ADVISORY COUNCIL ON AGING. >> RIGHT. GOOD MORNING EVERYONE. I'M JUST GOING TO ASK WHO'S ON THE LINE AT THE MOMENT SO CAN YOU IDENTIFY YOURSELF IN YOU'RE ON THE PHONE. >> [SPEAKING AT ONCE ] >> ONE AT A TIME. >> EILEAN KRIMMINGS. >> AMY WAGER. >> THANK YOU AMY AND. >> ALLISON [INDISCERNIBLE]. >> OKAY, THANKS SO WITH THAT WE WILL LAUNCH INTO THE DIRECTOR'S STATUS REPORT AND DR. HO DR. HO--DR. HODES IS AT THE PODIUM. >> WELL, THANK YOU AND WELCOME THIS YEAR, THE REMARKS WILL BEGIN AS ALWAYS WITH A LITTLE REVIEW OF SOME BUDGET ISSUES BUT THIS TIME RATHER HISTORIC LEVEL OF TIMELINESS AND DYNAMICS. SO MANY OF YOU MAY BE AWARE, I THINK THE SCORE'S ONLY LIKE 22 YEARS SINCE WE'VE ACTUALLY HAD A BUDGET APPROPRIATION BEFORE THE BEGINNING OF THE FISCAL YEAR, THAT MEANS THAT EVERY YEAR AROUND THIS TIME WE DON'T HAVE A BUDGET AND THE OPTIONS ARE THAT WE WILL HAVE A CONTINUING RESOLUTION TO LET US KEEP GOING FOR A WHILE WITH THE FINAL BUDGET RESOLUTION COMING SOMETIME IN THE SPRING OR WE HAVE THE THREAT OF A SHUT DOWN HAPPENING. NOTHING IS CERTAIN AS YET BUT IF YOU'VE BEEN FOLLOWING THE NEWS, YOU WILL KNOW THAT FOR THE FIRSTIME IN A LONG WHILE THERE ARE NOW HOUSE AND SEABT COMPATIBLE LANGUAGE PRESENTATIONS THAT OVER THESE NEXT DAYS WILL BE EXAMINED WITH PUNDITS ESTIMATE OR BETTER CHANCE THEY WILL HAVE A BUJ ELT AND APPROPRIATION BEFORE THE END OF THE YEAR AND YOU CAN IMAGINE ABOUT DISCUSSIONS ABOUT TRYING TO MANAGE OUR UNCERTAINTIES OF PAY LINES AND STRATEGIES IF WE ACTUALLY KNEW OUR BUDGET AS WE WENT INTO THE YEAR, HOW MUCH BETTER THIS WOULD BE IF ARE OUR ABILITY TO SUPPORT RESEARCH. SO IN TERMS OF WHERE WE ARE IN THE 2019 MINIBUS APPROPRIATION. MANY OF HAVE YOU HEARD OMNI BUS, THIS IS A TOTAL BUDGET FOR ALL AGENCIES, THIS YEAR IS THE STRATEGY IS A NUMBER OF MINIBUSES, NOT SO MANY, IS THE 1 THAT EFFECTS NHS AND NIH AS WELL AS DEFENSE. SO 2 OF THE LARGEST COMPONENTS OF THE FEDERAL BUDGET EXCUSE ME ARE IN THIS MINIBUS WHICH IS MAKING ITS WAY THROUGH. AND INTO LAST NIGHT WE WERE LOOKING THROUGH THE EMERGING LANGUAGE TO TRY AND READ AND SUMMARIZE FOR YOU WHERE WE STAND. SO RIGHT NOW WHAT THE BUDGET LOOKS LIKE IN THE MINIBUS WHICH I EMPHASIZE AGAIN AS NOT BEEN COMPLETED OR PRESENTED BOT PRESIDENT AND CERTAINLY NOT SIGNED INTO LAW WOULD HAVE AN NIH BUDGET AND FY19 OF 3.08 BILLION DOLLARS THAT'S AN INCREASE FROM 2.57 O A LITTLE OVER 500 MILLION-DOLLAR INCREASE FOR NIA, THE COMING YEAR OVER THIS YEAR. AND OF THAT $425 MILLION OF THE INCREASE WOULD BE TARGETED TO ALZHEIMER'S RELATED DISORDERS. THE NIH