1
00:00:05,480 --> 00:00:07,280
>> WELCOME TO THE DNA REPAIR

2
00:00:07,280 --> 00:00:09,600
INTEREST GROUP.

3
00:00:09,600 --> 00:00:11,280
TODAY OUR SPEAKER IS FROM THE

4
00:00:11,280 --> 00:00:14,520
UNIVERSITY OF ROCHESTER

5
00:00:14,520 --> 00:00:17,400
WILL BE SPEAKING AT THE AGING

6
00:00:17,400 --> 00:00:18,200
INSTITUTE IN BALTIMORE AND

7
00:00:18,200 --> 00:00:20,360
EVERYONE ELSE BE SURE TO MUTE

8
00:00:20,360 --> 00:00:21,680
AND LET'S UNMUTE IN BALTIMORE

9
00:00:21,680 --> 00:00:23,080
AND TAKE IT AWAY, WILL.

10
00:00:23,080 --> 00:00:24,240
>>THIS IS A JOINT

11
00:00:24,240 --> 00:00:28,400
LECTURE FOR THE NIA

12
00:00:28,400 --> 00:00:30,240
AND INTRAMURAL PROGRAM AND FOR

13
00:00:30,240 --> 00:00:32,440
THE DNA REPAIR INTEREST GROUP

14
00:00:32,440 --> 00:00:36,520
AND IT'S EXTREMELY BEFITTING

15
00:00:36,520 --> 00:00:39,440
THAT IT'S DONE BY VERA,

16
00:00:39,440 --> 00:00:41,080
GORBUNOVA WHO IS VERY MUCH

17
00:00:41,080 --> 00:00:42,360
ASSOCIATED WITH AGING AND DNA

18
00:00:42,360 --> 00:00:44,360
REPAIR SO WE'RE LOOKING VERY

19
00:00:44,360 --> 00:00:48,360
MUCH FORWARD TO THIS TALK.

20
00:00:48,360 --> 00:00:50,520
AND VERA IS--DID HER GRADUATE

21
00:00:50,520 --> 00:00:53,520
WORK IN ISRAEL, THEN WENT ON TO

22
00:00:53,520 --> 00:00:55,960
DIFFERENT OTHER PLACES AS A POST

23
00:00:55,960 --> 00:00:59,240
DOC AND BECAME A PROFESSOR AT

24
00:00:59,240 --> 00:01:02,360
ROCHESTER UNIVERSITY

25
00:01:02,360 --> 00:01:04,840
AND SHE IS NOW AN ESTABLISHED

26
00:01:04,840 --> 00:01:07,640
PROFESSOR IN NEED OF AN AGING

27
00:01:07,640 --> 00:01:11,120
CENTER THERE, SHE'S ALSO VERY

28
00:01:11,120 --> 00:01:13,200
POPULAR SPEAKER ON MANY MEETINGS

29
00:01:13,200 --> 00:01:14,600
AROUND THE WORLD THAT SOME OF

30
00:01:14,600 --> 00:01:17,400
THEM I HAD THE PLEASURE TO

31
00:01:17,400 --> 00:01:20,880
ATTEND AND YOU ARE ALSO ON MANY

32
00:01:20,880 --> 00:01:25,640
COMMITTEES AND BOARDS AND HAVE

33
00:01:25,640 --> 00:01:27,680
REALLY DONE A WONDERFUL JOB AT

34
00:01:27,680 --> 00:01:31,080
THIS INTERPHASE OF AGING AND DNA

35
00:01:31,080 --> 00:01:31,520
REPAIR.

36
00:01:31,520 --> 00:01:32,480
VERA DEVELOPED SOME EXCELLENT

37
00:01:32,480 --> 00:01:35,480
ASSAYS THAT MANY OF US ARE USING

38
00:01:35,480 --> 00:01:37,400
FOR CELL ASSESSMENT OF DNA

39
00:01:37,400 --> 00:01:40,680
REPAIR AND JOINING DOUBLE STRAND

40
00:01:40,680 --> 00:01:43,600
BREAK REPAIR, SHE'S ALSO WORLD

41
00:01:43,600 --> 00:01:44,800
ROAFING EXPERT AND WE WILL HEAR

42
00:01:44,800 --> 00:01:46,960
ABOUT ALL THIS AND SHE HAS--I

43
00:01:46,960 --> 00:01:48,800
HAD THE PLEASURE OF VISITING AND

44
00:01:48,800 --> 00:01:50,480
SEEING THE NAKED MOLE RAT WHICH

45
00:01:50,480 --> 00:01:53,320
IS A FANTASTIC CREATURE REALLY

46
00:01:53,320 --> 00:01:57,840
TELLS A LOT ABOUT AGING BUT ALSO

47
00:01:57,840 --> 00:02:01,360
LATELY SHE'S DONE SOME

48
00:02:01,360 --> 00:02:02,840
MAJOR--HAD SOME MAJOR FINDINGS

49
00:02:02,840 --> 00:02:05,040
AGAIN IN THIS INTERNATIONAL

50
00:02:05,040 --> 00:02:07,160
CLASSIFICATION FACE WITH SIRT6

51
00:02:07,160 --> 00:02:08,960
BEING A LONGEVITY GENE AND LINE

52
00:02:08,960 --> 00:02:09,960
ELEMENTS AND OTHER THINGS THAT I

53
00:02:09,960 --> 00:02:11,440
WILL HEAR ABOUT AND I WILL NOT

54
00:02:11,440 --> 00:02:12,920
TAKE MORE TIME BUT JUST SAY THAT

55
00:02:12,920 --> 00:02:14,640
WE ARE VERY PLEASED.

56
00:02:14,640 --> 00:02:17,120
IT WAS DELAYED, THIS LECTURE

57
00:02:17,120 --> 00:02:19,080
FROM WHEN WE HAVE PLANNED IT AND

58
00:02:19,080 --> 00:02:20,200
NOW WE'RE VERY PLEASED THAT YOU

59
00:02:20,200 --> 00:02:20,640
ARE HERE.

60
00:02:20,640 --> 00:02:21,920
WE LOOK FORWARD TO YOUR TALK AND

61
00:02:21,920 --> 00:02:23,880
WHEN YOU'RE DONE WITH THE TALK

62
00:02:23,880 --> 00:02:24,920
WE WILL FIRST HAVE SOME

63
00:02:24,920 --> 00:02:27,120
QUESTIONS HERE BEFORE WE TURN

64
00:02:27,120 --> 00:02:30,360
AROUND TO THE OTHER MEMBERS OF

65
00:02:30,360 --> 00:02:32,040
THE DNA INTEREST GROUP AND I

66
00:02:32,040 --> 00:02:33,320
WILL GUIDE THAT AFTERWARDS.

67
00:02:33,320 --> 00:02:34,280
SO THANK YOU VERY MUCH FOR

68
00:02:34,280 --> 00:02:35,040
COMING.

69
00:02:35,040 --> 00:02:36,840
>> THANK ARE FOR HOSTING

70
00:02:36,840 --> 00:02:40,600
ME AND THANK YOU FOR SHOWING AND

71
00:02:40,600 --> 00:02:42,080
UP AND SPEAKING ABOUT THIS ALL

72
00:02:42,080 --> 00:02:44,160
OVER THE COUNTRY, I WILL TRY NOT

73
00:02:44,160 --> 00:02:49,320
TO DISAPPOINT.

74
00:02:49,320 --> 00:02:53,880
SO SINCE IT'S DNA REPAIR

75
00:02:53,880 --> 00:02:55,040
INTEREST GROUP AND NOT ALL

76
00:02:55,040 --> 00:02:57,480
INTERESTED IN AGING SO I BROUGHT

77
00:02:57,480 --> 00:02:59,400
UP THIS SLIDE TO KIND OF

78
00:02:59,400 --> 00:03:02,600
DEMONSTRATE WHAT WE ARE TRYING

79
00:03:02,600 --> 00:03:07,200
TO ACHIEVE HERE,

80
00:03:07,200 --> 00:03:08,080
[INDISCERNIBLE].

81
00:03:08,080 --> 00:03:11,080
AND FOCUSING ON THE DNA REPAIR

82
00:03:11,080 --> 00:03:12,440
OF COURSE, PEOPLE ALWAYS WANTED

83
00:03:12,440 --> 00:03:14,560
TO FIND HOW THEY INFUSE AND

84
00:03:14,560 --> 00:03:15,800
THAT'S HOW MAY MENTION IT IN THE

85
00:03:15,800 --> 00:03:18,120
BOOK BEFORE AND NOW WE ARE DOING

86
00:03:18,120 --> 00:03:20,320
IT, YOU KNOW MAYBE THROUGH MORE

87
00:03:20,320 --> 00:03:22,520
MOLECULAR MEANS BUT AGAIN, THE

88
00:03:22,520 --> 00:03:24,760
IDEA IS LET'S FIND SOMETHING

89
00:03:24,760 --> 00:03:32,400
THAT CAN MAKE PEOPLE YOUNGER OR

90
00:03:32,400 --> 00:03:34,240
MAKE THE AGING SLOWING.

91
00:03:34,240 --> 00:03:36,960
THE APPROACH MY GROUP IS USING

92
00:03:36,960 --> 00:03:40,280
TO THAT IS A BIOLOGY APPROACH.

93
00:03:40,280 --> 00:03:41,720
SO WHAT THIS COMPARATIVE

94
00:03:41,720 --> 00:03:45,640
BIOLOGY, YOU KNOW WE ALSO USE

95
00:03:45,640 --> 00:03:47,840
MOUSE MODELS THAT ARE EXTREMELY

96
00:03:47,840 --> 00:03:50,280
USEFUL TO ANSWER MANY

97
00:03:50,280 --> 00:03:52,480
MECHANISTIC QUESTIONS, BUT TO

98
00:03:52,480 --> 00:03:54,480
UNDERSTAND AGING LIMITATION IS

99
00:03:54,480 --> 00:03:57,400
THAT MICE DON'T REALLY LIVE VERY

100
00:03:57,400 --> 00:03:57,720
LONG.

101
00:03:57,720 --> 00:03:59,320
THEY ACTUALLY LIVE EXTREMELY

102
00:03:59,320 --> 00:04:00,120
SHORT.

103
00:04:00,120 --> 00:04:03,920
SO THAT'S WHERE WE DECIDED TO

104
00:04:03,920 --> 00:04:05,600
EXPLORE WHAT NATURE GENERATED

105
00:04:05,600 --> 00:04:08,920
FOR US IN THE COURSE OF

106
00:04:08,920 --> 00:04:11,400
REVOLUTION SO YOU WORK WITHIN

107
00:04:11,400 --> 00:04:12,520
MAMMALIAN TRADE, YOU HAVE

108
00:04:12,520 --> 00:04:13,520
SPEECHES THAT DIFFER UP TO A

109
00:04:13,520 --> 00:04:18,400
HUNDRED FOLD IN THE LIFE SPAN

110
00:04:18,400 --> 00:04:21,600
FROM 2 YEARS IN A SHREW TO OVER

111
00:04:21,600 --> 00:04:23,200
200 YEARS IN [INDISCERNIBLE].

112
00:04:23,200 --> 00:04:27,720
SO THEN THE GOAL IS TO TRY TO

113
00:04:27,720 --> 00:04:29,320
FIND THE MECHANISMS THAT ARE

114
00:04:29,320 --> 00:04:30,920
DIFFERENT IN THE SHREW AND IN

115
00:04:30,920 --> 00:04:33,000
THE WHALE AND THEN ONCE YOU

116
00:04:33,000 --> 00:04:37,200
UNDERSTAND IT THEN THERE IS A

117
00:04:37,200 --> 00:04:39,560
POTENTIAL FOR SIGNIFICANT&

118
00:04:39,560 --> 00:04:40,480
IMPROVEMENT, YOU KNOW

119
00:04:40,480 --> 00:04:41,880
[INDISCERNIBLE] BECAUSE YOU KNOW

120
00:04:41,880 --> 00:04:43,680
HUMANS ARE LONG LIVED ALREADY SO

121
00:04:43,680 --> 00:04:48,040
WE REALLY NEED TO FIND SOMETHING

122
00:04:48,040 --> 00:04:50,080
THAT IS PRETTY STRONG TO BENEFIT

123
00:04:50,080 --> 00:04:50,440
HUMANS.

124
00:04:50,440 --> 00:04:52,400
SO THERE ARE DIFFERENT

125
00:04:52,400 --> 00:04:53,400
MECHANISMS OF LONGEVITY.

126
00:04:53,400 --> 00:04:54,760
THEY ARE CONSERVED, THE PUBLIC

127
00:04:54,760 --> 00:04:58,400
MECHANISMS SO I WILL BE TALKING

128
00:04:58,400 --> 00:04:59,040
PROBABLY MOSTLY ABOUT THIS

129
00:04:59,040 --> 00:05:01,240
THROUGH MY TALK TO BE ABLE TO

130
00:05:01,240 --> 00:05:02,440
TALK ABOUT DNA REPAIR.

131
00:05:02,440 --> 00:05:04,440
WE ALSO STUDY THOSE PRIVATE

132
00:05:04,440 --> 00:05:07,400
MECHANISMS THAT ONLY APPEAR IN

133
00:05:07,400 --> 00:05:08,120
CERTAIN [INDISCERNIBLE].

134
00:05:08,120 --> 00:05:09,720
FOR EXAMPLE, WE DO A LOT OF

135
00:05:09,720 --> 00:05:12,000
STUDIES ON NAKED MOLE RATS.

136
00:05:12,000 --> 00:05:14,600
THEY ARE THE LONGEST LIVE

137
00:05:14,600 --> 00:05:16,920
RODENTS, THEY LIVE OVER 30 YEARS

138
00:05:16,920 --> 00:05:19,200
AND WE FIND MANY INTERESTING

139
00:05:19,200 --> 00:05:21,120
THINGS ABOUT NAKED MOLE RATS BUT

140
00:05:21,120 --> 00:05:22,720
THAT WOULD HAVE TO BE A

141
00:05:22,720 --> 00:05:24,360
DIFFERENT SEMINAR SO I WOULD NOT

142
00:05:24,360 --> 00:05:27,320
TALK TOO MUCH ABOUT NAKED MOLE

143
00:05:27,320 --> 00:05:27,560
RAT.

144
00:05:27,560 --> 00:05:31,120
SO LET ME START WITH CONCERNED

145
00:05:31,120 --> 00:05:33,120
MECHANISM OF AGING.

146
00:05:33,120 --> 00:05:34,320
SO WE'RE WONDERING WHETHER DNA

147
00:05:34,320 --> 00:05:40,000
REPAIR IS 1 OF THOSE CONSERVED

148
00:05:40,000 --> 00:05:41,520
MECHANISMS AND WHETHER

149
00:05:41,520 --> 00:05:42,760
SHORT-LIVED SPECIES ARE LESS

150
00:05:42,760 --> 00:05:44,320
GOOD AT REPAIRING DNA DAMAGE AND

151
00:05:44,320 --> 00:05:46,960
WE KIND OF ALWAYS ASSUMED DNA

152
00:05:46,960 --> 00:05:50,000
REPAIR IS CENTRAL TO THE AGING

153
00:05:50,000 --> 00:05:51,360
PROCESS BUT MOST EVIDENCE CAME

154
00:05:51,360 --> 00:05:54,920
FROM THE STUDIES OF MUTANTS THAT

155
00:05:54,920 --> 00:05:56,680
THE DEFICIENT IN DNA REPAIR AND

156
00:05:56,680 --> 00:05:58,520
THEN THEY SHOW PREMATURE AGING

157
00:05:58,520 --> 00:06:00,520
PHENOTYPES SO THEN WE ASSUME IF

158
00:06:00,520 --> 00:06:03,440
THIS IS IMPORTANT FOR LONGEVITY,

159
00:06:03,440 --> 00:06:06,920
BUT WHAT CRITICS WAS SAYING THAT

160
00:06:06,920 --> 00:06:09,400
WELL, YOU KNOW, YOU KNOW

161
00:06:09,400 --> 00:06:11,000
JUST--YOU SCREW SOMETHING UP AND

162
00:06:11,000 --> 00:06:14,120
THE ANIMALS GET SICK AND WHAT

163
00:06:14,120 --> 00:06:15,120
DOES IT PROVE?

164
00:06:15,120 --> 00:06:17,400
IF WE COULD PROVE ASSOCIATION OF

165
00:06:17,400 --> 00:06:19,040
BETTER DNA REPAIR WITH LONGER

166
00:06:19,040 --> 00:06:22,720
LIFE SPAN SO THAT THEY COULD

167
00:06:22,720 --> 00:06:23,800
[INDISCERNIBLE] THINK IT IS

168
00:06:23,800 --> 00:06:27,040
IMPORTANT BUT BECAUSE IT'S NOT

169
00:06:27,040 --> 00:06:29,120
SO EASY TO IMPROVE DNA REPAIR,

170
00:06:29,120 --> 00:06:33,120
AND SO WE TALK ABOUT LET'S START

171
00:06:33,120 --> 00:06:35,040
WITH THE NATURAL COLLECTION,

172
00:06:35,040 --> 00:06:37,200
MEASURE DNA REPAIR IN SPECIES OF

173
00:06:37,200 --> 00:06:39,120
DIFFERENT LIFE SPAN AND SEE

174
00:06:39,120 --> 00:06:41,120
WHETHER THERE IS A RELATIONSHIP.

175
00:06:41,120 --> 00:06:43,520
AND THESE ARE MODEL SYSTEMS SO

176
00:06:43,520 --> 00:06:47,120
WE HAVE PRIMARY CELLS FROM MORE

177
00:06:47,120 --> 00:06:49,720
THAN 20 SPECIES OF RODENTS WITH

178
00:06:49,720 --> 00:06:53,160
VERY DIVERSE LIFE SPANS SO

179
00:06:53,160 --> 00:06:57,360
SHORTLY TO VERY LONG LIVED, AND

180
00:06:57,360 --> 00:07:00,120
WE FELT OKAY.

181
00:07:00,120 --> 00:07:03,760
SO THE MORE I WILL TELL YOU

182
00:07:03,760 --> 00:07:07,920
ABOUT THAT WAS MOSTLY DONE BY

183
00:07:07,920 --> 00:07:11,560
THIS VERY TALENTED STUDENT AND

184
00:07:11,560 --> 00:07:12,800
[INDISCERNIBLE] SO THEY WERE

185
00:07:12,800 --> 00:07:13,680
HOLDING CANNED WHAT.

186
00:07:13,680 --> 00:07:15,760
HIS OTHER WORK WAS WITH NAKED

187
00:07:15,760 --> 00:07:19,360
MOLE RAT BUT HERE HE DECIDED TO

188
00:07:19,360 --> 00:07:21,920
FOCUS ON DNA REPAIR AND

189
00:07:21,920 --> 00:07:26,280
THE--THERE ARE ALL KINDS OF

190
00:07:26,280 --> 00:07:29,080
IMAGE DAMAGES EXTERNAL, INTERNAL

191
00:07:29,080 --> 00:07:32,360
THAT GENERATE DIFFERENT TYPES OF

192
00:07:32,360 --> 00:07:35,480
LESIONS THAT THEN REPAIRED FROM

193
00:07:35,480 --> 00:07:36,360
THE REPAIR PATHWAYS.

194
00:07:36,360 --> 00:07:42,000
SO THE FIRST PATHWAY THAT XIAO

195
00:07:42,000 --> 00:07:43,000
DECIDED TO EXAMINE WAS EXCISION

196
00:07:43,000 --> 00:07:43,520
REPAIR.

197
00:07:43,520 --> 00:07:51,920
AND THIS PATHWAY WAS ALREADY

198
00:07:51,920 --> 00:07:55,920
STUDIED HISTORICALLY DIFFERENT

199
00:07:55,920 --> 00:07:57,440
[INDISCERNIBLE] THOSE PAPERS

200
00:07:57,440 --> 00:08:00,480
FROM THE 70S, THE PROBLEM WAS

201
00:08:00,480 --> 00:08:02,680
THAT THE RESULT IS SOMEWHAT

202
00:08:02,680 --> 00:08:03,880
UNCLEAR BECAUSE THERE ARE

203
00:08:03,880 --> 00:08:05,280
SEVERAL STUDIES OF

204
00:08:05,280 --> 00:08:07,640
[INDISCERNIBLE], SEVERAL STUDIES

205
00:08:07,640 --> 00:08:09,520
OF [INDISCERNIBLE].

