1 00:00:05,931 --> 00:00:08,667 WELCOME TO THE WEDNESDAY 2 00:00:08,667 --> 00:00:15,040 AFTERNOON LECTURE SERIES I'M 3 00:00:15,040 --> 00:00:17,076 WITH THE NIA AND IT'S MY 4 00:00:17,076 --> 00:00:20,546 PLEASURE TO INTRODUCE TODAY'S 5 00:00:20,546 --> 00:00:20,779 LECTURE. 6 00:00:20,779 --> 00:00:22,014 BEFORE I INTRODUCE HER PROPERLY 7 00:00:22,014 --> 00:00:25,885 I WANT TO SAY TWO ANNOUNCEMENTS. 8 00:00:25,885 --> 00:00:29,121 THE FIRST IS THE CODE FOR THE 9 00:00:29,121 --> 00:00:31,724 CONTINUING MEDICAL EDUCATION 10 00:00:31,724 --> 00:00:37,429 CREDITS IS 57685. 11 00:00:37,429 --> 00:00:40,799 AND THE SECOND ONE IS THAT FOR 12 00:00:40,799 --> 00:00:42,801 THOSE THAT ARE WATCHING YOU CAN 13 00:00:42,801 --> 00:00:43,435 SUBMIT YOUR QUESTION TO THE 14 00:00:43,435 --> 00:00:46,338 SPEAKER ANY TIME DURING THE 15 00:00:46,338 --> 00:00:46,572 LECTURE. 16 00:00:46,572 --> 00:00:49,341 SIMPLY CLICK ON THE BOTTOM THAT 17 00:00:49,341 --> 00:00:51,010 SAYS SEND LIVE FEEDBACK WHICH IS 18 00:00:51,010 --> 00:00:53,512 BELOW YOUR VIDEOCAST WINDOW. 19 00:00:53,512 --> 00:00:58,217 TYPE IN YOUR MESSAGE AND WE WILL 20 00:00:58,217 --> 00:01:00,286 RELAY YOUR QUESTION AT THE END 21 00:01:00,286 --> 00:01:00,719 OF THE LECTURE. 22 00:01:00,719 --> 00:01:02,521 LET'S GO BACK TO THE 23 00:01:02,521 --> 00:01:02,855 INTRODUCTION. 24 00:01:02,855 --> 00:01:12,064 DR. SUH IS A PROFESSOR CHARLES 25 00:01:12,064 --> 00:01:14,600 AND MARIE ROBERTSON PREVENTION 26 00:01:14,600 --> 00:01:16,735 IN REPRODUCTIVE SCIENCES AND 27 00:01:16,735 --> 00:01:18,737 OBSTETRICS AND SERVED AS THE 28 00:01:18,737 --> 00:01:22,441 DIRECTOR OF THE REPRODUCTIVE 29 00:01:22,441 --> 00:01:23,642 AGING PROGRAM AT COLUMBIA 30 00:01:23,642 --> 00:01:25,077 UNIVERSITY MEDICAL CENTER IN NEW 31 00:01:25,077 --> 00:01:25,344 YORK. 32 00:01:25,344 --> 00:01:29,615 DR. SUH IS AN EXPERT IN THE 33 00:01:29,615 --> 00:01:33,152 FIELD OF EPIGENETICS AND 34 00:01:33,152 --> 00:01:33,786 GENETICS. 35 00:01:33,786 --> 00:01:36,322 HER RESEARCH HAS LIED IN THE 36 00:01:36,322 --> 00:01:38,490 IDENTIFICATION OF EPIGENETIC 37 00:01:38,490 --> 00:01:39,158 SEQUENCE VARIANTS LEAD TO THE 38 00:01:39,158 --> 00:01:43,462 RISK OF AGE-RELATED DISEASES AND 39 00:01:43,462 --> 00:01:45,698 FACTOR CONTRIBUTING TO THE 40 00:01:45,698 --> 00:01:48,167 RESILIENCE AGAINST SUCH 41 00:01:48,167 --> 00:01:48,434 DISEASES. 42 00:01:48,434 --> 00:01:57,343 FOR EXAMPLE AS FOR THOSE IN S 43 00:01:57,343 --> 00:01:58,811 CENTENARIANS AND LOOK AT RNA IN 44 00:01:58,811 --> 00:02:01,547 HUMAN CODING AND LONGEVITY AND 45 00:02:01,547 --> 00:02:03,616 THE EPIGENETIC CODES ASSOCIATED 46 00:02:03,616 --> 00:02:06,418 WITH CELLULAR SENESCENCE. 47 00:02:06,418 --> 00:02:07,753 HER CONTRIBUTION HAS BEEN 48 00:02:07,753 --> 00:02:09,088 RECOGNIZED WIDELY THROUGH 49 00:02:09,088 --> 00:02:11,090 SEVERAL ORGANIZATIONS. 50 00:02:11,090 --> 00:02:13,892 SHE RECEIVED FOUNDATIONAL WORK 51 00:02:13,892 --> 00:02:16,795 AND CURRENTLY IS THE MEMBER OF 52 00:02:16,795 --> 00:02:19,365 THE ACADEMY OF HEALTH AND LIFE 53 00:02:19,365 --> 00:02:21,100 RESEARCH. 54 00:02:21,100 --> 00:02:24,003 IN ADDITION TO ALL HER RESEARCH, 55 00:02:24,003 --> 00:02:26,905 SHE ALSO HAS ORGANIZED NUMEROUS 56 00:02:26,905 --> 00:02:31,043 INTERNATIONAL SYMPOSIA AND 57 00:02:31,043 --> 00:02:32,778 SERVED ON EDITORIAL BOARDS AND 58 00:02:32,778 --> 00:02:35,080 HAS MORE THAN 100 PUBLICATIONS. 59 00:02:35,080 --> 00:02:36,882 TODAY WE'RE VERY LUCKY BECAUSE 60 00:02:36,882 --> 00:02:39,618 SHE'S GOING TO TALK ABOUT HER 61 00:02:39,618 --> 00:02:41,654 LATEST DISCOVERY IN SCIENCE. 62 00:02:41,654 --> 00:02:45,124 SHE IS LOOKING AT THE ROLE OF 63 00:02:45,124 --> 00:02:48,360 AGING IN COVARIANTS IN AGING. 64 00:02:48,360 --> 00:02:54,400 THIS IS A TOPIC THAT HAS BEEN 65 00:02:54,400 --> 00:02:56,435 VERY INTERESTING IN THE FIELD OF 66 00:02:56,435 --> 00:02:57,503 AGING. 67 00:02:57,503 --> 00:02:59,638 BEFORE WE DIDN'T HEAR ABOUT THIS 68 00:02:59,638 --> 00:03:01,106 BEFORE FIVE YEARS AGO WE NEVER 69 00:03:01,106 --> 00:03:04,243 HEAR OF IT. 70 00:03:04,243 --> 00:03:09,915 MOST RECENTLY, IT'S GAINED 71 00:03:09,915 --> 00:03:12,117 IMPORTANCE BECAUSE THE COMMUNITY 72 00:03:12,117 --> 00:03:14,787 HAS LEARNED THE SEX PLAYS A ROLE 73 00:03:14,787 --> 00:03:18,223 IN THE AGING THE TITLE IS 74 00:03:18,223 --> 00:03:28,300 MECHANISM OF AGING. 75 00:03:28,300 --> 00:03:31,003 WELCOME DR. SUH. 76 00:03:31,003 --> 00:03:34,807 >> THANK YOU FOR THE VERY KIND 77 00:03:34,807 --> 00:03:35,140 INTRODUCTION. 78 00:03:35,140 --> 00:03:39,712 CAN YOU HEAR ME OKAY? 79 00:03:39,712 --> 00:03:42,247 I'D LIKE TO START BY THANKING 80 00:03:42,247 --> 00:03:45,484 THE DIVISION OF AGING BIOLOGY 81 00:03:45,484 --> 00:03:48,287 AND VIVIAN PEREZ FOR INVITING ME 82 00:03:48,287 --> 00:03:52,324 TO VISIT AND TO GIVE A LECTURE 83 00:03:52,324 --> 00:03:54,693 AT NIH TODAY. 84 00:03:54,693 --> 00:03:56,028 I'VE BEEN ENJOYING IT VERY MUCH. 85 00:03:56,028 --> 00:04:00,099 I OFTEN SAY I GREW UP WITH AGING 86 00:04:00,099 --> 00:04:03,335 BIOLOGY SINCE I RECEIVED MY 87 00:04:03,335 --> 00:04:10,309 FIRST RO1 IN 2004 AS A JUNIOR 88 00:04:10,309 --> 00:04:12,010 FACULTY AND HAVE BEEN REALLY 89 00:04:12,010 --> 00:04:13,679 GRATEFUL TO THE NATIONAL 90 00:04:13,679 --> 00:04:16,749 INSTITUTES ON AGING AND NIH FOR 91 00:04:16,749 --> 00:04:18,283 THEIR SUPPORT AND THE ITEMS SHA 92 00:04:18,283 --> 00:04:21,920 SHAPED AND DEFINED MY CAREER. 93 00:04:21,920 --> 00:04:24,656 THANK YOU SO VERY MUCH. 94 00:04:24,656 --> 00:04:26,992 AS VIVIANIA INTRODUCED, MY LAB 95 00:04:26,992 --> 00:04:28,827 HAS BEEN USING HUMAN GENETICS 96 00:04:28,827 --> 00:04:32,498 AND FUNCTIONAL GENOMICS APPROACH 97 00:04:32,498 --> 00:04:34,433 TO UNDERSTAND THE FUNDAMENTAL 98 00:04:34,433 --> 00:04:36,068 MECHANISMS OF AGING AND 99 00:04:36,068 --> 00:04:36,335 LONGEVITY. 100 00:04:36,335 --> 00:04:39,204 TODAY I'D LIKE TO SHARE OUR VERY 101 00:04:39,204 --> 00:04:41,840 RECENT WORK ON MECHANISMS OF 102 00:04:41,840 --> 00:04:45,144 HUMAN OVARIAN AGING AND I HOPE 103 00:04:45,144 --> 00:04:48,046 BY THE END OF MY TALK I WILL 104 00:04:48,046 --> 00:04:51,049 CONVINCE YOU THAT BY TARGETING 105 00:04:51,049 --> 00:04:57,523 OVARIAN AGING WE MAY BE ABLE TO 106 00:04:57,523 --> 00:05:04,863 DELAY AGING IN THE OVARY THEREBY 107 00:05:04,863 --> 00:05:15,407 MAKING WOMEN A LITTLE WILL -- 108 00:05:20,712 --> 00:05:22,314 DELAY IN AGING. 109 00:05:22,314 --> 00:05:25,684 THIS AUDIENCE IS WELL VERSED IN 110 00:05:25,684 --> 00:05:27,052 AGING BIOLOGY BUT JUST TO FRAME 111 00:05:27,052 --> 00:05:29,855 MY TALK, I'D LIKE TO START WITH 112 00:05:29,855 --> 00:05:32,724 A SIMPLE QUESTION, WHY STUDY 113 00:05:32,724 --> 00:05:33,559 AGING? 114 00:05:33,559 --> 00:05:35,861 SO, WE KNOW THAT AGING IS BY FAR 115 00:05:35,861 --> 00:05:39,264 THE SINGLE LARGEST RISK FACTOR 116 00:05:39,264 --> 00:05:41,300 FOR DISEASE AND SHOWN HERE IS 117 00:05:41,300 --> 00:05:44,703 THE INCIDENCE RATE AT FUNCTIONAL 118 00:05:44,703 --> 00:05:51,043 AGE AND YOU SEE INCIDENTS OF ALL 119 00:05:51,043 --> 00:05:52,244 CHRONIC DISEASES INCREASE 120 00:05:52,244 --> 00:05:53,412 DRAMATICALLY FROM MIDDLE AGE 121 00:05:53,412 --> 00:05:57,049 ONWARDS FOR MEN AND WOMEN. 122 00:05:57,049 --> 00:05:59,451 FOR EXAMPLE, JUST SIMPLY GETTING 123 00:05:59,451 --> 00:06:03,021 OLD FROM AGE 50 TO 75 INCREASES 124 00:06:03,021 --> 00:06:07,025 RISK FOR DISEASE BY A 125 00:06:07,025 --> 00:06:08,861 HUNDREDFOLD WHICH DWARF TENFOLD 126 00:06:08,861 --> 00:06:12,965 INCREASE IN RISK BY ALL KNOWN 127 00:06:12,965 --> 00:06:16,501 RISK FACTORS COMBINED INCLUDING 128 00:06:16,501 --> 00:06:22,941 BEING A FEMALE, HYPERTENSION, 129 00:06:22,941 --> 00:06:23,442 SMOK 130 00:06:23,442 --> 00:06:25,244 SMOKING, PHYSICAL INACTIVITY AND 131 00:06:25,244 --> 00:06:28,480 THIS IS TRUE FOR ALL DISEASE, 132 00:06:28,480 --> 00:06:29,248 KIDNEY DISEASE, CARDIOVASCULAR 133 00:06:29,248 --> 00:06:30,649 DISEASE AND YOU NAME IT. 134 00:06:30,649 --> 00:06:34,953 FOR THOSE WHO STUDY AGING 135 00:06:34,953 --> 00:06:38,790 BIOLOGY, PROPOSE SINCE AGING IS 136 00:06:38,790 --> 00:06:40,058 THE DRIVER OF THIS MAJOR CHRONIC 137 00:06:40,058 --> 00:06:41,894 DISEASES BY TARGETING 138 00:06:41,894 --> 00:06:45,264 FUNDAMENTAL MECHANISMS OF AGING 139 00:06:45,264 --> 00:06:47,499 WE'LL BE ABLE TO DELAY THE ONSET 140 00:06:47,499 --> 00:06:49,968 AND PROGRESSION OF MANY IF NOT 141 00:06:49,968 --> 00:06:52,938 ALL AGE-RELATED CHRONIC 142 00:06:52,938 --> 00:06:53,205 DISEASES. 143 00:06:53,205 --> 00:06:56,642 AND THIS GERO SCIENCE HYPOTHESIS 144 00:06:56,642 --> 00:07:02,180 HAS BEEN FORM LASTED BASED ON 145 00:07:02,180 --> 00:07:04,950 MANY ELEGANT WORK AND NOW WE 146 00:07:04,950 --> 00:07:08,620 LEARNED AGING IS NOT SIMPLY WEAR 147 00:07:08,620 --> 00:07:12,624 AND TEAR, IT'S CONTROLLED BY 148 00:07:12,624 --> 00:07:14,026 UNDERLYING BIOLOGY REGULATED BY 149 00:07:14,026 --> 00:07:16,962 GENES AND PATHWAYS AND BY 150 00:07:16,962 --> 00:07:26,571 TARGETING THIS EVE -- 151 00:07:26,571 --> 00:07:28,006 EVOLUTIONARY PATHWAY AND WE KNOW 152 00:07:28,006 --> 00:07:31,043 A LOT ABOUT AGING BIOLOGY THAT 153 00:07:31,043 --> 00:07:36,248 DRIVES AGING PROCESSES FROM 154 00:07:36,248 --> 00:07:37,282 GENOMIC INSTABILITY 155 00:07:37,282 --> 00:07:39,718 TO REGULATION, MITOCHONDRIAL 156 00:07:39,718 --> 00:07:43,722 DYSFUNCTION AND CELLULAR 157 00:07:43,722 --> 00:07:44,022 SENESCENCE. 158 00:07:44,022 --> 00:07:48,226 THE DRUG THAT TARGETS THIS 159 00:07:48,226 --> 00:07:52,998 FUNDAMENTAL PROCESS OF AGING 160 00:07:52,998 --> 00:07:55,033 THEREBY ARE COLLECTIVELY CALLED 161 00:07:55,033 --> 00:07:57,269 GERO PROTECTERS. 