAVING SOME PAIN IN THE LEFT 2829 01:56:06,640 --> 01:56:07,920 SHOULDER AND THE DOCTOR LOOK AT 2830 01:56:07,920 --> 01:56:11,120 THEM, LOOK AT THE LEFT SHOULDER 2831 01:56:11,120 --> 01:56:21,680 AND THEN THEY ALSO TAKE 1 MILL F 2832 01:56:21,680 --> 01:56:25,120 BLOOD. THEY DO PROTEOMIC 2833 01:56:25,120 --> 01:56:27,440 METABOLOMICS METH LOAMICS AND 2834 01:56:27,440 --> 01:56:30,000 THESE TODAY IN RESEARCH WILL 2835 01:56:30,000 --> 01:56:33,200 COST $5,000 BUT THERE IS NO 2836 01:56:33,200 --> 01:56:34,960 REASON WHY SHOULDN'T COST 30 2837 01:56:34,960 --> 01:56:37,160 CENTS. THOSE 30 CENTS WILL 2838 01:56:37,160 --> 01:56:39,920 PRODUCE ENORMOUS AMOUNT OF 2839 01:56:39,920 --> 01:56:42,320 INFORMATION AND THERE IS ALREADY 2840 01:56:42,320 --> 01:56:43,640 STRONG EVIDENCE THAT PROFILE 2841 01:56:43,640 --> 01:56:47,080 THIS BIOMARKER PREDICT DISEASE, 2842 01:56:47,080 --> 01:56:50,640 INCLUDING ALZHEIMER'S DISEASE. 2843 01:56:50,640 --> 01:56:53,240 THOSE ARE ALGORITHM MAY NOT BE 2844 01:56:53,240 --> 01:56:55,040 PERFECT BUT IF WE CAN APPLY THE 2845 01:56:55,040 --> 01:56:56,360 BIOMARKERS TO MILLIONS OF PEOPLE 2846 01:56:56,360 --> 01:56:58,440 THAT GO TO A DOCTOR AND 2847 01:56:58,440 --> 01:57:01,160 INTRODUCE THOSE INFORMATION INTO 2848 01:57:01,160 --> 01:57:03,360 A MEDICAL RECORD, ELECTRONIC 2849 01:57:03,360 --> 01:57:06,160 MEDICAL RECORD THAT ALLOW 2850 01:57:06,160 --> 01:57:08,680 ARTIFICIAL INTELLIGENCE FAR 2851 01:57:08,680 --> 01:57:10,000 LOWER ON THOSE TAP INTO THESE 2852 01:57:10,000 --> 01:57:13,520 PEOPLE BASED ON INTERVENTION. 2853 01:57:13,520 --> 01:57:15,800 THOSE ARE MORE AUTOMATICALLY 2854 01:57:15,800 --> 01:57:17,360 IMPROVE ALGORITHM AND BE MORE 2855 01:57:17,360 --> 01:57:19,280 INFORMED SO WE WILL HAVE A 2856 01:57:19,280 --> 01:57:20,360 HEALTHCARE SYSTEM WHERE WHATEVER 2857 01:57:20,360 --> 01:57:24,080 WE DO, WE LEARN MORE, WE CAN 2858 01:57:24,080 --> 01:57:26,680 RELATE THAT EXPERIENCE AND THAT 2859 01:57:26,680 --> 01:57:28,680 WILL TELL US EARLY LIFE WHAT WE 2860 01:57:28,680 --> 01:57:37,680 NEED TO DO. WE DON'T HAVE THE 2861 01:57:37,680 --> 01:57:39,160 ENTIRE ARMAMENTARIUM TO ANSWER 2862 01:57:39,160 --> 01:57:39,960 THOSE QUESTIONS BUT WE ARE 2863 01:57:39,960 --> 01:57:42,080 DEVELOPING THEM AS WE DEVELOP 2864 01:57:42,080 --> 01:57:45,600 THEM AND INTRODUCE THEM INTO THE 2865 01:57:45,600 --> 01:57:47,000 SYSTEM, OUR KNOWLEDGE WILL 2866 01:57:47,000 --> 01:57:48,720 EXPAND PROGRESSIVELY. SO I AM 2867 01:57:48,720 --> 01:57:49,960 OPTIMISTIC. I THINK THIS IS 2868 01:57:49,960 --> 