1
00:00:06,913 --> 00:00:10,016
THIS IS WIN ARIAS AND

2
00:00:10,016 --> 00:00:13,853
WITH MY COLLEAGUE DAN KASTNER AT

3
00:00:13,853 --> 00:00:16,122
THE NATIONAL INSTITUTES OF

4
00:00:16,122 --> 00:00:16,923
HEALTH IN BETHESDA, MARYLAND

5
00:00:16,923 --> 00:00:18,291
EMPLOY WE WELCOME YOU TO ANOTHER

6
00:00:18,291 --> 00:00:23,763
EXCITING SESSION IN THE COURSE

7
00:00:23,763 --> 00:00:25,565
CALLED DEMYSTIFYING MEDICINE

8
00:00:25,565 --> 00:00:28,768
WHICH IS NOW IN ITS 22nd YEAR.

9
00:00:28,768 --> 00:00:31,404
THIS IS A COURSE IN BRIDGE

10
00:00:31,404 --> 00:00:32,605
BUILDING.

11
00:00:32,605 --> 00:00:34,140
THE INTENT IS TO BRIDGE THE

12
00:00:34,140 --> 00:00:36,676
EXCITING DEVELOP AMS IN BIOLOGY,

13
00:00:36,676 --> 00:00:39,078
ENGINEERING AND COMPUTER SCIENCE

14
00:00:39,078 --> 00:00:39,612
WITH MEDICINE.

15
00:00:39,612 --> 00:00:43,482
IT IS NOT LAST WEEK'S RESEARCH

16
00:00:43,482 --> 00:00:46,219
SEMINAR, NOR IS IT LAST WEEK'S

17
00:00:46,219 --> 00:00:47,787
STRICTLY CLINICAL ROUNDS, IT

18
00:00:47,787 --> 00:00:52,358
BRIDGES THESE 2 MAJOR

19
00:00:52,358 --> 00:00:54,060
DISCIPLINES AS ILLUSTRATED IN

20
00:00:54,060 --> 00:00:57,563
THE LOGO IN THE UPPER RIGHT OF

21
00:00:57,563 --> 00:00:58,898
MY PRESENTATION OF THE BROOKLYN

22
00:00:58,898 --> 00:01:00,967
BRIDGE AND WE WILL DISCUSS WHAT

23
00:01:00,967 --> 00:01:02,401
THE 2 INDIVIDUALSOT CAT WALK ARE

24
00:01:02,401 --> 00:01:05,037
CONSIDERING IN A MOMENT.

25
00:01:05,037 --> 00:01:08,574
THE COURSE IS HELD ON FRIDAYS

26
00:01:08,574 --> 00:01:09,775
FROM 3-5:00 P.M. EASTERN

27
00:01:09,775 --> 00:01:10,576
STANDARD TIME FROM JANUARY TO

28
00:01:10,576 --> 00:01:12,378
THE END OF MAY.

29
00:01:12,378 --> 00:01:17,383
YOU CAN WATCH IT LIVE, YOU CAN

30
00:01:17,383 --> 00:01:21,187
ALSO ACCESS IT ON AN NIH

31
00:01:21,187 --> 00:01:24,290
VIDEOCAST WHICH IS INDICATED ON

32
00:01:24,290 --> 00:01:26,926
MY SLIDE.

33
00:01:26,926 --> 00:01:32,999
THE CME CREDIT CODE IS 58785.

34
00:01:32,999 --> 00:01:35,401
AND MOST IMPORTANTLY, WE

35
00:01:35,401 --> 00:01:37,036
ENCOURAGE YOU TO SUBMIT

36
00:01:37,036 --> 00:01:38,738
QUESTIONS DURING THE

37
00:01:38,738 --> 00:01:39,905
PRESENTATIONS AND THEY WILL BE

38
00:01:39,905 --> 00:01:41,974
GIVEN TO THE SPEAKERS AND WILL

39
00:01:41,974 --> 00:01:45,911
BE PART OF WHAT WE ALMOST ALWAYS

40
00:01:45,911 --> 00:01:47,580
HAVE A VIGOROUS DISCUSSION AND

41
00:01:47,580 --> 00:01:50,416
QUESTION AND ANSWER PERIOD AFTER

42
00:01:50,416 --> 00:01:51,250
THE PRESENTATIONS.

43
00:01:51,250 --> 00:01:55,621
AND YOU CAN SUBMIT YOUR

44
00:01:55,621 --> 00:01:56,789
QUESTIONS BY CLICKINGOT SEND

45
00:01:56,789 --> 00:02:01,327
LIVE FEEDBACK ON YOUR VIDEOCAST

46
00:02:01,327 --> 00:02:01,694
DISPLAY.

47
00:02:01,694 --> 00:02:03,195
NOW I BRING YOUR ATTENTION AT

48
00:02:03,195 --> 00:02:05,598
ALL PREVIOUS SESSIONS FROM THE

49
00:02:05,598 --> 00:02:16,275
VERY BEGINNING, ARE ARCHIVED AND

50
00:02:16,275 --> 00:02:17,410
IT IS NOTED ON THE SLIDE.

51
00:02:17,410 --> 00:02:18,778
IF YOU HAVE ANY OTHER QUESTIONS,

52
00:02:18,778 --> 00:02:20,780
GET IN TOUCH WITH US.

53
00:02:20,780 --> 00:02:21,614
THE OVERALL PURPOSE OF THE

54
00:02:21,614 --> 00:02:30,790
PROGRAM IS TO BRIDGE SILOS AT

55
00:02:30,790 --> 00:02:33,859
THE NIH -- TO CHANGE SILOS INTO

56
00:02:33,859 --> 00:02:34,126
A BRIDGE.

57
00:02:34,126 --> 00:02:37,897
MAY WE HAVE THE NEXT SLIDE. 

58
00:02:37,897 --> 00:02:38,698
PLEASE.

59
00:02:38,698 --> 00:02:40,032
NEXT.

60
00:02:40,032 --> 00:02:40,533
NEXT.

61
00:02:40,533 --> 00:02:40,733
YEAH.

62
00:02:40,733 --> 00:02:42,101
ALL RIGHT.

63
00:02:42,101 --> 00:02:44,603
TODAY'S TOPIC IS AGING AND

64
00:02:44,603 --> 00:02:49,742
YOU'LL SEE THE ACTUAL TITLE IN A

65
00:02:49,742 --> 00:02:50,743
FEW MOMENTS AND I'VE LIST OFFICE

66
00:02:50,743 --> 00:02:53,212
OF DIVERSITY THIS INTRODUCTORY

67
00:02:53,212 --> 00:02:55,348
SLIDE, THE AGE OF AGING

68
00:02:55,348 --> 00:02:55,681
THEORIES.

69
00:02:55,681 --> 00:02:57,983
IT ACTUALLY GOES FROM GENESIS TO

70
00:02:57,983 --> 00:03:06,692
GENES BECAUSE IN GENESIS STATED

71
00:03:06,692 --> 00:03:09,995
THAT HIS DAYS SHALL BE 120 YEARS

72
00:03:09,995 --> 00:03:12,665
WHICH WILL BE THE LIFE THAT

73
00:03:12,665 --> 00:03:13,165
MOSES LED.

74
00:03:13,165 --> 00:03:17,937
AND EVEN TODAY IN JEWISH

75
00:03:17,937 --> 00:03:19,872
CIRCLES, IT IS SAID [SPEAKING

76
00:03:19,872 --> 00:03:23,109
HEBREW ] MAY YOU LIVE TO BE 120

77
00:03:23,109 --> 00:03:23,776
DAYS.

78
00:03:23,776 --> 00:03:27,380
SO WITH THAT'S WHERE THE 120

79
00:03:27,380 --> 00:03:29,715
DAYS -- 120 YEARS CAME FROM.

80
00:03:29,715 --> 00:03:32,451
THERE WAS MUCH WRITTEN IN THE

81
00:03:32,451 --> 00:03:34,553
ANCIENT TIMES MORE BY PHILOSOPHY

82
00:03:34,553 --> 00:03:36,255
AND SOME OBSERVATION AND I THINK

83
00:03:36,255 --> 00:03:43,362
IT REALLY WASN'T UNTIL THE

84
00:03:43,362 --> 00:03:49,201
19th CENTURY WHEN

85
00:03:49,201 --> 00:03:50,569
METCHNIKOFF TALKED ABOUT THESE

86
00:03:50,569 --> 00:03:52,438
IDEAS WITH THE DISCOVERY OF THE

87
00:03:52,438 --> 00:03:54,640
MICROBIOME AND THE DISCOVERY

88
00:03:54,640 --> 00:03:56,108
THAT THE MICROBIOME COULD

89
00:03:56,108 --> 00:03:58,144
PROLONG AGING AND IT DIDN'T WORK

90
00:03:58,144 --> 00:04:03,315
TOO WELL FOR METCHNIKOFF WHO

91
00:04:03,315 --> 00:04:05,418
DIED IN HIS 60S, I THINK.

92
00:04:05,418 --> 00:04:07,186
BUT IT WAS IN THE 20th

93
00:04:07,186 --> 00:04:11,123
CENTURY, WHEN A NUTRITIONIST

94
00:04:11,123 --> 00:04:16,462
NAMED OSBORN, INTERESTING,

95
00:04:16,462 --> 00:04:19,665
INTRODUCED THE IDEA THAT --

96
00:04:19,665 --> 00:04:22,935
DIETARY RESTRICTION COULD

97
00:04:22,935 --> 00:04:29,909
PROLONG LIFE TO, BUT MANY HAVE

98
00:04:29,909 --> 00:04:31,544
DISCREDITED THAT, PARTICULARLY A

99
00:04:31,544 --> 00:04:33,179
PROFESSOR FROM CAME BRIDGE WHO

100
00:04:33,179 --> 00:04:35,581
LIVED TO BE NIX, AT ANY RATE,

101
00:04:35,581 --> 00:04:37,116
THE IDEA OF PROLONGING LIFE IS

102
00:04:37,116 --> 00:04:39,952
SUSTAINED UNTIL TODAY EMPLOY IN

103
00:04:39,952 --> 00:04:50,429
THE MID20th CENTURY, LEONARD

104
00:04:50,729 --> 00:04:52,231
HA YFLICK INTRODUCED IDEA OF

105
00:04:52,231 --> 00:04:56,635
LIMITED DIVISION, THAT IS THE

106
00:04:56,635 --> 00:04:58,337
CELL COULD ONLY DIVIDE

107
00:04:58,337 --> 00:04:59,171
APPROXIMATELY 50 TIMES.

108
00:04:59,171 --> 00:05:01,207
AND THIS CONCEPT HAS BEEN

109
00:05:01,207 --> 00:05:02,508
RESURRECTED IN THE 21st SEBTRY

110
00:05:02,508 --> 00:05:06,111
WITH THE DISCOVERY OF TELOMERES.

111
00:05:06,111 --> 00:05:11,150
IN ABOUT THE 1980S, LEONARD

112
00:05:11,150 --> 00:05:14,053
GUARENTE AND OTHERS, PRODUCED

113
00:05:14,053 --> 00:05:14,887
THE INTERESTING CONCEPT THAT

114
00:05:14,887 --> 00:05:22,461
PART OF A SIGNALING PATHWAY AND

115
00:05:22,461 --> 00:05:23,262
ACTUALLY PROLONGED LONGEVITY AND

116
00:05:23,262 --> 00:05:30,269
THE QUESTION HAS ALWAYS BEEN IN

117
00:05:30,269 --> 00:05:33,138
MAMMALS AND EVEN SOMEWHAT

118
00:05:33,138 --> 00:05:34,640
COMMERCIALIZED IT AND STRESSING

119
00:05:34,640 --> 00:05:39,245
THE IDEA THAT AGING IN AN

120
00:05:39,245 --> 00:05:39,778
EPIGENETIC PHENOMENA.

121
00:05:39,778 --> 00:05:44,083
AND IT WAS SHOWN THAT ACTIVATION

122
00:05:44,083 --> 00:05:47,052
OF PI3 KINASE, NAD,

123
00:05:47,052 --> 00:05:48,087
ADMINISTRATION AND MET FORMIN

124
00:05:48,087 --> 00:05:51,790
AND THE IDEA OF RESERVE TROL IN

125
00:05:51,790 --> 00:05:58,764
RED WINE COULD BE A LIFE

126
00:05:58,764 --> 00:06:00,566
PROLONGING EFFECTS.

127
00:06:00,566 --> 00:06:04,937
BUT IN 1998, THE DISCOVERY THAT

128
00:06:04,937 --> 00:06:08,307
TELOMERE SHORTENING LED TO

129
00:06:08,307 --> 00:06:10,309
SENESCENCE APOPTOSIS AND EVEN

130
00:06:10,309 --> 00:06:15,781
ONCOGENIC TRANSFORMATION WITH AN

131
00:06:15,781 --> 00:06:17,816
ALTERED LIFE SPAN, INTRODUCED AN

132
00:06:17,816 --> 00:06:22,688
ENTIRELY NEW ERA AND FOR THIS

133
00:06:22,688 --> 00:06:24,657
BLACK BURN, RIDER AND OTHERS WON

134
00:06:24,657 --> 00:06:28,761
THE NOBEL PRIZE IN 2009.

135
00:06:28,761 --> 00:06:31,163
AROUND THAT TIME MANY

136
00:06:31,163 --> 00:06:39,772
LABORATORIES PARTICULARLY THAT

137
00:06:39,772 --> 00:06:43,275
OF DOCTORS AT ALBERT EINSTEIN

138
00:06:43,275 --> 00:06:47,546
STUDYING PATIENTS WITH LONG LIFE

139
00:06:47,546 --> 00:06:56,822
SPANS, LOOKING FOR LONG

140
00:06:56,822 --> 00:06:57,089
 LONGEVITY

141
00:06:57,089 --> 00:06:58,223
GENES AND IT'S INTERESTING THAT

142
00:06:58,223 --> 00:07:00,626
A LOT OF THESE STUDY VS BEEN LED

143
00:07:00,626 --> 00:07:02,361
ASTRAY, ON PROBABLY MORE

144
00:07:02,361 --> 00:07:04,296
INTERESTING 1S WHEN STORIES AGO

145
00:07:04,296 --> 00:07:06,899
OF STORIES OF LONG LIVED HILL,

146
00:07:06,899 --> 00:07:09,702
MOUNTAIN PEOPLE IN THE BALKANS,

147
00:07:09,702 --> 00:07:11,737
HAD A LARGE COMSUMPTION OF

148
00:07:11,737 --> 00:07:15,674
YOGURT, THAT THEY LIVED WAY

149
00:07:15,674 --> 00:07:16,875
BEYOND 110 YEARS OLD.

150
00:07:16,875 --> 00:07:18,844
OF COURSE, LATER IT TURNED OUT

151
00:07:18,844 --> 00:07:20,579
THAT THE GENETICS OF THESE

152
00:07:20,579 --> 00:07:22,214
FAMILIES WERE NOT QUITE AS

153
00:07:22,214 --> 00:07:25,117
PRESENTED AND SO THIS QUESTION

154
00:07:25,117 --> 00:07:29,555
WAS SORT OF UNDOUBTED.

155
00:07:29,555 --> 00:07:31,724
THERE'S NO QUESTION THESE VERY

156
00:07:31,724 --> 00:07:32,925
LARGE MEN WERE REALLY HEALTHY

157
00:07:32,925 --> 00:07:34,059
LOOKING BUT WHETHER THEY WERE

158
00:07:34,059 --> 00:07:36,595
REALLY THAT OLD WAS DEBATABLE

159
00:07:36,595 --> 00:07:37,663
AND EVEN A 120 YEAR-OLD FRENCH

160
00:07:37,663 --> 00:07:43,168
LADY WHO WAS RECENTLY DIED, AN

161
00:07:43,168 --> 00:07:45,638
AMAZING STORY, HER QUESTION HAS

162
00:07:45,638 --> 00:07:48,040
ALSO BEEN QUESTIONED THE

163
00:07:48,040 --> 00:07:50,142
ACCURACY OF HER AGE.

164
00:07:50,142 --> 00:07:52,978
THERE'S ALSO THE INTRIGUING

165
00:07:52,978 --> 00:07:56,348
CONCEPT ADVANCED BY A FAMOUS

166
00:07:56,348 --> 00:08:02,521
AMERICAN POET AND PHILOSOPHER

167
00:08:02,521 --> 00:08:06,158
DR. OLIVER WENDLE HOLMES, IN HIS

168
00:08:06,158 --> 00:08:08,627
POEM 1 HORSE SHAY, WHERE IT'S A

169
00:08:08,627 --> 00:08:10,863
1 HORSE CARRIAGE WAS BUILT OUT

170
00:08:10,863 --> 00:08:13,232
OF THE BEST OF ALL POSSIBLE

171
00:08:13,232 --> 00:08:14,867
PARTS AND THEN THEY ALL FELL

172
00:08:14,867 --> 00:08:16,935
APART AT THE SAME TIME AND THIS

173
00:08:16,935 --> 00:08:24,643
HAS BEEN CALLED THE DEACON'S 1

174
00:08:24,643 --> 00:08:25,778
HORSE SHAY SYNDROME?

175
00:08:25,778 --> 00:08:28,280
IS THAT WHAT AGE SUGGEST ALL

176
00:08:28,280 --> 00:08:28,947
ABOUT?

177
00:08:28,947 --> 00:08:30,482
IS IT PREDICTABLE AND

178
00:08:30,482 --> 00:08:30,849
ENVIRONMENTAL?

179
00:08:30,849 --> 00:08:33,018
IS 120 YEAR SURVIVAL POSSIBLE IN

180
00:08:33,018 --> 00:08:35,821
AND IT REALLY WORTH WHILE?

181
00:08:35,821 --> 00:08:37,723
AND SO TODAY WE'RE GOING TO HEAR

182
00:08:37,723 --> 00:08:40,526
FROM 2 EXPERTS ON HOW TO STUDY

183
00:08:40,526 --> 00:08:42,695
AND MAYBE EVEN HOW TO MAKE

184
00:08:42,695 --> 00:08:44,163
POLICY BASED ON THE RESULTS OF

185
00:08:44,163 --> 00:08:47,199
SOME OF THESE STUDIES BECAUSE OF

186
00:08:47,199 --> 00:08:49,435
THE BROAD IMPACT ON SOCIETY.

187
00:08:49,435 --> 00:08:52,237
SO LET ME INTRODUCE OUR 2

188
00:08:52,237 --> 00:08:54,273
SPEAKERS TODAY.

189
00:08:54,273 --> 00:08:55,174
NEXT SLIDE.

190
00:08:55,174 --> 00:08:59,411
OUR FIRST SPEAKER IS LUIGI

191
00:08:59,411 --> 00:09:01,080
FIDUCCI, WHO IS THE DIRECTOR OF

192
00:09:01,080 --> 00:09:02,681
THE NATIONAL

193
00:09:02,681 --> 00:09:04,750
EN--STRATEGIESITUTES OF AGING.

194
00:09:04,750 --> 00:09:08,020
LUIGI IS WORLD WIDE RENOWNED FOR

195
00:09:08,020 --> 00:09:10,422
HIS LONG TIEWF NADEL STUDIES AS

196
00:09:10,422 --> 00:09:11,623
REVEALING SUSCEPTIBILITY TO DEC

197
00:09:11,623 --> 00:09:14,293
AND DISABILITY PARTICULARLY IN

198
00:09:14,293 --> 00:09:14,960
ELDERLY PEOPLE.

199
00:09:14,960 --> 00:09:18,230
HE TRAINED IN MEDICINE AND

200
00:09:18,230 --> 00:09:19,832
EPIDEMIOLOGY IN FLORENCE WHERE

201
00:09:19,832 --> 00:09:22,101
HE RECEIVED BOTH AN MD AND

202
00:09:22,101 --> 00:09:25,204
Ph.D. DEGREES, CAME TO THE

203
00:09:25,204 --> 00:09:27,840
NATIONAL INNSITUTES OF AGING IN

204
00:09:27,840 --> 00:09:32,111
2002, AND IS THE SCIENTIFIC

205
00:09:32,111 --> 00:09:32,511
DIRECTOR.

206
00:09:32,511 --> 00:09:34,980
HE DOES MANY THINGS BUT IS BEST

207
00:09:34,980 --> 00:09:38,183
KNOWN FOR LEADING THE NIA

208
00:09:38,183 --> 00:09:40,352
LONGITUDINAL STUDY SECTION AND

209
00:09:40,352 --> 00:09:43,388
CONDUCTING AGING STUDIES

210
00:09:43,388 --> 00:09:46,325
INCLUDING SENTENARRIANS IN

211
00:09:46,325 --> 00:09:47,926
SARDINNIA AND THE FAMOUS WOMEN'S

212
00:09:47,926 --> 00:09:54,366
HEALTH AND AGING STUDY HERE.

213
00:09:54,366 --> 00:09:56,401
LUIGI IS AN ADVOCATE FOR THE

214
00:09:56,401 --> 00:09:58,871
HEALTHY LIFE SPAN CONCEPT, AN

215
00:09:58,871 --> 00:10:01,473
IDEA THAT ALLOWS PEOPLE TO LIVE

216
00:10:01,473 --> 00:10:04,143
HEALTHY INTO THEIR 90S AS OPPOSE

217
00:10:04,143 --> 00:10:05,978
TO MERELY EXTENDING THEIR LIFE

218
00:10:05,978 --> 00:10:06,745
EXPECTANCY.

219
00:10:06,745 --> 00:10:17,289
OUR SECOND SPEAKER, NEXT SLIDE,

220
00:10:24,897 --> 00:10:26,298
PLEASE.

221
00:10:26,298 --> 00:10:32,171
P A YEL SEN, WITH THE STADTMAN

222
00:10:32,171 --> 00:10:33,806
INVESTIGATOR AND RECEIVED HER

223
00:10:33,806 --> 00:10:37,376
Ph.D. AT GRAD YAWD OFICAL

224
00:10:37,376 --> 00:10:38,911
CUTTA UNIVERSITY IN BIOCHEMISTRY

225
00:10:38,911 --> 00:10:39,945
AND MOLECULAR BIOLOGY AND THEN

226
00:10:39,945 --> 00:10:44,149
DID A POST DOC WITH SHELLLY

227
00:10:44,149 --> 00:10:45,517
BERGER AT THE EPIGENETICS

228
00:10:45,517 --> 00:10:47,386
INSTITUTE OF UNIVERSITY OF

229
00:10:47,386 --> 00:10:49,588
PENNSYLVANIA, DURING WHICH TIME

230
00:10:49,588 --> 00:10:52,825
SHE IDENTIFIED NOVEL EPIGENETIC

231
00:10:52,825 --> 00:10:54,860
REGULATORS OF AGING.

232
00:10:54,860 --> 00:10:56,261
SHE HAS RECEIVED SEVERAL

233
00:10:56,261 --> 00:10:57,396
FELLOWSHIPS DURING THE COURSE OF

234
00:10:57,396 --> 00:10:58,530
HER CAREER.

235
00:10:58,530 --> 00:11:02,034
SHE IS A STADTMAN INVESTIGATOR

236
00:11:02,034 --> 00:11:03,869
AT THE NATIONAL INSTITUTES OF

237
00:11:03,869 --> 00:11:06,138
ANALLING WHERE SHE LEADS A

238
00:11:06,138 --> 00:11:08,974
FUNCTIONAL EPIGENOMICS UNIT IN

239
00:11:08,974 --> 00:11:10,843
THE RNA-REGULATION SECTION OF

240
00:11:10,843 --> 00:11:11,677
THAT INSTITUTE.

241
00:11:11,677 --> 00:11:14,780
HER GOAL IS TO UNCOVER

242
00:11:14,780 --> 00:11:17,015
EPIGENETIC MECHANISMS THAT DRIVE

243
00:11:17,015 --> 00:11:21,787
AGING AND SHE USES A MOUSE MODEL

244
00:11:21,787 --> 00:11:23,522
CAN COMBINES EXPERIMENTAL

245
00:11:23,522 --> 00:11:27,226
COMPUTATIONAL AND GENOME SCALE

246
00:11:27,226 --> 00:11:33,832
APPROACHES TO IDENTIFY NEW

247
00:11:33,832 --> 00:11:35,567
EPIGENETIC TARGETS WHICH

248
00:11:35,567 --> 00:11:37,970
HOPEFULLY WILL COUNTER THE

249
00:11:37,970 --> 00:11:41,673
FUNCTIONAL DECLINE AND DISEASES

250
00:11:41,673 --> 00:11:42,307
OF AGING.

251
00:11:42,307 --> 00:11:44,209
SO THESE ARE OUR 2 INDIVIDUALS

252
00:11:44,209 --> 00:11:45,544
ON OUR BRIDGE TODAY AND WE

253
00:11:45,544 --> 00:11:47,279
WELCOME YOU BOTH AND PLEASE

254
00:11:47,279 --> 00:11:50,382
SUBMIT YOUR QUESTIONS FROM THE

255
00:11:50,382 --> 00:11:51,984
AUDIENCE AND LUIGI, IF YOU WOULD

256
00:11:51,984 --> 00:11:58,390
PLEASE, BEGIN. 

257
00:11:58,390 --> 00:11:58,657
THANK YOU.

258
00:11:58,657 --> 00:12:01,226
>> THANK YOU VERY MUCH FOR
THE

259
00:12:01,226 --> 00:12:02,494
WONDERFUL INTRODUCTION AND FOR

260
00:12:02,494 --> 00:12:05,764
INVITING ME TO THIS FANTASTIC

261
00:12:05,764 --> 00:12:08,834
PROGRAM AND ABOUT SPEAKING ABOUT

262
00:12:08,834 --> 00:12:09,902
SOMETHING THAT I'M REALLY

263
00:12:09,902 --> 00:12:12,604
PASSIONATE ABOUT AND IT'S JUST

264
00:12:12,604 --> 00:12:15,040
NOT NOW, THAT WILL MAKE SENSE,

265
00:12:15,040 --> 00:12:16,808
BUT YOU KNOW MANY, MANY YEARS

266
00:12:16,808 --> 00:12:18,377
AGO, I WANTED TO STUDY AGING

267
00:12:18,377 --> 00:12:22,748
WHICH I WAS 15 YEARS OF AGE AND

268
00:12:22,748 --> 00:12:24,583
A LOT OF WHAT I PASSED FOR THE

269
00:12:24,583 --> 00:12:30,889
AGE THAT WAS SHOWING AND STILL,

270
00:12:30,889 --> 00:12:34,059
AN IMPORTANT ELEMENT OF AGING

271
00:12:34,059 --> 00:12:35,127
HAS GROWN STUDILY OVER TIME.

272
00:12:35,127 --> 00:12:43,702
IF I COULD HAVE MY FIRST TIME. 

273
00:12:43,702 --> 00:12:45,504
>> I'M SORRY DR. FERUCCI,
I

274
00:12:45,504 --> 00:12:48,373
THOUGHT 

275
00:12:48,373 --> 00:12:50,375
THOUGHT YOU WERE GOING TO SHARE.

276
00:12:50,375 --> 00:12:52,811
>> I THOUGHT DIANEA WAS
DOING

277
00:12:52,811 --> 00:12:52,978
IT.

278
00:12:52,978 --> 00:12:54,546
>> YOU ARE COMING ALONG,
YEAH,

279
00:12:54,546 --> 00:12:55,013
GOOD.

280
00:12:55,013 --> 00:12:57,849
>> CAN YOU SEE IT.

281
00:12:57,849 --> 00:13:03,789
>> YES, PERFECT.

282
00:13:03,789 --> 00:13:04,256
>> VERY GOOD.

283
00:13:04,256 --> 00:13:06,124
SO THE TALK THAT I'M GOING TO

284
00:13:06,124 --> 00:13:11,396
GIVE IS VERY PROVOCATIVE, I

285
00:13:11,396 --> 00:13:11,930
THINK.

286
00:13:11,930 --> 00:13:13,899
THAT YOU KNOW WITH AGING

287
00:13:13,899 --> 00:13:15,734
POPULATION WE TRULY NEED TO

288
00:13:15,734 --> 00:13:17,569
CHANGE PERSPECTIVE ABOUT WHAT WE

289
00:13:17,569 --> 00:13:21,206
THINK ABOUT HEALTH AND WHAT WE

290
00:13:21,206 --> 00:13:29,681
THINK ABOUT HEALTHCARE.

291
00:13:29,681 --> 00:13:29,982
NEXT.

292
00:13:29,982 --> 00:13:34,686
SO FIRST OF ALL, WHY WE ARE

293
00:13:34,686 --> 00:13:38,357
GAINING SO MUCH FROM AGING?

294
00:13:38,357 --> 00:13:40,926
IT'S A RECENT PHENOMENA, IN

295
00:13:40,926 --> 00:13:41,126
FACT.

296
00:13:41,126 --> 00:13:43,362
IF YOU LOOK AT WHAT HAPPENED

297
00:13:43,362 --> 00:13:46,431
BETWEEN THE 1500 AND MIDDLE OF

298
00:13:46,431 --> 00:13:48,166
THE 1800S, LIFE EXPECTANCY

299
00:13:48,166 --> 00:13:51,570
DURING THE WAR WAS VERY, VERY

300
00:13:51,570 --> 00:13:53,505
LOW, 34 YEARS ON AVERAGE AND

301
00:13:53,505 --> 00:13:57,909
DIDN'T CHANGE MUCH OVER TIME

302
00:13:57,909 --> 00:14:00,512
UNTIL MAGIC HAPPENED AROUND THE

303
00:14:00,512 --> 00:14:04,583
1860 AND WE SEE THAT THE

304
00:14:04,583 --> 00:14:06,418
STARTING OF LIFE EXPECTANCY IS

305
00:14:06,418 --> 00:14:10,522
AT THE SPEED THAT WAS HIGHER AND

306
00:14:10,522 --> 00:14:12,024
HIGHER AND HIGHER.

307
00:14:12,024 --> 00:14:14,826
IT'S QUESTIONABLE WHETHER, YOU

308
00:14:14,826 --> 00:14:17,429
KNOW THEY INCREASE IN THE SPEED

309
00:14:17,429 --> 00:14:20,298
OF LIFE EXPECTANCY IS CONTINUING

310
00:14:20,298 --> 00:14:21,233
OR NOT.

311
00:14:21,233 --> 00:14:25,170
ONE IMPORTANT EVALUATION HERE IS

312
00:14:25,170 --> 00:14:27,439
THAT THE INCREASING LIFE

313
00:14:27,439 --> 00:14:30,609
EXPECTANCY, SUCH A SHORT TIME,

314
00:14:30,609 --> 00:14:33,278
NOT REALLY BE DUE TO GENETIC

315
00:14:33,278 --> 00:14:34,413
CHANGES.

316
00:14:34,413 --> 00:14:38,183
YOU KNOW GENETICS CHANGE WITH

317
00:14:38,183 --> 00:14:40,485
THE EVOLUTION AND APPLY THROUGH

318
00:14:40,485 --> 00:14:45,657
MULTIPLE GENERATIONS. 

319
00:14:45,657 --> 00:14:51,063
SO 1860-2023, IT'S REALLY A

320
00:14:51,063 --> 00:14:52,464
GENETIC TIME.

321
00:14:52,464 --> 00:14:54,699
SO THE MOST IMPORTANT CAUSES OF

322
00:14:54,699 --> 00:14:56,201
INCREASING LONGEVITY AND IN

323
00:14:56,201 --> 00:15:00,372
FACT, IT'S LARGELY DUE TO BETTER

324
00:15:00,372 --> 00:15:04,309
NUTRITION, THE ABILITY OF CLEAN

325
00:15:04,309 --> 00:15:08,046
WATER, CLEAN WATER, AND SEWER

326
00:15:08,046 --> 00:15:09,648
AND UNDERSTAND, SOME PEOPLE SAY

327
00:15:09,648 --> 00:15:15,320
LESS THAN 10% IS TO INCREASE.

328
00:15:15,320 --> 00:15:16,788
NEXT SLIDE PLEASE.

329
00:15:16,788 --> 00:15:20,592
OF COURSE, THE INCREASE IN LIFE

330
00:15:20,592 --> 00:15:24,262
EXPECTANT DID NOT OCCUR

331
00:15:24,262 --> 00:15:25,297
HOMOGENIUSLY ACROSS THE WORLD

332
00:15:25,297 --> 00:15:28,700
AND IT WAS AFFECTING MOSTLY

333
00:15:28,700 --> 00:15:34,873
EUROPE AND THE U.S. AT THE

334
00:15:34,873 --> 00:15:35,774
BEGINNING AROUND THE 1800 AND

335
00:15:35,774 --> 00:15:38,009
THEN THEY AFFECT MANY OTHER

336
00:15:38,009 --> 00:15:41,713
COUNTRY, JAPAN, BRAZIL, AND

337
00:15:41,713 --> 00:15:44,916
THEN, MORE RECENTLY, HAVE REALLY

338
00:15:44,916 --> 00:15:52,224
EXPANDED AROUND THE WORLD AND IN

339
00:15:52,224 --> 00:15:53,959
AFRICA ARE STILL LINGERING

340
00:15:53,959 --> 00:15:55,794
BEHIND IN LIFE EXPECTANCY.

341
00:15:55,794 --> 00:15:58,864
SO ALSO IN THIS POPULATION, LIFE

342
00:15:58,864 --> 00:16:00,065
EXPECTANCY HAS BEEN INCREASING

343
00:16:00,065 --> 00:16:03,301
VERY, VERY RAPID LOAMACYY AND IN

344
00:16:03,301 --> 00:16:04,269
FACT, -- RAPIDLY AND IN FACT

345
00:16:04,269 --> 00:16:06,138
BECAUSE OF THE SPEED OF

346
00:16:06,138 --> 00:16:07,305
INCREASING LIFE EXPECTANCY IN

347
00:16:07,305 --> 00:16:10,709
THIS COUNTRY, YOU KNOW THE AGING

348
00:16:10,709 --> 00:16:11,910
OF THE POPULATION IS CREATING A

349
00:16:11,910 --> 00:16:13,278
LOT OF PROBLEMS THAT OCCUR

350
00:16:13,278 --> 00:16:16,648
WITHOUT THE NECESSARY TIME TO

351
00:16:16,648 --> 00:16:19,951
ADAPT THE SOCIETY OF THESE

352
00:16:19,951 --> 00:16:21,186
CHANGES.

353
00:16:21,186 --> 00:16:21,620
NEXT SLIDE.

