1 00:00:10,665 --> 00:00:13,101 >> A PIONEER IN TRANSLATIONAL 2 00:00:13,101 --> 00:00:16,404 AND CLINICAL SLEEP AND CIRCADIAN 3 00:00:16,404 --> 00:00:19,907 MEDICINE RESEARCH. 4 00:00:19,907 --> 00:00:22,210 DR. ZEE HOLDS MULTIPLE POSITIONS 5 00:00:22,210 --> 00:00:23,778 AT NORTHWESTERN'S UNIVERSITY'S 6 00:00:23,778 --> 00:00:25,680 FINEBERG'S SCHOOL OF MEDICINE. 7 00:00:25,680 --> 00:00:28,516 NOTABLY SHE CREATED AND IS 8 00:00:28,516 --> 00:00:30,485 CURRENTLY THE DIRECTOR OF THE 9 00:00:30,485 --> 00:00:31,386 CENTER FOR CIRCADIAN SLEEP 10 00:00:31,386 --> 00:00:33,454 MEDICINE AND SHE IS ALSO A 11 00:00:33,454 --> 00:00:36,758 PROFESSOR OF NEUROLOGY AND 12 00:00:36,758 --> 00:00:37,425 NEUROBIOLOGY. 13 00:00:37,425 --> 00:00:39,694 I EMBASSY IN HER SPARE TIME, YOU 14 00:00:39,694 --> 00:00:43,231 ARE ALSO DIRECTOR AND CHIEF OF 15 00:00:43,231 --> 00:00:45,433 SLEEP MEDICINE AND THE SLEEP 16 00:00:45,433 --> 00:00:50,738 DISORDERS CENTER AT NORTHWESTERN 17 00:00:50,738 --> 00:00:54,575 MEMORIAL HOSPITAL. 18 00:00:54,575 --> 00:00:58,179 DR. ZEE'S RESEARCH AND STUDIED 19 00:00:58,179 --> 00:00:59,680 HOW SLEEP CIRCADIAN RHYTHM AND 20 00:00:59,680 --> 00:01:01,883 DEVELOPMENT MEET THE EXPRESSION 21 00:01:01,883 --> 00:01:03,684 OF NEUROLOGICAL AND CARDIO 22 00:01:03,684 --> 00:01:04,452 METABOLIC DISORDERS. 23 00:01:04,452 --> 00:01:07,755 SHE ALSO DEVELOPED SLEEP AND 24 00:01:07,755 --> 00:01:09,390 CIRCADIAN BASED INTERVENTIONED, 25 00:01:09,390 --> 00:01:12,460 AIMED AT IMPROVING COGNITIVE AND 26 00:01:12,460 --> 00:01:14,529 CARDIO METRICS TAB O LOAMIC 27 00:01:14,529 --> 00:01:16,064 HEALTH POPULATIONS IN HEALTH AT 28 00:01:16,064 --> 00:01:16,497 RISK. 29 00:01:16,497 --> 00:01:17,932 TODAY'S LECTURE WILL EXPLORE 30 00:01:17,932 --> 00:01:21,502 THIS DYNAMIC INTERPLAY OF 31 00:01:21,502 --> 00:01:25,807 CIRCADIAN RHYTHMS AND SLEEP ON 32 00:01:25,807 --> 00:01:26,140 HEALTH. 33 00:01:26,140 --> 00:01:27,308 BEFORE CALLS 34 00:01:27,308 --> 00:01:28,076 DR. ZECERTAINLY--CERTAINLY TO 35 00:01:28,076 --> 00:01:29,744 THE PODIUM LET ME DO 2 36 00:01:29,744 --> 00:01:31,546 HOUSEKEEPING THINGS WHICH ARE 37 00:01:31,546 --> 00:01:31,913 VERY IMPORTANT. 38 00:01:31,913 --> 00:01:36,951 FIRST FOR IN OF YOU CME CODE FOR 39 00:01:36,951 --> 00:01:38,019 WEDNESDAY APRIL 3rd : 50119. 40 00:01:38,019 --> 00:01:41,255 OKAY, I THINK I DID THAT RIGHT 41 00:01:41,255 --> 00:01:42,924 AND SECOND FOR THOSE WHEN OF YOU 42 00:01:42,924 --> 00:01:46,227 WHO BRAVED THE ELEMENTS, THERE 43 00:01:46,227 --> 00:01:48,629 IS A SMALL RECEPTION OUTSIDE 44 00:01:48,629 --> 00:01:50,431 FOLLOWING THE LECTURE AND YOU 45 00:01:50,431 --> 00:01:52,600 GET THE DELICIOUS COOKIES THAT 46 00:01:52,600 --> 00:01:54,135 ARE MADE AVAILABLE FOR THESE 47 00:01:54,135 --> 00:01:54,469 PURPOSES. 48 00:01:54,469 --> 00:01:57,472 WITH THAT MY GREAT PLEASURE TO 49 00:01:57,472 --> 00:02:01,342 INTRODUCE DR. ZEE. 50 00:02:01,342 --> 00:02:11,552 [ APPLAUSE ] 51 00:02:13,554 --> 00:02:14,989 >> WELL, THANK YOU VERY MUCH FOR 52 00:02:14,989 --> 00:02:16,357 THIS IMMENSE HONOR AND I'M 53 00:02:16,357 --> 00:02:17,391 REALLY DELIGHTED TO BE HERE 54 00:02:17,391 --> 00:02:20,928 ALTHOUGH IT IS ON A FAIRLY RAINY 55 00:02:20,928 --> 00:02:26,434 DAY AND ALL THE PLOSES --BLOSSOE 56 00:02:26,434 --> 00:02:27,368 FALLEN ALREADY. 57 00:02:27,368 --> 00:02:29,103 I MISS THEM ALL THE TIME. 58 00:02:29,103 --> 00:02:31,038 I WANT TO ESPECIALLY THANK 59 00:02:31,038 --> 00:02:32,440 DR. NEAL SHORE FOR INVITING ME. 60 00:02:32,440 --> 00:02:35,776 I GOT A BOWFUL E-MAIL SEVERAL 61 00:02:35,776 --> 00:02:37,445 MONTHS AGO, DR. DAN CHI FOR 62 00:02:37,445 --> 00:02:42,550 HOSTING AND FOR THE AAN PH I FOR 63 00:02:42,550 --> 00:02:44,719 HOSTING ME, THE OFFICE OF 64 00:02:44,719 --> 00:02:47,021 WOMEN'S HEALTH RESEARCH AND ALSO 65 00:02:47,021 --> 00:02:49,524 HAD A LOVELY MEETING WITH THE 66 00:02:49,524 --> 00:02:50,791 WOMEN OF COLOR INTEREST GROUP 67 00:02:50,791 --> 00:02:55,463 HERE AT THE NIH, THIS MORNING. 68 00:02:55,463 --> 00:02:57,331 WHAT I THINK I'M ANYTHING TO DO 69 00:02:57,331 --> 00:03:00,034 IS GIVE YOU A LITTLE BIT OF AN 70 00:03:00,034 --> 00:03:03,971 OVERVIEW, BUT ALSO SOME SPECIFIC 71 00:03:03,971 --> 00:03:06,274 EXAMPLES OF HOW SLEEP AND 72 00:03:06,274 --> 00:03:12,680 CIRCADIAN HIGHT 73 00:03:12,680 --> 00:03:13,514 IMPEDIMENTS--IGHT HIMS ARE 74 00:03:13,514 --> 00:03:13,814 INTEGRATED. 75 00:03:13,814 --> 00:03:15,516 FIRST I HAVE A COUPLE CONFLICTS 76 00:03:15,516 --> 00:03:16,817 OF INTEREST YOU MAY WANT TO TAKE 77 00:03:16,817 --> 00:03:17,385 A LOOK AT. 78 00:03:17,385 --> 00:03:19,754 I DON'T THINK ANY OF THESE 79 00:03:19,754 --> 00:03:21,055 DIRECTLY AFFECT ANYTHING I'M 80 00:03:21,055 --> 00:03:22,590 SPEAKING ABOUT BUT AS MENTIONED 81 00:03:22,590 --> 00:03:25,359 I DO SEEM TO BE DOING A LITTLE 82 00:03:25,359 --> 00:03:26,027 TOO MUCH. 83 00:03:26,027 --> 00:03:27,962 SO HERE'S THE OUTLINE, I FIRST I 84 00:03:27,962 --> 00:03:30,932 WILL DESCRIBE VERY BRIEFLY HOW 85 00:03:30,932 --> 00:03:33,701 CIRCADIAN RHYTHMS AND SLEEP 86 00:03:33,701 --> 00:03:34,635 HOMEOSTATIC MECHANISMS ARE 87 00:03:34,635 --> 00:03:36,037 INTEGRATED AT VARIOUS LEVELS OF 88 00:03:36,037 --> 00:03:37,905 ORGANIZATION EMPLOY THEN WHAT IS 89 00:03:37,905 --> 00:03:39,540 THE MOST IMPLICATION OF THIS 90 00:03:39,540 --> 00:03:41,676 INTERACTION, NOT SO MUCH ABOUT 91 00:03:41,676 --> 00:03:43,744 OR THE OTHER BUT THEIR 92 00:03:43,744 --> 00:03:44,679 INTERACTION ON THE 2 COMMON 93 00:03:44,679 --> 00:03:46,781 DISEASES THAT WE WORK ON, SOME 94 00:03:46,781 --> 00:03:50,117 OF THE NEUROLOGICAL DECS LIKE 95 00:03:50,117 --> 00:03:51,552 NEURODEGENERATION, AND CARDIO 96 00:03:51,552 --> 00:03:53,421 METABOLIC DISORDERS. 97 00:03:53,421 --> 00:03:54,388 AND FINALLY, WHAT IS THAT 98 00:03:54,388 --> 00:03:57,858 FUTURE, WHAT IS THE PROMISE, 99 00:03:57,858 --> 00:04:00,928 POTENTIALLY HARNESSING THIS 100 00:04:00,928 --> 00:04:02,897 SYNCHRONIZED INTERPLAY, SLEEP 101 00:04:02,897 --> 00:04:05,566 AND CIRCADIAN RHYTHMS, BOTH ARE 102 00:04:05,566 --> 00:04:06,067 FUNDAMENTAL BIOLOGICAL 103 00:04:06,067 --> 00:04:07,802 PROCESSES, BOTH AT THE BRAIN 104 00:04:07,802 --> 00:04:09,370 LEVEL, BUT ALSO THROUGHOUT YOUR 105 00:04:09,370 --> 00:04:11,539 ENTIRE BODY AND MOST OF YOUR 106 00:04:11,539 --> 00:04:15,276 TISSUES AND HOW WE CAN MOVE THAT 107 00:04:15,276 --> 00:04:17,245 FORWARD IN CLINICAL RESEARCH, 108 00:04:17,245 --> 00:04:20,014 AND MEDICINE TO ENHANCE THE 109 00:04:20,014 --> 00:04:21,682 HEALTH SPAN OF COURSE, HOPEFULLY 110 00:04:21,682 --> 00:04:23,484 THE LIFE SPAN AS WELL. 111 00:04:23,484 --> 00:04:28,923 SO MY VIEW, IS THAT SLEEP AND 112 00:04:28,923 --> 00:04:30,891 CIRCADIAN RHYTHMS ARE KIND OF 113 00:04:30,891 --> 00:04:32,493 MIRROR IMAGES, THEY SHOULD NOT 114 00:04:32,493 --> 00:04:35,229 BE SPOKEN ABOUT NECESSARILY 115 00:04:35,229 --> 00:04:35,529 SEPARATELY. 116 00:04:35,529 --> 00:04:37,265 IT SHOULD BE SLEEP AND CIRCADIAN 117 00:04:37,265 --> 00:04:39,100 BECAUSE YOU WILL SEE HOW WELL 118 00:04:39,100 --> 00:04:42,136 INTEGRATED THEY ARE AND WHEN WE 119 00:04:42,136 --> 00:04:45,673 LOOK AT THE DISEASE, SOME OF THE 120 00:04:45,673 --> 00:04:47,541 CONSEQUENCES, IT USUALLY IS THE 121 00:04:47,541 --> 00:04:48,709 CONSEQUENCES OF THE INTERPLAY 122 00:04:48,709 --> 00:04:50,978 BETWEEN THESE 2 SYSTEMS, RATHER 123 00:04:50,978 --> 00:04:52,179 THAN HOW WE TEND TO THINK ABOUT 124 00:04:52,179 --> 00:04:54,515 IT WHEN WE DO OUR RESEARCH, WHEN 125 00:04:54,515 --> 00:04:57,718 WE--EVEN IN THE CLINIC THAT 126 00:04:57,718 --> 00:04:59,987 THEY'RE ACTUALLY SEPARATE AREAS. 127 00:04:59,987 --> 00:05:04,492 SO, FROM THE VERY BEGINNING OF 128 00:05:04,492 --> 00:05:06,560 THE EARTH'S ROTATION ON ITS 129 00:05:06,560 --> 00:05:10,131 AXIS, WE KNEW THAT THESE SYSTEMS 130 00:05:10,131 --> 00:05:11,098 WERE INTEGRATED. 131 00:05:11,098 --> 00:05:12,533 THERE WAS LIGHT. 132 00:05:12,533 --> 00:05:13,901 THERE WAS DAY. 133 00:05:13,901 --> 00:05:17,371 CIRCADIAN RHYTHMS HAD TO DEVELOP 134 00:05:17,371 --> 00:05:19,707 IN SOME WAY TO COORDINATE THE 135 00:05:19,707 --> 00:05:21,542 BIOLOGICAL CYCLES WITH THAT OF 136 00:05:21,542 --> 00:05:26,414 THIS REVELATION OF THE EARTH AND 137 00:05:26,414 --> 00:05:30,685 THESE PROMINENT PHYSICAL 138 00:05:30,685 --> 00:05:31,852 NIGHT-DAY CYCLES AND HENCE LATER 139 00:05:31,852 --> 00:05:34,822 ON WE DEVELOPED THESE 140 00:05:34,822 --> 00:05:37,024 REST/ACTIVITY CYCLES AND WHAT WE 141 00:05:37,024 --> 00:05:38,926 WOULD CALL AWAKE AND SLEEP IN 142 00:05:38,926 --> 00:05:39,860 ANIMALS AND HUMANS. 143 00:05:39,860 --> 00:05:42,296 AND PERHAPS THE BASIS OF THIS IS 144 00:05:42,296 --> 00:05:45,533 THE SIRCHG RONNIZATION OR 145 00:05:45,533 --> 00:05:47,068 ALIGNMENT OF BIOENERGETICS, 146 00:05:47,068 --> 00:05:48,402 METABOLIC ACTIVITY WHERE THERE'S 147 00:05:48,402 --> 00:05:50,037 A SINGLE CELL OR COMPLEX 148 00:05:50,037 --> 00:05:52,340 ORGANISM WITH THAT OF THE 149 00:05:52,340 --> 00:05:54,508 LIGHT-DARK CYCLE AND THUS IS NOT 150 00:05:54,508 --> 00:05:56,711 SURPRISING THAT OUR ACTIVITIES, 151 00:05:56,711 --> 00:06:01,415 WE ARE ACTIVE DURING THE DAY AND 152 00:06:01,415 --> 00:06:03,184 ACTIVE EXCEPT NOCT URNAL 1S AND 153 00:06:03,184 --> 00:06:05,252 WE ALSO TEND TO SLEEP WHEN 154 00:06:05,252 --> 00:06:06,754 THERE'S DARKNESS AND AS MOST OF 155 00:06:06,754 --> 00:06:09,623 YOU KNOW OUR MODERN SOCIETY'S 156 00:06:09,623 --> 00:06:11,659 HAVE CHANGED A LOT OF THAT 157 00:06:11,659 --> 00:06:14,295 BECAUSE WE CAN MANIPULATE OUR 158 00:06:14,295 --> 00:06:15,262 LIGHT-DARK CYCLES AND SO FORTH. 159 00:06:15,262 --> 00:06:18,366 SO IF YOU LOOK AT, THIS IS AN 160 00:06:18,366 --> 00:06:20,935 OLD OF COURSE, PICTURE BUT IT'S 161 00:06:20,935 --> 00:06:21,802 HOPEFULLY EXPRESSED HOW 162 00:06:21,802 --> 00:06:22,937 INTEGRATED THESE 2 SYSTEMS ARE, 163 00:06:22,937 --> 00:06:26,941 SO IF YOU LOOK AT CIRCADIAN, THE 164 00:06:26,941 --> 00:06:29,777 WORD CIRCA DIAMEANS ABOUT 24 165 00:06:29,777 --> 00:06:30,044 HOUR. 166 00:06:30,044 --> 00:06:32,213 SO WE'RE LOOKING AT THIS AND 167 00:06:32,213 --> 00:06:35,716 WE'RE SAYING, WELL ALL THIS 168 00:06:35,716 --> 00:06:36,417 PHYSIOLOGY BEHAVIOR, WHETHER 169 00:06:36,417 --> 00:06:39,053 WE'RE LOOKING AT THE RISE IN 170 00:06:39,053 --> 00:06:41,422 CORTISOL AND THAT BEGINS WHETHER 171 00:06:41,422 --> 00:06:44,291 YOU STAND UP OR GET UP IN 172 00:06:44,291 --> 00:06:47,528 PREPARATION FOR GETTING UP, 173 00:06:47,528 --> 00:06:49,263 METATONIN SECRETION STOPS, 174 00:06:49,263 --> 00:06:50,564 PROTHOM BOTTIC FACTORS, 175 00:06:50,564 --> 00:06:52,199 PLATELETS ARE MORE ACTIVE IN THE 176 00:06:52,199 --> 00:06:53,534 EARLY MORNING HOURS, PERHAPS 177 00:06:53,534 --> 00:06:55,202 THAT'S 1 OF THE REASONS, 178 00:06:55,202 --> 00:06:56,370 CERTAINLY NOT THE ONLY REASON 179 00:06:56,370 --> 00:06:58,906 WHY WE TEND TO HAVE MORE 180 00:06:58,906 --> 00:06:59,940 THROMBOTIC STROKES FOR EXAMPLE, 181 00:06:59,940 --> 00:07:03,944 DURING THAT PERIOD AS WELL AS 182 00:07:03,944 --> 00:07:06,046 OTHER TYPES OF COAGULOPATHYS. 183 00:07:06,046 --> 00:07:07,982 ALERTNESS IF YOU LOOK AT 184 00:07:07,982 --> 00:07:09,016 BEHAVIORS, THEY ALSO CHANGE 185 00:07:09,016 --> 00:07:11,318 ACROSS THE ENTIRE DAY, THEY'RE 186 00:07:11,318 --> 00:07:19,126 BETTER TIMES FOR EVERYTHING, SO 187 00:07:19,126 --> 00:07:21,095 THE--THE EXERCISE OFFICIALIAN 188 00:07:21,095 --> 00:07:22,229 ADOSSA WELLs AS PROFESSIONAL 189 00:07:22,229 --> 00:07:23,431 TEAMS, THEY'RE VERY INTERESTED 190 00:07:23,431 --> 00:07:26,200 IN THIS, SO WHEN CAN THEY GET 191 00:07:26,200 --> 00:07:27,701 THE BIGGEST ADVANTAGE BECAUSE 192 00:07:27,701 --> 00:07:29,537 THEY CAN BE VERY SMALL 193 00:07:29,537 --> 00:07:32,506 ADVANTAGES AS WELL. 194 00:07:32,506 --> 00:07:33,574 OF COURSE, THE 1 WE'RE MOST 195 00:07:33,574 --> 00:07:35,342 AWARE OF IS THAT OF OUR SLEEP 196 00:07:35,342 --> 00:07:38,279 AND WAKE CYCLE AND INDEED SLEEP 197 00:07:38,279 --> 00:07:41,382 HAS A VERY SPECIAL PLACE IN THIS 198 00:07:41,382 --> 00:07:43,117 KIND OF RHYTHMIC BEHAVIOR ACROSS 199 00:07:43,117 --> 00:07:45,453 THE ENTIRE DAY. 200 00:07:45,453 --> 00:07:47,888 SLEEP NOT ONLY IS A 201 00:07:47,888 --> 00:07:48,923 PHYSIOLOGICAL MARKER BUT WITHIN 202 00:07:48,923 --> 00:07:50,758 SLEEP WE HAVE DIFFERENT TYPES OF 203 00:07:50,758 --> 00:07:52,259 STAGES WHERE WE CALL IT STATES 204 00:07:52,259 --> 00:07:58,899 OF SLEEP WHICH WE WILL CALL 205 00:07:58,899 --> 00:08:02,002 NONREM, REM SLEEP, RAPID EYE 206 00:08:02,002 --> 00:08:03,971 MOVEMENT, AND BEHAVIORIALLY AND 207 00:08:03,971 --> 00:08:05,105 PHYSIOLOGICALLY THEY'RE ALL 208 00:08:05,105 --> 00:08:10,444 DIFFERENTITATES ALTHOUGH THEY 209 00:08:10,444 --> 00:08:12,046 ALL COALESCE WITHINIT SLEEP 210 00:08:12,046 --> 00:08:14,014 PERIOD AND AUTOQUITE DIFFERENT 211 00:08:14,014 --> 00:08:14,782 BETWEEN THESE 2 STATES. 212 00:08:14,782 --> 00:08:16,550 AND WITHIN SLEEP ITSELF WE KNOW 213 00:08:16,550 --> 00:08:18,285 THERE ARE PHYSIOLOGICAL THINGS 214 00:08:18,285 --> 00:08:18,652 THAT HAPPEN. 