206
00:08:09,520 --> 00:08:11,840
AND THEN WHAT WAS CRITICIZED FOR

207
00:08:11,840 --> 00:08:16,920
THE INSEVERE MITRAL LOW WORK,

208
00:08:16,920 --> 00:08:18,640
AND SPECIES WERE ALSO SPECIES

209
00:08:18,640 --> 00:08:21,720
THAT WERE DISCIPLINARY URNAL AND

210
00:08:21,720 --> 00:08:25,240
ARE EXPOSED TO SUN LIGHT AND

211
00:08:25,240 --> 00:08:27,840
CERTAIN SPECIES THAT ARE NOCT

212
00:08:27,840 --> 00:08:28,920
URNAL, SO THE CORRELATION WAS

213
00:08:28,920 --> 00:08:30,560
STRONG BUT IT WAS NOT CLEAR WAS

214
00:08:30,560 --> 00:08:32,360
IT BECAUSE OF LIFESTYLE OR

215
00:08:32,360 --> 00:08:35,400
BECAUSE OF THE [INDISCERNIBLE]?

216
00:08:35,400 --> 00:08:38,240
SO XIAO DECIDED TO USE OUR

217
00:08:38,240 --> 00:08:39,840
RODENT COLLECTION WHERE WE WERE

218
00:08:39,840 --> 00:08:41,840
KIND OF LESS BIASED IN TERMS OF

219
00:08:41,840 --> 00:08:45,520
SPECIES SELECTIONS OF THE OLD

220
00:08:45,520 --> 00:08:47,640
RODENTS. 

221
00:08:47,640 --> 00:08:55,920
HE USE PLASMA DIRECT DURATION

222
00:08:55,920 --> 00:08:59,160
WHERE SIMPLY MUTEGENERATEDDIZE

223
00:08:59,160 --> 00:09:04,200
THE CELLS AND SO THIS IS WHAT

224
00:09:04,200 --> 00:09:06,600
XIAO SHOWED, DNA EXCISION REPAIR

225
00:09:06,600 --> 00:09:09,920
SO THIS IS MAXIMUM LIFE SPAN,

226
00:09:09,920 --> 00:09:12,120
DEFICIENCY, THERE WAS NO

227
00:09:12,120 --> 00:09:14,400
CORRELATION WHATSOEVER.

228
00:09:14,400 --> 00:09:18,320
NEITHER WITH THE [INDISCERNIBLE]

229
00:09:18,320 --> 00:09:20,320
SO FROM THERE XAIO DECIDED TO

230
00:09:20,320 --> 00:09:21,600
GROUP SPECIES DIFFERENT NOT BY

231
00:09:21,600 --> 00:09:26,560
LIFE SPAN BUT BY THE AMOUNT OF

232
00:09:26,560 --> 00:09:30,040
UV EXPOSURE BECAUSE NUCLEIC WAS

233
00:09:30,040 --> 00:09:31,480
INDUCED IN DIMERS AND THEY

234
00:09:31,480 --> 00:09:35,360
PRODUCED BY UV LIGHT FROM THE

235
00:09:35,360 --> 00:09:35,960
SUN.

236
00:09:35,960 --> 00:09:41,760
SO HE GREW THE SPECIES TO

237
00:09:41,760 --> 00:09:43,680
NOCTURNAL AND AND THE DUSK WITH

238
00:09:43,680 --> 00:09:45,360
THE SPECIES WITH THE SQUIRRELS

239
00:09:45,360 --> 00:09:46,960
OR FOREST OR SPECIES

240
00:09:46,960 --> 00:09:50,680
[INDISCERNIBLE] AND THEN HE

241
00:09:50,680 --> 00:09:52,560
QUOTE TODAY BY SUFFICIENCY AND

242
00:09:52,560 --> 00:09:57,040
WE SAW STRONG CORRELATION SO IT

243
00:09:57,040 --> 00:10:00,600
WASN'T LIFE SPAN IT WAS THE--THE

244
00:10:00,600 --> 00:10:04,200
PSYCHOLOGICAL NEARBY AND HOW

245
00:10:04,200 --> 00:10:04,680
MUCH [INDISCERNIBLE].

246
00:10:04,680 --> 00:10:07,120
AND WHEN THE ONLY FOCUS TO THIS

247
00:10:07,120 --> 00:10:09,320
GROUP BECAUSE THESE 2 GROUPS, I

248
00:10:09,320 --> 00:10:12,720
KNOW IT'S A MIXED BAG AND SPEND

249
00:10:12,720 --> 00:10:15,320
A LITTLE MORE IN THE SIGN OF IT

250
00:10:15,320 --> 00:10:17,720
THIS IS KIND OF CLEAN, SO THESE

251
00:10:17,720 --> 00:10:22,800
ARE SPECEBS THAT ARE EITHER

252
00:10:22,800 --> 00:10:24,520
SUBTERANNIAN OR EXTREMELY

253
00:10:24,520 --> 00:10:25,800
NOCTURNAL SO THEY ARE NOT

254
00:10:25,800 --> 00:10:26,520
EXPOSED.

255
00:10:26,520 --> 00:10:29,120
SO IN THAT GROUP THERE WAS A

256
00:10:29,120 --> 00:10:30,920
TREND THAT WAS CORRELATION TO

257
00:10:30,920 --> 00:10:31,680
LIFE SPAN.

258
00:10:31,680 --> 00:10:33,320
IT DIDN'T QUITE REACH

259
00:10:33,320 --> 00:10:34,320
SIGNIFICANCE BECAUSE WE

260
00:10:34,320 --> 00:10:35,280
[INDISCERNIBLE] SPECIES IN THE

261
00:10:35,280 --> 00:10:37,520
GROUP, BUT IT SEEMS LIKE IF YOU

262
00:10:37,520 --> 00:10:41,520
REALLY REMOVE THE EFFECT OF UV

263
00:10:41,520 --> 00:10:43,320
EXPOSURE, THEN LONGEVITY

264
00:10:43,320 --> 00:10:44,120
ACTUALLY MATTERS.

265
00:10:44,120 --> 00:10:48,880
BUT THIS EFFECT IS MUCH WEAKER

266
00:10:48,880 --> 00:10:49,920
COMPARED TO EFFECTIVE LIFE SPAN

267
00:10:49,920 --> 00:10:52,080
SO YOU ALSO LOOK AT THE

268
00:10:52,080 --> 00:10:54,960
[INDISCERNIBLE] AND THAT WAS

269
00:10:54,960 --> 00:10:55,960
VERY SIMILAR SITUATION SO TO

270
00:10:55,960 --> 00:10:57,040
SUMMARIZE THIS PART, WHAT WE

271
00:10:57,040 --> 00:11:00,160
FOUND IS THAT LOOKING AT THE

272
00:11:00,160 --> 00:11:01,880
EXCISION REPAIR DOESN'T REALLY

273
00:11:01,880 --> 00:11:05,040
CORRELATE WITH LIFE SPAN, BUT IT

274
00:11:05,040 --> 00:11:06,520
CORRELATES TO YOU KNOW ECOLOGY

275
00:11:06,520 --> 00:11:09,320
OF THE SPECIES, THE AMOUNT OF

276
00:11:09,320 --> 00:11:12,360
SATELLITE THAT THESE SPECIES

277
00:11:12,360 --> 00:11:13,200
GET.

278
00:11:13,200 --> 00:11:16,040
SO THEN WE DECIDED TO LOOK AT

279
00:11:16,040 --> 00:11:17,480
DOUBLE STRAND REPAIR AND I THINK

280
00:11:17,480 --> 00:11:19,640
THIS TYPE OF REPAIR IS

281
00:11:19,640 --> 00:11:21,000
PARTICULARLY IMPORTANT TO

282
00:11:21,000 --> 00:11:22,440
LONGEVITY BECAUSE MAINLY MUTANTS

283
00:11:22,440 --> 00:11:24,640
IN THE GENES INVOLVED IN THE

284
00:11:24,640 --> 00:11:28,080
[INDISCERNIBLE] MATURE AGING AND

285
00:11:28,080 --> 00:11:32,400
PHENOTYPES, ALSO IN AGE TISSUES

286
00:11:32,400 --> 00:11:34,520
WE SEE OBESE, ADVANCE LOITION

287
00:11:34,520 --> 00:11:35,160
KACCTS AND EVEN MALIGNANCY IN

288
00:11:35,160 --> 00:11:40,720
THE TISSUE THAT IS THE FULL MARK

289
00:11:40,720 --> 00:11:41,600
BUT [INDISCERNIBLE] THEY START

290
00:11:41,600 --> 00:11:45,200
TO APPEAR AND IN THIS PATHWAY IT

291
00:11:45,200 --> 00:11:46,320
HASN'T BEEN [INDISCERNIBLE] THAT

292
00:11:46,320 --> 00:11:50,320
MUCH WITH RESPECT TO LONGEVITY.

293
00:11:50,320 --> 00:11:52,080
THERE ARE 2 MAJOR PATHWAYS OF

294
00:11:52,080 --> 00:11:54,200
DOUBLE STRAND BREAK REPAIR, YOU

295
00:11:54,200 --> 00:11:56,960
PROBABLY [INDISCERNIBLE] HERE

296
00:11:56,960 --> 00:12:00,560
AND SO JOINING FROM COMBINATION,

297
00:12:00,560 --> 00:12:02,960
WE DEVELOPED THOSE REPORTERS

298
00:12:02,960 --> 00:12:04,800
THAT CAN MEASURE QUANTITATIVELY

299
00:12:04,800 --> 00:12:07,520
THE EFFICIENCY OF THESE 2

300
00:12:07,520 --> 00:12:08,320
PATHWAYS.

301
00:12:08,320 --> 00:12:10,760
SO THEY'RE BOTH GFP BASED AND WE

302
00:12:10,760 --> 00:12:13,120
CAN INDUCE THE SITE SPECIFIC

303
00:12:13,120 --> 00:12:14,640
DOUBLE STRAND BREAK AND WHEN

304
00:12:14,640 --> 00:12:17,200
IT'S REPAIRED YOU CAN CONSITUTE

305
00:12:17,200 --> 00:12:19,640
THE ACTIVITY, AND HERE, SORT OF

306
00:12:19,640 --> 00:12:23,240
SIMILAR BACKBONE BUT WE USE THIS

307
00:12:23,240 --> 00:12:25,680
[INDISCERNIBLE] [INDISCERNIBLE]

308
00:12:25,680 --> 00:12:27,640
WITH THE REPEAT.

309
00:12:27,640 --> 00:12:30,120
SO WE INTEGRATED THESE REPORTERS

310
00:12:30,120 --> 00:12:31,520
INTO PRIMARY 1 BLASTS FROM ALL

311
00:12:31,520 --> 00:12:35,120
THOSE SPECIES THAT THEY SHOWED

312
00:12:35,120 --> 00:12:37,120
YOU, AND EXAMINED DEFICIENCY OF

313
00:12:37,120 --> 00:12:39,040
REPAIR VERSUS MAXIMUM LIFE SPAN.

314
00:12:39,040 --> 00:12:44,320
AND HERE, AFTER I SHOWED YOU IN

315
00:12:44,320 --> 00:12:44,920
THE [INDISCERNIBLE] QUARTERLY

316
00:12:44,920 --> 00:12:47,320
THE LIFE SPAN WE CAN APPRECIATE

317
00:12:47,320 --> 00:12:49,320
HOW STRONGLY IT CAN CORRELATE SO

318
00:12:49,320 --> 00:12:53,320
LIFE SPAN SO THIS IS

319
00:12:53,320 --> 00:12:54,200
[INDISCERNIBLE] COMBINATION AND

320
00:12:54,200 --> 00:12:55,720
SAME THING FOR [INDISCERNIBLE].

321
00:12:55,720 --> 00:13:02,960
BOTH OF THESE PATHWAYS ARE MUCH

322
00:13:02,960 --> 00:13:03,760
MORE EFFICIENT INVOLVED WITH

323
00:13:03,760 --> 00:13:04,960
THESE ISSUES AND OF COURSE THE

324
00:13:04,960 --> 00:13:12,280
NEXT QUESTION WE ASKED WAS ABOUT

325
00:13:12,280 --> 00:13:14,560
THE MECHANISM AND THE ENZYME

326
00:13:14,560 --> 00:13:16,280
THAT WORKS BETTER FOR THE

327
00:13:16,280 --> 00:13:18,200
SPECIES AND OF COURSE THERE ARE

328
00:13:18,200 --> 00:13:22,200
MANY TYPES INVOLVED BUT BECAUSE

329
00:13:22,200 --> 00:13:22,680
BOTH PATHWAYS SHOWED

330
00:13:22,680 --> 00:13:27,120
UPREGULATION SO WE FIGURED OUT

331
00:13:27,120 --> 00:13:30,880
THE TEST ASSEMBLING UPSTREAM FOR

332
00:13:30,880 --> 00:13:32,400
THE [INDISCERNIBLE] OF

333
00:13:32,400 --> 00:13:33,240
[INDISCERNIBLE] AND 1 GROUP

334
00:13:33,240 --> 00:13:35,240
WE'VE BEEN WORKING ON AND REALLY

335
00:13:35,240 --> 00:13:39,040
UPSTREAM FOR GOOD SEPARATION AND

336
00:13:39,040 --> 00:13:41,040
X06 SO WEEK LOOK AT RECEPTOR 2

337
00:13:41,040 --> 00:13:43,320
AND 6 AND THERE WAS ALSO

338
00:13:43,320 --> 00:13:45,640
ADDITIONAL REASON WHY WE

339
00:13:45,640 --> 00:13:48,320
DESIGHTED TO LOOK AT SIRT6, AND

340
00:13:48,320 --> 00:13:50,440
THIS IS QUICK INTRODUCTION IN

341
00:13:50,440 --> 00:13:54,320
INCLUDING 6 IT'S A HOMOLOGUE OF

342
00:13:54,320 --> 00:13:57,240
2 PROTEIN THAT IS BEST KNOWN AS

343
00:13:57,240 --> 00:14:00,120
ASIT LACE, IT'S PART CHROMATIN,

344
00:14:00,120 --> 00:14:05,080
IT'S DEPENDENT AND THERE ARE

345
00:14:05,080 --> 00:14:05,760
SEVERAL [INDISCERNIBLE], AND 6

346
00:14:05,760 --> 00:14:08,080
IS THE STRONGEST BECAUSE WE HAVE

347
00:14:08,080 --> 00:14:11,360
A PHENOTIP AND YOU GET MICE THAT

348
00:14:11,360 --> 00:14:15,280
HAVE A SMALL STABILITY, AGED,

349
00:14:15,280 --> 00:14:18,920
MATURITY, IF YOU OVEREXPRESS,

350
00:14:18,920 --> 00:14:23,120
YOU HAVE MICE, MICE

351
00:14:23,120 --> 00:14:25,280
OVEREXPRESSING, LEAVE ABOUT THAT

352
00:14:25,280 --> 00:14:28,840
PERCENT OVER, THAT WAS ANOTHER

353
00:14:28,840 --> 00:14:30,320
REASON FOR SIRT6, BECAUSE IT HAS

354
00:14:30,320 --> 00:14:33,120
SOMETHING TO DO WITH LONGEVITY,

355
00:14:33,120 --> 00:14:36,560
AND THIS IS AN EARLIER WORK FROM

356
00:14:36,560 --> 00:14:38,400
2011 WHERE WE STUDIED THE

357
00:14:38,400 --> 00:14:40,200
FRACTION OF 6 AND DOUBLE STRAND

358
00:14:40,200 --> 00:14:41,240
BREAK REMARE IN HUMAN CELLS AND

359
00:14:41,240 --> 00:14:44,720
WHAT WE SHOWED IS THAT IF YOU

360
00:14:44,720 --> 00:14:47,120
OVEREXPRESS SIRT6, CAN YOU

361
00:14:47,120 --> 00:14:49,120
STIMULATE BOTH IN HH, AND HR,

362
00:14:49,120 --> 00:14:51,480
WHICH IS VERY RARE BECAUSE

363
00:14:51,480 --> 00:14:52,320
TYPICALLY YOU OVEREXPRESS

364
00:14:52,320 --> 00:14:54,120
SOMETHING, YOU SHIFT BALANCE

365
00:14:54,120 --> 00:14:57,560
TWOON THE 2 PATHWAYS BUT SIRT6,

366
00:14:57,560 --> 00:14:58,800
WE CAN DO BOTH.

367
00:14:58,800 --> 00:15:01,000
SO THAT'S WHY WE FOCUS ON SIRT6,

368
00:15:01,000 --> 00:15:04,000
AND THIS IS A QUICK SUMMARY OF

369
00:15:04,000 --> 00:15:05,480
DIFFERENT FUNCTIONS OF 6 AND

370
00:15:05,480 --> 00:15:08,360
APPEARED COMING FROM MY GROUP SO

371
00:15:08,360 --> 00:15:11,120
WHAT WE SHOWED THAT SIRT 6 IS

372
00:15:11,120 --> 00:15:12,560
RECRUITED TO DOUBLE STRAND

373
00:15:12,560 --> 00:15:15,760
BREAKS WITHIN SECONDS AND AFTER

374
00:15:15,760 --> 00:15:18,880
INDUCTION OF THE DNA BREAK, AND

375
00:15:18,880 --> 00:15:21,280
WE ACTUALLY FURTHER, YOU KNOW

376
00:15:21,280 --> 00:15:23,880
FINE TUNE AND EXPANDED THIS FOR

377
00:15:23,880 --> 00:15:26,720
THE TIME OF RECRUITMENT WAS

378
00:15:26,720 --> 00:15:27,520
COOPERATION WITH WILL'S LAB SO

379
00:15:27,520 --> 00:15:30,320
WE USE THIS AMAZING SET UP WHERE

380
00:15:30,320 --> 00:15:33,480
WE COULD USE THE BREAK WITH THE

381
00:15:33,480 --> 00:15:35,880
SIRT6 COMING IN QUICKLY AND IT

382
00:15:35,880 --> 00:15:40,160
BECOMES THE BEFORE PART 1.

383
00:15:40,160 --> 00:15:42,720
AND THEN [INDISCERNIBLE] PART 1

384
00:15:42,720 --> 00:15:45,960
STIMULATES ITS ACTIVITY AND THEN

385
00:15:45,960 --> 00:15:47,760
IT PROMOTES RECRUITMENT

386
00:15:47,760 --> 00:15:48,840
[INDISCERNIBLE] FACTORS FOR DNA

387
00:15:48,840 --> 00:15:54,840
BREAK SO THAT'S WHY IT'S KIND OF

388
00:15:54,840 --> 00:16:01,000
UPSTREAM OF MULTIPLE REPAIR

389
00:16:01,000 --> 00:16:01,520
PATHWAYS.

390
00:16:01,520 --> 00:16:03,320
SO--OKAY, SO FROM ALL THOSE

391
00:16:03,320 --> 00:16:05,200
RODENTS, THAT I SHOWED AND YOU

392
00:16:05,200 --> 00:16:06,800
THEN EXPRESS THEM IN MOUSE CELLS

393
00:16:06,800 --> 00:16:09,520
THAT HAD THOSE INTEGRATED

394
00:16:09,520 --> 00:16:11,800
REPORTERS AND LOOK AT THE LEVEL

395
00:16:11,800 --> 00:16:14,440
OF STIMULATION THAT WE ACHIEVE.

396
00:16:14,440 --> 00:16:18,320
SO EVERY DOT IS 1 SPECIES WHERE

397
00:16:18,320 --> 00:16:19,200
SIRT6 VERSUS MAXIMUM LIFE SPAN

398
00:16:19,200 --> 00:16:22,760
AND YOU CAN SEE AGAIN, SIRT6 AND

399
00:16:22,760 --> 00:16:26,200
A SPECIES AND BETTER AT

400
00:16:26,200 --> 00:16:30,120
PROMOTING THE COMBINATION AND

401
00:16:30,120 --> 00:16:31,280
THOSE WHO [INDISCERNIBLE].