354
00:16:21,620 --> 00:16:23,388
AND THE OTHER THING I WANT TO

355
00:16:23,388 --> 00:16:25,991
SAY, THAT WHY INITIALLY, THE

356
00:16:25,991 --> 00:16:28,493
INCREASE IN LIFE EXPECTANCY WAS

357
00:16:28,493 --> 00:16:30,595
DUE TO, YOU KNOW BETTER SURVIVAL

358
00:16:30,595 --> 00:16:33,465
OF PEOPLE IN THE FIRST FEW YEARS

359
00:16:33,465 --> 00:16:36,101
OF LIFE, YOU KNOW HIGH MORTALITY

360
00:16:36,101 --> 00:16:40,238
IN THE FIRST YEAR OF LIFE WAS

361
00:16:40,238 --> 00:16:41,940
VERY TYPICAL AROUND THE

362
00:16:41,940 --> 00:16:44,142
BEGINNING OF THE 18th CENTURY.

363
00:16:44,142 --> 00:16:46,878
YOU KNOW INCREASING LIFE

364
00:16:46,878 --> 00:16:48,847
EXPECTANCY IS NOW OCCURRING IN

365
00:16:48,847 --> 00:16:50,148
THOSE THAT ARE 70 YEARS AND

366
00:16:50,148 --> 00:16:50,515
OLDER.

367
00:16:50,515 --> 00:16:52,784
SO WE HAVE AN OLDER POPULATION

368
00:16:52,784 --> 00:16:54,219
THAT IS LIVING LONGER AND

369
00:16:54,219 --> 00:16:54,586
LONGER.

370
00:16:54,586 --> 00:16:57,722
AND THE NEXT SLIDE, THE -- TO

371
00:16:57,722 --> 00:17:00,358
SHOW A SLIDE THAT I'M VERY, VERY

372
00:17:00,358 --> 00:17:04,763
FOND OF THAT WAS PUBLISHED BY

373
00:17:04,763 --> 00:17:06,831
PROBABLY THE MOST DEMOGRAPHER IN

374
00:17:06,831 --> 00:17:10,802
THE WORLD GENE P A PEL, AND

375
00:17:10,802 --> 00:17:12,904
PAPAL TOOK ALL THE DIFFERENT

376
00:17:12,904 --> 00:17:14,739
COUNTRIES IN THE WORLD THAT HAD

377
00:17:14,739 --> 00:17:16,708
THE LONGEST LIFE EXPECTANCY AND

378
00:17:16,708 --> 00:17:19,110
PLOTTED THEM OVER TIME AND

379
00:17:19,110 --> 00:17:22,347
DISCOVERED AND SHOWED IN THIS

380
00:17:22,347 --> 00:17:24,182
PAPER THAT PROBABLY BEEN SHOWN A

381
00:17:24,182 --> 00:17:29,721
HUNDRED THOUSAND TIMES THAT THEY

382
00:17:29,721 --> 00:17:31,790
WERE ALIENATED IN A PERFECT

383
00:17:31,790 --> 00:17:31,990
LINE.

384
00:17:31,990 --> 00:17:34,626
THESE WERE SHOW SHOCKING THAT

385
00:17:34,626 --> 00:17:37,028
THEY WERE, YOU KNOW UNITED

386
00:17:37,028 --> 00:17:38,863
NATIONS MEETINGS THAT DISCUSS

387
00:17:38,863 --> 00:17:40,131
WHETHER THERE'S INCREASE IN LIFE

388
00:17:40,131 --> 00:17:42,200
EXPECTANCY WAS GOING TO CONTINUE

389
00:17:42,200 --> 00:17:47,172
TO SLOW DOWN AND OF COURSE YOU

390
00:17:47,172 --> 00:17:48,907
SEE THOSE DASH RED LINES AND

391
00:17:48,907 --> 00:17:51,176
PEOPLE THOUGHT THEY CANNOT

392
00:17:51,176 --> 00:17:52,210
REALLY BE THINKING IT'S GOING TO

393
00:17:52,210 --> 00:17:54,212
SLOW DOWN AND GO TO SENESCENCE,

394
00:17:54,212 --> 00:17:59,884
AND OF COURSE, YOU KNOW, AS THE

395
00:17:59,884 --> 00:18:01,486
DATA WILL SHOW, THIS IS NOT

396
00:18:01,486 --> 00:18:04,022
TRUE, THE LIFE EXPECTANCY HAS

397
00:18:04,022 --> 00:18:04,289
CONTINUED.

398
00:18:04,289 --> 00:18:05,757
HOWEVER, IN MOST RECENT YEARS

399
00:18:05,757 --> 00:18:09,694
THIS APPROACH HAS BEEN HIGHLY

400
00:18:09,694 --> 00:18:12,230
CRITICIZED AND AS A RESULT FROM

401
00:18:12,230 --> 00:18:14,633
THE FACT THAT, YOU KNOW IF YOU

402
00:18:14,633 --> 00:18:17,335
SELECT ALL THIS POPULATION IN

403
00:18:17,335 --> 00:18:24,075
THE WORLD, YOU CAN ARTIFICIALLY

404
00:18:24,075 --> 00:18:25,443
CREATE THIS.

405
00:18:25,443 --> 00:18:25,910
NEXT SLIDE.

406
00:18:25,910 --> 00:18:30,548
OH, OKAY, I AM ITALIAN SO I HAVE

407
00:18:30,548 --> 00:18:32,250
TO SAY THEY HAVE THE LONGEST

408
00:18:32,250 --> 00:18:32,617
LIFE EXPECTANCY.

409
00:18:32,617 --> 00:18:33,785
CAN YOU JUST GO TO THE NEXT 1

410
00:18:33,785 --> 00:18:36,721
EMPLOY I WANT TO SKIP THIS 1.

411
00:18:36,721 --> 00:18:41,693
CAN I GIVE YOU THE NEXT?

412
00:18:41,693 --> 00:18:42,560
OKAY.

413
00:18:42,560 --> 00:18:45,063
SO 1 OF THE -- YOU KNOW

414
00:18:45,063 --> 00:18:45,630
INCREASING LIFE EXPECTANCY,

415
00:18:45,630 --> 00:18:47,065
CERTAINLY SOMETHING WE HAVE

416
00:18:47,065 --> 00:18:47,766
ACCOMPLISHED AND IT'S SOMETHING

417
00:18:47,766 --> 00:18:52,604
WE NEED TO CELEBRATE.

418
00:18:52,604 --> 00:18:54,005
HOWEVER, AS YOU INCREASE THE

419
00:18:54,005 --> 00:18:55,307
TOTAL AMOUNT OF LIFE, THEY

420
00:18:55,307 --> 00:18:59,311
INCREASE IN PART OF LIFE THAT'S

421
00:18:59,311 --> 00:19:00,478
CHARACTERIZED BY DISEASE OF

422
00:19:00,478 --> 00:19:05,050
DISABILITY, SOME PEOPLE SAY THAT

423
00:19:05,050 --> 00:19:09,054
LIFE, YOU KNOW EXPAND AND THEN

424
00:19:09,054 --> 00:19:10,422
THE BEGINNING.

425
00:19:10,422 --> 00:19:11,956
SO THIS CREATED A LOT OF PROBLEM

426
00:19:11,956 --> 00:19:15,293
BECAUSE THE OLDER POPULATION

427
00:19:15,293 --> 00:19:19,030
MEANS AN ACCUMULATION OF

428
00:19:19,030 --> 00:19:19,464
MORBIDITY.

429
00:19:19,464 --> 00:19:20,632
GIVE ME THE NEXT SLIDE.

430
00:19:20,632 --> 00:19:23,034
SO WHY THIS IS HAPPENING?

431
00:19:23,034 --> 00:19:25,403
I THINK THIS IS PROBABLY THE

432
00:19:25,403 --> 00:19:31,876
MOST IMPORTANT SLIDE OF MY

433
00:19:31,876 --> 00:19:36,247
ENTIRE SHOW, SO A VERY CLEVER

434
00:19:36,247 --> 00:19:37,382
DEMOGRAPHER SUGGESTED IN 2018

435
00:19:37,382 --> 00:19:41,820
THAT THE INCREASING LIFE

436
00:19:41,820 --> 00:19:43,855
EXPECTANCY IN THE WORLD WILL NOT

437
00:19:43,855 --> 00:19:44,689
CONTINUE AND WILL SLOW DOWN

438
00:19:44,689 --> 00:19:47,425
BECAUSE OF MORE AND MORE PEOPLE

439
00:19:47,425 --> 00:19:50,328
WERE ENTERING INTO THE AREA OF

440
00:19:50,328 --> 00:19:52,931
HIGH RISK OF FRAILTY AND

441
00:19:52,931 --> 00:19:57,435
DISABILITY AND THESE ENTERING IN

442
00:19:57,435 --> 00:19:59,804
THEIR AFFECTED  DISABILITY ONLY

443
00:19:59,804 --> 00:20:02,140
LEAD TO AN ARK KIEWMULATION OF

444
00:20:02,140 --> 00:20:03,875
MORE AND MORE DISABILITY AND

445
00:20:03,875 --> 00:20:04,109
FRAILTY.

446
00:20:04,109 --> 00:20:05,877
THIS IS ONLY BECAUSE OF THE PACE

447
00:20:05,877 --> 00:20:07,479
OF BIOLOGICAL AGE NOTHING OUR

448
00:20:07,479 --> 00:20:09,214
BODY HAS NOT BEEN SLOWING DOWN.

449
00:20:09,214 --> 00:20:14,052
AND SO AS MORE PEOPLE ENTER INTO

450
00:20:14,052 --> 00:20:18,156
THE AREA OF DISABILITY, THEY

451
00:20:18,156 --> 00:20:19,224
DEVELOP MORE IMMOBILITY AND THIS

452
00:20:19,224 --> 00:20:20,892
IS MORE OF A CHALLENGE FOR THE

453
00:20:20,892 --> 00:20:22,494
INDIVIDUAL AND THE SOCIETY.

454
00:20:22,494 --> 00:20:25,830
THE OTHER PART OF THIS SLIDE,

455
00:20:25,830 --> 00:20:26,297
PLEASE.

456
00:20:26,297 --> 00:20:28,233
SO SUMMARIZING OF THIS SLOW DOWN

457
00:20:28,233 --> 00:20:30,168
IN THE RISE OF LIFE EXPECTANCY

458
00:20:30,168 --> 00:20:33,438
IS A PRODUCT OF OUR SUCCESS,

459
00:20:33,438 --> 00:20:35,340
SHOULD NOT BE CONSIDERED

460
00:20:35,340 --> 00:20:36,741
FAILURE, MORE PEOPLE LIVE BEYOND

461
00:20:36,741 --> 00:20:40,912
OF AGE OF 70 AND ENTER INTO THE

462
00:20:40,912 --> 00:20:42,614
OTHER HIGH RISK OF THIS.

463
00:20:42,614 --> 00:20:48,420
SO OUR GOAL IS TO EXPAND THE

464
00:20:48,420 --> 00:20:49,721
HEALTH EXPECTANT -- DISABILITY

465
00:20:49,721 --> 00:20:53,224
LATE IN LIFE, SO THE OTHER PART

466
00:20:53,224 --> 00:20:54,959
OF THIS LIFE, THERE'S

467
00:20:54,959 --> 00:20:58,363
INFORMATION THAT SHOW WHAT WE

468
00:20:58,363 --> 00:20:58,830
NEED TO DO.

469
00:20:58,830 --> 00:21:00,665
WHAT WE NEED TO DO IS COMPRESS

470
00:21:00,665 --> 00:21:01,733
THE AREA OF DISABILITY AND I

471
00:21:01,733 --> 00:21:05,136
WILL ARGUE THAT LIVING TO 120 IS

472
00:21:05,136 --> 00:21:07,272
NOT SOMETHING MANY PEOPLE WANT.

473
00:21:07,272 --> 00:21:09,474
IF YOU ASK PEOPLE WHAT THEY

474
00:21:09,474 --> 00:21:12,677
REALLY WANT, THEY WANT TO LIVE A

475
00:21:12,677 --> 00:21:15,146
VERY SUCCESSFUL AND ENJOYABLE

476
00:21:15,146 --> 00:21:17,982
LIFE, FOR MANY, MANY YEARS AND

477
00:21:17,982 --> 00:21:19,517
THEN WHEN WE ARE SICK AND

478
00:21:19,517 --> 00:21:21,453
DISABLE, THEY DON'T WANT TO STAY

479
00:21:21,453 --> 00:21:24,422
SICK AND DISABLE FOR VERY LONG.

480
00:21:24,422 --> 00:21:26,891
SO EXPANDING THE LIFE EXPECTANCY

481
00:21:26,891 --> 00:21:27,959
FOR THE INDIVIDUAL FOR SOCIETY

482
00:21:27,959 --> 00:21:29,828
IS MORE IMPORTANT THAN

483
00:21:29,828 --> 00:21:33,231
INCREASING LIFE EXPECTANCY. 

484
00:21:33,231 --> 00:21:33,598
THE NEXT SLIDE.

485
00:21:33,598 --> 00:21:38,770
AND IN FACT, YOU KNOW THE

486
00:21:38,770 --> 00:21:40,171
PREDICTION APPEARED TO BE TRUE.

487
00:21:40,171 --> 00:21:43,508
IN 2024, AT END OF 2024, THIS

488
00:21:43,508 --> 00:21:45,677
PAPER WAS PUBLISHED IN NATURAL

489
00:21:45,677 --> 00:21:48,947
AGING SHOWING THAT IN MANY, MANY

490
00:21:48,947 --> 00:21:51,082
COUNTRIES THE RATE OF INCREASE

491
00:21:51,082 --> 00:21:53,151
IN LIFE EXPECTANCY IS DECLINED

492
00:21:53,151 --> 00:21:54,986
AND THIS IS THROUGH IN

493
00:21:54,986 --> 00:21:58,356
PARTICULAR IN THE UNITED STATES

494
00:21:58,356 --> 00:22:00,558
WHERE THE INCREASE IN LIFE

495
00:22:00,558 --> 00:22:01,593
EXPECTANCE SESLOWING DOWN MORE

496
00:22:01,593 --> 00:22:05,897
THAN ANY OTHER COUNTRY IN THE

497
00:22:05,897 --> 00:22:06,898
WORLD.

498
00:22:06,898 --> 00:22:07,499
NEXT SLIDE.

499
00:22:07,499 --> 00:22:07,699
OKAY.

500
00:22:07,699 --> 00:22:13,505
SO WHAT'S HAPPENING IS THAT

501
00:22:13,505 --> 00:22:15,807
AGING, THESE AGING MAKE US LIVE

502
00:22:15,807 --> 00:22:21,412
LONGER, BUT ALSO MAKE OUR LIFE

503
00:22:21,412 --> 00:22:23,214
FOR DISEASE AND DISABILITY BE

504
00:22:23,214 --> 00:22:23,448
LONG.

505
00:22:23,448 --> 00:22:25,583
YOU KNOW I USED TO TALK TO MY

506
00:22:25,583 --> 00:22:27,886
PATIENT WHEN I WAS A PRACTICING

507
00:22:27,886 --> 00:22:28,653
GERIATRICIAN AND THEY USED TO

508
00:22:28,653 --> 00:22:31,623
SAY WHEN YOU HAVE A DISEASE,

509
00:22:31,623 --> 00:22:35,226
WHEN YOU ARE SUFFERING, IN PAIN,

510
00:22:35,226 --> 00:22:36,861
YOUR TIME SEEMS LONGER AND

511
00:22:36,861 --> 00:22:37,195
LONGER.

512
00:22:37,195 --> 00:22:39,597
SO THOSE YEARS THAT PEOPLE LIVE

513
00:22:39,597 --> 00:22:40,665
WITH DISEASES AND DISABILITY GO

514
00:22:40,665 --> 00:22:46,104
SLOWLY AND SEEM TO BE INTERM

515
00:22:46,104 --> 00:22:46,337
MINABLE.

516
00:22:46,337 --> 00:22:48,006
SO THE NEXT SLIDE IS WHAT IS OUR

517
00:22:48,006 --> 00:22:48,239
MISSION?

518
00:22:48,239 --> 00:22:49,874
WHAT DO WE NEED TO DO?

519
00:22:49,874 --> 00:22:51,509
WE NEED TO INCREASE LIFE

520
00:22:51,509 --> 00:22:51,809
EXPECTANCY.

521
00:22:51,809 --> 00:22:53,011
THE REASON WHY YOU SHOULD DO

522
00:22:53,011 --> 00:22:55,079
THAT IS ALSO ECONOMICAL.

523
00:22:55,079 --> 00:22:58,383
IF YOU LOOK AT THIS SLIDE THAT

524
00:22:58,383 --> 00:23:00,618
WAS PUBLISHED NOT MANY YEARS

525
00:23:00,618 --> 00:23:03,888
AGO, IS SHOWING THAT IF YOU LOOK

526
00:23:03,888 --> 00:23:09,627
AT THE CURRENT HEALTH EXPANDER

527
00:23:09,627 --> 00:23:13,765
PER CAPITA, COMPARE THAT WITH

528
00:23:13,765 --> 00:23:16,601
THE DISABILITY, AND MOST

529
00:23:16,601 --> 00:23:18,002
SURPRISINGLY, THE PEOPLE THAT

530
00:23:18,002 --> 00:23:21,372
HAVE LONGER LIFE EXPECTANCY CAN

531
00:23:21,372 --> 00:23:22,774
DISABILITY ARE IN THOSE

532
00:23:22,774 --> 00:23:25,276
COUNTRIES, TO SPEND MORE MONEY

533
00:23:25,276 --> 00:23:26,010
FOR HEALTHCARE.

534
00:23:26,010 --> 00:23:30,715
SO SPENDING MORE MONEY WITH

535
00:23:30,715 --> 00:23:36,254
HEALTHCARE IS ASSOCIATED

536
00:23:36,254 --> 00:23:37,722
PROLONGING SELF.

537
00:23:37,722 --> 00:23:39,457
AND ALTHOUGH IT'S NOT LOGICAL, I

538
00:23:39,457 --> 00:23:41,092
WILL SHOW YOU THIS ABSOLUTELY

539
00:23:41,092 --> 00:23:43,695
MAKES SENSE.

540
00:23:43,695 --> 00:23:44,228
NEXT SLIDE.

541
00:23:44,228 --> 00:23:47,031
WE WANT THE LIFE WE LOST.

542
00:23:47,031 --> 00:23:51,769
HOW DO WE DO THAT?

543
00:23:51,769 --> 00:23:54,906
NEXT SLIDE. 

544
00:23:54,906 --> 00:23:58,610
OKAY, MANAGING THAT, THIS IS A

545
00:23:58,610 --> 00:24:00,011
PERSON AND THIS REPRESENT THE

546
00:24:00,011 --> 00:24:05,850
LIFE OF THIS PERSON AND THEN THE

547
00:24:05,850 --> 00:24:08,286
BLUE PART IS THE PART WHEN THEY

548
00:24:08,286 --> 00:24:09,887
LIVE WITHOUT DEC AND DISABILITY

549
00:24:09,887 --> 00:24:11,956
AND THEN AT SOME POINT IN THEIR

550
00:24:11,956 --> 00:24:16,094
LIFE, THEY DEVELOP THE FIRST

551
00:24:16,094 --> 00:24:17,695
DISEASE, SO SOMETIME BETWEEN

552
00:24:17,695 --> 00:24:19,297
BIRTH AND FIRST DISEASE WE CAN

553
00:24:19,297 --> 00:24:22,066
CALL THIS LIFE EXPECTANCY, OR

554
00:24:22,066 --> 00:24:23,134
HEALTH EXPECTANCY, DEPENDING ON

555
00:24:23,134 --> 00:24:24,602
THE DIFFERENT DEFINITION, AND

556
00:24:24,602 --> 00:24:26,871
THEN AFTER THE FIRST DISEASE,

557
00:24:26,871 --> 00:24:28,272
THIS PERSON WILL DEVELOP

558
00:24:28,272 --> 00:24:29,874
ANOTHER, THEN ANOTHER 1, AND

559
00:24:29,874 --> 00:24:31,042
THEN ANOTHER 1.

560
00:24:31,042 --> 00:24:34,646
AND THEN SHOW ME THE NEXT PART

561
00:24:34,646 --> 00:24:37,181
OF THIS SLIDE.

562
00:24:37,181 --> 00:24:38,783
SO THERE'S ANOTHER HYPOTHETICAL

563
00:24:38,783 --> 00:24:42,654
PERSON THAT HAS LONGER DISEASE

564
00:24:42,654 --> 00:24:46,057
LIFE EXPECTANCY OR HEALTH

565
00:24:46,057 --> 00:24:50,862
EXPECTANCY  IN SPITE OF THESE

566
00:24:50,862 --> 00:24:53,531
CONDITIONS, 1, 2, 3, DISEASE AND

567
00:24:53,531 --> 00:24:56,200
AGAIN, WE HAVE 1 WITH -- SHOW ME

568
00:24:56,200 --> 00:24:58,002
THE NEXT 1 -- WITH THE SLOWER,

569
00:24:58,002 --> 00:25:00,838
WITH THE SHORTER LIFE EXPECTANCY

570
00:25:00,838 --> 00:25:06,244
AND THE SAME ACCUMULATION OF

571
00:25:06,244 --> 00:25:06,744
MOBILITY ALSO.

572
00:25:06,744 --> 00:25:08,513
SHOW ME THE NEXT PART OF THIS

573
00:25:08,513 --> 00:25:09,380
SLIDE.

574
00:25:09,380 --> 00:25:11,582
THE PROBLEM IS THAT WE ONLY

575
00:25:11,582 --> 00:25:13,651
INTERVENE BY HEALTHCARE AT THIS

576
00:25:13,651 --> 00:25:15,653
POINT OF LIFE.

577
00:25:15,653 --> 00:25:20,358
IN FACT, IN THE UNITED STATES,

578
00:25:20,358 --> 00:25:23,728
WE SPEND 97.5% OF OUR HEALTHCARE

579
00:25:23,728 --> 00:25:26,330
MONEY FOR PEOPLE THAT HAVE SOME

580
00:25:26,330 --> 00:25:30,735
DISEASE AND DISABILITY AND ONLY

581
00:25:30,735 --> 00:25:40,411
2.5% OF THAT MONEY BEFORE THAT

582
00:25:40,411 --> 00:25:40,978
PERIOD.

583
00:25:40,978 --> 00:25:42,947
BUT IN FACT, WHEN WE LOOK AT

584
00:25:42,947 --> 00:25:45,349
PEOPLE WHO HAVE DISEASE, IT DOES

585
00:25:45,349 --> 00:25:48,286
EXPAND WITH THE AGING OF THE

586
00:25:48,286 --> 00:25:50,755
POPULATION AND THIS WILL

587
00:25:50,755 --> 00:25:52,824
ACCUMULATE UNTIL IT WILL BREAK

588
00:25:52,824 --> 00:25:53,291
THE BANK.

589
00:25:53,291 --> 00:25:55,293
WE WILL NOT ALL BE ABLE TO

590
00:25:55,293 --> 00:25:56,694
AFFORD THE HEALTHCARE, THE

591
00:25:56,694 --> 00:25:57,662
BENEFIT OF THE HEALTHCARE THAT

592
00:25:57,662 --> 00:25:59,097
WE HAVE NOW.

593
00:25:59,097 --> 00:26:02,767
SO OUR GOAL IS TO EXPAND HEALTH

594
00:26:02,767 --> 00:26:08,973
EXPECTANCY. 

595
00:26:08,973 --> 00:26:09,440
THE NEXT SLIDE.

596
00:26:09,440 --> 00:26:19,951
ONE WAY TO DO THAT IS TO THINK

597
00:26:19,951 --> 00:26:21,452
ABOUT THIS THRESHOLD, IT'S

598
00:26:21,452 --> 00:26:22,086
ACCUMULATING IN OUR BODY, EVERY

599
00:26:22,086 --> 00:26:24,388
YEAR I GO TO A DOCTOR AND THE

600
00:26:24,388 --> 00:26:30,328
DOCTOR LOOK AT ME, AND VISIT ME

601
00:26:30,328 --> 00:26:31,963
LOOK AT MY HEART AND MY LUNGS

602
00:26:31,963 --> 00:26:40,838
AND THEY SAY, YOU'RE FINE,

603
00:26:40,838 --> 00:26:43,174
YOU'RE OKAY AND THE PATHOLOGY

604
00:26:43,174 --> 00:26:45,710
ACCUMULATING IN MY BODY, SO I

605
00:26:45,710 --> 00:26:47,411
WANT TO KNOW WHAT'S GOING ON SO

606
00:26:47,411 --> 00:26:49,413
THAT WHEN I CAN INTERVENE MUCH

607
00:26:49,413 --> 00:26:52,416
EARLIER THAN, YOU KNOW WHEN I

608
00:26:52,416 --> 00:26:54,819
FINALLY DEVELOP A DISEASE AND

609
00:26:54,819 --> 00:26:58,556
SO, I THINK THE WAY I THINK --

610
00:26:58,556 --> 00:27:04,061
NEXT SLIDE -- THAT IN FACT,

611
00:27:04,061 --> 00:27:11,135
THESE ACCUMULATION OF THE

612
00:27:11,135 --> 00:27:12,203
AUTOLOGY THAT HAVE THIS.

613
00:27:12,203 --> 00:27:13,371
SO THE INDIVIDUALS THAT HAVE

614
00:27:13,371 --> 00:27:15,773
FASTER PACE OF AGING AND HAVE

615
00:27:15,773 --> 00:27:17,408
SHORTER LIFE EXPECTANCY WHILE

616
00:27:17,408 --> 00:27:20,211
THE PEOPLE THAT HAVE THE SLOW

617
00:27:20,211 --> 00:27:26,250
PACE OF AGING WILL HAVE A LONGER

618
00:27:26,250 --> 00:27:26,818
HEALTH EXPECTANCY.

619
00:27:26,818 --> 00:27:29,587
NOT ONLY THAT BUT THE PACE OF

620
00:27:29,587 --> 00:27:32,356
AGING CAN BE MEASURED.

621
00:27:32,356 --> 00:27:33,691
SO IF WE COULD MEASURE THE PACE

622
00:27:33,691 --> 00:27:37,195
OF AGING, WE WILL BE ABLE TO

623
00:27:37,195 --> 00:27:38,529
DETECT WHAT ARE INDIVIDUALS THAT

624
00:27:38,529 --> 00:27:41,699
ARE AGING FASTER THAN OTHERS AND

625
00:27:41,699 --> 00:27:42,900
INTERVENE TO SLOW DOWN THE PACE

626
00:27:42,900 --> 00:27:47,471
OF AGING SO THAT WE CAN PREVENT

627
00:27:47,471 --> 00:27:49,106
A NUMBER OF DISEASE ACCORDING TO

628
00:27:49,106 --> 00:27:50,408
THE JOURNAL OF SCIENCE

629
00:27:50,408 --> 00:27:51,309
HYPOTHESIS THAT ARE LINKED TO

630
00:27:51,309 --> 00:27:53,177
THE CASE OF AGING.

631
00:27:53,177 --> 00:27:55,780
THE NEXT SLIDE REALLY SUMMARIZE

632
00:27:55,780 --> 00:27:59,851
THIS CONCEPT IN A SIMPLE WAY.

633
00:27:59,851 --> 00:28:01,986
THE WAY WE DO NOW IS WE THINK OF

634
00:28:01,986 --> 00:28:03,154
AGING ASSOCIATED WITH THE NUMBER

635
00:28:03,154 --> 00:28:06,657
OF DISEASE, NEXT SLIDE, AND THEN

636
00:28:06,657 --> 00:28:12,196
WHEN THIS DISEASE OCCURRED, WE

637
00:28:12,196 --> 00:28:13,197
INTERVENE WITH FANTASTIC

638
00:28:13,197 --> 00:28:14,498
MOMENTARIUM OF DRUGS AND

639
00:28:14,498 --> 00:28:15,566
SURGICAL PROCEDURE THAT YOU KNOW

640
00:28:15,566 --> 00:28:19,437
WE NEED TO BE HAPPY ABOUT

641
00:28:19,437 --> 00:28:20,805
BECAUSE THEY DO IT FOR THESE

642
00:28:20,805 --> 00:28:23,808
PEOPLE BUT WE DO VERY LITTLE TO

643
00:28:23,808 --> 00:28:26,978
AVOID THIS DISEASE TO OCCUR AND

644
00:28:26,978 --> 00:28:28,512
IF WE COULD -- WITH THE NEXT

645
00:28:28,512 --> 00:28:32,216
SLIDE -- SLOW DOWN, GIVE ME THE

646
00:28:32,216 --> 00:28:32,817
NEXT SLIDE.

647
00:28:32,817 --> 00:28:35,987
SLOW DOWN THE PACE OF AGING,

648
00:28:35,987 --> 00:28:38,122
THEN WE CAN PREVENT THEM, YOU

649
00:28:38,122 --> 00:28:39,657
KNOW ALL 1 AT A TIME.

650
00:28:39,657 --> 00:28:43,494
SO HOW DO WE EXPLORE THIS 1

651
00:28:43,494 --> 00:28:43,828
SEPTORS?

652
00:28:43,828 --> 00:28:46,364
THE WAY TO EXPLORE THIS CONCEPT

653
00:28:46,364 --> 00:28:50,201
IS TO CONCEPTUALIZE AGING AS A

654
00:28:50,201 --> 00:28:52,403
RATIO BETWEEN DAMAGE

655
00:28:52,403 --> 00:28:53,037
ACCUMULATION AND RESILIENCE.

656
00:28:53,037 --> 00:29:00,845
SO 1 OF THE MOST ACCEPTED THEORY

657
00:29:00,845 --> 00:29:02,880
OF AGING IS THAT, YOU LEAN FROM

658
00:29:02,880 --> 00:29:05,983
THE AREA OF DYNAMIC, WHERE EVERY

659
00:29:05,983 --> 00:29:08,953
SYSTEM IS SUBJECT TO ANTHROPY,

660
00:29:08,953 --> 00:29:11,656
SO ANTHROPY CAN DAMAGE AT THE

661
00:29:11,656 --> 00:29:12,056
MOLECULAR LEVEL.

662
00:29:12,056 --> 00:29:13,824
BUT THERE ARE A NUMBER OF

663
00:29:13,824 --> 00:29:22,266
BIOLOGICAL MECHANISMS THAT HAVE

664
00:29:22,266 --> 00:29:24,335
BEEN DEVELOPED EVOLUTIONARY AND

665
00:29:24,335 --> 00:29:30,608
P A YEL WILL MORE ABOUT THIS

666
00:29:30,608 --> 00:29:30,841
LATER.

667
00:29:30,841 --> 00:29:33,377
AND THEN WITH AGING YOU HAVE AN

668
00:29:33,377 --> 00:29:36,781
IMBALANCE THEN SO THAT YOU HAVE

669
00:29:36,781 --> 00:29:37,815
DAMAGE ACCUMULATION AND CLOSE TO

670
00:29:37,815 --> 00:29:42,219
THE END OF LIFE, YOUR ABILITY TO

671
00:29:42,219 --> 00:29:46,057
DEAL WITH STRESS AND THEY HAVE

672
00:29:46,057 --> 00:29:49,694
THE ISSUE OF RESILIENCY DO NOT

673
00:29:49,694 --> 00:29:51,362
ALLOW YOU TO LIVE EVEN THE

674
00:29:51,362 --> 00:29:53,631
NORMALLIEST OF LIFE AND THEN YOU

675
00:29:53,631 --> 00:29:56,000
CAN TRANSLATE THIS CONCEPT INTO

676
00:29:56,000 --> 00:29:58,836
SOMETHING WE CAN START

677
00:29:58,836 --> 00:29:59,203
MEASURING.

678
00:29:59,203 --> 00:30:00,604
THIS IS WHEN THE LOWER PART OF

679
00:30:00,604 --> 00:30:03,407
MY SLIDE, YOU WILL SEE THAT OVER

680
00:30:03,407 --> 00:30:06,310
THE GENETIC BACKGROUND, THERE IS

681
00:30:06,310 --> 00:30:11,282
ACCUMULATION OF DAMAGE AND THE

682
00:30:11,282 --> 00:30:15,286
MACROMOLAR LEVEL, THE CALORIES,

683
00:30:15,286 --> 00:30:16,487
THE CARBOHYDRATES, THE DNA ARE

684
00:30:16,487 --> 00:30:19,290
DAMAGED AND THEN THERE ARE A

685
00:30:19,290 --> 00:30:21,859
NUMBER OF BEAUTIFULLY

686
00:30:21,859 --> 00:30:25,663
CONCEPTUALIZED MECHANISMS THAT

687
00:30:25,663 --> 00:30:27,164
REPAIR THEM OR SOMEWHAT PICK OUT

688
00:30:27,164 --> 00:30:29,667
THOSE DAMAGED AND THAT

689
00:30:29,667 --> 00:30:31,235
BIOLOGICAL DAMAGE TRANSLATE INTO

690
00:30:31,235 --> 00:30:34,038
WHAT WE CALL THE PHENOTYPE.

691
00:30:34,038 --> 00:30:41,345
AT SOME POINT WHEN THEY BECOME

692
00:30:41,345 --> 00:30:48,853
SEVERELY LOW, THOSE CALL LOW,

693
00:30:48,853 --> 00:30:50,021
PROBABLY ACCOUNT FOR VISUAL

694
00:30:50,021 --> 00:30:58,929
ACUITY AND HEARING, AND THEN

695
00:30:58,929 --> 00:31:00,364
ALSO STARTS IMMOBILITY AND

696
00:31:00,364 --> 00:31:01,032
DISABILITY AND GAIT.

697
00:31:01,032 --> 00:31:03,701
SO 1 OF THE 3 HERE AND THAT --

698
00:31:03,701 --> 00:31:07,338
YOU KNOW THIS IS AN EXAMPLE AND

699
00:31:07,338 --> 00:31:09,907
P A YEL WILL TALK MORE, I WILL

700
00:31:09,907 --> 00:31:11,909
JUST SHOW 1.

701
00:31:11,909 --> 00:31:16,080
THERE ARE ABOUT 10,000 DAMAGE OF

702
00:31:16,080 --> 00:31:21,952
DNA EACH CELL, EVERY DAY AND

703
00:31:21,952 --> 00:31:23,054
THIS COMPLEX NETWORK OF

704
00:31:23,054 --> 00:31:25,389
MOLECULE, THEY REPAIR THE DNA

705
00:31:25,389 --> 00:31:26,290
CONSTANT, THEY'RE CONTINUOUSLY

706
00:31:26,290 --> 00:31:28,125
AND IF THEY DON'T, THERE IS

707
00:31:28,125 --> 00:31:29,193
SEVERE CONSEQUENCE ON THE

708
00:31:29,193 --> 00:31:39,336
HEALTH. 