01:57:52,400 GOING TO HAPPEN. AND NEEDS TO 2869 01:57:52,400 --> 01:57:55,480 MAP BECAUSE IF IT DOESN'T HAPPEN 2870 01:57:55,480 --> 01:57:59,320 THE DEMOGRAPHIC IMPERATIVE WILL 2871 01:57:59,320 --> 01:58:00,120 COLLAPSE ANY HEALTHCARE SYSTEM 2872 01:58:00,120 --> 01:58:03,320 IN THE WORLD. IT DOESN'T MATTER 2873 01:58:03,320 --> 01:58:05,080 HOW MUCH MONEY THE COUNTRY HAS. 2874 01:58:05,080 --> 01:58:07,760 WE CAN'T AFFORD NOT TO 2875 01:58:07,760 --> 01:58:11,400 ACCOMPLISH THIS. 2876 01:58:11,400 --> 01:58:12,640 >>ONE STATEMENT ABOUT THE 2877 01:58:12,640 --> 01:58:13,760 STUDENTS YOU SAID ABOUT WHY THEY 2878 01:58:13,760 --> 01:58:15,360 SHOULD DO AGING VERGE. SO I WANT 2879 01:58:15,360 --> 01:58:16,640 TO POINT OUT THAT AGING IS ONE 2880 01:58:16,640 --> 01:58:19,000 OF THE FEW THINGS THAT'S 2881 01:58:19,000 --> 01:58:20,040 IMPACTING ABSOLUTELY EVERYONE 2882 01:58:20,040 --> 01:58:21,720 AND IT IS ABSOLUTELY BLIND TO 2883 01:58:21,720 --> 01:58:23,480 BACKGROUND. IT DOESN'T MATTER 2884 01:58:23,480 --> 01:58:25,800 WHETHER YOU GREW UP AFFLUENT OR 2885 01:58:25,800 --> 01:58:28,040 GREW UP POOR. AND I THINK WHAT 2886 01:58:28,040 --> 01:58:30,240 IS GREAT IS MYSELF, I'M A FIRST 2887 01:58:30,240 --> 01:58:33,720 GENERATION TO COLLEGE, MY 2888 01:58:33,720 --> 01:58:34,480 PARENTS CAME ILLEGALLY INTO THE 2889 01:58:34,480 --> 01:58:36,440 UNITED STATES, GREW UP POOR YET 2890 01:58:36,440 --> 01:58:37,680 THIS FIELD BECAUSE IT IS SO 2891 01:58:37,680 --> 01:58:40,200 BLIND, IT DOES IMPACT EVERYONE 2892 01:58:40,200 --> 01:58:41,520 INCLUSIVE SO NOT JUST THE 2893 01:58:41,520 --> 01:58:43,040 SCIENTIFIC CURIOSITY PERSPECTIVE 2894 01:58:43,040 --> 01:58:45,120 BUT ALSO BROADER FROM THE SOCIAL 2895 01:58:45,120 --> 01:58:46,280 PERSPECTIVE SOCIOECONOMIC, THIS 2896 01:58:46,280 --> 01:58:48,240 IS A WONDERFUL FEEL TO BE FROM 2897 01:58:48,240 --> 01:58:49,760 THE ACCEPTANCE PERSPECTIVE AND 2898 01:58:49,760 --> 01:58:51,840 THE IMPACT YOU CAN HAVE JUST 2899 01:58:51,840 --> 01:58:53,800 ACROSS SOCIETY. SO IN THINKING 2900 01:58:53,800 --> 01:58:54,680 ABOUT THOSE YOUNG STUDENTS THAT 2901 01:58:54,680 --> 01:58:56,800 ARE OUT THERE, I WOULD ENCOURAGE 2902 01:58:56,800 --> 01:58:58,200 THEM TO LOOK INTO THE SPACE OF 2903 01:58:58,200 --> 01:59:00,720 AGING. 