215 00:08:18,652 --> 00:08:20,054 BLOOD PRESSURE DIPS, THERE'S 216 00:08:20,054 --> 00:08:21,555 INCREASE IN HEARTERATE 217 00:08:21,555 --> 00:08:23,157 DURABILITY, I'LL TALK A LITTLE 218 00:08:23,157 --> 00:08:25,159 BIT ABOUT FILIC FLOW, ALL THESE 219 00:08:25,159 --> 00:08:26,994 THINGS BUT AT THE SAME TIME WE 220 00:08:26,994 --> 00:08:29,730 NOW KNOW THAT CLOCKS, THE 221 00:08:29,730 --> 00:08:31,098 CIRCADIAN RYTH HIMS ALSO 222 00:08:31,098 --> 00:08:33,100 REGULATE MANY OF THE SAME 223 00:08:33,100 --> 00:08:34,935 PARAMETERS, SO AGAIN, THESE ARE 224 00:08:34,935 --> 00:08:37,805 EPITHELIAL GREATED, THEY STARTED 225 00:08:37,805 --> 00:08:40,074 TOGETHER AND NATURALLY, AND 226 00:08:40,074 --> 00:08:41,041 THEY'RE STILL INDGREATED, SO 227 00:08:41,041 --> 00:08:43,878 JUST A LITTLE DRAWBACK TOWARD 228 00:08:43,878 --> 00:08:46,347 HISTORY OF WHY, PERHAPS UNTIL 229 00:08:46,347 --> 00:08:48,015 MAYBE THE LAST 15-20 YEARS THAT 230 00:08:48,015 --> 00:08:50,317 WE TENDED TO SEE THESE FEELS AS 231 00:08:50,317 --> 00:08:51,619 SEPARATE, SO LET'S FESTER TAKE A 232 00:08:51,619 --> 00:08:55,489 LOOK AT THE SLEEP FIELD AND WHAT 233 00:08:55,489 --> 00:08:58,893 YOU SEE HERE THIS IS JUST VERY, 234 00:08:58,893 --> 00:09:00,327 VERY SELECTED EMPLOY FIRST KIND 235 00:09:00,327 --> 00:09:02,062 OF SLEEP CYCLES, RECORDED REM 236 00:09:02,062 --> 00:09:04,498 SLEEP WHICH WAS COVERED IN THE 237 00:09:04,498 --> 00:09:06,934 1950S, REM SLEEP A BIT LATER, 238 00:09:06,934 --> 00:09:11,705 AND THEN WE HAD THE GENETIC 239 00:09:11,705 --> 00:09:14,441 EVOLUTION, REVOLUTION, OF OF 240 00:09:14,441 --> 00:09:17,044 LOOKING AT YEENS FOR NARCOLEPSY 241 00:09:17,044 --> 00:09:19,079 FOR EXAMPLE, DISCOVER MANY OF 242 00:09:19,079 --> 00:09:21,415 THESE SLEEP DISORDERS, SUCH AS 243 00:09:21,415 --> 00:09:23,717 REM BEHAVIOR DISORDER, BEING 244 00:09:23,717 --> 00:09:24,919 DRIEBED, SLEEP APNEA BEING 245 00:09:24,919 --> 00:09:26,086 DRIEBED DURING THIS WHOLE 246 00:09:26,086 --> 00:09:29,156 PERIOD, THE DORPHY IN THE 19, 247 00:09:29,156 --> 00:09:31,792 ALMOST 2000 OF THE AREXIN 248 00:09:31,792 --> 00:09:33,827 SYSTEM, ALSO THIS IS THE WAKE 249 00:09:33,827 --> 00:09:35,663 PROMOTING SYSTEM OF THE BRAIN, 250 00:09:35,663 --> 00:09:38,799 BUT ALSO THE VENTRAL LATERAL 251 00:09:38,799 --> 00:09:41,735 PREOPTIC NUCLEUS WHICH IS A 252 00:09:41,735 --> 00:09:44,705 SLEEP INDUCING PERIOD, 1999 BY 253 00:09:44,705 --> 00:09:46,073 DR. SAPERs GROUP AND THEN ONCE 254 00:09:46,073 --> 00:09:50,277 WE MOVE ON, THE FIELD AND FOCUS 255 00:09:50,277 --> 00:09:51,845 ON WHAT SLEEP LOST IT. 256 00:09:51,845 --> 00:09:54,648 IF YOU HAD SLEEP DEFICIENCY AND 257 00:09:54,648 --> 00:09:58,018 THIS DISORDER AND ASHING IMMUNE 258 00:09:58,018 --> 00:09:58,519 SYSTEM, CARDIOVASCULAR, 259 00:09:58,519 --> 00:10:00,120 COGNITION, ON AND ON, RIGHT IN 260 00:10:00,120 --> 00:10:02,323 NOW LET'S LOOK WHAT HAPPENED TO 261 00:10:02,323 --> 00:10:04,625 THE CIRCADIAN FIELD, SO AROUND 262 00:10:04,625 --> 00:10:07,161 THE SAME TIMELINE, IF YOU LOOK 263 00:10:07,161 --> 00:10:09,163 AT CIRCADIAN RHYTHMS IN HUMANS, 264 00:10:09,163 --> 00:10:12,232 IT WAS SHOWN THAT THESE CLOCKS 265 00:10:12,232 --> 00:10:13,734 ARE ENDOGENOUS, SO PUT A HUMAN 266 00:10:13,734 --> 00:10:17,438 HERE IN THE BUNKER STUDIES, IN 267 00:10:17,438 --> 00:10:19,974 GERMANY, THESE RHYTHMS WITHOUT 268 00:10:19,974 --> 00:10:22,309 ANY LIGHT-DARK CYCLES, CONTINUE 269 00:10:22,309 --> 00:10:26,180 TO TICK AT THIS NEAR 24 HOUR 270 00:10:26,180 --> 00:10:29,283 RHYTHM, HAND CIRCA RHYTHMS 271 00:10:29,283 --> 00:10:32,686 ATTRIBUTED HERE TO ASCHOFF, WE 272 00:10:32,686 --> 00:10:35,689 CAN ALSO SEE THE WORK THAT 273 00:10:35,689 --> 00:10:37,491 THEY'RE GENETICALLY REGULATED 274 00:10:37,491 --> 00:10:39,927 FROM WORK BY DROSOPHILA AND THAT 275 00:10:39,927 --> 00:10:43,330 THERE WAS A CLOCK IN THE BRAIN 276 00:10:43,330 --> 00:10:45,399 CALLED THE SUPER CHIASMATIC 277 00:10:45,399 --> 00:10:46,934 LESION IN THE. 278 00:10:46,934 --> 00:10:48,936 BECAUSE IF YOU STUDY THESE 279 00:10:48,936 --> 00:10:49,670 BEHAVIORS,A BEINGIVITY BEI 280 00:10:49,670 --> 00:10:51,505 REALLY HAS, THE REST OF THE 281 00:10:51,505 --> 00:10:53,273 OTHER BEHAVIORS WERE ABOLISHED 282 00:10:53,273 --> 00:10:54,441 AND THEN GENETICS SIMILARLY 283 00:10:54,441 --> 00:10:56,276 ACROSS THE SLEEP TIMELINE, 284 00:10:56,276 --> 00:10:58,012 CLONING OF THE PER CLOCK GENE, 285 00:10:58,012 --> 00:11:00,981 ET CETERA AND ALSO IN 286 00:11:00,981 --> 00:11:02,549 NORTHWESTERN, THE CLONING OF THE 287 00:11:02,549 --> 00:11:06,353 HOUSE GENE BY JOE TAKAASSHES HI, 288 00:11:06,353 --> 00:11:11,058 AND MARTHA AND FRED, AT THAT 289 00:11:11,058 --> 00:11:11,291 TIME. 290 00:11:11,291 --> 00:11:14,061 DISP THEN WE GO ON TO MORE 291 00:11:14,061 --> 00:11:15,162 GENETICS AND REALLY AG 292 00:11:15,162 --> 00:11:18,599 CELLERATED IN THE GENETICS AREA, 293 00:11:18,599 --> 00:11:21,669 AND WITH--REGARDS TO CIRCADIAN 294 00:11:21,669 --> 00:11:24,304 RHYTHMS AND IN 2017, THE KIND OF 295 00:11:24,304 --> 00:11:26,473 CULMINATION OF MUCH OF THIS FOR 296 00:11:26,473 --> 00:11:30,978 THE NOBEL PRIZE WAS GIVEN TO 297 00:11:30,978 --> 00:11:31,545 YEFERSON--JEFFERSON HALL 298 00:11:31,545 --> 00:11:32,846 [INDISCERNIBLE] AND MICHAEL 299 00:11:32,846 --> 00:11:37,184 YOUNG FOR THE DISCOVERY OF THE 300 00:11:37,184 --> 00:11:40,287 MOLECULAR MECHANISMS UNDERLYING 301 00:11:40,287 --> 00:11:41,689 CIRCADIAN RHYTHMS AND WHY THAT 302 00:11:41,689 --> 00:11:43,223 MIGHT BE, IS BECAUSE WE BEGIN TO 303 00:11:43,223 --> 00:11:47,728 REALIZE THAT IT HAS TREMENDOUS 304 00:11:47,728 --> 00:11:49,129 AFFECTS ACROSS ALL TISSUE YOU 305 00:11:49,129 --> 00:11:53,233 BUT ALSO PERHAPS IN DISEASE 306 00:11:53,233 --> 00:11:55,035 PREVENTION, MODIFICATION, AND 307 00:11:55,035 --> 00:11:56,837 PERHAPS EVEN A DISEASE 308 00:11:56,837 --> 00:11:57,504 DEVELOPMENT. 309 00:11:57,504 --> 00:11:59,173 SO 2 OF THE MAJOR THINGS I THINK 310 00:11:59,173 --> 00:12:00,340 WAS REALLY IMPORTANT WAS THAT WE 311 00:12:00,340 --> 00:12:01,842 THINK OF THESE AS BEING 312 00:12:01,842 --> 00:12:03,143 SEPARATELY, YOU KNOW THESE 2 313 00:12:03,143 --> 00:12:05,646 FIELDS KIND OF EVOLVE 314 00:12:05,646 --> 00:12:06,146 SEPARATELY. 315 00:12:06,146 --> 00:12:07,681 AT LEAST SCIENTIFICALLY, AND 316 00:12:07,681 --> 00:12:12,986 CERTAINLY CLINICALLY, WE'RE WAY 317 00:12:12,986 --> 00:12:13,220 BEHIND. 318 00:12:13,220 --> 00:12:18,258 BUT IN 1938, WE THINK OF 319 00:12:18,258 --> 00:12:20,894 KLEITMAN WE THINK OF HIM BEING 320 00:12:20,894 --> 00:12:22,062 THE FATHER OF SLEEP. 321 00:12:22,062 --> 00:12:25,699 AND HIS FIRST EXPERIMENTS WERE 322 00:12:25,699 --> 00:12:27,000 EXPERIMENTS IN THE MAP OGHT 323 00:12:27,000 --> 00:12:30,204 CAVES IN KENTUCKY WHICH WAS LIKE 324 00:12:30,204 --> 00:12:31,305 A BUNKY STUDIES, IN GERMANY 325 00:12:31,305 --> 00:12:33,807 WHERE HE WANTED TO LOOK AT WHAT 326 00:12:33,807 --> 00:12:36,243 WOULD HAPPEN TO SLEEP, THESE 327 00:12:36,243 --> 00:12:38,645 RHYTHMS AND METABOLIC ACTIVITY, 328 00:12:38,645 --> 00:12:39,847 DURING TIME ISOLATION, SO FROM 329 00:12:39,847 --> 00:12:41,348 THE VERY BEGINNING, YOU KNOW, 330 00:12:41,348 --> 00:12:42,549 FROM THE ROTATION OF THE EARTH 331 00:12:42,549 --> 00:12:43,951 AND REALLY EVEN FOR THE 332 00:12:43,951 --> 00:12:47,354 BEGINNING OF THIS HISTORICAL 333 00:12:47,354 --> 00:12:48,589 PERSPECTIVE, SLEEP AND RHYTHM 334 00:12:48,589 --> 00:12:50,591 WERE TOGETHER, THEY GOT A BIT 335 00:12:50,591 --> 00:12:50,858 SEPARATED. 336 00:12:50,858 --> 00:12:52,025 A COUPLE THINGS THAT HAPPENED 337 00:12:52,025 --> 00:12:54,094 HERE IN THE 1980S, IT WAS 338 00:12:54,094 --> 00:12:56,396 PROPOSED THAT SLEEP AND 339 00:12:56,396 --> 00:12:58,565 CIRCADIAN RHYTHMS AT LEAST WERE 340 00:12:58,565 --> 00:13:00,167 REGULATED IN THIS 2 PROCESS 341 00:13:00,167 --> 00:13:01,468 MODEL AND I'LL SHOW YOU A LITTLE 342 00:13:01,468 --> 00:13:02,770 BIT ABOUT THAT AND I THINK IT 343 00:13:02,770 --> 00:13:04,838 WAS A GAME CHANGER AND THEN MUCH 344 00:13:04,838 --> 00:13:07,374 LATER IN THE GENERIC ERA, 345 00:13:07,374 --> 00:13:10,778 MOLECULAR ERA, THAT WAS A CLOCK, 346 00:13:10,778 --> 00:13:12,913 A CIRCADIAN CLOCK MUTATION THAT 347 00:13:12,913 --> 00:13:15,949 SHOULD ONLY AFFECT TIMING, 348 00:13:15,949 --> 00:13:21,388 RIGHT, PRETTY MUCH, ACTUALLY 349 00:13:21,388 --> 00:13:22,589 ALSO AFFECTED SLEEP HOMEOSTASIS. 350 00:13:22,589 --> 00:13:23,791 IT WAS HARD TO IMAGINE THEA THE 351 00:13:23,791 --> 00:13:24,024 TIME. 352 00:13:24,024 --> 00:13:26,126 SO THESE WERE IN SOME WAYS GAME 353 00:13:26,126 --> 00:13:26,994 CHANGERS. 354 00:13:26,994 --> 00:13:28,529 AND THEN OF COURSE WE'RE IN THIS 355 00:13:28,529 --> 00:13:30,564 REALLY HOT PERIOD IS WHERE THE 356 00:13:30,564 --> 00:13:32,833 NIH, AND THE NATIONAL CENTER FOR 357 00:13:32,833 --> 00:13:34,334 SLEEP DISORDERS RESEARCH WAS 358 00:13:34,334 --> 00:13:37,738 MANDATED BY CONGRESS AND 359 00:13:37,738 --> 00:13:41,308 ESTABLISHED HERE AT NIH BUT 360 00:13:41,308 --> 00:13:42,042 UNDER NHLBI. 361 00:13:42,042 --> 00:13:44,344 SO WE CAN LOOK FORWARD TO THAT, 362 00:13:44,344 --> 00:13:48,015 LET'S GIVE YOU SOME EXAMPLES. 363 00:13:48,015 --> 00:13:50,951 HERE'S A PROPROCESS MODEL, 364 00:13:50,951 --> 00:13:52,686 CONCEPTUALLY THAT THERE ARE 2 365 00:13:52,686 --> 00:13:56,957 PROCESSES, 1 IS THE SLEEP 366 00:13:56,957 --> 00:13:58,225 HOMEOSTASIS, THAT'S REGULARLY 367 00:13:58,225 --> 00:13:59,960 HOMEOSTATICLY, THE MORE, THE 368 00:13:59,960 --> 00:14:01,028 MORE TIME YOU'RE AWAKE, THE 369 00:14:01,028 --> 00:14:04,331 BUILD UP OF THIS PROCESS, IT 370 00:14:04,331 --> 00:14:06,200 COULD BE AT A MOLECULAR LEVEL, 371 00:14:06,200 --> 00:14:08,468 IT COULD BE AT THAT TIME, WE DID 372 00:14:08,468 --> 00:14:11,638 NOT KNOW, ADEN O SEEN WOULD BE 1 373 00:14:11,638 --> 00:14:15,709 OF THESE POTENTIAL 374 00:14:15,709 --> 00:14:17,744 NEUROMODDULATORS THAT BUILD UP 375 00:14:17,744 --> 00:14:19,479 DRINK-WAKE, DURING SLEEP IT'S A 376 00:14:19,479 --> 00:14:21,248 MORE LINEAR PROCESS BUT WE KNOW 377 00:14:21,248 --> 00:14:22,449 THAT'S NOT EXACTLY WHAT IT LOOKS 378 00:14:22,449 --> 00:14:25,519 LIKE IN REAL LIFE AND THEN 379 00:14:25,519 --> 00:14:28,322 THEREFORE THEY PROPOSE THERE'S A 380 00:14:28,322 --> 00:14:29,022 CIRCADIAN PROCESS, C-PROCESS 381 00:14:29,022 --> 00:14:31,525 OVER HERE THAT THEN REGULATINGS 382 00:14:31,525 --> 00:14:33,760 NOT JUST THE TIMING OF SLEEP AND 383 00:14:33,760 --> 00:14:35,762 WAKE BUT ALSO THE PROPENSITY 384 00:14:35,762 --> 00:14:37,097 ACROSS THE 24 HOURS FOR SLEEP 385 00:14:37,097 --> 00:14:39,066 AND WAKE AND IT IS THE 386 00:14:39,066 --> 00:14:40,234 INTERACTION, THE INTEGRATION OF 387 00:14:40,234 --> 00:14:43,103 THESE 2 SYSTEMS, THAT THEN 388 00:14:43,103 --> 00:14:45,739 DETERMINES, HOW MUCH SLEEP, WHEN 389 00:14:45,739 --> 00:14:47,341 YOU SLEEP, AND PROBABLY HOW GO 390 00:14:47,341 --> 00:14:49,743 YOUR QUALITY OF YOUR SLEEP IS. 391 00:14:49,743 --> 00:14:52,846 SO IT WAS REALLY THIS MODEL IS 392 00:14:52,846 --> 00:14:54,348 NOT PERFECT BY ANY STRETCH OF 393 00:14:54,348 --> 00:14:55,983 THE IMAGINE, TODAY, BUT IT WAS 394 00:14:55,983 --> 00:14:59,820 REALLY A GAME CHANGER AND 395 00:14:59,820 --> 00:15:01,355 CONCEPTUALLY, 1 CAN APPLY IN 396 00:15:01,355 --> 00:15:03,190 RESEARCH AT ALL LEVELS, NEARLY 397 00:15:03,190 --> 00:15:04,191 ALL LEVELS OF INTEGRATION XI 398 00:15:04,191 --> 00:15:06,860 WILL SHOW YOU THAT FROM CELLS, 399 00:15:06,860 --> 00:15:10,697 TO REALLY TISSUES, AND 400 00:15:10,697 --> 00:15:11,999 PHYSIOLOGY AND ALSO OVER THE 401 00:15:11,999 --> 00:15:14,935 YEARS, YOU CAN ADAPT IT TO THE 402 00:15:14,935 --> 00:15:16,403 INFLUENCES OF EXTERNAL, VIERMAL 403 00:15:16,403 --> 00:15:17,738 LIKE LIGHT AND CERTAIN TYPES OF 404 00:15:17,738 --> 00:15:20,440 BEHAVIORS AND HOW THEY CAN 405 00:15:20,440 --> 00:15:21,842 MODIFY THIS SYNCHRONY BETWEEN 406 00:15:21,842 --> 00:15:23,510 THESE CIRCADIAN AND SLEEP 407 00:15:23,510 --> 00:15:23,977 PROCESSES. 408 00:15:23,977 --> 00:15:26,246 THERE'S MANY, MANY CITATIONS AND 409 00:15:26,246 --> 00:15:27,748 AS AN OLD, OLD STUDY, YOU CAN 410 00:15:27,748 --> 00:15:30,784 SEE THE NUMBER OF PUBLICATIONS, 411 00:15:30,784 --> 00:15:32,119 NUMBER OF CITED PUBLICATIONS ARE 412 00:15:32,119 --> 00:15:33,020 INCREASING BECAUSE I DO THINK 413 00:15:33,020 --> 00:15:36,056 THIS IS WHERE WE'RE BEGIN TO NOW 414 00:15:36,056 --> 00:15:37,991 RECOGNIZE, THAT THESE 2 415 00:15:37,991 --> 00:15:41,161 PROCESSES ARE VERY, VERY TIGHTLY 416 00:15:41,161 --> 00:15:42,596 INTEGRATE JUST TO GIVE YOU A BIT 417 00:15:42,596 --> 00:15:43,297 OF AN EXAMPLE. 418 00:15:43,297 --> 00:15:46,066 THIS IS A TODAY DONE BY THE 419 00:15:46,066 --> 00:15:48,001 HARVARD GROUP, CHUCK 420 00:15:48,001 --> 00:15:49,736 [INDISCERNIBLE]'S GROUP, THEY 421 00:15:49,736 --> 00:15:50,537 TOOK HUMANS, THERE'S 422 00:15:50,537 --> 00:15:52,072 30-SOMETHING DAYS IN HERE. 423 00:15:52,072 --> 00:15:53,607 THEY TOOK VERY HEALTHY HUMAN 424 00:15:53,607 --> 00:15:54,908 ANDS THEY PUT THEM UNDER THESE 425 00:15:54,908 --> 00:15:56,543 CYCLES WHERE IT WAS LONGER THAN 426 00:15:56,543 --> 00:15:58,679 24 HOURS, MUCH LONGER THIS, IS 427 00:15:58,679 --> 00:16:01,415 ALMOST 28 HOURS, SO THE 428 00:16:01,415 --> 00:16:03,583 CIRCADIAN SYSTEM WHICH HAS A 429 00:16:03,583 --> 00:16:07,955 MOLECULAR CLOCK OF ABOUT 430 00:16:07,955 --> 00:16:09,356 24-POINT WOP 7 HOURS COOPERATE 431 00:16:09,356 --> 00:16:11,258 TRAIN TO THIS SO THEY BEGIN TO 432 00:16:11,258 --> 00:16:14,494 FREE RUN, RIGHT, FROM THIS. 433 00:16:14,494 --> 00:16:16,296 AND FROM THIS TYPE CALLED FORCE 434 00:16:16,296 --> 00:16:19,700 OF SYNCHRONY, WE CAN THEN 435 00:16:19,700 --> 00:16:21,234 DISASSOCIATE THE SLEEP VERSUS 436 00:16:21,234 --> 00:16:24,104 THE CIRCADIAN PROCESSES AND WHAT 437 00:16:24,104 --> 00:16:26,807 THEY FOUND THAT WAS SLOW WAVE 438 00:16:26,807 --> 00:16:30,644 SLEEP WAS PRIMARILY UNDER THE 439 00:16:30,644 --> 00:16:32,946 S-CONTROL, THE HOMEOSTATIC 440 00:16:32,946 --> 00:16:33,447 CONTROL. 