709
00:31:43,674 --> 00:31:44,942
THE NEXT SLIDE.

710
00:31:44,942 --> 00:31:47,645
BECAUSE OUR BODIES IS REDUNDANT,

711
00:31:47,645 --> 00:31:54,018
THERE IS SOME  RESILIENCE, SOME

712
00:31:54,018 --> 00:31:57,054
RESEARCH, SO YOU CAN AFFORD SOME

713
00:31:57,054 --> 00:31:59,190
BIOLOGICAL DAMAGE WITHOUT HAVING

714
00:31:59,190 --> 00:31:59,723
PHENOTYPIC MANIFESTATION.

715
00:31:59,723 --> 00:32:01,725
SO FOR EXAMPLE, YOU CAN HAVE A

716
00:32:01,725 --> 00:32:04,428
LITTLE BIT OF ACCUMULATION OF

717
00:32:04,428 --> 00:32:07,298
SOMATIC MUTATION WITHOUT ANY

718
00:32:07,298 --> 00:32:08,299
MEASURABLE REDACTION OF THE

719
00:32:08,299 --> 00:32:13,437
FUNCTION OF THE DIFFERENT

720
00:32:13,437 --> 00:32:13,671
ORGANS.

721
00:32:13,671 --> 00:32:20,878
AT SOME POINT THE ACCUMULATION,

722
00:32:20,878 --> 00:32:22,980
AND OF COURSE PHENOTYPIC AGING

723
00:32:22,980 --> 00:32:25,516
AND FUNCTIONAL AGING AND

724
00:32:25,516 --> 00:32:26,917
BIOLOGICAL AGING AND THIS IS

725
00:32:26,917 --> 00:32:29,453
IMPORTANT BECAUSE IN BIOLOGICAL

726
00:32:29,453 --> 00:32:31,422
AGING OCCUR BEFORE PHENOTYPIC

727
00:32:31,422 --> 00:32:34,425
AND FUNCTIONAL AGING OCCUR, IF

728
00:32:34,425 --> 00:32:35,526
WE CAN DETECT THE DAMAGE AT THE

729
00:32:35,526 --> 00:32:41,565
ABOUT I ONY LOGICAL LEVEL, WE

730
00:32:41,565 --> 00:32:43,400
CAN INTERVENE EARLY AND AT THE

731
00:32:43,400 --> 00:32:46,137
TIME WHEN THE INTERVENTION IS

732
00:32:46,137 --> 00:32:48,839
MORE EFFECTIVE GIVE ME THE NEXT

733
00:32:48,839 --> 00:32:49,740
SLIDE.

734
00:32:49,740 --> 00:32:54,345
SO THE GLOBAL CHALLENGE FOR THIS

735
00:32:54,345 --> 00:32:58,015
IS TO ACHIEVE LONGEVITY, THE

736
00:32:58,015 --> 00:32:59,884
STATE IN WHICH GOOD HEALTH AND

737
00:32:59,884 --> 00:33:02,019
BIOLOGICAL LIFE SPAN WITH

738
00:33:02,019 --> 00:33:04,488
PHYSICAL CONJUGATE AND SOCIALLY,

739
00:33:04,488 --> 00:33:08,759
WITH THE CROSS POPULATION EMPLOY

740
00:33:08,759 --> 00:33:10,961
THE NEXT SLIDE REALLY PUT THIS

741
00:33:10,961 --> 00:33:14,899
IN CONTEXT, WHAT ARE THE

742
00:33:14,899 --> 00:33:15,933
ADVANTAGE OF THAT INDIVIDUAL

743
00:33:15,933 --> 00:33:20,905
WILL LIVE A VERY STRONG AND YOU

744
00:33:20,905 --> 00:33:21,906
KNOW ENJOYABLE LIFE.

745
00:33:21,906 --> 00:33:25,509
THEY WILL BE INTERGENERATIONAL

746
00:33:25,509 --> 00:33:27,244
SUPPORT, IN SOCIETY, THE ABILITY

747
00:33:27,244 --> 00:33:29,880
AND THE SKILL WITH THE AGE, IT

748
00:33:29,880 --> 00:33:31,782
WILL BE USEFUL FOR SOCIETY, THEY

749
00:33:31,782 --> 00:33:33,250
WILL BE MORE SOCIAL BEHAVIOR,

750
00:33:33,250 --> 00:33:36,053
WHILE THE COST OF INACTION IS TO

751
00:33:36,053 --> 00:33:38,489
HAVE MORE PEOPLE LIVING IN POOR

752
00:33:38,489 --> 00:33:38,789
HEALTH.

753
00:33:38,789 --> 00:33:40,291
THE GDP WILL GO DOWN.

754
00:33:40,291 --> 00:33:42,560
THERE WILL BE INCREASED BURDEN

755
00:33:42,560 --> 00:33:45,062
ON MEDICAL AND SOCIAL CARE FOR

756
00:33:45,062 --> 00:33:48,465
GOVERNMENT AND AT SOME POINT

757
00:33:48,465 --> 00:33:49,867
THERE'S INCREASING FINANCIAL

758
00:33:49,867 --> 00:33:52,970
BURDEN WILL GO INTO THE STRESS

759
00:33:52,970 --> 00:33:59,009
OF INDIVIDUAL AND THE FAMILY. 

760
00:33:59,009 --> 00:34:03,948
THE NEXT SLIDE. 

761
00:34:03,948 --> 00:34:06,217
SO MAXIMIZING HEALTH, MINIMIZING

762
00:34:06,217 --> 00:34:07,518
MOLECULAR DAMAGE.

763
00:34:07,518 --> 00:34:09,920
NEXT SLIDE.

764
00:34:09,920 --> 00:34:12,122
WITH THE NEXT SLIDE, I WANT TO

765
00:34:12,122 --> 00:34:14,925
TELL YOU WHAT I TELL WHEN THE

766
00:34:14,925 --> 00:34:16,427
NEWSPAPER INTERVIEW ME AND ASKS

767
00:34:16,427 --> 00:34:22,700
THE QUESTION, WHAT IS THE MAGIC?

768
00:34:22,700 --> 00:34:24,868
AND I ALWAYS SAY, THEY ALREADY

769
00:34:24,868 --> 00:34:29,607
HAVE THE MAGIC, YOU KNOW,

770
00:34:29,607 --> 00:34:31,575
CERTAIN BEHAVIOR, EFFECT, DURING

771
00:34:31,575 --> 00:34:32,710
HEALTH EXPECTANCY.

772
00:34:32,710 --> 00:34:34,011
SO BEING PHYSICALLY ACTIVE IS A

773
00:34:34,011 --> 00:34:36,013
GIFT, AND THE MESSAGE WE GIVE TO

774
00:34:36,013 --> 00:34:37,514
OUR OLDER PATIENTS IS WRONG, WE

775
00:34:37,514 --> 00:34:40,351
SAY YOU NEED TO JOG AND PEOPLE

776
00:34:40,351 --> 00:34:40,884
GET DISCOURAGED.

777
00:34:40,884 --> 00:34:43,320
WHAT WE SHOULD TELL THEM IS

778
00:34:43,320 --> 00:34:45,356
THAT, WALK AROUND THE BLOCK AND

779
00:34:45,356 --> 00:34:49,193
THAT IS ALREADY MUCH, MUCH

780
00:34:49,193 --> 00:34:50,761
BETTER THAN SEDENTARY.

781
00:34:50,761 --> 00:34:58,469
WORK ON PREVENTION, TRY TO --

782
00:34:58,469 --> 00:35:00,371
INCREDIBLY IMPORTANT FOR IT.

783
00:35:00,371 --> 00:35:02,539
LEARN SOMETHING NEW, MAINTAIN

784
00:35:02,539 --> 00:35:04,908
HEALTHY WEIGHT, USE YOUR BRAIN

785
00:35:04,908 --> 00:35:07,311
TO LEARN SOMETHING THAT YOU

786
00:35:07,311 --> 00:35:10,247
ENJOY, AVOID ALCOHOL, YOU KNOW I

787
00:35:10,247 --> 00:35:11,915
THINK THAT IT'S CONTROVERSIAL

788
00:35:11,915 --> 00:35:14,885
BUT I THINK YOU DRINK A GLASS OF

789
00:35:14,885 --> 00:35:16,320
WINE PER WEEK, I DON'T THINK YOU

790
00:35:16,320 --> 00:35:19,390
SHOULD BE CONCERNED VERY MUCH. 

791
00:35:19,390 --> 00:35:22,226
AND THEN, YOU KNOW HAVE THE

792
00:35:22,226 --> 00:35:24,495
HEALTHY DIET, PROBABLY THE

793
00:35:24,495 --> 00:35:25,763
MEDITERRANEAN DIET IS THE ONLY

794
00:35:25,763 --> 00:35:27,631
DIET AND THEN USE YOUR BRAIN.

795
00:35:27,631 --> 00:35:30,734
I THINK THAT FOLLOWING THIS VERY

796
00:35:30,734 --> 00:35:33,504
SIMPLE SUGGESTION, WILL INCREASE

797
00:35:33,504 --> 00:35:35,005
HEALTH EXPECTANCY AND CREATE A

798
00:35:35,005 --> 00:35:37,808
BETTER MORE HEALTHY LIFE.

799
00:35:37,808 --> 00:35:40,311
THE TRICK HERE IS TO UNDERSTAND

800
00:35:40,311 --> 00:35:45,883
WHAT ARE THE TRANSDUCER OF THIS

801
00:35:45,883 --> 00:35:46,150
MECHANISM.

802
00:35:46,150 --> 00:35:48,285
YOU KNOW, WHY SLEEP IS AFFECTING

803
00:35:48,285 --> 00:35:49,820
YOUR ABILITY TO DEVELOP CHRONIC

804
00:35:49,820 --> 00:35:50,154
DISEASE?

805
00:35:50,154 --> 00:35:52,790
WE DON'T KNOW THAT YET BUT IF WE

806
00:35:52,790 --> 00:35:54,625
ANYHOW MORE, THE PROBLEM IS THAT

807
00:35:54,625 --> 00:35:56,727
COULD BE AN INCREDIBLE POWERFUL

808
00:35:56,727 --> 00:36:01,799
TARGET FOR INTERVENTION, THE

809
00:36:01,799 --> 00:36:02,966
NEXT SLIDE.

810
00:36:02,966 --> 00:36:04,501
SO I WILL SKIP THIS BECAUSE I'M

811
00:36:04,501 --> 00:36:05,302
A LITTLE BIT LATE.

812
00:36:05,302 --> 00:36:09,940
GIVE ME THE NEXT 1 PLEASE. 

813
00:36:09,940 --> 00:36:14,778
SO I WANT TO SUMMARIZE MY TALK

814
00:36:14,778 --> 00:36:15,713
WITH A FEW THOUGHTS.

815
00:36:15,713 --> 00:36:16,914
YOU KNOW WE ALWAYS TALK ABOUT

816
00:36:16,914 --> 00:36:20,184
WHAT WE EAT, THE EXERCISE, BUT I

817
00:36:20,184 --> 00:36:22,720
THINK THAT YOU KNOW THE

818
00:36:22,720 --> 00:36:25,189
PSYCHOLOGICAL INTERVENTION THAT

819
00:36:25,189 --> 00:36:28,125
CAN AFFECT THE HEALTH SPAN AND

820
00:36:28,125 --> 00:36:31,695
HEALTHY LIFE ARE BECOMING

821
00:36:31,695 --> 00:36:33,163
EXTREMELY IMPORTANT AND EMERGE

822
00:36:33,163 --> 00:36:33,931
IN THE LITERATURE.

823
00:36:33,931 --> 00:36:39,303
FOR EXAMPLE, IN THIS PAPER, YOU

824
00:36:39,303 --> 00:36:44,675
KNOW NICOLETTI SHOWED THAT

825
00:36:44,675 --> 00:36:45,843
INDIVIDUALS ARE LESS LIKELY TO

826
00:36:45,843 --> 00:36:49,646
DEVELOP AN IMPAIRMENT, SO THAT

827
00:36:49,646 --> 00:36:52,349
CAME TO THE BALTIMORE AGENCY FOR

828
00:36:52,349 --> 00:36:55,786
AGING AND WENT TO THE BOXES, 40

829
00:36:55,786 --> 00:36:58,789
YEARS BEFORE,  FOUND THESE

830
00:36:58,789 --> 00:36:59,857
INTERVIEWS AND LOOK AT WHAT

831
00:36:59,857 --> 00:37:00,824
HAPPENED TO THESE PEOPLE AND SHE

832
00:37:00,824 --> 00:37:04,395
FOUND THAT JUST HAVING A

833
00:37:04,395 --> 00:37:06,029
POSITIVE BELIEF ABOUT THE AGING

834
00:37:06,029 --> 00:37:10,501
PROCESS AS A POSITIVE EFFECT FOR

835
00:37:10,501 --> 00:37:12,069
A LONG TIME IN THIS INDIVIDUAL.

836
00:37:12,069 --> 00:37:13,604
THE NEXT SLIDE.

837
00:37:13,604 --> 00:37:15,339
AND THEN, SHE ALSO FOUND THAT

838
00:37:15,339 --> 00:37:24,448
THOSE WITH THE POSITIVE BELIEF,

839
00:37:24,448 --> 00:37:26,383
HAD LESS TANG AND HE WILL

840
00:37:26,383 --> 00:37:28,886
AMYLOID PLAQUES, SO IT'S NOT

841
00:37:28,886 --> 00:37:30,421
JUST SOMETHING THAT SOFT

842
00:37:30,421 --> 00:37:31,455
SCIENCE, IT'S REALLY, REALLY

843
00:37:31,455 --> 00:37:32,856
SOMETHING THAT SEEMS TO BE VERY,

844
00:37:32,856 --> 00:37:35,659
VERY HARD AND VERY, VERY WELL,

845
00:37:35,659 --> 00:37:41,665
YOU KNOW DEFINED. 

846
00:37:41,665 --> 00:37:42,533
THE NEXT SLIDE.

847
00:37:42,533 --> 00:37:43,801
SO ANOTHER THING WE DISCOVER IS

848
00:37:43,801 --> 00:37:46,503
THAT, WE NEED TO THINK ABOUT

849
00:37:46,503 --> 00:37:49,540
HEALTH WITH THE LIFETIME

850
00:37:49,540 --> 00:37:49,840
PERSPECTIVE.

851
00:37:49,840 --> 00:37:52,409
AND THIS TIME THE EXAMPLE SHOWS

852
00:37:52,409 --> 00:37:55,345
THAT EXPERIENCING POOR ECONOMIC

853
00:37:55,345 --> 00:37:56,880
CONDITION AT YOUTH, WHILE

854
00:37:56,880 --> 00:38:02,019
LOOKING AT SOCIALIO ECONOMIC

855
00:38:02,019 --> 00:38:04,588
STATE AS ADULT WAS ASSOCIATE

856
00:38:04,588 --> 00:38:07,791
WIDE ACCELERATED AGING AND THAT

857
00:38:07,791 --> 00:38:12,095
FADED OVER TIME BUT IT WAS VERY,

858
00:38:12,095 --> 00:38:16,500
VERY EVIDENT DURING THE GREAT

859
00:38:16,500 --> 00:38:16,967
DEPRESSION.

860
00:38:16,967 --> 00:38:18,969
NEXT SLIDE.

861
00:38:18,969 --> 00:38:23,440
OKAY, SO DURING MY LAST PHASE

862
00:38:23,440 --> 00:38:23,874
SLIDE.

863
00:38:23,874 --> 00:38:28,645
SO 1 THING THAT IS BECOMING

864
00:38:28,645 --> 00:38:29,480
EVIDENT, THERE'S AN

865
00:38:29,480 --> 00:38:31,782
AUTOMECHANISM THAT AFFECT AGING,

866
00:38:31,782 --> 00:38:36,119
SO THAT YOU KNOW FOR EXAMPLE,

867
00:38:36,119 --> 00:38:38,689
EXERCISE AND FRUIT AND VEGETABLE

868
00:38:38,689 --> 00:38:40,591
COMSUMPTION WORK BECAUSE THEY

869
00:38:40,591 --> 00:38:43,293
ARE IN FACT, VERY, VERY MILD

870
00:38:43,293 --> 00:38:44,361
STRESS AND VERY, VERY MILD

871
00:38:44,361 --> 00:38:49,466
STRESS IS GOOD FOR YOU BECAUSE

872
00:38:49,466 --> 00:38:50,133
STIMULATE AND BUILD RESILIENCEY.

873
00:38:50,133 --> 00:38:51,668
GIVE ME THE NEXT SLIDE.

874
00:38:51,668 --> 00:38:55,405
EXAMPLE, I PUT HERE STRESSOR AND

875
00:38:55,405 --> 00:38:56,773
THEN POSITIVE STRESSOR, HEALTHY

876
00:38:56,773 --> 00:38:59,443
DIET, YOU KNOW SOME PHYSICALLY

877
00:38:59,443 --> 00:39:02,880
ACTIVE, GOOD SLEEP, STIMULATING

878
00:39:02,880 --> 00:39:07,050
JOB, NORMAL FAMILY, NORMAL

879
00:39:07,050 --> 00:39:08,485
FINANCIAL STATUS, LIVING IN

880
00:39:08,485 --> 00:39:10,320
NORMAL NEIGHBORHOOD, WHAT

881
00:39:10,320 --> 00:39:12,689
HAPPENS TO THIS, THE REACTIVITY

882
00:39:12,689 --> 00:39:19,963
TEND TO INCREASE AND GET

883
00:39:19,963 --> 00:39:21,231
ACCUMULATING IN INDIVIDUALS AND

884
00:39:21,231 --> 00:39:22,699
THIS MECHANISM ARE IMPORTANT TO

885
00:39:22,699 --> 00:39:25,802
AFFECT THE CASE OF AGING,

886
00:39:25,802 --> 00:39:28,171
REDUCING THEREFORE THE RISK OF

887
00:39:28,171 --> 00:39:29,907
DISABILITY, CHRONIC DISEASE, AND

888
00:39:29,907 --> 00:39:30,374
MORTALITY.

889
00:39:30,374 --> 00:39:32,109
ON THE CONTRARY, IF YOU THINK

890
00:39:32,109 --> 00:39:35,045
ABOUT THE NEGATIVE STRESSOR IN

891
00:39:35,045 --> 00:39:37,781
THE NEXT SLIDE, THE NEGATIVE

892
00:39:37,781 --> 00:39:40,050
STRESSOR DO EXACTLY THE

893
00:39:40,050 --> 00:39:41,585
OPPOSITE, THEY CONSUME THE

894
00:39:41,585 --> 00:39:45,255
ENERGY THAT IS ACCUMULATING, AND

895
00:39:45,255 --> 00:39:48,926
IF YOU ARE USING THIS, YOU KNOW

896
00:39:48,926 --> 00:39:51,028
ENERGY THAT IS ACCUMULATING

897
00:39:51,028 --> 00:39:55,098
EARLY IN LIFE, THAT YOU DON'T

898
00:39:55,098 --> 00:39:56,500
HAVE THE ENERGY LATER IN LIFE,

899
00:39:56,500 --> 00:40:00,003
SO THERE IS AN ACCELERATED

900
00:40:00,003 --> 00:40:02,973
DECLINE OF HEALTH AND

901
00:40:02,973 --> 00:40:05,242
ACCELERATED AGING IN THE END OF

902
00:40:05,242 --> 00:40:08,278
LIFE WHICH LEAD TO LONG PERIOD

903
00:40:08,278 --> 00:40:09,446
OF DISEASE AND DISABILITY.

904
00:40:09,446 --> 00:40:11,949
SO WE NEED TO START THINKING

905
00:40:11,949 --> 00:40:16,587
ABOUT HOW WE WILL AGE AT THE AGE

906
00:40:16,587 --> 00:40:16,820
OF 1.

907
00:40:16,820 --> 00:40:18,121
YOU KNOW THE EXPERIENCE WE MAKE,

908
00:40:18,121 --> 00:40:19,990
THE CHOICE WE MAKE OVER THE

909
00:40:19,990 --> 00:40:21,558
ENTIRE LIFE SPAN ARE GOING TO

910
00:40:21,558 --> 00:40:23,293
AFFECT THE QUALITY OF OUR AGING

911
00:40:23,293 --> 00:40:28,365
AND THIS IS BECOMING VERY, VERY

912
00:40:28,365 --> 00:40:31,802
EVIDENT AS THE EPIDEMIOLOGICAL

913
00:40:31,802 --> 00:40:33,303
STUDY THAT'S SPANNED MANY, MANY

914
00:40:33,303 --> 00:40:41,545
YEARS ARE BECOMING AVAILABLE.

915
00:40:41,545 --> 00:40:44,247
NEXT SLIDE.

916
00:40:44,247 --> 00:40:48,085
SO HELPFUL KEYS TO HAVING A LONG

917
00:40:48,085 --> 00:40:49,886
LIFE, WILL BE THE HEALTH AGENDA

918
00:40:49,886 --> 00:40:57,260
OF THE 21st CENTURY, I THINK

919
00:40:57,260 --> 00:41:03,200
IF YOU CAN MAKE THE 20 YEAR, IF

920
00:41:03,200 --> 00:41:05,068
YOU ARE INCREASING LIFE BY 20

921
00:41:05,068 --> 00:41:06,803
YEAR MEANS WE'RE EXPANDING THE

922
00:41:06,803 --> 00:41:08,639
PERIOD OF LIFE CHARACTERIZED BY

923
00:41:08,639 --> 00:41:10,941
THIS ABILITY AND DISEASE, I

924
00:41:10,941 --> 00:41:13,877
DON'T THINK THIS IS RELIABLE AND

925
00:41:13,877 --> 00:41:14,244
BENEFICIAL GOAL.

926
00:41:14,244 --> 00:41:16,847
THANK YOU VERY MUCH FOR

927
00:41:16,847 --> 00:41:27,357
LISTENING TO MY PRESENTATION.

928
00:41:35,365 --> 00:41:36,933
>> THANK YOU VERY MUCH.

929
00:41:36,933 --> 00:41:47,477
SO NOW P A YEL WILL YOU CONTINUE

930
00:41:51,181 --> 00:41:51,448
PLEASE?

931
00:41:51,448 --> 00:41:52,949
I ASSUME YOU CAN SEE MY SLIDES

932
00:41:52,949 --> 00:41:55,085
AND HEAR ME ALL RIGHT?

933
00:41:55,085 --> 00:41:56,987
>> YES, PERFECT, THANK
YOU.

934
00:41:56,987 --> 00:41:57,487
>> OKAY, THANK YOU.

935
00:41:57,487 --> 00:41:59,022
SO FIRST I WOULD LIKE TO THANK

936
00:41:59,022 --> 00:42:00,157
THE ORGANIZERS FOR GIVING ME

937
00:42:00,157 --> 00:42:02,259
THIS OPPORTUNITY AND I'M ALSO

938
00:42:02,259 --> 00:42:02,959
INCREDIBLY GRATEFUL THAT YOU

939
00:42:02,959 --> 00:42:06,830
KNOW I GET TO SHARE THE VIRTUAL

940
00:42:06,830 --> 00:42:10,100
STAGE WITH LUIGI, SO LUIGI, JUST

941
00:42:10,100 --> 00:42:13,303
GAVE YOU AN EPIDEMIOLOGICAL

942
00:42:13,303 --> 00:42:15,338
PERSPECTIVE OF THIS PARTICULAR

943
00:42:15,338 --> 00:42:16,773
QUESTION TODAY AND BEING AN

944
00:42:16,773 --> 00:42:17,541
EXPERIMENTAL BIOLOGIST, I'M

945
00:42:17,541 --> 00:42:22,245
GOING TO GIVE YOU SOME INSIGHT

946
00:42:22,245 --> 00:42:25,348
INTO HOW, YOU KNOW, MAYBE

947
00:42:25,348 --> 00:42:26,683
BIOLOGISTS VIEW THIS QUESTION.

948
00:42:26,683 --> 00:42:31,722
SO THIS FIRST SLIDE IS GIF THAT

949
00:42:31,722 --> 00:42:34,424
TRACES THE MEDIAN AGES ACROSS

950
00:42:34,424 --> 00:42:36,393
ALL COUNTRIES OVER A SPAN OF

951
00:42:36,393 --> 00:42:37,127
ABOUT A HUNDRED YEARS.

952
00:42:37,127 --> 00:42:39,996
AND YOU CAN SEE THE COLORS

953
00:42:39,996 --> 00:42:43,967
GETTING DARKER AS THE DECADES

954
00:42:43,967 --> 00:42:46,570
PROGRESS WHICH ESSENTIALLY MEANS

955
00:42:46,570 --> 00:42:49,206
THAT YOU KNOW, WE ARE GETTING

956
00:42:49,206 --> 00:42:51,074
INTO THE DECADES WHERE WE HAVE A

957
00:42:51,074 --> 00:42:54,678
LOT OF OLDER INDIVIDUALS AMONG

958
00:42:54,678 --> 00:42:57,748
US AND THAT IS CONCERNING, NOT

959
00:42:57,748 --> 00:42:58,682
ONLY BECAUSE YOU KNOW THERE'S

960
00:42:58,682 --> 00:43:03,320
GOING TO BE A LOT OF

961
00:43:03,320 --> 00:43:04,821
SOCIOECONOMIC PRESSURE BUT ALSO

962
00:43:04,821 --> 00:43:07,758
BECAUSE THE QUALITY OF LIFE

963
00:43:07,758 --> 00:43:09,726
HASN'T REALLY CHANGED MUCH IN

964
00:43:09,726 --> 00:43:12,295
RECENT THEORIES AND WE WILL

965
00:43:12,295 --> 00:43:15,232
CONTINUE -- IN SOME SORT OF

966
00:43:15,232 --> 00:43:15,532
DISABILITY.

967
00:43:15,532 --> 00:43:18,869
SO BEFORE I DIVE INTO THE

968
00:43:18,869 --> 00:43:20,036
LECTURE, THE AGING BIOLOGY

969
00:43:20,036 --> 00:43:21,772
LECTURE ITSELF, I WOULD LIKE TO

970
00:43:21,772 --> 00:43:25,308
RECAP JUST VERY QUICKLY, A FEW

971
00:43:25,308 --> 00:43:26,777
TIMES THAT LUIGI PROBABLY

972
00:43:26,777 --> 00:43:28,645
ALREADY INTRODUCED SO, BUT I GO

973
00:43:28,645 --> 00:43:30,280
THROUGH IT VERY QUICKLY, SO THE

974
00:43:30,280 --> 00:43:33,517
FIRST 1 IS LIFE SPAN EXPECTANCY,

975
00:43:33,517 --> 00:43:37,287
THE METRIC WE NORMALLY USE IS

976
00:43:37,287 --> 00:43:38,054
LIFE SPAN EXPECTANCY AT BIRTH

977
00:43:38,054 --> 00:43:39,890
AND YOU CAN THINK OF IT AS

978
00:43:39,890 --> 00:43:42,125
SIMPLY THE AVERAGE LIFE SPAN OF

979
00:43:42,125 --> 00:43:42,459
A POPULATION.

980
00:43:42,459 --> 00:43:45,529
IT IS VERY MUCH DEPENDENT ON

981
00:43:45,529 --> 00:43:48,532
YOUR GENETICS, WHAT YEAR YOU

982
00:43:48,532 --> 00:43:50,934
WERE BORN, WHETHER YOU'RE MALE

983
00:43:50,934 --> 00:43:52,903
OR FEMALE, SO FEMALES TEND TO

984
00:43:52,903 --> 00:43:57,340
LIVE LONGER AS LUIGI SHOWED AND

985
00:43:57,340 --> 00:43:58,141
THEN DEMOGRAPHIC FACTORS

986
00:43:58,141 --> 00:43:59,009
INCLUDING WHETHER YOU'RE LIVING

987
00:43:59,009 --> 00:44:04,681
IN A WEALTHY NATION OR NOT. 

988
00:44:04,681 --> 00:44:05,816
SADLY THOUGH, EVEN THOUGH THE

989
00:44:05,816 --> 00:44:07,250
U.S. IS 1 OF THE WEALTHIEST

990
00:44:07,250 --> 00:44:13,190
NATIONS IN THE PLANET, WE WILL

991
00:44:13,190 --> 00:44:15,058
SEE THAT IN 2030 THE U.S. IS

992
00:44:15,058 --> 00:44:17,961
EXPECTED TO TRAIL BEHIND A LOT

993
00:44:17,961 --> 00:44:19,763
OF RICH NATIONS BY A LOT BECAUSE

994
00:44:19,763 --> 00:44:24,267
MAIL LIFE SPAN IS AROUND 70 AND

995
00:44:24,267 --> 00:44:25,802
FEMALE IS 83.

996
00:44:25,802 --> 00:44:27,437
BUT BEYOND LIFE SPAN EXPECTANCY

997
00:44:27,437 --> 00:44:30,707
THERE ARE A FEW KEY TERMS OF

998
00:44:30,707 --> 00:44:33,476
MOST RELEVANCE DUE THAT IDENTIFY

999
00:44:33,476 --> 00:44:34,110
PRESENTATIONS TODAY, IS MAXIMUM

1000
00:44:34,110 --> 00:44:36,680
LIFE SPAN, SO THIS IS THE

1001
00:44:36,680 --> 00:44:38,448
MAXIMUM TIME THAT A MEMBER OF A

1002
00:44:38,448 --> 00:44:40,383
POPULATION HAS BEEN OBSERVED TO

1003
00:44:40,383 --> 00:44:45,989
SURVIVE IN CASE OF A HUMAN

1004
00:44:45,989 --> 00:44:48,158
POPULATION, IT IS 122 YEARS, THE

1005
00:44:48,158 --> 00:44:56,600
FATE OF A FRENCH WOMAN, SO

1006
00:44:56,600 --> 00:44:59,336
BECAUSE SHE LIVED TO 122 YEARS,

1007
00:44:59,336 --> 00:45:01,972
KEY KIND OF GENETICALLY SAY THAT

1008
00:45:01,972 --> 00:45:04,241
MAXIMUM HUMAN LIFE SPAN IS 120

1009
00:45:04,241 --> 00:45:06,109
YEARS SO REALLY IT IS JUST FROM

1010
00:45:06,109 --> 00:45:08,178
RECORDS AND IF THOSE RECORDS ARE

1011
00:45:08,178 --> 00:45:13,984
AROUND THEN WE ARE PROBABLY OFF.

1012
00:45:13,984 --> 00:45:15,685
-- ARE WRONG, THEN WE ARE

1013
00:45:15,685 --> 00:45:16,519
PROBABLY OFF.

1014
00:45:16,519 --> 00:45:18,488
I DON'T THINK SHE DIDN'T LEAD

1015
00:45:18,488 --> 00:45:19,990
THE MOST HEALTHIEST OF

1016
00:45:19,990 --> 00:45:20,290
LIFESTYLES.

1017
00:45:20,290 --> 00:45:22,726
FROM WHAT I HEAR SHE SMOKED

1018
00:45:22,726 --> 00:45:23,927
UNTIL SHE WAS 117 YEARS OLD.

1019
00:45:23,927 --> 00:45:27,664
SHE DRANK A LOT OF WINE, SO

1020
00:45:27,664 --> 00:45:29,466
THAT'S WHY MOST PEOPLE BELIEVE

1021
00:45:29,466 --> 00:45:35,105
THAT SHE PROBABLY HAD SOME KIND

1022
00:45:35,105 --> 00:45:35,972
OF GENETIC ADVANTAGE.

1023
00:45:35,972 --> 00:45:38,575
SO SHE HAD MAYBE SOME LONGEVITY

1024
00:45:38,575 --> 00:45:39,476
VARIANTS THAT ALLOWED HER TO

1025
00:45:39,476 --> 00:45:42,312
PUSH THE LIMIT AND LIVE UP TO

1026
00:45:42,312 --> 00:45:43,813
122 YEARS.

1027
00:45:43,813 --> 00:45:45,548
SO FOR LESSER MORTALS LIKE US

1028
00:45:45,548 --> 00:45:50,854
WHO PROBABLY DON'T HAVE THAT

1029
00:45:50,854 --> 00:45:53,156
ADVANTAGE, WHAT CAN BE TO LIVE

1030
00:45:53,156 --> 00:45:55,325
BETTER LIVES AND LUIGI STRESSED

1031
00:45:55,325 --> 00:45:57,160
THIS TOWARDS THE END OF HIS

1032
00:45:57,160 --> 00:45:58,495
TALK, I THINK WHAT WE SHOULD

1033
00:45:58,495 --> 00:46:02,065
REALLY PLAN TO DO IS RATHER THAN

1034
00:46:02,065 --> 00:46:04,501
CHASE THE 120 YEAR-OLD DREAM WE

1035
00:46:04,501 --> 00:46:05,335
COULD PROBABLY EXTEND THE PERIOD

1036
00:46:05,335 --> 00:46:07,604
OF TIME THAT WE ARE HEALTHY

1037
00:46:07,604 --> 00:46:10,607
WHICH IS CALLED HEALTH SPAN.

1038
00:46:10,607 --> 00:46:12,142
SO THANKFULLY HELT SPAN IS

1039
00:46:12,142 --> 00:46:14,678
DETERMINED BY BOTH GENETICS AS

1040
00:46:14,678 --> 00:46:17,113
WELL AS ENVIRONMENTAL

1041
00:46:17,113 --> 00:46:17,681
INFLUENCES, SO EPIGENETICS.

1042
00:46:17,681 --> 00:46:21,952
YOU CAN LOOK AT IT CONVERSELY,

1043
00:46:21,952 --> 00:46:24,154
MORE BIDDITY SPAN IS A STATE OF

1044
00:46:24,154 --> 00:46:26,356
BEING UNHEALTHY OR SYMPTOMATIC

1045
00:46:26,356 --> 00:46:29,526
WITH SOME DISEASE, SO THAT IS

1046
00:46:29,526 --> 00:46:31,761
ALSO OBVIOUSLY DETERMINED BY

1047
00:46:31,761 --> 00:46:33,663
GENETICS AND EPIGENETICS, SO

1048
00:46:33,663 --> 00:46:40,704
THEREFORE GIVEN THAT THAT 120,

1049
00:46:40,704 --> 00:46:43,340
YOU'RE FEELING IS A HARD 1 TO

1050
00:46:43,340 --> 00:46:46,643
BREAK, PERHAPS WE COULD FOCUS ON

1051
00:46:46,643 --> 00:46:49,813
EXPANDING OUR HEALTH SPAN AND

1052
00:46:49,813 --> 00:46:52,482
COMPRESSING MORBIDITY TO ACHIEVE

1053
00:46:52,482 --> 00:46:53,683
OPTIMUM LONGEVITY.