402
00:16:31,280 --> 00:16:36,360
SO THEN ASK WHERE IS ABOUT QUINN

403
00:16:36,360 --> 00:16:37,960
5, AND A LITTLE BIT BECAUSE WHEN

404
00:16:37,960 --> 00:16:39,480
WE TESTED CELLS FROM DIFFERENT

405
00:16:39,480 --> 00:16:43,680
SPECIES BUT IT SUGGESTS THAT

406
00:16:43,680 --> 00:16:44,920
SIRT6 EXPLAINS PARTIAL

407
00:16:44,920 --> 00:16:46,320
MANINNULATION, AND IN THE LIFE

408
00:16:46,320 --> 00:16:48,080
SPAN, THERE ARE PROBABLY SOME

409
00:16:48,080 --> 00:16:51,040
OTHER FACTORS CONTRIBUTING AS

410
00:16:51,040 --> 00:16:53,320
WELL, BUT SIRT6 IS 1 OF THE MAIN

411
00:16:53,320 --> 00:16:53,800
1S.

412
00:16:53,800 --> 00:16:56,960
SO THEN NEXT QUESTION WAS, OKAY,

413
00:16:56,960 --> 00:16:59,720
SO WHAT'S DIFFERENT ABOUT SIRT6

414
00:16:59,720 --> 00:17:03,720
FROM SHORT LIVED VERSUS LONG

415
00:17:03,720 --> 00:17:04,040
LIVED.

416
00:17:04,040 --> 00:17:05,920
WE CHOSE THE EXTREME CASES FROM

417
00:17:05,920 --> 00:17:08,760
OUR COLLECTION MODELS BECAUSE

418
00:17:08,760 --> 00:17:11,520
IT'S VERY SHORT LIVED.

419
00:17:11,520 --> 00:17:15,600
IT WAS AT WEEK 6 AND THEN WE

420
00:17:15,600 --> 00:17:17,480
CHOSE BEAVER, IT'S LONG LIVED,

421
00:17:17,480 --> 00:17:21,400
MORE THAN 20 YEARS AND MAYBE

422
00:17:21,400 --> 00:17:23,320
ANECDOTALLY 50 YEARS BUT 24

423
00:17:23,320 --> 00:17:26,480
YEARS THAT WAS 1 PARTICULAR

424
00:17:26,480 --> 00:17:27,880
BEAVER THAT WAS [INDISCERNIBLE]

425
00:17:27,880 --> 00:17:30,400
THIS ISSUE AND THEY HAD VERY

426
00:17:30,400 --> 00:17:33,520
GOOD DNA REPAIR, SO WE TOOK

427
00:17:33,520 --> 00:17:36,320
THOSE SIRT6 PROTEINS AND WE MADE

428
00:17:36,320 --> 00:17:39,640
A LOT OF CHIMERAS SO BEAVER,

429
00:17:39,640 --> 00:17:41,480
MOUSE,--THIS IS JUST A QUICK

430
00:17:41,480 --> 00:17:45,080
SUMMARY OF ALL THIS MUTE O

431
00:17:45,080 --> 00:17:46,560
GENESIS WORK THAT XIAO FORMED

432
00:17:46,560 --> 00:17:48,360
AND HERE IT'S THE SAME IN

433
00:17:48,360 --> 00:17:50,360
JOINING ASSAY BUT THEN MORE TO

434
00:17:50,360 --> 00:17:53,480
FEEL THE FORMAT IF WE

435
00:17:53,480 --> 00:17:55,240
OVEREXPRESS MOUSE SIRT6, IT

436
00:17:55,240 --> 00:17:58,320
STIMULATES REPAIR A LITTLE BIT

437
00:17:58,320 --> 00:18:00,640
BUT WITH BEAVER 6 THE EFFECT IS

438
00:18:00,640 --> 00:18:03,800
MUCH STRONGER AND THEN XIAO MADE

439
00:18:03,800 --> 00:18:05,720
ALL THESE SWATHS SO WE

440
00:18:05,720 --> 00:18:06,880
[INDISCERNIBLE] FROM THE

441
00:18:06,880 --> 00:18:07,920
C-TERMINALS UP TO HERE, UP TO

442
00:18:07,920 --> 00:18:10,920
HERE IT DOESN'T MAKE A BIG

443
00:18:10,920 --> 00:18:14,400
DIFFERENCE IF WE SWAP ALL THIS

444
00:18:14,400 --> 00:18:16,040
REGION, WE CAN HOUSE MOUSE

445
00:18:16,040 --> 00:18:17,800
RODENT QUITE A LOT AND THEN HE

446
00:18:17,800 --> 00:18:19,920
DID MANY OTHER COMBINATIONS AND

447
00:18:19,920 --> 00:18:22,320
HERE IS WHAT HE ENDED UP DOING

448
00:18:22,320 --> 00:18:26,840
IS JUST REPLACING THIS SEGMENT

449
00:18:26,840 --> 00:18:28,520
AND THAT WAS ENOUGH TO

450
00:18:28,520 --> 00:18:29,720
COMPLETELY SWAMP THE ACTIVITY OF

451
00:18:29,720 --> 00:18:31,560
THE MOUSE AND SO THAT WAS VERY

452
00:18:31,560 --> 00:18:35,400
NICE, WE LOOKED AT THIS REGION,

453
00:18:35,400 --> 00:18:38,800
THE 2270, THERE ARE 5 DIFFERENT

454
00:18:38,800 --> 00:18:40,160
DIFFERENCES BETWEEN MOUSE AND

455
00:18:40,160 --> 00:18:42,360
BEAVER.

456
00:18:42,360 --> 00:18:44,720
WE TRIED TO MUTATE EACH

457
00:18:44,720 --> 00:18:47,360
[INDISCERNIBLE] RAT AND IN VIRUS

458
00:18:47,360 --> 00:18:48,960
COMBINATIONS AND AGAIN TO MAKE A

459
00:18:48,960 --> 00:18:51,080
LONG STORY SHORT, WE ACTUALLY

460
00:18:51,080 --> 00:18:54,320
HAD TO REPLACE ALL 5.

461
00:18:54,320 --> 00:18:55,760
SO EACH 1 INDIVIDUALLY WAS GIVEN

462
00:18:55,760 --> 00:18:57,720
A BIT OF AN IMPROVEMENT BUT

463
00:18:57,720 --> 00:19:00,160
NEITHER OF THEM WAS ENOUGH SO

464
00:19:00,160 --> 00:19:01,520
IT'S REALLY THOSE SMALL CHANGES

465
00:19:01,520 --> 00:19:01,880
YOU GIVE IT.

466
00:19:01,880 --> 00:19:03,280
WHICH KIND OF MAKES SENSE

467
00:19:03,280 --> 00:19:05,320
BECAUSE THESE ARE 2 PROTEINS

468
00:19:05,320 --> 00:19:07,560
THAT THE WILD TYPE PROTEINS BUT

469
00:19:07,560 --> 00:19:10,040
1 COMES FROM A MOUSE, 1 SHORT

470
00:19:10,040 --> 00:19:11,160
LIVED, ANOTHER COMES THROUGH THE

471
00:19:11,160 --> 00:19:12,120
[INDISCERNIBLE] LONG LIVED SO

472
00:19:12,120 --> 00:19:14,240
THEY MOVE KIND OF FUNCTION BUT

473
00:19:14,240 --> 00:19:17,640
THE FUNCTION GETS ADJUSTED

474
00:19:17,640 --> 00:19:19,320
DEPENDING ON THE LIFE SPAN.

475
00:19:19,320 --> 00:19:23,120
SO THEN WE DID SOME INVITRO

476
00:19:23,120 --> 00:19:31,320
BIOCHEMISTRY WITH THESE

477
00:19:31,320 --> 00:19:31,880
PROTEINS, [INDISCERNIBLE]

478
00:19:31,880 --> 00:19:36,360
ACTIVITIES, AND THESE PROTEINS

479
00:19:36,360 --> 00:19:36,960
AND HISTONE H3--

480
00:19:36,960 --> 00:19:38,440
>> COULD YOU PLEASE USE THE

481
00:19:38,440 --> 00:19:39,840
COMPUTER MOUSE TO TELL US ABOUT

482
00:19:39,840 --> 00:19:42,440
YOUR MICE IN THE LAB?

483
00:19:42,440 --> 00:19:43,920
>> I WILL TRY, YES, SORRY ABOUT

484
00:19:43,920 --> 00:19:44,920
THAT.

485
00:19:44,920 --> 00:19:48,520
CAN YOU SEE THE ARROW RIGHT

486
00:19:48,520 --> 00:19:48,720
THERE?

487
00:19:48,720 --> 00:19:51,800
IT'S A BIT TRICKY.

488
00:19:51,800 --> 00:19:57,120
IT'S MY LAB TOP SO I WILL BE A

489
00:19:57,120 --> 00:20:01,280
LITTLE CLUMSY BUT--YEAH. 

490
00:20:01,280 --> 00:20:04,280
SO THIS IS--YEAH, SO THIS IS HCK

491
00:20:04,280 --> 00:20:06,560
9, YOU CAN SEE THAT MOUSE

492
00:20:06,560 --> 00:20:12,160
PROTEIN IS NOT VERY GOOD AT

493
00:20:12,160 --> 00:20:14,560
DEACETALATING IT BUT WITH BEAVER

494
00:20:14,560 --> 00:20:16,960
SUBSTITUTIONS IT BECOMES

495
00:20:16,960 --> 00:20:18,760
STRONGER WITH THE ACET LACE AND

496
00:20:18,760 --> 00:20:20,360
BEAVER PROTEIN IS GOOD, AND IT

497
00:20:20,360 --> 00:20:22,720
GETS WORSE WITH THE MOUSE.

498
00:20:22,720 --> 00:20:26,280
OH YEAH IS THIS IS KIND OF--I

499
00:20:26,280 --> 00:20:28,240
DIDN'T CORRECT THIS SLIDE SO

500
00:20:28,240 --> 00:20:29,800
[INDISCERNIBLE] PUBLISHED SO NOW

501
00:20:29,800 --> 00:20:32,640
WE TESTED THE SECOND ACTIVITY

502
00:20:32,640 --> 00:20:35,240
WHICH IS MORE SSETALATION AND

503
00:20:35,240 --> 00:20:37,040
HERE WE [INDISCERNIBLE] AND THEN

504
00:20:37,040 --> 00:20:39,200
THE MEASURE SELF-[INDISCERNIBLE]

505
00:20:39,200 --> 00:20:40,920
CHANNEL 6 SO IT TRANSFERRED

506
00:20:40,920 --> 00:20:42,440
LABEL TO ITSELF AND SO HERE

507
00:20:42,440 --> 00:20:45,440
AGAIN, YOU CAN SEE THAT MOUSE IS

508
00:20:45,440 --> 00:20:47,400
NOT VERY GOOD AT POSTULATING BUT

509
00:20:47,400 --> 00:20:51,520
IT BECOMES MUCH BETTER WITH

510
00:20:51,520 --> 00:20:52,720
BEAVER SUBSTITUTIONS AND VICE

511
00:20:52,720 --> 00:20:56,120
VERSA IN WILD TYPES AND ENZYME,

512
00:20:56,120 --> 00:21:00,160
BUT IT BECOMES DIFFICULT WITH

513
00:21:00,160 --> 00:21:00,720
MOUSE SUBTUITIONS.

514
00:21:00,720 --> 00:21:02,280
SO THIS IS THE STRUCTURE SO WE

515
00:21:02,280 --> 00:21:04,920
TRY TO FIGURE OUT WHERE THOSE

516
00:21:04,920 --> 00:21:08,960
ASH SIDS ARE LOCATED--ACIDS ARE

517
00:21:08,960 --> 00:21:11,320
LOCATED USING HUMAN CRYSTAL

518
00:21:11,320 --> 00:21:12,920
STRUCTURE, WE CAN SEE THAT THEY

519
00:21:12,920 --> 00:21:14,960
ARE ALL 5OT SURFACE OF THE

520
00:21:14,960 --> 00:21:16,720
PROTEIN--5 ON THE SURFACE OF THE

521
00:21:16,720 --> 00:21:18,320
PROTEIN AND 2 OF THEM ARE CLOSE

522
00:21:18,320 --> 00:21:20,480
TO SUBSTRATE BINDING SITE SO

523
00:21:20,480 --> 00:21:22,160
THAT'S WHERE HUMAN CELL SET WAS

524
00:21:22,160 --> 00:21:24,080
KRIOF THE ALTHOUGHAISED WITH H3

525
00:21:24,080 --> 00:21:26,280
PEPTIDE AND THEY'RE CLOSED AND

526
00:21:26,280 --> 00:21:28,360
WE--I DON'T HAVE THE SLIDE, THE

527
00:21:28,360 --> 00:21:30,960
DATA SLIDES FOR IT, BUT WE ALSO

528
00:21:30,960 --> 00:21:33,880
SHOWED THAT BEAVER CELL 6 HAS

529
00:21:33,880 --> 00:21:35,720
STRONGER BINDING TO NUCLEOSOME

530
00:21:35,720 --> 00:21:37,320
WHICH IS CONSISTENT.

531
00:21:37,320 --> 00:21:39,960
THE OTHER 3 AMINO ACIDS ARE ON

532
00:21:39,960 --> 00:21:40,920
THE OPPOSITE SIDE OF THE

533
00:21:40,920 --> 00:21:41,760
PROTEIN, WE DON'T KNOW EXACTLY

534
00:21:41,760 --> 00:21:44,840
WHAT THE IPAD DO, BUT 1 THING WE

535
00:21:44,840 --> 00:21:47,960
NOTICED IN THE MOUSE THERE IS A

536
00:21:47,960 --> 00:21:50,320
SOUTH BRIDGE AND IT'S ABSENT IN

537
00:21:50,320 --> 00:21:53,040
THE BEAVER SO PERHAPS THAT GIVES

538
00:21:53,040 --> 00:21:54,520
GREATER FLEXIBILITY TO THOSE

539
00:21:54,520 --> 00:21:58,040
ALPHA HELIXES MAY BE MOVING INTO

540
00:21:58,040 --> 00:21:58,920
ACTIVITY [INDISCERNIBLE].

541
00:21:58,920 --> 00:22:03,920
SO TO SUMMARIZE THIS PART OF MY

542
00:22:03,920 --> 00:22:08,600
STORY WHAT WE SHOWED WAS THAT

543
00:22:08,600 --> 00:22:10,720
STRONGLY CORRELATES TO MAX LIFE

544
00:22:10,720 --> 00:22:11,560
SPAN AND SIRT6 AND RESPONSIBLE

545
00:22:11,560 --> 00:22:13,280
FOR MOST OF IT.

546
00:22:13,280 --> 00:22:18,120
AND WE ALSO IDENTIFIED 5 AAMINO

547
00:22:18,120 --> 00:22:20,680
ACIDS THAT WAS SUFFICIENT TO

548
00:22:20,680 --> 00:22:22,680
CANNED WHAT MOUSE AND BEAVER TO

549
00:22:22,680 --> 00:22:26,520
CHANGE THE ACTIVITY, WE ALSO

550
00:22:26,520 --> 00:22:28,360
EXCISE NUCLEOTIDE EXCISION

551
00:22:28,360 --> 00:22:30,800
REPAIR WHERE WE DIDN'T FIND

552
00:22:30,800 --> 00:22:32,240
MAXIMUM LIFE SPAN.

553
00:22:32,240 --> 00:22:33,960
SO HERE OF COURSE THE NEXT

554
00:22:33,960 --> 00:22:36,480
QUESTION THAT COMES IN IS

555
00:22:36,480 --> 00:22:39,520
WHETHER YOU KNOW WE CAN IMPROVE,

556
00:22:39,520 --> 00:22:40,880
YOU KNOW BECAUSE HERE WE SHOWED

557
00:22:40,880 --> 00:22:43,840
THERE IS ASSOCIATION IN TERMS OF

558
00:22:43,840 --> 00:22:45,440
SPECIES THAT HAVE DIFFERENT

559
00:22:45,440 --> 00:22:46,840
MAXIMUM LIFE SPANS CAN MAKE

560
00:22:46,840 --> 00:22:49,480
MOUSE LIVE LONGER BY GIVING IT

561
00:22:49,480 --> 00:22:50,680
THE STRONGEST CELL 6 SO THAT'S

562
00:22:50,680 --> 00:22:53,920
WHAT WE ARE WORKING ON RIGHT

563
00:22:53,920 --> 00:22:55,120
NOW.

564
00:22:55,120 --> 00:22:59,520
WE ARE GENERATING THIS

565
00:22:59,520 --> 00:23:02,520
BEAVERRIZED MOUSE WITH KRSPR,

566
00:23:02,520 --> 00:23:04,000
AND THOSE 5 SUBTUITIONS SO WE

567
00:23:04,000 --> 00:23:05,920
THOUGHT WE WOULD HAVE THE MOUSE

568
00:23:05,920 --> 00:23:07,520
BUT IT WAS DIFFICULT WITH 5 AT

569
00:23:07,520 --> 00:23:08,720
THE SAME TIME AND WE STILL

570
00:23:08,720 --> 00:23:10,000
WORKING ON GETTING THE OTHER 5

571
00:23:10,000 --> 00:23:12,520
AND THEN WE WILL SEE, WELL, IF

572
00:23:12,520 --> 00:23:13,800
MOUSE LIVES LONGER, THEY THINK

573
00:23:13,800 --> 00:23:15,600
THEY WILL REALLY IMPROVE THE

574
00:23:15,600 --> 00:23:17,400
CONNECTION BETWEEN BETTER DNA

575
00:23:17,400 --> 00:23:18,320
REPAIR AND LIFE SPAN.

576
00:23:18,320 --> 00:23:20,120
WE ARE ALSO LOOKING AT OTHER

577
00:23:20,120 --> 00:23:23,560
PAIRS OF SPECIES, YOU KNOW WHALE

578
00:23:23,560 --> 00:23:26,880
FOR XMPLE IF WE MARK THOSE, IN

579
00:23:26,880 --> 00:23:28,320
ESSENCE THEY'RE DIFFERENT

580
00:23:28,320 --> 00:23:29,720
BETWEEN MOUSE AND WHALE SO MAYBE

581
00:23:29,720 --> 00:23:31,760
WE TRY A DIFFERENT SET OF

582
00:23:31,760 --> 00:23:33,880
RESIDUES THAT CAN BE MODULATED.

583
00:23:33,880 --> 00:23:36,480
SOMETHING ELSE THAT'S QUITE

584
00:23:36,480 --> 00:23:38,360
INTERESTING IS THAT CELL 6

585
00:23:38,360 --> 00:23:39,960
ACTIVATORS THAT WILL MAP WHERE

586
00:23:39,960 --> 00:23:43,120
THEY INTERACT, SO THERE WAS 1

587
00:23:43,120 --> 00:23:46,160
THAT LIKE BINDS RIGHT HERE WHICH

588
00:23:46,160 --> 00:23:49,720
IS CLOSE TO THOSE AND USING THIS

589
00:23:49,720 --> 00:23:50,560
TO CONFER WITH THE APPROACH

590
00:23:50,560 --> 00:23:54,680
AGAIN, YOU CAN USE THIS TO MAYBE

591
00:23:54,680 --> 00:23:58,040
DESIGN ACTIVATE THE CELL 6, SO

592
00:23:58,040 --> 00:23:59,640
WE--YOU KNOW WE MAY DISCOVER

593
00:23:59,640 --> 00:24:01,400
WHICH CELL DIDN'T TAKE BUT THEY

594
00:24:01,400 --> 00:24:03,120
STILL LIKE THE PICTURE.