TOTAL WOULD GO TO 39.08 BILLION WHICH IS 2 BILLION DOLLARS INCREASE OVER THE CURRENT FISCAL YEAR FY18. SO A 2 BILLION DOLLAR INCREASE FOR NIH OF WHICH 500 MILLION AND A BIT MORE WOULD BE GOING TOA. THE LANGUAGE YOU RECEIVE HERE REFLECTS THE COMMITMENT TO ALDZ HYMER'S RESEARCH. BOTH CHAMBERS HAVE PASSED A BILL TO ADDRESS DIFFERENCES AND THEN TELL BE PRESENTED TO GO INTO LAW AND DISCUSS ASPECTS OF THIS ONCE WE GO THROUGH OTHER INFORMATION SHARING BUT IT'S WHERE WE ARE AND FROM OUR HO HOUR, DAY-TO-DAY WE'RE HOPEFUL WE CAN HAVE A MUCH MORE ORDERLY ABILITY FOR RESEARCH THAN WE'VE HAD IN RECENT YEARS WITH A BUDGET IN PLACE AT THE BEGINNING OF THE FISCAL YEAR. SO THIS PAST PRESENT YEAR NOW COMPLETING HAS BEEN A VERY GOOD 1 FOR NIH WHETHER IT WAS A MULTIBILLION DOLLAR INCREASE OVERALL AND A SUBSTANTIAL INCREASE FOR NIA AGAIN AND THOSE ALLOWED US TO PROVIDE PAY LINES FOR FUBDING THAT REALLY HAD HISTORIC HIGHS FOR US. SO IN THE GENERAL PAY LINE THAT IS TARGETING ALZHEIMER'S DEMENTIA. ROBIN WHICH IS IT PROFESSOR OF BIOLOGY LICKLY ANNOUNCED. >> WEDNESDAY. >> I BRING OLD NEWS. >> IT WAS THE 23rd PERCENTILE, LESS THAN 500,000 WITH OUR SPECIAL CONSIDERATION FOR NEW AND EARLY STAGE INVESTIGATORS AND SOMEWHAT LOWER PAY LINE FOR MORE EXPENSIVE APPLICATIONS OVER 500,000. THE ALZHEIMER'S RELATED DISORDER PAY LINE 28th PERCENTILE AGAIN WITH EARLY STAGE AND LOWER PAY LINES FOR THE MORE EXPENSIVE AWARDS. WE'RE EXTREMELY GRATIFIED. AND THESE IT AV AND NONAV EXISTS AND BUT AT A MUCH MORE AH PICIOUS LEVEL THAN WE'VE HAD IN RECENT YEARS AND WE'LL SEE AS WE FIND OUT WHATAUR BUDGETS LOOK LIKE IN NEW YEAR AND PROJECTIONS WHETHER WE CAN AND RECOGNIZING THAT OUR APPLICATIONS THAT ARE NOT PERCENTILE THROUGH CSR REVIEW, AND HAVE INSTEAD PRIORITY SCORES, WE AGAIN HAVE FAR HIGHER THRESHOLDS HERE FOR GENERALLY THE PORE EXPENSIVE AND COMPLEX AWARDS WE'VE HAD BEFORE WITH THE PRIORITY SCORES LISTED HERE AS PAY LINES. AND TRAINING AND CAREER DEVELOPMENT AS WE'VE TALKED ABOUT TO A GREAT EXTENT INCLUDING WITH COUNCIL AND THE RECENT REVIEW OF THE DIVISION OF NEUROSCIENCE, MORE GENEROUS PAY LINES HAVE BEEN ABLE TO HAVE BEFORE. WE HOPE TO DO EVEN BETTER AS WE ATTRACT MORE APPLICATIONS FTs AND Fs AND CAREERS OF THE DIFFERENT YALE PAY LINE HERE BETWEEN THE GENERAL AND ALZHEIMER'S PAY LINES. SO THE BYPASS BUDGET. THIS IS SOMETHING WE TALKED ABOUT FOR THE LAST 3 YEARS AND THE MOST RECENT BYPASS BUDGET IS NEW SINCE OUR LAST COUNCIL MEETING, THIS IS THE ALZHEIMER'S DISEASE, RELATED DEMENTIAS, BYPASS BUDGET WHICH IS THE RESPONSE TO