1054
00:46:53,683 --> 00:46:54,784
AND LONGEVITY IS JUST DESCRIBED

1055
00:46:54,784 --> 00:46:57,954
AS THE ABILITY TO LIVE A LONG

1056
00:46:57,954 --> 00:47:00,090
LIFE BEYOND THE SPECIES SPECIFIC

1057
00:47:00,090 --> 00:47:00,323
AVERAGE.

1058
00:47:00,323 --> 00:47:01,992
SO IF YOU LIVE BEYOND 79 OR 83

1059
00:47:01,992 --> 00:47:05,061
YEARS RIGHT NOW, I THINK YOU'VE

1060
00:47:05,061 --> 00:47:12,402
ACHIEVED SOME FORM OF LONGEVITY.

1061
00:47:12,402 --> 00:47:16,439
SO AM I SO ACTIVE IN PUSHING THE

1062
00:47:16,439 --> 00:47:16,806
120 CEILING?

1063
00:47:16,806 --> 00:47:18,308
AND THAT IS REALLY BASED ON

1064
00:47:18,308 --> 00:47:19,242
RECENT DATA.

1065
00:47:19,242 --> 00:47:22,679
THIS 1 IS A LITTLE OLD, THIS IS

1066
00:47:22,679 --> 00:47:24,948
PUBLISHED IN 2016 AND IN THESE 2

1067
00:47:24,948 --> 00:47:26,483
NICE FIGURES, THEY ESSENTIALLY

1068
00:47:26,483 --> 00:47:28,752
SHOWED THAT IMPROVEMENTS IN

1069
00:47:28,752 --> 00:47:32,222
SURVIVAL WITH AGE TEND TO

1070
00:47:32,222 --> 00:47:33,857
DECLINE AFTER A HUNDRED, SO YOU

1071
00:47:33,857 --> 00:47:36,159
CAN SEE THE PRECIPITOUS DROP AND

1072
00:47:36,159 --> 00:47:38,061
IN A RELATED FIGURE RIGHT HERE,

1073
00:47:38,061 --> 00:47:40,230
THEY ESSENTIALLY SAID THAT THE

1074
00:47:40,230 --> 00:47:42,532
MAXIMUM HUMAN LIFE SPAN HAS NOT

1075
00:47:42,532 --> 00:47:49,072
REALLY CHANGED MUCH FROM THE

1076
00:47:49,072 --> 00:47:53,143
1990S AND THE WOMAN DIED IN 1997

1077
00:47:53,143 --> 00:47:56,246
FROM WHAT I SAW, SO REALLY WE

1078
00:47:56,246 --> 00:47:57,414
HAVEN'T EXTENDED BEYOND THAT

1079
00:47:57,414 --> 00:47:59,115
MAXIMUM LIFE SPAN AND THEN A

1080
00:47:59,115 --> 00:48:01,684
MORE RECENT PAPER IN THIS LUIGI

1081
00:48:01,684 --> 00:48:07,557
HIGHLIGHTED AS WELL, IT WAS

1082
00:48:07,557 --> 00:48:09,392
SHOWING BY O'SHANSKI'S GROUP IS

1083
00:48:09,392 --> 00:48:10,593
THAT IMPROVEMENTS OVER LIFE

1084
00:48:10,593 --> 00:48:11,795
EXPECTANCY HAVE IN FACT DECLINED

1085
00:48:11,795 --> 00:48:13,063
AND I THINK WHAT THIS REALLY

1086
00:48:13,063 --> 00:48:15,465
MEAN SYSTEM EITHER WE ARE

1087
00:48:15,465 --> 00:48:16,733
GETTING SICKER, OR IT COULD EVEN

1088
00:48:16,733 --> 00:48:19,335
MEAN THAT YOU KNOW WE NEED SOME

1089
00:48:19,335 --> 00:48:21,938
RADICAL OUT OF THE BOX THINKING

1090
00:48:21,938 --> 00:48:26,810
ABOUT HOW TO PUSH YOU KNOW LIFE

1091
00:48:26,810 --> 00:48:27,610
SPAN EXPECTANCY FURTHER.

1092
00:48:27,610 --> 00:48:31,281
SO BASED ON THESE 2 STUDIES, I

1093
00:48:31,281 --> 00:48:34,818
THINK CHASING THAT 120 GOAL IS

1094
00:48:34,818 --> 00:48:36,986
DIFFICULT BUT MEAN WHILE WE CAN

1095
00:48:36,986 --> 00:48:40,123
FOCUS ON HEALTH SPAN EXTENSION

1096
00:48:40,123 --> 00:48:45,228
AND  MORBIDITY COMPRESSION.

1097
00:48:45,228 --> 00:48:47,530
AND AS I MENTIONED BEFORE, THOSE

1098
00:48:47,530 --> 00:48:49,966
2 ARE REALLY DEPENDENT ON

1099
00:48:49,966 --> 00:48:50,700
GENETICS AND EPIGENETICS BUT

1100
00:48:50,700 --> 00:48:54,471
THEN WHAT IS THE RELEVANT

1101
00:48:54,471 --> 00:48:55,538
CONTRIBUTION TO THOSE 2

1102
00:48:55,538 --> 00:48:56,606
PARAMETERS.

1103
00:48:56,606 --> 00:49:00,110
SO THIS WAS SHOWN, THAT THIS WAS

1104
00:49:00,110 --> 00:49:03,313
INTERROGATED IN THIS STUDY BACK

1105
00:49:03,313 --> 00:49:05,748
IN 1990S, USING TWINS, SO HERE

1106
00:49:05,748 --> 00:49:07,884
THE SCIENTISTS JUST SIMPLY

1107
00:49:07,884 --> 00:49:12,322
PLOTTED LIFE SPAN OF TWIN 1

1108
00:49:12,322 --> 00:49:13,790
VERSUS TWIN 2 AND YOU CAN

1109
00:49:13,790 --> 00:49:19,529
IMAGINE IF GENETICS WAS THE SOLE

1110
00:49:19,529 --> 00:49:21,264
DETERMINANT THIS WOULD BE A

1111
00:49:21,264 --> 00:49:21,731
DISCIPLINARY NAG LINE.

1112
00:49:21,731 --> 00:49:22,599
BUT THAT IS NOT THE CASE EMPLOY

1113
00:49:22,599 --> 00:49:25,301
IT'S A CLOUD OF DATA AND

1114
00:49:25,301 --> 00:49:27,504
EPIDEMIOLOGISTS SUCH AS LUIGI

1115
00:49:27,504 --> 00:49:29,439
CAN DETERMINE WHAT'S CALLED A

1116
00:49:29,439 --> 00:49:31,274
HERITABILITY SCORE FROM THIS

1117
00:49:31,274 --> 00:49:32,675
KIND OF DATA DISTRIBUTION AND IT

1118
00:49:32,675 --> 00:49:39,282
TURNS OUT THAT THE HERITABILITY

1119
00:49:39,282 --> 00:49:41,651
SCORE HERE WAS .25.

1120
00:49:41,651 --> 00:49:43,486
WHICH ESSENTIALLY MEANS THAT

1121
00:49:43,486 --> 00:49:46,656
GENETIC CANS ONLY EXPLAIN 25% OF

1122
00:49:46,656 --> 00:49:48,992
LIFE SPAN IN TWINS SUGGESTING

1123
00:49:48,992 --> 00:49:56,099
THAT THE OVERWHELMING 75% IS

1124
00:49:56,099 --> 00:49:56,566
PROBABLY ENVIRONMENTAL

1125
00:49:56,566 --> 00:49:56,866
INFLUENCES.

1126
00:49:56,866 --> 00:49:58,902
BUT BEYOND THAT A MORE RECENT

1127
00:49:58,902 --> 00:50:09,445
PAPER LOOKEDDA THE RELATIONSHIP

1128
00:50:10,313 --> 00:50:11,548
BETWEEN THE DEVELOPMENT OF

1129
00:50:11,548 --> 00:50:19,455
GENETICS, THAT IT CONTRIBUTES 2%

1130
00:50:19,455 --> 00:50:20,957
WHEREAS YOUR EXPOSOME, IS ABOUT

1131
00:50:20,957 --> 00:50:23,126
17% AND THIS WAS A VERY RECENT

1132
00:50:23,126 --> 00:50:26,095
PAPER WHICH LOOKED AT THE I

1133
00:50:26,095 --> 00:50:29,599
THINK 500,000 INDIVIDUALS AND

1134
00:50:29,599 --> 00:50:33,203
USING THE HUMAN MORTALITY

1135
00:50:33,203 --> 00:50:34,170
DATABASE.

1136
00:50:34,170 --> 00:50:39,409
SO GIVEN -- GIVEN THESE SORT OF

1137
00:50:39,409 --> 00:50:40,777
CONTRIBUTIONS, I THINK, YOU KNOW

1138
00:50:40,777 --> 00:50:42,312
MAYBE WE CAN GET A LOT OF

1139
00:50:42,312 --> 00:50:44,948
INSIGHTS IF WE LOOK INTO GENETIC

1140
00:50:44,948 --> 00:50:45,815
MECHANISMS WHICH IS SOMETHING

1141
00:50:45,815 --> 00:50:47,517
THAT I AM GREATLY INTERESTED IN

1142
00:50:47,517 --> 00:50:49,485
BUT THAT DOESN'T MEAN THAT WE

1143
00:50:49,485 --> 00:50:51,988
SHOULDN'T BE LOOKING AT

1144
00:50:51,988 --> 00:50:52,488
GENETICS, RIGHT?

1145
00:50:52,488 --> 00:50:58,628
AND SOME PEOPLE HAVE BEEN

1146
00:50:58,628 --> 00:51:01,064
STUDYING GENE VARIANTS FROM

1147
00:51:01,064 --> 00:51:03,566
CENTENARIANS FOR EXAMPLE, AND

1148
00:51:03,566 --> 00:51:04,734
THEY'VE BEEN PUTTING THOSE CELLS

1149
00:51:04,734 --> 00:51:07,303
IN CULTURE AND SEE IF THOSE

1150
00:51:07,303 --> 00:51:08,805
CELLS HAVE INCREASED CELLULAR

1151
00:51:08,805 --> 00:51:11,341
STRESS RESISTANCE OR MAYBE SOME

1152
00:51:11,341 --> 00:51:13,643
OTHER ADVANTAGES, SUCH AS TUMOR

1153
00:51:13,643 --> 00:51:15,945
SUPPRESS AND SUCH SO THAT IS 1

1154
00:51:15,945 --> 00:51:18,881
WAY TO LOOK AT THE FUNCTION OF

1155
00:51:18,881 --> 00:51:24,420
THESE  LONGEVITY GENE VARIANTS.

1156
00:51:24,420 --> 00:51:26,422
BUT ANOTHER WAY I WOULD TALK

1157
00:51:26,422 --> 00:51:28,992
ABOUT BRIEFLY IS THE COMPARITTOR

1158
00:51:28,992 --> 00:51:30,960
BIOLOGY, SO THIS IS THIS

1159
00:51:30,960 --> 00:51:31,694
INCREDIBLE POSITIVE CORRELATION

1160
00:51:31,694 --> 00:51:33,096
BETWEEN BODY MASS AND MAXIMUM

1161
00:51:33,096 --> 00:51:34,931
LIFE SPAN.

1162
00:51:34,931 --> 00:51:37,567
SO HERE, THIS IS A DIAGRAM THAT

1163
00:51:37,567 --> 00:51:39,002
ONLY SHOWS MAMMALS BUT EVEN

1164
00:51:39,002 --> 00:51:40,503
WITHIN MAMMALS, YOU CAN SEE THAT

1165
00:51:40,503 --> 00:51:43,573
YOU KNOW, ON THIS END OF THE

1166
00:51:43,573 --> 00:51:47,043
SPECTRUM, THE LONG LIFE SPAN

1167
00:51:47,043 --> 00:51:50,246
ANIMALS ARE ALL LARGE MAMMALS

1168
00:51:50,246 --> 00:51:52,849
SUCH AS THE BULL HEAD WHALE AND

1169
00:51:52,849 --> 00:51:54,917
HUMP BACK WHALE AND SO ON, AND

1170
00:51:54,917 --> 00:51:55,885
THEN ON THIS END OF THE SHORT

1171
00:51:55,885 --> 00:51:58,154
END OF THE SPECTRUM, YOU HAVE

1172
00:51:58,154 --> 00:51:58,988
THESE RODENTS LIKE SMALL MICE

1173
00:51:58,988 --> 00:52:00,590
AND RATS AND SUCH.

1174
00:52:00,590 --> 00:52:02,892
SO IF YOU NOTICE, HUMANS ARE

1175
00:52:02,892 --> 00:52:05,995
PRETTY MUCH AT THIS END OF THE

1176
00:52:05,995 --> 00:52:07,597
SPECTRUM, EVEN THOUGH WE ARE NOT

1177
00:52:07,597 --> 00:52:10,533
REALLY THAT LARGE OF AN ANIMAL.

1178
00:52:10,533 --> 00:52:13,136
SO THAT'S WHY I THINK AS HUMANS

1179
00:52:13,136 --> 00:52:14,704
MAYBE DUE TO OUR EVOLVED BRAINS

1180
00:52:14,704 --> 00:52:16,306
OR SOMETHING, WE MAY HAVE

1181
00:52:16,306 --> 00:52:18,975
ALREADY PUSHED THE LIMITS OF THE

1182
00:52:18,975 --> 00:52:21,577
LONGEVITY TO SOME EXTENT AND

1183
00:52:21,577 --> 00:52:24,347
THAT'S WHAT I BELIEVE, SO

1184
00:52:24,347 --> 00:52:24,947
COMPARATIVE BIOLOGIST THOUGH,

1185
00:52:24,947 --> 00:52:28,518
WHAT THEY DO IS THEY STUDY

1186
00:52:28,518 --> 00:52:29,986
WITHIN A PARTICULAR AND THEY

1187
00:52:29,986 --> 00:52:33,089
LOOK AT LIFE SPAN VARIATION

1188
00:52:33,089 --> 00:52:33,990
BETWEEN SPECIES WITHIN THAT

1189
00:52:33,990 --> 00:52:35,024
GROUP.

1190
00:52:35,024 --> 00:52:39,595
SO FOR EXAMPLE, A CURIOUS CASE

1191
00:52:39,595 --> 00:52:43,499
IS OF THE ORDER RODENTS, ON 1

1192
00:52:43,499 --> 00:52:45,435
END OF THE SPECTRUM LIKE MICE

1193
00:52:45,435 --> 00:52:47,837
AND RATS THAT LIVE MAYBE 5 YEARS

1194
00:52:47,837 --> 00:52:49,439
BUT ON THE OTHER END OF THE

1195
00:52:49,439 --> 00:52:52,442
SPECTRUM YOU HAVE THESE REALLY

1196
00:52:52,442 --> 00:52:54,277
STRANGE ANIMALS, THE BLIND MOLE

1197
00:52:54,277 --> 00:52:56,279
RAT AND THE NAKED MOLE RAT THAT

1198
00:52:56,279 --> 00:52:58,815
LIVE UP TO 20 OR 30 YEARS WHICH

1199
00:52:58,815 --> 00:53:03,419
IS INCREDIBLY LONG LIFE SPANS.

1200
00:53:03,419 --> 00:53:07,457
SO WHAT DO COMPARATIVE

1201
00:53:07,457 --> 00:53:09,592
BIOLOGISTS DO, IS THEY GO INTO

1202
00:53:09,592 --> 00:53:11,561
THESE ANIMALS AND THEY TRY TO

1203
00:53:11,561 --> 00:53:15,631
FIND OUT WHAT'S DIFFERENT IN THE

1204
00:53:15,631 --> 00:53:17,800
MOLECULAR COMPOSITION AS WELL AS

1205
00:53:17,800 --> 00:53:19,502
GENETIC COMPOSITION OF THESE

1206
00:53:19,502 --> 00:53:22,605
ANIMALS VERSUS THESE ANIMALS.

1207
00:53:22,605 --> 00:53:24,173
SO WHAT THEY FOUND WAS, AND THIS

1208
00:53:24,173 --> 00:53:28,244
IS JUST 1 EXAMPLE, BOTH NAKED

1209
00:53:28,244 --> 00:53:31,748
MOLE RAT AND BLIND MOLE RATS

1210
00:53:31,748 --> 00:53:41,324
HAVE THIS LONG OR THIS HIGH

1211
00:53:41,324 --> 00:53:44,026
MOLECULAR MASS, HYALLUREONIC

1212
00:53:44,026 --> 00:53:45,428
ACID, IS HELPS YOUR SKIN, JOINTS

1213
00:53:45,428 --> 00:53:46,963
AND HELPS TO RETAIN WATER, AND

1214
00:53:46,963 --> 00:53:50,867
WHAT THEY FOUND WAS THIS

1215
00:53:50,867 --> 00:53:51,601
PARTICULAR MOLECULE PREFERS

1216
00:53:51,601 --> 00:53:53,102
STRESS RESISTANCE TO THE CELLS

1217
00:53:53,102 --> 00:53:55,938
DERIVE FRIDAY THESE 2 KINDS OF

1218
00:53:55,938 --> 00:53:58,775
RATS AND THEN IN THE CASE OF THE

1219
00:53:58,775 --> 00:54:00,510
BLIND -- SORRY, THE NAKED MOLE

1220
00:54:00,510 --> 00:54:04,914
RAT, IF YOU HAVE THIS MOLECULE,

1221
00:54:04,914 --> 00:54:06,816
IT ALSO HELPS IN EARLY CONTACT

1222
00:54:06,816 --> 00:54:08,785
INHIBITION, SO IF YOU TAKE

1223
00:54:08,785 --> 00:54:10,620
FIBROBLASTS FROM THESE RATS, PUT

1224
00:54:10,620 --> 00:54:13,790
THEM IN A DISH, YOUR SOLES DON'T

1225
00:54:13,790 --> 00:54:15,458
GROW ON TOP OF EACH OTHER, SO AS

1226
00:54:15,458 --> 00:54:18,528
SOON AS THE NEIGHBORS TOUCH EACH

1227
00:54:18,528 --> 00:54:19,629
OTHER, THEY UNDERGO

1228
00:54:19,629 --> 00:54:20,596
PROLIFERATIVE ARREST.

1229
00:54:20,596 --> 00:54:23,399
SO THEY HAVE VERY POTENT EARLY

1230
00:54:23,399 --> 00:54:24,434
CONTACT INHIBITION IS THIS CAN

1231
00:54:24,434 --> 00:54:26,869
BE PART OF AS A CANCER

1232
00:54:26,869 --> 00:54:35,278
RESISTANCE MECHANISM, SO WITH

1233
00:54:35,278 --> 00:54:36,512
IMPROVED STRESS RESISTANCE,

1234
00:54:36,512 --> 00:54:38,147
CANCER RESISTANCE, THEY CAN

1235
00:54:38,147 --> 00:54:40,349
PERHAPS EXTEND THEIR LIFE SPANS,

1236
00:54:40,349 --> 00:54:41,951
BUT BEYOND THESE EXTREME

1237
00:54:41,951 --> 00:54:43,453
LONGEVITY CREATURES, YOU KNOW

1238
00:54:43,453 --> 00:54:47,423
WE'VE LEARNED A LOT FROM OUR

1239
00:54:47,423 --> 00:54:52,929
ARGUMENTS OVER THE YEARS AND I

1240
00:54:52,929 --> 00:54:58,768
MYSELF, I STARTED MY CAREER

1241
00:54:58,768 --> 00:54:59,702
LOOKING AND STUDYING YEAST.

1242
00:54:59,702 --> 00:55:02,905
SO HERE I'M SHOWING AGING AND

1243
00:55:02,905 --> 00:55:04,941
LONGEVITY STUDIES SO YEAST AND

1244
00:55:04,941 --> 00:55:06,209
WORMS AND FLIES HAVE CONTRIBUTED

1245
00:55:06,209 --> 00:55:10,179
A LOT TO OUR UNDERSTANDING OF

1246
00:55:10,179 --> 00:55:13,716
THE NUTRIENT SIGNALING LIKE THE

1247
00:55:13,716 --> 00:55:16,752
MTORE PATHWAY OR INSULIN

1248
00:55:16,752 --> 00:55:19,188
PATHWAY, SO THEN WE STARTED

1249
00:55:19,188 --> 00:55:21,390
GETTING MORE VERTEBRATE MODELS

1250
00:55:21,390 --> 00:55:24,861
OF AGING LIKE ZEBRAFISH AND THE

1251
00:55:24,861 --> 00:55:27,296
NEW KELLY FISH MODEL, AND THIS

1252
00:55:27,296 --> 00:55:29,065
KELLY FISH ONLY LIVES 6 MONTHS

1253
00:55:29,065 --> 00:55:31,701
SO VERY EASY TO DO LIFE SPAN

1254
00:55:31,701 --> 00:55:33,436
STUDIES ON, RODENTS OBVIOUSLY

1255
00:55:33,436 --> 00:55:35,338
HAVE CONTRIBUTED A LOT, AND

1256
00:55:35,338 --> 00:55:36,672
CONTINUE TO DO SO, RECENTLY, YOU

1257
00:55:36,672 --> 00:55:40,743
MAY HAVE HEARD OF THE AGING

1258
00:55:40,743 --> 00:55:43,312
PROJECT THAT WAS AT SOME POINT

1259
00:55:43,312 --> 00:55:44,547
FUNDED BY NIH, AND YOU KNOW

1260
00:55:44,547 --> 00:55:46,749
WE'VE LEARNED A LOT FROM THAT

1261
00:55:46,749 --> 00:55:50,686
PROJECT, AND YOU MAY HAVE

1262
00:55:50,686 --> 00:55:54,957
RECENTLY HEARD OF A PARTICULAR

1263
00:55:54,957 --> 00:56:00,630
MOLECULE BEING EVALUATED BY FDA

1264
00:56:00,630 --> 00:56:03,165
FOR MOLECULES TARGETING METADOLL

1265
00:56:03,165 --> 00:56:04,367
BOLLICI AND PRIMATES ARE CLOSE

1266
00:56:04,367 --> 00:56:06,669
TO HUMANS AND IF YOU WANT TO

1267
00:56:06,669 --> 00:56:08,304
STUDY HUMANS THEMSELVES, CAN YOU

1268
00:56:08,304 --> 00:56:10,573
STUDY HUMAN CELLS AND ORGANOIDS

1269
00:56:10,573 --> 00:56:12,341
AND MAYBE EVEN DIRECTLY LOOK AT

1270
00:56:12,341 --> 00:56:13,042
TISSUE BIOPSIES.

1271
00:56:13,042 --> 00:56:17,613
SO WHAT WE HAVE WE REALLY

1272
00:56:17,613 --> 00:56:19,081
LEARNED FROM ALL THOSE MODEL

1273
00:56:19,081 --> 00:56:21,384
SYSTEMS AND ORGANISMS. 

1274
00:56:21,384 --> 00:56:23,219
WE HAVE LEARNED THAT THERE ARE

1275
00:56:23,219 --> 00:56:24,520
CERTAIN MOLECULAR PATTERNS THAT

1276
00:56:24,520 --> 00:56:26,255
EMERGE DURING AGE XG THESE HAVE

1277
00:56:26,255 --> 00:56:31,761
BEEN ORGANIZED INTO WHAT'S CALLS

1278
00:56:31,761 --> 00:56:32,862
FOR SPECULATIONED THE HALLMARKS

1279
00:56:32,862 --> 00:56:34,430
OF AGING AND THERE ARE 12 OF

1280
00:56:34,430 --> 00:56:36,966
THEM AND THEY ARE CATEGORIZED

1281
00:56:36,966 --> 00:56:38,167
INTO THESE 3 GROUPS.

1282
00:56:38,167 --> 00:56:39,602
IN BLUE ARE THE PRIMARY

1283
00:56:39,602 --> 00:56:42,405
HALLMARKS WHICH ARE THE MOST

1284
00:56:42,405 --> 00:56:50,713
UPSTREAM, MAYBE HER HAPPENS EVEN

1285
00:56:50,713 --> 00:56:52,381
CAUSAL CHANGES THAT OCCUR, MORE

1286
00:56:52,381 --> 00:56:54,150
CELLULAR RESPONSE TO THE PRIMARY

1287
00:56:54,150 --> 00:56:55,484
CHANGES AND FINALLY INTEGRATIVE

1288
00:56:55,484 --> 00:57:00,756
HALLMARK IS MORE OF A SYSTEMIC

1289
00:57:00,756 --> 00:57:02,725
RESPONSE TO THE PRIMARY AND

1290
00:57:02,725 --> 00:57:03,759
ANTAGONISTIC CHANGES.

1291
00:57:03,759 --> 00:57:05,294
NOW EVEN THOUGH THESE DIFFERENT

1292
00:57:05,294 --> 00:57:07,697
HALLMARKS IN THIS PICTURE LOOK

1293
00:57:07,697 --> 00:57:09,165
VERY DISCONNECTED FROM EACH

1294
00:57:09,165 --> 00:57:10,800
OTHER, THE TRUTH IS THEY ARE

1295
00:57:10,800 --> 00:57:12,768
VERY MUCH CONNECTED SO FOR

1296
00:57:12,768 --> 00:57:16,072
EXAMPLE, GENOMIC INSTABILITY CAN

1297
00:57:16,072 --> 00:57:18,841
AUSCELLULAR SENESCENCE RESPONSE,

1298
00:57:18,841 --> 00:57:19,875
AND THEN SENESCENT CELLS AND I

1299
00:57:19,875 --> 00:57:21,877
WILL TALK ABOUT THIS A LOT MORE,

1300
00:57:21,877 --> 00:57:24,914
THEY RELEASE A WHOLE LOT OF PRO

1301
00:57:24,914 --> 00:57:28,050
INFLAMMATORY CYTOKINES AND THAT

1302
00:57:28,050 --> 00:57:31,487
CAN CAUSE, YOU KNOW, CHRONIC

1303
00:57:31,487 --> 00:57:32,989
INFLAMMATION SYSTEMICALLY.

1304
00:57:32,989 --> 00:57:34,190
SIMILARLY ALL OTHER HALLMARKS

1305
00:57:34,190 --> 00:57:35,458
ARE IN SOME WAY CONNECTED TO

1306
00:57:35,458 --> 00:57:37,193
EACH OTHER FORM THANKSGIVING

1307
00:57:37,193 --> 00:57:39,028
REALLY COMPLEX NETWORK, WHICH I

1308
00:57:39,028 --> 00:57:41,397
THINK IS BOTH GOOD AND BAD.

1309
00:57:41,397 --> 00:57:45,034
IT IS BAD BECAUSE IT IS

1310
00:57:45,034 --> 00:57:46,736
IMPOSSIBLE ALMOST, TO DETERMINE

1311
00:57:46,736 --> 00:57:47,136
CAUSALITY.

1312
00:57:47,136 --> 00:57:49,572
YOU DON'T KNOW WHAT HAPPENS

1313
00:57:49,572 --> 00:57:50,606
FIRST, WHAT HAPPENS SECOND, BUT

1314
00:57:50,606 --> 00:57:54,644
IT IS GOOD BECAUSE IN CASE YOU

1315
00:57:54,644 --> 00:57:56,045
SOMEHOW DISCOVER AN INTERVENTION

1316
00:57:56,045 --> 00:57:57,446
THAT MOVES 1 OF THESE HIGH

1317
00:57:57,446 --> 00:57:59,081
MARKS, IT WILL LIKELY MOVE THE

1318
00:57:59,081 --> 00:58:03,285
OTHER HALLMARKS AS WELL IN THE

1319
00:58:03,285 --> 00:58:06,889
BENEFICIAL DIRECTION, SO WHICH

1320
00:58:06,889 --> 00:58:08,858
MEANS ESSENTIALLY THAT AGING

1321
00:58:08,858 --> 00:58:10,559
PERHAP SYSTEM TARGETABLE.

1322
00:58:10,559 --> 00:58:12,628
SO BECAUSE, YOU KNOW, WE DON'T

1323
00:58:12,628 --> 00:58:14,730
HAVE AS MUCH TIME TODAY, I WILL

1324
00:58:14,730 --> 00:58:16,799
QUICKLY, YOU KNOW DELVE A LITTLE

1325
00:58:16,799 --> 00:58:19,001
BIT DEEPER INTO 3 OF THESE

1326
00:58:19,001 --> 00:58:22,505
HALLMARKS, THE FIRST 1 WOULD BE

1327
00:58:22,505 --> 00:58:23,806
A PRIMARY 1, EPIGENETIC

1328
00:58:23,806 --> 00:58:27,309
ALTERATIONS AND THEN CELLULAR

1329
00:58:27,309 --> 00:58:29,045
SENESCENCE FROM THE CATEGORY AND

1330
00:58:29,045 --> 00:58:31,280
THEN CHRONIC INFLAMMATION FROM

1331
00:58:31,280 --> 00:58:33,315
THE INTEGRATIVE PATHWAY.

1332
00:58:33,315 --> 00:58:34,984
SO FIRST EPIGENETIC ALTERATIONS

1333
00:58:34,984 --> 00:58:37,753
AND AS I MENTIONED, THIS IS WHAT

1334
00:58:37,753 --> 00:58:40,189
I STUDY IN MY OWN LAB, SO WHEN I

1335
00:58:40,189 --> 00:58:45,861
WAS A POST DOC, WE YOU KNOW RAN

1336
00:58:45,861 --> 00:58:46,696
THIS REVIEW, ALMOST 10 YEARS

1337
00:58:46,696 --> 00:58:48,898
AGO, BUT WHAT WE DID WAS WE

1338
00:58:48,898 --> 00:58:50,833
COMBINED INFORMATION FROM

1339
00:58:50,833 --> 00:58:52,234
LITERATURE ACROSS MODEL

1340
00:58:52,234 --> 00:58:55,504
ORGANISMS TO BRING OUT CERTAIN

1341
00:58:55,504 --> 00:58:57,873
THEMEATIC CHANGES THAT ARE KNOWN

1342
00:58:57,873 --> 00:59:00,176
TO HAPPEN TO OUR EPIGENOME.

1343
00:59:00,176 --> 00:59:03,045
AND WHEN I TALK ABOUT EPIGENETIC

1344
00:59:03,045 --> 00:59:05,681
ALTERATIONS, I MEAN CHANGES IN

1345
00:59:05,681 --> 00:59:08,751
OUR NUCLEUS, IN THE CHROMATIN

1346
00:59:08,751 --> 00:59:13,189
COMPLEX, MADE UP OF HISTONE, SO

1347
00:59:13,189 --> 00:59:15,157
1 THING THAT HAPPENS WITH AGE IS

1348
00:59:15,157 --> 00:59:16,892
LOSS OF HISTONES AND THIS AS YOU

1349
00:59:16,892 --> 00:59:20,696
CAN IMAGINE OPENS UP OUR GENOME

1350
00:59:20,696 --> 00:59:23,833
AND FIRST DISCOVERED IN YEAST.

1351
00:59:23,833 --> 00:59:24,667
NEXT.

1352
00:59:24,667 --> 00:59:26,802
WE MAY HAVE IMBALANCE OF HISTONE

1353
00:59:26,802 --> 00:59:28,537
MODIFICATION, SO THERE ARE

1354
00:59:28,537 --> 00:59:29,805
CERTAIN MODIFICATIONS ON

1355
00:59:29,805 --> 00:59:32,875
HISTONES WHICH ARE ACTIVATING,

1356
00:59:32,875 --> 00:59:34,276
SOME ARE REPRESSIVE, IN VIEW,

1357
00:59:34,276 --> 00:59:36,679
THERE IS A BALANCE BETWEEN THE

1358
00:59:36,679 --> 00:59:38,581
2, BUT AS WE.

1359
00:59:38,581 --> 00:59:39,315
 Q.OLDER THERE IS THIS

1360
00:59:39,315 --> 00:59:40,149
BALANCE AND THERE ARE

1361
00:59:40,149 --> 00:59:44,920
MANY STUDIES ON THIS:

1362
00:59:44,920 --> 00:59:46,055
PERHAPS THE BEST STUDY AND MAYBE

1363
00:59:46,055 --> 00:59:49,058
MOST OF YOU HAVE HEARD ABOUT

1364
00:59:49,058 --> 00:59:50,693
EPIGENETIC CLOCKS WHICH ARE

1365
00:59:50,693 --> 00:59:52,995
BASED ON DNA METHYLATION READ

1366
00:59:52,995 --> 00:59:54,463
OUTS ESSENTIALLY AND I WILL TALK

1367
00:59:54,463 --> 00:59:57,366
ABOUT THIS A BIT MORE AS WELL,

1368
00:59:57,366 --> 00:59:59,034
THEN WE HAVE CHROMATIN

1369
00:59:59,034 --> 01:00:01,771
REMODELING, NOT MUCH IS KNOWN

1370
01:00:01,771 --> 01:00:03,839
ABOUT IT BUT THESE ARE PROCESSES

1371
01:00:03,839 --> 01:00:05,474
AND IT DECLINES WITH AGE, WE

1372
01:00:05,474 --> 01:00:08,277
ALSO HAVE FOCAL AND

1373
01:00:08,277 --> 01:00:09,011
HETEROCHROMATIN FORMATION,

1374
01:00:09,011 --> 01:00:10,279
ESSENTIALLY THIS MEANS THERE ARE

1375
01:00:10,279 --> 01:00:13,149
ALTERATIONS IN THE 3D GENOME

1376
01:00:13,149 --> 01:00:15,351
THAT IS HOW THE GENOME FOLDS

1377
01:00:15,351 --> 01:00:17,987
WITHIN OUR NUCLEUS, AND ALL OF

1378
01:00:17,987 --> 01:00:19,088
THESE DIFFERENT EPIGENETIC

1379
01:00:19,088 --> 01:00:21,390
CHANGES ARE ACTUALLY TRIGGERED

1380
01:00:21,390 --> 01:00:22,725
BY 1 UPSTREAM PROCESS WHICH IS

1381
01:00:22,725 --> 01:00:25,361
THE BREAK DOWN OF THE NUCLEAR

1382
01:00:25,361 --> 01:00:30,432
LAMINA, SO YOU CAN THINK OF THE

1383
01:00:30,432 --> 01:00:33,135
LAMINA AS THIS NETWORK OF

1384
01:00:33,135 --> 01:00:35,838
PROTEINS ON THE PERIPHERY OF THE

1385
01:00:35,838 --> 01:00:37,606
NUCLEUS AND OUR GENOME ATTACHES,

1386
01:00:37,606 --> 01:00:39,375
CERTAIN PARTS OF OUR GENOME

1387
01:00:39,375 --> 01:00:43,679
ATTACHES TO THE NUCLEAR LAMINA,

1388
01:00:43,679 --> 01:00:44,713
AND THEY ATTACH BECAUSE THEY

1389
01:00:44,713 --> 01:00:46,816
WANT TO BE KEPT REPRESSED OR

1390
01:00:46,816 --> 01:00:49,819
CONDENSES AND YOU CAN IMAGINE IF

1391
01:00:49,819 --> 01:00:52,655
THE LAMINA BREAKS DOWN, THOSE

1392
01:00:52,655 --> 01:00:59,261
GENOMIC REGIONS CAN DETACH THEY

1393
01:00:59,261 --> 01:01:00,529
CAN BECOME DEPRESSED AND

1394
01:01:00,529 --> 01:01:02,298
ATTACHED TO CELLS AND ALL OF

1395
01:01:02,298 --> 01:01:04,266
THESE TOGETHER HAVE

1396
01:01:04,266 --> 01:01:05,968
TRANSCRIPTIONAL OUTCOMES THAT I

1397
01:01:05,968 --> 01:01:06,468
WILL DISCUSS.