441 00:16:33,447 --> 00:16:34,481 REM SLEEP WAS HOMEOSTATIC 442 00:16:34,481 --> 00:16:36,350 CONTROL BUT MUCH MORE UNDER 443 00:16:36,350 --> 00:16:37,317 CIRCADIAN CONTROL, THE TIMING, 444 00:16:37,317 --> 00:16:39,286 THIS IS WHY WE DON'T GET REM 445 00:16:39,286 --> 00:16:42,189 SLEEP DURING THE DAY. 446 00:16:42,189 --> 00:16:43,056 ONLY NARCOLEPSY PATIENTS GET 447 00:16:43,056 --> 00:16:45,325 SLEEP DURING THE DAY, OKAY IN 448 00:16:45,325 --> 00:16:47,294 AND EVEN THOSE NOW THAT WE'RE 449 00:16:47,294 --> 00:16:49,029 RECOGNIZING A SLEEP AND SLEEP 450 00:16:49,029 --> 00:16:50,764 SPINDLES WHICH ARE VERY 451 00:16:50,764 --> 00:16:52,265 IMPORTANT FOR MEMORY 452 00:16:52,265 --> 00:16:56,536 CONSOLIDATION, THEY ARE ALSO 453 00:16:56,536 --> 00:16:58,305 CIRCADIAN AND SLEEP GATED SO YOU 454 00:16:58,305 --> 00:16:59,606 CAN SEE THE COMBINATION OF THE 455 00:16:59,606 --> 00:17:00,073 2. 456 00:17:00,073 --> 00:17:01,942 SO WHAT ABOUT CIRCADIAN RHYTHMS. 457 00:17:01,942 --> 00:17:03,910 I THOUGHT FOR THE AUDIENCE, I 458 00:17:03,910 --> 00:17:06,179 GISTLED AN INTRODUCTION OF THIS, 459 00:17:06,179 --> 00:17:10,851 THIS IS COURTESY OF JOE 460 00:17:10,851 --> 00:17:13,420 TAKAHASH, AND CIRCADIAN RHYTHMS 461 00:17:13,420 --> 00:17:14,721 ARE GENETICALLY GENERATED BUT 462 00:17:14,721 --> 00:17:16,890 THEY'RE ALSO REGULATED BY A 463 00:17:16,890 --> 00:17:23,230 SUPER CLOCK IN THE BRAIN . 464 00:17:23,230 --> 00:17:24,798 WHEN I WAS GROWING UP, THIS IS 465 00:17:24,798 --> 00:17:27,134 ALL I KNEW, IT WAS ALL ABOUT THE 466 00:17:27,134 --> 00:17:28,268 BRAIN, A SEBTERALLY GENERATED 467 00:17:28,268 --> 00:17:30,704 HIGHT IMPEDIMENTS AND ALL THESE 468 00:17:30,704 --> 00:17:32,439 OSCILLATORS WERE SLAVE 469 00:17:32,439 --> 00:17:33,573 OSCILLATORS MEANING THEY WERE 470 00:17:33,573 --> 00:17:34,441 RHYTHMIC BECAUSE OF THE BRAIN 471 00:17:34,441 --> 00:17:38,645 AREA, YOU CAN SEE THE NEURONS 472 00:17:38,645 --> 00:17:41,148 ARE RHYTHMIC, THEY HAVE NIGHT, 473 00:17:41,148 --> 00:17:43,417 THEY ARE RHYTHMIC AND HAVE NEAR 474 00:17:43,417 --> 00:17:45,252 24 HOUR FOGZ, AND WITH THAT OF 475 00:17:45,252 --> 00:17:47,020 COURSE IS THE MOLECULAR LEVEL 476 00:17:47,020 --> 00:17:48,755 AND THIS IS REALLY IMPORTANT 477 00:17:48,755 --> 00:17:49,322 DISCOVERIES. 478 00:17:49,322 --> 00:17:50,957 I THINK WHAT'S REALLY IN MY 479 00:17:50,957 --> 00:17:52,125 OPINION CHANGED SOME OF THE WAY 480 00:17:52,125 --> 00:17:53,760 WE THINK ABOUT THIS IS THAT NOW 481 00:17:53,760 --> 00:17:57,564 WE KNOW THAT THE CIRCADIAN 482 00:17:57,564 --> 00:17:59,433 RHYTHM ANDS PERHAPS EACH SLEEP, 483 00:17:59,433 --> 00:18:02,002 DEPENDING HOW YOU DEFINE SLEEP, 484 00:18:02,002 --> 00:18:03,403 AS ENERGY CYCLES, BUT NOT 485 00:18:03,403 --> 00:18:05,172 ASENTIOUS EG OF COURSE MAY EXIST 486 00:18:05,172 --> 00:18:08,175 AT THE CELLULAR MOLECULAR LEVEL 487 00:18:08,175 --> 00:18:10,277 AND ALL TISSUES AS WELL AS A 488 00:18:10,277 --> 00:18:12,312 METABOLIC SIGNAL AND ALSO THAT 489 00:18:12,312 --> 00:18:14,648 NEARLY 50% OF OUR GENOME IS 490 00:18:14,648 --> 00:18:18,251 ACTUALLY RHYTHMIC, AND THIS IS 491 00:18:18,251 --> 00:18:19,886 THE CORE CIRCADIAN MACHINERY. 492 00:18:19,886 --> 00:18:23,490 SO YOU HAVE B-MAIL--OOPS, SORRY. 493 00:18:23,490 --> 00:18:25,158 YOU HAVE B-MAIL AND CLOCK AND 494 00:18:25,158 --> 00:18:27,160 THEY DIMERIZE IN THE NUCLEUS AND 495 00:18:27,160 --> 00:18:30,397 THEY BEGIN TRANSCRIPTION AND 496 00:18:30,397 --> 00:18:31,665 TRANSLATION OF PERIOD AND CRY, 497 00:18:31,665 --> 00:18:34,968 PERIOD IS 1 OF THE GENES THAT 498 00:18:34,968 --> 00:18:37,237 WAS ACTUALLY DISCOVERED BUT ALSO 499 00:18:37,237 --> 00:18:42,275 UNDERSTOOD BY THE NOBEL TEAM. 500 00:18:42,275 --> 00:18:43,944 AND THEN THEY EXIT, THE PROTEINS 501 00:18:43,944 --> 00:18:46,513 THEY EXIT INTO THE CYTOPLASM AND 502 00:18:46,513 --> 00:18:48,782 THEY GET PHOSPHORYLATED BY THESE 503 00:18:48,782 --> 00:18:50,984 LITTLE PINK THING ANDS THEY THEN 504 00:18:50,984 --> 00:18:53,386 THEN DIMERIZE AGAIN AND THEY 505 00:18:53,386 --> 00:18:55,455 REENTRY INTO THE NUCLEUS, AND AS 506 00:18:55,455 --> 00:18:58,024 YOU WILL SEE, VERY, VERY SHORTLY 507 00:18:58,024 --> 00:19:00,427 DEPENDING HOW MUCH IS BUILD UP 508 00:19:00,427 --> 00:19:02,529 INTO THAT NUCLEUS, IT THEN SITS 509 00:19:02,529 --> 00:19:04,898 BACK ON THIS EBOX AND SHUTS ITS 510 00:19:04,898 --> 00:19:07,134 OWN PRODUCTION DOWN. 511 00:19:07,134 --> 00:19:09,202 SO IT'S R-O REGULATORY FORWARD 512 00:19:09,202 --> 00:19:10,737 NEGATIVE FEEDBACK LOOP, HOW 513 00:19:10,737 --> 00:19:13,974 QUICKLY ALL THIS OCCURS, KIND OF 514 00:19:13,974 --> 00:19:15,609 DETERMINES THAT CYCLE WHETHER 515 00:19:15,609 --> 00:19:18,211 24, 25 HOURS, 23 OR SHORTENED TO 516 00:19:18,211 --> 00:19:18,879 24 HOURS. 517 00:19:18,879 --> 00:19:22,816 NOW, AS I SAID EARLIER, ALL 518 00:19:22,816 --> 00:19:23,884 THESE CLOCKS ARE NEARLY ALL 519 00:19:23,884 --> 00:19:26,052 TISSUES OF THE BODY, WHERE 520 00:19:26,052 --> 00:19:28,588 THEY'RE LOOKING AT THE SEN OR 521 00:19:28,588 --> 00:19:30,223 WHETHER YOU'RE LOOKING HERE 522 00:19:30,223 --> 00:19:33,026 PERIPHERALLY, A LIVER OR LUNG, 523 00:19:33,026 --> 00:19:36,263 THEY ARE SUSTAINED EVEN IN 524 00:19:36,263 --> 00:19:40,033 TISSUE CULTURES, AT LEAST FOR A 525 00:19:40,033 --> 00:19:40,534 LITTLE BIT. 526 00:19:40,534 --> 00:19:43,403 BUT NOT ONLY THAT, ARE A 527 00:19:43,403 --> 00:19:44,704 RHYTHMIC IN ALL TISSUES BUT IF 528 00:19:44,704 --> 00:19:49,976 YOU LOOK AT THIS DROSOPHILA 529 00:19:49,976 --> 00:19:51,678 PICTURE HERE, EACH OF THESE DOTS 530 00:19:51,678 --> 00:19:53,313 ARE THE MODULES OF GENES THAT 531 00:19:53,313 --> 00:19:54,381 ARE BEING EXPRESSED AND IF YOU 532 00:19:54,381 --> 00:19:56,116 LOOK AT THE BEHAVIOR, THESE 533 00:19:56,116 --> 00:19:58,652 YEENS ARE BEING EXPRESSED VERY 534 00:19:58,652 --> 00:19:59,452 DIFFERENTLY, DIFFERENT TIMES OF 535 00:19:59,452 --> 00:20:00,654 THE DAY, WHETHER IT'S DURING THE 536 00:20:00,654 --> 00:20:02,722 LIGHT PHASE OR DURING THE DARK 537 00:20:02,722 --> 00:20:05,525 PHASE, SO IT'S RHYTHMIC ACROSS 538 00:20:05,525 --> 00:20:10,730 THE DAY AND NOT ALL OF THEM, ARE 539 00:20:10,730 --> 00:20:11,231 DIFFERENTIALLY RHYTHMIC 540 00:20:11,231 --> 00:20:14,568 DEPENDING ON THE SYSTEM THAT IS 541 00:20:14,568 --> 00:20:15,001 INVOLVED. 542 00:20:15,001 --> 00:20:16,703 SO I SAID EARLIER 1 OF THE GAME 543 00:20:16,703 --> 00:20:19,706 CHANGERS WAS THE DORPHY OF THE 544 00:20:19,706 --> 00:20:21,942 MAIL-IN CIRCADIAN CLOCK MUTATION 545 00:20:21,942 --> 00:20:24,644 AT NORTHWESTERN. 546 00:20:24,644 --> 00:20:25,378 DR. [INDISCERNIBLE] DISCOVERED 547 00:20:25,378 --> 00:20:26,713 THE PHENOTYPE UP THERE, THE 548 00:20:26,713 --> 00:20:27,981 WILD-TYPE WHEREAS THE MUTANT 549 00:20:27,981 --> 00:20:31,318 ACTUALLY ALMOST WAS VERY, VERY 550 00:20:31,318 --> 00:20:32,819 LONG CIRCADIAN PERIOD, SO EVERY 551 00:20:32,819 --> 00:20:34,921 DAY, IS HOPPING ON THE WHEEL, 552 00:20:34,921 --> 00:20:36,423 THIS ANIMAL LATER AND LATER 553 00:20:36,423 --> 00:20:37,657 THIS, HAS NEVER BEEN--THIS WAS 554 00:20:37,657 --> 00:20:39,226 NOT SEEN IN THE TYPICAL 555 00:20:39,226 --> 00:20:41,194 WILD-TYPE WHICH HAS A CLOCK 556 00:20:41,194 --> 00:20:43,029 FORWARD OF LITERALLY LESS THAN 557 00:20:43,029 --> 00:20:43,496 24 HOURS. 558 00:20:43,496 --> 00:20:46,600 TO MAKE A VERY LONG STORY SHORT, 559 00:20:46,600 --> 00:20:49,369 IS THAT THIS MUTATION ACTUALLY 560 00:20:49,369 --> 00:20:52,005 RESULTED IN THE SINGLE BASE PAIR 561 00:20:52,005 --> 00:20:53,740 SUBTITUTION AND THAT CREATED 562 00:20:53,740 --> 00:20:55,342 THAT MUTATION, 1 OF THE EARLY 563 00:20:55,342 --> 00:20:57,677 FIRST DISCOVERIES THAT A SINGLE, 564 00:20:57,677 --> 00:20:59,613 SIMPLE CHANGE LIKE THIS COULD 565 00:20:59,613 --> 00:21:02,148 AFFECT BEHAVIOR IN SUCH A 566 00:21:02,148 --> 00:21:02,482 DRAMATIC WAY. 567 00:21:02,482 --> 00:21:05,051 MORE, SO TO THE POINT OF THIS 568 00:21:05,051 --> 00:21:08,154 LECTURE IS THAT, THIS CLOCK, 569 00:21:08,154 --> 00:21:09,189 CIRCADIAN CLOCK MUTATION, 570 00:21:09,189 --> 00:21:10,490 REMEMBER THAT'S THE CLOCK GENE 571 00:21:10,490 --> 00:21:15,929 THAT'S IN THE NUCLEUS, THAT ALSO 572 00:21:15,929 --> 00:21:16,930 AVENGHTED SLEEP HOMEOSTASIS, 573 00:21:16,930 --> 00:21:19,032 IT'S 1 OF THE FIRST 574 00:21:19,032 --> 00:21:21,668 DEMONITRATIONS THAT IT PROMOTED 575 00:21:21,668 --> 00:21:23,136 MORE WAKEFULNESS, A LITTLE LESS 576 00:21:23,136 --> 00:21:26,573 NONREMETABOLISM SLEEP AND ALSO 577 00:21:26,573 --> 00:21:29,309 ALTERED THIS REM TO SLEEP RATIO. 578 00:21:29,309 --> 00:21:36,816 AND ALSO IN THE SAME THING THAL 579 00:21:36,816 --> 00:21:38,251 CLOCK MUTATION NOT ONLY AFFECTED 580 00:21:38,251 --> 00:21:42,589 SLEEP BUT IT AFFECTED THE BODY 581 00:21:42,589 --> 00:21:42,956 MASS. 582 00:21:42,956 --> 00:21:44,591 THESE WERE MORE OBESE, THEY WERE 583 00:21:44,591 --> 00:21:46,660 HEAVIER, SO THIS IS A 584 00:21:46,660 --> 00:21:48,361 DEMONSTRATION THAT A SINGLE CLO 585 00:21:48,361 --> 00:21:49,629 CLOCK GENE COULD AFFECT 586 00:21:49,629 --> 00:21:51,398 PHYSIOLOGY IN MANY OTHER 587 00:21:51,398 --> 00:21:51,665 BROADWAYS. 588 00:21:51,665 --> 00:21:56,970 SO THIS IS THAT INTEGRATION 589 00:21:56,970 --> 00:21:59,105 AGAIN BETWEEN SLEEP AND RHYTHM 590 00:21:59,105 --> 00:21:59,939 ANDS METABOLISM EMPLOY BUT YOU 591 00:21:59,939 --> 00:22:01,708 CAN GO THE OTHER WAY AROUND, YOU 592 00:22:01,708 --> 00:22:04,477 CAN SAY WHAT IF I SLEEP DEPRIVE 593 00:22:04,477 --> 00:22:06,579 HUMANS, SO JUMPING FROM ORGAN 594 00:22:06,579 --> 00:22:09,983 SYSTEM TO POINTS THIS IS IN 595 00:22:09,983 --> 00:22:11,284 HEALTHY HUMANS, WHAT THEY DID 596 00:22:11,284 --> 00:22:12,886 HERE, THIS IS GEORGE YOUNG'S 597 00:22:12,886 --> 00:22:14,421 GOWP, THEY SLEEP DEPRIVED 598 00:22:14,421 --> 00:22:15,689 INDIVIDUALS, THEY GAVE THEM 599 00:22:15,689 --> 00:22:17,657 EITHER, YOU KNOW THEIR 7-8 HOURS 600 00:22:17,657 --> 00:22:19,659 TIME IN BED OR RESTRICTED THEIR 601 00:22:19,659 --> 00:22:21,761 SLEEP, TO MAYBE 6 HOURS IN BED, 602 00:22:21,761 --> 00:22:23,930 AS I REMEMBER, AND SO THEY WERE 603 00:22:23,930 --> 00:22:25,365 GETTING LESS SLEEP THAN A 604 00:22:25,365 --> 00:22:26,032 NORMALLY WOULD. 605 00:22:26,032 --> 00:22:27,467 WELL, WE SAW AND AS YOU WOULD 606 00:22:27,467 --> 00:22:30,036 EXEC, THERE WERE SOME DOWN 607 00:22:30,036 --> 00:22:31,438 REGULATION AND SOME UPREGULATION 608 00:22:31,438 --> 00:22:33,340 UNDER THESE SLEEP DEPRIVED 609 00:22:33,340 --> 00:22:36,409 CONDITIONS MAINLY IN THE 610 00:22:36,409 --> 00:22:38,945 METABOLIC INFLAMMATORY IMMUNE 611 00:22:38,945 --> 00:22:39,646 CELL GENERATION PATHWAYS. 612 00:22:39,646 --> 00:22:42,182 BUT NOT ONLY DID THE SLEEP 613 00:22:42,182 --> 00:22:45,785 DEPRIVATION ALTER THE EXPRESSION 614 00:22:45,785 --> 00:22:48,455 OF THESE GENES BUT ALSO SLEEP 615 00:22:48,455 --> 00:22:51,725 DEPRIVATION ALTERED THE NUMBER 616 00:22:51,725 --> 00:22:54,661 OF GENES WITH CIRCADIAN 617 00:22:54,661 --> 00:22:55,795 ALTERATION BY HALF. 618 00:22:55,795 --> 00:22:58,631 THAT'S WHAT IT BASICALLY SHOWS 619 00:22:58,631 --> 00:23:00,834 AND SLEEP DEPRIVATION WITHOUT 620 00:23:00,834 --> 00:23:02,235 CHANGING TIMING NOW, ALSO 621 00:23:02,235 --> 00:23:04,404 CHANGED THE PHASE OF WHEN THESE 622 00:23:04,404 --> 00:23:06,339 SIR YAIDIAN GENES ARE BEING 623 00:23:06,339 --> 00:23:08,641 EXPRESSED SO THAT IT'S BIMODAL, 624 00:23:08,641 --> 00:23:10,043 YOU CAN SEE SLEEP RESTRICTION, 625 00:23:10,043 --> 00:23:11,711 NOW YEENS NOW ARE IN THE RED ARE 626 00:23:11,711 --> 00:23:13,079 EXPRESSED HERE AT THE NIGHT TIME 627 00:23:13,079 --> 00:23:17,650 AND THE WRONG TIME OF THE DAY. 628 00:23:17,650 --> 00:23:18,818 SO A BI-DIRECTIONAL LOOK, YOU 629 00:23:18,818 --> 00:23:20,954 CAN DO BOTH WAYS, YOU ULTRA 630 00:23:20,954 --> 00:23:23,490 CLOCK, YOU ULTRA SLEEP, YOU 631 00:23:23,490 --> 00:23:26,326 ULTRA SLEEP, YOU CAN ALSO ALTER 632 00:23:26,326 --> 00:23:27,394 CLOCK FUNCTION. 633 00:23:27,394 --> 00:23:29,362 SO THEY'RE INTEGRATED, THE 634 00:23:29,362 --> 00:23:31,364 PROPROCESS MODEL AS BEEN APPLIED 635 00:23:31,364 --> 00:23:33,099 BOTH AT MOLECULAR AND CELLULAR 636 00:23:33,099 --> 00:23:35,668 LEVELS, AND JUST SHOW YOU, NOT 637 00:23:35,668 --> 00:23:38,772 SO MUCH, THE DATA ON THIS, BUT 638 00:23:38,772 --> 00:23:40,373 THERE'S--THERE'S MANY NOW 639 00:23:40,373 --> 00:23:42,208 STUDIES AND BEAUTIFUL, BEAUTIFUL 640 00:23:42,208 --> 00:23:44,744 SCIENCE STUDY SHOWING THE YEENS 641 00:23:44,744 --> 00:23:46,045 IN SLEEP HOMEOSTASIS AND I WILL 642 00:23:46,045 --> 00:23:47,847 TALK A LITTLE BIT ABOUT THIS 643 00:23:47,847 --> 00:23:49,282 NEURON WHICH IS RECENT DATA FROM 644 00:23:49,282 --> 00:23:53,987 THE GROUP, AND ALSO THAT CLOCK 645 00:23:53,987 --> 00:23:56,289 CHANGE CHANGES IN PERHIVERAL 646 00:23:56,289 --> 00:23:57,557 TISSUE, ALL THESE PERIPHERAL 647 00:23:57,557 --> 00:23:59,125 CLOCKS EVERYWHERE AS WELL, 648 00:23:59,125 --> 00:24:02,328 RIGHT, CAN ALTER SLEEP, SO IT'S 649 00:24:02,328 --> 00:24:03,296 MUCH FURTHER AWAY NOW FROM THE 650 00:24:03,296 --> 00:24:05,832 BRAIN AND I WILL SHOW YOU SOME 651 00:24:05,832 --> 00:24:06,833 DATA ON THAT. 652 00:24:06,833 --> 00:24:10,603 THIS IS JUST 1 EXAMPLE FROM 653 00:24:10,603 --> 00:24:11,638 DR. SEGAL'S GROUP WHERE THEY'RE 654 00:24:11,638 --> 00:24:13,006 LOOKING AT THE SLEEP PRESSURE 655 00:24:13,006 --> 00:24:18,912 NEURONS WHICHY --WHICH WE WILL 656 00:24:18,912 --> 00:24:20,380 CALL SLEEP NEURONS. 