162 00:07:57,269 --> 00:08:06,678 MY LAB HAS BASEBEEN FOCUSSED ON 163 00:08:06,678 --> 00:08:10,649 THESE DISCOVERIES BY ASKING 164 00:08:10,649 --> 00:08:16,822 QUESTIONS, IS THIS THE SAME C 165 00:08:16,822 --> 00:08:19,591 CONSERVED PATHWAYS TO HUMANS AND 166 00:08:19,591 --> 00:08:23,061 THANKS TO THIS ENORMOUSLY LARGE 167 00:08:23,061 --> 00:08:27,032 HUMAN DATA SET WE CAN DO REVERSE 168 00:08:27,032 --> 00:08:29,501 TRANSLATIONAL GERO SCIENCE 169 00:08:29,501 --> 00:08:29,768 APPROACH. 170 00:08:29,768 --> 00:08:33,171 SO HUMANS, BY FAR THE BEST 171 00:08:33,171 --> 00:08:34,906 PHENOTYPE SPECIES WHEN IT COMES 172 00:08:34,906 --> 00:08:39,044 TO AGING RELATED DISEASE AND 173 00:08:39,044 --> 00:08:47,019 CONDITIONS. 174 00:08:47,019 --> 00:08:48,653 NOW THERE'S A LARGE DATA SET 175 00:08:48,653 --> 00:08:50,355 FROM MULTI-OMICS AND HEALTH 176 00:08:50,355 --> 00:08:54,292 RECORDS, WE CAN USE HUMAN AS A 177 00:08:54,292 --> 00:08:55,627 DISCOVERY PLATFORM TO GENERATE 178 00:08:55,627 --> 00:08:59,031 HYPOTHESIS AND TEST THAT IN 179 00:08:59,031 --> 00:09:02,300 HUMAN CELLS AND MODEL ORGANISMS. 180 00:09:02,300 --> 00:09:07,039 SO NOW, WHY STUDYING AGING IN 181 00:09:07,039 --> 00:09:08,040 WOMEN? 182 00:09:08,040 --> 00:09:10,542 AS VIVIANA INTRODUCED, WOMEN'S 183 00:09:10,542 --> 00:09:14,746 HEALTH HAS RECEIVED LIMITED 184 00:09:14,746 --> 00:09:15,714 ATTENTION SO HISTORICALLY THE 185 00:09:15,714 --> 00:09:19,518 BIO MEDICAL RESEARCH HAD BEEN 186 00:09:19,518 --> 00:09:23,021 FOCUSSED ON MALE BIOLOGY, STUDY 187 00:09:23,021 --> 00:09:25,524 SUBJECTS INCLUDING ANIMALS AND 188 00:09:25,524 --> 00:09:28,994 MAINLY MALE TO THE POINT WHERE 189 00:09:28,994 --> 00:09:32,597 IN 2016, NIH MANDATED TO 190 00:09:32,597 --> 00:09:38,270 INCLUSION OF BOTH SEXES IN ALL 191 00:09:38,270 --> 00:09:38,570 RESEARCH. 192 00:09:38,570 --> 00:09:43,942 AND UNDER THIS SEX BIOLOGICAL 193 00:09:43,942 --> 00:09:45,477 VARIABLE POLICY. 194 00:09:45,477 --> 00:09:50,649 SO AND OF COURSE THE FUNDING HAS 195 00:09:50,649 --> 00:09:52,451 LAGGED BEHIND. 196 00:09:52,451 --> 00:09:54,086 AS A CONSEQUENCE THE KNOWLEDGE 197 00:09:54,086 --> 00:09:57,422 ABOUT HOW FEMALE SYSTEM WORKS 198 00:09:57,422 --> 00:09:59,057 AND AGE IS LIMITED AND THE 199 00:09:59,057 --> 00:10:03,028 KNOWLEDGE GAP HAS REALLY 200 00:10:03,028 --> 00:10:07,032 PRACTICAL NEGATIVE CLINICAL 201 00:10:07,032 --> 00:10:09,334 CONVERSATIONS AND OFTEN TIMES 202 00:10:09,334 --> 00:10:11,770 IT'S MISDIAGNOSED OR DIAGNOSED 203 00:10:11,770 --> 00:10:11,970 LATER. 204 00:10:11,970 --> 00:10:14,940 THEY RESPOND LESS EFFECTIVELY TO 205 00:10:14,940 --> 00:10:17,008 TREATMENT AND THEY SUFFER MORE 206 00:10:17,008 --> 00:10:26,952 ADVERSE DRUG SIDE EFFECTS. 207 00:10:26,952 --> 00:10:29,020 AND THERE'S MORE PUBLIC 208 00:10:29,020 --> 00:10:36,228 ATTENTION CALLING FOR CHANGE. 209 00:10:36,228 --> 00:10:37,729 AND WE ISSUED SPECIAL NOTICE IN 210 00:10:37,729 --> 00:10:41,833 RESEARCH IN WOMEN'S HEALTH, SO 211 00:10:41,833 --> 00:10:42,767 EXCITING. 212 00:10:42,767 --> 00:10:44,369 SO FINALLY WHY ARE WE STUDYING 213 00:10:44,369 --> 00:10:54,713 AGING IN THE OVARY? 214 00:10:55,113 --> 00:10:57,249 AND IT DOES NOT ONLY INFLUENCE 215 00:10:57,249 --> 00:11:00,485 REPRODUCTION BUT AFFECTS THE 216 00:11:00,485 --> 00:11:02,454 WHOLE BODY THEREBY INFLUENCING 217 00:11:02,454 --> 00:11:04,389 OVER ALL HEALTH IN WOMEN. 218 00:11:04,389 --> 00:11:05,991 FIRST OF ALL, OVARY IS ONE OF 219 00:11:05,991 --> 00:11:09,227 THE FIRST ORGAN TO AGE IN THE 220 00:11:09,227 --> 00:11:11,229 HUMAN BODY. 221 00:11:11,229 --> 00:11:13,431 SO AGING STARTS IN MIDDLE 30s 222 00:11:13,431 --> 00:11:18,470 WITH DRAMATIC DECLINE IN 223 00:11:18,470 --> 00:11:21,806 FUNCTION WHICH COMPLETELY STOPS 224 00:11:21,806 --> 00:11:25,076 WITH MENOPAUSE AROUND AGE 51. 225 00:11:25,076 --> 00:11:27,045 MALE REPRODUCTIVE FUNCTION 226 00:11:27,045 --> 00:11:30,382 DECLINES AS WELL BUT RATHER 227 00:11:30,382 --> 00:11:31,049 GRADUAL. 228 00:11:31,049 --> 00:11:34,085 SO REPRODUCTIVE LONGEVITY OR 229 00:11:34,085 --> 00:11:35,053 REPRODUCTIVE LIFE SPAN IS 230 00:11:35,053 --> 00:11:35,687 DIFFERENT IN WOMEN COMPARED TO 231 00:11:35,687 --> 00:11:44,529 MEN. 232 00:11:44,529 --> 00:11:47,032 AND THE LIFE EXPECTANCY HAS 233 00:11:47,032 --> 00:11:48,700 INCREASED DRAMATICALLY BUT THE 234 00:11:48,700 --> 00:11:50,769 AGE OF NATURAL MENOPAUSE HAS 235 00:11:50,769 --> 00:11:52,037 REMAINED LARGELY UNCHANGED. 236 00:11:52,037 --> 00:11:55,540 WHAT THAT MEANS IS MORE AND MORE 237 00:11:55,540 --> 00:11:58,877 WOMEN LIVE GREATER PROPORTION OF 238 00:11:58,877 --> 00:12:02,247 THEIR LIVES IN POST MENOPAUSAL 239 00:12:02,247 --> 00:12:04,082 STATE AND WE KNOW THIS IS BAD 240 00:12:04,082 --> 00:12:09,020 BECAUSE MENOPAUSE COINCIDES WITH 241 00:12:09,020 --> 00:12:10,322 VERY DELETERIOUS HEALTH OUTCOME 242 00:12:10,322 --> 00:12:15,093 AND COGNITIVE, IMMUNE, BONE AND 243 00:12:15,093 --> 00:12:20,565 CARDIOVASCULAR SYSTEMS. 244 00:12:20,565 --> 00:12:27,505 AND MENOPAUSE ACCELERATED AGING 245 00:12:27,505 --> 00:12:29,074 THERE'S A GENETIC COMPONENT IN 246 00:12:29,074 --> 00:12:33,845 THIS MENOPAUSE INDUCED 247 00:12:33,845 --> 00:12:34,613 ACCELERATED AGING CONSISTENT 248 00:12:34,613 --> 00:12:36,481 WITH THE GENETIC LINK. 249 00:12:36,481 --> 00:12:38,049 WOMEN WHO UNDER GO MENOPAUSE 250 00:12:38,049 --> 00:12:40,585 LATER TEND TO LIVE LONGER THAN 251 00:12:40,585 --> 00:12:43,021 WOMEN WHO UNDER GO MENOPAUSE 252 00:12:43,021 --> 00:12:45,023 EARLIER. 253 00:12:45,023 --> 00:12:48,226 SO ACTUALLY, FAMILY WITH HISTORY 254 00:12:48,226 --> 00:12:54,466 OF EARLY MENOPAUSE HAS SIX TIMES 255 00:12:54,466 --> 00:12:57,068 HIGHER RISK FOR THIS AND 256 00:12:57,068 --> 00:12:58,803 BREEDERS OF WOMEN WITH LATER 257 00:12:58,803 --> 00:13:02,507 MENOPAUSE HAVE A PROLONGEVITY 258 00:13:02,507 --> 00:13:04,409 COMPARED COMPARED TO BREEDERS OF 259 00:13:04,409 --> 00:13:05,644 WOMEN WITH EARLIER MENOPAUSE. 260 00:13:05,644 --> 00:13:09,881 THIS SUGGESTS TO US THAT OVARY 261 00:13:09,881 --> 00:13:12,584 DOES MUCH MORE THAN REPRODUCTION 262 00:13:12,584 --> 00:13:18,823 AND REALLY INFLUENCES OVER ALL 263 00:13:18,823 --> 00:13:19,057 HEALTH. 264 00:13:19,057 --> 00:13:23,028 WHAT HAPPENS IF YOU REMOVE 265 00:13:23,028 --> 00:13:27,332 OVARY, IT REDUCES THE RISK FOR 266 00:13:27,332 --> 00:13:28,800 DEMENTIA AND CARDIOVASCULAR 267 00:13:28,800 --> 00:13:33,004 DISEASE AND INCREASED RISK FOR 268 00:13:33,004 --> 00:13:35,040 MORBIDITY AND ALL CAUSE 269 00:13:35,040 --> 00:13:45,216 MORTALITY. 270 00:13:50,488 --> 00:13:55,026 AND REPLACING OVARY FROM OLD 271 00:13:55,026 --> 00:14:00,332 MICE TO YOUNG MICE IS ENOUGH TO 272 00:14:00,332 --> 00:14:02,567 IMPROVE INSULIN SENSITIVITY AND 273 00:14:02,567 --> 00:14:03,868 REDUCING INFLAMMATION. 274 00:14:03,868 --> 00:14:10,275 FROM THE EYE OF THIS GEROSIN 275 00:14:10,275 --> 00:14:11,276 SCIENTIST IT WAS CLEAR TO US 276 00:14:11,276 --> 00:14:16,881 OVARY AND AGING CAN BE TARGETED 277 00:14:16,881 --> 00:14:18,483 FOR GERO PROTECTION IN AGING. 278 00:14:18,483 --> 00:14:22,087 WHAT'S THE UNDERLYING BIOLOGY WE 279 00:14:22,087 --> 00:14:23,621 CAN TARGET? 280 00:14:23,621 --> 00:14:33,865 UNFORTUNA 281 00:14:34,466 --> 00:14:36,201 UNFORTUNATELY AND WHAT'S BEEN 282 00:14:36,201 --> 00:14:39,337 DOCUMENTED IN HUMANS IS ENORMOUS 283 00:14:39,337 --> 00:14:41,072 HETEROGENEITY IN AGING. 284 00:14:41,072 --> 00:14:43,908 WHAT'S SHOWN IS NATURAL 285 00:14:43,908 --> 00:14:48,146 MENOPAUSE IN THE U.K. BIO BANK 286 00:14:48,146 --> 00:14:56,755 AND THE DISTRIBUTION. 287 00:14:56,755 --> 00:14:59,023 SOME WOMEN UNDER GO MENOPAUSE IN 288 00:14:59,023 --> 00:15:03,261 THEIR 30s AND SOME WOMEN 289 00:15:03,261 --> 00:15:13,571 DEPENDS, LATE 50s. 290 00:15:19,110 --> 00:15:21,212 YOU CAN PERFORM GENOME WIDE 291 00:15:21,212 --> 00:15:22,614 ASSOCIATION STUDIES. 292 00:15:22,614 --> 00:15:23,848 ONE OF THE LARGEST STUDIES 293 00:15:23,848 --> 00:15:29,087 INVOLVES MORE THAN 200,000 WOMEN 294 00:15:29,087 --> 00:15:33,124 IDENTIFIED IDENTIFIED 290 LOCI 295 00:15:33,124 --> 00:15:36,594 ASSOCIATED WITH MENOPAUSE 296 00:15:36,594 --> 00:15:39,030 TIMING. 297 00:15:39,030 --> 00:15:49,574 WHEN IT DOES ANYTHING IT DOES IT 298 00:15:57,415 --> 00:16:05,156 THROUGH REGULATORY CHANGES. 299 00:16:05,156 --> 00:16:08,960 THE HUMAN GENOME HAS EXTENSIVE 300 00:16:08,960 --> 00:16:11,729 LINKS TO EQUILIBRIUM. 301 00:16:11,729 --> 00:16:13,965 IN THE LOCUS YOU FIND MANY IF 302 00:16:13,965 --> 00:16:17,035 NOT VARIANTS ASSOCIATED WITH 303 00:16:17,035 --> 00:16:19,037 MENOPAUSE TIMING AND REGULAR 304 00:16:19,037 --> 00:16:21,806 ELEMENTS SUCH AS ENHANCER AND 305 00:16:21,806 --> 00:16:23,908 PROMOTER, THEY TEND TO INTERACT 306 00:16:23,908 --> 00:16:27,946 IN A DISTURBED WAY SO SOMETIMES 307 00:16:27,946 --> 00:16:31,115 SKIPPING IN BETWEEN SO TO 308 00:16:31,115 --> 00:16:33,251 IDENTIFY REAL CAUSAL CHANCE THAT 309 00:16:33,251 --> 00:16:35,687 ARE UNDER INFLUENCED THE 310 00:16:35,687 --> 00:16:38,656 REGULATORY VARIANT IS A PRIORITY 311 00:16:38,656 --> 00:16:41,159 UNKNOWN AND REGULATORY ELEMENTS 312 00:16:41,159 --> 00:16:43,027 THEY HAVE SELL TYPE SPECIFIC 313 00:16:43,027 --> 00:16:44,095 FUNCTION. 314 00:16:44,095 --> 00:16:46,030 SO TO IDENTIFY CAUSAL CELL TYPES 315 00:16:46,030 --> 00:16:48,366 THAT ARE UNDER INFLUENCED OF 316 00:16:48,366 --> 00:16:50,435 THIS CAUSAL VARIANT ARE UNKNOWN 317 00:16:50,435 --> 00:16:54,539 LET ALONE THE MECHANISMS. 318 00:16:54,539 --> 00:16:56,174 SO TO ADDRESS THIS CHALLENGE, WE 319 00:16:56,174 --> 00:16:59,544 AND OTHERS HAVE BEEN INTEGRATING 320 00:16:59,544 --> 00:17:03,047 HUMAN GENETIC DATA FROM GENOME 321 00:17:03,047 --> 00:17:07,018 WIDE ASSOCIATION STUDIES TO 322 00:17:07,018 --> 00:17:10,088 EPIGENOME AND EPIGENETIC DATA 323 00:17:10,088 --> 00:17:10,288 SETS. 324 00:17:10,288 --> 00:17:14,058 EVERY INCREASING NOWADAYS AND TO 325 00:17:14,058 --> 00:17:15,894 MAP THEM IN DIFFERENT CELL TYPES 326 00:17:15,894 --> 00:17:17,962 TO IDENTIFY CHANGES IN 327 00:17:17,962 --> 00:17:20,498 TRANSCRIPTION FACTOR BINDING AND 328 00:17:20,498 --> 00:17:25,436 LOOK AT ALSO EXPRESSION CHANGES 329 00:17:25,436 --> 00:17:32,343 CALLED EQTL ANALYSIS AND PREDICT 330 00:17:32,343 --> 00:17:35,046 CAUSAL VARIANTS AS WELL AS 331 00:17:35,046 --> 00:17:42,787 CAUSAL GENES. 