595
00:24:03,120 --> 00:24:07,560
SO YOU CAN SEE THAT IT'S KIND OF

596
00:24:07,560 --> 00:24:08,760
THE [INDISCERNIBLE], PROBABLY

597
00:24:08,760 --> 00:24:10,720
WILL USE THIS POINTER, SO THIS

598
00:24:10,720 --> 00:24:12,920
IS THE BEAVER PREPARING DNA,

599
00:24:12,920 --> 00:24:16,000
IT'S VERY GOOD AT IT, AND IT'S

600
00:24:16,000 --> 00:24:17,520
PROBABLY SIRT6, AND IN MOUSE,

601
00:24:17,520 --> 00:24:19,520
DOESN'T REALLY KNOW HOW TO

602
00:24:19,520 --> 00:24:20,200
REPAIR DNA WELL.

603
00:24:20,200 --> 00:24:24,200
THERE ARE LOTS OF BREAKS IN THE

604
00:24:24,200 --> 00:24:29,920
CELL 6 IS SMALL.

605
00:24:29,920 --> 00:24:31,480
SO HERE CONTINUATION OF THIS

606
00:24:31,480 --> 00:24:33,680
STORY THIS IS WORK OF ANOTHER

607
00:24:33,680 --> 00:24:35,480
TALENTED POST DOC MATT SIMON, HE

608
00:24:35,480 --> 00:24:38,520
KIND OF TOOK OFF FROM WHERE XIAO

609
00:24:38,520 --> 00:24:39,800
FINISHED AND HE ASKED THE

610
00:24:39,800 --> 00:24:41,960
QUESTION, OKAY, SO WE

611
00:24:41,960 --> 00:24:44,560
DEMONSTRATED THE DIFFERENT

612
00:24:44,560 --> 00:24:46,160
SPECIES THAT WITNESSED

613
00:24:46,160 --> 00:24:47,360
ACTIVITIES ASSOCIATE WIDE LONGER

614
00:24:47,360 --> 00:24:51,840
LIFE SPAN BUT WHAT ABOUT OUR

615
00:24:51,840 --> 00:24:53,160
FAVORITE SPECIES HUMANS?

616
00:24:53,160 --> 00:24:57,720
SO FOR HUMANS IF WE IMPROVE

617
00:24:57,720 --> 00:24:59,120
SIRT6 ACTIVITIES WILL BENEFIT US

618
00:24:59,120 --> 00:25:01,120
IN EMERGING ITS OF LONGEVITY.

619
00:25:01,120 --> 00:25:03,240
SO WE WERE VERY FORTUNATE THAT

620
00:25:03,240 --> 00:25:07,120
WE WERE COLLABORATING AT THIS

621
00:25:07,120 --> 00:25:09,240
TIME WITH [INDISCERNIBLE] WHO

622
00:25:09,240 --> 00:25:10,200
DOES STUDIES OF [INDISCERNIBLE]

623
00:25:10,200 --> 00:25:13,680
SO SHE WAS DOING EXOME

624
00:25:13,680 --> 00:25:15,120
SEQUENCING ON ALL GENES THAT I

625
00:25:15,120 --> 00:25:16,720
INVOLVE TO DNA DAMAGE AND

626
00:25:16,720 --> 00:25:16,920
REPAIR.

627
00:25:16,920 --> 00:25:24,160
AND SHE WAS LOOKING FOR

628
00:25:24,160 --> 00:25:25,400
[INDISCERNIBLE] IN SEN

629
00:25:25,400 --> 00:25:26,800
ILLEGALSEN 10AURIANS MOST OF

630
00:25:26,800 --> 00:25:29,520
THEM ARE NONCODING AND FOR MANY

631
00:25:29,520 --> 00:25:31,200
OF THEM IT'S DIFFICULT TO

632
00:25:31,200 --> 00:25:32,400
DETERMINE THE FUNCTION BUT SHE

633
00:25:32,400 --> 00:25:35,120
DID FIND THE CLOSING VARIANT AND

634
00:25:35,120 --> 00:25:37,600
IT WASN'T SIRT6 SO WE WERE VERY

635
00:25:37,600 --> 00:25:37,920
EXCITED.

636
00:25:37,920 --> 00:25:42,120
SO SHE FOUND THESE 2 MUTATIONS

637
00:25:42,120 --> 00:25:44,320
THAT ONLY APPEARED IN

638
00:25:44,320 --> 00:25:47,480
CENTENARIAN AND IT'S A RARE

639
00:25:47,480 --> 00:25:50,480
ITEM, AND SMALL PERCENTAGES OF

640
00:25:50,480 --> 00:25:54,120
THEM HAVE IT [INDISCERNIBLE] AND

641
00:25:54,120 --> 00:25:55,160
THEY ALSO APPEARED TOGETHER.

642
00:25:55,160 --> 00:25:56,680
SO WE DECIDED, OKAY, LET'S TEST

643
00:25:56,680 --> 00:26:00,520
WHAT IT DOES TO THE PROTEIN.

644
00:26:00,520 --> 00:26:04,320
WE MADE THIS PROTEIN REDOMAIN

645
00:26:04,320 --> 00:26:06,120
BIN ANTLY AND THEN WE TESTED IT

646
00:26:06,120 --> 00:26:08,120
IN DNA REPAIR AND THEN THE

647
00:26:08,120 --> 00:26:09,120
MUTATION AND [INDISCERNIBLE]

648
00:26:09,120 --> 00:26:10,720
PULL TOGETHER LIKE

649
00:26:10,720 --> 00:26:11,520
[INDISCERNIBLE].

650
00:26:11,520 --> 00:26:13,640
AND THIS IS HOMOLOGOUS

651
00:26:13,640 --> 00:26:16,120
COMBINATION JOINING US YOU CAN

652
00:26:16,120 --> 00:26:18,560
SEE THAT CENTENARIAN IS ACTUALLY

653
00:26:18,560 --> 00:26:22,320
BETTER DNA REPAIR SO THAT WAS

654
00:26:22,320 --> 00:26:23,120
REALLY EXCITING.

655
00:26:23,120 --> 00:26:27,520
YOU KNOW WE CAN DETECT IT.

656
00:26:27,520 --> 00:26:29,720
WE ALSO LOOKED AT BASAL LEVEL OF

657
00:26:29,720 --> 00:26:32,720
DNA DAMAGE SO HERE WE MEASURED

658
00:26:32,720 --> 00:26:37,520
GAMMA 3 X FORSIGHT, AND CELLS

659
00:26:37,520 --> 00:26:42,600
AND CELLS EXPRESSING THOSE

660
00:26:42,600 --> 00:26:46,240
OBSERVATIONS OF SIRT6, AND

661
00:26:46,240 --> 00:26:46,760
[INDISCERNIBLE] VARIANCES.

662
00:26:46,760 --> 00:26:50,600
WE ALSO HAD THE PREVIOUS ASSAY

663
00:26:50,600 --> 00:26:54,720
WHERE WE SHOWED THAT SIRT6 CAN

664
00:26:54,720 --> 00:26:56,960
SHOW CELLS THROUGH P53 DEPENDENT

665
00:26:56,960 --> 00:27:00,160
MECHANISM AND WHEN WE EXPRESS

666
00:27:00,160 --> 00:27:01,880
CENTENARIAN PART, WE ALSO HAVE

667
00:27:01,880 --> 00:27:02,920
STRONGER KILLING OF CANCER CELLS

668
00:27:02,920 --> 00:27:06,640
THAN IN THE WILD TYPES.

669
00:27:06,640 --> 00:27:08,440
SO NOW SOMETHING, YOU KNOW WE

670
00:27:08,440 --> 00:27:10,160
THOUGHT OKAY, LET'S LOOK AT

671
00:27:10,160 --> 00:27:13,440
ENZYMATIC ACTIVITY AND THAT WAS

672
00:27:13,440 --> 00:27:15,720
A BIT UNEXPECTED WITH THIS, SO

673
00:27:15,720 --> 00:27:18,120
WE TESTED ENZYMATIC ACTIVITY ON

674
00:27:18,120 --> 00:27:20,840
THE H3 SUBSTRATE, SO THIS IS

675
00:27:20,840 --> 00:27:26,240
JUST A SITUATION AND YOU SEE

676
00:27:26,240 --> 00:27:28,320
THAT WELL CENTENARIANS SIRT6

677
00:27:28,320 --> 00:27:30,040
INVITRO WAS WORSE OFF THAN THE

678
00:27:30,040 --> 00:27:31,920
WILD TYPES AND THAT WAS VERY

679
00:27:31,920 --> 00:27:32,640
STRANGE.

680
00:27:32,640 --> 00:27:34,640
WE ALSO MEASURED KINEETICS AND

681
00:27:34,640 --> 00:27:38,720
AGAIN WE SEE THE SAME THING,

682
00:27:38,720 --> 00:27:41,440
CENTENARIAN, IS REALLY GOD ACET

683
00:27:41,440 --> 00:27:42,000
LACE.

684
00:27:42,000 --> 00:27:47,800
THEN WE LOOKED INVIVO IN CELLS

685
00:27:47,800 --> 00:27:50,400
THAT HAVE KNOCK-IN VERSIONS OF,

686
00:27:50,400 --> 00:27:52,400
YOU KNOW USING CRSPR, THEY HAVE

687
00:27:52,400 --> 00:27:55,720
CELL 6 WITH THOSE MUTATIONS AND

688
00:27:55,720 --> 00:27:57,640
IN CELLS WE DIDN'T REALLY SEE

689
00:27:57,640 --> 00:28:01,560
MUCH DIFFERENCE SO MAYBE INVITRO

690
00:28:01,560 --> 00:28:02,360
BECAUSE THESE ARE CONDITIONS

691
00:28:02,360 --> 00:28:04,720
WHERE THEY'RE NOT OPTIMAL WE CAN

692
00:28:04,720 --> 00:28:06,440
SEE IN THAT ENVIRONMENT IS NOT

693
00:28:06,440 --> 00:28:09,480
SO GOOD AND INVIVO WE DON'T GET

694
00:28:09,480 --> 00:28:11,920
THE BIG DIFFERENCE, WE ALSO HAVE

695
00:28:11,920 --> 00:28:14,560
MASS SPEC ON THE CELLS TO SEE IF

696
00:28:14,560 --> 00:28:17,040
WE CAN MEASURE DIFFERENCES IN

697
00:28:17,040 --> 00:28:18,680
THESE HISTONE LEVELS AGAIN,

698
00:28:18,680 --> 00:28:22,440
INVIVO WE COULDN'T SEE.

699
00:28:22,440 --> 00:28:25,720
AND THEN HAY IMAGINED WELL, IT

700
00:28:25,720 --> 00:28:28,800
WAS MUCH WORSE THAN THE WILD

701
00:28:28,800 --> 00:28:31,240
TYPE DOESN'T EXPLAIN VERY MUCH

702
00:28:31,240 --> 00:28:36,640
BECAUSE IT [INDISCERNIBLE] SO WE

703
00:28:36,640 --> 00:28:37,920
MEASURED SIRT6 ACTIVITY, AND

704
00:28:37,920 --> 00:28:40,120
THAT WAS ACTUALLY QUITE AMAZING.

705
00:28:40,120 --> 00:28:43,040
IT IS MUCH BETTER

706
00:28:43,040 --> 00:28:44,200
[INDISCERNIBLE] THAN THE WILD

707
00:28:44,200 --> 00:28:45,840
TYPE.

708
00:28:45,840 --> 00:28:47,480
SO THIS IS THE SELF-REGULATION

709
00:28:47,480 --> 00:28:52,520
ASSAY, YOU CAN SEE THAT THE

710
00:28:52,520 --> 00:28:56,520
EFFECT AND THERE IS ANOTHER

711
00:28:56,520 --> 00:28:57,800
SCENE OF REGULATION ACTIVITY

712
00:28:57,800 --> 00:28:59,600
WHERE IF YOU REMEMBER IN THE

713
00:28:59,600 --> 00:29:04,600
INTRODUCTION, I SHOWED THAT CELL

714
00:29:04,600 --> 00:29:06,320
6 [INDISCERNIBLE] MANIPULATES

715
00:29:06,320 --> 00:29:06,920
PARTNERSHIP 1 DOUBLE STRAND

716
00:29:06,920 --> 00:29:08,320
BREAK SO WE CAN USE THIS ASSAY,

717
00:29:08,320 --> 00:29:09,600
SO IF WE INTERNATIONAL

718
00:29:09,600 --> 00:29:10,840
CLASSIFICATION BEAUTY

719
00:29:10,840 --> 00:29:14,000
INDUSTRIED, IF WE INCUBATED WITH

720
00:29:14,000 --> 00:29:15,600
PARTNERSHIP 1 IN THE PRESENCE OF

721
00:29:15,600 --> 00:29:17,600
BROKEN DNA SO WE CAN SEE THAT

722
00:29:17,600 --> 00:29:20,680
THIS WILL COST US A LITTLE BIT

723
00:29:20,680 --> 00:29:23,320
BUT RELATIVE TO LOAD SIRT6, AND

724
00:29:23,320 --> 00:29:25,120
ACTIVITIES A BIT STRONGER, BUT

725
00:29:25,120 --> 00:29:30,520
IF WE NOW ADD CENTENARIAN SIRT6,

726
00:29:30,520 --> 00:29:32,120
IT ENHANCES ACTIVITY BY A LOT.

727
00:29:32,120 --> 00:29:37,080
SO IT'S A LOT OF EVIDENCE THAT

728
00:29:37,080 --> 00:29:39,080
THE UPREGULATION ACTIVITY WAS

729
00:29:39,080 --> 00:29:41,280
STRONGER, SO WE ALSO TRIED TO

730
00:29:41,280 --> 00:29:44,040
YOU KNOW CONNECT IT TO FUNCTIONS

731
00:29:44,040 --> 00:29:45,360
SO THE STAGE WHERE WE ARE AT

732
00:29:45,360 --> 00:29:50,960
RIGHT NOW SO WE LOOKED AT WHERE

733
00:29:50,960 --> 00:29:52,520
THE CENTENARIAN PART INTERACTS

734
00:29:52,520 --> 00:29:54,080
DIFFERENTLY WITH PROTEINS IN THE

735
00:29:54,080 --> 00:29:56,920
CELL BECAUSE AS YOU NOTICE THOSE

736
00:29:56,920 --> 00:29:59,240
2 MESSAGE MUTATIONS ARE IN THE

737
00:29:59,240 --> 00:30:02,440
C-TERMINALS, AND THAT IS LIKELY

738
00:30:02,440 --> 00:30:03,120
RESPONSIBLE FOR PROTEIN-PROTEIN

739
00:30:03,120 --> 00:30:09,320
INTERACTION SO WITH THAT, WE

740
00:30:09,320 --> 00:30:11,120
HAVE IMMUNE O PRECIPITATIONS AND

741
00:30:11,120 --> 00:30:12,720
MASS SPEC AND LOOK THAT IF

742
00:30:12,720 --> 00:30:15,520
SOMETHING IS DNCHTD BETWEEN WILD

743
00:30:15,520 --> 00:30:17,800
TYPE CELL 6 AND CENTENARIAN

744
00:30:17,800 --> 00:30:19,600
VARIANT SO THESE ARE SEVERAL

745
00:30:19,600 --> 00:30:22,520
PROTEINS THAT CAME UP THAT

746
00:30:22,520 --> 00:30:24,600
SHOWED STRONG INTERACTION WITH

747
00:30:24,600 --> 00:30:25,400
CENTENARIANS IN 6 WITH THE WILD

748
00:30:25,400 --> 00:30:27,600
TYPE AND I THINK THE MOST

749
00:30:27,600 --> 00:30:29,200
INTERESTING HERE IS

750
00:30:29,200 --> 00:30:29,680
[INDISCERNIBLE].

751
00:30:29,680 --> 00:30:35,320
SO ACTUALLY IT WAS REPORTED THAT

752
00:30:35,320 --> 00:30:36,160
SIRT6 INTERACTING WITH

753
00:30:36,160 --> 00:30:38,080
[INDISCERNIBLE], AND WE SEE THAT

754
00:30:38,080 --> 00:30:39,720
THE CENTENARIARS HAVE STRONGER

755
00:30:39,720 --> 00:30:42,880
INTERACTION SO HERE CAN YOU SEE

756
00:30:42,880 --> 00:30:45,320
QUANTIFICATION SO THIS IS LAMIN8

757
00:30:45,320 --> 00:30:48,320
AND THIS IS WILD TYPE, SO IT'S

758
00:30:48,320 --> 00:30:49,680
ABOUT 20% DIFFERENCE BUT WITH

759
00:30:49,680 --> 00:30:52,160
MASS SPEC WE CAN DO IT IN A VERY

760
00:30:52,160 --> 00:30:54,320
QUANTITATIVE WAY SO WE ARE

761
00:30:54,320 --> 00:30:58,560
CONFIDENT THAT IT'S A REAL

762
00:30:58,560 --> 00:31:00,880
DIFFERENCE. 

763
00:31:00,880 --> 00:31:05,040
SO THIS IS QUICK SCENARIO OF THE

764
00:31:05,040 --> 00:31:09,240
CENTENARIAN PROJECT SO SIRT6

765
00:31:09,240 --> 00:31:10,520
PROVIDES BETTER STIMULATION OF

766
00:31:10,520 --> 00:31:13,320
DNA REPAIR BUT IT'S NOT ACROSS

767
00:31:13,320 --> 00:31:15,400
SPECIES BUT WITH HUMANS THIS IS

768
00:31:15,400 --> 00:31:18,320
STRONGER ASSOCIATED WITH

769
00:31:18,320 --> 00:31:18,720
LONGEVITY.

770
00:31:18,720 --> 00:31:21,320
INTERESTINGLY CROSS SPECIES WE

771
00:31:21,320 --> 00:31:23,320
SAW THAT BOTH ENZYMATIC

772
00:31:23,320 --> 00:31:25,200
ACTIVITIES WERE IN CURRENT BUT

773
00:31:25,200 --> 00:31:27,120
WITH THE HUMAN CENTENARIAN

774
00:31:27,120 --> 00:31:28,400
ENVIRONMENT, THERE WAS ONLY 1

775
00:31:28,400 --> 00:31:31,200
REGULATION THAT WAS

776
00:31:31,200 --> 00:31:31,720
[INDISCERNIBLE].

777
00:31:31,720 --> 00:31:35,720
AND WE ALSO--THIS IS THE LATEST

778
00:31:35,720 --> 00:31:36,600
RESULT THAT INTERACTS MOST

779
00:31:36,600 --> 00:31:38,520
STRONGLY WITH THE

780
00:31:38,520 --> 00:31:39,160
[INDISCERNIBLE].

781
00:31:39,160 --> 00:31:40,400
RIGHT NOW WE ALMOST TRIED TO

782
00:31:40,400 --> 00:31:43,960
SUBMIT THIS PAPER BUT SINCE WE

783
00:31:43,960 --> 00:31:45,320
FOLLOWED THIS LAMIN 8

784
00:31:45,320 --> 00:31:47,760
INTERACTION WE SHOW THAT LAMINA

785
00:31:47,760 --> 00:31:48,920
IS MORE [INDISCERNIBLE] THESE

786
00:31:48,920 --> 00:31:50,720
CELLS SO IT'S A LITTLE BIT

787
00:31:50,720 --> 00:31:52,280
TRICKIER WITH MASS SPEC BUT I

788
00:31:52,280 --> 00:31:53,960
HOPE WILL GET THE DATA WITH THE

789
00:31:53,960 --> 00:31:59,520
NEXT WEEK AND THEN WE CAN SUBMIT

790
00:31:59,520 --> 00:32:03,640
THE PAPER. 