2904 01:59:00,720 --> 01:59:04,360 >>WELL, ON BEHALF OF THE 2905 01:59:04,360 --> 01:59:06,800 HUNDREDS IF NOT THOUSANDS WHO 2906 01:59:06,800 --> 01:59:08,880 HAVE BEEN WATCHING THIS PROGRAM, 2907 01:59:08,880 --> 01:59:11,640 I'M SURE THEY SHARE THE 2908 01:59:11,640 --> 01:59:13,080 MR. SIMON: THAT I HAVE IN 2909 01:59:13,080 --> 01:59:22,920 LEASAME, YOUGAVE ELOQUENT TALKSA 2910 01:59:22,920 --> 01:59:24,720 PICTURE OF WHAT THE CHALLENGES 2911 01:59:24,720 --> 01:59:26,120 ARE AND WHAT THE EXCITING 2912 01:59:26,120 --> 01:59:29,040 DEVELOPMENTS ARE, AND 2913 01:59:29,040 --> 01:59:33,360 FURTHERMORE I THINK IT WAS NEAL 2914 01:59:33,360 --> 01:59:36,960 SPORE WHO SAID PREDICTION IS 2915 01:59:36,960 --> 01:59:37,640 VERY DIFFICULT PARTICULARLY 2916 01:59:37,640 --> 01:59:41,800 ABOUT THE FUTURE. BUT I THINK 2917 01:59:41,800 --> 01:59:42,960 THE PICTURE BOTH OF YOU 2918 01:59:42,960 --> 01:59:44,440 PRESENTED CAN BE SUMMED UP INTO 2919 01:59:44,440 --> 01:59:49,120 ONE BIG WORD. WHICH IS 2920 01:59:49,120 --> 01:59:51,320 EXCITEMENT. CERTAINLY A LOT IS 2921 01:59:51,320 --> 01:59:53,480 GOING TO HAPPEN THOUGH AT THE 2922 01:59:53,480 --> 01:59:54,480 MOMENT NOBODY QUITE KNOWS WHAT 2923 01:59:54,480 --> 01:59:56,600 THAT IS GOING TO BE. AND THAT IS 2924 01:59:56,600 --> 02:00:00,600 THE WAY SCIENCE MOVIN MOVES. SON 2925 02:00:00,600 --> 02:00:01,640 BEHALF OF EVERYONE, THANK YOU 2926 02:00:01,640 --> 02:00:02,760 VERY MUCH. THIS HAS BEEN AN 2927 02:00:02,760 --> 02:00:04,920 EXCITING AFTERNOON. AND I HOPE 2928 02:00:04,920 --> 02:00:08,160 YOU ENJOY BEING PART OF IT. 2929 02:00:08,160 --> 02:00:11,000 LASTLY, I WOULD JUST MENTION -- 2930 02:00:11,000 --> 02:00:18,000 WHAT HAPPENED? FOR THE CME 2931 02:00:18,000 --> 02:00:22,320 CREDIT, 45385. (443)541-5052. I 2932 02:00:22,320 --> 02:00:25,600 WANT TO MENTION THAT NEXT WEEK 2933 02:00:25,600 --> 02:00:29,360 MARCH 21ST, WE HAVE AN UNUSUAL 2934 02:00:29,360 --> 02:00:32,840 PROGRAM. WE WILL HAVE ONE 2935 02:00:32,840 --> 02:00:37,760 SPEAKER ANDREW KNOLL, THE 2936 02:00:37,760 --> 02:00:39,000 CHAIRMAN OF THE DEPARTMENT OF 2937 02:00:39,000 --> 02:00:44,040 GEOLOGY AT HARVARD UNIVERSITY. 2938 02:00:44,040 --> 02:00:47,040 AND EXTRAORDINARY BIOLOGIST. HE 2939 02:00:47,040 --> 02:00:49,080 IS GOING TO TALK ABOUT SUBJECT 2940 02:00:49,080 --> 02:00:52,360 OF IT'S A BACTERIAL WORLD AND 2941 02:00:52,360 --> 02:00:54,920 I'M SURE THIS WILL BE AN 2942 02:00:54,920 --> 02:00:56,920 EXCITING REWARDING PRESENTATION 2943 02:00:56,920 --> 02:00:59,800 AND WE HOPE YOU WILL ALL JOIN US 2944 02:00:59,800 --> 02:01:01,760 THEN. THANK YOU ONCE AGAIN. 2945 02:01:01,760 --> 02:01:02,960 IT'S BEEN A PLEASURE TO MEET 2946 02:01:02,960 --> 02:01:03,360 YOU. 2947 02:01:03,360 --> 02:01:04,440 >>THANK YOU, EVERYBODY. 2948 02:01:04,440 --> 00:00:00,000 >>THANK YOU, EVERYONE, TAKE CARE