332 00:17:42,787 --> 00:17:46,424 AND TO LOOK FOR CHROMATIN 333 00:17:46,424 --> 00:17:47,926 ACCESSIBILITY, THERE ARE 220 334 00:17:47,926 --> 00:17:51,029 HUMAN CELL TYPES DERIVED FROM 30 335 00:17:51,029 --> 00:17:53,665 DIFFERENT HUMAN TISSUES BUT 336 00:17:53,665 --> 00:17:55,867 UNTIL VERY RECENTLY, OVARY DATA 337 00:17:55,867 --> 00:17:59,037 WASN'T AVAILABLE, WHICH IS 338 00:17:59,037 --> 00:18:00,939 REALLY UNFORTUNATE BECAUSE 339 00:18:00,939 --> 00:18:04,475 OVARIES IS A VERY COMPLEX ORGAN 340 00:18:04,475 --> 00:18:07,211 TO MAINTAIN THIS OVARIAN 341 00:18:07,211 --> 00:18:10,114 FUNCTION AND THERE ARE DIFFERENT 342 00:18:10,114 --> 00:18:10,815 CELL TYPES. 343 00:18:10,815 --> 00:18:17,155 FOR EXAMPLE, OVARY SPECIFIC CELL 344 00:18:17,155 --> 00:18:22,193 TYPES ARE MAIN COMPONENTS OF 345 00:18:22,193 --> 00:18:25,630 FOLLICLES THAT PROMOTE GROWTH 346 00:18:25,630 --> 00:18:26,531 AND MATURATION AND THERE ARE 347 00:18:26,531 --> 00:18:29,167 OTHER CELL TYPES SUCH AS STROMA 348 00:18:29,167 --> 00:18:33,071 CELLS AND EPITHELIAL CELLS, 349 00:18:33,071 --> 00:18:34,739 SMOOTH MUSCLE CELLS AND 350 00:18:34,739 --> 00:18:35,506 LYMPHATIC AND BLOOD ORIGIN AND 351 00:18:35,506 --> 00:18:45,750 IMMUNE CELLS. 352 00:18:56,094 --> 00:18:59,030 TO UNDERSTAND THIS, THEY TOOK AN 353 00:18:59,030 --> 00:19:05,703 IT SYSTEMIC APPROACH AND TOOK 354 00:19:05,703 --> 00:19:08,640 OVARIES FROM YOUNG WOMEN IN 355 00:19:08,640 --> 00:19:10,141 THEIR 20s AND REPRODUCTIVELY OLD 356 00:19:10,141 --> 00:19:11,509 WOMEN IN THEIR 50s. 357 00:19:11,509 --> 00:19:14,312 SO WE ARE TALKING ABOUT AGING 358 00:19:14,312 --> 00:19:20,451 FROM 20 TO 50 AND PERFORMED 359 00:19:20,451 --> 00:19:23,021 SIN 360 00:19:23,021 --> 00:19:25,857 SINGLE NUC RNA SEQ AND 361 00:19:25,857 --> 00:19:28,326 REGULATORY LANDSCAPE CHANGE AND 362 00:19:28,326 --> 00:19:31,029 WE WERE HAPPY TO DETECT ALL 363 00:19:31,029 --> 00:19:34,165 MAJOR CELL TYPES IN THE OVARY. 364 00:19:34,165 --> 00:19:38,536 SO WITH THE DATA NOW YOU CAN 365 00:19:38,536 --> 00:19:42,173 INTEGRATE THE MENOPAUSAL GWAS 366 00:19:42,173 --> 00:19:48,179 AND VARIANTS AND WE FOUND THAT 367 00:19:48,179 --> 00:19:51,049 THE MENOPAUSAL TIMING OF 368 00:19:51,049 --> 00:19:54,152 VARIANTS ARE OCCUR IN REGULATORY 369 00:19:54,152 --> 00:19:56,254 ELEMENTS THAT ARE ACTIVE IN NOT 370 00:19:56,254 --> 00:19:58,222 JUST ONE CELL TYPE, ACROSS MANY 371 00:19:58,222 --> 00:19:59,323 CELL TYPES IF NOT ALL CELL TYPES 372 00:19:59,323 --> 00:20:03,027 IN THE OVARY. 373 00:20:03,027 --> 00:20:06,464 AT THE VARIANT LEVEL, THEY HAVE 374 00:20:06,464 --> 00:20:09,100 RATHER GLOBAL IMPACT. 375 00:20:09,100 --> 00:20:14,739 WHEN YOU LOOK AT THE PREDICTED 376 00:20:14,739 --> 00:20:19,243 TARGET JIN IT'S NEAREST FROM THE 377 00:20:19,243 --> 00:20:22,513 VARIANTS THEY'RE INRICHED IN 378 00:20:22,513 --> 00:20:25,450 JINS EXPRESSED NOT JUST IN ONE 379 00:20:25,450 --> 00:20:28,886 CELL TYPE BUT ALL TYPES OF THE 380 00:20:28,886 --> 00:20:29,087 OVARY. 381 00:20:29,087 --> 00:20:32,156 FROM STROMA CELLS DOWN AND 382 00:20:32,156 --> 00:20:33,858 ENDOTHELIAL CELLS DOWN TO 383 00:20:33,858 --> 00:20:35,026 THICKER CELLS INDICATING THE 384 00:20:35,026 --> 00:20:37,829 GLOBAL IMPACT. 385 00:20:37,829 --> 00:20:41,232 IN COMPARISON, CHANNELS OF TWO 386 00:20:41,232 --> 00:20:47,238 GWAS DATA FROM POLY CYSTIC OVARY 387 00:20:47,238 --> 00:20:50,441 SYNDROME A HORMONAL DISORDER 388 00:20:50,441 --> 00:20:52,210 FOUND IN REPRODUCTIVELY YOUNG 389 00:20:52,210 --> 00:20:55,046 WOMEN AND HORMONE IS PRODUCED IN 390 00:20:55,046 --> 00:20:58,182 GRANULOSA CELLS AND THEY'RE 391 00:20:58,182 --> 00:20:59,016 ENRICHED IN GRANULOSA CELL 392 00:20:59,016 --> 00:21:03,621 SPECIFICALLY. 393 00:21:03,621 --> 00:21:06,557 WHAT ABOUT OVARIAN EPITHELIAL 394 00:21:06,557 --> 00:21:07,525 CANCERS? 395 00:21:07,525 --> 00:21:11,062 WHEN YOU TAKE GWAS DATA FROM 396 00:21:11,062 --> 00:21:13,231 THAT CANCER THEY'RE ENRICHED IN 397 00:21:13,231 --> 00:21:16,033 EPITHELIAL CELLS WITH THE CANCER 398 00:21:16,033 --> 00:21:16,567 IS ORIGINATING. 399 00:21:16,567 --> 00:21:21,906 SO THIS DATA CONVINCED US THAT 400 00:21:21,906 --> 00:21:22,840 MENOPAUSE ASSOCIATED TIMING 401 00:21:22,840 --> 00:21:26,377 VARIANTS HAVE GLOBAL IMPACT ON 402 00:21:26,377 --> 00:21:27,945 THE REGULATORY NETWORK IN THE 403 00:21:27,945 --> 00:21:29,247 OVARY ACROSS DIFFERENT CELL 404 00:21:29,247 --> 00:21:32,517 TYPES. 405 00:21:32,517 --> 00:21:36,320 SO USING THE DATA YOU CAN NOW 406 00:21:36,320 --> 00:21:37,789 START IDENTIFYING POTENTIALLY 407 00:21:37,789 --> 00:21:39,924 CAUSAL VARIANTS AND GENES. 408 00:21:39,924 --> 00:21:42,527 I'LL SHARE WITH YOU A COUPLE 409 00:21:42,527 --> 00:21:43,895 EXAMPLES. 410 00:21:43,895 --> 00:21:47,932 WE FOUND A VARIANT NEAR A LOCUS 411 00:21:47,932 --> 00:21:51,903 ASSOCIATED WITH LATER MENOPAUSE 412 00:21:51,903 --> 00:21:54,472 AND IT OCCURS IN REGULATORY 413 00:21:54,472 --> 00:21:57,041 ELEMENTS THAT'S ACTIVE IN ALL 414 00:21:57,041 --> 00:21:59,977 THESE OVARIAN CELL TYPES FROM 415 00:21:59,977 --> 00:22:02,613 STROMA CELLS, ENDOTHELIAL CELL 416 00:22:02,613 --> 00:22:05,249 DOWN TO EPITHELIAL CELLS. 417 00:22:05,249 --> 00:22:14,425 SO WE CALL IT PURATIVE CAUSAL 418 00:22:14,425 --> 00:22:15,026 VARIANTS. 419 00:22:15,026 --> 00:22:17,094 THIS LATER MENOPAUSE ASSOCIATED 420 00:22:17,094 --> 00:22:18,830 VARIANTS WE IDENTIFY AS 421 00:22:18,830 --> 00:22:21,866 POTENTIALLY CAUSAL, IS 422 00:22:21,866 --> 00:22:23,234 CORRELATED WITH REDUCED 423 00:22:23,234 --> 00:22:27,038 EXPRESSION OF HELB. 424 00:22:27,038 --> 00:22:29,707 BUT WHEN THEY LOOK AT THE OTHER 425 00:22:29,707 --> 00:22:31,776 TISSUES IN THE DATABASE IT WAS 426 00:22:31,776 --> 00:22:33,077 SURPRISING THAT ALL THE TISSUES 427 00:22:33,077 --> 00:22:36,080 THAT HAVE BEEN PROFILED, THIS IS 428 00:22:36,080 --> 00:22:38,316 49 TISSUES SHOW THE SAME 429 00:22:38,316 --> 00:22:38,749 PATTERN. 430 00:22:38,749 --> 00:22:41,252 IN OTHER WORDS, OVARIAN AGING 431 00:22:41,252 --> 00:22:43,888 ASSOCIATED VARIANTS HAS 432 00:22:43,888 --> 00:22:45,923 IMPACT -- POTENTIAL IMPACT 433 00:22:45,923 --> 00:22:49,760 ACROSS ALL TISSUE TYPE IN HUMAN 434 00:22:49,760 --> 00:22:50,695 BODY. 435 00:22:50,695 --> 00:22:53,598 SO OVARIES IS NOT EVEN NUMBER 436 00:22:53,598 --> 00:22:54,165 ONE. 437 00:22:54,165 --> 00:22:56,934 YOU CAN SEE MUSCLE FOR EXAMPLE, 438 00:22:56,934 --> 00:22:58,769 SKELETAL MUSCLE, THE MAGNITUDE 439 00:22:58,769 --> 00:23:02,306 OF DOWN REGULATION IS MUCH MORE 440 00:23:02,306 --> 00:23:04,909 THAN WHAT IS FOUND IN OVARY. 441 00:23:04,909 --> 00:23:07,011 YOU CAN SEE FROM MUSCLE TO BRAIN 442 00:23:07,011 --> 00:23:17,521 TO HEART AND ALL THE TISSUES. 443 00:23:22,827 --> 00:23:23,928 THIS LATER MENOPAUSAL VARIANT IS 444 00:23:23,928 --> 00:23:27,031 COMPARED TO NON-RISK VARIANT. 445 00:23:27,031 --> 00:23:32,637 WHAT I HAVE SHOWN YOU HERE IS 446 00:23:32,637 --> 00:23:34,939 PREDICTION. 447 00:23:34,939 --> 00:23:37,441 YOU INTEGRATE ALL THE RELEVANT 448 00:23:37,441 --> 00:23:38,843 DATA AND PREDICT CAUSAL VARIANTS 449 00:23:38,843 --> 00:23:40,077 AND CAUSAL GENES. 450 00:23:40,077 --> 00:23:45,449 THE QUESTION IS, HOW DO WE BRING 451 00:23:45,449 --> 00:23:51,022 THIS PREDICTION AND ASSOCIATION 452 00:23:51,022 --> 00:23:53,057 TO EXPERIMENTAL VALIDATION TO 453 00:23:53,057 --> 00:23:53,624 ESTABLISH CAUSALITY? 454 00:23:53,624 --> 00:23:54,625 WE'VE BEEN THINKING VERY HARD 455 00:23:54,625 --> 00:23:58,195 ABOUT THE BEST WAY TO APPROACH 456 00:23:58,195 --> 00:24:02,967 THIS AND ANOTHER POSTDOC IN MY 457 00:24:02,967 --> 00:24:07,004 LAB SPEARHEADED THIS APPROACH. 458 00:24:07,004 --> 00:24:16,814 WHAT HE DOES IS HE TAKES HUMAN 459 00:24:16,814 --> 00:24:18,182 PLURIPOTENT STEM CELL AND 460 00:24:18,182 --> 00:24:20,651 ENGINEER THEM WITH CRISPR SO IT 461 00:24:20,651 --> 00:24:22,586 CARRIES THE CAUSAL VARIANTS. 462 00:24:22,586 --> 00:24:23,955 EVERYTHING ELSE IS THE SAME 463 00:24:23,955 --> 00:24:26,958 EXCEPT FOR THE SINGLE 464 00:24:26,958 --> 00:24:27,258 NUCLEOTIDE. 465 00:24:27,258 --> 00:24:29,794 NOW YOU CAN DIFFERENTIATE THE 466 00:24:29,794 --> 00:24:32,730 ENGINEERED CELLS TO MULTIPLE 467 00:24:32,730 --> 00:24:35,032 CELL TYPES IN THE OVARY 468 00:24:35,032 --> 00:24:39,971 INCLUDING GRANULOSA CELLS AND 469 00:24:39,971 --> 00:24:40,771 ENDOTHELIAL CELLS AND SMOOTH 470 00:24:40,771 --> 00:24:42,540 MUSCLE CELLS. 471 00:24:42,540 --> 00:24:46,510 NOW, COMPARING TO ISO GENIC 472 00:24:46,510 --> 00:24:50,281 CONTROL YOU CAN CONFORM THE REAL 473 00:24:50,281 --> 00:24:55,019 CAUSAL VARIANT YOU PREDICT AND 474 00:24:55,019 --> 00:24:57,221 CONFIRM THE DIRECTIONAL OUTCOME 475 00:24:57,221 --> 00:25:00,191 AND ALSO MAGNITUDE, IN OTHER 476 00:25:00,191 --> 00:25:02,727 WORDS, THE VARIANT DOESN'T MAKE 477 00:25:02,727 --> 00:25:04,762 GENE EXPRESSION LESS OR MORE AND 478 00:25:04,762 --> 00:25:07,098 OF COURSE FROM DIFFERENT CELL 479 00:25:07,098 --> 00:25:11,035 TYPES YOU CAN CONFIRM THE CELL 480 00:25:11,035 --> 00:25:12,570 TYPES SPECIFICITY AND REALLY 481 00:25:12,570 --> 00:25:14,605 TREAT DOWN THE MECHANISMS 482 00:25:14,605 --> 00:25:17,308 INCLUDING TRANSCRIPTION FACTORS 483 00:25:17,308 --> 00:25:25,049 AND MEDIATE THIS CHANGE. 484 00:25:25,049 --> 00:25:28,152 I'LL GIVE YOU ONE EXAMPLE, THE 485 00:25:28,152 --> 00:25:32,790 GENE THAT'S PREDICTED TO SHOW 486 00:25:32,790 --> 00:25:34,191 REDUCED EXPRESSION IN MULTIPLE 487 00:25:34,191 --> 00:25:36,293 TISSUE TYPE, IT'S NOT ALL TISSUE 488 00:25:36,293 --> 00:25:38,429 TYPE THAT HAS BEEN PROFILED. 