1398
01:01:06,468 --> 01:01:09,438
SO, I THINK IF YOU WERE TO

1399
01:01:09,438 --> 01:01:13,843
SYNERGIZE ALL OF THESE

1400
01:01:13,843 --> 01:01:15,811
EPIGENETIC OLTERATIONS AND

1401
01:01:15,811 --> 01:01:18,113
PROPOSE 1 FUNDAMENTAL MODEL OF

1402
01:01:18,113 --> 01:01:19,715
EPIGENETIC OPERATIONS AND AGING,

1403
01:01:19,715 --> 01:01:21,917
I THINK THE MOST VIABLE 1 WOULD

1404
01:01:21,917 --> 01:01:25,421
BE THE LOSS OF HETEROCHROMATIN

1405
01:01:25,421 --> 01:01:25,754
MODEL IMAGING.

1406
01:01:25,754 --> 01:01:27,156
SO WHAT DO I MEAN BY THAT?

1407
01:01:27,156 --> 01:01:29,024
SO AS I TOLD YOU CERTAIN REGIONS

1408
01:01:29,024 --> 01:01:33,028
OF THE GENOME ARE CONSTITTATIVE

1409
01:01:33,028 --> 01:01:34,096
HETEROCHROMATIN AND BOUND TO THE

1410
01:01:34,096 --> 01:01:37,266
LAMINA, AND I JUST CALLED THEM

1411
01:01:37,266 --> 01:01:38,334
HETEROCHROMATIN FOR SIMPLICITY.

1412
01:01:38,334 --> 01:01:39,835
AND OTHER REGIONS OF OUR GENOME

1413
01:01:39,835 --> 01:01:42,471
WHICH ARE AWAY FROM THE NUCLEAR

1414
01:01:42,471 --> 01:01:46,342
LAMINA, AND ARE MOSTLY OPEN NOW

1415
01:01:46,342 --> 01:01:48,277
IN YOUTH, THERE'S A PERFECT

1416
01:01:48,277 --> 01:01:49,378
BALANCE BETWEEN THE 2, BUT WITH

1417
01:01:49,378 --> 01:01:52,915
AGE, WHAT HAPPENS IS THAT THE

1418
01:01:52,915 --> 01:01:55,951
HETEROCHROMATIN OPENS UP WHEREAS

1419
01:01:55,951 --> 01:01:57,786
IN THE U-CHROMATIN YOU CAN GET

1420
01:01:57,786 --> 01:01:59,788
OTHER CHANGES WHICH INCLUDES

1421
01:01:59,788 --> 01:02:01,957
SOME REGIONS OPENING AND SOME

1422
01:02:01,957 --> 01:02:02,391
CLOSING.

1423
01:02:02,391 --> 01:02:05,027
BUT THE MOST DELETEEROUS EFFECT

1424
01:02:05,027 --> 01:02:06,595
IS REALLY FROM THE

1425
01:02:06,595 --> 01:02:07,329
HETEROCHROMATIN OPENING AND WHY

1426
01:02:07,329 --> 01:02:09,365
IS THAT BECAUSE THE

1427
01:02:09,365 --> 01:02:11,800
HETEROCHROMATIN, THE

1428
01:02:11,800 --> 01:02:13,602
CONSTITTATIVE HETEROCHROMATIN

1429
01:02:13,602 --> 01:02:17,139
THEY HAVE CERTAIN VIRAL ELEMENTS

1430
01:02:17,139 --> 01:02:18,874
AND SO THIS IS A LONG TIME AGO

1431
01:02:18,874 --> 01:02:22,745
AND THESE ARE CALLED

1432
01:02:22,745 --> 01:02:23,512
RETROTRANSPOSON ELEMENTS AND

1433
01:02:23,512 --> 01:02:25,748
THESE NEED TO BE KEPT TO

1434
01:02:25,748 --> 01:02:26,348
REPRESSED AND SILENT.

1435
01:02:26,348 --> 01:02:28,017
SO IF THESE REGIONS NOW START

1436
01:02:28,017 --> 01:02:32,187
OPENING UP, YOU CAN IMAGINE THE

1437
01:02:32,187 --> 01:02:34,623
CONSEQUENCES, SO IN HIGHLIGHT 1

1438
01:02:34,623 --> 01:02:36,191
PAPER THAT STUDIED PRECISELY

1439
01:02:36,191 --> 01:02:39,728
THIS IS THIS WAS FROM JOHN'S

1440
01:02:39,728 --> 01:02:41,230
GROUP, PUBLISHED IN TWEBT 19 AND

1441
01:02:41,230 --> 01:02:42,631
THEY FOUND, THEY BASICALLY

1442
01:02:42,631 --> 01:02:45,034
LOOKED AT THIS 1 TYPE OF

1443
01:02:45,034 --> 01:02:51,140
TRANSPOSE ON, CALLED L1 OR 9-1,

1444
01:02:51,140 --> 01:02:53,108
RNA EXPRESSION WENT UP IN

1445
01:02:53,108 --> 01:02:54,476
SENESCENT CELL WHICH IS IS IN

1446
01:02:54,476 --> 01:02:57,980
GRAY HERE, THE YELLOW IS

1447
01:02:57,980 --> 01:02:59,381
PROLIFERATING CELLS OR LEAD

1448
01:02:59,381 --> 01:03:03,652
PASSAGE CELLS AND THE EXPRESSION

1449
01:03:03,652 --> 01:03:05,921
OF LINE 1 RESULT INDEED

1450
01:03:05,921 --> 01:03:09,591
EXPRESSION OF INTERFERON PATHWAY

1451
01:03:09,591 --> 01:03:14,763
GENES AND THIS WAS A LATE

1452
01:03:14,763 --> 01:03:15,497
SENESCENCE EVENT.

1453
01:03:15,497 --> 01:03:16,365
THROUGH OTHER EXPERIMENTS WE

1454
01:03:16,365 --> 01:03:18,267
DETERMINED WHICH WAS NOT REALLY

1455
01:03:18,267 --> 01:03:19,635
THE MRNA, ALTHOUGH THAT MAY

1456
01:03:19,635 --> 01:03:23,072
STILL CONTRIBUTE, IT WAS MOSTLY

1457
01:03:23,072 --> 01:03:27,009
THE L1 CDNA THAT CONTRIBUTED TO

1458
01:03:27,009 --> 01:03:27,943
THIS PROINFLAMMATORY INTERFERON

1459
01:03:27,943 --> 01:03:28,210
RESPONSE.

1460
01:03:28,210 --> 01:03:30,212
SO THEY DETERMINED IF YOU

1461
01:03:30,212 --> 01:03:33,082
SOMEHOW CAN TARGET THE REVERSE

1462
01:03:33,082 --> 01:03:34,016
TRANSCRIPT ACE THAT WAS

1463
01:03:34,016 --> 01:03:36,118
CONVERTING IT THROUGH THE CDNA,

1464
01:03:36,118 --> 01:03:40,923
CAN YOU PERHAPS MITIGATE SOME OF

1465
01:03:40,923 --> 01:03:41,790
THESE CHANGES.

1466
01:03:41,790 --> 01:03:42,992
SO HERE, THAT'S EXACTLY WHAT

1467
01:03:42,992 --> 01:03:45,828
THEY DID AND THEY DID IT IN

1468
01:03:45,828 --> 01:03:47,930
MICE, WHICH IS PUBLISHED IN A

1469
01:03:47,930 --> 01:03:51,967
HIGH IMPACT JOURNAL, SO, IN OLD

1470
01:03:51,967 --> 01:03:54,903
MICE, THEY SHOWED THE EXPRESSION

1471
01:03:54,903 --> 01:04:01,076
OF THESE ELEMENTS AND LOOKING AT

1472
01:04:01,076 --> 01:04:02,845
THE PROTEIN, AND IN THIS FIGURE,

1473
01:04:02,845 --> 01:04:04,913
THEY SHOWED IF YOU TREAT THE

1474
01:04:04,913 --> 01:04:06,315
ANIMALS WITH THE REVERSE

1475
01:04:06,315 --> 01:04:09,551
TRANSCRIPT ACE, YOU CAN GET

1476
01:04:09,551 --> 01:04:11,754
SIGNATURES 95 REDUCTIONS OF

1477
01:04:11,754 --> 01:04:14,490
SEVERAL MARKERS OF SENESCENCE

1478
01:04:14,490 --> 01:04:17,559
AND AGING PRIMARILY P16, P16 IS

1479
01:04:17,559 --> 01:04:21,930
A VERY WELL KNOWN MARKER AND

1480
01:04:21,930 --> 01:04:24,099
INTERFERON A AS WELL AS

1481
01:04:24,099 --> 01:04:25,234
INTERLEUKIN 6.

1482
01:04:25,234 --> 01:04:28,404
SO I THINK IT IS ALSO IMPORTANT

1483
01:04:28,404 --> 01:04:29,938
TO TALK ABOUT DNA METHYLATION

1484
01:04:29,938 --> 01:04:34,043
WHEN WE TALK ABOUT EPIGENETIC

1485
01:04:34,043 --> 01:04:35,744
ALTERATIONS.

1486
01:04:35,744 --> 01:04:40,215
THIS WAS PIONEERED BY STEVE

1487
01:04:40,215 --> 01:04:41,617
HARBACK PRIMARILY BUT ALSO MANY

1488
01:04:41,617 --> 01:04:44,353
OTHER PEOPLE, SO ESSENTIALLY

1489
01:04:44,353 --> 01:04:47,756
WHAT HE NOTICED WAS DNA

1490
01:04:47,756 --> 01:04:50,459
METHYLATION AT CERTAIN CPGs

1491
01:04:50,459 --> 01:04:52,628
WERE REALLY WELL CORRELATED TO

1492
01:04:52,628 --> 01:04:57,132
CHRONOLOGICAL AGE AND THEN HE

1493
01:04:57,132 --> 01:04:58,967
SORT OF MODELED VARIOUS CPGs

1494
01:04:58,967 --> 01:05:00,803
AND MADE A CLOCK OUT OF IT SUCH

1495
01:05:00,803 --> 01:05:05,441
THAT YOU COULD THEN TAKE A

1496
01:05:05,441 --> 01:05:06,975
SUBSET OF THOSE CPGs AND USE

1497
01:05:06,975 --> 01:05:15,784
IT TO ESTIMATE AGE IN OTHER

1498
01:05:15,784 --> 01:05:16,919
PEOPLE.

1499
01:05:16,919 --> 01:05:19,188
I THINK LUIGI KNOWS MORE ABOUT

1500
01:05:19,188 --> 01:05:22,825
PLOTS THAN I DO BUT VERY

1501
01:05:22,825 --> 01:05:25,894
RECENTLY AGAIN, STEVE HARVATH'S

1502
01:05:25,894 --> 01:05:28,330
GROUP DEVELOPED A MAMMALIAN

1503
01:05:28,330 --> 01:05:31,166
PLOT, SO THESE ARE LESS THAN A

1504
01:05:31,166 --> 01:05:32,234
THOUSAND CPGs BUT THIS PLOT

1505
01:05:32,234 --> 01:05:35,904
YOU CAN USE IT ACROSS MANY, MANY

1506
01:05:35,904 --> 01:05:36,839
DIFFERENT MAMMALIAN SPECIES, BUT

1507
01:05:36,839 --> 01:05:41,143
TO ME WHAT WAS MOST, AND THE

1508
01:05:41,143 --> 01:05:44,680
VERY FACT YOU CAN DEVELOP THESE

1509
01:05:44,680 --> 01:05:46,982
CLOCKS SUGGEST THAT THERE'S

1510
01:05:46,982 --> 01:05:49,551
PERHAPS A PSEUDOAGING PROGRAM

1511
01:05:49,551 --> 01:05:51,920
THAT IS PRESENT IN ALL MAMMALS

1512
01:05:51,920 --> 01:05:58,494
AND PERHAPS THAT'S WHAT WE NEED

1513
01:05:58,494 --> 01:05:59,061
TO TAP INTO.

1514
01:05:59,061 --> 01:06:03,565
SO THEN WE MOVE TO SENESCENCE,

1515
01:06:03,565 --> 01:06:07,002
SO SENESCENCE IS A STATE OF CELL

1516
01:06:07,002 --> 01:06:07,603
CYCLE ARREST.

1517
01:06:07,603 --> 01:06:10,439
SENESCENT CELLS HAVE A LOT OF

1518
01:06:10,439 --> 01:06:14,009
LYSOSOMES AND YOU CAN ADD SOME

1519
01:06:14,009 --> 01:06:17,813
CHROMOGENIC SUBSTRATE AND THESE

1520
01:06:17,813 --> 01:06:26,555
LYSOSOMES, THEY HAVE AN END ZYME

1521
01:06:26,555 --> 01:06:29,491
CALLED SENESCENCE WITH THE SO

1522
01:06:29,491 --> 01:06:32,161
THIS WAS THE TRADITIONAL RATE,

1523
01:06:32,161 --> 01:06:35,764
SENESCENT CELLS FOR SORT OF

1524
01:06:35,764 --> 01:06:36,698
FIRST ASSAYED BUT SINCE THEN

1525
01:06:36,698 --> 01:06:39,434
WE'VE COME TO KNOW A LOT MORE

1526
01:06:39,434 --> 01:06:40,569
ABOUT SENESCENT, IT'S NOT JUST

1527
01:06:40,569 --> 01:06:42,671
THE LIES STUDIES OF MULTIPLE

1528
01:06:42,671 --> 01:06:44,139
ENDOCRINAL CONTENT, BUT THERE

1529
01:06:44,139 --> 01:06:47,476
ARE MANY, MANY RPGHT FEATURES,

1530
01:06:47,476 --> 01:06:48,744
BUT PERHAPS 2 VERY IMPORTANT

1531
01:06:48,744 --> 01:06:52,181
FEATURES ARE THE RESISTANCE TO

1532
01:06:52,181 --> 01:06:54,016
APOP TOAZIS AND SENESCENT CELLS

1533
01:06:54,016 --> 01:06:59,421
DON'T DIE  VERY EASILY, AND THEN

1534
01:06:59,421 --> 01:07:06,128
THE RELEASE OF A LOT OF

1535
01:07:06,128 --> 01:07:06,728
PROINFLAMMATORY PHENOTYPE.

1536
01:07:06,728 --> 01:07:17,239
BY TAPPING OR TARGETING THIS,

1537
01:07:17,973 --> 01:07:20,309
PEOPLE HAVE TARGETED CERTAIN

1538
01:07:20,309 --> 01:07:26,148
TYPES OF DRUGS FOR THERAPEUTICS

1539
01:07:26,148 --> 01:07:29,952
FOR EXAMPLE, 2 CLASS OF DRUGS,

1540
01:07:29,952 --> 01:07:38,527
CENOMORPH  ICS AND THEY TARGET D

1541
01:07:38,527 --> 01:07:39,795
PREVENT THE FORMATION OF THESE.

1542
01:07:39,795 --> 01:07:44,433
SO NOW, THE QUESTION IS, YOU

1543
01:07:44,433 --> 01:07:46,735
KNOW IS CELLULAR SENESCENCE EVEN

1544
01:07:46,735 --> 01:07:47,436
RELEVANT IN PEOPLE.

1545
01:07:47,436 --> 01:07:52,140
SO I THINK THESE 2 PAPERS BY

1546
01:07:52,140 --> 01:07:54,409
DARREN'S GROUP BACK IN 2011 WHEN

1547
01:07:54,409 --> 01:07:57,613
HE FIRST POINTED OUT IT'S REALLY

1548
01:07:57,613 --> 01:07:59,147
A CRUCIAL ROLE IN VIVO, AND WHAT

1549
01:07:59,147 --> 01:08:04,886
THEY DID WAS, THIS IS A CLEVER

1550
01:08:04,886 --> 01:08:06,955
PHARMA CO GENETIC APPROACH AND I

1551
01:08:06,955 --> 01:08:08,790
WON'T GO THROUGH THIS TOO MUCH

1552
01:08:08,790 --> 01:08:12,327
BUT ESSENTIALLY JUST BY ADDING

1553
01:08:12,327 --> 01:08:17,633
THIS MOLECULE, YOU CAN INVOKE

1554
01:08:17,633 --> 01:08:19,701
APOPTOSIS IN THE CELLS, AND WHY

1555
01:08:19,701 --> 01:08:21,003
THE CELLS BECAUSE THIS CONCEPT

1556
01:08:21,003 --> 01:08:23,405
HERE IS DRIVEN BY THE P16

1557
01:08:23,405 --> 01:08:26,008
PROMOTER WHICH IS EXPRESSED IN

1558
01:08:26,008 --> 01:08:31,513
SENESCENCE AND WE CAN TALK ABOUT

1559
01:08:31,513 --> 01:08:35,250
WYOMING THEY MAY NOT BE

1560
01:08:35,250 --> 01:08:35,717
COMPLETELY TRUE.

1561
01:08:35,717 --> 01:08:39,288
ANYWAY, THIS IS A MECHANISM AND

1562
01:08:39,288 --> 01:08:43,125
IT IS IN A NATURAL AGING MODEL,

1563
01:08:43,125 --> 01:08:47,062
ADDITIONAL THE MOLECULE  LOWERED

1564
01:08:47,062 --> 01:08:48,897
SEN ILLEGALSEN CESSENTS CAN

1565
01:08:48,897 --> 01:08:50,499
IMPROVE LIFE SPAN AS WELL AS

1566
01:08:50,499 --> 01:08:50,866
HEALTH SPAN.

1567
01:08:50,866 --> 01:08:55,570
SINCE THEN A LOT OF EFFORT HAS

1568
01:08:55,570 --> 01:08:58,373
BEEN DEDICATED TO FINDING THE

1569
01:08:58,373 --> 01:08:59,641
RIGHT SENESCENCE MARKERS ACROSS

1570
01:08:59,641 --> 01:09:01,143
DIFFERENT TISSUES BUT THAT HAS

1571
01:09:01,143 --> 01:09:04,980
PROVED TO BE QUITE DIFFICULT

1572
01:09:04,980 --> 01:09:06,948
BECAUSE SENESCENT MARKERS IN

1573
01:09:06,948 --> 01:09:08,984
PEOPLE ARE HIGHLY HETEROGENEOUS

1574
01:09:08,984 --> 01:09:13,355
AND IT GAVE BIRTH TO THE SENNET

1575
01:09:13,355 --> 01:09:15,357
CONSORTIUM FROM NIH THAT FIND

1576
01:09:15,357 --> 01:09:17,726
THIS IS PARTICULAR EFFORT IN

1577
01:09:17,726 --> 01:09:19,328
FINDING THE RIGHT SENESCENCE

1578
01:09:19,328 --> 01:09:29,838
MARKERS FOR DIFFERENT TISSUES.

1579
01:09:32,741 --> 01:09:34,376
FINALLY, AND WITH INFORMATION,

1580
01:09:34,376 --> 01:09:36,011
AGE IS A HALLMARK AND IT IS AT

1581
01:09:36,011 --> 01:09:37,746
THE CELLULAR LEVEL OR TISSUE OR

1582
01:09:37,746 --> 01:09:39,915
ORGAN LEVEL OR EVEN AT THE

1583
01:09:39,915 --> 01:09:41,016
SYSTEMIC LEVEL, 1 PAPER I WANT

1584
01:09:41,016 --> 01:09:49,157
TO HIGHLIGHT HERE IS FROM MATT

1585
01:09:49,157 --> 01:09:51,793
IN 2021 WHERE THE MAIN

1586
01:09:51,793 --> 01:09:53,328
TRANSGENIC MODEL MOUSE, IT'S NOT

1587
01:09:53,328 --> 01:09:57,032
A NATURAL AGING MODEL BUT THEY

1588
01:09:57,032 --> 01:09:59,668
WERE ABLE TO USE THIS MOUSE TO

1589
01:09:59,668 --> 01:10:00,736
SPECIFICALLY AGE THE IMMUNE

1590
01:10:00,736 --> 01:10:03,238
SYSTEM, AND THEN WE FOUND IF YOU

1591
01:10:03,238 --> 01:10:05,540
WILL SIMPLY HAVE AN AGED IMMUNE

1592
01:10:05,540 --> 01:10:07,509
SYSTEM, YOU CAN ACTUALLY AGE

1593
01:10:07,509 --> 01:10:09,544
YOUR OTHER ORGANS WHICH IS SHOWN

1594
01:10:09,544 --> 01:10:17,386
RIGHT HERE, MANY ORGANS AND DOWN

1595
01:10:17,386 --> 01:10:20,355
BELOW HERE, LIVER STAIN, AND

1596
01:10:20,355 --> 01:10:23,091
SENESCENT CELL MARKER AND AGED

1597
01:10:23,091 --> 01:10:25,127
CELL MARKER, AND IT IS HIGH NOT

1598
01:10:25,127 --> 01:10:28,063
ONLY IN OLD MICE BUT ALSO IN

1599
01:10:28,063 --> 01:10:31,066
OTHER MICE WITH AN AGED IMMUNE

1600
01:10:31,066 --> 01:10:31,299
SYSTEM.

1601
01:10:31,299 --> 01:10:34,236
AND ANOTHER EXAMPLE IS OF

1602
01:10:34,236 --> 01:10:36,538
COURSE, INCAS RELATED DISEASE

1603
01:10:36,538 --> 01:10:37,606
ALZHEIMERS, THIS IS MENTIONED

1604
01:10:37,606 --> 01:10:44,246
WHICH I THOUGHT WAS STRIKING,

1605
01:10:44,246 --> 01:10:45,514
USING THE AND SHOWING THESE 2

1606
01:10:45,514 --> 01:10:46,915
PEOPLE ARE HYMN THE SAME AGE BUT

1607
01:10:46,915 --> 01:10:51,620
YOU CAN SEE IT'S COMPLETELY, AND

1608
01:10:51,620 --> 01:10:54,556
THIS IS TARGETING THE ACTIVATION

1609
01:10:54,556 --> 01:11:04,032
WHICH IS A PROINFLAMMATORY

1610
01:11:04,032 --> 01:11:04,332
FEATURE.

1611
01:11:04,332 --> 01:11:05,801
SO FINALLY, I WON'T SPEND MUCH

1612
01:11:05,801 --> 01:11:07,269
TIME HERE SO WE CAN DISCUSS

1613
01:11:07,269 --> 01:11:09,671
THIS, BUT WE KNOW ALL THESE

1614
01:11:09,671 --> 01:11:11,306
DIFFERENT BIOMARKERS BUT ARE

1615
01:11:11,306 --> 01:11:12,474
THESE MOLECULAR CHANGES

1616
01:11:12,474 --> 01:11:14,609
REVERSIBLE, SO THERE IS SOME

1617
01:11:14,609 --> 01:11:17,345
EVIDENCE, SO I'LL POINT OUT 4

1618
01:11:17,345 --> 01:11:22,451
KIND OF INTERVENTIONS IF YOU

1619
01:11:22,451 --> 01:11:26,988
WILL IN ANIMALS, PARABIOSIS,

1620
01:11:26,988 --> 01:11:27,522
NUTRITIONAL INTERVENTION,

1621
01:11:27,522 --> 01:11:28,223
PHENOTHERAPY WHICH I TALKED

1622
01:11:28,223 --> 01:11:30,525
ABOUT A LITTLE BIT AND CELLULAR

1623
01:11:30,525 --> 01:11:32,027
REPROGRAMMING WHICH I THINK WE

1624
01:11:32,027 --> 01:11:35,063
ALLUDED TO DAVID SIN CLAIR'S

1625
01:11:35,063 --> 01:11:35,397
PAPER.

1626
01:11:35,397 --> 01:11:37,032
SO THESE HAVE SHOWN PROMISE BUT

1627
01:11:37,032 --> 01:11:39,034
THEY ARE NOT PERFECT OBVIOUSLY.

1628
01:11:39,034 --> 01:11:43,738
BUT IF YOU REALLY WANT TO

1629
01:11:43,738 --> 01:11:45,707
TRANSLATE THESE INTERVENTIONS TO

1630
01:11:45,707 --> 01:11:47,075
HUMANS, TELL BE DIFFICULT.

1631
01:11:47,075 --> 01:11:50,712
BUT THE VERY FACT THAT YOU KNOW

1632
01:11:50,712 --> 01:11:51,746
THERE ARE NEWS AROUND THE WORLD

1633
01:11:51,746 --> 01:11:55,183
WHERE THERE ARE A LOT OF

1634
01:11:55,183 --> 01:11:57,719
CENTENARIANS OR HIGH DENSITY OF

1635
01:11:57,719 --> 01:11:58,753
CENTENARIANS, YOU CAN SEE THAT

1636
01:11:58,753 --> 01:12:02,958
YOU KNOW THEY MUST BE DOING

1637
01:12:02,958 --> 01:12:04,693
SOMETHING AND HOPEFULLY IT'S NOT

1638
01:12:04,693 --> 01:12:06,628
JUST THE GENETICS THAT GETS THEM

1639
01:12:06,628 --> 01:12:09,164
THIS LONG LIFE SPAN, SO PERHAPS

1640
01:12:09,164 --> 01:12:11,366
WE CAN ADOPT SOME OF THE HABITS

1641
01:12:11,366 --> 01:12:13,668
AND LIFESTYLES AND IF YOU WANT

1642
01:12:13,668 --> 01:12:17,439
TO KNOW MORE, YOU CAN WATCH THIS

1643
01:12:17,439 --> 01:12:20,275
DOCUMENTARY, THANK YOU FOR

1644
01:12:20,275 --> 01:12:21,843
NETFLIX, AND SO WITH THAT, THANK

1645
01:12:21,843 --> 01:12:22,744
YOU VERY MUCH FOR YOUR

1646
01:12:22,744 --> 01:12:23,411
ATTENTION.

1647
01:12:23,411 --> 01:12:26,314
THESE ARE MY ACKNOWLEDGMENTS,

1648
01:12:26,314 --> 01:12:34,289
NIA HAS BEEN AN INCREDIBLE PLACE

1649
01:12:34,289 --> 01:12:35,924
TO BE DOING MY WORK AND I

1650
01:12:35,924 --> 01:12:37,425
COULDN'T HAVE ASKED TR MORE AND

1651
01:12:37,425 --> 01:12:39,728
I LOVE THE SUPPORT HERE AND I AM

1652
01:12:39,728 --> 01:12:50,138
HAPPY TO TAKE QUESTIONS.

1653
01:13:00,382 --> 01:13:02,117
>> OKAY, THANK YOU BOTH
FOR

1654
01:13:02,117 --> 01:13:04,386
TAKING US ON 2 SOMEWHAT

1655
01:13:04,386 --> 01:13:05,754
DIFFERENT BUT HOPEFULLY AT LEAST

1656
01:13:05,754 --> 01:13:13,261
IN THE FUTURE OVERLAPPING I

1657
01:13:13,261 --> 01:13:14,896
HAVAGES I WONDER IF THEY HAVE

1658
01:13:14,896 --> 01:13:16,298
HEARD EACH OTHER'S PRESENTATION

1659
01:13:16,298 --> 01:13:17,666
AND I'M SURE NOT FOR THE FIRST

1660
01:13:17,666 --> 01:13:18,533
TIME BUT CONSIDERING THAT EACH

1661
01:13:18,533 --> 01:13:22,404
OF YOU ARE LOOKING AT THESE HUGE

1662
01:13:22,404 --> 01:13:26,007
PROBLEMS RELATED TO AGING FROM A

1663
01:13:26,007 --> 01:13:26,641
SOMEWHAT DIFFERENT PERSPECTIVE,

1664
01:13:26,641 --> 01:13:27,742
DO HAVE YOU QUESTIONS THAT YOU

1665
01:13:27,742 --> 01:13:31,947
WOULD LIKE TO ASK 1 ANOTHER TO

1666
01:13:31,947 --> 01:13:35,116
DISCUSS ANY OF THIS FURTHER?

1667
01:13:35,116 --> 01:13:37,152
PERHAPS LUIGI, DO YOU WANT TO GO

1668
01:13:37,152 --> 01:13:37,385
FIRST?

1669
01:13:37,385 --> 01:13:39,087
YOU HAVE ANY QUESTIONS YOU WISH

1670
01:13:39,087 --> 01:13:41,089
TO ASK P A YEL IN.

1671
01:13:41,089 --> 01:13:43,625
>> HAPPY TO DO THAT, YEAH,
THAT

1672
01:13:43,625 --> 01:13:44,926
WAS A FANTASTIC PRESENTATION OF

1673
01:13:44,926 --> 01:13:47,429
AND COURSE, I HEARD SOME OF IT

1674
01:13:47,429 --> 01:13:51,633
BUT EVERY TIME I LISTEN TO YOU,

1675
01:13:51,633 --> 01:13:53,335
YOU KNOW I REALLY GET EXCITED.

1676
01:13:53,335 --> 01:13:58,773
ONE OF THE THINGS I WANTED TO

1677
01:13:58,773 --> 01:14:01,209
ASK YOU IS YOU KNOW, WE

1678
01:14:01,209 --> 01:14:05,847
MENTIONED IT, AND YOU KNOW,

1679
01:14:05,847 --> 01:14:07,115
BETWEEN MY PRESENTATION THAT ARE

1680
01:14:07,115 --> 01:14:13,622
A COUPLE OF MILLIONS HERE OF THE

1681
01:14:13,622 --> 01:14:16,992
EVOLUTIONARY CHANGES AND THE WAY

1682
01:14:16,992 --> 01:14:20,962
EVOLUTION WORKS IS THAT FIND THE

1683
01:14:20,962 --> 01:14:21,663
IMPERFECTION, EFFECT, AND THEN

1684
01:14:21,663 --> 01:14:27,202
CORRECT THEM SO THAT THE SPECIES

1685
01:14:27,202 --> 01:14:30,605
LIVE LONGER, AND SO THAT MEANS

1686
01:14:30,605 --> 01:14:32,340
THAT WHEN WE WORK ON ANIMAL

1687
01:14:32,340 --> 01:14:35,844
MODEL OR IN CELL MODEL, WE

1688
01:14:35,844 --> 01:14:38,580
REALLY NEED TO THINK ABOUT IS

1689
01:14:38,580 --> 01:14:40,749
THIS WHAT I'M FINDING HERE

1690
01:14:40,749 --> 01:14:43,218
ASSOCIATE WIDE AGING ALREADY

1691
01:14:43,218 --> 01:14:45,954
BEEN SOLVED FOR EVOLUTION AND

1692
01:14:45,954 --> 01:14:47,389
THE REASON I'M SAYING THAT IS

1693
01:14:47,389 --> 01:14:51,626
FOR EXAMPLE, YOU KNOW WHEN I DO

1694
01:14:51,626 --> 01:14:54,763
A LOT OF INSPECTION, IN EAST AND

1695
01:14:54,763 --> 01:14:57,265
IN C.ELEGANS, AND IT IS

1696
01:14:57,265 --> 01:14:58,566
INCREDIBLE LOAMACYY AFFECTING

1697
01:14:58,566 --> 01:15:02,237
AND THEN WHEN YOU GO UP OUT OF

1698
01:15:02,237 --> 01:15:06,741
THE GENETICALLY, THEN IN THE

1699
01:15:06,741 --> 01:15:08,143
PRIMATE, WE DON'T REALLY KNOW

1700
01:15:08,143 --> 01:15:10,445
AND IN HUMANS IT'S REALLY

1701
01:15:10,445 --> 01:15:11,846
QUESTIONABLE WHETHER IT WORKS OR

1702
01:15:11,846 --> 01:15:12,080
NOT.

1703
01:15:12,080 --> 01:15:14,716
SO I KNOW IT'S A VERY GENERAL

1704
01:15:14,716 --> 01:15:15,984
QUESTION, BUT IT'S SOMETHING

1705
01:15:15,984 --> 01:15:21,623
THAT IS CONSTANTLY IN MY MIND.

1706
01:15:21,623 --> 01:15:24,993
>> THANK YOU LUIGI, VERY
THAT

1707
01:15:24,993 --> 01:15:26,394
VERY DEEP QUESTION, BUT I DON'T

1708
01:15:26,394 --> 01:15:27,595
KNOW IF I HAVE AN ANSWER.

1709
01:15:27,595 --> 01:15:29,964
BUT I THINK YOU ARE RIGHT.