LEGISLATION THAT REQUIRES EACH YEAR THROUGH 2025 FOR THE NIH DIRECTOR TO SUBMIT TO CONGRESS A PROFESSIONAL JUDGMENT BUDGET OF THE INCREASE IN FUNDS OVER CURRENT FUNDING LEVEL NEEDED TO SUSTAIN MAXIMAL EFFICIENCY AND PACE ARE AIMS AND PROGRESS OF THE GOALS OF THE NATIONAL PLAN INCLUDING OUR TARGETED 2025 SUCCESS AND MAKING SIGNIFICANT DIFFERENCES AND PREVENTING TREATING OR SLOWING THE PROGRESSION OF ALZHEIMER'S. THE PROCESS LOOKS LIKE THIS. WE RELY IN THIS BYPASS BUDGET ON A VERY SERIOUS AND SUBSTANTIVE PROCESS FOR GENERATING OUR ESTIMATE--OUR BEING NIH ESTIMATE OF FUNDS NEEDED. THIS IS NOT A GENERIC OR SUBJECTIVE OR SENSE OF WHATY - NEED, IT'S BUILT FROM A SERIES OF PROMULGATEITS, ALZHEIMER'S SUMMITS, DISORDER SUMMITS, MOST RECENTLY THE ALZHEIMER'S CARE SUMMITS, ALL OF WHICH PROVIDE INPUT FROM HUNDREDS OF SCIENTISTS, NATIONALLY AND GLOBAL TO LET US GENERATE FIELDS OF ESTIMATE PRIORITIES AND THOSE PRIORITIES ARE THEN WHAT DRIVES THE GENERATION IN THE BYPASS BUDGET SO OUR INPULT AS YOU'VE SEEN HERE THROUGH OUR MEETINGS IN 2017 AND 2018 THEN DEVELOPED WITH THE HELP OF STAFF AT NIH, NINDS AND OTHER INSTITUTES AND I'LL ELABORATE TO ATTACH MILESTONES AND ACHIEVE A COST AND WE BUILD UP TO THE PROFESSIONAL JUDGMENT OR BYPASS BUDGET. STRESS THE BYPASS ASTHMAPOLIS SPECT OF IT AS THOUGH THIS DOES NOT GO THROUGH A USUAL PROCESS OF NEEDING CLEARANCE AND APPROVAL FOR THE WHITE HOUSE AND THE DEPARTMENT FOR CONGRESS, IT IS A REQUIREMENT FOR A DIRECT PRESENTATION TO CONGRESS WITH OPPORTUNITIES FOR COMMENT BUT NOT FOR MODIFICATION BY THE DEPARTMENT OR BY THE WHITE HOUSE. THIS YEAR SOME 13 CENTERS AND INNSITUTES OF NIH PARTICIPATED WITH US IN MEETINGS DESIGNED TO FORMULATE OUR PRIORITIES PLANS DRIVING TO THE BYPASS BUDGET. THE BOTTOM LINE THAT YOU'LL SEE WITH ELABORATION ON HOW IT IS GENERATED AND WHAT IT MEANS WAS AN ADDITIONAL $477.125 MILLION ABOVE CURRENT LEVELS IN FY2020. SO 2018 AS HAVING BEEN RELEASE INDEED JULY. WE ARE PROVIDING THE BYPASS BUDGET FOR 2020 OF THE ADDITIONAL FUNDS NEEDED IN THAT YEAR. THE ORGANIZATION OF CATEGORIES HAS BEEN BASED ON THE CADRO RESEARCH ONTOLOGY GENERATED A FEW YEARS AGO AND ORGANIZA AS AN ORGANIZING PRINCIPLE THE VARIOUS MILESTONES AROUND WHICH THE BYPASS BUDGET IS FORMULATE TD. THIS IS A TABLE THAT ILLUSTRATES FOR EACH OF THESE HIGH LEVEL CATEGORIES THE FUNDING WHICH ADDS UP TO THE 477 MILLION-DOLLAR PLUS INCREASE. JUST TO ILLUSTRATE THE APPROACHES, THE FY18 LEVEL, THE LEVEL WE JUST COMPLETED ALZHEIMERIME HIGHER'S--ALZHEIMER'S BUDGET, THE PRESIDENT'S IS THE STANDING