489 00:25:38,429 --> 00:25:40,164 SO IN THIS CASE, FOR THE 490 00:25:40,164 --> 00:25:43,167 REGULATORY VARIANT, THE BEST 491 00:25:43,167 --> 00:25:52,176 APPROACH IS TO TAKE HETEROZYGOUS 492 00:25:52,176 --> 00:25:54,945 CELL AND FIND A CODING VARIANT 493 00:25:54,945 --> 00:25:59,283 AS A PROXY FOR REGULATORY 494 00:25:59,283 --> 00:26:01,318 ACTIVITY. 495 00:26:01,318 --> 00:26:06,524 WHEN YOU LOOK AT THE AABUNDANCE 496 00:26:06,524 --> 00:26:07,925 -- ABUNDANCE OF PROXY MARKERS 497 00:26:07,925 --> 00:26:11,796 YOU CAN REDUCE THEY WILL 498 00:26:11,796 --> 00:26:12,830 REGULATORY CAPACITY. 499 00:26:12,830 --> 00:26:14,832 THIS IS A CONTROLLED EXPERIMENT 500 00:26:14,832 --> 00:26:17,735 WHEN YOU TAKE GENOMIC DNA AND 501 00:26:17,735 --> 00:26:19,737 PERFORM PCR, HALF AND HALF. 502 00:26:19,737 --> 00:26:23,040 WHEN YOU TAKE CB AND A FROM 503 00:26:23,040 --> 00:26:24,909 DIFFERENTIATED CELLS THEN YOU 504 00:26:24,909 --> 00:26:29,346 SEE LATER MENOPAUSE ASSOCIATED 505 00:26:29,346 --> 00:26:31,715 VARIANT CAUSED REDUCE EXPRESSION 506 00:26:31,715 --> 00:26:34,018 OF A HEALTHY GENE. 507 00:26:34,018 --> 00:26:37,421 SO THIS IS NOW CONFIRMATION OF 508 00:26:37,421 --> 00:26:37,855 THE PREDICTION. 509 00:26:37,855 --> 00:26:40,057 AND ACROSS ALL CELL TYPES WE 510 00:26:40,057 --> 00:26:45,429 HAVE TESTED AGAIN SHOWING GLOBAL 511 00:26:45,429 --> 00:26:46,730 IMPACT. 512 00:26:46,730 --> 00:26:49,633 WE WERE LUCKY TO HAVE PRIMARY 513 00:26:49,633 --> 00:26:50,701 GRANULOSA CELLS AROUND THIS IS 514 00:26:50,701 --> 00:26:53,304 COLUMBIA FERTILITY CENTER. 515 00:26:53,304 --> 00:26:59,043 WE COULD GET FOUR CELLS, 516 00:26:59,043 --> 00:27:05,316 HETEROZYGOUS CARRIER AND LOOK AT 517 00:27:05,316 --> 00:27:15,860 REDUCED EXPRESSION AND HELB IS A 518 00:27:15,860 --> 00:27:20,898 DNA HE LACASE AND IT'S A WAY OF 519 00:27:20,898 --> 00:27:23,033 PREPARING DOUBLE-STRAND BREAK. 520 00:27:23,033 --> 00:27:27,304 THIS IS ALSO INVOLVED IN MYOTIC 521 00:27:27,304 --> 00:27:28,672 RECOMBINATION. 522 00:27:28,672 --> 00:27:33,310 OUR STUDY DEMONSTRATING LATER 523 00:27:33,310 --> 00:27:34,745 MENOPAUSE ASSOCIATED VARIANT 524 00:27:34,745 --> 00:27:38,415 REDUCED EXPRESSION OF HELB GENE 525 00:27:38,415 --> 00:27:42,553 SUCH THAT TO US, THE GENE 526 00:27:42,553 --> 00:27:46,924 DEFICIENCY MAY IMPROVE OVARIAN 527 00:27:46,924 --> 00:27:50,561 FUNCTION OR IMPROVE OVARIAN 528 00:27:50,561 --> 00:27:52,363 RESERVE AND PRESERVE THE LIFE 529 00:27:52,363 --> 00:27:52,730 SPAN. 530 00:27:52,730 --> 00:27:58,102 TO TEST THAT HYPOTHESIS, WE HAVE 531 00:27:58,102 --> 00:28:01,272 GENERATED HEALTHY KNOCKOUT MICE 532 00:28:01,272 --> 00:28:04,875 IN COLLABORATION WITH COLUMBIA 533 00:28:04,875 --> 00:28:08,812 AND WE ARE GOING TO TEST IF THIS 534 00:28:08,812 --> 00:28:11,015 DEFICIENCY AS WE PREDICT 535 00:28:11,015 --> 00:28:12,917 IMPROVES REPRODUCTIVE LIFE SPAN 536 00:28:12,917 --> 00:28:14,818 AND OVARIAN RESERVE AND ALSO WE 537 00:28:14,818 --> 00:28:20,090 ARE GOING TO TEST IF IT HAS ANY 538 00:28:20,090 --> 00:28:24,061 IMPACT ON HEALTH SPAN IN PEOPLE. 539 00:28:24,061 --> 00:28:32,436 IT'S GOING TO BE SPEARHEADED BY 540 00:28:32,436 --> 00:28:36,373 SHWETA DIPALI IN THE LAB. 541 00:28:36,373 --> 00:28:40,144 AND THE OTHER LOCUS WAS DETECTED 542 00:28:40,144 --> 00:28:45,883 MORE THAN 10 YEARS AGO WITH MUCH 543 00:28:45,883 --> 00:28:48,185 LESS INDIVIDUAL, I THINK 7,000 544 00:28:48,185 --> 00:28:49,253 WOMEN. 545 00:28:49,253 --> 00:28:52,056 AND IT WAS HAILED AS A LOCUS 546 00:28:52,056 --> 00:28:53,357 ASSOCIATED WITH REPRODUCTIVE 547 00:28:53,357 --> 00:28:58,128 AGING IN WOMEN. 548 00:28:58,128 --> 00:29:03,434 THE QUESTION IS, IS BRCA1 THE 549 00:29:03,434 --> 00:29:04,268 CAUSAL GENE? 550 00:29:04,268 --> 00:29:09,740 AS I EXPLAINED THE LOCUS HAS 551 00:29:09,740 --> 00:29:14,445 MANY VARIANTS AND MORE THAN 400 552 00:29:14,445 --> 00:29:15,613 VARIANTS ARE ASSOCIATED WITH 553 00:29:15,613 --> 00:29:17,348 LATER MENOPAUSE. 554 00:29:17,348 --> 00:29:25,322 YOU CAN SEE THIS IS VCONTAINS M 555 00:29:25,322 --> 00:29:26,857 GENES INCLUDING BRCA 1 SO HOW DO 556 00:29:26,857 --> 00:29:31,028 WE KNOW IT'S THE CAUSAL GENE? 557 00:29:31,028 --> 00:29:37,801 WHEN A POSTDOC IN THE LAB LOOKED 558 00:29:37,801 --> 00:29:40,938 AT THE VARIANT FOUND IT'S 559 00:29:40,938 --> 00:29:42,239 CORRELATED WITH EXPRESSION 560 00:29:42,239 --> 00:29:45,075 CHANGES IN NBR2 GENE HAS NOTHING 561 00:29:45,075 --> 00:29:47,344 TO DO WITH BRCA 1 OR ANY OTHER 562 00:29:47,344 --> 00:29:50,481 GENES IN THIS LOCUS. 563 00:29:50,481 --> 00:29:55,919 SO THE PURATIVE CAUSAL IS MBR2 564 00:29:55,919 --> 00:29:59,023 NOT BRCA1. 565 00:29:59,023 --> 00:30:06,897 SO TO CONFIRM THIS, HE PERFORMED 566 00:30:06,897 --> 00:30:17,441 AGAIN EXPRESSIONAL ANALYSIS AND 567 00:30:18,976 --> 00:30:21,845 CONTROL WHEN YOU TAKE GENOMIC 568 00:30:21,845 --> 00:30:23,080 DNA AND YOU SEE CONTRIBUTION 569 00:30:23,080 --> 00:30:24,915 FROM EACH ALLELE BUT WHEN YOU 570 00:30:24,915 --> 00:30:28,485 TAKE CDNA FROM DIFFERENT CELL 571 00:30:28,485 --> 00:30:30,254 TYPES, NOW IT'S IMMEDIATELY 572 00:30:30,254 --> 00:30:30,487 CLEAR. 573 00:30:30,487 --> 00:30:32,990 YOU DON'T EVEN NEED TO DO 574 00:30:32,990 --> 00:30:37,494 STATISTICS THAT MBR2 IS THE GENE 575 00:30:37,494 --> 00:30:45,536 THAT CHANGES AND MENOPAUSE 576 00:30:45,536 --> 00:30:47,438 ASSOCIATED ALLELE CAUSE 577 00:30:47,438 --> 00:30:50,908 REDUCTION IN EXPRESSION IN 578 00:30:50,908 --> 00:30:55,012 BRC -- SORRY, NBR2. 579 00:30:55,012 --> 00:30:59,016 SO THIS IS NOW CAUSAL GENES IN 580 00:30:59,016 --> 00:31:02,619 THE LOCUS BUT WHAT ABOUT THE 581 00:31:02,619 --> 00:31:03,987 CAUSAL VARIANT? 582 00:31:03,987 --> 00:31:07,024 SO WE TOOK 400 VARIANTS THAT 583 00:31:07,024 --> 00:31:09,660 LINKED IN THIS REGION AND 584 00:31:09,660 --> 00:31:11,028 CONNECTED THEM IN REGULATORY 585 00:31:11,028 --> 00:31:14,498 ELEMENTS THAT ARE ACTIVE IN 586 00:31:14,498 --> 00:31:18,569 OVARIAN CELL TYPE THROUGH OUR 587 00:31:18,569 --> 00:31:19,036 SIN 588 00:31:19,036 --> 00:31:22,806 SIN 589 00:31:22,806 --> 00:31:25,576 SINGLE NUC ATTACK SEQ AND FOUND 590 00:31:25,576 --> 00:31:27,544 FIVE VARIANTS IN OVARY CELL 591 00:31:27,544 --> 00:31:27,745 TYPES. 592 00:31:27,745 --> 00:31:31,014 SO HOW DO WE TEST THIS? 593 00:31:31,014 --> 00:31:37,054 SO WE DECIDED TO USE CRISPR 594 00:31:37,054 --> 00:31:47,431 PERTURBATIONS AND DID 595 00:31:53,470 --> 00:31:55,005 COMPRESSIONAL ANALYSIS AFTER THE 596 00:31:55,005 --> 00:31:57,374 CRISPR SCREEN AND FOUND THIS 597 00:31:57,374 --> 00:32:01,044 VARIANT IN THE DISTAL LOCUS 598 00:32:01,044 --> 00:32:09,420 BETWEEN V8T IS AND R2 GENE IS 599 00:32:09,420 --> 00:32:12,756 WHAT DYSREGULATE THE NBR2 600 00:32:12,756 --> 00:32:15,225 EXPRESSION AND WE IDENTIFIED 601 00:32:15,225 --> 00:32:17,828 CANDIDATE CAUSAL GENES AND 602 00:32:17,828 --> 00:32:19,163 VARIANTS AND THROUGH THIS STEM 603 00:32:19,163 --> 00:32:22,232 CELL DIFFERENTIATION PARADIGM 604 00:32:22,232 --> 00:32:24,601 AND SPECIFIC EXPRESSION AND 605 00:32:24,601 --> 00:32:27,304 CRISPR SCREEN WE PINPOINT CAUSAL 606 00:32:27,304 --> 00:32:27,905 VARIANT. 607 00:32:27,905 --> 00:32:33,777 OKAY, THESE ARE TWO LOCUS. 608 00:32:33,777 --> 00:32:37,014 OH, I HAVE TO SAY THIS, SO NBR2 609 00:32:37,014 --> 00:32:41,452 IS A LONG KNOWN CODING RNA 610 00:32:41,452 --> 00:32:44,788 THAT'S PRIMATE SPECIFIC. 611 00:32:44,788 --> 00:32:48,158 MICE DOESN'T HAVE IT. 612 00:32:48,158 --> 00:32:51,662 IT'S INTERESTING HOW THE LONG 613 00:32:51,662 --> 00:32:56,800 KNOWN VARIANT CONTRIBUTES TO 614 00:32:56,800 --> 00:33:02,739 IMAGINATION OF OVARIAN AGING AND 615 00:33:02,739 --> 00:33:03,307 MAG 616 00:33:03,307 --> 00:33:04,942 MAG 617 00:33:04,942 --> 00:33:06,977 MAGGIE KANE IN MY LAB IS LOOKING 618 00:33:06,977 --> 00:33:10,013 TO HOW IT CONTRIBUTES TO OVARIAN 619 00:33:10,013 --> 00:33:11,782 AGING IN HUMAN. 620 00:33:11,782 --> 00:33:15,018 SO TWO LOCI. 621 00:33:15,018 --> 00:33:16,720 IT TOOK US A WHILE. 622 00:33:16,720 --> 00:33:18,622 BUT WHEN WE DID INSILICA 623 00:33:18,622 --> 00:33:20,824 PREDICTION WE FOUND MORE THAN 624 00:33:20,824 --> 00:33:24,328 100 POTENTIALLY CAUSAL VARIANTS 625 00:33:24,328 --> 00:33:26,296 LINKED TO AGING NATURAL 626 00:33:26,296 --> 00:33:26,563 MENOPAUSE. 627 00:33:26,563 --> 00:33:29,900 HOW ARE WE GOING TO TEST IT? 628 00:33:29,900 --> 00:33:31,969 ARE WE GOING TO TAKE OUR 629 00:33:31,969 --> 00:33:41,311 FAVORITE GENE AND TEST THOSE OR 630 00:33:41,311 --> 00:33:44,381 LOOK AT TARGETS? 631 00:33:44,381 --> 00:33:47,384 SINCE WE PERFORMED THE HIGH 632 00:33:47,384 --> 00:33:48,485 THROUGHPUT SCREEN TO IDENTIFY 633 00:33:48,485 --> 00:33:52,556 CAUSAL GENES AND CAUSAL VARIANTS 634 00:33:52,556 --> 00:33:58,161 IN ENDOGENOUS GENOMIC CONTESTS 635 00:33:58,161 --> 00:33:59,930 BY USING SINGLE CELL CRISPR I 636 00:33:59,930 --> 00:34:00,797 METHOD. 637 00:34:00,797 --> 00:34:02,799 THIS IS A SIMPLIFIED SCHEMATIC. 638 00:34:02,799 --> 00:34:04,601 YOU HAVE A CAUSAL VARIANT IN THE 639 00:34:04,601 --> 00:34:08,372 MIDDLE THAT SITS IN THE 640 00:34:08,372 --> 00:34:09,706 REGULATORY ELEMENT. 641 00:34:09,706 --> 00:34:13,977 THERE ARE SIX SIX NEIGHBORING 642 00:34:13,977 --> 00:34:16,480 GENES AND HOW DO YOU KNOW THE 643 00:34:16,480 --> 00:34:17,414 CAUSAL VARIANT? 644 00:34:17,414 --> 00:34:26,356 BY TARGETING CRISPR DCAS9 AND 645 00:34:26,356 --> 00:34:28,325 YOU SEE GENE F IS DOWN REGULATED 646 00:34:28,325 --> 00:34:31,028 BY THE CRISPR TARGETING. 647 00:34:31,028 --> 00:34:31,995 BY COMBINING THIS WITH A SINGLE 648 00:34:31,995 --> 00:34:35,332 CELL YOU CAN REALLY LOOK AT THE 649 00:34:35,332 --> 00:34:39,036 DOWN STREAM TRANSCRIPTOMIC WIDE 650 00:34:39,036 --> 00:34:43,006 NETWORK EFFECT. 