791
00:32:03,640 --> 00:32:05,640
OKAY SO NOW, A LITTLE BIT OF

792
00:32:05,640 --> 00:32:08,040
DIFFERENT FUNCTION OF CELL 6, WE

793
00:32:08,040 --> 00:32:10,120
ALSO VERY INTERESTED IN GENOME

794
00:32:10,120 --> 00:32:14,840
STABILITY FROM THE POINT OF VIEW

795
00:32:14,840 --> 00:32:16,920
OF [INDISCERNIBLE] DNA,

796
00:32:16,920 --> 00:32:17,520
COMPARATIVE DEVELOPMENTS THAT

797
00:32:17,520 --> 00:32:23,040
MAKE A HUGE PORTION OF OUR

798
00:32:23,040 --> 00:32:25,120
GENOMES AND WE FOUND SO THAT WAS

799
00:32:25,120 --> 00:32:28,320
PUBLISHED YEARS AGO THAT CELL 6

800
00:32:28,320 --> 00:32:32,520
PLAYS IMPORTANT ROLE IN

801
00:32:32,520 --> 00:32:33,080
SILENCING [INDISCERNIBLE]

802
00:32:33,080 --> 00:32:37,320
BECAUSE YOU KNOW AS WE GET OLDER

803
00:32:37,320 --> 00:32:38,160
THESE ANIMALS BECOME DEPRESSED

804
00:32:38,160 --> 00:32:41,000
SO THAT CAN LEAD TO ACTUALLY

805
00:32:41,000 --> 00:32:42,600
VERY SEVERE CONSEQUENCES AND

806
00:32:42,600 --> 00:32:44,000
WHEN WE ANALYZED THESE CELL 6

807
00:32:44,000 --> 00:32:46,520
KNOCK OUT MICE THAT THEY MENTION

808
00:32:46,520 --> 00:32:49,200
INNED BEGINNING SO BESIDES JUST

809
00:32:49,200 --> 00:32:51,120
GENERAL GENOMIC STABILITY, THEY

810
00:32:51,120 --> 00:32:53,520
ALSO SHOW A HUGE ACTIVATION OF

811
00:32:53,520 --> 00:33:00,760
LINE 1 ELEMENTS SO LINE 1S THOSE

812
00:33:00,760 --> 00:33:02,360
AUTONOMOUS RETROTRANSPOSONS THAT

813
00:33:02,360 --> 00:33:03,880
CAN WRAP AROUND DNA DAMAGE AND

814
00:33:03,880 --> 00:33:05,680
IF WE PUT CELL 6 BACK INTO THESE

815
00:33:05,680 --> 00:33:09,360
CELLS WE CAN RESCUE THIS

816
00:33:09,360 --> 00:33:09,840
ACTIVATION.

817
00:33:09,840 --> 00:33:12,080
SO THAT'S WHAT WE PUBLISHED BACK

818
00:33:12,080 --> 00:33:13,120
THEN.

819
00:33:13,120 --> 00:33:14,840
NOW MORE RECENT WORK, WHAT WE

820
00:33:14,840 --> 00:33:17,840
FOUND WAS THAT BESIDES JUST

821
00:33:17,840 --> 00:33:20,720
HOPPING AROUND AND MAKING DNA

822
00:33:20,720 --> 00:33:22,920
BREAKS, WHAT LINE 1S CAN DO

823
00:33:22,920 --> 00:33:25,320
THAT'S ACTUALLY [INDISCERNIBLE]

824
00:33:25,320 --> 00:33:28,320
PERHAPS MORE DAMAGING, THEY

825
00:33:28,320 --> 00:33:30,720
GENERATE YOU KNOW A LOT OF LINE

826
00:33:30,720 --> 00:33:33,040
1 DNA, IN THE CELL IS AT 50 I

827
00:33:33,040 --> 00:33:34,400
DEPARTMENT KNOW WHERE THE DNA

828
00:33:34,400 --> 00:33:36,920
IS, WE MEASURED IT BY PC R,

829
00:33:36,920 --> 00:33:40,000
QUANTITATIVE PC R AND WE FOUND

830
00:33:40,000 --> 00:33:41,240
THAT SIRT6 MUTANT CELLS AND

831
00:33:41,240 --> 00:33:45,520
CELLS FROM AGE ANIMALS THAT HUGE

832
00:33:45,520 --> 00:33:46,240
ELEVATION OF [INDISCERNIBLE],

833
00:33:46,240 --> 00:33:48,120
AND IT WAS VERY DIFFICULT TO

834
00:33:48,120 --> 00:33:49,320
UNDERSTAND BECAUSE IF YOU

835
00:33:49,320 --> 00:33:51,400
IMAGINE IT'S IN THE GENOME AND

836
00:33:51,400 --> 00:33:52,600
THEN HAVE YOU 10 TIMES MORE LINE

837
00:33:52,600 --> 00:33:55,320
1 SO THAT MEANS WITH GENOME IS

838
00:33:55,320 --> 00:33:56,880
10 TIMES BIGGER DIDN'T MAKE ANY

839
00:33:56,880 --> 00:34:04,200
SENSE UNTIL WE TRIED TO FIND

840
00:34:04,200 --> 00:34:05,680
WHERE THEY'RE LOCATED AND EVEN

841
00:34:05,680 --> 00:34:07,800
EXTRA NUCLEUS, SO THIS IS

842
00:34:07,800 --> 00:34:08,880
STAYING IN [INDISCERNIBLE].

843
00:34:08,880 --> 00:34:11,280
DNA AND IT'S AROUND THE

844
00:34:11,280 --> 00:34:13,760
[INDISCERNIBLE], IT'S NOT

845
00:34:13,760 --> 00:34:18,120
EXCITED SO SOMEHOW THESE

846
00:34:18,120 --> 00:34:20,080
TRANSPOSONS MAKE THOSE DNA

847
00:34:20,080 --> 00:34:21,280
COPIES THAT FIND THEIR WAY

848
00:34:21,280 --> 00:34:23,320
OUTSIDE OF THE NUCLEUS AND WE

849
00:34:23,320 --> 00:34:26,560
ALSO THEN CELL FRACTIONATION AND

850
00:34:26,560 --> 00:34:28,520
VERY SIMILAR RESULT IN SIRT6 IMK

851
00:34:28,520 --> 00:34:31,040
OUTS ALSO IN OLD CELLS, WE SEE A

852
00:34:31,040 --> 00:34:36,240
LOT OF LINE 1 DNA THAT'S IN THE

853
00:34:36,240 --> 00:34:36,920
CYTOPLASM.

854
00:34:36,920 --> 00:34:40,040
SO THAT'S FROM A MOUSE LONG,

855
00:34:40,040 --> 00:34:41,440
MOUSE SPLEEN, THE SAME THING SO

856
00:34:41,440 --> 00:34:43,240
THERE IS DNA IN THE CYTOPLASM

857
00:34:43,240 --> 00:34:46,640
AND THERE IS DNA IN THE

858
00:34:46,640 --> 00:34:49,040
CYTOPLASM IT'S USUALLY WHEN

859
00:34:49,040 --> 00:34:49,600
YOU--[INDISCERNIBLE] BECAUSE

860
00:34:49,600 --> 00:34:51,840
USUALLY DNA IN THE CYTOPLASM

861
00:34:51,840 --> 00:34:53,440
MEANS IT'S AN INFECTION, A

862
00:34:53,440 --> 00:34:56,760
VIRUS, SO THERE ARE THESE

863
00:34:56,760 --> 00:35:02,080
NUCLEIC SENSORS IN THE CELL THAT

864
00:35:02,080 --> 00:35:03,600
EVOLVE TO DETECT CYTOPLASM DNA

865
00:35:03,600 --> 00:35:05,280
AND IMMUNE RESPONSE SO 1 OF

866
00:35:05,280 --> 00:35:11,680
THOSE SENSORS IS PROTEIN CALLED

867
00:35:11,680 --> 00:35:13,760
CGAS, IT BINDS CYTOPLASMIC DNA

868
00:35:13,760 --> 00:35:18,560
AND THEN YOU GET THE RESPONSE.

869
00:35:18,560 --> 00:35:22,320
SO WE MADE IP FOR CGAS AND WE

870
00:35:22,320 --> 00:35:24,480
LOOKEDDA THE WHAT DNA ASSOCIATES

871
00:35:24,480 --> 00:35:26,680
WITH IT AND WE FOUND IN CELL 6

872
00:35:26,680 --> 00:35:28,920
KNOCK OUTS THERE WAS A LOT OF

873
00:35:28,920 --> 00:35:31,640
LINE 1 DNA THAT WAS BOUND TO

874
00:35:31,640 --> 00:35:32,080
CGAS.

875
00:35:32,080 --> 00:35:40,320
SO IN BIND CGAS AND THEN IT ALSO

876
00:35:40,320 --> 00:35:41,120
INDUCES INTERFERONS.

877
00:35:41,120 --> 00:35:42,840
SO THAT WAS KIND OF A NEW WAY WE

878
00:35:42,840 --> 00:35:45,720
FOUND THAT WELL BESIDES DAMAGE

879
00:35:45,720 --> 00:35:49,720
IN DNA THOSE TRANSPOSONS CAN

880
00:35:49,720 --> 00:35:50,520
ALSO INFUSE INFLAMMATION AND

881
00:35:50,520 --> 00:35:54,640
THEN WE THOUGHT, WELL, CAN WE

882
00:35:54,640 --> 00:35:55,840
SOMEHOW EXTERMINATE THEM, LIKE

883
00:35:55,840 --> 00:35:59,400
THESE ARE FILE O GENOMIC PESTS,

884
00:35:59,400 --> 00:36:04,720
AND THERE ARE DRUGS THAT CAN

885
00:36:04,720 --> 00:36:05,640
SUPPRESS RETROTRANSPOSITIONS SO

886
00:36:05,640 --> 00:36:07,800
THESE WERE DRUGS THAT WERE

887
00:36:07,800 --> 00:36:09,760
DEVELOPED AGAINST HIV, THEY

888
00:36:09,760 --> 00:36:10,480
INHIBIT REVERSE TRANSCRIPT ACE

889
00:36:10,480 --> 00:36:13,320
OF HIV AND SOME OF THEM CLOSELY

890
00:36:13,320 --> 00:36:15,120
ACT WITH LINE 1 CANNED WHAT.

891
00:36:15,120 --> 00:36:19,120
SO WE TREATED OUR MICE, THOSE

892
00:36:19,120 --> 00:36:20,960
SIRT6 KNOCK OUT MICE, WE TREATED

893
00:36:20,960 --> 00:36:23,960
THEM WITH THESE DRUGS AND WHAT

894
00:36:23,960 --> 00:36:26,360
WE OBSERVED THAT THESE MICE HAD

895
00:36:26,360 --> 00:36:27,720
VERY STRONG INTERFERON RESPONSE

896
00:36:27,720 --> 00:36:29,080
BUT IF WE TREAT THEM WITH THE

897
00:36:29,080 --> 00:36:32,320
DRUGS WE CAN COMPLETE THE

898
00:36:32,320 --> 00:36:33,560
RESCUE, INTERFERON CANNED WHAT

899
00:36:33,560 --> 00:36:37,560
AND WE ALSO MAKE THESE MICE LIVE

900
00:36:37,560 --> 00:36:39,720
A LITTLE BIT LONGER.

901
00:36:39,720 --> 00:36:41,760
SO NORMALLY THEY'RE ALL DEAD BY

902
00:36:41,760 --> 00:36:43,440
30 DAYS BUT [INDISCERNIBLE]

903
00:36:43,440 --> 00:36:46,600
DRUGS WE COULD MAKE THEM LIVE

904
00:36:46,600 --> 00:36:49,640
ALMOST TO 60 DAYS.

905
00:36:49,640 --> 00:36:51,040
SO THESE ARE CELL 6 KNOCK OUTS

906
00:36:51,040 --> 00:36:52,840
OF COURSE WHAT ABOUT THE WILD

907
00:36:52,840 --> 00:36:54,520
TYPE, WE ARE VERY INTERESTED IN

908
00:36:54,520 --> 00:36:57,120
THE WILD TYPE, IF WE PUT MICE,

909
00:36:57,120 --> 00:36:59,720
WE TOOK FIRST, WE THOUGHT, YOU

910
00:36:59,720 --> 00:37:00,520
KNOW JUST PURCHASED VERY OLD

911
00:37:00,520 --> 00:37:02,600
MICE AND WE PUT THEM ON THESE

912
00:37:02,600 --> 00:37:04,600
DRUGS AND THEY DIDN'T HELP THEM.

913
00:37:04,600 --> 00:37:07,600
AND THEN WE THOUGHT, WELL, WE

914
00:37:07,600 --> 00:37:08,920
OBSERVED SOME LIVER INFLAMMATION

915
00:37:08,920 --> 00:37:11,920
SO THE DRUGS MAY BE WERE JUST

916
00:37:11,920 --> 00:37:13,800
CLOSING TOXICITY IN THESE VERY

917
00:37:13,800 --> 00:37:15,720
OLD MICE, SO THEY'LL BE TREATED

918
00:37:15,720 --> 00:37:17,200
MIDDLE AGE MICE FOR A FEW MONTHS

919
00:37:17,200 --> 00:37:20,840
AND THEN WE MEASURED THE

920
00:37:20,840 --> 00:37:22,800
BIOMARKERS, SO THIS IS

921
00:37:22,800 --> 00:37:23,800
METHYLATION CLOAK AND WE SEE

922
00:37:23,800 --> 00:37:27,760
THAT MICE THAT WERE TREATED WITH

923
00:37:27,760 --> 00:37:30,800
THE DRUGS HAD LOWER METHYLATION

924
00:37:30,800 --> 00:37:34,120
AGE, WE ALSO TREATED MICE THAT

925
00:37:34,120 --> 00:37:35,280
HAD THE P16 LUCIFERASE CONSTRUCT

926
00:37:35,280 --> 00:37:40,400
SO P16 IS ANOTHER PROTEIN THAT'S

927
00:37:40,400 --> 00:37:44,160
ELEVATED IN SENESCENSEL AND THEN

928
00:37:44,160 --> 00:37:45,000
WE MEASURED LUCIFERASE SIGNAL

929
00:37:45,000 --> 00:37:46,880
AND IT WAS LOWER IN THE TREATED

930
00:37:46,880 --> 00:37:49,560
MICE AGAIN BUT THIS BIOMARKER WE

931
00:37:49,560 --> 00:37:51,680
COULD SEE REDUCES STAGE IN THE

932
00:37:51,680 --> 00:37:53,160
TREATED MICE.

933
00:37:53,160 --> 00:37:58,440
SO THIS IS THE SUMMARY THAT WE

934
00:37:58,440 --> 00:38:01,320
HAVE THOSE ELEMENTS OF, YOU KNOW

935
00:38:01,320 --> 00:38:03,320
WAKING UP BIG PORTION OF OUR DNA

936
00:38:03,320 --> 00:38:07,000
AS WE GET OLDER THEY BECOME

937
00:38:07,000 --> 00:38:08,040
ACTIVATED SO THEY--THIS

938
00:38:08,040 --> 00:38:09,800
DEPRESSIVE MECHANISM IS 1 OF

939
00:38:09,800 --> 00:38:13,200
WHICH IS CELL 6, THEY START TO

940
00:38:13,200 --> 00:38:17,000
FAIL WITH AGE ACCIDENT LINE 1S

941
00:38:17,000 --> 00:38:19,120
BECOME TRANSCRIBED AND IN THE

942
00:38:19,120 --> 00:38:22,200
PROCESS, THEY ALSO GENERATE THE

943
00:38:22,200 --> 00:38:24,200
CYTOPLASMIC DNA THAT TRIGGERS

944
00:38:24,200 --> 00:38:29,600
THE STAYING PATHWAY, AND CAN

945
00:38:29,600 --> 00:38:32,400
TRIGGER [INDISCERNIBLE] SO THIS

946
00:38:32,400 --> 00:38:34,280
[INDISCERNIBLE] INFORMATION FOR

947
00:38:34,280 --> 00:38:36,800
THE BASIS OF MULTIPLE AGING

948
00:38:36,800 --> 00:38:37,360
PATHOLOGIES.

949
00:38:37,360 --> 00:38:38,080
YEAH, SOPHISTICATEDY THIS

950
00:38:38,080 --> 00:38:39,920
ANOTHER PICTURE WITH MAMMALIAN,

951
00:38:39,920 --> 00:38:43,280
THE JOURNAL DIDN'T LIKE,

952
00:38:43,280 --> 00:38:44,920
BUT--[LAUGHTER]

953
00:38:44,920 --> 00:38:48,160
--SO HERE, THIS IS YOUNG CELL

954
00:38:48,160 --> 00:38:49,880
TRAZ POSEONS OF THE DOGS AND

955
00:38:49,880 --> 00:38:52,720
THEY'RE SLEEPING AND SIRT6 AND

956
00:38:52,720 --> 00:38:53,880
[INDISCERNIBLE] DNA SO THEY

957
00:38:53,880 --> 00:38:58,280
DON'T RUN AROUND BUT IN OLD

958
00:38:58,280 --> 00:39:01,560
CELLS, CELL 6 IS NOT HOLDING

959
00:39:01,560 --> 00:39:02,840
VERY WELL, TRANSPOSONS GET

960
00:39:02,840 --> 00:39:03,880
ACTIVATED AND START CHEWING ON

961
00:39:03,880 --> 00:39:05,840
THE DNA WHICH IS BAD, BUT THE

962
00:39:05,840 --> 00:39:07,840
WORSE IS THAT THEY ESCAPE IN THE

963
00:39:07,840 --> 00:39:11,760
CYTOPLASM AND THEN THEY TRIGGER

964
00:39:11,760 --> 00:39:14,080
THOSE SENSORS THAT DRIVE THE

965
00:39:14,080 --> 00:39:18,360
[INDISCERNIBLE] THE POLICE CAR.

966
00:39:18,360 --> 00:39:19,600
SO THAT WAS RECENTLY PUBLISHED

967
00:39:19,600 --> 00:39:23,800
AND NOW IN THE REMAINING FEW

968
00:39:23,800 --> 00:39:27,120
MINUTES, I WANT TO SHOW YOU SOME

969
00:39:27,120 --> 00:39:30,120
RECENT THINGS AS WELL,

970
00:39:30,120 --> 00:39:31,680
CENTENARIAN STORIES ARE NOT

971
00:39:31,680 --> 00:39:33,440
PUBLISHED YET BUT OUR DNA REPAIR

972
00:39:33,440 --> 00:39:37,440
WAS PUBLISHED THIS YEAR, AND

973
00:39:37,440 --> 00:39:38,320
NOW, SOMETHING ELSE INTERESTING

974
00:39:38,320 --> 00:39:40,000
THAT WE ARE DEVELOPING RIGHT

975
00:39:40,000 --> 00:39:44,720
NOW, SO THIS IS THE DIAGRAM OF

976
00:39:44,720 --> 00:39:46,840
WHAT SIRT6 IS DOING SO WE TALKED

977
00:39:46,840 --> 00:39:49,920
ABOUT DNA REPAIR, WE DISCUSSED

978
00:39:49,920 --> 00:39:51,440
THE LINE 1 TRANSPOSONS AND WE

979
00:39:51,440 --> 00:39:55,400
FOUND THAT THERE IS THIS

980
00:39:55,400 --> 00:39:57,000
INTERESTING PHOSPHORYLATION SITE

981
00:39:57,000 --> 00:39:59,360
AND 6 IT THIS WAS DONE IN

982
00:39:59,360 --> 00:40:00,320
COLLABORATION WITH WILLS GROUP

983
00:40:00,320 --> 00:40:03,280
AND WE SHOWED THAT THE

984
00:40:03,280 --> 00:40:05,200
PHOSPHORYLATION OF THE S10 WHICH

985
00:40:05,200 --> 00:40:08,120
IS DONE BY GMP IS IMPORTANT FOR

986
00:40:08,120 --> 00:40:10,160
DRIVING CELL 6 TO DOUBLE STRAND

987
00:40:10,160 --> 00:40:13,160
BREAKS AND WE COULD ENHANCE

988
00:40:13,160 --> 00:40:17,720
RECRUITMENT WITH THIS

989
00:40:17,720 --> 00:40:18,480
PHOSPHORYLATION, SO, SOMETHING

990
00:40:18,480 --> 00:40:21,560
MORE RECENT AND HERE IS FINGER

991
00:40:21,560 --> 00:40:26,720
FROM THE PAPER THAT WE MADE FROM

992
00:40:26,720 --> 00:40:28,840
A MUTANT OF SIRT6 RECRUITMENT

993
00:40:28,840 --> 00:40:32,040
AND IT WAS BETTER THAN THE WILD

994
00:40:32,040 --> 00:40:35,240
TYPE DOUBLE STRAND BREAKS AND

995
00:40:35,240 --> 00:40:38,160
THIS S10 AMUTANT WHICH CAN NOT

996
00:40:38,160 --> 00:40:39,440
BE PHOSPHORALATED GOES A LITTLE

997
00:40:39,440 --> 00:40:41,720
SLOWER SO MORE RECENTLY WE FOUND

998
00:40:41,720 --> 00:40:43,880
THAT THIS MUTANT CAN ACTUALLY,

999
00:40:43,880 --> 00:40:45,320
IT'S LESS GOOD FOR DNA REPAIR

1000
00:40:45,320 --> 00:40:49,920
BUT IT'S BETTER TO BE PRESSING

1001
00:40:49,920 --> 00:40:50,400
[INDISCERNIBLE] SO THIS

1002
00:40:50,400 --> 00:40:53,320
PHOSPHORYLATION SITE MAY BE

1003
00:40:53,320 --> 00:40:54,520
DIRECTING SIRT6 TO WHAT THESE

1004
00:40:54,520 --> 00:40:55,840
MAY FUNCTION AND IN THE MEAN

1005
00:40:55,840 --> 00:41:00,360
TIME SO THIS SAWLS WORK OF MARK

1006
00:41:00,360 --> 00:41:01,920
SIMON.