1710
01:15:29,964 --> 01:15:33,134
I KIND OF MADE MENTION OF IT,

1711
01:15:33,134 --> 01:15:36,137
WHEN I SHOWED THAT, YOU KNOW THE

1712
01:15:36,137 --> 01:15:38,540
HUMANS ARE PRETTY UP THERE IN

1713
01:15:38,540 --> 01:15:40,108
THAT MAXIMUM LIFE SPAN SPECTRUM,

1714
01:15:40,108 --> 01:15:44,546
AND I DO THINK THAT WE HAVE

1715
01:15:44,546 --> 01:15:48,550
ALREADY EVOLVED MECHANISMS TO

1716
01:15:48,550 --> 01:15:50,485
LIVE LONGER AND SOMETIMES AND

1717
01:15:50,485 --> 01:15:52,454
AGAIN, I DON'T HAVE AN ANSWER

1718
01:15:52,454 --> 01:15:54,222
PER SE BUT SOMETIMES I WONDER

1719
01:15:54,222 --> 01:15:56,491
WHETHER SOME OF THE CHANGES THAT

1720
01:15:56,491 --> 01:15:59,527
OCCUR IN HUMANS WITH AGE ARE

1721
01:15:59,527 --> 01:16:03,098
EVEN GOOD FOR US, I MEAN, ARE

1722
01:16:03,098 --> 01:16:10,004
THEY ADAPTIVE AND HELPING US TO

1723
01:16:10,004 --> 01:16:14,542
CURB CANCER OR OTHER NEURO-- OR

1724
01:16:14,542 --> 01:16:15,009
DEGENERATIVE DISEASES.

1725
01:16:15,009 --> 01:16:18,646
BUT I THINK THAT YOU KNOW, AS WE

1726
01:16:18,646 --> 01:16:21,583
GET OLDER WE CAN TAKE 1 OF 2

1727
01:16:21,583 --> 01:16:21,850
PATHS.

1728
01:16:21,850 --> 01:16:24,652
ONE PATH IS CANCER WHICH IS

1729
01:16:24,652 --> 01:16:27,055
EXTREMELY DELETERIOUS, BUT THE

1730
01:16:27,055 --> 01:16:28,523
ALTERNATIVE PATH IS DEGENERATION

1731
01:16:28,523 --> 01:16:32,193
AND I THINK WE'VE EVOLVED

1732
01:16:32,193 --> 01:16:34,028
MECHANISMS TOWARDS DEGENERATION

1733
01:16:34,028 --> 01:16:35,430
RATHER THAN CANCER BECAUSE

1734
01:16:35,430 --> 01:16:36,564
DEGENERATION AT LEAST HELPS US

1735
01:16:36,564 --> 01:16:41,336
TO LIVE A BIT LONGER.

1736
01:16:41,336 --> 01:16:42,871
AND BY CURBING THOSE MECHANISMS

1737
01:16:42,871 --> 01:16:46,307
IN HUMANS, I THINK WOULD ONLY

1738
01:16:46,307 --> 01:16:48,209
ENABLE CANCER, SO, I DON'T KNOW.

1739
01:16:48,209 --> 01:16:50,612
I THINK WE'VE ALREADY REACHED A

1740
01:16:50,612 --> 01:16:57,152
LIMIT IF YOU ASK ME.

1741
01:16:57,152 --> 01:16:57,719
>> THAT'S GREAT.

1742
01:16:57,719 --> 01:17:01,756
I THINK WE THINK A LIKE.

1743
01:17:01,756 --> 01:17:04,659
>> DO YOU HAVE ANY
QUESTIONS FOR

1744
01:17:04,659 --> 01:17:07,095
ME?

1745
01:17:07,095 --> 01:17:09,764
>> YES.

1746
01:17:09,764 --> 01:17:11,633
>> YES, SO, I THINK 1 OF
THE

1747
01:17:11,633 --> 01:17:13,234
QUESTIONS WAS REGARDING ADAPTIVE

1748
01:17:13,234 --> 01:17:14,869
CHAIRVELGS WHICH I THINK I

1749
01:17:14,869 --> 01:17:16,805
ALREADY ASKED YOU BUT I UPONNED

1750
01:17:16,805 --> 01:17:20,675
TO GET YOUR OPINION ON HOW TO

1751
01:17:20,675 --> 01:17:23,178
STUDY THESE MOLECULAR MECHANISMS

1752
01:17:23,178 --> 01:17:27,916
IN HUMANS GIVEN THE HUGE GENETIC

1753
01:17:27,916 --> 01:17:29,884
VARIABILITY AS A LAB SCIENTISTS,

1754
01:17:29,884 --> 01:17:32,921
I FIND IT INCREDIBLY DIFFICULT

1755
01:17:32,921 --> 01:17:39,093
TO WORK WITH HUMAN SAMPLES

1756
01:17:39,093 --> 01:17:41,629
BECAUSE I MEAN THE PROJECTED

1757
01:17:41,629 --> 01:17:42,797
NUMBER OF SAMPLES I WOULD HAVE

1758
01:17:42,797 --> 01:17:44,966
TO LOOK AT IN ORDER TO REALLY

1759
01:17:44,966 --> 01:17:49,137
DETERMINE IF SOMETHING IS

1760
01:17:49,137 --> 01:17:49,771
CAUSALLY AFFECTING AGING, THERE

1761
01:17:49,771 --> 01:17:52,006
WILL BE A HUGE AMOUNT.

1762
01:17:52,006 --> 01:17:54,876
SO I FEEL MORE SAFE, I DON'T

1763
01:17:54,876 --> 01:17:58,580
KNOW, TO STUDY, YOU KNOW MICE

1764
01:17:58,580 --> 01:17:59,981
MAYBE WITH A STABLE GENETIC

1765
01:17:59,981 --> 01:18:04,018
BACKGROUND SO THAT I KNOW THAT

1766
01:18:04,018 --> 01:18:06,321
THEY'RE STUDYING THE EPIGENETIC

1767
01:18:06,321 --> 01:18:07,956
EFFECTS SO I WAS WONDERING IF

1768
01:18:07,956 --> 01:18:09,390
YOU HAVE ANY THOUGHTS ON

1769
01:18:09,390 --> 01:18:13,161
STUDYING HUMANS IN THE LAB?

1770
01:18:13,161 --> 01:18:16,931
>> YOU KNOW I THINK THAT
VERY

1771
01:18:16,931 --> 01:18:19,367
GREAT, NOW ABOUT WHAT YOU CAN DO

1772
01:18:19,367 --> 01:18:20,869
IN HUMANS IS MUCH LESS THAN CAN

1773
01:18:20,869 --> 01:18:24,873
YOU DO IN ANIMAL MODELS AND THE

1774
01:18:24,873 --> 01:18:28,142
TRADE-OFF IS THAT WHAT YOU FIND

1775
01:18:28,142 --> 01:18:30,879
IS LIKELY RELEVANT FOR HUMAN, SO

1776
01:18:30,879 --> 01:18:35,116
BECAUSE, YOU KNOW WE WORK REALLY

1777
01:18:35,116 --> 01:18:36,885
TO IMPROVE THE HEALTH OF HUMANS,

1778
01:18:36,885 --> 01:18:39,187
YOU GET SOMETHING THAT MAY BE

1779
01:18:39,187 --> 01:18:40,655
IMMEDIATELY TRANALATABLE AND

1780
01:18:40,655 --> 01:18:40,989
USEABLE.

1781
01:18:40,989 --> 01:18:43,958
AND YES, YOU'RE RIGHT, IT'S

1782
01:18:43,958 --> 01:18:50,965
QUITE CHALLENGING AS YOU KNOW,

1783
01:18:50,965 --> 01:18:53,768
YOU KNOW I DO 50 TO 60 MASSIVE

1784
01:18:53,768 --> 01:18:55,703
BIOPSIES A YEAR AND IT'S QUITE

1785
01:18:55,703 --> 01:18:56,871
CHALLENGING TO DO THAT BECAUSE

1786
01:18:56,871 --> 01:19:03,177
IT'S REALLY A SURGICAL PROCEDURE

1787
01:19:03,177 --> 01:19:04,913
AND SO THE NUMBER OF SAMPLES YOU

1788
01:19:04,913 --> 01:19:07,181
CAN GET IS SMALL.

1789
01:19:07,181 --> 01:19:08,816
BUT SOMETHING WE'RE LEARNING AND

1790
01:19:08,816 --> 01:19:10,685
HAS TO DO WITH WHAT YOU SAID

1791
01:19:10,685 --> 01:19:14,088
BEFORE IS THAT MANY OF THE

1792
01:19:14,088 --> 01:19:19,227
THINGS WE SEE CHANGING, ARE

1793
01:19:19,227 --> 01:19:20,795
REALLY ACTIVE AND RECEIVING

1794
01:19:20,795 --> 01:19:21,095
MECHANISMS.

1795
01:19:21,095 --> 01:19:21,996
YOU KNOW YOU TALKED ABOUT

1796
01:19:21,996 --> 01:19:27,802
INFLAMMATION AND I'M SURE THAT

1797
01:19:27,802 --> 01:19:30,071
INFLAMMATION BY ITSELF HAS A

1798
01:19:30,071 --> 01:19:32,907
NEGATIVE EFFECT ON SOME DISEASE

1799
01:19:32,907 --> 01:19:34,909
AND SOME VASCULAR EFFECTS,

1800
01:19:34,909 --> 01:19:39,948
HOWEVER, I ALSO THINK IF OUR

1801
01:19:39,948 --> 01:19:42,283
MISSION DOESN'T START THAT WAY,

1802
01:19:42,283 --> 01:19:48,523
IF THE MEASURE STARTS WITH THE

1803
01:19:48,523 --> 01:19:49,590
RESILIENCE MECHANISM SETS WITH

1804
01:19:49,590 --> 01:19:51,392
THE ACCUMULATION OF DAMAGE.

1805
01:19:51,392 --> 01:19:53,061
AND WHEN ACCUMULATION OF DAMAGE

1806
01:19:53,061 --> 01:19:54,862
OCCUR THOSE MOLECULES NO LONGER

1807
01:19:54,862 --> 01:19:59,334
CONSIDER ITSELF, THEY ARE

1808
01:19:59,334 --> 01:20:01,736
MOLECULE THAT MAYBE STRANDULES

1809
01:20:01,736 --> 01:20:04,038
AND THOSE MOLECULES BIGGER

1810
01:20:04,038 --> 01:20:05,907
INFLAMMATORY -- TRIGGER AN

1811
01:20:05,907 --> 01:20:07,775
INFLAMMATORY RESPONSE, SO THE

1812
01:20:07,775 --> 01:20:09,110
PRIMARY MODEL IS THIS DAMAGED

1813
01:20:09,110 --> 01:20:09,978
ACCUMULATION AND THEN LATER ON

1814
01:20:09,978 --> 01:20:12,447
WHEN YOU HAVE THE INFLAMMATION,

1815
01:20:12,447 --> 01:20:15,416
DOESN'T GO OFF, YOU HAVE THE

1816
01:20:15,416 --> 01:20:16,117
DEGENERATIVE DISEASE EMPLOY YOU

1817
01:20:16,117 --> 01:20:21,689
KNOW THAT WHEN YOU HAVE THE

1818
01:20:21,689 --> 01:20:22,790
INTEGRATED RESPONSE, PROTEIN

1819
01:20:22,790 --> 01:20:24,225
RESPONSE AND INFLAMMATION, BUT

1820
01:20:24,225 --> 01:20:27,061
ALSO YOU HAVE A COMPLETE BLOCK

1821
01:20:27,061 --> 01:20:29,664
OF PROTEIN SYNTHESIS, AND WHEN

1822
01:20:29,664 --> 01:20:32,867
YOU CAN, YOU KNOW MODIFY IT,

1823
01:20:32,867 --> 01:20:35,603
WHEN YOU CANNOT RECYCLE AND

1824
01:20:35,603 --> 01:20:37,405
REGENERATE YOUR PROTEIN, THE

1825
01:20:37,405 --> 01:20:38,172
PROTEIN ACCUMULATE DAMAGE AND

1826
01:20:38,172 --> 01:20:41,442
THAT IS 1 OF THE MECHANISMS THAT

1827
01:20:41,442 --> 01:20:43,745
WE THINK IS SOMETHING YOU KNOW

1828
01:20:43,745 --> 01:20:45,113
DEGENERATIVE DEC EMPLOY NOW THE

1829
01:20:45,113 --> 01:20:50,885
REAL ISSUE IS HOW DO WE

1830
01:20:50,885 --> 01:20:52,587
DISTINGUISH BETWEEN CAUSAL EVENT

1831
01:20:52,587 --> 01:20:55,857
AND RESILIENCE EVENT.

1832
01:20:55,857 --> 01:20:57,492
AND THAT'S NOT A STUPID QUESTION

1833
01:20:57,492 --> 01:20:59,827
BECAUSE WE DON'T WANT TO TOUCH

1834
01:20:59,827 --> 01:21:02,663
THE RESILIENCE EEIVET BECAUSE WE

1835
01:21:02,663 --> 01:21:05,066
WOULD BE REMOVING WHAT IS GOOD.

1836
01:21:05,066 --> 01:21:06,467
WE WANT TO IDENTIFY THE CAUSE OF

1837
01:21:06,467 --> 01:21:10,738
CHANGE SO THAT WE CAN INTERVENE

1838
01:21:10,738 --> 01:21:12,740
ON IT AND THE EPIDEMIOLOGIST

1839
01:21:12,740 --> 01:21:15,910
STARTED TO DO A LOT OF MEN

1840
01:21:15,910 --> 01:21:17,478
DEALIAN RANDOMIZATION ON THE

1841
01:21:17,478 --> 01:21:19,313
DISEASE WHERE BECAUSE YOU'RE

1842
01:21:19,313 --> 01:21:22,817
LOOKING AT GENETIC VARIABLE, THE

1843
01:21:22,817 --> 01:21:24,986
POINT, THE PHENOTYPE AND NOW

1844
01:21:24,986 --> 01:21:26,387
WITH THE AVAILABILITY FOR LARGE

1845
01:21:26,387 --> 01:21:28,256
POPULATION SUCH AS THE UK

1846
01:21:28,256 --> 01:21:31,893
BIOBANK, THEY ARE STARTING TO

1847
01:21:31,893 --> 01:21:32,827
DISTINGUISH BETWEEN WHO IS GOOD

1848
01:21:32,827 --> 01:21:35,763
AND WHAT IS BAD. 

1849
01:21:35,763 --> 01:21:38,833
AND I HOPE THAT THESE, YOU KNOW

1850
01:21:38,833 --> 01:21:42,637
WORK WITH -- THIS WORK WILL

1851
01:21:42,637 --> 01:21:45,773
CONTINUE UNTIL, IT'S THE WHOLE

1852
01:21:45,773 --> 01:21:47,909
PROBLEM OF THE WORKING BIOME

1853
01:21:47,909 --> 01:21:50,311
BIOMARKER, WE NEVER KNOW WHETHER

1854
01:21:50,311 --> 01:21:51,045
THE BIOMARK, CODED THAT.

1855
01:21:51,045 --> 01:21:54,148
SO WHEN YOU LOOK AT BIOMARKER

1856
01:21:54,148 --> 01:21:54,949
THAT'S PREDICTIVE, IT DOESN'T

1857
01:21:54,949 --> 01:21:58,352
MATTER BUT WHEN YOU LOOK AT HINT

1858
01:21:58,352 --> 01:22:00,288
FOR TARGET FOR INTERVENTION,

1859
01:22:00,288 --> 01:22:05,226
THAT BECOMES ABSOLUTELY

1860
01:22:05,226 --> 01:22:05,626
IMPORTANT.

1861
01:22:05,626 --> 01:22:05,993
>> THANK YOU.

1862
01:22:05,993 --> 01:22:08,329
SO MAYBE IF I CAN NOW COUNTER

1863
01:22:08,329 --> 01:22:13,134
QUESTION AND I DON'T QUITE

1864
01:22:13,134 --> 01:22:15,436
REMEMBER, BUT MAYBE, A GROUP

1865
01:22:15,436 --> 01:22:16,437
ATTEMPTED SOMETHING LIKE THIS

1866
01:22:16,437 --> 01:22:19,874
AND THEY TRIED TO CORRELATE WITH

1867
01:22:19,874 --> 01:22:22,810
MORETALLITY INSTEAD OF LIFE SPAN

1868
01:22:22,810 --> 01:22:24,645
OR SOMETHING LIKE THAT?

1869
01:22:24,645 --> 01:22:28,649
SO BUT THEN ANYTHING THAT

1870
01:22:28,649 --> 01:22:31,085
AFFECTS MORTALITY IS CORRELATED

1871
01:22:31,085 --> 01:22:34,255
NEGATIVELY WITH LIFESTYLE,

1872
01:22:34,255 --> 01:22:34,589
RIGHT?

1873
01:22:34,589 --> 01:22:37,358
>> YES, YES, BUT, YOU KNOW
-- I

1874
01:22:37,358 --> 01:22:39,293
KNOW THAT PAPER QUITE WELL, I

1875
01:22:39,293 --> 01:22:40,695
KNOW THE WORK QUITE WELL AND

1876
01:22:40,695 --> 01:22:43,764
THAT PAPER ACTUALLY DID NOT LOOK

1877
01:22:43,764 --> 01:22:46,667
AT THE BIOMARKER PREDICTER OF

1878
01:22:46,667 --> 01:22:47,001
MORTALITY.

1879
01:22:47,001 --> 01:22:54,642
THEY CREATED A GENETIC SCORE FOR

1880
01:22:54,642 --> 01:22:55,676
THAT BIOMARKER AND THEN THEY

1881
01:22:55,676 --> 01:22:58,112
LOOK AT WHETHER THOSE GENETIC

1882
01:22:58,112 --> 01:22:59,947
SCORE, THAT VARIABLE THAT ARE

1883
01:22:59,947 --> 01:23:02,016
REALLY GENETIC THAT DON'T CHANGE

1884
01:23:02,016 --> 01:23:06,287
OVER TIME PREDICTED MORTALITY OR

1885
01:23:06,287 --> 01:23:09,991
NOT, THAT PREDICT THE LEVEL OF

1886
01:23:09,991 --> 01:23:11,859
THAT BIOMARKER THAT PREDICT

1887
01:23:11,859 --> 01:23:14,962
MORTALITY BECAUSE THEN YOU

1888
01:23:14,962 --> 01:23:17,365
BECOME ALMOST INDEPENDENT FROM

1889
01:23:17,365 --> 01:23:21,135
ENVIRONMENTAL CHANGES SUCH AS

1890
01:23:21,135 --> 01:23:22,336
THOUGH THAT TRIGGER RESILIENT

1891
01:23:22,336 --> 01:23:23,671
RESPONSE, AND IF THAT IS TRUE,

1892
01:23:23,671 --> 01:23:25,473
IT'S 1 OF THE -- OF COURSE

1893
01:23:25,473 --> 01:23:29,110
NOTHING IS PERFECT, YOU KNOW MEN

1894
01:23:29,110 --> 01:23:29,944
DEALIAN RANDOMIZATION HAS ITS

1895
01:23:29,944 --> 01:23:34,215
OWN PROBLEMS SO I THINK THAT IS

1896
01:23:34,215 --> 01:23:36,984
A GOOD START AND WE NEED TO

1897
01:23:36,984 --> 01:23:38,019
REPLICATE AGAIN A LARGER

1898
01:23:38,019 --> 01:23:39,187
POPULATION AND I THINK THAT'S A

1899
01:23:39,187 --> 01:23:42,423
MATTER THAT WILL GROW IN THE

1900
01:23:42,423 --> 01:23:43,157
FUTURE. 

1901
01:23:43,157 --> 01:23:46,594
>> THANK YOU. 

1902
01:23:46,594 --> 01:23:48,095
>> WELL, FEEL FREE TO ASK

1903
01:23:48,095 --> 01:23:50,231
QUESTIONS OF EACH OTHER AS WE

1904
01:23:50,231 --> 01:23:53,701
PROCEED BUT WE HAVE A LARGE

1905
01:23:53,701 --> 01:23:55,836
NUMBER OF QUESTIONS THAT HAVE

1906
01:23:55,836 --> 01:23:57,138
BEEN SUBMITTED AND IT'S

1907
01:23:57,138 --> 01:24:04,278
INTERESTING, LOOKING AT THE

1908
01:24:04,278 --> 01:24:07,148
LIST, I THINK IT'S 2 PHENOMENA,

1909
01:24:07,148 --> 01:24:09,984
1 IS THE MULTIPLICITY OF IDEAS

1910
01:24:09,984 --> 01:24:15,189
AND THE OTHER IS MORE FROM LET'S

1911
01:24:15,189 --> 01:24:20,127
CALL IT THE CLINICAL ASPECT,

1912
01:24:20,127 --> 01:24:23,531
WHAT EXPOSURES MAKE AGING WORSE?

1913
01:24:23,531 --> 01:24:27,868
OR WHAT BENEFITS SPECIFICALLY

1914
01:24:27,868 --> 01:24:30,871
CAN HELP TO SOFTEN THE DECLINE.

1915
01:24:30,871 --> 01:24:33,207
AND IT'S INTERESTING THAT THE

1916
01:24:33,207 --> 01:24:34,742
QUESTIONS ALL REFLECT THIS

1917
01:24:34,742 --> 01:24:36,344
MULTIPLE DISCIPLINE, YOU GET THE

1918
01:24:36,344 --> 01:24:40,114
FEELING THAT WE'RE DEALING WITH

1919
01:24:40,114 --> 01:24:42,850
A HUGE COMPLEX PROBLEM IN WHICH

1920
01:24:42,850 --> 01:24:45,786
FORTUNATELY, DUE TO WORK LIKE

1921
01:24:45,786 --> 01:24:47,088
BOTH OF YOU, MUCH PROGRESS IS

1922
01:24:47,088 --> 01:24:48,723
BEING MADE EMPLOY SO LET'S GET

1923
01:24:48,723 --> 01:24:52,994
ON WITH SOME OF THE QUESTIONS

1924
01:24:52,994 --> 01:24:58,699
HERE THAT HAVE BEEN ASKED AND

1925
01:24:58,699 --> 01:25:01,102
LET ME SEE, OH YES, SO WILLIAM

1926
01:25:01,102 --> 01:25:04,805
CALLS TENSION TO A REPORT FROM

1927
01:25:04,805 --> 01:25:08,409
NASA THAT WAS PUBLISHED LAST

1928
01:25:08,409 --> 01:25:14,315
YEAR, STRESSING THE IMPORTANCE

1929
01:25:14,315 --> 01:25:15,950
OF MITOCHONDRIA AS SORT OF THE

1930
01:25:15,950 --> 01:25:19,553
HUB OF VARIOUS OMICS STUDIES OF

1931
01:25:19,553 --> 01:25:22,823
SPACE FLIGHT INJURY AND

1932
01:25:22,823 --> 01:25:23,624
POTENTIALLY LONGEVITY AND THERE

1933
01:25:23,624 --> 01:25:27,094
HAVE BEEN SEVERAL QUESTIONS

1934
01:25:27,094 --> 01:25:31,766
GOING BACK TO MITOCHONDRIA IN

1935
01:25:31,766 --> 01:25:32,300
PARTICULARLY MITOCHONDRIA

1936
01:25:32,300 --> 01:25:33,200
DYNAMICS.

1937
01:25:33,200 --> 01:25:35,503
PERHAPS EACH OF YOU WOULD LIKE

1938
01:25:35,503 --> 01:25:37,371
TO TAKE A TURN.

1939
01:25:37,371 --> 01:25:40,541
P A YEL, WHAT IS YOUR VIEW ABOUT

1940
01:25:40,541 --> 01:25:41,475
THAT?

1941
01:25:41,475 --> 01:25:44,078
>> GIVEN THE QUESTION, YOU
KNOW,

1942
01:25:44,078 --> 01:25:47,348
I THINK, I DEFINE MYSELF

1943
01:25:47,348 --> 01:25:47,948
MITOCHONDRIA-CENTRIC SCIENTIST

1944
01:25:47,948 --> 01:25:49,650
BECAUSE I THINK THAT

1945
01:25:49,650 --> 01:25:50,518
MITOCHONDRIA ARE REALLY THE

1946
01:25:50,518 --> 01:25:52,186
CULPRIT OF WHAT'S HAPPENING WITH

1947
01:25:52,186 --> 01:26:00,328
AGING AND THE REASON IS THAT ALL

1948
01:26:00,328 --> 01:26:01,762
THOSE THAT THEY WERE TALKING

1949
01:26:01,762 --> 01:26:04,332
ABOUT, THE DNA REPAIR, THE PHOTO

1950
01:26:04,332 --> 01:26:07,301
STATIC MICANISM, ALL OF THEM

1951
01:26:07,301 --> 01:26:08,569
REQUIRE ENERGY, MASSIVE AMOUNT

1952
01:26:08,569 --> 01:26:09,870
OF ENERGY AND YOU KNOW, YOU

1953
01:26:09,870 --> 01:26:11,605
THINK ABOUT THE IMMUNE SYSTEM,

1954
01:26:11,605 --> 01:26:14,241
YOU KNOW THEY HAVE AN IMMUNE

1955
01:26:14,241 --> 01:26:17,945
RESPONSE, YOU NEED TO HAVE A LOT

1956
01:26:17,945 --> 01:26:24,018
OF, YOU KNOW PROTEIN SYNTHESIS,

1957
01:26:24,018 --> 01:26:25,953
AND PROTEIN SYNTHESIS IS

1958
01:26:25,953 --> 01:26:27,154
REQUIRING MASSIVE AMOUNTS OF

1959
01:26:27,154 --> 01:26:27,588
ENERGY.

1960
01:26:27,588 --> 01:26:28,856
SO UNLESS YOU HAVE GOOD

1961
01:26:28,856 --> 01:26:30,925
MITOCHONDRIA YOU DON'T HAVE

1962
01:26:30,925 --> 01:26:34,595
RESILIENCYS, AND SO YOU END UP

1963
01:26:34,595 --> 01:26:37,431
WITH ACCELERATED AGING AND IN

1964
01:26:37,431 --> 01:26:40,067
OUR WORK, WE DEMONSTRATED THAT

1965
01:26:40,067 --> 01:26:42,036
THE LOW MITOCHONDRIA FUNCTION

1966
01:26:42,036 --> 01:26:44,939
MEASURED BY MRI, WE USE THE MRI

1967
01:26:44,939 --> 01:26:47,575
SPECTROSCOPY TO DO THAT, IT'S

1968
01:26:47,575 --> 01:26:49,610
PREDICTIVE OF ACCELERATED

1969
01:26:49,610 --> 01:26:53,147
DECLINE BOTH IMMOBILITY AND

1970
01:26:53,147 --> 01:26:53,781
COGNITIVE FUNCTION.

1971
01:26:53,781 --> 01:26:58,018
I WILL FINISH BY SAYING IF YOU

1972
01:26:58,018 --> 01:27:01,555
LOOK AT 1 OF THE BIG GLOBAL

1973
01:27:01,555 --> 01:27:02,890
MEASURE OF VITALITY IN PEOPLE IS

1974
01:27:02,890 --> 01:27:04,925
FITNESS, HOW FIT YOU ARE.

1975
01:27:04,925 --> 01:27:08,362
AND IF YOU LOOK AT WHAT OTHER

1976
01:27:08,362 --> 01:27:09,830
PREDICTER OF FITNESS, 1 IS

1977
01:27:09,830 --> 01:27:15,069
CARDIAC FUNCTION AND THE OTHER 1

1978
01:27:15,069 --> 01:27:17,538
IS PERIPHERAL DELIVERY OF OXYGEN

1979
01:27:17,538 --> 01:27:19,874
AND AT THE BEGINNING, THEY

1980
01:27:19,874 --> 01:27:21,742
STARTED WITH THE DECLINE IN THE

1981
01:27:21,742 --> 01:27:23,811
ANALLING BUT THE EXTRACTION OF

1982
01:27:23,811 --> 01:27:25,513
OXYGEN IN THE PERIPHERY DOES

1983
01:27:25,513 --> 01:27:29,683
SUGGEST THAT THE PROBLEM IS THAT

1984
01:27:29,683 --> 01:27:31,419
THOSE MITOCHONDRIA CANNOT BE

1985
01:27:31,419 --> 01:27:41,128
UTILIZED, ALL THAT OXYGEN THAT

1986
01:27:41,128 --> 01:27:43,130
CAN BE PUT.

1987
01:27:43,130 --> 01:27:44,632
>> I CAN CHIME IN.

1988
01:27:44,632 --> 01:27:47,668
I WAS ACTUALLY GOING TO LET

1989
01:27:47,668 --> 01:27:50,771
LUIGI GO FIRST BECAUSE HE IS

1990
01:27:50,771 --> 01:27:52,706
INDEED THE MITOCHONDRIA EXPERT,

1991
01:27:52,706 --> 01:27:55,776
I TEND TO AT A WITHIN THE

1992
01:27:55,776 --> 01:27:59,180
NUCLEUS, BUT I CAN TELL YOU VERY

1993
01:27:59,180 --> 01:28:01,816
BRIEFLY THAT, YOU KNOW IN RECENT

1994
01:28:01,816 --> 01:28:04,685
WORK, VERY PRELIMINARY DATA, NOT

1995
01:28:04,685 --> 01:28:06,387
EVEN, YOU KNOW ESTABLISHED, BUT

1996
01:28:06,387 --> 01:28:09,390
THERE ARE CERTAIN REPORTS OF YOU

1997
01:28:09,390 --> 01:28:11,826
KNOW THIS METABOLIC SHIFT WITH

1998
01:28:11,826 --> 01:28:16,263
AGE, RIGHT IN SO YOU KNOW A

1999
01:28:16,263 --> 01:28:19,066
CHANGE FROM OFF STARTS IN THE

2000
01:28:19,066 --> 01:28:20,134
MITOCHONDRIA, THE MORE

2001
01:28:20,134 --> 01:28:22,837
MITOCHONDRIA BECOME DAMAGED, THE

2002
01:28:22,837 --> 01:28:26,207
MORE THE GLYCOLYSIS, THE

2003
01:28:26,207 --> 01:28:27,475
GLYCOLYSIS PRODUCES MAYBE ACETYL

2004
01:28:27,475 --> 01:28:30,110
TAKE AWAY WHICH IS LIPID

2005
01:28:30,110 --> 01:28:32,179
METABOLISM, WHICH IS ALSO

2006
01:28:32,179 --> 01:28:33,113
PROBABLY ACETALATES THE

2007
01:28:33,113 --> 01:28:37,284
EPIGENOME AND THEN ACTIVATES

2008
01:28:37,284 --> 01:28:40,254
CERTAIN PERHAPS PRO INFLAMMATORY

2009
01:28:40,254 --> 01:28:44,658
GENES, SO THIS IS A HYPOTHESIS

2010
01:28:44,658 --> 01:28:47,094
AT THIS STAGE AND ESPECIALLY AND

2011
01:28:47,094 --> 01:28:51,699
I THINK MACROPHAGE CLASS OF CELL

2012
01:28:51,699 --> 01:28:51,966
TYPES.

2013
01:28:51,966 --> 01:28:54,802
THIS METABOLIC SHIFT IS PRETTY

2014
01:28:54,802 --> 01:28:56,937
PROMINENT DURING AGING AND MAYBE

2015
01:28:56,937 --> 01:28:59,473
DRIVES SOME OF THE PHENOTYPES

2016
01:28:59,473 --> 01:29:02,543
THAT WE SEE AND 1 OTHER LITTLE

2017
01:29:02,543 --> 01:29:06,380
THING TO SAY IS THAT, YOU KNOW

2018
01:29:06,380 --> 01:29:08,782
BOTH LUIGI AND OUR GROUP WE

2019
01:29:08,782 --> 01:29:10,150
STUDY THE SKELETAL MUSCLE WHICH

2020
01:29:10,150 --> 01:29:13,654
IS REALLY RICH IN MITOCHONDRIA

2021
01:29:13,654 --> 01:29:17,925
AND IT'S ALMOST 40-50% OF OUR

2022
01:29:17,925 --> 01:29:21,262
BODY MASS AND SARCOPENIA, WHICH

2023
01:29:21,262 --> 01:29:24,265
IS A VERY NOTICEABLE EVENT AND

2024
01:29:24,265 --> 01:29:32,106
THAT CHANGES YOUR METABOLIC

2025
01:29:32,106 --> 01:29:33,240
OUTPUT COMPLETELY, AND THAT IS

2026
01:29:33,240 --> 01:29:38,812
ALSO BECAUSE ALL OF THE

2027
01:29:38,812 --> 01:29:40,314
MITOCHONDRIA, BASICALLY THE

2028
01:29:40,314 --> 01:29:41,882
TOTAL MITOCHONDRIA OUTPUT

2029
01:29:41,882 --> 01:29:43,050
OVERALL IS DEMINNISHING AND

2030
01:29:43,050 --> 01:29:46,453
YEAH, I WILL LEAVE IT AT THAT.

2031
01:29:46,453 --> 01:29:49,223
>> SO MAY I INQUIRE ABOUT
THAT.

2032
01:29:49,223 --> 01:29:52,726
YOU RAISE ESSENTIA WILY THE

2033
01:29:52,726 --> 01:29:55,195
LDKAMP1 PATHWAY AS BEING

2034
01:29:55,195 --> 01:29:57,097
INCREASINGLY DOMINANT IN AGING

2035
01:29:57,097 --> 01:30:01,001
AND IT'S IN THAT AREA THAT

2036
01:30:01,001 --> 01:30:07,308
THINGS LIKE  SURTOMBIN AND SOME

2037
01:30:07,308 --> 01:30:08,842
OF DAVID SIN CLAIR'S IDEAS COME

2038
01:30:08,842 --> 01:30:10,244
INTO THE PROCESS BECAUSE OF THE

2039
01:30:10,244 --> 01:30:12,813
LINK AS YOU POINT IN WITH

2040
01:30:12,813 --> 01:30:15,015
MITOCHONDRIA AND WITH OTHER

2041
01:30:15,015 --> 01:30:15,683
ORGANELLE METABOLISM.

2042
01:30:15,683 --> 01:30:19,420
WHAT IS YOUR VIEW ABOUT THAT

2043
01:30:19,420 --> 01:30:22,456
FROM A BIOLOGICAL STANDPOINT?

2044
01:30:22,456 --> 01:30:27,595
AND PERHAPS EVEN FROM A CLINICAL

2045
01:30:27,595 --> 01:30:29,530
PERSPECTIVE WHICH LUIGI MAY WANT

2046
01:30:29,530 --> 01:30:33,067
TO COMMENT UPON, THAT'S BEING

2047
01:30:33,067 --> 01:30:35,469
PROMOTED IN CERTAIN PARTS OF THE

2048
01:30:35,469 --> 01:30:35,803
WORLD.

2049
01:30:35,803 --> 01:30:40,808
SO P A YEL, WHAT IS YOUR VIEW?