651 00:34:43,006 --> 00:34:46,476 SO TO BE ABLE TO DO THIS, THEY 652 00:34:46,476 --> 00:34:52,215 SET UP THE STRONG DUAL REPRESSOR 653 00:34:52,215 --> 00:34:55,452 SYSTEM LINKED TO DCAS9 DESIGN 654 00:34:55,452 --> 00:34:57,154 GRNA THAT CAN BE SEQUENCED BY 655 00:34:57,154 --> 00:35:01,458 10X AND THEN YOU CAN ANALYZE 656 00:35:01,458 --> 00:35:03,860 EXPRESSION OF THE NEIGHBORING 657 00:35:03,860 --> 00:35:05,429 GENES AS WELL AS TRANSCRIPTOME 658 00:35:05,429 --> 00:35:10,500 WIDE CHANGES. 659 00:35:10,500 --> 00:35:13,604 SO JINPING DID ALL 100 VARIANTS 660 00:35:13,604 --> 00:35:17,140 AND IT WORKED BEAUTIFULLY. 661 00:35:17,140 --> 00:35:18,542 THIS IS GRANULOSA CELL. 662 00:35:18,542 --> 00:35:21,311 HE STARTED WITH THIS BECAUSE 663 00:35:21,311 --> 00:35:24,615 THIS IS OVER SPECIFIC YOU CAN 664 00:35:24,615 --> 00:35:28,418 SEE COMPARED TO NON-TARGETING 665 00:35:28,418 --> 00:35:31,488 CONTROL YOU SEE HUGE REGULATED 666 00:35:31,488 --> 00:35:35,492 GENES ABOUT 70 OF THEM AND MANY 667 00:35:35,492 --> 00:35:36,927 SHOWDOWN REGULATION AS YOU WOULD 668 00:35:36,927 --> 00:35:39,963 PREDICT FROM PERTURBATION. 669 00:35:39,963 --> 00:35:43,934 THESE ARE THE TARGET GENES. 670 00:35:43,934 --> 00:35:45,736 THE SIZE OF THE LETTER INDICATES 671 00:35:45,736 --> 00:35:48,505 THE FREQUENCY OF THE DETECTION 672 00:35:48,505 --> 00:35:50,073 AND YOU CAN APPRECIATE THE 673 00:35:50,073 --> 00:35:53,944 FUNCTION OF THE GENES ARE REALLY 674 00:35:53,944 --> 00:35:54,811 NOT KNOWN MUCH. 675 00:35:54,811 --> 00:36:02,853 THAT MEANS WE HAVE A LOT TO DO. 676 00:36:02,853 --> 00:36:08,258 I'LL PRESENT A COUPLE COUPLE 677 00:36:08,258 --> 00:36:10,661 EXAMPLES WHEN WE TARGETED WITH 678 00:36:10,661 --> 00:36:14,031 CRISPRI IT DOWN REGULATED 679 00:36:14,031 --> 00:36:24,908 HEALTHY GENE AGAIN CONFIRM II 680 00:36:25,409 --> 00:36:27,010 HELB AND WE LOOKED AT PLIO 681 00:36:27,010 --> 00:36:30,580 TROPIC VARIANTS AND WHEN YOU 682 00:36:30,580 --> 00:36:41,024 TARGET THE VARIANT IS THE 683 00:36:42,726 --> 00:36:45,629 EXPRESSION IS SHOWN AND THE 684 00:36:45,629 --> 00:36:50,834 PHOSPHO LIPID PROTEIN IS SEEN IN 685 00:36:50,834 --> 00:36:53,537 SIGNAL TRANSACTION AND STUDIES 686 00:36:53,537 --> 00:36:56,673 HAVE BEEN DONE AND ONE SHOWS 687 00:36:56,673 --> 00:36:59,109 TATE CORRELATED WITH OVARIAN 688 00:36:59,109 --> 00:36:59,543 CANCER. 689 00:36:59,543 --> 00:37:02,612 EXPRESSION OF THE GENE IS 690 00:37:02,612 --> 00:37:05,549 CORRELATED WITH BAD PROGNOSIS 691 00:37:05,549 --> 00:37:12,723 AND MORE TUMOR GROWTH. 692 00:37:12,723 --> 00:37:13,490 THE REASON WE'RE INTERESTED IN 693 00:37:13,490 --> 00:37:17,060 THE GENE AND VARIANT IS WHEN YOU 694 00:37:17,060 --> 00:37:21,198 TARGET THE VARIANT THEREBY 695 00:37:21,198 --> 00:37:22,999 DECREASING THE EXPRESSION OF 696 00:37:22,999 --> 00:37:23,734 THERE'S ENORMOUS TRANSCRIPTOME 697 00:37:23,734 --> 00:37:28,672 WIDE IMPACT. 698 00:37:28,672 --> 00:37:31,041 BY TARGETING HUNDREDS OF 699 00:37:31,041 --> 00:37:32,843 VARIANTS WE TARGET GENES GOING 700 00:37:32,843 --> 00:37:36,279 UP AND DOWN AND MORE THAN HALF 701 00:37:36,279 --> 00:37:43,086 OR CLOSE TO HALF ARE DUE TO 702 00:37:43,086 --> 00:37:46,389 TARGETING AND WHEN WE LOOK AT 703 00:37:46,389 --> 00:37:49,059 THE GENES THEY'RE ENRICHED IN 704 00:37:49,059 --> 00:37:53,196 THE HALLMARK OF AGING INCLUDING 705 00:37:53,196 --> 00:37:55,232 MITOCHONDRIAL DYSFUNCTION AND 706 00:37:55,232 --> 00:37:59,202 THIS IS OXIDATIVE 707 00:37:59,202 --> 00:38:02,806 PHOSPHORYLATION AND APOPTOSIS 708 00:38:02,806 --> 00:38:03,106 SIGNALLING. 709 00:38:03,106 --> 00:38:04,341 SO THIS IS GOING TO BE ANOTHER 710 00:38:04,341 --> 00:38:11,014 SET OF A STUDY WE DELVE INTO TO 711 00:38:11,014 --> 00:38:13,250 UNDERSTAND THE UNDERLYING 712 00:38:13,250 --> 00:38:16,853 MECHANISM OF CONTRIBUTION, THIS 713 00:38:16,853 --> 00:38:19,022 GENE TO AGING IN OVARY IN HUMAN 714 00:38:19,022 --> 00:38:25,962 IN WOMEN. 715 00:38:25,962 --> 00:38:26,163 OKAY. 716 00:38:26,163 --> 00:38:30,567 SO FINALLY WHAT ABOUT AGING 717 00:38:30,567 --> 00:38:31,001 TRANSCRIPTOME. 718 00:38:31,001 --> 00:38:35,539 IF WE PERFORMED A SINGLE NUC RNA 719 00:38:35,539 --> 00:38:39,009 SEQ IN YOUNG VERSUS OLDER OVARY, 720 00:38:39,009 --> 00:38:40,944 HOW DO THEY CHANGE? 721 00:38:40,944 --> 00:38:46,082 CELL TYPES IN THE OVARY. 722 00:38:46,082 --> 00:38:51,021 WE IDENTIFIED 3,000 GENES GOING 723 00:38:51,021 --> 00:38:52,355 UP AND DOWN WITH AGE AND SURE 724 00:38:52,355 --> 00:38:53,523 YOU CAN APPRECIATE WHEN YOU LOOK 725 00:38:53,523 --> 00:38:57,394 AT THIS THE DIRECTIONAL CHANGE 726 00:38:57,394 --> 00:38:58,261 IS THE SAME ACROSS DIFFERENT 727 00:38:58,261 --> 00:38:59,596 CELL TYPES. 728 00:38:59,596 --> 00:39:01,731 THERE'S COORDINATION. 729 00:39:01,731 --> 00:39:05,602 THIS WAS QUITE STRIKING AND JIN 730 00:39:05,602 --> 00:39:09,539 DECIDED TO LOOK AT THE EXTEND OF 731 00:39:09,539 --> 00:39:16,413 COORDINATION SO HE COULD LOOK AT 732 00:39:16,413 --> 00:39:19,616 PAIRWISE IN TERMS OF SIMILARITY 733 00:39:19,616 --> 00:39:23,053 AND YOU CAN APPRECIATE THE 734 00:39:23,053 --> 00:39:24,688 COORDINATION. 735 00:39:24,688 --> 00:39:28,158 AND IT'S A COORDINATED MANNER. 736 00:39:28,158 --> 00:39:30,293 TO SEE IF THIS IS OVARY SPECIFIC 737 00:39:30,293 --> 00:39:35,031 OR GENERAL AGING PHENOMENON, JIN 738 00:39:35,031 --> 00:39:36,900 ALSO LOOKED AT OTHER SINGLE CELL 739 00:39:36,900 --> 00:39:39,035 DATA FROM OTHER HUMAN TISSUES 740 00:39:39,035 --> 00:39:42,505 DURING AGING PROCESSES IN THE 741 00:39:42,505 --> 00:39:43,740 SAME AGE. 742 00:39:43,740 --> 00:39:46,076 INCLUDING ADIPOSE, BLOOD, 743 00:39:46,076 --> 00:39:47,911 MARROW, BRAIN, LIVER, BRAINS AND 744 00:39:47,911 --> 00:39:48,478 LUNG. 745 00:39:48,478 --> 00:39:51,748 YOU CAN SEE COMPARED TO OVARY, 746 00:39:51,748 --> 00:39:53,617 THERE'S LITTLE OR NO 747 00:39:53,617 --> 00:39:58,188 COORDINATION. 748 00:39:58,188 --> 00:39:59,055 THIS TRANSCRIPTOME WIDE 749 00:39:59,055 --> 00:40:00,824 COORDINATED CHANGING IS A 750 00:40:00,824 --> 00:40:01,391 STRIKING FEATURE OF OVARIAN 751 00:40:01,391 --> 00:40:05,629 AGING. 752 00:40:05,629 --> 00:40:09,532 ANOTHER FEATURE THAT WE THOUGHT 753 00:40:09,532 --> 00:40:11,568 WAS INTERESTING IS THAT THIS 754 00:40:11,568 --> 00:40:14,037 AGING TRANSCRIPT OME THAT 755 00:40:14,037 --> 00:40:16,172 CHANGES WITH AGE IN DIFFERENT 756 00:40:16,172 --> 00:40:18,475 CELL TYPES IN THE OVARY, THEY'RE 757 00:40:18,475 --> 00:40:21,144 REALLY ENRICHED IN THE HALLMARKS 758 00:40:21,144 --> 00:40:23,046 OF AGING AS WE KNOW IT. 759 00:40:23,046 --> 00:40:26,816 THIS IS SOME OF THE EXAMPLES. 760 00:40:26,816 --> 00:40:32,722 YOU CAN SEE MITOCHONDRIAL 761 00:40:32,722 --> 00:40:35,759 DYSFUNCTION, DESENSING 762 00:40:35,759 --> 00:40:39,062 SIGNALLING AND HOMEOSTASIS AND 763 00:40:39,062 --> 00:40:42,832 GENOME INSTABILITY, CELLULAR 764 00:40:42,832 --> 00:40:47,037 SENESCENCE AND TELOMERE 765 00:40:47,037 --> 00:40:50,340 SHORTENING AND AGAIN YOU SEE THE 766 00:40:50,340 --> 00:40:51,374 COORDINATED CHANGE ACROSS 767 00:40:51,374 --> 00:40:52,842 DIFFERENT CELL TYPE. 768 00:40:52,842 --> 00:40:58,348 WHAT CAUGHT OUR EYES WAS REALLY 769 00:40:58,348 --> 00:41:00,483 NTOR SIGNALLING PATHWAY THAT'S 770 00:41:00,483 --> 00:41:03,053 ACTIVATED IN THE OVARY ACROSS 771 00:41:03,053 --> 00:41:08,558 MULTIPLE CELL TYPES. 772 00:41:08,558 --> 00:41:11,795 SO USING THE HUMAN TISSUE DATA 773 00:41:11,795 --> 00:41:13,930 FROM OTHER TISSUES WE COMPARED 774 00:41:13,930 --> 00:41:15,065 AND LOOKED AT HOW SPECIFIC IS 775 00:41:15,065 --> 00:41:19,035 THIS SO THE AGING TISSUES, AND 776 00:41:19,035 --> 00:41:24,274 SO JIN MEASURED THE AMPLITUDE 777 00:41:24,274 --> 00:41:26,710 INDEX AS WELL AS THE PREVALENCE 778 00:41:26,710 --> 00:41:28,311 RATIO ACROSS DIFFERENT CELL 779 00:41:28,311 --> 00:41:29,746 TYPES AND OVARY REALLY STOOD 780 00:41:29,746 --> 00:41:31,047 OUT. 781 00:41:31,047 --> 00:41:35,085 SO AT LEAST IN THIS AGE MTOR 782 00:41:35,085 --> 00:41:38,922 SIGNALLING ACTIVATION IS TRULY 783 00:41:38,922 --> 00:41:41,758 OVARY SPECIFIC. 784 00:41:41,758 --> 00:41:43,626 AS YOU KNOW, MTOR SIGNALLING IS 785 00:41:43,626 --> 00:41:47,263 A MAJOR CONTROL MECHANISM OF 786 00:41:47,263 --> 00:41:51,034 AGING. 787 00:41:51,034 --> 00:42:01,578 IT'S INHIBITOR, RAP RAPAMYCIN 788 00:42:03,947 --> 00:42:06,383 IT INCREASES LIFE SPAN IN ALL 789 00:42:06,383 --> 00:42:10,086 MOTOR ORGANISMS TESTED SO FAR. 790 00:42:10,086 --> 00:42:20,597 SO VERY ROBUST GEROPROTECTOR. 791 00:42:21,698 --> 00:42:23,433 AND THIS SIGNALLING IN ALL THE 792 00:42:23,433 --> 00:42:26,236 OVARY SUGGESTS TO US THAT OVARY 793 00:42:26,236 --> 00:42:31,041 CAN BE MAYBE A GEROTHERAPEUTIC 794 00:42:31,041 --> 00:42:33,710 TARGET OF RAPAMYCIN. 795 00:42:33,710 --> 00:42:35,412 AND THIS WAS ALSO IN LINE WITH 796 00:42:35,412 --> 00:42:38,915 THE DATA FROM US AND RODENT 797 00:42:38,915 --> 00:42:41,751 STUDIES IN MICE, RAPAMYCIN 798 00:42:41,751 --> 00:42:43,653 TREATMENT INCREASED OVARIAN LIFE 799 00:42:43,653 --> 00:42:47,757 SPAN AND FERTILITY AND EVEN 800 00:42:47,757 --> 00:42:49,826 UNDER CHEMOTHERAPY TREATMENT 801 00:42:49,826 --> 00:42:50,226 CONDITION. 802 00:42:50,226 --> 00:42:53,763 SO TOGETHER WITH OUR DATA, WE 803 00:42:53,763 --> 00:42:56,466 NOW INITIATED CLINICAL TRIAL TO 804 00:42:56,466 --> 00:43:00,937 TEST THE EFFICACY OF RAPAMYCIN 805 00:43:00,937 --> 00:43:03,173 TO EXTEND FEMALE REPRODUCTIVE 806 00:43:03,173 --> 00:43:07,744 LIFE SPAN IN HUMANS. 807 00:43:07,744 --> 00:43:09,546 THE TRIAL IS CALLED VIBRANT 808 00:43:09,546 --> 00:43:12,882 STUDY VALIDATING BENEFITS OF 809 00:43:12,882 --> 00:43:16,252 RAPAMYCIN FOR REPRODUCTIVE AGING 810 00:43:16,252 --> 00:43:18,388 TREATMENT IN COLLABORATION WITH 811 00:43:18,388 --> 00:43:21,558 THE DIRECTOR OF COLUMBIA 812 00:43:21,558 --> 00:43:23,026 FERTILITY CENTER. 