1007
00:41:01,920 --> 00:41:03,160
HE GENERATED CRSPR 6 MICE WITH

1008
00:41:03,160 --> 00:41:05,960
THESE 2 STEM MUTATIONS SO HE

1009
00:41:05,960 --> 00:41:07,360
MADE THIS A, CANNOT BE

1010
00:41:07,360 --> 00:41:10,160
PHOSPHORALATED AND IS BETTER FOR

1011
00:41:10,160 --> 00:41:11,880
[INDISCERNIBLE] DEPRESSION AND

1012
00:41:11,880 --> 00:41:16,800
HE MADE S10 E THAT IS REMIXED

1013
00:41:16,800 --> 00:41:17,440
CONSTITTATIVE PHOSPHORYLATION.

1014
00:41:17,440 --> 00:41:21,040
SO WE ARE BEGINNING TO

1015
00:41:21,040 --> 00:41:22,360
CHARACTERIZE THESE MICE, SO

1016
00:41:22,360 --> 00:41:24,240
SOMETHING VERY INTERESTING THAT

1017
00:41:24,240 --> 00:41:26,080
MARK FOUND.

1018
00:41:26,080 --> 00:41:28,160
S10 EMICE, A SUPER GOOD AT

1019
00:41:28,160 --> 00:41:30,680
DEALING WITH THE DNA DAMAGE SO

1020
00:41:30,680 --> 00:41:34,520
HE RADIATED THESE MICE, WITH 10

1021
00:41:34,520 --> 00:41:36,320
DEAGREE OF GAMMA RADIATION WHICH

1022
00:41:36,320 --> 00:41:37,600
IS SUPPOSED TO [INDISCERNIBLE]

1023
00:41:37,600 --> 00:41:41,880
THEM AND WHICH IT DID FOR THE

1024
00:41:41,880 --> 00:41:45,120
WILD TYPES BUT S10 E, ACTUALLY

1025
00:41:45,120 --> 00:41:47,520
MANY MICE SURVIVED SO THAT WAS

1026
00:41:47,520 --> 00:41:48,640
UNBELIEVABLE SO THEY'RE SO GOOD

1027
00:41:48,640 --> 00:41:51,560
AT DEALING WITH THE DNA DAMAGE

1028
00:41:51,560 --> 00:41:55,520
AND THEN WE ALSO HAVE LIFE SPAN

1029
00:41:55,520 --> 00:41:58,120
STUDY THAT IS ONGOING AND THAT

1030
00:41:58,120 --> 00:42:00,320
WAS KIND OF FIRST DIFFICULT TO

1031
00:42:00,320 --> 00:42:02,680
UNDERSTAND RESULT, BUT WHAT WE

1032
00:42:02,680 --> 00:42:04,800
SEE THAT S10 E, DOESN'T SEEM TO

1033
00:42:04,800 --> 00:42:10,920
BE VERY DIFFERENT FROM THE WILD

1034
00:42:10,920 --> 00:42:11,320
TYPE.

1035
00:42:11,320 --> 00:42:15,080
BUT S10A IT'S ALMOST 20%, LONGER

1036
00:42:15,080 --> 00:42:16,960
LIVED WHICH IS SOMETHING

1037
00:42:16,960 --> 00:42:18,480
UNEXPECTED SO WHAT WE THINK, YOU

1038
00:42:18,480 --> 00:42:21,280
KNOW MAY BE GOING ON HERE IS

1039
00:42:21,280 --> 00:42:24,440
THAT THERE ARE THESE 2 FUNCTIONS

1040
00:42:24,440 --> 00:42:27,800
OF SIRT6, 1 IN PROMOTING DNA AND

1041
00:42:27,800 --> 00:42:28,960
ANOTHER 1 SILENCING.

1042
00:42:28,960 --> 00:42:33,080
THEY ARE BOTH IMPORTANT BUT BY

1043
00:42:33,080 --> 00:42:38,920
PLAYING WITH THIS SIGHT WE CAN

1044
00:42:38,920 --> 00:42:41,160
NATURALLY CHALLENGE SIRT6, WITH

1045
00:42:41,160 --> 00:42:42,720
THE OTHER ACTIVITY AND

1046
00:42:42,720 --> 00:42:45,080
REPRESSING LINE 1 SEEMS TO MORE

1047
00:42:45,080 --> 00:42:46,880
IMPORTANT FOR LONGEVITY BECAUSE

1048
00:42:46,880 --> 00:42:48,560
THAT'S PROBABLY WHAT PREVENS

1049
00:42:48,560 --> 00:42:49,640
AGE RELATED INFLAMMATION SO WE

1050
00:42:49,640 --> 00:42:51,280
ARE NOW ALSO LOOKING AT

1051
00:42:51,280 --> 00:42:53,520
INFLAMMATION IN THESE MICE, SO

1052
00:42:53,520 --> 00:42:57,160
THIS IS AN ONGOING PROJECT AND

1053
00:42:57,160 --> 00:42:58,120
PERHAPS ALSO WITH SIRT6

1054
00:42:58,120 --> 00:43:01,000
ACTIVATORS WE CAN TRY TO, YOU

1055
00:43:01,000 --> 00:43:02,720
KNOW EITHER STIMULATE THIS

1056
00:43:02,720 --> 00:43:04,720
FUNCTION OR THAT FUNCTION.

1057
00:43:04,720 --> 00:43:06,920
YOU KNOW, MAYBE SOME

1058
00:43:06,920 --> 00:43:08,320
IMPLICATIONS THERE AND YOU KNOW

1059
00:43:08,320 --> 00:43:11,480
I SAID LINE 1 SILENCING BUT THIS

1060
00:43:11,480 --> 00:43:12,760
MAY BE ALSO CHROMATIN

1061
00:43:12,760 --> 00:43:15,520
MAINTENANCE IN GENERAL SO IT'S

1062
00:43:15,520 --> 00:43:19,680
LIKE MORE EPIGENETIC ROLE VERSUS

1063
00:43:19,680 --> 00:43:20,240
[INDISCERNIBLE] DNA.

1064
00:43:20,240 --> 00:43:24,720
SO LET ME SUMMARIZE AND WE

1065
00:43:24,720 --> 00:43:26,000
DISCUSSED DIFFERENT LONGEVITY

1066
00:43:26,000 --> 00:43:26,760
MECHANISM SO AGAIN WE DIDN'T

1067
00:43:26,760 --> 00:43:29,880
HAVE TIME TO TALK ABOUT

1068
00:43:29,880 --> 00:43:30,560
[INDISCERNIBLE] SPECIFIC

1069
00:43:30,560 --> 00:43:32,600
MECHANISM WE FOUND

1070
00:43:32,600 --> 00:43:34,680
[INDISCERNIBLE] THINGS, SO HERE

1071
00:43:34,680 --> 00:43:36,400
ARE DIFFERENT SPECIES THAT ARE

1072
00:43:36,400 --> 00:43:41,160
LONG LIVED AS OPPOSE TO TYPICAL

1073
00:43:41,160 --> 00:43:43,240
LABORATORY ORGANISMS SO WOO FIND

1074
00:43:43,240 --> 00:43:44,680
THIS SPECIFIC MECHANISM AND ALSO

1075
00:43:44,680 --> 00:43:46,280
CONSERVED MECHANISM THAT THE

1076
00:43:46,280 --> 00:43:47,480
SAME, YOU KNOW--TUNE THE SAME

1077
00:43:47,480 --> 00:43:50,280
WAY, NO LONG LIVED SPECIES AND

1078
00:43:50,280 --> 00:43:54,120
MECHANISMS WE'VE BEEN REPORTED

1079
00:43:54,120 --> 00:43:55,880
FOR SOMETIME THESE NUTRIENT

1080
00:43:55,880 --> 00:43:58,560
SENSING PATHWAYS SUCH AS

1081
00:43:58,560 --> 00:44:00,400
[INDISCERNIBLE] AND IGF AND MORE

1082
00:44:00,400 --> 00:44:01,920
THAT ARE IMPORTANT FOR LONGEVITY

1083
00:44:01,920 --> 00:44:05,440
AND NOW WE CAN ADD HERE, DNA

1084
00:44:05,440 --> 00:44:06,720
DOUBLE STRAND BREAK REPAIR SO WE

1085
00:44:06,720 --> 00:44:10,480
KNOW A PATHWAY IS A PATHWAY OF

1086
00:44:10,480 --> 00:44:12,400
LONGEVITY AND ALL SIRT6 AND BY

1087
00:44:12,400 --> 00:44:13,520
COMBINING, YOU KNOW SOMETHING

1088
00:44:13,520 --> 00:44:14,600
FROM HERE, SOMETHING FROM HERE,

1089
00:44:14,600 --> 00:44:18,240
YOU KNOW THEN WE HOPEFULLY CAN

1090
00:44:18,240 --> 00:44:21,000
DEVELOP SOME USEFUL

1091
00:44:21,000 --> 00:44:23,200
INTERVENTIONS FOR HUMAN HEALTH

1092
00:44:23,200 --> 00:44:23,560
SPOT.

1093
00:44:23,560 --> 00:44:26,120
SO THESE ARE PEOPLE WHO DID THE

1094
00:44:26,120 --> 00:44:27,800
WORK, I ACTUALLY NAMED MOST OF

1095
00:44:27,800 --> 00:44:30,320
THEM WHILE I WAS GOING ALONG SO

1096
00:44:30,320 --> 00:44:34,800
THIS IS MARK HERE, THIS IS

1097
00:44:34,800 --> 00:44:37,680
XIAO BEFORE HE MOVED ON TO HIS

1098
00:44:37,680 --> 00:44:39,560
NEXT POST DOC, ALL THIS WAS DONE

1099
00:44:39,560 --> 00:44:42,280
IN COLLABORATION WITH

1100
00:44:42,280 --> 00:44:43,960
[INDISCERNIBLE] WITH MY CO-PI ON

1101
00:44:43,960 --> 00:44:48,760
ALL MY PROJECTS AND WE HAVE MANY

1102
00:44:48,760 --> 00:44:50,040
EXTERNAL COLLABORATORS SO WE'RE

1103
00:44:50,040 --> 00:44:51,320
ALWAYS RIGHT HERE.

1104
00:44:51,320 --> 00:44:53,360
WE HAVE THESE 2 BIG PROGRAM

1105
00:44:53,360 --> 00:44:59,560
PROJECTS, 1 IS FOCUSED ON

1106
00:44:59,560 --> 00:45:01,440
COMPRATIVE BIOLOGY,

1107
00:45:01,440 --> 00:45:02,000
[INDISCERNIBLE] AND

1108
00:45:02,000 --> 00:45:04,160
[INDISCERNIBLE] PROGRAM FOR

1109
00:45:04,160 --> 00:45:05,120
[INDISCERNIBLE] AND I WILL BE

1110
00:45:05,120 --> 00:45:09,160
HAPPY TO TAKE QUESTIONS.

1111
00:45:09,160 --> 00:45:18,520
[APPLAUSE ]

1112
00:45:18,520 --> 00:45:19,720
>> THANK YOU FOR A WONDERFUL

1113
00:45:19,720 --> 00:45:19,920
TALK.

1114
00:45:19,920 --> 00:45:21,520
WE WILL START WITH A COUPLE

1115
00:45:21,520 --> 00:45:22,520
QUESTIONS FROM HERE BEFORE WE

1116
00:45:22,520 --> 00:45:29,920
MOVE,A ROUND TO THE OTHER SITES.

1117
00:45:29,920 --> 00:45:31,920
>> MAYBE I CAN JUST ASK YOU

1118
00:45:31,920 --> 00:45:34,200
WHILE THEY'RE LANGUAGING ABOUT

1119
00:45:34,200 --> 00:45:37,520
T6 IS INVOLVED IN BR, EVER SINCE

1120
00:45:37,520 --> 00:45:39,000
BR IS 1 OF THE 5, WHAT DO YOU

1121
00:45:39,000 --> 00:45:45,680
THINK ABOUT BR AND LONGEVITY.

1122
00:45:45,680 --> 00:45:48,280
>> WELL I'M ALMOST SURE IT'S

1123
00:45:48,280 --> 00:45:56,320
IMPORTANT AND THERE'S SO MUCH

1124
00:45:56,320 --> 00:45:57,840
WITH THEOXIDATIVE DAMAGE AND

1125
00:45:57,840 --> 00:45:59,720
DOUBLE STRAND BEPAIR BECAUSE IF

1126
00:45:59,720 --> 00:46:08,760
YOU ARE REALLY DESTROYED BR,

1127
00:46:08,760 --> 00:46:09,360
IT'S LETHAL.

1128
00:46:09,360 --> 00:46:11,640
MAYBE THAT'S PART OF THE REASON

1129
00:46:11,640 --> 00:46:13,640
THAT THERE ARE A FEW BUT THEY'RE

1130
00:46:13,640 --> 00:46:15,840
NOT--YOU DON'T TELL THEM WHAT

1131
00:46:15,840 --> 00:46:19,720
BECAUSE MOSTLY THEY WERE

1132
00:46:19,720 --> 00:46:20,920
MEASURING INDIVIDUAL ENZYMES

1133
00:46:20,920 --> 00:46:22,920
THAT DIDN'T SHOW VERY STRONG

1134
00:46:22,920 --> 00:46:26,800
ASSOCIATION BUT MAYBE THAT NEEDS

1135
00:46:26,800 --> 00:46:28,880
TO BE REVISITED AND FOR THE ROLE

1136
00:46:28,880 --> 00:46:30,720
OF 6, YES, IT IS ALSO INVOLVED

1137
00:46:30,720 --> 00:46:32,240
THEY WOULD SUGGEST THAT MAYBE

1138
00:46:32,240 --> 00:46:34,640
THERE IS VERY SIMILAR

1139
00:46:34,640 --> 00:46:43,320
ASSOCIATION FOR LONGEVITY.

1140
00:46:43,320 --> 00:46:46,520
>> OKAY, SO BEING SIRT6,

1141
00:46:46,520 --> 00:46:47,800
[INDISCERNIBLE] LINE 1

1142
00:46:47,800 --> 00:46:48,920
EXPRESSION, ARE WE ABLE TO LOOK

1143
00:46:48,920 --> 00:46:53,320
AT THIS IN THE CENTENARIANS?

1144
00:46:53,320 --> 00:46:54,920
>> OH YES, I DIDN'T SHOW THE

1145
00:46:54,920 --> 00:46:55,120
DATA.

1146
00:46:55,120 --> 00:46:59,280
YES, YES, WE DID.

1147
00:46:59,280 --> 00:47:00,560
AND CENTENARIANS SIRT6 IS BETTER

1148
00:47:00,560 --> 00:47:02,520
THROUGH [INDISCERNIBLE] SO IT'S

1149
00:47:02,520 --> 00:47:07,880
ACTUALLY DOES BOTH.

1150
00:47:07,880 --> 00:47:08,040
YES.

1151
00:47:08,040 --> 00:47:09,160
>> WILL, CAN PEOPLE USE THE

1152
00:47:09,160 --> 00:47:11,120
MICROPHONE TO ASK QUESTIONS

1153
00:47:11,120 --> 00:47:11,680
BECAUSE THEY AREN'T COMING

1154
00:47:11,680 --> 00:47:13,760
THROUGH ON THE BROADCAST.

1155
00:47:13,760 --> 00:47:16,040
>> WE WILL TRY REPEATING

1156
00:47:16,040 --> 00:47:16,480
QUESTIONS TOO.

1157
00:47:16,480 --> 00:47:56,960
>> WHAT WAS THE QUESTION?

1158
00:47:56,960 --> 00:47:57,440
>> [INDISCERNIBLE].

1159
00:47:57,440 --> 00:47:57,880
>> [INDISCERNIBLE]

1160
00:47:57,880 --> 00:48:00,440
>> OH YES, SO IT WAS PREPORTED

1161
00:48:00,440 --> 00:48:01,120
THAT CELL 6--

1162
00:48:01,120 --> 00:48:02,520
>> CAN YOU REPEAT THE QUESTION

1163
00:48:02,520 --> 00:48:02,760
PLEASE.

1164
00:48:02,760 --> 00:48:03,760
>> YES, YES.

1165
00:48:03,760 --> 00:48:08,160
SO THE QUESTION IS:  IT WAS

1166
00:48:08,160 --> 00:48:12,480
REPORT THAD SIRT6 CAN

1167
00:48:12,480 --> 00:48:13,120
TRANSCRIPTIONALLY CONTROL

1168
00:48:13,120 --> 00:48:14,680
NFCAPPA B AND INFLAMMATION

1169
00:48:14,680 --> 00:48:16,960
PATHWAY SO THIS IS IMPORTANT

1170
00:48:16,960 --> 00:48:19,160
VERSUS EFFECT ON LINE 1 THAT WE

1171
00:48:19,160 --> 00:48:23,360
SHOWED IS WELL, YES WE COULD

1172
00:48:23,360 --> 00:48:24,240
DISASSOCIATE IT BECAUSE FOR

1173
00:48:24,240 --> 00:48:25,440
EXAMPLE THAT MICE SHOW IN

1174
00:48:25,440 --> 00:48:26,920
CONSTANT WITH THE HUMAN

1175
00:48:26,920 --> 00:48:28,440
RESPONSE, WE COULD, YOU KNOW IN

1176
00:48:28,440 --> 00:48:31,320
1 BLAST ON THESE MICE, WE COULD

1177
00:48:31,320 --> 00:48:34,840
JUST USE THIS HRNA TO LINE 1 AND

1178
00:48:34,840 --> 00:48:35,880
BE COMPLETELY APPROPRIATE

1179
00:48:35,880 --> 00:48:38,000
INTERFERON RESPONSE SO THIS

1180
00:48:38,000 --> 00:48:40,840
NFCAPPA B, PERHAP ITS PLAYS SOME

1181
00:48:40,840 --> 00:48:43,040
ROLE BUT WE [INDISCERNIBLE] SO

1182
00:48:43,040 --> 00:48:49,680
THAT IT WAS REALLY LINE 1

1183
00:48:49,680 --> 00:48:50,120
DEPENDENT.

1184
00:48:50,120 --> 00:48:50,320
OKAY.

1185
00:48:50,320 --> 00:48:51,840
>> OKAY THEN WE'LL GO ON TO THE

1186
00:48:51,840 --> 00:48:54,360
CENTERS, LET'S START WITH YOU

1187
00:48:54,360 --> 00:48:58,040
STEVE IN OREGON, SO EVERYONE

1188
00:48:58,040 --> 00:49:00,720
ELSE MUTES AND 1 QUESTION PER

1189
00:49:00,720 --> 00:49:00,920
SITE.

1190
00:49:00,920 --> 00:49:05,720
>> THANK YOU VERY MUCH.

1191
00:49:05,720 --> 00:49:07,520
WILL YOU ACTUALLY TOOK THE

1192
00:49:07,520 --> 00:49:09,000
INITIAL QUESTION WE HAD HERE IN

1193
00:49:09,000 --> 00:49:11,320
REGARD TO THE ROLE OF V. E. R.