657 00:24:20,380 --> 00:24:22,315 YOU DEPRIVE SLEEP, SEE THE SLEEP 658 00:24:22,315 --> 00:24:23,883 BUILDING UP, THE FIRING OF THE 659 00:24:23,883 --> 00:24:25,585 NEURONS BUT THEN THERE ARE 660 00:24:25,585 --> 00:24:28,154 NEURONS, ABOUT 75 ON EACH SIDE, 661 00:24:28,154 --> 00:24:29,689 CLOCK NEURONS OR CIRCADIAN 662 00:24:29,689 --> 00:24:32,992 NEURONS IN THE DNY REASON REGION 663 00:24:32,992 --> 00:24:34,928 IS WHAT THE GROUP FOUND WAS THAT 664 00:24:34,928 --> 00:24:37,297 HERE THEY ARE, THEY CALLED THEM 665 00:24:37,297 --> 00:24:40,500 HUGGING NEURONS, THESE NEURONS 666 00:24:40,500 --> 00:24:42,068 ACTUALLY RELAYED INFORMATION 667 00:24:42,068 --> 00:24:44,070 FROM THE CLOCK NEURONS, THE 668 00:24:44,070 --> 00:24:46,673 SLEEP PRESSURE NEURONS AND VICE 669 00:24:46,673 --> 00:24:47,240 VERSA. 670 00:24:47,240 --> 00:24:52,445 SO, NOW YOU CAN SEE, THAT THIS 2 671 00:24:52,445 --> 00:24:55,348 PROCESS, AND IN SOME WAYS 672 00:24:55,348 --> 00:24:57,884 INTEGRATEDDA THE CELLULAR AND 673 00:24:57,884 --> 00:25:00,620 MOLEC LA LEVEL, SO HERE'S THE 674 00:25:00,620 --> 00:25:02,055 COOL STUFF, DR. PAUL SHOWED 675 00:25:02,055 --> 00:25:04,624 SEVERAL YEARS AGO, THAT IF YOU 676 00:25:04,624 --> 00:25:07,660 KNOCK OUT B-MALL, IN THE BRAIN 677 00:25:07,660 --> 00:25:09,963 IT DOESN'T DO MUCH FOR SLEEP, 678 00:25:09,963 --> 00:25:18,438 BUT IF YOU KNOCK OUT BMAL IN THE 679 00:25:18,438 --> 00:25:22,275 SKELETAL MUSCLE, IT INCREASES 680 00:25:22,275 --> 00:25:22,642 SLEEP. 681 00:25:22,642 --> 00:25:24,210 INTERESTING, AND BDNF ON 1 OF 682 00:25:24,210 --> 00:25:26,379 THE MODULATORS HERE AND YOU SEE 683 00:25:26,379 --> 00:25:28,014 THEN WHEN HE OVEREXPRESSES THIS 684 00:25:28,014 --> 00:25:30,350 MORE RECENT WORK, I THINK IT'S 685 00:25:30,350 --> 00:25:32,552 HASN'T BEEN PUBLISHED YET, BUT 686 00:25:32,552 --> 00:25:34,754 WHEN HE OVEREXPRESSES THE BMALL, 687 00:25:34,754 --> 00:25:36,856 THE CLOGGED GENE, YOU CAN SEE 688 00:25:36,856 --> 00:25:40,226 BDNF IS HIGHER IN THE MUSCLE, 689 00:25:40,226 --> 00:25:43,663 AND HE'S SLEEP DEPRIVED OR HIS 690 00:25:43,663 --> 00:25:45,098 GROUP SLEEP DEPRIVED THESE 691 00:25:45,098 --> 00:25:46,699 ANIMALS 5 DAYS FOR CHRONIC SLEEP 692 00:25:46,699 --> 00:25:52,939 LOSS AND IN THIS OVEREXPRESSED 693 00:25:52,939 --> 00:25:53,640 SKELETAL MUSCLE, BMALL 694 00:25:53,640 --> 00:25:54,874 OVEREXPRESSION, THERE WAS NO 695 00:25:54,874 --> 00:25:55,408 SLEEP REBOUND. 696 00:25:55,408 --> 00:25:58,878 SO WHEN YOU SLEEP DEPRIVE, THE 697 00:25:58,878 --> 00:26:00,280 HOMEOSTATIC SLEEP PROCESS KICKS 698 00:26:00,280 --> 00:26:02,982 IN, RIGHT TO RECOVER IT, AND IT 699 00:26:02,982 --> 00:26:04,817 DIDN'T LOOK ANY DIFFERENT. 700 00:26:04,817 --> 00:26:06,519 SO THESE SLEEP REGULATORY 701 00:26:06,519 --> 00:26:07,554 PROCESSES ARE SOON TO BE 702 00:26:07,554 --> 00:26:09,622 EXCLUSIVE TO THE BRAIN, THAT'S 703 00:26:09,622 --> 00:26:13,359 WHAT WE THOUGHT, BUT BY THESE 704 00:26:13,359 --> 00:26:14,994 EXPERIMENTS LIKE XOKING OUT COL 705 00:26:14,994 --> 00:26:16,496 YEENS AND MUSCLE, IT AFFECTED 706 00:26:16,496 --> 00:26:20,266 THE AMOUNT OF SLEEP AND 707 00:26:20,266 --> 00:26:21,167 OVEREXPRESSION REDUCES RECOVERY 708 00:26:21,167 --> 00:26:24,370 RESPONSE TO SLEEP LOSS. 709 00:26:24,370 --> 00:26:26,773 SO, WE CAN CONCLUDE THAT MUSCLE, 710 00:26:26,773 --> 00:26:29,042 AND MAYBE OTHER PERIPHERAL 711 00:26:29,042 --> 00:26:30,810 TISSUES, CLOCKS REGULATE BRAIN 712 00:26:30,810 --> 00:26:31,377 SLEEP HOMEOSTASIS. 713 00:26:31,377 --> 00:26:33,279 NOW YOU'RE LOOKING AT THIS, AT 714 00:26:33,279 --> 00:26:34,480 THE MOLECULAR LEVEL. 715 00:26:34,480 --> 00:26:35,982 SO COMING BACK TO HUMANS AND 716 00:26:35,982 --> 00:26:39,519 COMING BACK TO THE NORMAL KIND 717 00:26:39,519 --> 00:26:40,820 OF PHYSIOLOGY LIFE, YOU CAN SEE 718 00:26:40,820 --> 00:26:42,789 THAT WHAT HAPPENS IS THAT THESE 719 00:26:42,789 --> 00:26:46,292 CLOCKS ARE RUNNING AT A NEAR 24 720 00:26:46,292 --> 00:26:47,493 HOURS, BECAUSE THEY'RE NEVER 721 00:26:47,493 --> 00:26:49,495 EXACTLY 24 HOURS, TO BE EXACTLY 722 00:26:49,495 --> 00:26:52,098 24 HOURS, YOU HAVE TO GET THEN 723 00:26:52,098 --> 00:26:54,267 GET INPUT OR TIME GIVERS, LIGHT 724 00:26:54,267 --> 00:26:55,802 IS THE STRONGEST AT THESE TIME 725 00:26:55,802 --> 00:26:58,237 GIVERS AND HERE'S THE SEN, IT'S 726 00:26:58,237 --> 00:27:00,640 NOT THAT BIG BUT HERE IT IS. 727 00:27:00,640 --> 00:27:01,441 AND IT'S RECEIVING LIGHT 728 00:27:01,441 --> 00:27:04,210 INFORMATION THROUGH THE RETINAL 729 00:27:04,210 --> 00:27:07,113 HYPOTHALAMIC TRACT AND THEN THIS 730 00:27:07,113 --> 00:27:10,750 INFORMATION GETS RELAYED TO 731 00:27:10,750 --> 00:27:11,784 OTHER BRAIN REGIONS AND ALMOST 732 00:27:11,784 --> 00:27:13,419 ALL OTHER BRAIN REGIONS AND 733 00:27:13,419 --> 00:27:14,821 TRANSMITTED TO THE PERIPHERAL 734 00:27:14,821 --> 00:27:17,457 TISSUES, IN OF IT, AT LEAST 1 735 00:27:17,457 --> 00:27:19,492 PATHWAY THROUGH THE AUTONOMIC 736 00:27:19,492 --> 00:27:19,892 NERVOUS SYSTEM. 737 00:27:19,892 --> 00:27:21,294 BUT OF COURSE WE DO KNOW NOT 738 00:27:21,294 --> 00:27:23,429 ONLY IS THAT, BUT WE KNOW THE 739 00:27:23,429 --> 00:27:26,466 MELA TONIN SECRETED BY THE 740 00:27:26,466 --> 00:27:28,635 GLAND, THAT CAN AFFECT SLEEP AND 741 00:27:28,635 --> 00:27:30,536 WAKE CYCLES, SLEEP ITSELF IS 742 00:27:30,536 --> 00:27:31,571 BI-DIRECTIONAL NOW, SLEEP ITSELF 743 00:27:31,571 --> 00:27:35,742 ALSO WHAT YOU SEAT, --EAT, I WIL 744 00:27:35,742 --> 00:27:37,543 SHOW YOU ABOUT THAT, YOUR 745 00:27:37,543 --> 00:27:38,711 MICROBIOME, I WILL NOT TALK 746 00:27:38,711 --> 00:27:40,346 ABOUT THAT BUT CLEARLY THEY ARE 747 00:27:40,346 --> 00:27:42,815 IN THE HORIZON THAT PEOPLE ARE 748 00:27:42,815 --> 00:27:43,983 LOOKING AT BUT 1 THINK THIS WE 749 00:27:43,983 --> 00:27:46,986 DO MESS UP A LOT IS WHERE EATING 750 00:27:46,986 --> 00:27:49,188 OR DOING THESE BEHAVIORS AT THE 751 00:27:49,188 --> 00:27:53,092 WRONG TIME, OUT OF SYNCH WITH 752 00:27:53,092 --> 00:27:54,227 THE MASTER CIRCADIAN CLOCK, WELL 753 00:27:54,227 --> 00:27:56,029 I CALL IT CENTRAL CLOCK, WE 754 00:27:56,029 --> 00:27:58,865 DON'T CALL IT MASTERS ANYMORE, 755 00:27:58,865 --> 00:28:00,366 CENTRAL CLOCK AND ALSO WHEN WE 756 00:28:00,366 --> 00:28:02,135 EXPOSE OURSELVES TO THE LIGHT 757 00:28:02,135 --> 00:28:03,503 DARK CYCLES, LATE AT NIGHT 758 00:28:03,503 --> 00:28:05,038 AND/OR LIVE IN THESE LARGE 759 00:28:05,038 --> 00:28:08,775 CITIES, WE ARE PROVIDING THE 760 00:28:08,775 --> 00:28:10,677 WRONG LIGHTING INFORMATION TO 761 00:28:10,677 --> 00:28:13,312 THE CLOCK AND LIGHT IS THE MOST 762 00:28:13,312 --> 00:28:21,521 POWERFUL MOST OF THESE TIME 763 00:28:21,521 --> 00:28:22,455 GIVERS FOR [INDISCERNIBLE] OF 764 00:28:22,455 --> 00:28:23,056 THE LIGHT CLOCK. 765 00:28:23,056 --> 00:28:24,757 SO IF YOU CHANGE SOCIAL WORK, 766 00:28:24,757 --> 00:28:26,693 WALL CLOCKS AND CYCLE, BEHAVIORS 767 00:28:26,693 --> 00:28:28,428 SUCH AS EATING, EXERCISE OR 768 00:28:28,428 --> 00:28:31,064 SLEEP TIMING, IT'S GOING TO 769 00:28:31,064 --> 00:28:31,998 AFFECT THE SYNCHRONIZATION 770 00:28:31,998 --> 00:28:32,932 BETWEEN THE ENVIRONMENT 771 00:28:32,932 --> 00:28:34,701 BEHAVIORS WITH YOUR INTERNAL 772 00:28:34,701 --> 00:28:36,969 BIOLOGICAL CLOCKS AND THIS OF 773 00:28:36,969 --> 00:28:40,173 COURSE AS I SAID IS IN ALL THIS. 774 00:28:40,173 --> 00:28:42,341 AND MISALIGNMENT CAN CREATE BOTH 775 00:28:42,341 --> 00:28:44,210 CIRCADIAN AND SLEEP DISRUPTION 776 00:28:44,210 --> 00:28:45,812 AND MISALIGNMENT CAN ALSO THEN 777 00:28:45,812 --> 00:28:48,614 INCLUDE NOT JUST BETWEEN THE 778 00:28:48,614 --> 00:28:51,117 INSIDE WORLD AND THE OUTSIDE 779 00:28:51,117 --> 00:28:53,186 WORLD BUT ALSO WOULD THIN THE 780 00:28:53,186 --> 00:28:55,722 INSIDE CLOCKS THEMSELVES OR 781 00:28:55,722 --> 00:28:57,523 PERIPHERAL CLOCKS THEMSELVES AND 782 00:28:57,523 --> 00:28:59,826 THAT HAS BEEN SHOWN IN MULTIPLE 783 00:28:59,826 --> 00:29:03,696 STUDIES NOW TO SHOW THAT IT HAS 784 00:29:03,696 --> 00:29:07,967 BROAD IMPLICATIONS AS RISK FOR 785 00:29:07,967 --> 00:29:09,535 NEUROLOGIC, PSYCHIATRIC, 786 00:29:09,535 --> 00:29:10,103 CARDIOVASCULAR, WHATEVER 787 00:29:10,103 --> 00:29:12,405 INSTITUTE YOU'RE IN, IT SHOULD 788 00:29:12,405 --> 00:29:13,439 AFFECT THAT, OKAY, IT SHOULD 789 00:29:13,439 --> 00:29:16,876 AFFECT THAT WE'RE DOING SOME 790 00:29:16,876 --> 00:29:18,177 WORK, MATERNAL FETAL DATA AS 791 00:29:18,177 --> 00:29:19,345 WELL, SO IT'S REALLY EVERYTHING, 792 00:29:19,345 --> 00:29:20,880 MOST THINGS THAT PEOPLE HAVE 793 00:29:20,880 --> 00:29:22,181 LOOKED AT, YOU REALLY SEE THAT, 794 00:29:22,181 --> 00:29:24,417 BUT AS A CLINICIAN, I WOULD SAY, 795 00:29:24,417 --> 00:29:26,953 IF YOU HAVE THESE DISORDERS, YOU 796 00:29:26,953 --> 00:29:29,155 CAN ALSO AFFECT THE CIRCADIAN 797 00:29:29,155 --> 00:29:31,023 SYSTEM, YOU CAN ALSO AFFECT 798 00:29:31,023 --> 00:29:33,426 SLEEP, SO IN MANY WAYS AGAIN 799 00:29:33,426 --> 00:29:34,961 IT'S BI-DIRECTIONAL OR 800 00:29:34,961 --> 00:29:36,229 MULTIDIRECTIONAL PROCESS, SO TO 801 00:29:36,229 --> 00:29:41,134 SUMMARIZE THAT WE HAVE THESE 2 802 00:29:41,134 --> 00:29:42,034 PROCESSES CONCEPTUALLY, THE 803 00:29:42,034 --> 00:29:43,770 SLEEP HOMEOSTATIC DRIVE WHICH IS 804 00:29:43,770 --> 00:29:45,071 VERY SIMPLY GETS MORE AND MORE, 805 00:29:45,071 --> 00:29:46,939 BUILDS UP AND YOU DISSIPATE 806 00:29:46,939 --> 00:29:48,908 DURING SLEEP, ALMOST ON A LINEAR 807 00:29:48,908 --> 00:29:51,010 WAY, AND THIS IS DISSIPATED 808 00:29:51,010 --> 00:29:53,880 DURING SLEEP PERIOD, AND THEN 809 00:29:53,880 --> 00:29:54,747 HERE'S A CIRCADIAN SYSTEM. 810 00:29:54,747 --> 00:29:57,383 ONE OF THE ROLES OF THE SCN IS 811 00:29:57,383 --> 00:30:00,486 TO SEND THE SIGNAL TO SECRETE 812 00:30:00,486 --> 00:30:03,322 MELATONIN FROM THE PINEALL 813 00:30:03,322 --> 00:30:03,523 GLAND. 814 00:30:03,523 --> 00:30:05,324 THE OTHER ROLE IS THAT IT 815 00:30:05,324 --> 00:30:07,226 PROTIEWSS THIS COUNTER ALERTING 816 00:30:07,226 --> 00:30:08,394 SIGNAL, THESE NEURONS WHEN 817 00:30:08,394 --> 00:30:09,962 THEY'RE FIRING DURING THE DAY, 818 00:30:09,962 --> 00:30:12,598 DURING THE LIGHT PERIOD, THEY'RE 819 00:30:12,598 --> 00:30:14,801 PROY DUCING LEARNING SIGNALS TO 820 00:30:14,801 --> 00:30:16,869 COUNTERACT THIS INCREASING DRIVE 821 00:30:16,869 --> 00:30:18,037 FOR HOMEOSTATIC SLEEP. THIS IS 822 00:30:18,037 --> 00:30:20,173 WHY WE CAN STAY AWAKE DURING THE 823 00:30:20,173 --> 00:30:22,241 DAY AND RIGHT NOW, DIPPING RIGHT 824 00:30:22,241 --> 00:30:23,776 HERE AND YOU SEE THAT, I FORGIVE 825 00:30:23,776 --> 00:30:25,411 YOU IF YOU FALL ASLEEP, EXCEPT 826 00:30:25,411 --> 00:30:29,982 FOR THOSE WHO ARE REMOTE AND YOU 827 00:30:29,982 --> 00:30:31,017 CAN SEE THAT. 828 00:30:31,017 --> 00:30:32,819 AND THEN REALLY, IT PICKS UP 829 00:30:32,819 --> 00:30:33,519 THIS ALERTING SIGNAL RIGHT 830 00:30:33,519 --> 00:30:38,558 BEFORE YOU GO TO SLEEP, MAYBE 831 00:30:38,558 --> 00:30:39,358 IMPLICATING INSOMNIA DISORDERS, 832 00:30:39,358 --> 00:30:41,661 MEL AN TONEIN GETS SECRETED, 833 00:30:41,661 --> 00:30:42,395 SIGNALS GO DOWN, PERFECT TIME 834 00:30:42,395 --> 00:30:44,463 FOR YOU TO RECOVER THE 835 00:30:44,463 --> 00:30:46,699 HOMEOSTATIC DEBT HERE AS WELL AS 836 00:30:46,699 --> 00:30:48,835 PERFECKLY ALIGNED TO GET YOUR 837 00:30:48,835 --> 00:30:49,836 7-8 HOURS OF SLEEP. 838 00:30:49,836 --> 00:30:53,539 AND OF COURSE, ALL OF THIS CAN 839 00:30:53,539 --> 00:30:55,508 CHANGE WITH AGE, THERE ARE SEX 840 00:30:55,508 --> 00:30:56,776 DIFFERENCES AND ALL THIS LIFE 841 00:30:56,776 --> 00:31:00,279 TILE DISEASE CAN ALL AFFECT THE 842 00:31:00,279 --> 00:31:04,917 INTERACTION BETWEEN THESE 2 843 00:31:04,917 --> 00:31:05,618 MAJOR PROCESSES. 844 00:31:05,618 --> 00:31:06,986 ALL RIGHT, WHAT ABOUT SLEEP 845 00:31:06,986 --> 00:31:08,154 CLOCKS AND BRAIN HEALTH AREAS 846 00:31:08,154 --> 00:31:13,025 THAT WE'VE BEEN INTERESTED IN? 847 00:31:13,025 --> 00:31:14,994 SO THERE'S REIS Z ACTIVITY, 848 00:31:14,994 --> 00:31:16,662 SMLITUDE, WITH ANY ORGANISM, 849 00:31:16,662 --> 00:31:18,664 WHETHER WE'RE LOOKING HERE AT 850 00:31:18,664 --> 00:31:21,534 THE MOUSE, YOUNG MOUSE, 851 00:31:21,534 --> 00:31:23,336 BEAUTIFUL RHYTHM, 24 HOUR 852 00:31:23,336 --> 00:31:25,404 RHYTHMS, OLD MOUSE, LITTLE 853 00:31:25,404 --> 00:31:26,672 FRAGMENTED ALREADY, IF WE LOOK 854 00:31:26,672 --> 00:31:31,244 HUMANS IN THE RUNNING WHEEL 855 00:31:31,244 --> 00:31:33,679 WHICH WE DON'T DO BUT WE DO 856 00:31:33,679 --> 00:31:36,215 HERE, WE SEE SIMILAR PATTERNS. 857 00:31:36,215 --> 00:31:38,184 YOUNG HEALTHY PERSON, STRONG 858 00:31:38,184 --> 00:31:40,119 RHYTHMS HERE, THIS IS SLEEP IN 859 00:31:40,119 --> 00:31:43,289 THE WHITE PERIOD AND THIS IS THE 860 00:31:43,289 --> 00:31:43,856 ACTIVITY LEVELS. 