813 00:43:23,026 --> 00:43:33,536 AND THIS IS A SMALL COHORT 15 814 00:43:37,740 --> 00:43:40,643 INDIVIDUALS, HALF PLACEBO, OF 815 00:43:40,643 --> 00:43:40,944 COURSE. 816 00:43:40,944 --> 00:43:42,145 WHEN THE CLINICAL TRIAL SITE 817 00:43:42,145 --> 00:43:44,047 BECAME LIVE WE GOT E-MAILS FROM 818 00:43:44,047 --> 00:43:44,747 200 WOMEN. 819 00:43:44,747 --> 00:43:47,050 THEY REALLY WANTED TO 820 00:43:47,050 --> 00:43:53,756 PARTICIPATE IN THIS TRIAL. 821 00:43:53,756 --> 00:43:56,626 THE STUDY DESIGN THAT WE GIVE 822 00:43:56,626 --> 00:43:59,762 LOW DOSE RAPAMYCIN, 5 MILLIGRAMS 823 00:43:59,762 --> 00:44:02,332 PER WEEK. 824 00:44:02,332 --> 00:44:05,235 THIS IS THE DOSE PEOPLE TAKE OFF 825 00:44:05,235 --> 00:44:09,472 LABEL FOR GEROPROTECTIVE EFFECT 826 00:44:09,472 --> 00:44:10,940 AND FOLLOW ADDITIONALLY FOR NINE 827 00:44:10,940 --> 00:44:11,174 MONTHS. 828 00:44:11,174 --> 00:44:12,108 DURING THE TREATMENT THEY HAVE 829 00:44:12,108 --> 00:44:15,578 TO COME TO THE CLINIC EVERY 830 00:44:15,578 --> 00:44:15,845 WEEK. 831 00:44:15,845 --> 00:44:19,315 SO IT'S REALLY LIMITED TO THE 832 00:44:19,315 --> 00:44:22,819 GREATER NEW YORK AREA FOR THAT 833 00:44:22,819 --> 00:44:23,052 REASONS. 834 00:44:23,052 --> 00:44:28,791 WE RECRUITED EVERYONE AND ALMOST 835 00:44:28,791 --> 00:44:31,461 AT THE END OF THE FOLLOW-UP 836 00:44:31,461 --> 00:44:34,264 STUDY. 837 00:44:34,264 --> 00:44:35,031 IT'S ALL BRIALINDED. 838 00:44:35,031 --> 00:44:39,769 WE DON'T KNOW THE RESULTS AROUND 839 00:44:39,769 --> 00:44:41,938 THERE'S NO SIDE EFFECT OR 840 00:44:41,938 --> 00:44:43,273 TOXICITY AND EVEN MENSTRUAL 841 00:44:43,273 --> 00:44:44,741 CYCLE IS NOT ALTERED. 842 00:44:44,741 --> 00:44:45,508 IT'S VERY SAFE. 843 00:44:45,508 --> 00:44:49,312 THE PRIMARY OUTCOME OF THE TRIAL 844 00:44:49,312 --> 00:44:49,879 IS OVARIAN RESEARCH. 845 00:44:49,879 --> 00:44:51,281 WE'RE LOOKING AT MARKERS OF 846 00:44:51,281 --> 00:44:54,117 OVARIAN RESERVE. 847 00:44:54,117 --> 00:44:59,055 AT THE END WE ALSO WANT TO 848 00:44:59,055 --> 00:45:01,624 COLLECT MULTI-OMIC BIOMARKER FOR 849 00:45:01,624 --> 00:45:03,059 POTENTIAL MECHANISTIC INSIGHTS. 850 00:45:03,059 --> 00:45:05,762 AS YOU CAN SEE THIS IS PILOT 851 00:45:05,762 --> 00:45:08,598 PROOF OF CONCEPT STUDY. 852 00:45:08,598 --> 00:45:10,934 NOW WE ARE PLANNING 853 00:45:10,934 --> 00:45:14,070 MULTI-CENTERED TRIAL ACROSS THE 854 00:45:14,070 --> 00:45:15,038 U.S. 855 00:45:15,038 --> 00:45:17,040 THERE ARE SEVEN CENTERS 856 00:45:17,040 --> 00:45:18,575 INTERESTED IN THE STUDY. 857 00:45:18,575 --> 00:45:19,509 SO WE'RE QUITE EXCITED ABOUT 858 00:45:19,509 --> 00:45:23,580 THIS TRIAL. 859 00:45:23,580 --> 00:45:25,281 IT FORMED OUR BASIC SCIENCE 860 00:45:25,281 --> 00:45:30,220 MECHANISTIC WORK. 861 00:45:30,220 --> 00:45:31,754 OBVIOUSLY THE HUMAN TRIAL HAS 862 00:45:31,754 --> 00:45:32,889 ALSO LIMITATIONS. 863 00:45:32,889 --> 00:45:36,092 FOR EXAMPLE, WE CANNOT GET 864 00:45:36,092 --> 00:45:38,127 TISSUES INCLUDING OVARY. 865 00:45:38,127 --> 00:45:43,566 SO WE SAID, OH, MICE STUDY AND 866 00:45:43,566 --> 00:45:50,139 THE HUMAN TRIAL EXACTLY AND THIS 867 00:45:50,139 --> 00:45:54,811 IS TWO-MONTH RAPAMYCIN TREATMENT 868 00:45:54,811 --> 00:45:58,414 FOLLOWED BY TWO MONTHS AND IN 869 00:45:58,414 --> 00:46:02,085 THIS CASE WE CAN DO THOROUGH 870 00:46:02,085 --> 00:46:04,020 COMPREHENSIVE ANALYSIS INCLUDING 871 00:46:04,020 --> 00:46:06,155 TISSUES, OVARY IN THE LIVER. 872 00:46:06,155 --> 00:46:07,824 THE LIVER -- THE REASON WHY WE 873 00:46:07,824 --> 00:46:12,195 TOOK LIVER WAS BY THE END, I 874 00:46:12,195 --> 00:46:17,900 KNOW IT WITH THE RECENT TALK THE 875 00:46:17,900 --> 00:46:22,939 EPI GEN 876 00:46:22,939 --> 00:46:23,573 EPIGEN 877 00:46:23,573 --> 00:46:24,207 EPIGEN 878 00:46:24,207 --> 00:46:25,275 EPIGENETICS OF LIVER IS 879 00:46:25,275 --> 00:46:26,609 IMPORTANT AND WE'RE DOING 880 00:46:26,609 --> 00:46:28,778 EXTENSIVE MULTI-OMIC ANALYSIS 881 00:46:28,778 --> 00:46:31,781 FROM SINGLE CELL TO EPIGENETIC 882 00:46:31,781 --> 00:46:34,384 PROFILING, SPATIAL 883 00:46:34,384 --> 00:46:35,084 TRANSCRIPTOMICS AND EPIGENETIC 884 00:46:35,084 --> 00:46:38,388 AGE BY DEMETHYLATION. 885 00:46:38,388 --> 00:46:42,992 THIS IS ONE OF THE LARGEST 886 00:46:42,992 --> 00:46:43,693 COLLABO 887 00:46:43,693 --> 00:46:44,594 COLLABORATIVE STUDIES WE'VE DONE 888 00:46:44,594 --> 00:46:45,261 IN THE LAB. 889 00:46:45,261 --> 00:46:47,063 I'M VERY EXCITED ABOUT MOUSE 890 00:46:47,063 --> 00:46:51,567 RAPAMYCIN TRIAL. 891 00:46:51,567 --> 00:46:53,903 SO WITH THAT I WOULD LIKE TO 892 00:46:53,903 --> 00:46:58,207 SUMMARIZE MY TALK. 893 00:46:58,207 --> 00:47:03,046 AS I SAY, THE OVARY DOES MUCH 894 00:47:03,046 --> 00:47:07,550 MORE THAN REPRODUCTION AND 895 00:47:07,550 --> 00:47:09,619 INCREASES LIFE SPAN IN WOMEN AND 896 00:47:09,619 --> 00:47:11,988 BY INTEGRATING HUMAN GENETIC 897 00:47:11,988 --> 00:47:14,824 DATA WITH EPIGENOME MULTI-OMIC 898 00:47:14,824 --> 00:47:20,029 DATA SET WE COULD PREDICT CAUSAL 899 00:47:20,029 --> 00:47:22,965 VARIANTS IN GENES AND CELL TYPE 900 00:47:22,965 --> 00:47:27,003 AND WE VALIDATE USING STEM CELL 901 00:47:27,003 --> 00:47:28,371 ENGINEERING AND DIFFERENTIATION 902 00:47:28,371 --> 00:47:29,238 MODEL TO ESTABLISH THE CAUSALITY 903 00:47:29,238 --> 00:47:33,042 AND USE THEM AS A TARGET. 904 00:47:33,042 --> 00:47:36,879 AND OUR SINGLE CELL 905 00:47:36,879 --> 00:47:37,613 TRANSCRIPTOMIC ANALYSIS CLEARLY 906 00:47:37,613 --> 00:47:43,052 SHOWED THAT OVARY IS A MODEL OF 907 00:47:43,052 --> 00:47:46,856 ACCELERATED AGING. 908 00:47:46,856 --> 00:47:48,891 BUT INTERESTINGLY IT PROCEEDS 909 00:47:48,891 --> 00:47:51,227 TRUE THE EVOLUTIONARY CONSERVED 910 00:47:51,227 --> 00:47:53,363 PATHWAY OF AGING, WHAT WE CALL 911 00:47:53,363 --> 00:47:54,464 HALLMARKS OF AGING. 912 00:47:54,464 --> 00:47:59,035 THIS SUGGESTS TO US THAT KNOWN 913 00:47:59,035 --> 00:48:00,470 GERO PROTECTERS THAT TARGET 914 00:48:00,470 --> 00:48:02,338 HALLMARKS OF AGING CAN BE USED 915 00:48:02,338 --> 00:48:05,341 TO DELAY AGING IN THE OVARY. 916 00:48:05,341 --> 00:48:09,245 SO TO TEST THIS HYPOTHESIS WE 917 00:48:09,245 --> 00:48:13,049 HAVE INITIATED A STUDY USING 918 00:48:13,049 --> 00:48:15,885 RAPAMYCIN AS A PROOF OF 919 00:48:15,885 --> 00:48:16,285 PRINCIPLE. 920 00:48:16,285 --> 00:48:17,854 I'M SURE THERE WILL BE MANY MORE 921 00:48:17,854 --> 00:48:22,024 THERAPEUTIC AGENTS WE CAN TEST 922 00:48:22,024 --> 00:48:23,192 IN THE OVARY. 923 00:48:23,192 --> 00:48:25,962 SO WITH THAT, I'D LIKE TO THANK 924 00:48:25,962 --> 00:48:28,097 PEOPLE IN THE LAB. 925 00:48:28,097 --> 00:48:31,701 I THINK I ACKNOWLEDGED ALMOST 926 00:48:31,701 --> 00:48:35,037 EVERYONE AND ALSO WONDERFUL 927 00:48:35,037 --> 00:48:36,539 COLLABORATOR 928 00:48:36,539 --> 00:48:37,974 COLLABORATORS WITHOUT THEM THE 929 00:48:37,974 --> 00:48:39,342 WORK WOULD NOT HAVE BEEN 930 00:48:39,342 --> 00:48:41,878 POSSIBLE AND FUNDING FROM NIA. 931 00:48:41,878 --> 00:48:46,149 THANK YOU FOR YOUR ATTENTION. 932 00:48:46,149 --> 00:48:46,516 >> THANK YOU. 933 00:48:46,516 --> 00:48:50,453 QUITE A FEW QUESTIONS ONLINE BUT 934 00:48:50,453 --> 00:48:51,654 IF ANYONE HAS A QUESTION HERE 935 00:48:51,654 --> 00:48:53,222 YOU KNOW WHERE THE MICS ARE. 936 00:48:53,222 --> 00:48:55,825 I'LL START WITH THIS ONE BECAUSE 937 00:48:55,825 --> 00:48:56,926 THIS JUST CAME IN. 938 00:48:56,926 --> 00:48:58,461 WHAT IS THE AGE RANGE OF THE 939 00:48:58,461 --> 00:48:59,862 WOMEN IN YOUR VIBRANT STUDY AND 940 00:48:59,862 --> 00:49:03,199 THIS IS CUTE, DID THE MOUSE 941 00:49:03,199 --> 00:49:04,500 VERSION CORRESPOND WITH THE 942 00:49:04,500 --> 00:49:05,868 HUMAN AGE RANGE? 943 00:49:05,868 --> 00:49:07,637 >> YES. 944 00:49:07,637 --> 00:49:10,306 THE HUMAN -- WE WENT THROUGH 945 00:49:10,306 --> 00:49:11,874 MANY DIFFERENT ROUNDS. 946 00:49:11,874 --> 00:49:16,879 INITIALLY WE WANTED TO TARGET 947 00:49:16,879 --> 00:49:21,684 WOMEN WHO HAD DIFFICULTY 948 00:49:21,684 --> 00:49:22,819 INFERTILITY BUT THAT WAS VERY 949 00:49:22,819 --> 00:49:24,487 DIFFICULT TO RECRUIT AND DECIDED 950 00:49:24,487 --> 00:49:26,923 TO STICK TO NORMAL HEALTHY WOMEN 951 00:49:26,923 --> 00:49:31,661 IN AGE RANGE 35 TO 45. 952 00:49:31,661 --> 00:49:35,031 AND MOUSE AGE SORT OF ALIGNED 953 00:49:35,031 --> 00:49:44,474 WITH THE AGE RANGE. 954 00:49:44,474 --> 00:49:47,043 >> GREAT TALK. 955 00:49:47,043 --> 00:49:47,510 IT'S VERY INTERESTING. 956 00:49:47,510 --> 00:49:49,378 THANK YOU. 957 00:49:49,378 --> 00:49:51,481 SO MY QUESTION IS REPRODUCTIVE 958 00:49:51,481 --> 00:49:53,883 SYSTEM IS VERY SPECIAL. 959 00:49:53,883 --> 00:49:57,587 IT'S VERY IMPORTANT FOR 960 00:49:57,587 --> 00:49:59,055 EVOLUTION. 961 00:49:59,055 --> 00:50:04,594 OVARY IS VERY PROTECTED BUT AGE 962 00:50:04,594 --> 00:50:05,628 FASTER AND CEASE TO FUNCTION AT 963 00:50:05,628 --> 00:50:09,298 A SPECIFIC AGE RANGE, RIGHT. 964 00:50:09,298 --> 00:50:15,605 SO IS IT POSSIBLE OVARIAN AGING 965 00:50:15,605 --> 00:50:18,574 LIKE GENERAL AGING AS OTHER 966 00:50:18,574 --> 00:50:18,875 SYSTEM? 967 00:50:18,875 --> 00:50:23,045 IF THAT'S THE CASE, RIGHT, SO 968 00:50:23,045 --> 00:50:28,784 GET GEROPROTECTOR BASED ON AGING 969 00:50:28,784 --> 00:50:30,620 OF OTHER ORGANS WOULD NOT WORK, 970 00:50:30,620 --> 00:50:33,756 CAN YOU COMMENT ON THAT? 971 00:50:33,756 --> 00:50:34,991 >> YEAH, THAT'S A VERY 972 00:50:34,991 --> 00:50:36,592 INTERESTING QUESTION. 973 00:50:36,592 --> 00:50:38,895 ACTUALLY, I WAS REALLY PUZZLED 974 00:50:38,895 --> 00:50:40,363 BY OUR RESULTS. 975 00:50:40,363 --> 00:50:43,966 AND I WAS TRAINED IN AGING 976 00:50:43,966 --> 00:50:46,469 BIOLOGY -- PROGRAMMED AGING. 977 00:50:46,469 --> 00:50:47,837 >> AS IT A TOOL CANDIDATE CAN 978 00:50:47,837 --> 00:50:51,040 YOU IDENTIFY FOR THE GWAS AND 979 00:50:51,040 --> 00:50:54,410 OTHER AGING GENES, RIGHT. 