1194
00:49:11,320 --> 00:49:12,600
AND WHETHER THERE HAD BEEN

1195
00:49:12,600 --> 00:49:16,280
ANYTHING LOOKED AT RELATIVE TO

1196
00:49:16,280 --> 00:49:18,720
THE LEVELS OF OGG 1 ESPECIALLY

1197
00:49:18,720 --> 00:49:20,320
IN LIGHT OF DIRECT MEANS

1198
00:49:20,320 --> 00:49:23,400
RELATIVELY RECENT WORK SHOWING

1199
00:49:23,400 --> 00:49:24,800
THE NECESSITY WE'RE CREATING

1200
00:49:24,800 --> 00:49:26,400
THOSE BREAKS THAT WE'RE GOING TO

1201
00:49:26,400 --> 00:49:30,120
BE P A RT DEPENDENT SO IT SOUNDS

1202
00:49:30,120 --> 00:49:31,600
LIKE THAT THAT'S NOT BEEN

1203
00:49:31,600 --> 00:49:32,880
ADEQUATELY LOOKED AT BUT 1 OF

1204
00:49:32,880 --> 00:49:34,880
THE QUESTIONS CONCERNING SOME OF

1205
00:49:34,880 --> 00:49:35,720
THESE TRANSGENIC MICE WHERE

1206
00:49:35,720 --> 00:49:38,320
YOU'VE DONE SOME OF THE DOMAIN

1207
00:49:38,320 --> 00:49:42,280
SWAPPING ARE THERE ANY RPGHT

1208
00:49:42,280 --> 00:49:43,360
BEHAVIORIAL EFFECTS OR METABOLIC

1209
00:49:43,360 --> 00:49:46,920
EFFECTS THAT YOU SEE ASSOCIATED

1210
00:49:46,920 --> 00:49:47,680
WITH THOSE MICE?

1211
00:49:47,680 --> 00:49:50,560
>> WELL THAT'S A GOOD QUESTION.

1212
00:49:50,560 --> 00:49:52,080
YEAH, SO THE SWAPPING MOUSE WE

1213
00:49:52,080 --> 00:49:54,480
DON'T HAVE YET, SO WE HAVE THE

1214
00:49:54,480 --> 00:49:55,560
MICE WITH PHOSPHORYLATION SITE

1215
00:49:55,560 --> 00:49:57,640
MUTATION SO WE ARE

1216
00:49:57,640 --> 00:49:59,240
CHARACTERIZING IT.

1217
00:49:59,240 --> 00:50:01,440
I DON'T REALLY HAVE MUCH TO TELL

1218
00:50:01,440 --> 00:50:05,600
YOU RIGHT NOW BECAUSE IT'S SLOW

1219
00:50:05,600 --> 00:50:07,120
GOING.

1220
00:50:07,120 --> 00:50:11,920
WE NOTICED THAT YOUNG S10

1221
00:50:11,920 --> 00:50:15,200
E MICE, REPAIR THEY SEEM TO BE

1222
00:50:15,200 --> 00:50:18,600
MORE ACTIVE BUT OVERTIME THOSE

1223
00:50:18,600 --> 00:50:20,800
LINES KIND OF MEET AGAIN SO WITH

1224
00:50:20,800 --> 00:50:22,920
MIDDLE AGED MICE WE DON'T SEE

1225
00:50:22,920 --> 00:50:24,120
THE DIFFERENCE BECAUSE S10 MICE

1226
00:50:24,120 --> 00:50:26,040
TEND TO BE A LITTLE BIT HEAVIER,

1227
00:50:26,040 --> 00:50:28,400
SO AGAIN, WHEN THE ORGANISM

1228
00:50:28,400 --> 00:50:30,280
LEVEL, THERE ARE ALL THOSE

1229
00:50:30,280 --> 00:50:30,920
COMPLICATIONS SO WE'RE STILL

1230
00:50:30,920 --> 00:50:35,120
TRYING TO SOLVE THIS OUT.

1231
00:50:35,120 --> 00:50:36,200
>> I ASSUME YOU'RE JUST KEEPING

1232
00:50:36,200 --> 00:50:39,280
THOSE MICE ON A NORMAL CHOW DIET

1233
00:50:39,280 --> 00:50:43,320
AND NOT WHERE THERE WOULD BE A

1234
00:50:43,320 --> 00:50:45,000
REALLY RELATIVELY LOW FAT

1235
00:50:45,000 --> 00:50:47,360
CONTENT IN THEIR CHOW?

1236
00:50:47,360 --> 00:50:49,480
>> WELL, SO FAR IT'S ALL BEEN

1237
00:50:49,480 --> 00:50:51,560
REGULAR CHOW BUT THAT'S A VERY

1238
00:50:51,560 --> 00:50:54,080
GOOD IDEA TO TRY TO CHALLENGE

1239
00:50:54,080 --> 00:50:55,400
THEM METABOLICALLY.

1240
00:50:55,400 --> 00:50:56,600
INTERESTING.

1241
00:50:56,600 --> 00:50:56,760
YES.

1242
00:50:56,760 --> 00:50:58,680
>> OKAY, THANKS.

1243
00:50:58,680 --> 00:51:00,040
STEVEN THANKS, OREGON AND THEN

1244
00:51:00,040 --> 00:51:05,480
LET'S MOVE OVER TO PITTSBURGH.

1245
00:51:05,480 --> 00:51:08,440
EVERYBODY ELSE MUTE PLEASE?

1246
00:51:08,440 --> 00:51:10,520
>> HI, VERA THIS IS BEN

1247
00:51:10,520 --> 00:51:12,120
[INDISCERNIBLE] WE ENJOYED YOUR

1248
00:51:12,120 --> 00:51:13,640
SEMINAR VERY MUCH HERE IN

1249
00:51:13,640 --> 00:51:13,920
PITTSBURGH.

1250
00:51:13,920 --> 00:51:18,040
I HAD A COMMENT AND A QUESTION.

1251
00:51:18,040 --> 00:51:19,320
THE COMMENT IS JOHN

1252
00:51:19,320 --> 00:51:20,720
[INDISCERNIBLE] CAME AND GAVE A

1253
00:51:20,720 --> 00:51:23,480
TALK HERE RECENTLY AT THE AGING

1254
00:51:23,480 --> 00:51:24,080
INSTITUTE AND HE TALKED ABOUT

1255
00:51:24,080 --> 00:51:25,840
HIS BEAUTIFUL WORK WITH THE LINE

1256
00:51:25,840 --> 00:51:28,080
ELEMENTS AND THE NRTIs AND 1

1257
00:51:28,080 --> 00:51:29,200
CONCERN THAT PEOPLE RAISED WAS

1258
00:51:29,200 --> 00:51:31,320
THAT TOO MUCH OF A GOOD THING IS

1259
00:51:31,320 --> 00:51:37,240
A BAD THING AND THE NRTIs

1260
00:51:37,240 --> 00:51:38,720
COULD HURT MITOCHONDRIAL

1261
00:51:38,720 --> 00:51:39,920
FUNCTION BECAUSE GAMMA COULD

1262
00:51:39,920 --> 00:51:42,120
INSERT THEM INTO THE

1263
00:51:42,120 --> 00:51:43,400
MITOCHONDRIA, YOU SHOWED 1 DOSE

1264
00:51:43,400 --> 00:51:45,280
BUT MAYBE IT DIDN'T WORK IN

1265
00:51:45,280 --> 00:51:46,400
OLDER ANIMALS BECAUSE MAYBE YOU

1266
00:51:46,400 --> 00:51:48,000
DIDN'T GET THE DOSE RIGHT.

1267
00:51:48,000 --> 00:51:51,200
BUT MY QUESTION HAS TO DO WITH

1268
00:51:51,200 --> 00:51:54,600
MONORIEBS ONALATED P A RP AT

1269
00:51:54,600 --> 00:51:58,560
LISINE 521, DO YOU KNOW IF JOHN

1270
00:51:58,560 --> 00:52:00,160
PASCAL OR ANYBODY ELSE HAS SHOWN

1271
00:52:00,160 --> 00:52:03,680
THAT BINDS MORE AVIDLY TO DOUBLE

1272
00:52:03,680 --> 00:52:06,280
STRAND BREAKS OR A-BASIC SITES

1273
00:52:06,280 --> 00:52:09,720
OR IS IT JUST NOR CATALYTICALLY

1274
00:52:09,720 --> 00:52:10,200
ACTIVE?

1275
00:52:10,200 --> 00:52:11,280
>> THESE ARE ACTUALLY, THERE ARE

1276
00:52:11,280 --> 00:52:12,040
2 QUESTIONS RIGHT?

1277
00:52:12,040 --> 00:52:14,040
SO LET'S START WITH THE P A RP,

1278
00:52:14,040 --> 00:52:16,720
NO, WE HAVEN'T CHARACTERIZED IT

1279
00:52:16,720 --> 00:52:17,080
ENOUGH.

1280
00:52:17,080 --> 00:52:18,240
I THINK THIS WOULD BE VERY

1281
00:52:18,240 --> 00:52:20,480
INTERESTING TO DO SOPHISTICATED

1282
00:52:20,480 --> 00:52:23,040
SEE WHAT EXACTLY THAT

1283
00:52:23,040 --> 00:52:25,040
MODIFICATION DOES IN THE P A RP

1284
00:52:25,040 --> 00:52:26,240
LEVEL.

1285
00:52:26,240 --> 00:52:27,920
SO I THINK--I AM GOING TO GET

1286
00:52:27,920 --> 00:52:30,040
SOMEONE TO DID IT BECAUSE THAT

1287
00:52:30,040 --> 00:52:31,920
REALLY CHANGES SOMETHING WITH P

1288
00:52:31,920 --> 00:52:34,240
A RP, BUT WE HAVEN'T SIGNIFY

1289
00:52:34,240 --> 00:52:35,520
SECTIONAL ANALYSISSED IT FURTHER

1290
00:52:35,520 --> 00:52:39,960
AND NOW TO YOUR FIRST QUESTION

1291
00:52:39,960 --> 00:52:41,320
ABOUT NRTIS WHETHER IT'S A GOOD

1292
00:52:41,320 --> 00:52:42,840
THING OR A BAD THING, WE HAVE

1293
00:52:42,840 --> 00:52:44,520
ANOTHER PROJECT WHICH WOULD TAKE

1294
00:52:44,520 --> 00:52:46,400
ME TO ANOTHER SEMINAR TO PRESENT

1295
00:52:46,400 --> 00:52:48,120
WHICH I DIDN'T TALK ABOUT WHERE

1296
00:52:48,120 --> 00:52:51,120
WE ACTUALLY FOUND EXECUTIVE

1297
00:52:51,120 --> 00:52:51,560
[INDISCERNIBLE].

1298
00:52:51,560 --> 00:52:54,720
SOEE USED A DIFFERENT ORGANISM,

1299
00:52:54,720 --> 00:52:57,280
BLIND MOLE RAT THAT THEY DID

1300
00:52:57,280 --> 00:52:58,280
PROPERLY INTRODUCED, IT'S

1301
00:52:58,280 --> 00:52:59,440
ANOTHER LONG LIVED RODENT AND

1302
00:52:59,440 --> 00:53:02,560
USING THAT ANIMAL SO WE FOUND

1303
00:53:02,560 --> 00:53:07,320
THAT LINE 1S IN THE ANIMAL, ARE

1304
00:53:07,320 --> 00:53:08,760
IMPORTANT FOR [INDISCERNIBLE].

1305
00:53:08,760 --> 00:53:12,360
SO WHAT HAPPENS THERE, SAME

1306
00:53:12,360 --> 00:53:14,800
STORY ACTIVATED TRANSPOSONS, 3

1307
00:53:14,800 --> 00:53:16,040
[INDISCERNIBLE], TRIGGER

1308
00:53:16,040 --> 00:53:19,640
[INDISCERNIBLE], AND THAT'S WHAT

1309
00:53:19,640 --> 00:53:20,720
ELIMINATE PREMALIGNANT LESIONS

1310
00:53:20,720 --> 00:53:23,240
AND THEN IT FITS WELL BUT IF WE

1311
00:53:23,240 --> 00:53:24,520
COMPLETE LYE DEPRESS THOSE

1312
00:53:24,520 --> 00:53:26,360
ELEMENTS WE ACTUALLY CAN MAKE

1313
00:53:26,360 --> 00:53:27,760
ANIMALS MORE SENSITIVE TO CANCER

1314
00:53:27,760 --> 00:53:30,120
SO THIS IS KIND OF THIS OTHER

1315
00:53:30,120 --> 00:53:31,520
IDEA WE'RE DEVELOPING RIGHT NOW

1316
00:53:31,520 --> 00:53:34,760
THAT LINE 1S MAY BE THE DOUBLE

1317
00:53:34,760 --> 00:53:38,640
EDGED SWORD BECAUSE IN THE YOUNG

1318
00:53:38,640 --> 00:53:40,520
ANIMAL THEY PLAY TUMOR

1319
00:53:40,520 --> 00:53:42,720
SUPPRESSIVE ROLE BUT AS THEY GET

1320
00:53:42,720 --> 00:53:44,880
OLDER THEY GET ACTIVE AND LEAKY

1321
00:53:44,880 --> 00:53:47,600
AND THEN THAT TRIGGERS

1322
00:53:47,600 --> 00:53:50,320
FORMULATION AND THEN SIMILAR

1323
00:53:50,320 --> 00:53:51,000
PROCESS LIKE SENESCENSEL P53

1324
00:53:51,000 --> 00:53:53,320
WOULD BE THE YOUNG AND THEN THE

1325
00:53:53,320 --> 00:53:54,320
[INDISCERNIBLE] INTO THE OLD BUT

1326
00:53:54,320 --> 00:53:55,920
THEN IN TERMS OF DEVELOPING

1327
00:53:55,920 --> 00:53:57,520
THERAPEUTICS THAT MAKES YOU

1328
00:53:57,520 --> 00:54:02,520
THINK ALL RIGHT, IF WE JUST WANT

1329
00:54:02,520 --> 00:54:03,440
TO REFRESES THEM ALTOGETHER LIKE

1330
00:54:03,440 --> 00:54:05,960
IS IT GOING TO HURT US AT SOME

1331
00:54:05,960 --> 00:54:06,680
POINT.

1332
00:54:06,680 --> 00:54:08,400
SO WE DON'T KNOW AT THIS POINT

1333
00:54:08,400 --> 00:54:09,960
WE DON'T KNOW, WE GENERATED

1334
00:54:09,960 --> 00:54:12,560
ANOTHER MOUSE MODEL WHICH WE

1335
00:54:12,560 --> 00:54:16,640
HAVEN'T CHARACTERIZED BUT YET,

1336
00:54:16,640 --> 00:54:19,080
WE'RE--WE ARE USING SEVERAL

1337
00:54:19,080 --> 00:54:20,680
LINKED SHRNAs WHERE WE REPRESS

1338
00:54:20,680 --> 00:54:21,480
LINE 1 BY 50%.

1339
00:54:21,480 --> 00:54:24,720
SO I CAN TELL YOU THESE MICE ARE

1340
00:54:24,720 --> 00:54:24,920
ALIVE.

1341
00:54:24,920 --> 00:54:27,160
YOU KNOW?

1342
00:54:27,160 --> 00:54:28,680
SO, YOU KNOW THESE DON'T USE

1343
00:54:28,680 --> 00:54:31,320
LINE 1 ACTIVITY BUT HOW WE GO AT

1344
00:54:31,320 --> 00:54:34,160
THE CANCER AGING, WE DON'T KNOW

1345
00:54:34,160 --> 00:54:34,320
YET.

1346
00:54:34,320 --> 00:54:36,840
>> THANK YOU.

1347
00:54:36,840 --> 00:54:37,080
THANKS.

1348
00:54:37,080 --> 00:54:40,840
NOW LET'S GO TO KENTUCKY.

1349
00:54:40,840 --> 00:54:41,240
DAVE?

1350
00:54:41,240 --> 00:54:44,000
>> IS HI, REALLY ENJOYED YOUR

1351
00:54:44,000 --> 00:54:47,520
TALK VERA, I HAD 1 QUESTION, I

1352
00:54:47,520 --> 00:54:50,320
NOTICED THAT SIRT6 FROM

1353
00:54:50,320 --> 00:54:52,520
CENTENARIANS THAT INTERACT

1354
00:54:52,520 --> 00:54:54,480
STRONGLY WITH LAMINA, THAT'S

1355
00:54:54,480 --> 00:54:56,640
CORRECT, RIGHT?

1356
00:54:56,640 --> 00:54:59,200
>> YES, SO OBVIOUSLY LAMINA IS

1357
00:54:59,200 --> 00:55:00,600
DIFFERENT AND HAVE YOU LOOKAD

1358
00:55:00,600 --> 00:55:05,320
THE WHETHER THAT INTERACTION IS

1359
00:55:05,320 --> 00:55:08,480
ABOLISHED IN CELLS FROM

1360
00:55:08,480 --> 00:55:09,520
PROGERIATRICKIZATIONIA PATIENTS?

1361
00:55:09,520 --> 00:55:13,320
>> SO THAT IS ACTUALLY THE WORK

1362
00:55:13,320 --> 00:55:14,400
FROM [INDISCERNIBLE] LAB.

1363
00:55:14,400 --> 00:55:17,960
I THINK HE REPORTED THAT THERE

1364
00:55:17,960 --> 00:55:22,360
S&P INTERACTION BETWEEN

1365
00:55:22,360 --> 00:55:23,760
LAMINACE, AND PROGERIAN, IT

1366
00:55:23,760 --> 00:55:27,760
WASN'T ABOLISHED IT WAS THE

1367
00:55:27,760 --> 00:55:30,880
OPPOSITE, AS THE PROGENERRIAN

1368
00:55:30,880 --> 00:55:34,680
WAS TRAPPING IT CLOSE TO THE

1369
00:55:34,680 --> 00:55:35,120
MEMBRANE.

1370
00:55:35,120 --> 00:55:39,560
SO I THINK THATIA KIND OF WHAT

1371
00:55:39,560 --> 00:55:42,480
PROGERRIAN DOES, SO INSTEAD OF

1372
00:55:42,480 --> 00:55:43,840
LOSING INTERACTION, IT

1373
00:55:43,840 --> 00:55:46,440
SEQUESTERS PROTEINS IN THE

1374
00:55:46,440 --> 00:55:48,520
APPROPRIATE SO NOW WHAT

1375
00:55:48,520 --> 00:55:49,240
CENTENARIAN BINDS BECAUSE THAT

1376
00:55:49,240 --> 00:55:51,720
ISN'T WHAT THE WILD TYPE KIND SO

1377
00:55:51,720 --> 00:55:54,720
THEN IT'S KIND OF--THE CORRECT

1378
00:55:54,720 --> 00:55:57,120
INTERACTION AND THEN IT'S

1379
00:55:57,120 --> 00:55:57,520
BENEFICIAL.

1380
00:55:57,520 --> 00:56:02,720
>> SO DOES THAT ACCELERATE IN

1381
00:56:02,720 --> 00:56:05,720
OUR STRAND BREAKS OR INCREASED

1382
00:56:05,720 --> 00:56:06,200
STRAND BREAKS AND

1383
00:56:06,200 --> 00:56:06,880
PROGERIATRICKIZATIONIA CELLS

1384
00:56:06,880 --> 00:56:12,120
BECAUSE IF YOU SEQUESTER CERTAIN

1385
00:56:12,120 --> 00:56:13,360
6 THEN YOU--

1386
00:56:13,360 --> 00:56:15,160
>> YES SO--

1387
00:56:15,160 --> 00:56:17,960
>> TO BE REGRESSED AND?

1388
00:56:17,960 --> 00:56:18,960
>> RIGHT AND AGAIN FROM

1389
00:56:18,960 --> 00:56:20,480
[INDISCERNIBLE] WORK SO HE

1390
00:56:20,480 --> 00:56:22,920
MEASURED THE DNA REPAIR TO USING

1391
00:56:22,920 --> 00:56:26,760
OUR ASSAYS AND THERE WAS REDUCED

1392
00:56:26,760 --> 00:56:28,680
THAT WAS [INDISCERNIBLE], YEAH.