861 00:31:43,856 --> 00:31:45,625 MITTED AGE WE SEE ALREADY SOME 862 00:31:45,625 --> 00:31:47,593 FRAGMENTATION OF THE SLEEP HERE 863 00:31:47,593 --> 00:31:49,262 ACROSS SEVERAL DAYS, THIS IS 7 864 00:31:49,262 --> 00:31:51,764 DAYS OF RECORDING FROM THE WATCH 865 00:31:51,764 --> 00:31:54,300 AND HERE'S A--BITS OLDER ADULT 866 00:31:54,300 --> 00:31:55,601 WITH DEMENTIA, IT'S HARD TO EVEN 867 00:31:55,601 --> 00:31:59,038 SO WHERE THE RHYTHM IS AT, THAT 868 00:31:59,038 --> 00:32:00,172 SLEEP-WAKE RHYTHM AND AT AND 869 00:32:00,172 --> 00:32:02,041 INDEED THIS TYPE OF SLEEP 870 00:32:02,041 --> 00:32:02,675 FRAGMENTATION HAS BEEN SHOWN 871 00:32:02,675 --> 00:32:04,610 EARLY ON, THIS IS A CLASSICAL 872 00:32:04,610 --> 00:32:07,480 STUDY BY ADAPTED RUE LIMPs 873 00:32:07,480 --> 00:32:09,148 GROUP SHOWING THE AMOUNT OF 874 00:32:09,148 --> 00:32:11,751 FRAGMENTATION OF THE SLEEP-WAKE 875 00:32:11,751 --> 00:32:14,053 CYCLE PREDICTS INCIDENT 876 00:32:14,053 --> 00:32:16,555 ALZHEIMER'S DEDISEASE AND 877 00:32:16,555 --> 00:32:17,723 COGNITIVE DECLINES AND 6 YEARS 878 00:32:17,723 --> 00:32:19,225 LATER AND THERE'S MANY STUDIES 879 00:32:19,225 --> 00:32:20,993 SINCE THEN THAT CONSISTENTLY 880 00:32:20,993 --> 00:32:22,228 SHOW THIS PATTERN, HOWEVER, THIS 881 00:32:22,228 --> 00:32:24,363 WAS 1 OF THE FIRST 1S. 882 00:32:24,363 --> 00:32:27,099 MORE RECENT STUDY LOOKING AT A 883 00:32:27,099 --> 00:32:29,635 MORE HYPER COMMON DEGENERATION 884 00:32:29,635 --> 00:32:31,370 IN PARKINSON'S DISEASE, HERE'S A 885 00:32:31,370 --> 00:32:33,239 HEALTHIER PERSON SPECIAL HERE'S 886 00:32:33,239 --> 00:32:33,973 THOSE WITH PARKINSON'S DISEASE 887 00:32:33,973 --> 00:32:36,943 AND WHAT WE SEE IS THIS CHANGE 888 00:32:36,943 --> 00:32:39,378 IN THE AMPPLITUDE. 889 00:32:39,378 --> 00:32:41,647 LOTS MORE VARIABILITY BUT 890 00:32:41,647 --> 00:32:48,487 OVERALL LOWER AMPLITUDE AND WHEN 891 00:32:48,487 --> 00:32:51,157 LENG YING'S GROUP DID ANALYSIS, 892 00:32:51,157 --> 00:32:53,259 AND THEY SAW A DECREASE--I CAN'T 893 00:32:53,259 --> 00:32:55,828 REMEMBER HOW MANY THOUSANDS OF 894 00:32:55,828 --> 00:32:57,897 PEOPLE THIS CAME FROM, THAT THE 895 00:32:57,897 --> 00:33:00,833 AMP LIAISON FEUD CAN OTHER 896 00:33:00,833 --> 00:33:03,235 MEASURES OF CIRCADIAN ROBUSTNESS 897 00:33:03,235 --> 00:33:06,706 WERE FAVORED, THE DEVELOPMENT OF 898 00:33:06,706 --> 00:33:07,974 INCIDENT PARKINSON'S DISEASE, SO 899 00:33:07,974 --> 00:33:09,942 THERE'S SOMETHING ABOUT THAT, SO 900 00:33:09,942 --> 00:33:13,846 IT'S VERY SIMILAR, ALL THESE 901 00:33:13,846 --> 00:33:14,814 NEURODEGENERATIVE DISORDERS, AND 902 00:33:14,814 --> 00:33:17,083 HE'S AT MASS GENERAL, PART OF 903 00:33:17,083 --> 00:33:19,719 THE K23, WORK WITH ME. 904 00:33:19,719 --> 00:33:21,487 AND AGAIN, IN PARKINSON'S DEC, 905 00:33:21,487 --> 00:33:23,122 YOU SEE ALREADY, THIS 906 00:33:23,122 --> 00:33:24,590 FRAGMENTATION BUT HE DREW BLOOD 907 00:33:24,590 --> 00:33:25,658 FROM THESE INDIVIDUALS EVERY 908 00:33:25,658 --> 00:33:27,159 HOUR OR EVERY 2 HOURS, BRING 909 00:33:27,159 --> 00:33:30,596 THEM INTO THE CLINICAL RESEARCH 910 00:33:30,596 --> 00:33:32,898 UNIT FOR MELATONIN AND YOU CAN 911 00:33:32,898 --> 00:33:34,600 SEE THE PARKINSON PATIENT WAS 912 00:33:34,600 --> 00:33:36,802 NOT ONLY ACTIVITY BEHAVIOR, LOW 913 00:33:36,802 --> 00:33:38,904 AMPLITUDE BUT ALSO THEIR 914 00:33:38,904 --> 00:33:40,272 MELATONIN RHYTHM AND IN 915 00:33:40,272 --> 00:33:41,741 PARTICULAR WITH THOSE 916 00:33:41,741 --> 00:33:43,609 INDIVIDUALS WERE THE SLEEPIEST 917 00:33:43,609 --> 00:33:45,845 OF THE PARKINSON'S PATIENTS, AT 918 00:33:45,845 --> 00:33:49,682 THE LOWEST SUGGUESTING THAT 919 00:33:49,682 --> 00:33:52,218 MAYBE THE LACK OF ALERTNESS IN 920 00:33:52,218 --> 00:33:55,321 THE INDIVIDUALS MAY BE A 921 00:33:55,321 --> 00:33:56,555 CIRCADIAN, PARTIALLY A CIRCADIAN 922 00:33:56,555 --> 00:33:56,922 PROCESS. 923 00:33:56,922 --> 00:33:58,724 THIS IS A REVIEW WHICH IS A 924 00:33:58,724 --> 00:34:03,362 REALLY NICE REVIEW FROM USEC, 925 00:34:03,362 --> 00:34:05,865 AND [INDISCERNIBLE] AND 926 00:34:05,865 --> 00:34:06,332 [INDISCERNIBLE] GROUP. 927 00:34:06,332 --> 00:34:07,600 HOW TO INTEGRATE CLOCKS AND 928 00:34:07,600 --> 00:34:08,801 SLEEP, RIGHT? 929 00:34:08,801 --> 00:34:10,369 THEY'RE BI-DIRECTIONAL AS I 930 00:34:10,369 --> 00:34:12,238 SHOWED YOU ALREADY, THIS IS SEN 931 00:34:12,238 --> 00:34:13,639 AFFECTS SLEEP AND OF COURSE THE 932 00:34:13,639 --> 00:34:16,342 CLOCKS AND ALSO THESE PERIPHERAL 933 00:34:16,342 --> 00:34:19,512 METABOLIC AND/OR INFLAMMATORY, 934 00:34:19,512 --> 00:34:21,347 ET CETERA, TISSUES WHICH THEN 935 00:34:21,347 --> 00:34:23,916 CAN AFFECT THE PERIPHERAL, 936 00:34:23,916 --> 00:34:24,650 METABOLISM, HOME VASCULAR 937 00:34:24,650 --> 00:34:27,353 REGULATION AND ALSO AT THIS 938 00:34:27,353 --> 00:34:28,421 LEVEL, BRAIN HOMEOSTASIS FROM 939 00:34:28,421 --> 00:34:31,690 ALL THESE DIFFERENT ANGLES. 940 00:34:31,690 --> 00:34:34,193 SO I'M SURE ALL OF YOU HAVE 941 00:34:34,193 --> 00:34:36,429 HEARD ABOUT THE LYMPHATIC 942 00:34:36,429 --> 00:34:37,063 SYSTEM, RIGHT? 943 00:34:37,063 --> 00:34:38,697 ABOUT HOW THE BRAIN DOESN'T HAVE 944 00:34:38,697 --> 00:34:40,800 A GREAT LYMPHATIC SYSTEM AND 945 00:34:40,800 --> 00:34:43,669 THESE TOXIC MOLECULES OR 946 00:34:43,669 --> 00:34:46,639 PROTEINS GET FLUSHED OUT LIKE 947 00:34:46,639 --> 00:34:48,774 ABETTA AMYLOID OR TAU THROUGH 948 00:34:48,774 --> 00:34:50,342 THE LYMPHATIC PROCESS. 949 00:34:50,342 --> 00:34:52,078 WELL DURING SLEEP, CLASSIC 950 00:34:52,078 --> 00:34:54,380 STUDIES SCIENCE, DURING SLEEP, 951 00:34:54,380 --> 00:34:58,317 THERE WAS HIGHER FLOW RIGHT 952 00:34:58,317 --> 00:35:00,820 THROUGH THE INTERSTITIAL FLUID 953 00:35:00,820 --> 00:35:02,822 AND WHEN YOU'RE AWAKE, THERE WAS 954 00:35:02,822 --> 00:35:06,158 NOT, SO IT APPEARS TO BE 1 OF 955 00:35:06,158 --> 00:35:07,793 THE METHODS, THIS BRAIN 956 00:35:07,793 --> 00:35:09,061 ORGANIZED FLOW AND DYNAMICS WAS 957 00:35:09,061 --> 00:35:11,197 1 OF THE WAYS TO FLUSH OUT THIS 958 00:35:11,197 --> 00:35:12,965 MATERIAL, THIS IS THE--THIS IS 959 00:35:12,965 --> 00:35:17,803 THE MRI HERE IS FROM LAURA 960 00:35:17,803 --> 00:35:19,238 LEWIS' GROUP AND THEY SHOWED 961 00:35:19,238 --> 00:35:23,776 WITH THE EEG, THEY WERE ABLE TO 962 00:35:23,776 --> 00:35:26,745 SEE THIS FLUID FLUXES THAT EACH 963 00:35:26,745 --> 00:35:31,150 OF THESE, MANY OF THOSE WERE 964 00:35:31,150 --> 00:35:33,085 PROCEEDED BY SLEEP AND IN 965 00:35:33,085 --> 00:35:34,753 PARTICULAR THIS DEEP SLEEP WHICH 966 00:35:34,753 --> 00:35:36,555 IS ABOUT 1 HERTZ--LESS THAN HALF 967 00:35:36,555 --> 00:35:39,658 TO MAYBE 2 OR 3-HERTZ PER 968 00:35:39,658 --> 00:35:41,293 SECOND, SO IT WAS SAWL SLEEP 969 00:35:41,293 --> 00:35:43,395 REGULATED AND THAT'S WHAT WE ALL 970 00:35:43,395 --> 00:35:43,629 THOUGHT. 971 00:35:43,629 --> 00:35:45,364 WELL, THIS IS A REVIEW ARTICLE, 972 00:35:45,364 --> 00:35:46,432 BECAUSE I'M NOT GOING TO GO 973 00:35:46,432 --> 00:35:48,534 THROUGH ALL THE DATA. 974 00:35:48,534 --> 00:35:49,568 THERE'S REALLY BUILDING DATA 975 00:35:49,568 --> 00:35:51,003 BOTH FROM AN ASTRO SIGHT LEVEL 976 00:35:51,003 --> 00:35:54,373 OR NOT, BUT THAT THE BLOOD BRAIN 977 00:35:54,373 --> 00:35:55,541 BARRIER IS CIRCADIAN CLOCK 978 00:35:55,541 --> 00:35:57,309 REGULATED AS WELL BECAUSE 979 00:35:57,309 --> 00:36:00,913 THERE'S DIFFERENT WAYS YOU CAN 980 00:36:00,913 --> 00:36:02,448 KNOCK OUT CLOCK GENES AND SO 981 00:36:02,448 --> 00:36:03,849 FORTH AND YOU BEGIN TO SEE A 982 00:36:03,849 --> 00:36:05,484 BREAK DOWN OF THE BLOOD BRAIN 983 00:36:05,484 --> 00:36:08,454 BARRIER AS WELL AND THAT ITSELF 984 00:36:08,454 --> 00:36:09,155 COULD BE PROMISE. 985 00:36:09,155 --> 00:36:11,524 AGAIN IT'S NOT JUST ABOUT SLEEP 986 00:36:11,524 --> 00:36:13,926 BUT ALSO THEY HAVE TO BE 987 00:36:13,926 --> 00:36:15,161 INTERNATIONAL CLASSIFICATION 988 00:36:15,161 --> 00:36:15,394 GRADED. 989 00:36:15,394 --> 00:36:16,095 [INDISCERNIBLE] BROWN SAID TO 990 00:36:16,095 --> 00:36:17,763 ME, I'M A NEUROLOGIST, TELL ME 991 00:36:17,763 --> 00:36:19,732 HOW DOES THIS REALLY WORK, HE 992 00:36:19,732 --> 00:36:23,068 SAYS, WELL, CLOCKS ARE LIKE, HE 993 00:36:23,068 --> 00:36:27,006 SAYS, IT TELLS YOU WHEN TO MAKE 994 00:36:27,006 --> 00:36:28,674 SOMETHING, LET'S SAY THESE 995 00:36:28,674 --> 00:36:32,211 MOLECULES OR THESE PROTEINS, 996 00:36:32,211 --> 00:36:33,279 SLEEP TELLS YOU HOW MUCH. 997 00:36:33,279 --> 00:36:37,883 SO WE CAN TURNOVERLY ENHANCE 998 00:36:37,883 --> 00:36:38,884 RYTH--CERTAINLY ENHANCE RHYTHMS 999 00:36:38,884 --> 00:36:40,085 WITH ALL THE THINGS, I'M TRYING 1000 00:36:40,085 --> 00:36:41,854 TO SEE THE CLOCK, IT SAYS 2 1001 00:36:41,854 --> 00:36:47,560 MINUTES DOES IT MEAN I ONLY HAVE 1002 00:36:47,560 --> 00:36:49,562 2 MORE MINUTES? 1003 00:36:49,562 --> 00:36:50,229 >> [INDISCERNIBLE]. 1004 00:36:50,229 --> 00:36:50,529 >> GREAT. 1005 00:36:50,529 --> 00:36:51,931 ENHANCING SLEEP SO I THINK WE 1006 00:36:51,931 --> 00:36:55,134 HAVE NOW THE POTENTIAL WITH THIS 1007 00:36:55,134 --> 00:36:58,170 TYPE OF UNDERSTANDING TO USE 1008 00:36:58,170 --> 00:36:59,338 CIRCADIAN SLEEP-BASED PRINCIPLES 1009 00:36:59,338 --> 00:37:00,506 TO PERHAPS ENLANCE SLEEP. 1010 00:37:00,506 --> 00:37:02,975 NOW LET'S TALK ABOUT ANOTHER 1011 00:37:02,975 --> 00:37:06,712 AREA THAT I'VE BEEN ACTUALLY 1012 00:37:06,712 --> 00:37:08,948 WORKING ON OR OUR GROUP AND 1013 00:37:08,948 --> 00:37:10,683 OTHERS, IS ABOUT CIRCADIAN 1014 00:37:10,683 --> 00:37:13,319 INTEGRATION FEETING AND 1015 00:37:13,319 --> 00:37:14,320 METABOLISM. 1016 00:37:14,320 --> 00:37:24,797 WE KNOW THAT--YEAH, IT'S MY 1017 00:37:34,106 --> 00:37:34,673 PHONE. 1018 00:37:34,673 --> 00:37:35,007 SORRY. 1019 00:37:35,007 --> 00:37:36,909 SO ANOTHER AREA WOULD BE HOW IT 1020 00:37:36,909 --> 00:37:38,210 AFFECTS METABOLISM WHERE WE TOLD 1021 00:37:38,210 --> 00:37:43,048 YOU THAT EVEN A CIRCADIAN CLOCK 1022 00:37:43,048 --> 00:37:44,883 MUTATION CAN RESULT IN WEIGHT 1023 00:37:44,883 --> 00:37:49,488 GAIN OR OBESITY IN THE CLOCK 1024 00:37:49,488 --> 00:37:50,089 VIEWED MOUSE. 1025 00:37:50,089 --> 00:37:52,725 SO WE HAVE LIGHT, BRAIN, SCN, 1026 00:37:52,725 --> 00:37:54,226 THE SAME THING WE TALKED ABOUT 1027 00:37:54,226 --> 00:37:57,096 AT THE CLOCK OSULAR LEVEL AND 1028 00:37:57,096 --> 00:37:59,365 REMEMBER ALL THESE PERIPHERAL 1029 00:37:59,365 --> 00:38:00,532 TISSUES, MUSCLE, LIVER, THEY ALL 1030 00:38:00,532 --> 00:38:01,934 HAVE THE SAME MOLECULAR 1031 00:38:01,934 --> 00:38:04,436 MACHINERY OF THE CLOCK. 1032 00:38:04,436 --> 00:38:06,505 AND THEN WE HAVE FOOD, AND 1033 00:38:06,505 --> 00:38:09,942 LIGHT, SOMETIMES THEY'RE NOT 1034 00:38:09,942 --> 00:38:10,976 SYNCHRONIZED WITH EACH OTHER. 1035 00:38:10,976 --> 00:38:12,845 WE'RE EATING AT THE WRONG TIME 1036 00:38:12,845 --> 00:38:14,446 AND THAT'S VERY LIKELY NOT TO 1037 00:38:14,446 --> 00:38:17,416 OHM AFFECT THE OUTPUTS OF THE 1038 00:38:17,416 --> 00:38:20,185 CLOCK BUT ALSO REALLY THE STATE 1039 00:38:20,185 --> 00:38:22,454 OF WHICH THE TISSUES ARE GOING 1040 00:38:22,454 --> 00:38:31,163 TO BE ABLE TO BE MORE RESISTANT, 1041 00:38:31,163 --> 00:38:31,764 METABOLICALLY MORE CHALLENGED, 1042 00:38:31,764 --> 00:38:33,532 SO OOPS I DON'T KNOW WHERE THAT 1043 00:38:33,532 --> 00:38:44,043 MEANT, SO HERE'S 1 OF THE HERE'S 1044 00:38:44,043 --> 00:38:47,546 ANOTHER STUDY WHERE BY THIS IS A 1045 00:38:47,546 --> 00:38:50,049 STUDY BY FRANK SHEER, A CLASSIC 1046 00:38:50,049 --> 00:38:51,784 EARLY STUDY WE TOOK HEALTHY 1047 00:38:51,784 --> 00:38:53,319 HUMAN ANDS YOUNG RELATIVELY 1048 00:38:53,319 --> 00:38:57,189 HEALTHY AND YOUNG AND HE CALLED 1049 00:38:57,189 --> 00:38:57,790 CIRCADIAN MISALIGNMENT YOU 1050 00:38:57,790 --> 00:38:59,325 SHOULD THE PROTOCOL I TALKED TO 1051 00:38:59,325 --> 00:39:01,727 YOU WHERE YOU CAN PUT PEOPLE IN 1052 00:39:01,727 --> 00:39:02,995 THESE FORCED SIRCHG RONNIE 1053 00:39:02,995 --> 00:39:09,234 PROTOCOLS AND TRY TO,A LIEN OR 1054 00:39:09,234 --> 00:39:10,636 MISALIGN THEIR RHYTHM WITH SLEEP 1055 00:39:10,636 --> 00:39:10,936 AND AWAKE. 1056 00:39:10,936 --> 00:39:12,438 SO IF YOU LOOK AT THE GREEN, 1057 00:39:12,438 --> 00:39:14,873 THIS IS L LINE, YOU CAN SEE THE 1058 00:39:14,873 --> 00:39:19,611 TOP LEVELS, LEPTIN LEVELS UNDER 1059 00:39:19,611 --> 00:39:21,013 CIRCADIAN MISALIGNMENT WAS LOWER 1060 00:39:21,013 --> 00:39:22,614 WHICH MEANS THESE INDIVIDUALS 1061 00:39:22,614 --> 00:39:33,158 WERE LIKELY TO BE HUNGRIER, IT'S 1062 00:39:34,326 --> 00:39:38,097 A SATIETY PROBLEM. 1063 00:39:38,097 --> 00:39:40,165 LOOK AT THE CORTISOL, IT'S 1064 00:39:40,165 --> 00:39:43,068 ALMOST FLIPPED OVER. 1065 00:39:43,068 --> 00:39:45,137 SO CIRCADIAN RHYTHMS WERE 1066 00:39:45,137 --> 00:39:47,306 CONNECKED TO APPETITE AND 1067 00:39:47,306 --> 00:39:49,508 HORMONE AND TBLUICOSE METABOLISM 1068 00:39:49,508 --> 00:39:50,876 DISREGULATION, AND LATER SLEEP 1069 00:39:50,876 --> 00:39:52,878 TIMING ARE RELATED TO POOR 1070 00:39:52,878 --> 00:39:54,646 DIETARY HABIT ANDS BMI, SO 1071 00:39:54,646 --> 00:39:55,914 THERE'S A WHOLE HOST OF STUDIES 1072 00:39:55,914 --> 00:39:57,983 THAT SHOW THE LATE TIME EATING 1073 00:39:57,983 --> 00:40:01,620 RELATIVE TO THAT TIME, MAYBE A 1074 00:40:01,620 --> 00:40:03,021 STATE OF MISALIGNMENT AND THAT 1075 00:40:03,021 --> 00:40:05,257 INCREASE OF RISK BOTH FROM 1076 00:40:05,257 --> 00:40:07,493 EPIDEMIOLOGIC STUDIESAs WELL 1077 00:40:07,493 --> 00:40:10,195 AS VERY CONTROLLED EXPERIMENTAL 1078 00:40:10,195 --> 00:40:14,933 STUDIES OF RISK FOR METABOLIC 1079 00:40:14,933 --> 00:40:15,234 DYSFUNCTION. 