980 00:50:54,410 --> 00:50:55,278 IT MAKES ME THINK THE 981 00:50:55,278 --> 00:50:59,048 POSSIBILITY. 982 00:50:59,048 --> 00:51:02,919 >> SO, I CALLED UP A COUPLE 983 00:51:02,919 --> 00:51:05,555 EVOLUTIONARY BIOLOGISTS AND IS 984 00:51:05,555 --> 00:51:06,589 IT REALLY PROGRAMMED? 985 00:51:06,589 --> 00:51:09,458 TO ME IT LOOKS LIKE IT. 986 00:51:09,458 --> 00:51:11,994 AND OF COURSE THERE'S NO CLEAR 987 00:51:11,994 --> 00:51:12,228 ANSWER. 988 00:51:12,228 --> 00:51:16,432 BUT I THINK IT'S POSSIBLE. 989 00:51:16,432 --> 00:51:22,405 THERE ARE HYPOTHESIS WHY HUMANS 990 00:51:22,405 --> 00:51:26,475 HAVE MENOPAUSE AND OVARIAN AGES 991 00:51:26,475 --> 00:51:28,611 SO MUCH RAPIDLY AND THIS IS 992 00:51:28,611 --> 00:51:31,047 SOMETHING I WOULD LEAVE TO 993 00:51:31,047 --> 00:51:33,082 EVOLUTIONARY BIOLOGISTS BUT ONE 994 00:51:33,082 --> 00:51:35,051 THING I'D LIKE TO SAY IS WHEN 995 00:51:35,051 --> 00:51:40,590 YOU'RE AGING PROCESS IS SO 996 00:51:40,590 --> 00:51:42,391 COMPRESSED IN A RAPIDLY AGING 997 00:51:42,391 --> 00:51:45,795 ORGAN LIKE OVARY -- YOU SEE THIS 998 00:51:45,795 --> 00:51:46,896 ENORMOUS COORDINATION AS IF 999 00:51:46,896 --> 00:51:49,732 THERE'S A SIGNAL COMING SAYING, 1000 00:51:49,732 --> 00:51:52,568 LET'S AGE NOW. 1001 00:51:52,568 --> 00:51:54,003 AND THEN YOU GO THROUGH VERY 1002 00:51:54,003 --> 00:51:55,671 RAPIDLY. 1003 00:51:55,671 --> 00:51:59,041 SO I THINK WHEN WE ARE TALKING 1004 00:51:59,041 --> 00:52:02,144 ABOUT TRANSLATION OF GE 1005 00:52:02,144 --> 00:52:05,748 GEROTHERAPEUTICS WE DON'T HAVE A 1006 00:52:05,748 --> 00:52:10,620 GOOD WAY FORWARD -- RAPID, I'M 1007 00:52:10,620 --> 00:52:11,053 SORRY. 1008 00:52:11,053 --> 00:52:15,057 I THINK THE OVARY COULD BE A 1009 00:52:15,057 --> 00:52:19,328 GOOD EXAMPLE AND IF RAPAMYCIN WE 1010 00:52:19,328 --> 00:52:23,499 CAN USE THE OVARY AS A RAPID 1011 00:52:23,499 --> 00:52:24,900 TEST SYSTEM TO TEST 1012 00:52:24,900 --> 00:52:27,036 GEROTHERAPEUTICS. 1013 00:52:27,036 --> 00:52:27,370 >> THANK YOU. 1014 00:52:27,370 --> 00:52:29,038 >> THANK YOU. 1015 00:52:29,038 --> 00:52:31,774 >> SO, IT'S REALLY FASCINATING 1016 00:52:31,774 --> 00:52:35,011 STUDIES ESPECIALLY THE 1017 00:52:35,011 --> 00:52:37,113 CONNECTION LINKED TO ENCODING OF 1018 00:52:37,113 --> 00:52:38,781 THE GENE EXPRESSIONS. 1019 00:52:38,781 --> 00:52:40,116 SO MY QUESTION IS SIMPLE. 1020 00:52:40,116 --> 00:52:42,985 TWO QUESTIONS. 1021 00:52:42,985 --> 00:52:47,056 SO ONE IS PROBABLY THE 1022 00:52:47,056 --> 00:52:49,325 REGULATING GENE ITSELF IS NOT 1023 00:52:49,325 --> 00:52:50,826 SPECIFICALLY EXPRESSED IN THE 1024 00:52:50,826 --> 00:52:51,027 OVARY. 1025 00:52:51,027 --> 00:52:58,067 PROBABLY LIKE THE HELB OR THE 1026 00:52:58,067 --> 00:53:03,005 NBR1 AND EXPRESSED AND ONE 1027 00:53:03,005 --> 00:53:10,513 QUESTION IS THE WHAT YOU 1028 00:53:10,513 --> 00:53:12,048 DISCOVERED CLUSTERED IN THE 1029 00:53:12,048 --> 00:53:15,985 SYSTEMS OR CLUSTERS TO THE 1030 00:53:15,985 --> 00:53:18,020 IDENTIFIED GENE IS REGULATED IN 1031 00:53:18,020 --> 00:53:18,287 PATHWAYS. 1032 00:53:18,287 --> 00:53:20,489 THAT'S MY FIRST QUESTION. 1033 00:53:20,489 --> 00:53:23,025 THE SECOND QUESTION IS JUST 1034 00:53:23,025 --> 00:53:25,127 LINKED TO THE PREVIOUS MENTION 1035 00:53:25,127 --> 00:53:26,629 THE GENE IS PROBABLY NOT JUST 1036 00:53:26,629 --> 00:53:30,800 EXPRESSED IN OVARY BUT ALSO 1037 00:53:30,800 --> 00:53:32,568 OTHER TISSUES. 1038 00:53:32,568 --> 00:53:35,905 SO WITH THE OTHER LIVER OR 1039 00:53:35,905 --> 00:53:37,239 MUSCLE, THE GENE EXPRESSION 1040 00:53:37,239 --> 00:53:38,307 CHANGES ALSO HAS A BENEFICIAL 1041 00:53:38,307 --> 00:53:40,910 FOR THE FITNESS OF THE SPECIFIC 1042 00:53:40,910 --> 00:53:43,713 TISSUES RATHER THAN THE OVARIES. 1043 00:53:43,713 --> 00:53:47,416 >> YEAH, TWO VERY IMPORTANT 1044 00:53:47,416 --> 00:53:47,783 QUESTION. 1045 00:53:47,783 --> 00:53:52,321 SO THE FIRST QUESTION SO WHEN 1046 00:53:52,321 --> 00:53:54,356 THIS MENOPAUSE GWAS CAME OUT, IT 1047 00:53:54,356 --> 00:53:57,093 WAS A BIG SURPRISE BECAUSE WHEN 1048 00:53:57,093 --> 00:54:01,530 WE LOOK AT THE POTENTIAL CAUSAL 1049 00:54:01,530 --> 00:54:03,032 GENES THERE ARE REALLY 1050 00:54:03,032 --> 00:54:04,033 SIGNIFICANT ENRICHED IN DNA 1051 00:54:04,033 --> 00:54:08,170 DAMAGE RESPONSE AND REPAIR. 1052 00:54:08,170 --> 00:54:11,040 WHICH, PERSONALLY I HAVE NEVER 1053 00:54:11,040 --> 00:54:11,607 SEEN. 1054 00:54:11,607 --> 00:54:16,212 THIS IS THE ONLY TRAIT THAT SO 1055 00:54:16,212 --> 00:54:19,548 DRAMATICALLY SHOW ENRICHMENT OF 1056 00:54:19,548 --> 00:54:24,253 THE MAJOR GENOME STABILITY 1057 00:54:24,253 --> 00:54:24,520 MECHANISM. 1058 00:54:24,520 --> 00:54:28,457 SO I THINK BUT THEY'RE NOT 1059 00:54:28,457 --> 00:54:28,724 CLUSTERED. 1060 00:54:28,724 --> 00:54:34,430 THEY'RE ALL OVER THE GENOME. 1061 00:54:34,430 --> 00:54:35,631 SOMEHOW THERE'S SOME SELECTION 1062 00:54:35,631 --> 00:54:39,034 GOING ON DURING AGING PROCESSES 1063 00:54:39,034 --> 00:54:41,103 IN THE OVARY THAT ARE OVER 1064 00:54:41,103 --> 00:54:42,071 REPRESENTED IN THE GWAS. 1065 00:54:42,071 --> 00:54:45,241 THAT'S NUMBER ONE. 1066 00:54:45,241 --> 00:54:49,044 NUMBER TWO, ABOUT THE 1067 00:54:49,044 --> 00:54:50,112 IMPLICATION. 1068 00:54:50,112 --> 00:54:53,649 >> NOT ONLY FOR THE OVARY BUT 1069 00:54:53,649 --> 00:54:56,886 OTHER TISSUES MIGHT BE AFFECTED 1070 00:54:56,886 --> 00:54:58,287 BY THE CHANGE OF GENE 1071 00:54:58,287 --> 00:54:58,587 EXPRESSION. 1072 00:54:58,587 --> 00:55:00,422 >> I DIDN'T MENTION -- I FORGOT. 1073 00:55:00,422 --> 00:55:02,658 THANK YOU FOR BRINGING THAT UP. 1074 00:55:02,658 --> 00:55:05,728 WE STARTED WITH THE GRANULOSA 1075 00:55:05,728 --> 00:55:05,928 CELLS. 1076 00:55:05,928 --> 00:55:08,097 THE CRISPR SCREEN AND IDENTIFIED 1077 00:55:08,097 --> 00:55:18,541 TARGET GENES AND VARIANTS. 1078 00:55:23,112 --> 00:55:25,281 WE EXPECT TO SEE THE GLOBAL 1079 00:55:25,281 --> 00:55:26,549 VARIANTS AND CELL TYPE SPECIFIC 1080 00:55:26,549 --> 00:55:27,750 VARIANT IN GENES. 1081 00:55:27,750 --> 00:55:28,984 MUST BE, RIGHT? 1082 00:55:28,984 --> 00:55:33,689 SO THIS SOMETHING WE TRIED TO 1083 00:55:33,689 --> 00:55:34,156 TEASE OUT. 1084 00:55:34,156 --> 00:55:37,660 ALL THE PREDICTIONS THROUGH THE 1085 00:55:37,660 --> 00:55:38,627 INTEGRATION SIGNALS AGAIN IT'S A 1086 00:55:38,627 --> 00:55:38,928 PREDICTION. 1087 00:55:38,928 --> 00:55:41,664 WE REALLY DON'T KNOW IF THIS IS 1088 00:55:41,664 --> 00:55:42,731 REALLY HAPPENING IN THE OVARY 1089 00:55:42,731 --> 00:55:43,699 AND CELL TYPE. 1090 00:55:43,699 --> 00:55:45,100 THAT'S SOMETHING THAT WE'RE 1091 00:55:45,100 --> 00:55:48,103 GOING AFTER. 1092 00:55:48,103 --> 00:55:51,040 SO, MY PREDICTION, YES, IT WILL 1093 00:55:51,040 --> 00:55:53,642 HAVE GLOBAL INFLUENCE BUT WE'LL 1094 00:55:53,642 --> 00:55:55,044 ALSO FIND CELL TYPE SPECIFIC 1095 00:55:55,044 --> 00:55:59,048 VARIANTS ESPECIALLY FOLLICULAR 1096 00:55:59,048 --> 00:56:03,018 CELLS LIKE GRANULOSA CELLS. 1097 00:56:03,018 --> 00:56:04,019 >> THANK YOU. 1098 00:56:04,019 --> 00:56:05,554 >> VERY NICE TALK. 1099 00:56:05,554 --> 00:56:09,258 I HAVE TWO QUESTIONS. 1100 00:56:09,258 --> 00:56:14,163 FIRST IS THE SYNCHRONIZATION 1101 00:56:14,163 --> 00:56:16,665 ACROSS THE CELL TYPE TO THE 1102 00:56:16,665 --> 00:56:18,100 OVARY IS PARTICULAR BECAUSE WHEN 1103 00:56:18,100 --> 00:56:20,569 YOU WANT TO TEST THE AGING OF 1104 00:56:20,569 --> 00:56:22,304 THE ISSUE IT TYPICALLY FIND 1105 00:56:22,304 --> 00:56:23,038 DIFFERENT MARKERS. 1106 00:56:23,038 --> 00:56:27,042 HAVE YOU CHECKED OTHER AGING 1107 00:56:27,042 --> 00:56:31,080 MARKERS IN THE CELL TYPES AND DO 1108 00:56:31,080 --> 00:56:32,514 YOU HAVE SOMETHING TO COMMENT 1109 00:56:32,514 --> 00:56:34,884 ABOUT WHY DO YOU THINK YOU HAVE 1110 00:56:34,884 --> 00:56:41,123 THIS SYNCHRONY AMONG THE CELLS? 1111 00:56:41,123 --> 00:56:42,124 >> THAT'S A VERY INTERESTING 1112 00:56:42,124 --> 00:56:44,793 QUESTION. 1113 00:56:44,793 --> 00:56:49,565 AGAIN, AS I SAID TO MAX'S 1114 00:56:49,565 --> 00:56:51,033 QUESTION, AS IF SOMETHING IS 1115 00:56:51,033 --> 00:56:54,270 VERY EXPRESSED AND THE SIGNAL 1116 00:56:54,270 --> 00:56:55,037 MAKES AGE VERY FAST. 1117 00:56:55,037 --> 00:56:58,140 WE DON'T KNOW. 1118 00:56:58,140 --> 00:57:02,745 SOME OTHER MARKERS WE LOOK ARE 1119 00:57:02,745 --> 00:57:06,115 PURATIVE CELL SENESCENCE 1120 00:57:06,115 --> 00:57:06,548 MARKERS. 1121 00:57:06,548 --> 00:57:09,685 WE SAW P21 EXPRESSION LEVEL 1122 00:57:09,685 --> 00:57:10,719 INCREASED QUITE SIGNIFICANTLY 1123 00:57:10,719 --> 00:57:21,163 WITH AGE IN THIS SETTING. 1124 00:57:22,197 --> 00:57:23,732 AND WE SEE SOME SYNCHRONY 1125 00:57:23,732 --> 00:57:24,333 CLEARLY SENESCENCE IS ONE OF 1126 00:57:24,333 --> 00:57:31,974 THEM. 1127 00:57:31,974 --> 00:57:39,348 I THINK THERE'S MORE DISCOVERED. 1128 00:57:39,348 --> 00:57:42,418 >> AND FOR GALS LISTENING, HOW 1129 00:57:42,418 --> 00:57:45,654 EARLY IS EARLY MENOPAUSE? 1130 00:57:45,654 --> 00:57:48,724 >> EARLY MENOPAUSE? 1131 00:57:48,724 --> 00:57:55,030 I THINK AGE 40 IS EXTREME EARLY 1132 00:57:55,030 --> 00:57:55,965 MENOPAUSE. 1133 00:57:55,965 --> 00:58:03,038 45, EARLY AND THEN 50, 51 IS 1134 00:58:03,038 --> 00:58:04,473 NORMAL RANGE. 1135 00:58:04,473 --> 00:58:05,074 >> OKAY. 1136 00:58:05,074 --> 00:58:07,042 LET ME SNEAK IN ONE QUESTION 1137 00:58:07,042 --> 00:58:09,078 FROM ONLINE. 1138 00:58:09,078 --> 00:58:11,981 GREAT TALK, EXPLANATION MARK. 1139 00:58:11,981 --> 00:58:13,449 IN THE UNDERLYING DNA SEQUENCES 1140 00:58:13,449 --> 00:58:17,286 HARBORING THE OVARY AGING 1141 00:58:17,286 --> 00:58:18,153 ASSOCIATED VARIANTS, HAVE YOU 1142 00:58:18,153 --> 00:58:21,623 FOUND AN ENRICHMENT OF CERTAIN 1143 00:58:21,623 --> 00:58:23,058 TF BINDING MOTIFS. 1144 00:58:23,058 --> 00:58:26,729 THESE TFs MAY BE CANDIDATED FOR 1145 00:58:26,729 --> 00:58:28,630 MEDIATING THE CHANGE OF THE 1146 00:58:28,630 --> 00:58:29,131 CAUSAL GENE EXPRESSION. 