1393
00:56:28,680 --> 00:56:32,320
>> AND ALSO REDUCE THE

1394
00:56:32,320 --> 00:56:33,560
[INDISCERNIBLE]

1395
00:56:33,560 --> 00:56:33,960
>> MM-HMMEASURE.

1396
00:56:33,960 --> 00:56:34,960
>> OKAY, THANK YOU, DAVE.

1397
00:56:34,960 --> 00:56:36,280
THANK YOU GOOD TO SEE YOU AND

1398
00:56:36,280 --> 00:56:43,320
THEN WE GO TO GAINSVILLE,

1399
00:56:43,320 --> 00:56:43,520
FLORIDA.

1400
00:56:43,520 --> 00:56:44,480
>> HI THERE.

1401
00:56:44,480 --> 00:56:46,480
>> HI, THANK YOU FOR THE TALK,

1402
00:56:46,480 --> 00:56:48,480
THIS IS MICHAEL MCINTOSH FROM

1403
00:56:48,480 --> 00:56:49,320
UNIVERSITY OF FLORIDA.

1404
00:56:49,320 --> 00:56:53,400
I HAVE 2 QUESTIONS.

1405
00:56:53,400 --> 00:56:54,840
ONE HAVE YOU-- 

1406
00:56:54,840 --> 00:56:59,000
>> JUST 1 NOW.

1407
00:56:59,000 --> 00:57:01,000
>> SO, ALL RIGHT, I WILL--ALL

1408
00:57:01,000 --> 00:57:01,920
RIGHT, SO THE FIRST QUESTION I

1409
00:57:01,920 --> 00:57:04,520
CAN THINK OF IS THE--HAVE YOU

1410
00:57:04,520 --> 00:57:06,400
LOOKED AT THE SPINY MOUSE MODEL

1411
00:57:06,400 --> 00:57:09,320
THAT SEEMED TO BE THESE REALLY

1412
00:57:09,320 --> 00:57:10,320
LONG LIVED MICE.

1413
00:57:10,320 --> 00:57:12,680
THEY LIVE LIKE 5 YEARS INSTEAD

1414
00:57:12,680 --> 00:57:13,000
OF 3.

1415
00:57:13,000 --> 00:57:15,920
>> RIGHT WE WANT TO LOOK AT THE

1416
00:57:15,920 --> 00:57:17,600
SPINY MICE, SO THEY'RE NOT PART

1417
00:57:17,600 --> 00:57:19,200
OF OUR COLLECTION YET BUT WE

1418
00:57:19,200 --> 00:57:26,520
WERE PLANNING ON GETTING THEM SO

1419
00:57:26,520 --> 00:57:28,200
COLLABORATING WITH LAB WITH

1420
00:57:28,200 --> 00:57:28,640
KENTUCKY.

1421
00:57:28,640 --> 00:57:29,960
SOY WE DON'T KNOW YET.

1422
00:57:29,960 --> 00:57:34,360
SO 5 YEARSOOSE NOT SUPER LONG

1423
00:57:34,360 --> 00:57:35,320
LIVED RIGHT?

1424
00:57:35,320 --> 00:57:38,080
NAKED ROLE RATLIFFS 30 YEARS, I

1425
00:57:38,080 --> 00:57:40,280
THINK THEY'RE GENERATED FOR THE

1426
00:57:40,280 --> 00:57:41,880
MORE THAN LONGER LIFE SPAN SO

1427
00:57:41,880 --> 00:57:43,080
THAT'S WHY, YOU KNOW WE WILL

1428
00:57:43,080 --> 00:57:45,080
NOTE THE FIRST THING AND WE WILL

1429
00:57:45,080 --> 00:57:47,320
GET, YOU KNOW WORK IN OUR ANIMAL

1430
00:57:47,320 --> 00:57:48,880
COLLECTION BUT OF COURSE WE WANT

1431
00:57:48,880 --> 00:57:49,960
TO LOOK AT IT.

1432
00:57:49,960 --> 00:57:51,560
>> OKAY, WE WILL COME BACK FOR

1433
00:57:51,560 --> 00:57:55,080
ROUND FOR ANY FOLLOW UPS.

1434
00:57:55,080 --> 00:57:57,040
SO THANK YOU GAINSVILLE.

1435
00:57:57,040 --> 00:57:58,600
>> I WILL GET MY [INDISCERNIBLE]

1436
00:57:58,600 --> 00:58:03,520
>> NOW WE GO TO NIEHS.

1437
00:58:03,520 --> 00:58:05,720
>> HI, THIS IS MATT AT NIEHS,

1438
00:58:05,720 --> 00:58:09,320
CAN YOU HEAR ME?

1439
00:58:09,320 --> 00:58:09,600
>> YES.

1440
00:58:09,600 --> 00:58:10,480
>> WONDERFUL.

1441
00:58:10,480 --> 00:58:12,600
I WANT TO EXTEND A QUESTION THAT

1442
00:58:12,600 --> 00:58:14,600
STEVEN AND BEN WERE TOUCHING ON,

1443
00:58:14,600 --> 00:58:17,320
ON THE MICE THAT HAVE AN

1444
00:58:17,320 --> 00:58:19,800
EXTENDED LIFE SPAN, DO THEY DIE

1445
00:58:19,800 --> 00:58:21,400
OF DIFFERENT PATHOLOGIES

1446
00:58:21,400 --> 00:58:23,000
COMPARED TO THE UNINFECTED

1447
00:58:23,000 --> 00:58:24,920
MYSELF TO THE WILD TYPE MICE?

1448
00:58:24,920 --> 00:58:26,600
>> WELL WE DEPARTMENT SEE

1449
00:58:26,600 --> 00:58:27,520
ANYTHING, YOU KNOW--DIDN'T SEE

1450
00:58:27,520 --> 00:58:30,120
ANYTHING YOU KNOW STRIKING BUT

1451
00:58:30,120 --> 00:58:52,680
WE HAVEN'T REALLY DONE YET AND--

1452
00:58:52,680 --> 00:58:55,120
>> CHANGED THE ABILITY OF INNATE

1453
00:58:55,120 --> 00:58:57,000
IMMUNITY BECAUSE OF THE NRTIs,

1454
00:58:57,000 --> 00:58:58,280
ALL OF THAT WOULD BE INTERESTING

1455
00:58:58,280 --> 00:59:01,320
TO SEE IF YOU HAVE THE CHANGES.

1456
00:59:01,320 --> 00:59:03,000
>> THANK YOU MATT, THANK YOU.

1457
00:59:03,000 --> 00:59:03,680
>> THANK YOU.

1458
00:59:03,680 --> 00:59:10,120
>> LET'S GO TO NCI.

1459
00:59:10,120 --> 00:59:10,640
>> THANK YOU.

1460
00:59:10,640 --> 00:59:14,520
IT'S NICE WATCHING YOU DO THIS,

1461
00:59:14,520 --> 00:59:14,720
WILL.

1462
00:59:14,720 --> 00:59:16,320
IT'S REALLY VERY WONDERFUL TALK.

1463
00:59:16,320 --> 00:59:19,280
HERE WE ARE IN THE CANCER

1464
00:59:19,280 --> 00:59:21,080
INSTITUTE, COULD YOU SAY A

1465
00:59:21,080 --> 00:59:22,920
LITTLE MORE ABOUT THE INCREASED

1466
00:59:22,920 --> 00:59:25,000
OR DECREASED CANCER

1467
00:59:25,000 --> 00:59:27,840
SUSCEPTIBILITY WITH THE MICE FOR

1468
00:59:27,840 --> 00:59:29,840
INSTANCE, THE 1S WHERE CHANGED

1469
00:59:29,840 --> 00:59:33,160
THE AMINO ACID COMPOSITION OF

1470
00:59:33,160 --> 00:59:33,920
THE SIRT6?

1471
00:59:33,920 --> 00:59:36,720
>> YEAH, WELL, SO I DON'T HAVE

1472
00:59:36,720 --> 00:59:39,240
THE DATA FOR THE S10 MICE ON

1473
00:59:39,240 --> 00:59:39,480
CANCER.

1474
00:59:39,480 --> 00:59:44,840
I THINK WE STILL ARE GOING TO

1475
00:59:44,840 --> 00:59:49,320
FINALIZE THE PATHOLOGY AND

1476
00:59:49,320 --> 00:59:51,800
CANCER ACCESS, AND WE ARE 2

1477
00:59:51,800 --> 00:59:53,200
COHORTS THAT WILL SHOW YOU

1478
00:59:53,200 --> 00:59:56,200
THEY'RE NOT VERY LARGE, BUT IT

1479
00:59:56,200 --> 00:59:57,760
SHOULD PROBABLY BE ENOUGH TO SEE

1480
00:59:57,760 --> 00:59:59,880
IF THERE IS A BIG CHANGE BUT YOU

1481
00:59:59,880 --> 01:00:02,920
KNOW I THINK THAT COULD BE VERY

1482
01:00:02,920 --> 01:00:05,560
GOOD POINT TO START IT BECAUSE

1483
01:00:05,560 --> 01:00:07,280
IF WE--YOU KNOW IT'S KIND OF--WE

1484
01:00:07,280 --> 01:00:11,560
CAN EXPECT TO HAVE MORE CANCER

1485
01:00:11,560 --> 01:00:13,680
EITHER WITH SUFFICIENT DNA

1486
01:00:13,680 --> 01:00:15,160
REPAIR OR WITH [INDISCERNIBLE]

1487
01:00:15,160 --> 01:00:17,160
BEING OVERLY ACTIVE SO I DON'T

1488
01:00:17,160 --> 01:00:19,960
EVEN HAVE A HYPOTHESIS AT THIS

1489
01:00:19,960 --> 01:00:20,920
POINT BUT--

1490
01:00:20,920 --> 01:00:22,920
>> INTERESTING TO LOOK AT

1491
01:00:22,920 --> 01:00:23,520
[INDISCERNIBLE] IS HAPPENING.

1492
01:00:23,520 --> 01:00:26,120
>> I WAS MORE THINKING OF AN

1493
01:00:26,120 --> 01:00:28,840
INDUCED CANCER WITH RADIATION

1494
01:00:28,840 --> 01:00:30,360
EXPOSURE OR SOME OTHER AGENT.

1495
01:00:30,360 --> 01:00:31,200
>> YEH, YEAH THAT,'S SOMETHING

1496
01:00:31,200 --> 01:00:33,960
WE SHOULD BE DOING IT, WE ARE

1497
01:00:33,960 --> 01:00:37,000
DOING RIGHT NOW, THAT'S AGAIN A

1498
01:00:37,000 --> 01:00:37,920
WHOLE DIFFERENT STORY.

1499
01:00:37,920 --> 01:00:40,240
WE HAVE MICE WITH NAKED MOLE RAT

1500
01:00:40,240 --> 01:00:43,120
GENES AND THERE WE'VE DONE

1501
01:00:43,120 --> 01:00:44,440
SUSCEPTIBILITY AND WE'VE DONE

1502
01:00:44,440 --> 01:00:46,120
[INDISCERNIBLE] ON THOSE MICE,

1503
01:00:46,120 --> 01:00:47,600
AND WE CAN EFFECT DIFFERENCES

1504
01:00:47,600 --> 01:00:50,560
BUT YEAH, WE SHOULD DO IT ON

1505
01:00:50,560 --> 01:00:52,120
THOSE SIRT6 MUTANTS.

1506
01:00:52,120 --> 01:00:56,720
>> OKAY, THANK YOU KEN.

1507
01:00:56,720 --> 01:00:58,880
NOW WE WILL OPEN IT UP FOR

1508
01:00:58,880 --> 01:01:00,200
ANYONE WITH A QUESTION.

1509
01:01:00,200 --> 01:01:02,720
>> IT WAS STONY BROOK, I DON'T

1510
01:01:02,720 --> 01:01:03,680
THINK--

1511
01:01:03,680 --> 01:01:04,600
>> STONY BROOK, SORRY. 

1512
01:01:04,600 --> 01:01:05,360
YOUR TURN.

1513
01:01:05,360 --> 01:01:07,920
>> YES, WE'VE BEEN WAITING

1514
01:01:07,920 --> 01:01:09,160
PATIENTLY, THANK YOU THERE WAS A

1515
01:01:09,160 --> 01:01:10,480
LOT OF INTERESTING DATA.

1516
01:01:10,480 --> 01:01:11,960
>> GOOD IT TO SEE YOU.

1517
01:01:11,960 --> 01:01:15,480
>> AND I WANTED TO ASK, GO BACK

1518
01:01:15,480 --> 01:01:17,280
TO THE BEGINNING ABOUT N. E. R.

1519
01:01:17,280 --> 01:01:19,760
SO WE USED TO HEAR A LOT ABOUT

1520
01:01:19,760 --> 01:01:21,880
SOMETHING CALLED THE RODENT

1521
01:01:21,880 --> 01:01:23,120
PARADOX WHICH THERE APPEARED TO

1522
01:01:23,120 --> 01:01:27,880
BE A LOT OF UNREPAIRED UV DAMAGE

1523
01:01:27,880 --> 01:01:30,680
LEFT IN RODENTS DNA COMPARED TO

1524
01:01:30,680 --> 01:01:32,480
HUMAN DNA AND I THINK THAT'S

1525
01:01:32,480 --> 01:01:34,160
LARGELY BEEN DESCRIBED OUT TO

1526
01:01:34,160 --> 01:01:36,360
DIFFERENCES IN ON GLOBAL GENOME

1527
01:01:36,360 --> 01:01:39,960
REPAIR AS OPPOSE TO ACTIVE GENE

1528
01:01:39,960 --> 01:01:40,880
TRANSCRIBED AND ACTIVE GENE

1529
01:01:40,880 --> 01:01:43,120
REPAIR AND IN THE ASSAY YOU'RE

1530
01:01:43,120 --> 01:01:46,360
SUING, I THINK YOU SEE ONLY

1531
01:01:46,360 --> 01:01:49,000
ACTIVE GENE REPAIR, SO AS YOU

1532
01:01:49,000 --> 01:01:50,360
EXAMINE GLOBAL GENE REPAIR, YOU

1533
01:01:50,360 --> 01:01:51,720
SEE BIGGER DIFFERENCES, SMALLER

1534
01:01:51,720 --> 01:01:55,120
DIFFERENCES ARE THE SAME THING?

1535
01:01:55,120 --> 01:01:57,600
>> WELL, WE HAVEN'T DONE THAT

1536
01:01:57,600 --> 01:02:00,720
AND YOU KNOW IT'S A GOOD POINT

1537
01:02:00,720 --> 01:02:02,200
AND PREPARE AGAIN, IT WAS

1538
01:02:02,200 --> 01:02:06,360
BASICALLY, I THINK LIMITED TO

1539
01:02:06,360 --> 01:02:07,400
CANCER CELLS.

1540
01:02:07,400 --> 01:02:14,520
>> THE SAME IN MOUSE

1541
01:02:14,520 --> 01:02:15,720
[INDISCERNIBLE]

1542
01:02:15,720 --> 01:02:20,520
>> SO THEY HAD GENE IN THE

1543
01:02:20,520 --> 01:02:21,960
KD--SALLY WAAND IS EXPRESSED AND

1544
01:02:21,960 --> 01:02:25,080
IT'S POSSIBLE THAT MANY OF THE

1545
01:02:25,080 --> 01:02:29,360
SPECIES IN OUR NOCTURNAL GROUP

1546
01:02:29,360 --> 01:02:33,400
AS IN THE PICTURES AND THEN I'M

1547
01:02:33,400 --> 01:02:35,400
PRETTY SURE THAT THE SPECIES

1548
01:02:35,400 --> 01:02:37,880
THAT THE OTHER END OF THE

1549
01:02:37,880 --> 01:02:39,040
SPECTRUM LIKE THE SQUIRRELS

1550
01:02:39,040 --> 01:02:41,680
THEY'RE JUST AS GOOD AS HUMANS,

1551
01:02:41,680 --> 01:02:45,040
SO I WOULDN'T CALL IT RODENT

1552
01:02:45,040 --> 01:02:46,680
REPAIR, SO MAYBE

1553
01:02:46,680 --> 01:02:47,040
[INDISCERNIBLE].

1554
01:02:47,040 --> 01:02:48,760
BUT,A BACK TO YOUR QUESTION, I

1555
01:02:48,760 --> 01:02:53,080
MEAN WE HAVEN'T DISSECTED IT

1556
01:02:53,080 --> 01:02:56,120
[INDISCERNIBLE] IN THE NER SO I

1557
01:02:56,120 --> 01:02:57,240
DON'T KNOW.

1558
01:02:57,240 --> 01:03:00,600
>> YOU SAID YOU DID SEE--YOU DID

1559
01:03:00,600 --> 01:03:00,840
EXAMINE?

1560
01:03:00,840 --> 01:03:03,120
>> WE ONLY USE THIS 1 SARKS A

1561
01:03:03,120 --> 01:03:05,200
THAT'S WITH THE TRANSCRIBED

1562
01:03:05,200 --> 01:03:05,560
[INDISCERNIBLE].

1563
01:03:05,560 --> 01:03:07,200
>> WHAT I'M SAYING IS YOU MIGHT

1564
01:03:07,200 --> 01:03:08,200
ACTUALLY MISS SOMETHING BY NOT

1565
01:03:08,200 --> 01:03:12,600
LOOKING AT THE REST OF IT.

1566
01:03:12,600 --> 01:03:17,320
>> SO IN THIS CASE, I WOULD SAY

1567
01:03:17,320 --> 01:03:23,120
THAT MAYBE GLOBAL REPAIR, WE

1568
01:03:23,120 --> 01:03:28,040
SHOW MORE APPRECIATION WITH LIFE

1569
01:03:28,040 --> 01:03:28,400
SPAN?

1570
01:03:28,400 --> 01:03:28,880
>> THAT'S POSSIBLE.

1571
01:03:28,880 --> 01:03:29,760
I'M NOT SURE WHAT KIND OF

1572
01:03:29,760 --> 01:03:31,200
PREDICTION TO MAKE BECAUSE I

1573
01:03:31,200 --> 01:03:33,480
WOULD THINK REPAIRING THESE

1574
01:03:33,480 --> 01:03:34,240
GENES IS [INDISCERNIBLE]

1575
01:03:34,240 --> 01:03:36,720
IMPORTANT, YOU KNOW FOR LIFE

1576
01:03:36,720 --> 01:03:37,960
SPAN, SO MAYBE--I DON'T KNOW IF

1577
01:03:37,960 --> 01:03:40,200
WE WOULD SEE ANY KIND OF

1578
01:03:40,200 --> 01:03:41,640
DIVERGENCE OF THESE PATHWAYS

1579
01:03:41,640 --> 01:03:42,680
WITH RESPECT TO [INDISCERNIBLE].

1580
01:03:42,680 --> 01:03:45,400
BUT THAT WAS INTERESTING TO

1581
01:03:45,400 --> 01:03:46,080
TEST.

1582
01:03:46,080 --> 01:03:46,320
>> OKAY.

1583
01:03:46,320 --> 01:03:48,280
THANKS A LOT EVERYONE, I THINK

1584
01:03:48,280 --> 01:03:51,280
WE HAVE TO FINISH HERE NOW

1585
01:03:51,280 --> 01:03:54,280
BECAUSE WE'RE OVER TIME.

1586
01:03:54,280 --> 01:03:55,560
THANKSFOR EVERYONE FOR THE

1587
01:03:55,560 --> 01:03:56,680
ATTENDANCE.

1588
01:03:56,680 --> 01:03:59,240
THANK YOU KEN AND THANKS TO THE

1589
01:03:59,240 --> 01:04:00,280
SPEAKER AGAIN.

1590
01:04:00,280 --> 01:04:01,240
GOODBYE FOR NOW!

1591
01:04:01,240 --> 01:04:03,240
SEE YOU NEXT MONTH.

1592
01:04:03,240 --> 01:08:21,560
[APPLAUSE ]