1080 00:40:15,234 --> 00:40:17,469 THIS IS A FIELD STUDY WHERE 1081 00:40:17,469 --> 00:40:24,176 CHRIS AND CANNED 1082 00:40:24,176 --> 00:40:24,877 CANNED--[INDISCERNIBLE] AT 1083 00:40:24,877 --> 00:40:29,181 NORTHWESTERN SHE JUST LOOKED AT 1084 00:40:29,181 --> 00:40:31,683 A MEAL CATEGORY WHERE PEOPLE 1085 00:40:31,683 --> 00:40:34,253 CONSUME 25, 50, AND 75% OF THE 1086 00:40:34,253 --> 00:40:35,354 TOTAL CALORIE INTAKE FOR THE 1087 00:40:35,354 --> 00:40:35,587 DAY. 1088 00:40:35,587 --> 00:40:39,057 AND LOOKING AT THE MATSUDA 1089 00:40:39,057 --> 00:40:42,361 INDEX, YOU CAN SEE CLEARLY, 1090 00:40:42,361 --> 00:40:45,164 EARLIER THEY CONSUMED THEIR 1091 00:40:45,164 --> 00:40:47,933 CALORIES OR 50%, THEY HAD BETTER 1092 00:40:47,933 --> 00:40:49,435 INDID YOU LYNN SENSITIVITY AND 1093 00:40:49,435 --> 00:40:50,636 THIS WAS THE CASE WHERE YOU LOOK 1094 00:40:50,636 --> 00:40:52,371 AT A PROPORTION OF THE ENERGY 1095 00:40:52,371 --> 00:40:54,306 INTAKE IN THE MORNING AS WELL AS 1096 00:40:54,306 --> 00:40:57,209 LATE IN THE EVENTING AS WELL. 1097 00:40:57,209 --> 00:40:58,977 SO THE EARLIER YOU STARTED 1098 00:40:58,977 --> 00:41:01,180 EATING AND THE MOST OF YOUR 1099 00:41:01,180 --> 00:41:02,581 FOOD, THE BETTER INSULIN 1100 00:41:02,581 --> 00:41:04,183 RESISTANCE BUT IT DOESN'T TELL 1101 00:41:04,183 --> 00:41:07,186 US MUCH ABOUT WHY OR HOW, SO 1102 00:41:07,186 --> 00:41:08,487 IT'S NOT REALLY HOW MUCH WE EAT 1103 00:41:08,487 --> 00:41:09,788 OR SLEEP BUT I THINK THE MESSAGE 1104 00:41:09,788 --> 00:41:12,558 IS IT HAS TO BE COMBINED AND 1105 00:41:12,558 --> 00:41:14,293 INTEGRATED WITH WHEN YOU SLEEP, 1106 00:41:14,293 --> 00:41:18,564 AND EAT AND OF COURSE GET LIGHT. 1107 00:41:18,564 --> 00:41:20,098 THESE ARE OUR LIGHT HILLS ACROSS 1108 00:41:20,098 --> 00:41:21,366 THE UNITED STATES, YOU CAN SEE 1109 00:41:21,366 --> 00:41:23,235 WHERE YOU MAY BE LIVING, I CAN'T 1110 00:41:23,235 --> 00:41:25,537 SEE BUT LOOK AT ALL THESE, THIS 1111 00:41:25,537 --> 00:41:27,439 IS AT NIGHT, RIGHT? 1112 00:41:27,439 --> 00:41:29,908 THIS IS--THERE'S NO REAL GOOD 1113 00:41:29,908 --> 00:41:31,777 NIGHT, DARKNESS ON EARTH. 1114 00:41:31,777 --> 00:41:36,148 IF YOU'RE STAYING UP LATE, YOU 1115 00:41:36,148 --> 00:41:37,716 GOT LIGHT LATE, YOU ARE ALSO 1116 00:41:37,716 --> 00:41:39,485 EATING LATE, SO ALL THESE 1117 00:41:39,485 --> 00:41:40,486 BEHAVIORS ARE MOVING TOGETHER, 1118 00:41:40,486 --> 00:41:42,054 JUST A LITTLE BIT ABOUT LIGHT. 1119 00:41:42,054 --> 00:41:49,695 THIS IS A STUDY DONE BY 1120 00:41:49,695 --> 00:41:51,430 [INDISCERNIBLE] LOOKING AT 1121 00:41:51,430 --> 00:41:53,499 HEALTHY ADULTS IN CHICAGO WITH A 1122 00:41:53,499 --> 00:41:55,767 STUDY FUNDING BY THE NIH. 1123 00:41:55,767 --> 00:41:57,302 AND IF LOOK AT ANY LIGHT, ANY 1124 00:41:57,302 --> 00:41:59,505 LIGHT AT ALL WAS ASSOCIATE WIDE 1125 00:41:59,505 --> 00:42:01,807 INCREASED RISK FOR OBESITY, 1126 00:42:01,807 --> 00:42:04,243 CHANGE IN BIN, I OF MORE THAN 1127 00:42:04,243 --> 00:42:05,644 10%, DIABETES, AS WELL AS 1128 00:42:05,644 --> 00:42:06,745 HYPERTENSION, I'M NOT SAYING THE 1129 00:42:06,745 --> 00:42:08,814 LIGHT IS DOING THAT, BUT LIGHT 1130 00:42:08,814 --> 00:42:11,116 MAY BE CAUSING THIS MISALIGNMENT 1131 00:42:11,116 --> 00:42:13,051 BECAUSE THOSE PEOPLE MAY BE 1132 00:42:13,051 --> 00:42:13,685 EATING LATER. 1133 00:42:13,685 --> 00:42:15,587 WE DON'T HAVE THAT DATA, WE ONLY 1134 00:42:15,587 --> 00:42:17,489 HAVE THE OTHER DATA BUT IF 1135 00:42:17,489 --> 00:42:18,690 SOMETHING IS FOOD BASICALLY FOR 1136 00:42:18,690 --> 00:42:21,960 THOUGHT, SHE DID THE SAME STUDY 1137 00:42:21,960 --> 00:42:25,998 HERE IN THE NICHD AND NHLBI 1138 00:42:25,998 --> 00:42:27,499 FUNDED STUDY CALLED 1139 00:42:27,499 --> 00:42:30,602 [INDISCERNIBLE] TO BE, AND IN 1140 00:42:30,602 --> 00:42:32,638 HEALTHY PREGNANT WOMEN, 1141 00:42:32,638 --> 00:42:34,006 RELATIVELY HEALTHY PREGNANT 1142 00:42:34,006 --> 00:42:37,976 WOMEN, SHE LOOKED AT ACTIGER 1143 00:42:37,976 --> 00:42:39,912 DATABASEROPHY, AND REST WITH 1144 00:42:39,912 --> 00:42:41,613 LIGHT ACTIVITY AND NO DIFFERENCE 1145 00:42:41,613 --> 00:42:43,715 BETWEEN THOSE WITH GUESTATIONAL 1146 00:42:43,715 --> 00:42:45,450 DIABETES AND THOSE WHO DID NOT 1147 00:42:45,450 --> 00:42:46,752 WITH THE AMOUNT OF PHYSICAL 1148 00:42:46,752 --> 00:42:48,453 ACTIVITY OR THE TIMES OF 1149 00:42:48,453 --> 00:42:49,922 PHYSICAL ACTIVITY ACROSS THE 1150 00:42:49,922 --> 00:42:50,289 ENTIRE 24 HOURS. 1151 00:42:50,289 --> 00:42:52,658 BUT IF YOU LOOK AT THE LIGHT 1152 00:42:52,658 --> 00:42:56,929 INFORMATION LOOK AT THE RED LINE 1153 00:42:56,929 --> 00:42:59,197 HERE, THOSE WITH GUESTATIONAL 1154 00:42:59,197 --> 00:43:00,799 DIABETES WERE ALSO THOSE MORE 1155 00:43:00,799 --> 00:43:02,200 LIKELY TO HAVE EXPOSURE TO LIGHT 1156 00:43:02,200 --> 00:43:05,571 WITHIN 3 HOURS OF AT BED TIME. 1157 00:43:05,571 --> 00:43:08,540 SO THAT LIGHT IS CAUSING SOME 1158 00:43:08,540 --> 00:43:09,875 KIND OF DISREGULATION OR 1159 00:43:09,875 --> 00:43:11,043 MISALIGNMENT AND THIS IS A 1160 00:43:11,043 --> 00:43:11,977 REFLECTION OF THIS, THAT IF YOU 1161 00:43:11,977 --> 00:43:14,746 ELECTRIC AT THOSE WHO HAD THE 1162 00:43:14,746 --> 00:43:16,481 HIGHEST LIGHT, BEFORE BED TIME, 1163 00:43:16,481 --> 00:43:19,251 YOU CAN SEE THAT IT'S 1164 00:43:19,251 --> 00:43:21,219 PRETTY--IT'S--YOU KNOW WE HAVE 1165 00:43:21,219 --> 00:43:22,955 THESE, EVEN ADJUSTED UNAJUSTED 1166 00:43:22,955 --> 00:43:25,724 ODDS RATIO OF LIKE 3 OR 4 SO 1167 00:43:25,724 --> 00:43:31,530 IT'S REALLY A LARGE AFFECT SIZE. 1168 00:43:31,530 --> 00:43:37,202 SO WE WENT OVER THIS KIND OF 1169 00:43:37,202 --> 00:43:39,805 REGULATORY SYSTEM FROM SYSTEM TO 1170 00:43:39,805 --> 00:43:40,973 PERIPHERAL AND HOW THEY'RE 1171 00:43:40,973 --> 00:43:43,175 INTEGRATE WIDE THE BEHAVIORS OF 1172 00:43:43,175 --> 00:43:45,310 THE EXTERNAL LIGHT DARK CYCLE, 1173 00:43:45,310 --> 00:43:46,612 SLEEP, WAKE, AND FEEDING 1174 00:43:46,612 --> 00:43:47,212 BEHOUSTON AND RICE FOOTBALLS. 1175 00:43:47,212 --> 00:43:48,814 SO WE CAN CLEARLY NOW SAY, WELL 1176 00:43:48,814 --> 00:43:50,115 WHAT CAN WE DO ABOUT THAT, 1177 00:43:50,115 --> 00:43:52,451 RIGHT, WE DID DO A LIGHT, WE 1178 00:43:52,451 --> 00:43:54,720 TALKED ABOUT WE CAN ACTUALLY DO 1179 00:43:54,720 --> 00:43:56,088 LIGHT THERAPY, THERE ARE MANY 1180 00:43:56,088 --> 00:43:59,157 STUDIES LOOKING AT THAT IN 1181 00:43:59,157 --> 00:44:01,827 NEURODEGENERATION, MAYBE LESS IN 1182 00:44:01,827 --> 00:44:04,129 METABOLIC SYNDROMES, WE CAN GIVE 1183 00:44:04,129 --> 00:44:07,032 MELATONIN, CAN I TAKE MELATONIN, 1184 00:44:07,032 --> 00:44:09,368 SURE, WE HAD THE PERIPHERAL 1185 00:44:09,368 --> 00:44:11,003 CLOCKS, WE CAN DO ACTIVITY, ALL 1186 00:44:11,003 --> 00:44:12,170 OF THESE WE HAVE DONE IN THE 1187 00:44:12,170 --> 00:44:13,271 PAST AND MANY OTHERS IN THE 1188 00:44:13,271 --> 00:44:14,806 FIELD ARE WORKING ON VERY, VERY 1189 00:44:14,806 --> 00:44:17,643 IMPORTANT TYPES OF THINGS MUCH 1190 00:44:17,643 --> 00:44:19,411 WE CAN IMPROVE SLEEP, REMEMBER 1191 00:44:19,411 --> 00:44:23,215 SLEEP IS THIS KIND OF GEAR, 1192 00:44:23,215 --> 00:44:23,749 BI-DIRECTIONAL GEAR, 1193 00:44:23,749 --> 00:44:25,017 MULTIDIRECTIONAL GEAR FOR ALL OF 1194 00:44:25,017 --> 00:44:26,485 THESE THINGS BUT I WANT TO FOCUS 1195 00:44:26,485 --> 00:44:30,322 ALL THESE THINGS ON THE SLEEP 1196 00:44:30,322 --> 00:44:30,656 CYCLE. 1197 00:44:30,656 --> 00:44:33,525 THIS IS WORK WE'RE DOING 1198 00:44:33,525 --> 00:44:33,959 RECENTLY. 1199 00:44:33,959 --> 00:44:36,528 WHAT IS TIME RESTRICTED FEEDING, 1200 00:44:36,528 --> 00:44:38,163 THERE'S A SUBSTANTIAL AMOUNT OF 1201 00:44:38,163 --> 00:44:39,698 NICE, REALLY IMPORTANT DATA IN 1202 00:44:39,698 --> 00:44:41,266 ANIMAL STUDIES, YOU CAN SEE IN 1203 00:44:41,266 --> 00:44:45,504 REALLY, REALLY NICE ARTICLES, 1204 00:44:45,504 --> 00:44:46,071 TIME RESTRICTED FEEDING. 1205 00:44:46,071 --> 00:44:51,610 BASED ON A CIRCADIAN PRINCIPLE 1206 00:44:51,610 --> 00:44:52,377 CAN IMPROVE METABOLIC FUNCTION 1207 00:44:52,377 --> 00:44:56,882 AND WE ALSO KNOW THAT LATE 1208 00:44:56,882 --> 00:44:59,518 ISOCALORIC EATING DECREASES 1209 00:44:59,518 --> 00:45:01,620 HUNGER, ENERGY EXPENDITURE AND 1210 00:45:01,620 --> 00:45:05,057 WE DID STUDIES IN OTHERS, FRANK 1211 00:45:05,057 --> 00:45:06,591 SCHEER'S GROUP AND MANY OF THESE 1212 00:45:06,591 --> 00:45:11,830 STUDIES SHOWING THE FASTING THAT 1213 00:45:11,830 --> 00:45:13,665 THEY'RE REALLY RELATED TO EACH 1214 00:45:13,665 --> 00:45:15,967 OTHER AND TIME RESTRICTED 1215 00:45:15,967 --> 00:45:17,002 FEEDINGS DURING CERTAIN WINDOWS 1216 00:45:17,002 --> 00:45:18,770 OF THE DAY MAY HAVE BENEFICIAL 1217 00:45:18,770 --> 00:45:19,004 EFFECTS. 1218 00:45:19,004 --> 00:45:22,207 SO THIS IS A STUDY THAT WE ENDED 1219 00:45:22,207 --> 00:45:25,444 UP DOING, THIS IS FUNDED BY AN 1220 00:45:25,444 --> 00:45:27,746 RO-1 FROM NHLBI AS FAR AS PART 1221 00:45:27,746 --> 00:45:30,515 OF THE PEEL 1 BY NIA WHERE WE 1222 00:45:30,515 --> 00:45:32,050 LOOK AT MIDDLE AGE AS WELL AS 1223 00:45:32,050 --> 00:45:33,251 OLDER ADULTS WE THOUGHT, WELL 1224 00:45:33,251 --> 00:45:37,823 WHAT WE IF JUST ENHANCE THE 1225 00:45:37,823 --> 00:45:41,059 CIRCADIAN SIGNAL BY USING THE 1226 00:45:41,059 --> 00:45:44,262 FEED FAST CYCLE AS A PERIPHERAL 1227 00:45:44,262 --> 00:45:48,133 KIND OF METABOLIC SIGNAL, RIGHT? 1228 00:45:48,133 --> 00:45:51,503 BEING WE THEN IMPROVE THIS CROSS 1229 00:45:51,503 --> 00:45:54,806 TALK BETWEEN THE CENTRAL CLOCK, 1230 00:45:54,806 --> 00:45:55,974 PERIPHERAL CLOCKS, SLEEP AND 1231 00:45:55,974 --> 00:46:00,078 RHYTHMS AND COULD WE THROUGH 1232 00:46:00,078 --> 00:46:02,514 THOSE MECHANISMS, IMPROVE CARDIO 1233 00:46:02,514 --> 00:46:04,082 METABOLIC FUNCTION IN THESE 1234 00:46:04,082 --> 00:46:08,086 ACULTS WHO WERE NOT DIABETIC, 1235 00:46:08,086 --> 00:46:12,124 THEY WERE OVERWEIGHT IN GENERAL 1236 00:46:12,124 --> 00:46:15,761 AND THEY MAY HAVE CONTROL, THEY 1237 00:46:15,761 --> 00:46:17,496 WERE HYPERTENSION BUT THEY WERE 1238 00:46:17,496 --> 00:46:19,331 FAIRLY WELL CONTROLLED AND WE 1239 00:46:19,331 --> 00:46:21,099 JUST LOOKED AT THE FEEDING 1240 00:46:21,099 --> 00:46:21,600 DURATION. 1241 00:46:21,600 --> 00:46:22,567 THE INTERVENTION WAS THAT THEY 1242 00:46:22,567 --> 00:46:25,337 HAD TO DIM ALL THE LIGHTS OUT, 1243 00:46:25,337 --> 00:46:27,539 EVERYBODY IN THE CONTROL GROUP 1244 00:46:27,539 --> 00:46:28,774 OR EXPERIMENTAL GROUP 3 HOURS 1245 00:46:28,774 --> 00:46:29,841 BEFORE BED TIME BECAUSE WE 1246 00:46:29,841 --> 00:46:32,544 DIDN'T WANT LIGHT TO AFFECT 1247 00:46:32,544 --> 00:46:32,744 THEM. 1248 00:46:32,744 --> 00:46:35,280 WE HAD DATA FROM BEFORE THAT 1249 00:46:35,280 --> 00:46:38,150 HAVING BRIGHT LIGHT WHEN EATING 1250 00:46:38,150 --> 00:46:39,317 ASHINGS YOUR METABOLISM AND IT 1251 00:46:39,317 --> 00:46:40,752 DIFFERS BETWEEN THE MORNING AND 1252 00:46:40,752 --> 00:46:41,019 AFTERNOON. 1253 00:46:41,019 --> 00:46:41,586 SOPHISTICATEDY WE WANT TO 1254 00:46:41,586 --> 00:46:44,523 CONTROL FOR THAT AND THEN WE 1255 00:46:44,523 --> 00:46:48,193 EXTENDED THEIR OVERNIGHT FAST 1256 00:46:48,193 --> 00:46:49,594 FROM 3-12 HOURS, 12-16 DEPENDING 1257 00:46:49,594 --> 00:46:51,329 ON THE INDIVIDUAL AND WE ASKED 1258 00:46:51,329 --> 00:46:52,864 THEM TO STOP EATING 3 HOURS 1259 00:46:52,864 --> 00:46:54,599 BEFORE BED TIME THIS, IS THE 1260 00:46:54,599 --> 00:46:55,801 INTERVENTION GROUP, THE OTHER 1261 00:46:55,801 --> 00:46:57,636 GROUP JUST DIMMED THEIR LIGHTS 1262 00:46:57,636 --> 00:46:59,638 OUT 3 HOURS BEFORE BED TIME AND 1263 00:46:59,638 --> 00:47:00,572 PARTICIPANTS WERE ALLOWED TO 1264 00:47:00,572 --> 00:47:01,873 CHOOSE WHETHER TO STOP EATING 1265 00:47:01,873 --> 00:47:05,177 EARLIER TO MAKE THAT LONGER 1266 00:47:05,177 --> 00:47:06,745 FASTING FORWARD, WITH THE 1267 00:47:06,745 --> 00:47:08,847 OVERNIGHT FAST OR START EATING 1268 00:47:08,847 --> 00:47:09,915 LATER AFTER AWAKENING AND THIS 1269 00:47:09,915 --> 00:47:13,652 IS THE GROUP OF TALENTED WOMEN 1270 00:47:13,652 --> 00:47:16,588 WHO ALSO WERE CO INVESTIGATORS 1271 00:47:16,588 --> 00:47:20,659 IN THIS STUDY, CATHY REID, 1272 00:47:20,659 --> 00:47:25,063 DANIELA AND [INDISCERNIBLE] 1273 00:47:25,063 --> 00:47:27,499 ABBOT, AND CHRISTEN KNUTSON. 