1147 00:58:29,131 --> 00:58:32,901 >> WE DID. 1148 00:58:32,901 --> 00:58:33,635 YES. 1149 00:58:33,635 --> 00:58:34,370 IT'S PUBLISHED. 1150 00:58:34,370 --> 00:58:37,506 IT'S IN OUR NATURE AGING PAPER 1151 00:58:37,506 --> 00:58:39,041 WHICH JUST CAME OUT. 1152 00:58:39,041 --> 00:58:39,708 CVP DELTA. 1153 00:58:39,708 --> 00:58:43,045 WE THINK IT'S A MASTER REGULATOR 1154 00:58:43,045 --> 00:58:44,847 OF OVARIAN AGING ACROSS 1155 00:58:44,847 --> 00:58:47,049 DIFFERENT CELL TYPES. 1156 00:58:47,049 --> 00:58:54,289 THAT'S QUITE STRIKING ACTUALLY. 1157 00:58:54,289 --> 00:58:56,025 DUE TO THE INTEREST OF TIME I 1158 00:58:56,025 --> 00:58:57,559 DIDN'T TALK ABOUT IT BUT THE 1159 00:58:57,559 --> 00:58:59,028 AUDIENCE CAN FIND THE PAPER. 1160 00:58:59,028 --> 00:59:01,363 IT'S VERY INTERESTING. 1161 00:59:01,363 --> 00:59:06,135 >> SO, MY QUESTION IS ON THE IPS 1162 00:59:06,135 --> 00:59:06,535 CELLS. 1163 00:59:06,535 --> 00:59:11,040 DIFFERENTIATED INTO OVARIAN CELL 1164 00:59:11,040 --> 00:59:18,147 TYPES. 1165 00:59:18,147 --> 00:59:22,017 I'M TRYING TO CHALLENGE AN 1166 00:59:22,017 --> 00:59:23,552 INITIATIVE ON MICROPHYSIOLOGY 1167 00:59:23,552 --> 00:59:24,153 SYSTEM. 1168 00:59:24,153 --> 00:59:25,621 I'M THINKING FOR DEVELOPING AND 1169 00:59:25,621 --> 00:59:28,857 USING OVARY AS A TESTING 1170 00:59:28,857 --> 00:59:31,393 PLATFORM FOR GEROTHERAPEUTICS, 1171 00:59:31,393 --> 00:59:38,667 WOULDN'T IT BE NICE IF YOU COULD 1172 00:59:38,667 --> 00:59:39,301 BUILD SOME SMALL MICROPHYSIOLOGY 1173 00:59:39,301 --> 00:59:39,535 SYSTEMS. 1174 00:59:39,535 --> 00:59:41,437 >> PLEASE SIGN ME IN. 1175 00:59:41,437 --> 00:59:42,905 WE CAN PROVIDE OVARIAN CELL 1176 00:59:42,905 --> 00:59:44,239 TYPES. 1177 00:59:44,239 --> 00:59:48,977 IT TOOK US A WHILE TO ESTABLISH 1178 00:59:48,977 --> 00:59:58,654 DIFFERENTIATION BUT YES, PLEASE. 1179 00:59:58,654 --> 01:00:02,091 THERE'S A POSTDOC THAT DEVELOPED 1180 01:00:02,091 --> 01:00:02,357 ORGANOIDS. 1181 01:00:02,357 --> 01:00:05,727 WE'RE NOW TRYING TO DEVELOP 1182 01:00:05,727 --> 01:00:08,197 HUMAN ORGANOIDS BY ADDING CELL 1183 01:00:08,197 --> 01:00:08,397 TYPES. 1184 01:00:08,397 --> 01:00:10,032 THAT WOULD BE REALLY COOL. 1185 01:00:10,032 --> 01:00:11,767 >> THAT WAS MY QUESTION. 1186 01:00:11,767 --> 01:00:13,936 ARE YOU WORKING ON THE ORGANOIDS 1187 01:00:13,936 --> 01:00:18,841 OR ARE YOU THINKING TO LITERALLY 1188 01:00:18,841 --> 01:00:20,442 ENGINEER THREE DIMENSIONAL 1189 01:00:20,442 --> 01:00:20,676 MODELS? 1190 01:00:20,676 --> 01:00:26,048 >> THAT WAS A POSTDOCTORAL AWARD 1191 01:00:26,048 --> 01:00:26,348 APPLICATION. 1192 01:00:26,348 --> 01:00:30,786 SO WE ARE USING ORGANOIDS FIRST. 1193 01:00:30,786 --> 01:00:32,788 >> OKAY. 1194 01:00:32,788 --> 01:00:34,456 TO SCREEN KNOWN NEUROPROTECTERS 1195 01:00:34,456 --> 01:00:38,160 AND PRIORITIZE AND THEN GO. 1196 01:00:38,160 --> 01:00:39,128 THAT WAS THE WHOLE PLAN. 1197 01:00:39,128 --> 01:00:39,461 >> THANK YOU. 1198 01:00:39,461 --> 01:00:42,431 >> THANK YOU. 1199 01:00:42,431 --> 01:00:44,800 >> A QUESTION ABOUT THE 1200 01:00:44,800 --> 01:00:46,168 RAPAMYCIN STUDY. 1201 01:00:46,168 --> 01:00:47,035 PRESUMABLY IN PREPARATION YOU 1202 01:00:47,035 --> 01:00:50,405 DID SURVEY THE PUBLISHED 1203 01:00:50,405 --> 01:00:52,875 CLINICAL LITERATURE ON USE OF 1204 01:00:52,875 --> 01:00:53,142 RAPAMYCIN. 1205 01:00:53,142 --> 01:00:53,842 WAS THERE SUFFICIENT DATA THERE 1206 01:00:53,842 --> 01:00:57,312 TO BE ABLE TO LOOK TO SEE FROM 1207 01:00:57,312 --> 01:00:59,848 THE NATURAL HISTORY MEDICAL 1208 01:00:59,848 --> 01:01:01,316 RECORDS INVOLVED IN THOSE 1209 01:01:01,316 --> 01:01:03,819 STUDIES WHETHER THERE WAS HINT 1210 01:01:03,819 --> 01:01:07,089 OR CLUE OF AFFECTS OF MENOPAUSE 1211 01:01:07,089 --> 01:01:07,756 ? 1212 01:01:07,756 --> 01:01:09,625 >> WE TRIED HARD TO FIND 1213 01:01:09,625 --> 01:01:14,363 INFORMATION BUT THUS FAR THE 1214 01:01:14,363 --> 01:01:16,231 RAPAMYCIN TAKERS ARE OLDER 1215 01:01:16,231 --> 01:01:25,207 INDIVIDUALS MOSTLY 60 PLUS. 1216 01:01:25,207 --> 01:01:35,684 WE COULD FIND ONE WOMAN 50. 1217 01:01:36,285 --> 01:01:39,988 YOUNGER WOMEN ARE IN TRIAL. 1218 01:01:39,988 --> 01:01:42,791 NO ONE SUFFERED FROM ANYTHING 1219 01:01:42,791 --> 01:01:46,395 NOT EVEN MOUTH SORE. 1220 01:01:46,395 --> 01:01:48,397 MAYBE BECAUSE YOUNG PEOPLE ARE 1221 01:01:48,397 --> 01:01:49,898 MORE RESILIENT. 1222 01:01:49,898 --> 01:01:55,003 >> MAYBE I CAN SNEAK IN ONE MORE 1223 01:01:55,003 --> 01:01:55,270 QUESTION. 1224 01:01:55,270 --> 01:01:59,041 WHAT HAPPENS WHEN YOUR OVARIES 1225 01:01:59,041 --> 01:02:01,243 ARE SURGICALLY REMOVED? 1226 01:02:01,243 --> 01:02:03,212 >> I HAD A SLIDE MAYBE THE 1227 01:02:03,212 --> 01:02:06,014 PERSON MISSED IT. 1228 01:02:06,014 --> 01:02:08,750 IF YOU SURGICALLY REMOVE OVARY, 1229 01:02:08,750 --> 01:02:11,954 THIS IS SURGICALLY INDUCED 1230 01:02:11,954 --> 01:02:13,822 MENOPAUSE, IT'S NOT GOOD AND 1231 01:02:13,822 --> 01:02:16,158 THEY HAVE A SHORTER LIFE SPAN 1232 01:02:16,158 --> 01:02:18,227 AND HAVE A HIGHER RISK FOR 1233 01:02:18,227 --> 01:02:22,331 AGE-RELATED DISEASES. 1234 01:02:22,331 --> 01:02:25,200 NOWADAYS AT THE TIME OF 1235 01:02:25,200 --> 01:02:27,035 HYSTERECTOMY THEY TRY TO SAVE 1236 01:02:27,035 --> 01:02:27,669 THE OVARY BECAUSE IF YOU 1237 01:02:27,669 --> 01:02:30,205 CONSERVE OVARY, THEY TEND TO 1238 01:02:30,205 --> 01:02:36,211 LIVE LONGER AND SUFFER LESS WITH 1239 01:02:36,211 --> 01:02:41,016 AGE-RELATED DISEASE COMPARED TO 1240 01:02:41,016 --> 01:02:49,858 COMPLETELY OVA ECTOMIZED WOMEN. 1241 01:02:49,858 --> 01:02:51,026 >> MY QUESTION IS RELATED TO 1242 01:02:51,026 --> 01:02:51,593 PREVIOUS QUESTIONS. 1243 01:02:51,593 --> 01:02:54,096 FOR THOSE AS YOU MENTIONED, 1244 01:02:54,096 --> 01:02:55,731 THOSE ALSO HAVE THE OVARY 1245 01:02:55,731 --> 01:03:03,839 REMOVED HAVE A LONGER REDUCED 1246 01:03:03,839 --> 01:03:04,106 MORTALITY. 1247 01:03:04,106 --> 01:03:05,841 DOES TREATMENT WITH THE 1248 01:03:05,841 --> 01:03:07,609 GEROPROTECTERS HELP REDUCE THEIR 1249 01:03:07,609 --> 01:03:08,310 MORTALITY? 1250 01:03:08,310 --> 01:03:11,046 >> NO ONE HAS EVER TESTED BUT 1251 01:03:11,046 --> 01:03:14,116 THAT'S A VERY GOOD WAY TO START. 1252 01:03:14,116 --> 01:03:16,818 SO WE'VE BEEN THINKING A LOT 1253 01:03:16,818 --> 01:03:19,021 ABOUT HOW TO EXPAND OUR VIBRANT 1254 01:03:19,021 --> 01:03:19,755 STUDIES. 1255 01:03:19,755 --> 01:03:23,025 NOW WE START WITH YOUNG HEALTHY 1256 01:03:23,025 --> 01:03:30,198 WOMEN BUT WOMEN WITH DIFFICULTY 1257 01:03:30,198 --> 01:03:33,835 GETTING PREGNANT OR OVARIAN 1258 01:03:33,835 --> 01:03:35,304 INSUFFICIENCY WILL HAVE 1259 01:03:35,304 --> 01:03:36,805 IMMEDIATE BENEFIT IF IT WORKS. 1260 01:03:36,805 --> 01:03:38,006 WE'VE BEEN TALKING ABOUT THIS 1261 01:03:38,006 --> 01:03:46,682 WITH POI PATIENTS. 1262 01:03:46,682 --> 01:03:47,616 >> I'M SURE THERE'S AN OBVIOUS 1263 01:03:47,616 --> 01:03:51,353 ANSWER TO THIS BUT THE NEGATIVE 1264 01:03:51,353 --> 01:03:55,791 EFFECTS OF SURGICAL REMOVAL 1265 01:03:55,791 --> 01:03:57,693 DESPITE EFFORTS OF HORMONE 1266 01:03:57,693 --> 01:04:00,896 REPLACEMENT, DO YOU HAVE ANY 1267 01:04:00,896 --> 01:04:03,765 IDEA WHAT THE SYSTEMIC EFFECTS 1268 01:04:03,765 --> 01:04:08,003 ARE BEYOND THE MEASURABLE HOE 1269 01:04:08,003 --> 01:04:08,670 MOAN CHANGES? 1270 01:04:08,670 --> 01:04:09,871 >> -- HORMONE CHANGES. 1271 01:04:09,871 --> 01:04:11,440 >> I CAN TELL YOU TWO STORIES. 1272 01:04:11,440 --> 01:04:14,443 NUMBER ONE, BASED ON OUR STUDY, 1273 01:04:14,443 --> 01:04:17,979 I MEAN ACROSS ALL THE CELL TYPES 1274 01:04:17,979 --> 01:04:28,457 IN THE OVARY, IT'S NOT JUST 1275 01:04:29,658 --> 01:04:31,026 STROMAL CELLS AND EVERYONE SHOWS 1276 01:04:31,026 --> 01:04:33,695 THE SAME. 1277 01:04:33,695 --> 01:04:37,566 THE OVARY INTERACTED WITH THE 1278 01:04:37,566 --> 01:04:42,604 SOMA AND INFLUENCE EACH OTHER. 1279 01:04:42,604 --> 01:04:47,275 YOU CAN REJUVENATE OLD LOCI WITH 1280 01:04:47,275 --> 01:04:52,814 A YOUNGER ONE AND A GROUP IN 1281 01:04:52,814 --> 01:04:54,583 SINGAPORE RECONSTITUTE THE OLD 1282 01:04:54,583 --> 01:04:59,020 WITH THE YOUNG FOLLICLES AND 1283 01:04:59,020 --> 01:05:09,398 SHOW THEY REGENERATE. 1284 01:05:09,865 --> 01:05:13,168 IF YOU REPLACE OLD OVARY WITH 1285 01:05:13,168 --> 01:05:14,269 YOUNG OVARY IT'S BENEFICIAL. 1286 01:05:14,269 --> 01:05:16,338 THOUGH THE SAMPLE SIZE WAS TOO 1287 01:05:16,338 --> 01:05:16,638 LITTLE. 1288 01:05:16,638 --> 01:05:19,307 I CANNOT MAKE CONCLUSION OF IT 1289 01:05:19,307 --> 01:05:23,044 BUT THE EFFECT WAS DRAMATIC. 1290 01:05:23,044 --> 01:05:24,679 BEFORE TRANSPLANTATION, THEY 1291 01:05:24,679 --> 01:05:29,117 REMOVED FOLLICLES THAT PRODUCE 1292 01:05:29,117 --> 01:05:30,118 HORMONE. 1293 01:05:30,118 --> 01:05:32,521 THERE'S A CHEMICAL THAT REMOVES 1294 01:05:32,521 --> 01:05:32,788 FOLLICLES. 1295 01:05:32,788 --> 01:05:34,790 NOW YOU HAVE A YOUNG OVARY 1296 01:05:34,790 --> 01:05:37,259 WITHOUT HORMONE WAS ENOUGH TO 1297 01:05:37,259 --> 01:05:40,429 EXTEND THE LIFE SPAN. 1298 01:05:40,429 --> 01:05:47,035 LOOKS EVEN BETTER. 1299 01:05:47,035 --> 01:05:51,039 THE COMPARTMENT HAVE LONGEVITY 1300 01:05:51,039 --> 01:05:56,745 EFFECTS. 1301 01:05:56,745 --> 01:05:58,313 AND SOMA DOES A LOT TO THE 1302 01:05:58,313 --> 01:05:59,014 HEALTH OF THE OVARY. 1303 01:05:59,014 --> 01:06:00,182 >> OKAY. 1304 01:06:00,182 --> 01:06:04,286 I'M GOING TO REPEAT OUR CME 1305 01:06:04,286 --> 01:06:05,987 CODE, 57685. 1306 01:06:05,987 --> 01:06:07,589 REMIND PEOPLE THERE'S A 1307 01:06:07,589 --> 01:06:09,424 RECEPTION JUST OUTSIDE THE DOORS 1308 01:06:09,424 --> 01:06:11,226 HERE AND MAYBE THANK OUR SPEAKER 1309 01:06:11,226 --> 01:06:12,294 ONE MORE TIME. 1310 01:06:12,294 --> 01:06:22,671 >> THANK YOU SO MUCH.