2050
01:30:40,808 --> 01:30:42,543
>> I THINK MORE STUFF FOR
VIABLE

2051
01:30:42,543 --> 01:30:47,381
ISHT VENTIONS OUT THERE, SO FAR

2052
01:30:47,381 --> 01:30:50,985
THAT GAINED A LOT OF PRESS,

2053
01:30:50,985 --> 01:30:55,089
THERE'S OBVIOUSLY THE RAPOMICE O

2054
01:30:55,089 --> 01:30:57,725
SIN AND mTOR, INTAKE

2055
01:30:57,725 --> 01:30:58,492
INHIBITOR, CALORIC RESTRICTION,

2056
01:30:58,492 --> 01:31:01,161
ALL OF THESE ARE VERY

2057
01:31:01,161 --> 01:31:01,895
INTRICATELY INTERCONNECT WIDE

2058
01:31:01,895 --> 01:31:04,064
EACH OTHER AND ULTIMATELY, I

2059
01:31:04,064 --> 01:31:08,435
THINK THEY ALL IMPINGE ON

2060
01:31:08,435 --> 01:31:10,404
WHETHER -- ON ENERGY PRODUCTION,

2061
01:31:10,404 --> 01:31:12,973
RIGHT IN SO THE mTOR PATHWAY,

2062
01:31:12,973 --> 01:31:20,814
IF YOU HAVE NUTRIENT  EXCESS FOR

2063
01:31:20,814 --> 01:31:23,751
EXAMPLE, THAT IS ACTIVE AND

2064
01:31:23,751 --> 01:31:25,019
TRANSLATIONAL RESEARCH PROMOTES

2065
01:31:25,019 --> 01:31:31,191
AUTOPHAGE EXPE THAT IS BIND, BUT

2066
01:31:31,191 --> 01:31:33,227
THE NUTRIENT DEPRIVATION LIKE

2067
01:31:33,227 --> 01:31:35,629
CALORIC INSTRIKS, IT INHIBITS

2068
01:31:35,629 --> 01:31:39,299
THE MTORE PATHWAY AND THAT'S

2069
01:31:39,299 --> 01:31:39,867
SOMEHOW GOOD.

2070
01:31:39,867 --> 01:31:41,602
SO MY UNDERSTANDING OF THE

2071
01:31:41,602 --> 01:31:43,337
COMPLEXITY OF THE PATHWAYS IS

2072
01:31:43,337 --> 01:31:45,673
NOT VERY GOOD BUT ALL I CAN SAY

2073
01:31:45,673 --> 01:31:49,176
IS MAYBE THE UNDERLYING MESSAGES

2074
01:31:49,176 --> 01:31:53,580
WE SHOULD LIMIT TRANSLATION AND

2075
01:31:53,580 --> 01:31:55,015
FUTILE ENERGY UTILIZATION IN OUR

2076
01:31:55,015 --> 01:31:58,752
BODY AND THAT COULD HAVE SOME

2077
01:31:58,752 --> 01:32:00,354
LONGEVITY BENEFITS.

2078
01:32:00,354 --> 01:32:02,723
>> SO LET'S LOOK AT THE
SPECIFIC

2079
01:32:02,723 --> 01:32:03,791
QUESTIONS THAT HAVE BEEN ASKED

2080
01:32:03,791 --> 01:32:05,592
AND MAYBE SO WE CAN COVER MORE

2081
01:32:05,592 --> 01:32:09,329
IF WE COULD KEEP OUR RESPONSES

2082
01:32:09,329 --> 01:32:10,531
SOMEWHAT AS BRIEF AS REASONABLE

2083
01:32:10,531 --> 01:32:13,867
EMPLOY SO SEVERAL PEOPLE HAVE

2084
01:32:13,867 --> 01:32:17,004
ASKED ABOUT THE RELATIONSHIP

2085
01:32:17,004 --> 01:32:22,176
BETWEEN AGING AND COSMIC

2086
01:32:22,176 --> 01:32:25,412
BACKGROUND SO THEY PARTICULARLY

2087
01:32:25,412 --> 01:32:28,315
REFER TO DROSOPHILA EXPERIMENTS

2088
01:32:28,315 --> 01:32:33,287
WHICH WE'VE DONE MANY YEARS AGO

2089
01:32:33,287 --> 01:32:34,788
AND ALSO CONCERNED FOR EXAMPLE

2090
01:32:34,788 --> 01:32:36,690
IN NASA ABOUT PEOPLE BEING OUT

2091
01:32:36,690 --> 01:32:40,294
IN SPACE TOO LONG.

2092
01:32:40,294 --> 01:32:42,129
IS THERE SOLID EVIDENCE

2093
01:32:42,129 --> 01:32:43,297
FORCOSMIC BACKGROUND RADIATION

2094
01:32:43,297 --> 01:32:45,866
HAVING AN EFFECT?

2095
01:32:45,866 --> 01:32:48,402
LUIGI WANT TO COMMENT?

2096
01:32:48,402 --> 01:32:50,871
>> I KNOW NOTHING ABOUT IT
TO BE

2097
01:32:50,871 --> 01:32:52,473
HONEST.

2098
01:32:52,473 --> 01:32:54,875
I AM ABSOLUTELY COMPLETELY

2099
01:32:54,875 --> 01:32:58,312
UNAWARE SO I AM NOT THE RIGHT

2100
01:32:58,312 --> 01:32:59,113
PERSON TO ADDRESS.

2101
01:32:59,113 --> 01:33:02,349
P A YEL, DO YOU KNOW ANYTHING

2102
01:33:02,349 --> 01:33:02,850
ABOUT IT?

2103
01:33:02,850 --> 01:33:05,586
>> ALMOST NOTHING BUT I
READ IN

2104
01:33:05,586 --> 01:33:09,223
THE PRESS, THAT YOU KNOW THE

2105
01:33:09,223 --> 01:33:10,390
TELOMERES BECAME SHORTER,

2106
01:33:10,390 --> 01:33:12,493
ASTRONAUTS WHO CAME TO SPACE AND

2107
01:33:12,493 --> 01:33:13,894
THEIR TELOMERES BECAME SHORTER

2108
01:33:13,894 --> 01:33:17,164
EMPLOY I CAN IMAGINE THAT COSMIC

2109
01:33:17,164 --> 01:33:20,234
RADIATION MAY CAUSE SOME LEVEL

2110
01:33:20,234 --> 01:33:23,270
OF DAMAGE, PERHAPS ACCELERATED

2111
01:33:23,270 --> 01:33:27,741
TELOMERE SHORTENING, BUT THERE'S

2112
01:33:27,741 --> 01:33:32,646
NO EVIDENT, I THINK, NUMBERS,

2113
01:33:32,646 --> 01:33:33,947
NOT MANY PEOPLE HAVE BEEN

2114
01:33:33,947 --> 01:33:37,217
STUDIED THIS WAY BUT I DON'T

2115
01:33:37,217 --> 01:33:38,986
KNOW WHERE THAT CAN -- THOSE

2116
01:33:38,986 --> 01:33:40,954
KIND OF TRANSIENT DAMAGES CAN BE

2117
01:33:40,954 --> 01:33:43,023
REPAIRED EASILY OR NOT ONCE THEY

2118
01:33:43,023 --> 01:33:45,592
COME BACK TO EARTH.

2119
01:33:45,592 --> 01:33:47,294
SO HOW THAT HAS AN EFFECT ON

2120
01:33:47,294 --> 01:33:49,596
LIFE SPAN OR DEVELOPMENT OF

2121
01:33:49,596 --> 01:33:53,667
CANCER, I DON'T KNOW.

2122
01:33:53,667 --> 01:33:53,967
RESPIRATORY.

2123
01:33:53,967 --> 01:33:55,135
>> SO IF I MAY, I WOULD
LIKE TO

2124
01:33:55,135 --> 01:33:58,038
GO BACK TO THE MITOCHONDRIA FOR

2125
01:33:58,038 --> 01:34:02,609
A SECOND, FOR A MOMENT.

2126
01:34:02,609 --> 01:34:06,480
AND YOU KNOW THE ONLY PATIENTS

2127
01:34:06,480 --> 01:34:10,384
IN HUMAN IS CALORIE, THE CALORIE

2128
01:34:10,384 --> 01:34:12,186
STUDY PUT PEOPLE ON 25%, AND

2129
01:34:12,186 --> 01:34:15,589
THEY WERE UNABLE TO DO IT, BUT

2130
01:34:15,589 --> 01:34:19,693
THEY REACHED 14% AND WE STUDIED

2131
01:34:19,693 --> 01:34:23,197
THOSE MASSIVE BIOPSY FROM PEOPLE

2132
01:34:23,197 --> 01:34:24,598
THAT WERE UNCHARACTERISTIC FOR 2

2133
01:34:24,598 --> 01:34:27,501
YEAR ANDS IN CONTROLS AND WHAT

2134
01:34:27,501 --> 01:34:30,204
WAS INTERESTING IS THAT YOU KNOW

2135
01:34:30,204 --> 01:34:34,708
OF COURSE WE'RE LOSING WEIGHT,

2136
01:34:34,708 --> 01:34:37,578
YOU LOSE MUSCLE MASS BUT THE

2137
01:34:37,578 --> 01:34:39,546
FOLDS DPENERATED BY THAT MASS

2138
01:34:39,546 --> 01:34:41,248
DID NOT CHANGE.

2139
01:34:41,248 --> 01:34:42,583
WHICH MEANS THAT THAT MUSCLE WAS

2140
01:34:42,583 --> 01:34:44,017
MUCH MORE EFFECTIVE IN

2141
01:34:44,017 --> 01:34:45,719
GENERATING FOLD, AND THEN WE

2142
01:34:45,719 --> 01:34:49,323
LOOK AT GENE EXPRESSION IN THOSE

2143
01:34:49,323 --> 01:34:52,693
MUSCLE AND WHAT WE FIND THAT IS,

2144
01:34:52,693 --> 01:35:01,034
YOU KNOW OVERREGULATED,

2145
01:35:01,034 --> 01:35:02,870
OVEREXPRESSED, SILT1, Foxp3,

2146
01:35:02,870 --> 01:35:05,405
AND PGC1 ALPHA WHICH IS THE

2147
01:35:05,405 --> 01:35:06,840
MASTER REGULATOR OF MITOCHONDRIA

2148
01:35:06,840 --> 01:35:07,608
BIOGENESIS.

2149
01:35:07,608 --> 01:35:10,010
SO I THINK THAT, THAT IS

2150
01:35:10,010 --> 01:35:12,412
EVIDENCE IN HUMANS THAT

2151
01:35:12,412 --> 01:35:14,248
SUGGESTING THAT 1 OF THE, YOU

2152
01:35:14,248 --> 01:35:15,549
KNOW INTERVENTION THAT IS

2153
01:35:15,549 --> 01:35:17,484
SUPPOSED TO BE REYOU'VEINATING

2154
01:35:17,484 --> 01:35:21,188
AND IN THAT CASE, REALLY HAD

2155
01:35:21,188 --> 01:35:25,993
POSITIVE EFFECT ON MUSCLE WAS

2156
01:35:25,993 --> 01:35:29,396
MEDIATED BY THE EXPECTED, YOU

2157
01:35:29,396 --> 01:35:31,465
KNOW TRANSCRIPTION FACTOR AND

2158
01:35:31,465 --> 01:35:31,732
MOLECULE.

2159
01:35:31,732 --> 01:35:32,900
SO I THINK THERE'S SOMETHING

2160
01:35:32,900 --> 01:35:34,134
IMPORTANT THERE AND I WILL TELL

2161
01:35:34,134 --> 01:35:38,805
YOU 1 MORE THING, THAT WITH THIS

2162
01:35:38,805 --> 01:35:41,675
WE DISCOVERED IS THAT OF COURSE

2163
01:35:41,675 --> 01:35:43,277
IF YOU EXERCISE YOU HAVE MORE

2164
01:35:43,277 --> 01:35:45,812
MUSCLE THAT, IS NOT SURPRISING,

2165
01:35:45,812 --> 01:35:48,181
YOU KNOW YOU CONTRACT THE

2166
01:35:48,181 --> 01:35:51,084
MUSCLE, AND YOUR MUSCLE ADAPT,

2167
01:35:51,084 --> 01:35:54,588
BY CREATING MORE ENERGY BUT YOU

2168
01:35:54,588 --> 01:35:56,590
ALSO HAVE MORE MITOCHONDRIA IN

2169
01:35:56,590 --> 01:35:59,826
THE SKIN, IN YOUR IMMUNE CELLS,

2170
01:35:59,826 --> 01:36:02,062
IN THE FIBROBLASTS, SO THAT

2171
01:36:02,062 --> 01:36:03,563
EFFECT ON MITOCHONDRIA IS NOT

2172
01:36:03,563 --> 01:36:05,198
LIMITED TO THE MUSCLE, NOW, WE

2173
01:36:05,198 --> 01:36:07,601
DON'T KNOW WHAT THIS MECHANISM

2174
01:36:07,601 --> 01:36:10,637
BY WHICH THE EXERCISE INCREASE

2175
01:36:10,637 --> 01:36:12,339
THE MITOCHONDRIA YOU KNOW

2176
01:36:12,339 --> 01:36:19,713
PRESENT IN THESE OTHER TISSUE,

2177
01:36:19,713 --> 01:36:21,281
PERSISTENTLY THE MITOCHONDRIA

2178
01:36:21,281 --> 01:36:23,417
ISSUE ARE TALKING TOGETHER.

2179
01:36:23,417 --> 01:36:24,051
>> VERY GOOD.

2180
01:36:24,051 --> 01:36:25,919
WELL, LET'S MOVE ON.

2181
01:36:25,919 --> 01:36:27,454
WE HAVE HERE --

2182
01:36:27,454 --> 01:36:28,989
>> MAY I MAKE A QUICK
COMMENT

2183
01:36:28,989 --> 01:36:31,291
HERE IF YOU DON'T MIND?

2184
01:36:31,291 --> 01:36:31,558
>> YEAH.

2185
01:36:31,558 --> 01:36:38,899
>> YEAH, SO I JUST WANTED
TO

2186
01:36:38,899 --> 01:36:42,402
TELL LUIGI, THAT NEARBY STUDIES

2187
01:36:42,402 --> 01:36:45,138
THE TRIALS, MET FORMIN TRIALS

2188
01:36:45,138 --> 01:36:45,739
AND ALSO I HEARD HIM TALK AND

2189
01:36:45,739 --> 01:36:47,040
THERE WAS A PANEL DISCUSSION

2190
01:36:47,040 --> 01:36:48,141
WHERE HE MENTIONED THAT MET

2191
01:36:48,141 --> 01:36:53,113
FORMIN, SOME PEOPLE SAY THAT IT

2192
01:36:53,113 --> 01:36:55,916
DEACTIVATES THE TOR PATHWAY SO

2193
01:36:55,916 --> 01:36:58,518
YOU DON'T GET MUCH MUSCLE MASS

2194
01:36:58,518 --> 01:37:00,787
AND IT'S BAD BUT I THINK HE MADE

2195
01:37:00,787 --> 01:37:02,889
THE POINT THAT THE MET FORMIN

2196
01:37:02,889 --> 01:37:05,158
TREATED MUSCLE IS ABOUT THE

2197
01:37:05,158 --> 01:37:08,061
SAME, SO I WANTED TO PROVIDE IT.

2198
01:37:08,061 --> 01:37:11,198
>> YES,  LET'S CONSIDER
SOME OF

2199
01:37:11,198 --> 01:37:21,708
THE OTHER QUESTIONS THAT HAVE

2200
01:37:22,442 --> 01:37:22,809
BEEN ASKED HERE.

2201
01:37:22,809 --> 01:37:25,278
ALL RIGHT, WE HAVE AN

2202
01:37:25,278 --> 01:37:30,717
INTERESTING QUESTION HERE, THIS

2203
01:37:30,717 --> 01:37:36,323
IS ABOUT HYDRA, HYDRA, ABLE TO

2204
01:37:36,323 --> 01:37:38,158
LIVE FOREVER BECAUSE THEY LIVE

2205
01:37:38,158 --> 01:37:40,594
THROUGH STEM CELLS WHICH

2206
01:37:40,594 --> 01:37:41,495
REGENERATE THROUGH DUPLICATION

2207
01:37:41,495 --> 01:37:42,329
OR CLONING.

2208
01:37:42,329 --> 01:37:43,830
SO THESE ANIMALS DON'T

2209
01:37:43,830 --> 01:37:45,866
DETERIORATE AS THEY GET OLDER

2210
01:37:45,866 --> 01:37:49,836
BUT THEY DIE UNDER NATURAL

2211
01:37:49,836 --> 01:37:50,537
CONDITIONS PREDOMINANTLY ATORS

2212
01:37:50,537 --> 01:37:53,907
AND SO FORTH AND SO ON.

2213
01:37:53,907 --> 01:37:56,843
THEY KEEP GOING, ALMOST FOREVER,

2214
01:37:56,843 --> 01:37:59,312
DO YOU SEE ANY RELATIONSHIP

2215
01:37:59,312 --> 01:38:02,549
BETWEEN THIS AND MAMMALIAN

2216
01:38:02,549 --> 01:38:03,150
PHYSIOLOGY?

2217
01:38:03,150 --> 01:38:08,155
IT'S A BIT WAY OUT, BUT MAYBE

2218
01:38:08,155 --> 01:38:09,289
HAVE YOU SOME BRIEF THOUGHTS

2219
01:38:09,289 --> 01:38:09,689
ABOUT THAT.

2220
01:38:09,689 --> 01:38:11,324
I GUESS WE COULD EXPAND IT

2221
01:38:11,324 --> 01:38:13,960
BECAUSE PEOPLE HAVE ASKED ABOUT

2222
01:38:13,960 --> 01:38:17,864
OTHER SPECIES, TOO, CERTAIN

2223
01:38:17,864 --> 01:38:19,232
SHARKS, CLAMS, DIFFERENT SPECIES

2224
01:38:19,232 --> 01:38:22,903
HAVE DIFFERENT -- AS YOU POINT

2225
01:38:22,903 --> 01:38:24,438
OUT DIFFERENT LIVE SPANS AND

2226
01:38:24,438 --> 01:38:25,272
DIFFERENT ADAPTATIONS SO IN

2227
01:38:25,272 --> 01:38:30,577
BRIEF IS THAT DUE TO COMPLETELY

2228
01:38:30,577 --> 01:38:32,045
DIFFERENT EVOLUTIONARY CHANGES?

2229
01:38:32,045 --> 01:38:35,515
IS THERE SOME LINEAR

2230
01:38:35,515 --> 01:38:37,150
RELATIONSHIP TO PROCESSES IN

2231
01:38:37,150 --> 01:38:37,851
MAMMALS?

2232
01:38:37,851 --> 01:38:40,253
>> WELL AS A HUMAN
SCIENTIST, I

2233
01:38:40,253 --> 01:38:42,355
DON'T KNOW VERY MUCH ABOUT IT

2234
01:38:42,355 --> 01:38:47,260
BUT I TRY AND PARTICIPATED

2235
01:38:47,260 --> 01:38:49,763
AROUND THE TABLE WITH HUMAN

2236
01:38:49,763 --> 01:38:51,798
SCIENTISTS AND BASIC SCIENCE,

2237
01:38:51,798 --> 01:38:57,037
SCIENTISTS THAT WERE DISCUSSING

2238
01:38:57,037 --> 01:38:58,338
WHETHER HY DRA, LIVE FOREVER OR

2239
01:38:58,338 --> 01:38:58,705
NOT.

2240
01:38:58,705 --> 01:39:00,774
AND THE DISCUSSION FOCUS ON, YOU

2241
01:39:00,774 --> 01:39:03,677
KNOW WHAT IS AN INDIVIDUAL.

2242
01:39:03,677 --> 01:39:09,649
ARE WE THINKING ABOUT YOU KNOW

2243
01:39:09,649 --> 01:39:10,784
BECAUSE HYDRA LIVE FOREVER BUT

2244
01:39:10,784 --> 01:39:15,322
THE CELL THAT EITHER HAS YOU

2245
01:39:15,322 --> 01:39:18,992
KNOW 4 WEEKS LATER, ARE NOT THE

2246
01:39:18,992 --> 01:39:22,329
SAME CELLS THAT THE HYDRA HAD

2247
01:39:22,329 --> 01:39:22,696
BEFORE.

2248
01:39:22,696 --> 01:39:26,633
SO THE REGENERATION THAT IS --

2249
01:39:26,633 --> 01:39:37,177
DOES NOT IMPLY THE PARTITIONING

2250
01:39:42,682 --> 01:39:45,252
AND I WILL ARGUE, IF YOU CAN

2251
01:39:45,252 --> 01:39:47,053
THINK ABOUT MORTALITY OR NOT,

2252
01:39:47,053 --> 01:39:50,357
BECAUSE YOU CAN THINK THAT THE

2253
01:39:50,357 --> 01:39:57,697
HUMANS LIVE FOREVER BECAUSE THEY

2254
01:39:57,697 --> 01:39:59,099
HAVE GENESIS, AND THEY ARE USING

2255
01:39:59,099 --> 01:40:01,735
TO CREATE THEIR CHILDREN, AND

2256
01:40:01,735 --> 01:40:04,838
THEIR CHILDREN START FROM THE

2257
01:40:04,838 --> 01:40:07,207
SAME CELL OF THE OTHER

2258
01:40:07,207 --> 01:40:07,507
INDIVIDUAL.

2259
01:40:07,507 --> 01:40:09,209
THE FACT THAT THEY ARE

2260
01:40:09,209 --> 01:40:09,910
PHYSICALLY SEPARATED FROM THE

2261
01:40:09,910 --> 01:40:11,745
MOTHER AND THE FATHER, YOU KNOW

2262
01:40:11,745 --> 01:40:19,119
MAY NOT BE SO IMPORTANT AND SO

2263
01:40:19,119 --> 01:40:20,387
THE SAME PHENOMENON CAN OCCUR

2264
01:40:20,387 --> 01:40:26,493
WITHIN THE SAME INDIVIDUAL

2265
01:40:26,493 --> 01:40:27,661
WITHOUT SEPARATION OF WHAT WE

2266
01:40:27,661 --> 01:40:29,529
CALL INDIVIDUAL, SO I'M NOT SURE

2267
01:40:29,529 --> 01:40:30,497
THIS IS BIOLOGICAL BUT I THINK

2268
01:40:30,497 --> 01:40:32,465
THAT WAS THE CONE OF THE

2269
01:40:32,465 --> 01:40:33,633
DISCUSSION, AT SOME POINT IT

2270
01:40:33,633 --> 01:40:35,135
GENERATED A LITTLE BIT BECAUSE

2271
01:40:35,135 --> 01:40:40,607
WANE CAME INTO IT, SO IT BECAME

2272
01:40:40,607 --> 01:40:42,642
MORE CONFUSED.

2273
01:40:42,642 --> 01:40:43,710
>> LUIGI, WHILE YOU'RE

2274
01:40:43,710 --> 01:40:44,711
COMMENTING, WE HAVE A QUESTION

2275
01:40:44,711 --> 01:40:48,315
IN HERE, YOU USED THE PHRASE I

2276
01:40:48,315 --> 01:40:51,618
KIND OF DIFFERENTIATED WHAT YOU

2277
01:40:51,618 --> 01:40:58,658
CALLED THE BIOLOGICAL LIFE SPAN

2278
01:40:58,658 --> 01:40:59,826
AS DISTINGUISHED FROM LIFE

2279
01:40:59,826 --> 01:41:00,126
EXPECTANCY.

2280
01:41:00,126 --> 01:41:01,294
WHAT DO YOU HAVE IN MIEBD WHEN

2281
01:41:01,294 --> 01:41:09,502
YOU REFER TO THE BIOLOGICAL LIFE

2282
01:41:09,502 --> 01:41:10,003
SPAN?

2283
01:41:10,003 --> 01:41:11,104
LUIGI? 

2284
01:41:11,104 --> 01:41:14,841
ARE YOU ON?

2285
01:41:14,841 --> 01:41:15,709
>> HE'S UNFORTUNATELY
MUTED FOR

2286
01:41:15,709 --> 01:41:16,209
A SECOND.

2287
01:41:16,209 --> 01:41:22,849
HE'S TRYING TO UNMUTE NOKAY,  --

2288
01:41:22,849 --> 01:41:23,984
>> OKAY, I AM HERE.

2289
01:41:23,984 --> 01:41:25,852
I DON'T TALK ABOUT BIOLOGICAL

2290
01:41:25,852 --> 01:41:27,387
LIFE SPAN, I TALK ABOUT

2291
01:41:27,387 --> 01:41:28,922
BIOLOGICAL AGING AND WHEN I

2292
01:41:28,922 --> 01:41:33,393
THINK ABOUT BIOLOGICAL AGING, I

2293
01:41:33,393 --> 01:41:35,328
AM THINKING ABOUT THE ARK

2294
01:41:35,328 --> 01:41:36,796
KIEWMULATION OF ORGANELLE DAMAGE

2295
01:41:36,796 --> 01:41:39,132
SPECIFICALLY AND WE CAN DEMON

2296
01:41:39,132 --> 01:41:42,669
TRAIT THAT THAT MICROMOLECULAR

2297
01:41:42,669 --> 01:41:43,503
CHANGES OCCUR EVEN YOU KNOW IN

2298
01:41:43,503 --> 01:41:48,742
THE FIRST YEAR OF LIFE, SO

2299
01:41:48,742 --> 01:41:51,378
THEY'RE THERE, THEY'RE NOT

2300
01:41:51,378 --> 01:41:54,180
EVIDENT PHENOTYPICALLY BECAUSE

2301
01:41:54,180 --> 01:41:55,815
THEY DEVELOPMENT PROGRAM THAT IS

2302
01:41:55,815 --> 01:41:59,753
INSCRIBING OUR DNA IS INCREDIBLY

2303
01:41:59,753 --> 01:42:01,955
POWERFUL, REDUNDANT AND FULL OF

2304
01:42:01,955 --> 01:42:05,558
CHECK POINTS THAT MAKE IT SO

2305
01:42:05,558 --> 01:42:09,129
EVIDENT THAT WE HIDE EVERYTHING

2306
01:42:09,129 --> 01:42:11,231
UNDERNEATH BUT STEVE HORVATH,

2307
01:42:11,231 --> 01:42:13,266
SHOW THAT THE CHANGE IN

2308
01:42:13,266 --> 01:42:14,801
METHYLATION THAT CHARACTERIZE

2309
01:42:14,801 --> 01:42:16,970
AGING OCCUR EVEN FASTER IN THE

2310
01:42:16,970 --> 01:42:21,641
FIRST YEAR OF LIFE.

2311
01:42:21,641 --> 01:42:23,777
AND SO WHEN I TALK ABOUT

2312
01:42:23,777 --> 01:42:29,215
BIOLOGICAL AGING, I'M THINKING

2313
01:42:29,215 --> 01:42:29,916
ABOUT, YOU KNOW, THAT BALANCE

2314
01:42:29,916 --> 01:42:38,625
BETWEEN MACROMOLECULAR DAMAGE

2315
01:42:38,625 --> 01:42:39,292
AND RESILIENCE.

2316
01:42:39,292 --> 01:42:41,261
>> ALL RIGHT, WHILE YOU'RE
ON

2317
01:42:41,261 --> 01:42:43,263
LUIGI, WHAT IS YOUR VIEW ABOUT

2318
01:42:43,263 --> 01:42:47,334
CALORIC RESTRICTION AND AGING. 

2319
01:42:47,334 --> 01:42:49,903
TAKING ALL OF THE EXISTING DATA,

2320
01:42:49,903 --> 01:42:53,540
SOME OF ITS CONFUSION, PEOPLE

2321
01:42:53,540 --> 01:42:56,142
WANT SPECIFIC ADVICE AS BOTH THE

2322
01:42:56,142 --> 01:42:59,079
SCIENTISTS AND ALSO A SCIENTIFIC

2323
01:42:59,079 --> 01:43:00,380
CLINICIAN, WHAT DO YOU ADVISE

2324
01:43:00,380 --> 01:43:02,782
PEOPLE ON THAT SUBJECT.

2325
01:43:02,782 --> 01:43:04,984
>> IT'S A HARD QUESTION.

2326
01:43:04,984 --> 01:43:07,220
YOU KNOW I THINK THAT, YOU KNOW,

2327
01:43:07,220 --> 01:43:10,657
IF YOU LOOK AT THE

2328
01:43:10,657 --> 01:43:11,991
EPIDEMIOLOGICAL STUDIES, I'LL

2329
01:43:11,991 --> 01:43:13,460
START WITH THERE, WILL TELL YOU

2330
01:43:13,460 --> 01:43:16,129
THAT THE PEOPLE THAT LIVE

2331
01:43:16,129 --> 01:43:20,667
LONGER, ARE THOSE INDIVIDUALS

2332
01:43:20,667 --> 01:43:22,869
THAT DO NOT CHANGE, MINIMAL

2333
01:43:22,869 --> 01:43:24,971
CHANGE WAYS ACROSS THE LINE ANDS

2334
01:43:24,971 --> 01:43:26,873
NOW THOSE PEOPLE, THE DECLINING

2335
01:43:26,873 --> 01:43:27,907
WEIGHT, GAINING WEIGHT, THOSE

2336
01:43:27,907 --> 01:43:30,844
ARE BOTH OF HIGHER MORTALITY.

2337
01:43:30,844 --> 01:43:34,948
THE SWEET SPOT FOR LOWER

2338
01:43:34,948 --> 01:43:38,618
MORTALITY IS NOT BELOW A BMI OF

2339
01:43:38,618 --> 01:43:43,857
25, IT'S A BMI OF 26-27, SO

2340
01:43:43,857 --> 01:43:44,357
SLIGHTLY OVERWEIGHT.

2341
01:43:44,357 --> 01:43:48,027
NOW IT'S DIFFICULT TO KNOW

2342
01:43:48,027 --> 01:43:49,429
WHETHER THAT IS A BIAS DUE TO

2343
01:43:49,429 --> 01:43:52,198
THE FACT THAT THE PEOPLE THAT

2344
01:43:52,198 --> 01:43:55,602
GET SICK, YOU KNOW LOSE WEIGHT,

2345
01:43:55,602 --> 01:43:58,638
EVEN IN STUDIES LIKE THE UK BY O

2346
01:43:58,638 --> 01:44:01,174
BANK WHICH ARE HUGE, FAMILIAR

2347
01:44:01,174 --> 01:44:03,443
WITH PEOPLE, WE COULD NOT

2348
01:44:03,443 --> 01:44:04,144
DISTINGUISH MORTALITY BETWEEN

2349
01:44:04,144 --> 01:44:07,347
THE PEOPLE WITH THE BMI WITH 25

2350
01:44:07,347 --> 01:44:11,985
AND THE BMI OF 26.

2351
01:44:11,985 --> 01:44:13,453
YOU KNOW 26 IS BETTER AND THERE

2352
01:44:13,453 --> 01:44:15,855
WE HAD THE HUGE AMOUNT OF

2353
01:44:15,855 --> 01:44:18,925
CONFOUNDING VARIABLE THAT WE

2354
01:44:18,925 --> 01:44:20,794
COULD USE, FOR A VERY, VERY

2355
01:44:20,794 --> 01:44:22,028
LARGE DATABASE.

2356
01:44:22,028 --> 01:44:23,997
SO I THINK THAT YOU KNOW

2357
01:44:23,997 --> 01:44:26,366
MAINTAINING WEIGHT IS THE MOST

2358
01:44:26,366 --> 01:44:29,636
IMPORTANT NOW AND WE GO TO

2359
01:44:29,636 --> 01:44:31,805
SHAPE, IF WE TALK ABOUT PEOPLE

2360
01:44:31,805 --> 01:44:33,573
THAT ARE SERIOUSLY OVERWEIGHT OR

2361
01:44:33,573 --> 01:44:34,641
OBESE, THERE'S ABSOLUTELY NO

2362
01:44:34,641 --> 01:44:35,809
DOUBT THAT LOSING WEIGHT IS GOOD

2363
01:44:35,809 --> 01:44:38,044
FOR YOU.

2364
01:44:38,044 --> 01:44:44,284
I MEAN THAT'S BEEN  DEMONSTRATED

2365
01:44:44,284 --> 01:44:47,487
HUNDREDS OF TIMES YOU NEED TO DO

2366
01:44:47,487 --> 01:44:48,288
IT PROPERLY, UNDER MEDICAL

2367
01:44:48,288 --> 01:44:49,255
CONTROL, YOU HAVE TO MAKE SURE

2368
01:44:49,255 --> 01:44:52,325
YOU HAVE THE ESSENTIAL PROTEIN

2369
01:44:52,325 --> 01:44:53,827
AND VITAMINS BUT LOSING WEIGHT

2370
01:44:53,827 --> 01:44:56,796
IS ASSOCIATE WIDE DRASTIC

2371
01:44:56,796 --> 01:44:59,933
REDUCTION OF INFLAMMATION, IS

2372
01:44:59,933 --> 01:45:02,569
ASSOCIATE WIDE REDUCTION OF THE

2373
01:45:02,569 --> 01:45:03,603
CARDIOVASCULAR MORTALITY AS AN

2374
01:45:03,603 --> 01:45:06,906
EFFECT ON THE RISK OF CERTAIN

2375
01:45:06,906 --> 01:45:08,541
CANCER, AND NOT ALL CANCER BUT

2376
01:45:08,541 --> 01:45:09,042
CERTAIN CANCER.

2377
01:45:09,042 --> 01:45:12,445
NOW THE REAL ISSUE IS, IF YOU

2378
01:45:12,445 --> 01:45:16,182
ARE NORMAL WEIGHT OR SLIGHTLY

2379
01:45:16,182 --> 01:45:16,716
OVERWEIGHT, THIS CALORIC

2380
01:45:16,716 --> 01:45:24,691
RESTRICTION GOING TO BE

2381
01:45:24,691 --> 01:45:25,058
EFFECTIVE?