1274 00:47:27,499 --> 00:47:29,234 SO THIS IS 1 DURING THE 1275 00:47:29,234 --> 00:47:30,669 PANDEMIC, THIS WAS REALLY HARD. 1276 00:47:30,669 --> 00:47:31,937 WE DID A SCREENING PERIOD, THEY 1277 00:47:31,937 --> 00:47:35,273 CAME INTO THE CLINIC SO WE CAN 1278 00:47:35,273 --> 00:47:37,509 DRAW BLOOD AND DO SLEEP 1279 00:47:37,509 --> 00:47:39,377 RECORDINGS FOR THROW DAYS. 1280 00:47:39,377 --> 00:47:41,546 WE ADMITTED THEM AND THEN WE GOT 1281 00:47:41,546 --> 00:47:42,714 THE FIRST BASE LINE INFORMATION 1282 00:47:42,714 --> 00:47:46,051 FROM THEM EMPLOY AND THEN WE 1283 00:47:46,051 --> 00:47:47,219 RANDOMIZED THEM, AND THE 1284 00:47:47,219 --> 00:47:48,753 HABITUAL AND THEN WE FOLLOW THEM 1285 00:47:48,753 --> 00:47:51,256 FOR, IT WAS A 6 WEEK 1286 00:47:51,256 --> 00:47:52,524 INTERVENTION AND THEN AFTER THE 1287 00:47:52,524 --> 00:47:56,828 6 WEEKS THEY CAME BACK INTO THE 1288 00:47:56,828 --> 00:47:58,196 CLINICAL RESEARCH UNIT AND WE 1289 00:47:58,196 --> 00:48:00,599 DRAW ALL THEIR BLOODS AGAIN FOR 1290 00:48:00,599 --> 00:48:01,633 3 DAYS AND THEIR SLEEP AND 1291 00:48:01,633 --> 00:48:03,168 PERFOR THE PURPOSANCE MEASURES, 1292 00:48:03,168 --> 00:48:04,336 THERE'S REALLY QUITE A FEW 1293 00:48:04,336 --> 00:48:05,503 MEASURES THAT WE DID. 1294 00:48:05,503 --> 00:48:06,972 WHILE THEY'RE IN THE FIELD 1295 00:48:06,972 --> 00:48:13,011 DURING THE 6 WEEKS THEY GOT 1296 00:48:13,011 --> 00:48:13,879 CONTINUOUS ACTIGER DATABASERAPHY 1297 00:48:13,879 --> 00:48:16,147 AND SLEEP AND FOOD LOGS AND 1298 00:48:16,147 --> 00:48:18,884 CGMS, AND LOOK AT GLUCOSE 1299 00:48:18,884 --> 00:48:20,852 MONITORING ON A CONTINUOUS LEVEL 1300 00:48:20,852 --> 00:48:22,554 FOR SEVERAL DAYS AND A HEART 1301 00:48:22,554 --> 00:48:22,754 RATE. 1302 00:48:22,754 --> 00:48:25,657 SO THIS IS THE ACTIVERAPHY 1303 00:48:25,657 --> 00:48:27,759 RECORDING IN THE INDIVIDUAL, AND 1304 00:48:27,759 --> 00:48:30,295 IN THE BLUE HERE IS THEIR SLEEP 1305 00:48:30,295 --> 00:48:32,564 PERIOD AND IN THE DASH LINES 1306 00:48:32,564 --> 00:48:35,767 WILL BE THEIR FEEDING INTERVAL, 1307 00:48:35,767 --> 00:48:36,835 SO HERE'S AT BASE LINE. 1308 00:48:36,835 --> 00:48:38,737 THEY WERE ALL FAIRLY NORMAL 1309 00:48:38,737 --> 00:48:39,004 SLEEPERS. 1310 00:48:39,004 --> 00:48:41,373 WE DIDN'T WANT ANYBODY WHO WAS A 1311 00:48:41,373 --> 00:48:42,674 SLEEP DEPRIVED OR SHORT SLEEPERS 1312 00:48:42,674 --> 00:48:46,144 OR THEY HAD A CIRCADIAN EXTREME 1313 00:48:46,144 --> 00:48:46,711 CROHN O TYPES. 1314 00:48:46,711 --> 00:48:48,380 SO THIS WAS THE INTERVENTION, WE 1315 00:48:48,380 --> 00:48:50,849 INCREASE THE DURATION OF THEIR 1316 00:48:50,849 --> 00:48:52,884 FAST, AND THEY MAINTAIN THAT 1317 00:48:52,884 --> 00:48:54,085 THROUGHOUT THOSE 6 WEEKS. 1318 00:48:54,085 --> 00:48:55,587 WE CALLED THEM EVERY OTHER DAY 1319 00:48:55,587 --> 00:48:56,688 TO MAKE SURE THEY WERE DOING 1320 00:48:56,688 --> 00:48:58,623 THAT AND IT CAME BACK TO THE 1321 00:48:58,623 --> 00:49:00,358 CLINICAL RESEARCH UNIT, AFTER 1322 00:49:00,358 --> 00:49:03,495 THE INTERVENTION HERE, TO SEE 1323 00:49:03,495 --> 00:49:05,096 WHAT AFFECT THIS HAD. 1324 00:49:05,096 --> 00:49:06,731 THEY KEPT THESE FOOD DIARIES 1325 00:49:06,731 --> 00:49:10,302 EVERY DAY AND WE WERE ABLE TO 1326 00:49:10,302 --> 00:49:11,202 LOOK AT MACRONUTRIENTS, WE WERE 1327 00:49:11,202 --> 00:49:13,905 ABLE TO LOOK AT TIMING, TIME 1328 00:49:13,905 --> 00:49:15,540 STAMPS AND LOOKING AT WHEN THEY 1329 00:49:15,540 --> 00:49:17,609 WERE BUILDING IT AND THIS IS 1 1330 00:49:17,609 --> 00:49:20,211 EXAMPLE PLUS WHERE WE CAN LOOK 1331 00:49:20,211 --> 00:49:21,413 AT THE RELATIONSHIP BETWEEN 1332 00:49:21,413 --> 00:49:23,715 MODAL THINGS SO IN THIS LITTLE 1333 00:49:23,715 --> 00:49:29,254 PART IS THE--IF YOU LOOK AT THE 1334 00:49:29,254 --> 00:49:30,989 FASTING INTERVAL HERE, CAN YOU 1335 00:49:30,989 --> 00:49:34,626 SEE THAT DURING THE INTERVENTION 1336 00:49:34,626 --> 00:49:35,894 THE FEEDING--THE FASTING 1337 00:49:35,894 --> 00:49:38,029 INTERVAL DID INCREASE, RIGHT? 1338 00:49:38,029 --> 00:49:40,432 BUT THIS IS ACTIGRAPHY DATA HERE 1339 00:49:40,432 --> 00:49:42,534 SO WE SEE THE SLEEP-WAKE TIMING, 1340 00:49:42,534 --> 00:49:44,202 ALL THE PEAKS WERE RELATIVE 1341 00:49:44,202 --> 00:49:47,939 ACROSS THE 24 HOURS AS WELL AS 1342 00:49:47,939 --> 00:49:49,607 LOOKING AT OTHER PARAMETERS, WE 1343 00:49:49,607 --> 00:49:52,610 COULD LOOK AT ACTIVITY, HEART 1344 00:49:52,610 --> 00:49:53,912 RATE VALID AND RELIABLABILITYS, 1345 00:49:53,912 --> 00:49:55,580 WE CAN PLOT THESE IN THE 1346 00:49:55,580 --> 00:49:57,983 CIRCULAR PLOT TO LOOK AT THESE 1347 00:49:57,983 --> 00:49:59,284 RELATIONSHIP BETWEEN MULTIPLE 1348 00:49:59,284 --> 00:50:00,819 PHYSIOLOGICAL AND BEHAVIORIAL 1349 00:50:00,819 --> 00:50:03,121 ACTIVITIES, WITH EACH OTHER AND 1350 00:50:03,121 --> 00:50:05,223 WHETHER THAT IS THAT 1351 00:50:05,223 --> 00:50:06,024 SYNCHRONIZATION ALIGNMENT WOULD 1352 00:50:06,024 --> 00:50:08,360 IN ANY WAY BE--WE'RE STILL NOT 1353 00:50:08,360 --> 00:50:10,328 THERE YET, WE NEED SOME REALLY 1354 00:50:10,328 --> 00:50:11,696 COMPUTATIONAL POWER TO DO THAT. 1355 00:50:11,696 --> 00:50:13,965 SO JUST A LITTLE BIT THIS, IS 1356 00:50:13,965 --> 00:50:15,633 SOME PRELIMINARY DATA WE JUST 1357 00:50:15,633 --> 00:50:18,336 FINISHED ANALYZING SOME OF THIS, 1358 00:50:18,336 --> 00:50:20,672 WE CLOSED THE STUDY, AND WHAT 1359 00:50:20,672 --> 00:50:24,009 YOU CAN SEE, THIS IS FROM 1360 00:50:24,009 --> 00:50:26,845 THE--OUR PRIMARY OUTCOME WAS THE 1361 00:50:26,845 --> 00:50:27,712 ORAL DPLU COSTOLERANCE TEST IN 1362 00:50:27,712 --> 00:50:30,148 THE MORNING AS A METABOLIC 1363 00:50:30,148 --> 00:50:31,082 PARAMETER. 1364 00:50:31,082 --> 00:50:32,684 AND HERE'S THE DPLUICOSE BETWEEN 1365 00:50:32,684 --> 00:50:36,421 VISIT 3, BLUE IS BASE LINE, 1366 00:50:36,421 --> 00:50:37,789 ORANGE IS POST INTERVENTION. 1367 00:50:37,789 --> 00:50:40,025 THERE WAS NOT MUCH DIFFERENCE IN 1368 00:50:40,025 --> 00:50:40,959 DPLUICOSE. 1369 00:50:40,959 --> 00:50:42,660 YOU MAY SEE, MAYBE BUT THERE WAS 1370 00:50:42,660 --> 00:50:44,829 NOT MUCH DIFFERENCE IN GLUCOSE, 1371 00:50:44,829 --> 00:50:45,897 AT LEAST NOT SIGNIFICANT. 1372 00:50:45,897 --> 00:50:47,999 BUT THERE WAS A SIGNIFICANT 1373 00:50:47,999 --> 00:50:49,834 DECREASE IN THE AMOUNT OF 1374 00:50:49,834 --> 00:50:52,270 INSULIN THAT WAS SECRETED AND 1375 00:50:52,270 --> 00:50:54,672 ESPECIALLY WHEN YOU LOOK AT THE 1376 00:50:54,672 --> 00:50:57,075 2-HOUR GLUCOSE PERIOD HERE, 120 1377 00:50:57,075 --> 00:50:57,442 MINUTES. 1378 00:50:57,442 --> 00:51:00,211 AND IT LOOKED LIKE, IT TOOK THEM 1379 00:51:00,211 --> 00:51:02,047 A LITTLE BIT--LITTLE BIT SHORTER 1380 00:51:02,047 --> 00:51:06,384 TO GET TO BASE LINE IN THE ORAL 1381 00:51:06,384 --> 00:51:08,353 DPLUICOSE TOLERANCE TASK AND 1382 00:51:08,353 --> 00:51:12,791 HERE'S THE INSULIN AS WELL. 1383 00:51:12,791 --> 00:51:14,192 THIS IS THE NON--THIS IS THE 1384 00:51:14,192 --> 00:51:15,060 CONTROL GROUP. 1385 00:51:15,060 --> 00:51:18,630 WHAT WAS REALLY INTERESTING, 1386 00:51:18,630 --> 00:51:20,965 SURPRISING WAS THE FREE FATTY 1387 00:51:20,965 --> 00:51:23,835 ACIDS, SO THE OGT OF COURSE AT 1388 00:51:23,835 --> 00:51:27,272 0-POINT HERE AND SO BEFORE THIS 1389 00:51:27,272 --> 00:51:28,006 IS FASTING, RIGHT? 1390 00:51:28,006 --> 00:51:30,542 MINUS 15 IS FASTING, THERE'S 1391 00:51:30,542 --> 00:51:32,744 DECREASE IN THE PRE3 FATTY ACIDS 1392 00:51:32,744 --> 00:51:36,347 WHEREAS YOU DON'T SEE THIS IN 1393 00:51:36,347 --> 00:51:41,052 THE NONEXTENDED OVERNIGHT FAST 1394 00:51:41,052 --> 00:51:42,087 GROUP. 1395 00:51:42,087 --> 00:51:44,255 HOOK AT PLASMA CORTISOL, WE CREW 1396 00:51:44,255 --> 00:51:45,790 BLOOD FROM THEM LIKE EVERY 2 1397 00:51:45,790 --> 00:51:48,960 HOURS, SO ACROSS THE 24 HOURS 1398 00:51:48,960 --> 00:51:52,297 THIS IS THE CORTISOL PLASMA, AND 1399 00:51:52,297 --> 00:51:53,565 THE EXTENDED OVERNIGHT FAST 1400 00:51:53,565 --> 00:51:57,435 GROUP, BASE LINE, VERSUS END OF 1401 00:51:57,435 --> 00:51:59,504 THE INTERVENTION, YOU CAN SEE 1402 00:51:59,504 --> 00:52:01,506 DURING THE SLEEP, THIS FIRST 1403 00:52:01,506 --> 00:52:03,775 LEAP PERIOD, THERE IS A 1404 00:52:03,775 --> 00:52:07,078 SIGNIFICANT DECREASE IN CORTISOL 1405 00:52:07,078 --> 00:52:13,718 COMPARED TO HERE IN THE NONOOF 1406 00:52:13,718 --> 00:52:15,753 CONDITION, AND IN THE PEER 1407 00:52:15,753 --> 00:52:16,921 GROUP, THE SLEEP PERIOD AT THE 1408 00:52:16,921 --> 00:52:18,890 END OF THE STUDY ARE 1409 00:52:18,890 --> 00:52:22,627 SIGNIFICANTLY LOWER ABOUT A 33% 1410 00:52:22,627 --> 00:52:25,930 REDUCTION IN THE SLEEP TOWARD, 1411 00:52:25,930 --> 00:52:27,432 SO THAT'S VERY INTERESTING. 1412 00:52:27,432 --> 00:52:29,501 WE ALSO LOOKEDDA THE CARD QUO 1413 00:52:29,501 --> 00:52:30,668 VASCULAR FUNCTION AND SLEEP. 1414 00:52:30,668 --> 00:52:33,771 WE LOOK AT HEART RATE AND ALSO 1415 00:52:33,771 --> 00:52:34,873 PLP, HEART RATE AT THE TOP, 1416 00:52:34,873 --> 00:52:36,574 BLOOD PRESSURE AT THE BOTTOM AND 1417 00:52:36,574 --> 00:52:39,177 THE DARK BAR HERE INDICATES THE 1418 00:52:39,177 --> 00:52:41,312 SLEEP AND/OR AT LEAST THE TIME 1419 00:52:41,312 --> 00:52:42,080 OF LIGHTS OUT. 1420 00:52:42,080 --> 00:52:46,417 AND MOST OF THESE INDIVIDUALS 1421 00:52:46,417 --> 00:52:48,186 FELL ASLEEP FAIRLY QUICKLY, THEY 1422 00:52:48,186 --> 00:52:49,821 DID NOT HAVE INSOMNIA ISSUES. 1423 00:52:49,821 --> 00:52:51,923 AND YOU CAN SEE THE DIPPING OF 1424 00:52:51,923 --> 00:52:53,291 THE BLOOD PRESSURE, MORE 1425 00:52:53,291 --> 00:52:54,926 PROMINENTLY HERE IN THE OOF 1426 00:52:54,926 --> 00:52:57,629 GROUP AND NOT SO MUCH NO REAL 1427 00:52:57,629 --> 00:53:01,166 CHANGE HERE IN THE CONTROL GROUP 1428 00:53:01,166 --> 00:53:02,901 AND THE SAME THING HERE WITH 1429 00:53:02,901 --> 00:53:03,501 HEART RATE? 1430 00:53:03,501 --> 00:53:07,238 SO IT TURNS OUT THAT IT'S ABOUT 1431 00:53:07,238 --> 00:53:10,608 3% REDUCTION IN HEART RATE 1432 00:53:10,608 --> 00:53:11,876 DURING THE SLEEP PERIOD. 1433 00:53:11,876 --> 00:53:14,445 AND ABOUT A 6% REDUCTION IN 1434 00:53:14,445 --> 00:53:15,213 DIASTOLIC BLOOD PRESSURE. 1435 00:53:15,213 --> 00:53:17,215 WE DID NOT SEE CHANGES IN SIS 1436 00:53:17,215 --> 00:53:19,717 TOLL-LIKE RECEPTORIC BLOOD 1437 00:53:19,717 --> 00:53:19,984 PRESSURE. 1438 00:53:19,984 --> 00:53:23,922 MORE OVER WHEN WE LOOKED AT THE 1439 00:53:23,922 --> 00:53:26,124 CHANGES IN THE PLP DIPPING IT 1440 00:53:26,124 --> 00:53:27,292 WAS CORRELATED WITH THE 1441 00:53:27,292 --> 00:53:29,260 CONTINUOUS SLEEP SO THE TIME OF 1442 00:53:29,260 --> 00:53:31,429 WAKE AFTER SLEEP ONSET OF 1443 00:53:31,429 --> 00:53:33,364 FRAGMENTATION OF SLEEP, THE 1444 00:53:33,364 --> 00:53:34,766 IMPROVEMENT IN THAT WAS 1445 00:53:34,766 --> 00:53:37,635 ASSOCIATED WITH IMPROVEMENT IN 1446 00:53:37,635 --> 00:53:39,804 THE--IN SOME OF THESE 1447 00:53:39,804 --> 00:53:40,471 CARDIOVASCULAR POINTS. 1448 00:53:40,471 --> 00:53:43,608 SO I'M GOING TO KIND OF ALMOST 1449 00:53:43,608 --> 00:53:45,009 END BY SAYING THAT IT IS PERHAPS 1450 00:53:45,009 --> 00:53:48,112 TIME NOW TO BE TARGETING 1451 00:53:48,112 --> 00:53:51,416 CIRCADIAN AND SLEEP INTERACTIONS 1452 00:53:51,416 --> 00:53:52,917 TOGETHER BETWEEN AND ALSO 1453 00:53:52,917 --> 00:53:54,819 BETWEEN CENTRAL AND PERIPHERAL 1454 00:53:54,819 --> 00:53:56,287 MECHANISMS WHETHER IT'S CLOCK OR 1455 00:53:56,287 --> 00:53:57,689 SLEEP MECH NICHES, THERE ARE 1456 00:53:57,689 --> 00:54:00,525 MULTIPLE THINGS WE CAN DO AS WE 1457 00:54:00,525 --> 00:54:04,963 TALKED ABOUT EARLIER AND I THINK 1458 00:54:04,963 --> 00:54:07,699 IT'S REALLY RECIPROCAL BETWEEN 1459 00:54:07,699 --> 00:54:09,534 CENTRAL CLOCKS, PERIPHERAL 1460 00:54:09,534 --> 00:54:10,702 CLOCKS AND SLEEP WAKE TIMING, 1461 00:54:10,702 --> 00:54:12,437 HOW CAN WE USE THIS TYPE OF 1462 00:54:12,437 --> 00:54:15,139 INFORMATION THAT WE ALREADY HAVE 1463 00:54:15,139 --> 00:54:16,674 TODAY TO LOOK AT INTERVENTIONS. 1464 00:54:16,674 --> 00:54:18,876 THIS IS WHAT IS MISSING DURING 1465 00:54:18,876 --> 00:54:20,812 THIS TIME, WE HAVE HONE THAT 1466 00:54:20,812 --> 00:54:24,282 MAYBE IT IS EFFECTIVE FOR CARDIO 1467 00:54:24,282 --> 00:54:25,984 METABOLIC DISEASE RISK BUT WE 1468 00:54:25,984 --> 00:54:26,918 DON'T KNOW ABOUT NEURODEN 1469 00:54:26,918 --> 00:54:28,920 GENERATION BUT THAT IS QUITE 1470 00:54:28,920 --> 00:54:31,022 POSSIBLE, SO AGAIN, CIRCADIAN 1471 00:54:31,022 --> 00:54:32,357 AND SLEEP MEDICINE COULD BE PART 1472 00:54:32,357 --> 00:54:36,995 OF WHAT I WOULD HOPE IS PART OF 1473 00:54:36,995 --> 00:54:38,830 MY FUTURE HERE. 1474 00:54:38,830 --> 00:54:40,331 THEY'RE REALLY INTEGRATED. 1475 00:54:40,331 --> 00:54:43,234 WE NEED BIOMARKERS, WEARABLES, 1476 00:54:43,234 --> 00:54:45,703 CLINIC DATA, TIMING OF DIAGNOSIS 1477 00:54:45,703 --> 00:54:46,738 COULD BE IMPROVED, WE COULD 1478 00:54:46,738 --> 00:54:50,408 CONTINUE TO USE TYPICAL METHODS 1479 00:54:50,408 --> 00:54:51,843 LIKE LIGHT, MELATONIN, EXERCISE, 1480 00:54:51,843 --> 00:54:52,910 TIME RESTRICTED EATING AND 1481 00:54:52,910 --> 00:54:54,846 PERHAPS WITH THE MOLECULAR 1482 00:54:54,846 --> 00:54:56,347 MECHANISMS TO DRUG THE CLOCK AS 1483 00:54:56,347 --> 00:54:58,182 WELL TO CHANGE THE PERIOD OF 1484 00:54:58,182 --> 00:55:00,385 CLOCK, TO CHANGE THE FACE OF THE 1485 00:55:00,385 --> 00:55:01,185 CLOCK WITH MEDICATIONS. 1486 00:55:01,185 --> 00:55:04,055 AND AS MENTIONED EARLIER, WE DO 1487 00:55:04,055 --> 00:55:06,824 AT NORTHWESTERN HAVE THE FIRST 1488 00:55:06,824 --> 00:55:07,458 CIRCADIAN MEDICINE CLINIC. 1489 00:55:07,458 --> 00:55:10,828 IT TOOK ME THE LONGEST TIME, 1490 00:55:10,828 --> 00:55:13,665 TOOK YEARS TO CHANGE THE PLAQUE. 1491 00:55:13,665 --> 00:55:17,935 IT WAS JUST CALLED THE SLEEP 1492 00:55:17,935 --> 00:55:18,202 CENTER. 