BUDGET PROPOSAL FROM THE ADMINISTRATION IS A VERY SUBSTANTIAL CUT TO 1.516. AND THAT'S $399 MILLION. SO RELEVANT TO THE PRESIDENT'S AND IT'S ABOVE OUR CURRENT FY18 AND 29 MILLION LESS THAN THAT IN FY19 SO RELATIVE TO THE PRESIDENT'S BUDGET WE NEED TO BOTH MAKE UP THE 399 AND ADD THE 477 BUT THE RELEVANT BOTTOM LINE NUMBER IS IN FACT IS THAT THE TOTAL RESOURCES NEEDED WOULD BE 3.29 BILLION DOLLARS. WE ARE TRACKING FOR OURSELVES AND FOR PURPOSES OF TRANSPARENCY IN SHARING WITH THE PUBLIC THE EYE DROP PORTFOLIO ANALYSIS INTERACTIVE DATABASE THAT SHOWS ALL OF THE RESEARCH SUPPORT BY ALL OF NIH. BUT TO IT WE TRACK UNDER THESE CASUAL CATEGORIES LINKS TO THE MILESTONES THAT ARE IN THE PLAN. SO IT ALLOWS US AND YOU TO SEE AS WE LOOK AT THE RESEARCH ACTIVITIES THAT ARE ONGOING DOCUMENTED GRANTS AWARDS AND INITIATIVES HOW THOSE TRACK TO THE COMPONENTS OF THE BYPASS BUDGET PRIORITIES MILESTONES AND PLAN. SO JUST A FEW MORE BITS OF INFORMATION ABOUT CURRENT EVENTS. WE HAD THIS PAST SUMMER, AGAIN, THE ANNUAL EVENT WE LOOK FORWARD TO. THE AMS HYM EROZAN SO ASSOCIATION IN CHICAGO. THERE WAS AN OPPORTUNITY AS ALLUDED TO AND GRATEFUL FOR THE LEADERSHIP OF THE ASSOCIATION FOR THIS WORKING TOGETHER, WE WERE ABLE TO HAVE A SYMPOSIUM, PLENARY SYMPOSIUM, PLENARY BY THE FACT THAT YOU CAN'T EVEN SEE THE SPEAKER, ME, IN THIS LARGE ROOM WELL PROJECTED BUT IT WAS AN OPPORTUNITY TO TALK ABOUT ACCOMPLISHMENTS THAT HAVE ESTABLISHED INFRASTRUCTURE AND FOR THE COMMUNITIES AND WEB CONNECTED SPITE OUR EFFORTS WE HAVE TO DO MORE THAN WE CAN TO LET THE EVERYONE KNOW ABOUT COMMUNITIES AND MAXIMIZE RECRUITMENT OF GOOD SCIENCE AND GOOD SCIENCE PROPROSALS AND THIS WAS A WONDERFUL OPPORTUNITY TO DO THAT FOR PARTICIPATES IN THE CONFERENCE. WE ALSO HAD COUPLE OF OPPORTUNITIES THAT APPROPRIATIONS HEARINGS TO PARTICIPATE. THIS IS THE ILLUSTRATION HERE FRANCIS COLLINS TO THE APPROPRIATION HEARING OF LAST MONTH WHICH WAS AGAIN ALWAYS A WELCOME OPPORTUNITY DIRECTLY WITH OUR APPROPRIATORS WHO HAVE ALWAYS BEEN SO SUPPORTIVE AND ONCE AGAIN THE BIPARTISAN SUPPORT IN BOTH THE HOUSE AND SENATE WHICH IS A SELF-DECLARED GRADDIFYING EXPERIENCE FOR THE CONGRESSIONAL MEMBERS THEMSELVES AND NOT CONSIST AND THEN THE CONTINUES AND WE THANK ALL OF YOU WHO HELP US IN THAT EFFORT BUT WE'VE BURN CERTAINLY FORTUNATE AND INDEED BLESSED TO HAVE IT KIND OF SUPPORT. OTHER EVENTS, SEPTEMBER IS GO FOR LIFE MONTH. EVEN AS WE SIT HER SEDENTARY EPTARY MAYBE WE WILL HAVE MORE 5 MINUTE BREAKS AS INNOVATIVE BY ROBIN IN THE SPIRIT OF GO FOR LIFE AND GO FOR