2382
01:45:25,058 --> 01:45:26,759
NOW, LOSING WEIGHT IS VERY

2383
01:45:26,759 --> 01:45:27,827
DIFFICULT, VERY, VERY FEW PEOPLE

2384
01:45:27,827 --> 01:45:28,761
ARE EFFECTIVE AND WITH THE

2385
01:45:28,761 --> 01:45:32,098
NORMAL WAY WE DO WITH THE DIET,

2386
01:45:32,098 --> 01:45:34,567
IF YOU LOOK AT PEOPLE FOR A LONG

2387
01:45:34,567 --> 01:45:36,769
TIME ALMOST ALL OF THEM OVER

2388
01:45:36,769 --> 01:45:44,110
TIME REGAIN WHAT THEY LOST AND

2389
01:45:44,110 --> 01:45:45,912
THIS HAS BEEN DUE TO THE FACT

2390
01:45:45,912 --> 01:45:48,815
THAT WHEN YOU LOSE WEIGHT, YOUR

2391
01:45:48,815 --> 01:45:51,084
ORGANIZATIONSISM ADAPT, AND YOU

2392
01:45:51,084 --> 01:45:54,854
ADAPT BY REDUCING RESTING

2393
01:45:54,854 --> 01:45:55,288
METABOLIC RATE.

2394
01:45:55,288 --> 01:46:02,862
SO YOU LOSE THAT EFFECT AND SO

2395
01:46:02,862 --> 01:46:04,397
WHAT IS NOW MORE THINKING IS THE

2396
01:46:04,397 --> 01:46:07,834
MORE EFFICIENT WAY OF DOING

2397
01:46:07,834 --> 01:46:08,902
CALORIC RESTRICTION IS

2398
01:46:08,902 --> 01:46:10,837
INTERMITTENT FASTING, SO THE

2399
01:46:10,837 --> 01:46:12,739
INTERMITTENT FASTING CAN BE DONE

2400
01:46:12,739 --> 01:46:14,374
IN MANY WAYS, 2 DAYS A WEEK, 1

2401
01:46:14,374 --> 01:46:16,576
DAY A WEEK, REDUCING INTAKE FOR

2402
01:46:16,576 --> 01:46:19,579
6 TIMES THE CALORIE 2 DAYS A

2403
01:46:19,579 --> 01:46:22,115
WEEK, MANY, MANY MECHANISMS, OR

2404
01:46:22,115 --> 01:46:24,317
EVEN AND SOON TO BE 1 OF THE

2405
01:46:24,317 --> 01:46:26,452
MOST SUCCESSFUL NOT EATING FOR

2406
01:46:26,452 --> 01:46:29,255
14 HOUR FOR DAY AND EATING ONLY

2407
01:46:29,255 --> 01:46:31,858
IN THE REMAINING HOURS.

2408
01:46:31,858 --> 01:46:33,493
THAT SEEMED TO BE QUITE

2409
01:46:33,493 --> 01:46:35,528
EFFECTIVE ESPECIALLY IF YOU DO

2410
01:46:35,528 --> 01:46:39,465
RESTRICTION IN THE MORNING.

2411
01:46:39,465 --> 01:46:41,968
NOW, THOSE HAVE SHOWN THAT THESE

2412
01:46:41,968 --> 01:46:45,572
PEOPLE ARE ABLE TO MAINTAIN THIS

2413
01:46:45,572 --> 01:46:46,706
CHARACTERISTIC AND SHOWED THE

2414
01:46:46,706 --> 01:46:48,074
LOSING OF THE WEIGHT FOR A VERY

2415
01:46:48,074 --> 01:46:49,642
LONG TIME.

2416
01:46:49,642 --> 01:46:51,578
I RECENTLY HAD A DISCUSSION AT

2417
01:46:51,578 --> 01:46:57,717
THE MEETING OF THE DIETITIANS

2418
01:46:57,717 --> 01:46:59,586
WHEN I INTRODUCED THE AGING AND

2419
01:46:59,586 --> 01:47:03,990
SOME OF THEM TOLD ME THAT ALL

2420
01:47:03,990 --> 01:47:05,959
THEIR LIFE, THERE HAVE BEEN SO

2421
01:47:05,959 --> 01:47:07,827
MUCH DISAPPOINTED WITH THE

2422
01:47:07,827 --> 01:47:08,628
NORNLAL DIET BECAUSE PEOPLE LOSE

2423
01:47:08,628 --> 01:47:10,463
WEIGHT AND A YEAR LATER IT'S

2424
01:47:10,463 --> 01:47:13,967
OBVIOUS THEY HAVE REGAINED

2425
01:47:13,967 --> 01:47:14,200
WEIGHT.

2426
01:47:14,200 --> 01:47:16,469
BUT WE START THE FASTING, THEY

2427
01:47:16,469 --> 01:47:17,937
ARE SEEING SOMETHING DIFFERENT.

2428
01:47:17,937 --> 01:47:21,574
OF KOWRGS IT REQUIRE ALSO A LOT

2429
01:47:21,574 --> 01:47:22,275
OF SELF-CONTROL, BUT PEOPLE SEEM

2430
01:47:22,275 --> 01:47:29,382
TO BE ABLE TO DO IT SO I THINK

2431
01:47:29,382 --> 01:47:30,016
THERE'S SOMETHING THERE.

2432
01:47:30,016 --> 01:47:31,985
AND THERE IS A LOT OF TRIALS

2433
01:47:31,985 --> 01:47:32,418
COMING UP.

2434
01:47:32,418 --> 01:47:34,153
YOU KNOW THERE WAS 1 FAIRLY

2435
01:47:34,153 --> 01:47:35,221
RECENTLY IN THE NEW ENGLAND

2436
01:47:35,221 --> 01:47:42,729
JOURNAL  OF MEDICINE SHOWING THE

2437
01:47:42,729 --> 01:47:42,962
EFFECTS.

2438
01:47:42,962 --> 01:47:45,231
>> SO I ASSUME WE WILL
HEAR A

2439
01:47:45,231 --> 01:47:50,003
LOT AT SOME POINT IN THE FUTURE,

2440
01:47:50,003 --> 01:47:54,507
NOT NOW, ABOUT THE GLUE CO

2441
01:47:54,507 --> 01:47:55,775
GONZALEZ ANTAGGISTIC DRUGS WHICH

2442
01:47:55,775 --> 01:47:57,143
HAVE MULTIPLE EFFECTS AND BY THE

2443
01:47:57,143 --> 01:48:01,514
WAY WE'RE HAVING A SESSION IN

2444
01:48:01,514 --> 01:48:07,620
DEMYSTIFYING MEDICINE WITH 1 OF

2445
01:48:07,620 --> 01:48:09,088
THE DISCOVERERS OF THAT LATER IN

2446
01:48:09,088 --> 01:48:09,822
THE YEAR.

2447
01:48:09,822 --> 01:48:11,424
SO HERE'S ANOTHER QUESTION.

2448
01:48:11,424 --> 01:48:16,963
NOW, YES, P A YEL, THIS IS AN

2449
01:48:16,963 --> 01:48:20,199
IMPORTANT PROBABLY 1 OF THE MOST

2450
01:48:20,199 --> 01:48:20,967
SIGNIFICANT QUESTIONS.

2451
01:48:20,967 --> 01:48:22,969
THERE ARE REALLY 3 OF THEM AND I

2452
01:48:22,969 --> 01:48:24,570
DON'T KNOW HOW YOU CAN ANSWER IT

2453
01:48:24,570 --> 01:48:29,208
IN A SHORT PERIOD OF TIME BUT

2454
01:48:29,208 --> 01:48:29,375
TRY.

2455
01:48:29,375 --> 01:48:31,310
THIS IS REGARDING EPIGENETICS IN

2456
01:48:31,310 --> 01:48:34,514
A CAUSAL PATHWAY OF AGING.

2457
01:48:34,514 --> 01:48:37,150
DO YOU SEE IT PRIMARILY AS A

2458
01:48:37,150 --> 01:48:40,687
CAUSE, A MARKER OF WHETHER

2459
01:48:40,687 --> 01:48:41,621
UNDERLYING PROCESSES OR AN

2460
01:48:41,621 --> 01:48:50,897
EFFECT OF AGING ITSELF?

2461
01:48:50,897 --> 01:48:53,499
ADDITIONALLY HOW SIGNIFICANT IS

2462
01:48:53,499 --> 01:48:54,567
ITSELF CONTRIBUTION REGARDING

2463
01:48:54,567 --> 01:48:56,035
OTHER AGING MECHANISMS AND I

2464
01:48:56,035 --> 01:49:04,844
MIGHT THROW IN THE TELOMERE

2465
01:49:04,844 --> 01:49:06,045
CONTRIBUTION, AND LASTLY WOULD

2466
01:49:06,045 --> 01:49:10,983
YOU SAY THAT THE GENERATION IS

2467
01:49:10,983 --> 01:49:13,086
PART OF EPIGENETIC TARGET FOR

2468
01:49:13,086 --> 01:49:13,453
THERAPY?

2469
01:49:13,453 --> 01:49:15,088
YOU CAN'T ANSWER ALL OF THOSE

2470
01:49:15,088 --> 01:49:16,155
QUESTIONS BUT PLEASE DO YOUR

2471
01:49:16,155 --> 01:49:18,124
BEST IN A SHORT PERIOD OF TIME.

2472
01:49:18,124 --> 01:49:18,925
THANK YOU.

2473
01:49:18,925 --> 01:49:19,425
>> YEAH, SURE.

2474
01:49:19,425 --> 01:49:23,463
I THINK THERE'S QUESTIONS FROM

2475
01:49:23,463 --> 01:49:25,364
MIN Q, SHE'S ALSO HERE AT THE

2476
01:49:25,364 --> 01:49:26,532
NIH, SO OBVIOUSLY A VERY HARD

2477
01:49:26,532 --> 01:49:27,900
QUESTION, I THINK THAT AT THIS

2478
01:49:27,900 --> 01:49:32,038
POINT, IT IS VERY HARD TO

2479
01:49:32,038 --> 01:49:33,606
DISTINGUISH WHAT EPIGENETIC

2480
01:49:33,606 --> 01:49:36,042
CHANGES OCCURRED FIRST AND THEN

2481
01:49:36,042 --> 01:49:42,615
WHAT EPIGENETIC CHANGES OCCURRED

2482
01:49:42,615 --> 01:49:42,849
SECOND.

2483
01:49:42,849 --> 01:49:44,817
SO TO ESTABLISH CAUSALITY, THE

2484
01:49:44,817 --> 01:49:48,788
WAY WE DO IT IN THE LAB IS YOU

2485
01:49:48,788 --> 01:49:50,623
KNOW VERY SIMPLY, KNOCK DOWN AN

2486
01:49:50,623 --> 01:49:55,128
IMPORTANT FACTOR, SEE IF THAT

2487
01:49:55,128 --> 01:49:56,329
AFFECTS ALL OTHER DOWN STREAM

2488
01:49:56,329 --> 01:50:00,633
KNOWN PHENOTYPES OF AGING OR

2489
01:50:00,633 --> 01:50:02,001
OVEREXPRESSED, SAY THE OPPOSITE

2490
01:50:02,001 --> 01:50:03,069
EFFECT BUT THAT'S ALL PRETTY

2491
01:50:03,069 --> 01:50:05,571
MUCH WHAT WE CAN DO NOW

2492
01:50:05,571 --> 01:50:08,875
EXPERIMENTALLY TO GET AT

2493
01:50:08,875 --> 01:50:09,208
CAUSALITY.

2494
01:50:09,208 --> 01:50:11,744
NOW WHETHER -- HOW SIGNIFICANT

2495
01:50:11,744 --> 01:50:13,579
IS THE CONTRIBUTION RELATIVE TO

2496
01:50:13,579 --> 01:50:15,214
OTHER AGING MECHANISMS, AS I

2497
01:50:15,214 --> 01:50:20,386
SHOWED IN MY HALLMARKS OF AGING

2498
01:50:20,386 --> 01:50:21,788
SLIDE, EVERY HALLMARK IS

2499
01:50:21,788 --> 01:50:23,589
CONNECTED TO EVERY OTHER

2500
01:50:23,589 --> 01:50:25,925
HALLMARK, BUT I PERSONALLY THINK

2501
01:50:25,925 --> 01:50:27,894
THAT EPIGENETIC ALERATIONS ARE

2502
01:50:27,894 --> 01:50:29,228
PRETTY FUNDAMENTAL BECAUSE

2503
01:50:29,228 --> 01:50:32,431
THAT'S WHERE YOU KNOW YOU CHANGE

2504
01:50:32,431 --> 01:50:37,003
THAT, AND YOU KNOW, YOU CAN HAVE

2505
01:50:37,003 --> 01:50:39,539
WIDE SPREAD EFFECTS THROUGH GENE

2506
01:50:39,539 --> 01:50:40,306
REGULATION.

2507
01:50:40,306 --> 01:50:45,344
SO I WOULD SEE IF YOU REALLY

2508
01:50:45,344 --> 01:50:46,245
IDENTIFY CAUSAL TRANSCRIPTION

2509
01:50:46,245 --> 01:50:48,214
FACTOR, YOU SHOULD BE ABLE TO --

2510
01:50:48,214 --> 01:50:52,485
YOU SHOULD BE ABLE TO YOU KNOW

2511
01:50:52,485 --> 01:50:54,253
MITIGATE SOME OF THOSE PROBLEMS

2512
01:50:54,253 --> 01:51:00,726
BUT YEAH, IT'S A VERY DIFFICULT

2513
01:51:00,726 --> 01:51:01,127
QUESTION.

2514
01:51:01,127 --> 01:51:02,895
>> IT'S A GREAT ANSWER FOR
A

2515
01:51:02,895 --> 01:51:04,163
VERY COMPLEX AND IMPORTANT

2516
01:51:04,163 --> 01:51:06,432
PROBLEM WHICH NEEDS MORE

2517
01:51:06,432 --> 01:51:08,167
SCIENCE, RIGHT?

2518
01:51:08,167 --> 01:51:08,434
>> YES.

2519
01:51:08,434 --> 01:51:11,204
>> LUIGI IS THERE ANY
CONNECTION

2520
01:51:11,204 --> 01:51:12,605
BETWEEN LIFE EXPECTANCY AND

2521
01:51:12,605 --> 01:51:15,508
REPRODUCTIVE AGE SPAN IN THAT'S

2522
01:51:15,508 --> 01:51:17,643
A QUESTION THAT AMEET ASKS, AND

2523
01:51:17,643 --> 01:51:19,579
THEN PRIMARILY CONCERNED BY THE

2524
01:51:19,579 --> 01:51:21,581
FACT THAT PUBERTY IS COMING TO

2525
01:51:21,581 --> 01:51:24,083
KIDS EARLIER NOW, THAN IT USED

2526
01:51:24,083 --> 01:51:26,419
TO BE WHICH DOES THIS HAVE ANY

2527
01:51:26,419 --> 01:51:29,889
POTENTIAL IMPACT ON LIFE SPAN OR

2528
01:51:29,889 --> 01:51:36,562
HEALTH SPAN, WHAT DO YOU THINK?

2529
01:51:36,562 --> 01:51:37,663
>> NOT MY STRONG KNOWLEDGE
BUT I

2530
01:51:37,663 --> 01:51:41,133
READ OF COURSE ABOUT THIS

2531
01:51:41,133 --> 01:51:42,301
CONTROVERSIAL AND THERE ARE

2532
01:51:42,301 --> 01:51:48,107
DIFFERENCES OF OPINION, BUT I

2533
01:51:48,107 --> 01:51:50,443
THINK THAT 1 LINE OF THE SEARCH

2534
01:51:50,443 --> 01:51:52,511
SEEMS TO BE VERY INTERESTING,

2535
01:51:52,511 --> 01:51:54,213
THE FACT THAT THE ANTICIPATION

2536
01:51:54,213 --> 01:52:04,056
OF PUBERTY SEEMED TO BE DUE TO

2537
01:52:04,056 --> 01:52:05,091
ENVIRONMENTAL EXPOSURE AND

2538
01:52:05,091 --> 01:52:07,827
DELIVER SOME EEIVETS AND OTHERS

2539
01:52:07,827 --> 01:52:10,463
SEEM TO BE ASSOCIATED WITH

2540
01:52:10,463 --> 01:52:18,905
ANTICIPATED PUBERTY IN SOME PART

2541
01:52:18,905 --> 01:52:20,406
OF THE WORLD WHETHER THE

2542
01:52:20,406 --> 01:52:23,142
PRODUCTIVE AGE IS ASSOCIATE WIDE

2543
01:52:23,142 --> 01:52:23,910
LONGEVITY.

2544
01:52:23,910 --> 01:52:27,046
I REALLY DON'T KNOW.

2545
01:52:27,046 --> 01:52:30,850
BUT WOMEN THAT HAVE MULTIPLE

2546
01:52:30,850 --> 01:52:32,852
CHILDREN THAT ARE NOT KNOWN TO

2547
01:52:32,852 --> 01:52:42,662
PRIOR, AND LONGER, THAT WE KNOW.

2548
01:52:42,662 --> 01:52:44,630
YEAH, SO CHRISTOPHER SAYS WITH

2549
01:52:44,630 --> 01:52:45,665
ADEQUATE NUTRITION?

2550
01:52:45,665 --> 01:52:51,504
THAT'S A VERY, VERY INTERESTING.

2551
01:52:51,504 --> 01:52:57,576
YOU KNOW LIFE CAUSE STUDIES HAVE

2552
01:52:57,576 --> 01:53:00,513
SHOWN THAT GAINING WEIGHT

2553
01:53:00,513 --> 01:53:02,048
THROUGH PRIOR TO PUBERTY IS A

2554
01:53:02,048 --> 01:53:04,116
GOOD THING, IF YOU GAIN WEIGHT

2555
01:53:04,116 --> 01:53:06,252
PRIOR TO PUBERTY THAT IS

2556
01:53:06,252 --> 01:53:08,220
PREDICTIVE OF HEALTH LATE OR IN

2557
01:53:08,220 --> 01:53:08,654
LIFE.

2558
01:53:08,654 --> 01:53:11,090
BY GAINING WEIGHT AFTER PUBERTY,

2559
01:53:11,090 --> 01:53:13,993
SEEMS TO BE ASSOCIATED WITH BAD

2560
01:53:13,993 --> 01:53:14,393
OUT COME.

2561
01:53:14,393 --> 01:53:16,696
WHAT IS THE MECHANISM THERE.

2562
01:53:16,696 --> 01:53:17,363
I DON'T KNOW.

2563
01:53:17,363 --> 01:53:18,998
AND IT'S MUCH STRONGER IN WOMEN

2564
01:53:18,998 --> 01:53:21,534
THAN IN MEN, BUT IN WOMEN, THE

2565
01:53:21,534 --> 01:53:28,174
EFFECT IS REALLY POWERFUL.

2566
01:53:28,174 --> 01:53:37,616
>> THAT'S VERY, VERY

2567
01:53:37,616 --> 01:53:38,050
INTERESTING.

2568
01:53:38,050 --> 01:53:39,218
LET ME AND SEE.

2569
01:53:39,218 --> 01:53:41,921
THERE WERE SOME VERY INTERESTING

2570
01:53:41,921 --> 01:53:47,660
QUESTIONS HERE WHICH SOMEHOW I

2571
01:53:47,660 --> 01:53:48,127
HAVE.

2572
01:53:48,127 --> 01:53:58,337
 -- AH, YES.

2573
01:54:01,173 --> 01:54:09,048
YOU REFERRED TO AGING PRETTY

2574
01:54:09,048 --> 01:54:15,921
MUCH AS A DISEASE OF CELLULAR

2575
01:54:15,921 --> 01:54:20,793
DAMAGE OF LIMITATION OF CELLULAR

2576
01:54:20,793 --> 01:54:26,232
RENEWAL AND REFERRED TO THE

2577
01:54:26,232 --> 01:54:29,635
APOPTOTIC CYCLE AND OTHERS AS

2578
01:54:29,635 --> 01:54:34,774
BEING ACCENTUATED IN THE AGING

2579
01:54:34,774 --> 01:54:36,976
PROCESS SO IF THAT'S CENTRAL, IS

2580
01:54:36,976 --> 01:54:44,250
THAT THE MAJOR LOCUST AT WHICH

2581
01:54:44,250 --> 01:54:45,451
BIOLOGICAL AGING BEGINS AND IF

2582
01:54:45,451 --> 01:54:45,818
SO --

2583
01:54:45,818 --> 01:54:48,220
>> FIRST OF ALL I THINK

2584
01:54:48,220 --> 01:54:49,121
BIOLOGICAL AGING STARTS

2585
01:54:49,121 --> 01:54:49,455
IMMEDIATELY.

2586
01:54:49,455 --> 01:54:53,893
I THINK THAT WE CANNOT ESCAPE

2587
01:54:53,893 --> 01:54:56,362
YOU KNOW THE CENTRAL DYNAMIC,

2588
01:54:56,362 --> 01:54:57,096
IT'S THERE.

2589
01:54:57,096 --> 01:55:02,635
AND SO I THINK THAT YOU KNOW I

2590
01:55:02,635 --> 01:55:04,870
DIDN'T HAVE THE TIME TO EXPLAIN

2591
01:55:04,870 --> 01:55:06,605
BEFORE BUT THINK ABOUT AGING

2592
01:55:06,605 --> 01:55:08,374
SOMETHING THAT IN THE OFF SENSE

2593
01:55:08,374 --> 01:55:11,210
OF ANYTHING CONTRASTING IT, WILL

2594
01:55:11,210 --> 01:55:13,279
OCCUR VERY RAPIDLY, YOU KNOW YOU

2595
01:55:13,279 --> 01:55:15,314
HAVE DAMAGE AND THIS DAMAGE IS

2596
01:55:15,314 --> 01:55:19,718
SO STRONG THAT AT SOME POINT,

2597
01:55:19,718 --> 01:55:23,589
IT'S NOT BY CHANCE THAT MASTER

2598
01:55:23,589 --> 01:55:24,590
PROGERIATRICKIZATIONIAS ARE

2599
01:55:24,590 --> 01:55:25,991
ASSOCIATED WITH THE EFFECT OF

2600
01:55:25,991 --> 01:55:27,993
DNA REPAIR BECAUSE THE DNA, THE

2601
01:55:27,993 --> 01:55:32,364
ONLY PART OF THE CELL THAT YOU

2602
01:55:32,364 --> 01:55:32,731
CANNOT EXCHANGE.

2603
01:55:32,731 --> 01:55:34,633
IT'S NOT THAT YOU'RE LIMITED IN

2604
01:55:34,633 --> 01:55:36,035
YOUR DNA, YOUR SYNTHESIS,

2605
01:55:36,035 --> 01:55:37,436
PROTEIN, CAN YOU DO THAT,

2606
01:55:37,436 --> 01:55:40,873
ALLEVIATE, YOU CAN DO THAT, THE

2607
01:55:40,873 --> 01:55:43,809
DNA IS THERE FOREVER UNTIL THE

2608
01:55:43,809 --> 01:55:48,981
CELL DIES, AND SO I THINK THAT

2609
01:55:48,981 --> 01:55:55,154
THE PRINCIPAL IS THAT AGING IS

2610
01:55:55,154 --> 01:55:57,389
ANOTHER PHYSICAL PHENOMENON, AND

2611
01:55:57,389 --> 01:56:01,093
THE QUESTION IS HOW WE CAN SLOW

2612
01:56:01,093 --> 01:56:04,964
IT DOWN AND NATURAL POURED SO

2613
01:56:04,964 --> 01:56:07,299
MUCH EFFORT IN SLOWING IT DOWN

2614
01:56:07,299 --> 01:56:09,368
THAT IT'S ABLE TO CREATE HUMAN

2615
01:56:09,368 --> 01:56:10,836
THAT LIVE 100 YEARS, THAT IS

2616
01:56:10,836 --> 01:56:13,172
BECAUSE OF THAT, BECAUSE OF

2617
01:56:13,172 --> 01:56:15,941
THOSE MECHANISMS -- AND I WANT

2618
01:56:15,941 --> 01:56:17,943
TO POINT THE EXAMPLE FROM THIS,

2619
01:56:17,943 --> 01:56:21,780
IF WE COULD ENHANCE THE EFFECT

2620
01:56:21,780 --> 01:56:24,517
OF THOSE MECHANISMS, THAT WOULD

2621
01:56:24,517 --> 01:56:26,118
BE THE MOST POWERFUL MEDICAL

2622
01:56:26,118 --> 01:56:28,020
APPROACH TO HEALTH THAT WE CAN

2623
01:56:28,020 --> 01:56:28,654
THINK OF.

2624
01:56:28,654 --> 01:56:32,057
AND SO, I DON'T THINK AGING IS A

2625
01:56:32,057 --> 01:56:32,458
DISEASE.

2626
01:56:32,458 --> 01:56:36,962
I THINK THAT AGING IS ENOUGH OF

2627
01:56:36,962 --> 01:56:39,265
A PHENOMENON AND WE FIGHT

2628
01:56:39,265 --> 01:56:43,536
CONSTANTLY DURING OUR ENTIRE

2629
01:56:43,536 --> 01:56:45,604
LIFEY TO SLOW DOWN, THAT'S THE

2630
01:56:45,604 --> 01:56:47,406
WAY TO THINK ABOUT IT.

2631
01:56:47,406 --> 01:56:49,875
>> ALL RIGHT, P A YEL, DO
YOU

2632
01:56:49,875 --> 01:56:52,912
WANT TO COMMENT ABOUT THAT?

2633
01:56:52,912 --> 01:57:02,421
WHAT IS YOUR CONCEPT OF AGING?

2634
01:57:02,421 --> 01:57:04,957
>> I WOULD AGREE WITH
LUIGI.

2635
01:57:04,957 --> 01:57:08,394
I DON'T THINK AGING IS A

2636
01:57:08,394 --> 01:57:09,094
DISEASE.

2637
01:57:09,094 --> 01:57:11,597
AGING, MY NAIVE IDEA OF AGE

2638
01:57:11,597 --> 01:57:15,301
SUGGEST THAT IT'S A NATURAL

2639
01:57:15,301 --> 01:57:16,535
PROCESS LIKE LUIGI SAID AND IN

2640
01:57:16,535 --> 01:57:22,141
FACT, I ALMOST THINK OF IT AS

2641
01:57:22,141 --> 01:57:23,709
BENEFICIAL, BENEFICIAL TO

2642
01:57:23,709 --> 01:57:27,613
PREVENT CANCER AND THAT'S -- BUT

2643
01:57:27,613 --> 01:57:31,517
UNFORTUNATELY SOME SIDE EFFECTS

2644
01:57:31,517 --> 01:57:36,722
COULD BE, YOU KNOW THE ONSET OF

2645
01:57:36,722 --> 01:57:37,356
DEGENERATIVE DISEASES AS I

2646
01:57:37,356 --> 01:57:39,959
MENTIONED SO I REALLY THINK IT

2647
01:57:39,959 --> 01:57:44,563
IS A BALANCE OF PREVENTING

2648
01:57:44,563 --> 01:57:45,531
CANCER AND MAINTAINING FUNCTION

2649
01:57:45,531 --> 01:57:48,367
AND THE ONLY WAY TO DO THAT IS

2650
01:57:48,367 --> 01:57:51,303
UNFORTUNATELY GO DOWN THE

2651
01:57:51,303 --> 01:57:52,538
DEGENERATIVE ROUTE AND

2652
01:57:52,538 --> 01:57:56,475
THEREFORE, I DON'T THINK AGING

2653
01:57:56,475 --> 01:58:00,980
ITSELF IS A DISEASE, IT MAKES

2654
01:58:00,980 --> 01:58:03,249
THE CELLS MAYBE GET DISEASE AT

2655
01:58:03,249 --> 01:58:08,921
SOME POINT OR BE ASSOCIATED WITH

2656
01:58:08,921 --> 01:58:09,955
A DISEASE STATE.

2657
01:58:09,955 --> 01:58:15,794
>> SO YES, LET ME THROW IN
JUST

2658
01:58:15,794 --> 01:58:17,396
A BRIEF COMMENT HERE, SOMEWHERE

2659
01:58:17,396 --> 01:58:19,398
IN DISCUSSION OF AGING AND A LOT

2660
01:58:19,398 --> 01:58:21,934
OF THINGS, ATTENTION IS DIRECTED

2661
01:58:21,934 --> 01:58:31,176
TO CELLULAR TURNOVER, TO

2662
01:58:31,176 --> 01:58:33,579
ORGANELLE TURNOVER, BUT EVERY

2663
01:58:33,579 --> 01:58:34,947
MEMBRANE, EVERY STRUCTURE WITHIN

2664
01:58:34,947 --> 01:58:36,682
THE CELL CONSISTS OF HUGE

2665
01:58:36,682 --> 01:58:38,217
NUMBERS OF PROTEINS, LIPIDS AND

2666
01:58:38,217 --> 01:58:40,386
SO FORTH EACH 1 OF WHICH HAS ITS

2667
01:58:40,386 --> 01:58:43,656
OWN INDEPENDENT RATE OF

2668
01:58:43,656 --> 01:58:45,224
DEGRADATION AND PARTICULARLY,

2669
01:58:45,224 --> 01:58:46,525
AND SYNTHESIS AND DEGRADATION,

2670
01:58:46,525 --> 01:58:48,827
SO ALTHOUGH LIKE THE MEMBRANE

2671
01:58:48,827 --> 01:58:51,797
LOOKS INTACT, IN FACT, ALL OF

2672
01:58:51,797 --> 01:58:54,033
ITS COMPONENTS INDIVIDUALLY ARE

2673
01:58:54,033 --> 01:58:55,334
RAPIDLY TURNING OVER, THERE'S A

2674
01:58:55,334 --> 01:58:57,436
WHOLE DIMENSION OF DYNAMICS THAT

2675
01:58:57,436 --> 01:59:00,039
IS NOT -- THAT IS ONLY SEEN WHEN

2676
01:59:00,039 --> 01:59:03,842
YOU BEGIN TO SEE HIGH RESOLUTION

2677
01:59:03,842 --> 01:59:05,811
MICROSCOPY FOR EXAMPLE.

2678
01:59:05,811 --> 01:59:09,381
SO I'M CURIOUS, AT ANY POINT IN

2679
01:59:09,381 --> 01:59:10,749
THE CONSIDERATION OF AGING IS

2680
01:59:10,749 --> 01:59:14,887
THIS LEVEL OF DYNAMICS

2681
01:59:14,887 --> 01:59:15,187
CONSIDERED?

2682
01:59:15,187 --> 01:59:21,560
PEOPLE WHO ARE DOING SUPER

2683
01:59:21,560 --> 01:59:22,428
RESOLUTION MICROSCOPY OF

2684
01:59:22,428 --> 01:59:30,869
MOLECULES CONCERNED WITH THE

2685
01:59:30,869 --> 01:59:32,037
AGING PROCESS?

2686
01:59:32,037 --> 01:59:34,073
>> WELL, AS FARs I KNOW,
WE

2687
01:59:34,073 --> 01:59:35,341
KNOW LITTLE ABOUT THAT BUT 1

2688
01:59:35,341 --> 01:59:37,209
STUDY THAT THE NIA IS DOING IS

2689
01:59:37,209 --> 01:59:38,610
LOOKING AT THE HALF LIFE OF

2690
01:59:38,610 --> 01:59:40,446
PROTEIN, WHETHER THE HALF LIFE

2691
01:59:40,446 --> 01:59:43,415
OF PROTEIN CHANGE WITH AGING AND

2692
01:59:43,415 --> 01:59:49,722
WE DO THAT BY, YOU KNOW,

2693
01:59:49,722 --> 01:59:50,756
STUDYING HUMANS, HEAVY WATER,

2694
01:59:50,756 --> 01:59:52,725
AND THEY TAKE THE HEAVY WATER

2695
01:59:52,725 --> 01:59:55,327
FOR A CERTAIN PERIOD OF TIME.

2696
01:59:55,327 --> 02:00:02,401
OF COURSE, THAT DID MARK THE

2697
02:00:02,401 --> 02:00:05,003
SAMPLE TO SIPGHTICIZE AND THEN

2698
02:00:05,003 --> 02:00:06,405
YOU DO A SECOND SAMPLE AND YOU

2699
02:00:06,405 --> 02:00:08,474
ASSUME THAT THE SYNTH SCIZZ AND

2700
02:00:08,474 --> 02:00:10,943
DEGRADATION SHOULD BE IN THE

2701
02:00:10,943 --> 02:00:12,211
EQUILL LIP RIBIUM BECAUSE THEY

2702
02:00:12,211 --> 02:00:15,314
REMAIN CONSTANT AND YOU CAN

2703
02:00:15,314 --> 02:00:16,548
UNDERSTAND WHAT IS THE HALF LIFE

2704
02:00:16,548 --> 02:00:18,917
OF THE PROTEIN AND YOU STUDYING

2705
02:00:18,917 --> 02:00:23,155
YOU CAN IMAGINE WOULD REQUIRE

2706
02:00:23,155 --> 02:00:26,191
TIME BECAUSE IT REQUIRE A LONG

2707
02:00:26,191 --> 02:00:27,826
PERIOD OF FINDING THE HEAVY

2708
02:00:27,826 --> 02:00:30,195
WATER AND SO, WE WILL KNOW THE

2709
02:00:30,195 --> 02:00:32,965
RESULT BUT WE DON'T KNOW THOSE

2710
02:00:32,965 --> 02:00:33,899
YET.

2711
02:00:33,899 --> 02:00:34,800
>> ALL RIGHT, WELL,
LISTEN,

2712
02:00:34,800 --> 02:00:37,336
WE'VE RUN OUT OF TIME BUT I WANT

2713
02:00:37,336 --> 02:00:40,539
TO THANK ON BEHALF OF ALL THE

2714
02:00:40,539 --> 02:00:42,374
PEOPLE WATCHING, AND WE ARE

2715
02:00:42,374 --> 02:00:50,182
AROUND THE WORLD, I AM TOLD AT

2716
02:00:50,182 --> 02:00:52,251
LAST, SO, THANK YOU AGAIN AND WE

2717
02:00:52,251 --> 02:00:53,952
LOOK FORWARD TO FURTHER

2718
02:00:53,952 --> 02:00:55,387
DISCUSSIONS BECAUSE ALL OF US

2719
02:00:55,387 --> 02:00:58,157
ARE AGING NTHANK YOU VERY MUCH.

2720
02:00:58,157 --> 02:00:59,491
IT'S BEEN A PLEASURE REALLY TO

2721
02:00:59,491 --> 02:01:02,828
BE HERE WITH YOU, ALL OF YOU.

2722
02:01:02,828 --> 02:01:03,195
>> THANK YOU.

2723
02:01:03,195 --> 02:01:04,563
>> THANK YOU.

2724
02:01:04,563 --> 02:01:04,930
YES. 

2725
02:01:04,930 --> 02:01:15,274
>> SO WE'RE OFF.