1493 00:55:18,202 --> 00:55:21,272 AND NOW YOU CAN SEE SLEEP 1494 00:55:21,272 --> 00:55:22,807 CLINIC, CIRCADIAN CLINIC AND 1495 00:55:22,807 --> 00:55:25,243 SLEEP LABORATORY AND THE NAME AS 1496 00:55:25,243 --> 00:55:26,844 CHANGED TO CIRCADIAN AND SLEEP 1497 00:55:26,844 --> 00:55:28,613 DISORDERS CENTER WHERE ALL THE 1498 00:55:28,613 --> 00:55:30,682 PATIENTS CAN SEE, SO I SAID THE 1499 00:55:30,682 --> 00:55:33,718 FUTURE WILL BE IN CROHNAL 1500 00:55:33,718 --> 00:55:34,552 DIAGNOSTICS BIOLOGICAL TIME 1501 00:55:34,552 --> 00:55:39,023 INNING IN THE CLINIC, USING 1502 00:55:39,023 --> 00:55:42,160 SENSORS MULTIPLE SENSORS, USING 1503 00:55:42,160 --> 00:55:43,094 DIFFERENT MODELS, ALGORITHMS TO 1504 00:55:43,094 --> 00:55:44,629 LOOK AT TEMPORAL PROFILE AND SO 1505 00:55:44,629 --> 00:55:47,065 FOR EXAMPLE, WE HAVE DIFFERENT 1506 00:55:47,065 --> 00:55:49,133 OMICs TO DETERMINE WITH 1 OR 2 1507 00:55:49,133 --> 00:55:51,235 BLOOD SAMPLES WHAT PHASES IT IN 1508 00:55:51,235 --> 00:55:52,737 YOUR BODY, RIGHT? 1509 00:55:52,737 --> 00:55:55,239 BECAUSE WE CAPTAIN BE DOING 24 1510 00:55:55,239 --> 00:55:56,541 HOUR BLOOD DRAWS FROM PEOPLE 1511 00:55:56,541 --> 00:55:58,276 EVERY 2 HOURS, THAT'S GREAT, BUT 1512 00:55:58,276 --> 00:56:01,112 THAT IS NOT GOING TO BE SCALABLE 1513 00:56:01,112 --> 00:56:02,146 TO TO THE CLINIC. 1514 00:56:02,146 --> 00:56:03,214 SO THIS IS SOMETHING THAT'S 1515 00:56:03,214 --> 00:56:07,151 MOVING INTO THE FUTURE AS WELL. 1516 00:56:07,151 --> 00:56:08,820 THIS IS JUST--I THOUGHT I WOULD 1517 00:56:08,820 --> 00:56:10,888 SHOW THIS, A DARPA STUDY THAT 1518 00:56:10,888 --> 00:56:13,057 WAS GIVEN TO JONATHAN 1519 00:56:13,057 --> 00:56:17,428 [INDISCERNIBLE], FRED CANNED 1520 00:56:17,428 --> 00:56:19,530 CANNED--FRED [INDISCERNIBLE] AND 1521 00:56:19,530 --> 00:56:20,031 MARTHA [INDISCERNIBLE], 1522 00:56:20,031 --> 00:56:20,932 COLLABORATORS ON THIS. 1523 00:56:20,932 --> 00:56:24,569 THIS IS CRAZY, THIS IS FROM THE 1524 00:56:24,569 --> 00:56:25,370 FUTURE. 1525 00:56:25,370 --> 00:56:29,006 HOW WILL WE DETECT CENTRAL AND 1526 00:56:29,006 --> 00:56:30,675 PERIPHERAL CLOCK AND ACLE 1527 00:56:30,675 --> 00:56:32,210 CELLERATE ARK DATA 1528 00:56:32,210 --> 00:56:32,944 PROTECTIONATION? 1529 00:56:32,944 --> 00:56:35,079 THIS IS JUST 1 POSSIBILITY, WE 1530 00:56:35,079 --> 00:56:37,849 CAN ESTIMATE PHASE, OOPS IN THE 1531 00:56:37,849 --> 00:56:38,783 CLOSED LOOP SYSTEM, DETERMINE 1532 00:56:38,783 --> 00:56:41,519 DOSE AND TIMING OF ANYTHING, 1533 00:56:41,519 --> 00:56:42,387 CREATE THIS FACE RESPONSE GROUP 1534 00:56:42,387 --> 00:56:44,255 SO IN A CLOSED GROUP SYSTEM, WE 1535 00:56:44,255 --> 00:56:46,457 CAN SAY, WE CAN ESTIMATE, WE CAN 1536 00:56:46,457 --> 00:56:51,095 DETECT THE TIME AND WE CAN ALSO 1537 00:56:51,095 --> 00:56:52,463 AFFECT A TREATMENT BASED ON A 1538 00:56:52,463 --> 00:56:55,066 SPECIFIC TIME AND THIS IS AN 1539 00:56:55,066 --> 00:56:58,469 IMPLANTABLE DEVICE RIGHT NOW. 1540 00:56:58,469 --> 00:56:59,971 SO I WANT TO END BY SAYING THAT 1541 00:56:59,971 --> 00:57:03,141 WE HAVE MANY WAYS IN WHICH WE 1542 00:57:03,141 --> 00:57:05,777 CAN USE SLEEP AND CIRCADIAN 1543 00:57:05,777 --> 00:57:08,513 PRINCIPLES AND APPROACHES TO 1544 00:57:08,513 --> 00:57:09,347 AFFECT MULTIPLE OUTCOMES WHERE 1545 00:57:09,347 --> 00:57:12,350 THEY WERE LOOKING AT 1546 00:57:12,350 --> 00:57:14,051 NEUROLOGICAL CARDIOVASCULAR, 1547 00:57:14,051 --> 00:57:15,553 POPULATION HEALTH, SURGICAL 1548 00:57:15,553 --> 00:57:16,487 CRITICAL CARE, STUDIES ARE 1549 00:57:16,487 --> 00:57:18,456 ONGOING AND ALMOST ALL OF THESE 1550 00:57:18,456 --> 00:57:22,126 AREAS, SO THIS FIELD IS REALLY 1551 00:57:22,126 --> 00:57:23,594 GROWING BEYOND, INCLUDING BUT 1552 00:57:23,594 --> 00:57:26,497 BEYOND JUST SLEEP AND WAKE 1553 00:57:26,497 --> 00:57:27,131 REGULATION. 1554 00:57:27,131 --> 00:57:28,232 AND WAWHAT REALLY EXCITES ME A 1555 00:57:28,232 --> 00:57:30,868 LOT IS THAT WE CAN AMRI THE 1556 00:57:30,868 --> 00:57:32,503 CIRCADIAN AND SLEEP SCIENCE TO 1557 00:57:32,503 --> 00:57:33,771 PUBLIC HEALTH, NOT JUST TO MY 1558 00:57:33,771 --> 00:57:36,174 CLINIC BUT ALSO TO PUBLIC HEALTH 1559 00:57:36,174 --> 00:57:37,742 AND MEDICINE TO ADDRESS HEALTH 1560 00:57:37,742 --> 00:57:38,042 DISPARITIES. 1561 00:57:38,042 --> 00:57:39,177 I JUST WANT TO SHOW YOU THIS. 1562 00:57:39,177 --> 00:57:42,413 THIS IS FROM THE CDC THIS, IS A 1563 00:57:42,413 --> 00:57:45,750 PUBLICATION WE DID A FEW--LAST 1564 00:57:45,750 --> 00:57:48,419 YEAR IN LANCET PUBLIC HEALTH. 1565 00:57:48,419 --> 00:57:49,253 THIS IS INSUFFICIENT SLEEP, THIS 1566 00:57:49,253 --> 00:57:53,424 IS THE AREAS IN OUR COUNTRY OF 1567 00:57:53,424 --> 00:57:56,928 INSUFFICIENT SLEEP, SAME LOOK OF 1568 00:57:56,928 --> 00:57:59,497 POOR GENERAL HEALTH, POOR MENTAL 1569 00:57:59,497 --> 00:58:02,633 HEALTH, POOR BRAIN HEALTH, 1570 00:58:02,633 --> 00:58:03,167 OBESITY AND HYPERTENSION. 1571 00:58:03,167 --> 00:58:04,802 SO I THINK THIS IS AN 1572 00:58:04,802 --> 00:58:07,405 OPPORTUNITY ALSO TO THINK ABOUT 1573 00:58:07,405 --> 00:58:09,373 REGIONS WHERE THERE IS BOTH 1574 00:58:09,373 --> 00:58:11,742 HEALTH DISPARITY AND HOW CAN WE 1575 00:58:11,742 --> 00:58:13,678 USE SLEEP AS SLEEP INSUFFICIENCY 1576 00:58:13,678 --> 00:58:15,246 AS 1 OF THESE HEALTH 1577 00:58:15,246 --> 00:58:16,414 DISPARITIES, SO I WANT TO THANK 1578 00:58:16,414 --> 00:58:18,683 THOSE OF YOU WHO ARE HERE AND 1579 00:58:18,683 --> 00:58:21,319 THOSE OF YOU ONLINE FOR 1580 00:58:21,319 --> 00:58:24,422 LISTENING TO ME AND ALSO THANK 1581 00:58:24,422 --> 00:58:26,090 YOU, THE NIH, FOR MANYIERS OF 1582 00:58:26,090 --> 00:58:26,924 FUNDING AND CONTINUOUS FUNDING 1583 00:58:26,924 --> 00:58:29,427 FOR THE WORK THAT WE AND MANY 1584 00:58:29,427 --> 00:58:32,697 OTHERS IN OUR FIELD DO AS WELL 1585 00:58:32,697 --> 00:58:36,801 AS TO THOSE WHO I--WHOSE WORK I 1586 00:58:36,801 --> 00:58:39,670 ACTUALLY MENTIONED HERE, YOU SEE 1587 00:58:39,670 --> 00:58:40,705 THEIR PICTURES AND REALLY A 1588 00:58:40,705 --> 00:58:43,107 GREAT TEAM OF COLLABORATORS 1589 00:58:43,107 --> 00:58:47,044 ACROSS NORTHWESTERN AND ALSO 1590 00:58:47,044 --> 00:58:47,745 ACROSS THE COUNTRY. 1591 00:58:47,745 --> 00:58:52,016 SO THANK YOU AGAIN. 1592 00:58:52,016 --> 00:58:54,252 >> I WOULD LIKE TO GET IN A 1593 00:58:54,252 --> 00:58:55,219 COUPLE QUESTIONS. 1594 00:58:55,219 --> 00:58:56,554 IS THERE ANYTHING, ANYBODY HERE, 1595 00:58:56,554 --> 00:58:58,856 PLEASE USE THE MICs, I CAN 1596 00:58:58,856 --> 00:59:01,592 HAVE 1 TO GET STARTED. 1597 00:59:01,592 --> 00:59:05,830 WHY IS THE CIRCADIAN CYCLE 24.2 1598 00:59:05,830 --> 00:59:08,799 HOURS, WHEN THE DAY IS 24 HOURS? 1599 00:59:08,799 --> 00:59:10,334 ALSO, HOW DOES THE CYCLE APPLY 1600 00:59:10,334 --> 00:59:12,637 TO HUMAN WHO IS HAVE LIVED FOR 1601 00:59:12,637 --> 00:59:14,272 THOUSANDS OF YEARS IN ARCTIC 1602 00:59:14,272 --> 00:59:17,542 REGIONS WHERE THE DAY-NIGHT 1603 00:59:17,542 --> 00:59:18,376 CYCLE VARIES RADICALLY? 1604 00:59:18,376 --> 00:59:21,646 >> IT'S NOT ALWAYS, I MEAN 1605 00:59:21,646 --> 00:59:24,849 HUMANS, YOU KNOW WE THINK IT'S 1606 00:59:24,849 --> 00:59:27,251 ABOUT 24.17 HOURS BUT IN ANIMALS 1607 00:59:27,251 --> 00:59:30,121 IT CAN BE SHORTER, THEY CAN BE A 1608 00:59:30,121 --> 00:59:31,255 LITTLE BIT LONGER, OFTEN BUT 1609 00:59:31,255 --> 00:59:33,724 THEN ALSO VERY CLOSE, ALWAYS TO 1610 00:59:33,724 --> 00:59:38,095 24 HOURS AND I THINK IT'S 1611 00:59:38,095 --> 00:59:38,596 ADAPTATION, RIGHT? 1612 00:59:38,596 --> 00:59:40,464 AND THIS IS WHY YOU WANT--THAT'S 1613 00:59:40,464 --> 00:59:42,233 WHY YOU NEED THE TIME GIVERS, 1614 00:59:42,233 --> 00:59:46,837 YOU NEED THE LIGHT, THE DARK, 1615 00:59:46,837 --> 00:59:48,673 THE FEED, ALL THESE THAT TRAIN 1616 00:59:48,673 --> 00:59:51,042 YOU TO BE IN SYNCHRONY WITH THE 1617 00:59:51,042 --> 00:59:51,809 24 HOUR. 1618 00:59:51,809 --> 00:59:53,744 AND WE CAN MESS THIS UP SO 1619 00:59:53,744 --> 00:59:55,680 EASILY RIGHT BY EATING AT THE 1620 00:59:55,680 --> 00:59:57,782 WRONG TIME, BY HAVING OUR SOCIAL 1621 00:59:57,782 --> 00:59:59,350 ACTIVITY, GETTING LIGHT AT 1622 00:59:59,350 --> 00:59:59,850 NIGHT, RIGHT? 1623 00:59:59,850 --> 01:00:03,821 AND ALL OF THESE THINGS ARE 1624 01:00:03,821 --> 01:00:05,189 DECREASING THEIR ABILITY FOR 1625 01:00:05,189 --> 01:00:08,559 THAT MOLECULAR SO I THINK FOR 1626 01:00:08,559 --> 01:00:11,529 ADAPTATION PURPOSES AND FROM AN 1627 01:00:11,529 --> 01:00:12,530 EVOLUTIONARY STANDPOINT. 1628 01:00:12,530 --> 01:00:15,333 NAND THE SECOND PART, 1629 01:00:15,333 --> 01:00:16,601 DETRIMENTAL EFFECTS LIVING SOME 1630 01:00:16,601 --> 01:00:19,203 DAYS IN COMPLETE DARKNESS, THE 1631 01:00:19,203 --> 01:00:22,773 ARCTIC REFERENCE ? 1632 01:00:22,773 --> 01:00:25,276 >> WELL, EVEN THERE THEY TRY TO 1633 01:00:25,276 --> 01:00:26,711 USE VERY SPARINGLY THEIR LIGHTS 1634 01:00:26,711 --> 01:00:29,380 BUT THEY DO TRY TO GET THESE 1635 01:00:29,380 --> 01:00:30,615 LIGHT-DARK CYCLES EMPLOY YOU 1636 01:00:30,615 --> 01:00:32,984 DON'T HAVE TO HAVE LIGHT IN THE 1637 01:00:32,984 --> 01:00:35,086 ENTIRE DAY FOR 8 HOURS, YOU 1638 01:00:35,086 --> 01:00:36,687 COULD ACTUALLY JUST HAVE IT AT 1639 01:00:36,687 --> 01:00:38,522 THE ENDS BECAUSE I DIDN'T HAVE 1640 01:00:38,522 --> 01:00:41,158 TIME TO TALK ABOUT HOW THE 1641 01:00:41,158 --> 01:00:44,528 CIRCADIAN CLOCKS SYSTEM RESPONDS 1642 01:00:44,528 --> 01:00:45,596 TO LIGHT, RIGHT, AT CERTAIN 1643 01:00:45,596 --> 01:00:47,565 TIMES OF THE DAY, IT WILL DELAY 1644 01:00:47,565 --> 01:00:49,200 THE RHYTHM AND OTHER TIMES OF 1645 01:00:49,200 --> 01:00:50,801 THE DAY WHERE IT WILL ADVANCE 1646 01:00:50,801 --> 01:00:52,303 ITG IMPEDIMENTS SO THIS IS HOW 1647 01:00:52,303 --> 01:00:54,338 WE THINK THE SYNCHRONIZATIONS 1648 01:00:54,338 --> 01:00:55,439 ARE OCCURRING IS THAT LIGHT IN 1649 01:00:55,439 --> 01:00:57,742 THE MORNING AND ALSO AT DUSK, 1650 01:00:57,742 --> 01:00:59,043 LIGHT EMPLOY SO THEY DO BUT IT 1651 01:00:59,043 --> 01:01:00,311 IS A PROBLEM, ABSOLUTELY. 1652 01:01:00,311 --> 01:01:04,515 IT IS A PROBLEM. 1653 01:01:04,515 --> 01:01:06,817 MOOD DISORDERS, I MEAN YOU LOOK 1654 01:01:06,817 --> 01:01:08,653 AT THE NORTHERN CLIMATES, RIGHT? 1655 01:01:08,653 --> 01:01:09,587 >> THANK YOU VERY MUCH. 1656 01:01:09,587 --> 01:01:10,721 COOL TALK. 1657 01:01:10,721 --> 01:01:13,758 MY QUESTION IS ABOUT--I HAD A 1658 01:01:13,758 --> 01:01:15,259 FEW--I WAS WONDERING ABOUT 1659 01:01:15,259 --> 01:01:16,293 PLASTICITY OF THESE TRAITS SO 1660 01:01:16,293 --> 01:01:19,764 LIKE WHEN YOU PUT--SOMEONE WHO 1661 01:01:19,764 --> 01:01:21,298 GETS--WHO HAS LESS SLEEP THAN I 1662 01:01:21,298 --> 01:01:25,169 WOULD LIKE, AS YOU--WHEN 1663 01:01:25,169 --> 01:01:27,805 SOMEONE'S CIRCADIAN CLOCK HAS 1664 01:01:27,805 --> 01:01:29,874 BEEN PERTURBED BECAUSE OF THEIR 1665 01:01:29,874 --> 01:01:31,942 BEHAVIOR, HOW EASY IS IT, IF THE 1666 01:01:31,942 --> 01:01:33,644 CENTRAL CLOCKS AND PERIPHERAL 1667 01:01:33,644 --> 01:01:35,713 CLOCKS ARE OUT OF WHACK HOW EASY 1668 01:01:35,713 --> 01:01:38,983 IS IT TO KIND OF PERTURB THEM 1669 01:01:38,983 --> 01:01:40,651 BACK IN SYNCH OR DOES YOUR BODY 1670 01:01:40,651 --> 01:01:42,353 ADAPT SPECIAL HOW DOES IT CHANGE 1671 01:01:42,353 --> 01:01:43,054 IF YOU AGE? 1672 01:01:43,054 --> 01:01:46,290 LIKE IF YOU HAVE HAD YEARS OF-- 1673 01:01:46,290 --> 01:01:48,592 >> YEAH, FOR MOST PEOPLE IF 1674 01:01:48,592 --> 01:01:49,860 THERE'S NOTHING UNDERLYING THAT 1675 01:01:49,860 --> 01:01:51,796 THEIR GENETIC CLOCK MAY NOT BE 1676 01:01:51,796 --> 01:01:53,964 SO LONG. 1677 01:01:53,964 --> 01:01:56,167 I HAVE PATIENT'S WHO CLOCK MAY 1678 01:01:56,167 --> 01:01:58,602 BE RUNNING AT 28, OR 26 HOURS 1679 01:01:58,602 --> 01:02:00,738 THEY BECOME NON24 HOURS SO THEY 1680 01:02:00,738 --> 01:02:03,374 CAN'T EVEN DRAIN TO THE 1681 01:02:03,374 --> 01:02:04,875 LIGHT-DARK CYCLE ALTHOUGH 1682 01:02:04,875 --> 01:02:05,776 VISUALLY INTACT, THEY'RE NOT 1683 01:02:05,776 --> 01:02:07,978 BLIND, RIGHT IN SO IT WILL 1684 01:02:07,978 --> 01:02:09,647 DEPEND BUT FOR A USUAL PERSON, I 1685 01:02:09,647 --> 01:02:11,449 THINK YOU CAN. 1686 01:02:11,449 --> 01:02:12,983 WE DON'T KNOW THAT MANY, MANY 1687 01:02:12,983 --> 01:02:16,187 YEARS OF THIS, I DON'T KNOW WHAT 1688 01:02:16,187 --> 01:02:18,723 THAT WOULD AFFECT BUT IN GENERAL 1689 01:02:18,723 --> 01:02:23,627 WE CAN USE LIGHT, MELATONIN, 1690 01:02:23,627 --> 01:02:26,697 TIMING OF MEALS AND EXERCISE. 1691 01:02:26,697 --> 01:02:28,532 ALL THESE CAN BE TIME GIVERS FOR 1692 01:02:28,532 --> 01:02:30,167 THE CLOCK AND IT'S VERY 1693 01:02:30,167 --> 01:02:31,569 IMPORTANT, THE TIMING OF IT, IF 1694 01:02:31,569 --> 01:02:33,871 YOU GET THESE THINGS AT THE 1695 01:02:33,871 --> 01:02:35,072 WRONG TIME, YOU ACTUALLY CAN DO 1696 01:02:35,072 --> 01:02:36,607 THE OPPOSITE OF WHAT YOU REALLY 1697 01:02:36,607 --> 01:02:39,043 WANTED TO DO SO MELATONIN CAN 1698 01:02:39,043 --> 01:02:42,513 SHIFT YOUR RHYTHM, EITHER MORE 1699 01:02:42,513 --> 01:02:44,014 IN THE FORWARD DIRECTION WHEREAS 1700 01:02:44,014 --> 01:02:45,449 LIGHT CAN ACTUALLY DO BOTH, SO 1701 01:02:45,449 --> 01:02:48,519 TIMING OF THAT IS VERY 1702 01:02:48,519 --> 01:02:49,386 ESSENTIAL. 1703 01:02:49,386 --> 01:02:52,056 SO CERTAINLY WE CAN MANIPULATE 1704 01:02:52,056 --> 01:02:56,794 THE CLOCK >> OKAY, WELL, I HOPE 1705 01:02:56,794 --> 01:02:58,462 THIS IS THE RIGHT TIME, JUST 1706 01:02:58,462 --> 01:02:59,263 REMINDING EVERYBODY THAT THERE 1707 01:02:59,263 --> 01:03:00,765 ARE LIGHT REFRESH AMS OUTSIDE 1708 01:03:00,765 --> 01:03:06,003 AND PLEASE JOIN ME IN THANKING 1709 01:03:06,003 --> 01:03:06,237 DR. ZEE. 1710 01:03:06,237 --> 01:03:06,604 >> THANK YOU. 1711 01:03:06,604 --> 01:03:07,304 THANK YOU. 1712 01:03:07,304 --> 01:03:10,641 KD--SALLY ARK PLAWZ 1713 01:03:10,641 --> 01:03:20,851 [ APPLAUSE ]