LIFE MONTH. ONE WAS FACEBOOK LIVE, SORRY WE MISSED IT BECAUSE WE WERE HERE SITTING. EACH YEAR WE HAVE A REGIONAL MEETING AND GO TO A DIFFERENT AREA OF THE COUNTRY AND ASKLET SPONSORING HOST INSTITUTION IN THAT LOCATION TO BRING TOGETHER THROUGH INVITATION PARTICIPANTS FROM THAT GENERAL IN PARTICULAR, PAYING ATTENTION TO THOSE WHO DON'T NORMALLY CONTACT EASILY SO THIS CASE WE ARE HAPPY TO SAY THAT NOVEMBER 1 WILL BE AT THE UNIVERSITY OF KANSAS AND IT'S NOT JUST THE UNIVERSITY OF KANSAS AND THAT MEDICAL SCHOOL AND CENTER THAT WILL BE PARITICIPATING BUT THERE WILL BE OTHER INSTITUTIONS, 4 YEAR COLLEGES, 2 YEAR COLLEGES, ACADEMIC INSTITUTIONS THAT DON'T USUALLY INTERACT WITH NIH AND IT'S A CHANCE TO PROVIDE OUTREACH TO THESE ORGANIZATIONS AND TRY TO BRING THEM INTO THE RESEARCH FOLD. I THINK I FIRST MET MARIE AT OUR EVENT IN OKLAHOMA AND THAT WAS INDEED WORTH THE PRICE OF THE EVENT ALL BY ITSELF. SO, WE ARE EXCITED ABOUT THIS. IT WILL BE HOSTED BY THE UNIVERSITY AND SOME OF OUR GRANTEES THERE. WE EVEN--THAT'S WOE DON'T PUT IT ON PAPER BECAUSE WE CAN BE THE BE SURE ARE HOPING FOR THE EXPRESSED INTEREST OF SOME CONGRESSIONAL AATTENDANCE AND REPRESENTATION AT THIS WHICH WILL BE A GREAT MESSAGE TO HAVE POLICY MAKERS TOGETHER WITH THE PUBLIC AND NIH/NIA PRESENT FOR THIS EVENT. UPCOMING SUMMITS, THE ADRD, THE SUMMIT WITHIN NINDS AND THE LEAD WORKING WITHIN NIA AND MARCH 14 AND 15. I HOPE AS MANY OF YOU AS POSSIBLE WILL BE ABLE TO ATTEND THAT IN PERSON OR ONLINE. IN MARCH 24-25 OF 2020 WILL BE THE SECOND ADRD CARE AND SERVICES SUMMIT HERE IN BETHESDA AND WE'LL TAKE THE LEAD IN ORGANIZING THIS. OTHER UPDATES SO THERE ARE 2 NEW INSTITUTE DIRECTORS HERE AT NIH. NCCIH, NANZ--NATIONAL CENTER FOR COMPLIMENTARY AND CONTEMPORARY HEALTH, SPANS WILL ILITRATION OF RIGOROUS AND COLLABORATIVE INTEGRATIVE SCIENCE AND WILL BE A WONDER EDITION TO NIH LEADERSHIP LEAD THAGOREAN INSTITUTE AND MORE RECENTLY THE ANNOUNCEMENT THAT BRUCE STROMBERG WOULD BE THE NEW DIRECTOR OF NIBIBIB, NATIONAL EN--STRATEGIESITUTE OF BIOMEDICAL EMERGENCYING AND MEDICINE, IT WILL RESEARCHES THE KINDS OF TECHNOLOGIES THAT ARE IMPORTANT TO ALL OF THESE. SO WE'RE LOOKING FORWARD TO THESE 2 NEW COLLEAGUES COLLEAGUES AND WE'L L MAKE PLANS TO HAVE THEM COME AND MEET WITH OUR COUNCIL WITH YOU AS WELL. ALWAYS TRY TO PROVIDE A WAY FOR TO TO STAY INFORMED AND CONNECTED THROUGH VISITS VISITS AND OUTREACH THROUGH BLOGS AND STOP THERE TO ASK FOR ANY QUESTIONS THAT YOU MAY HAVE. APPLAUSE IS NOT CUSTOMARY ON THIS EOCCASION BUT THANK YOU. [ APPLAUSE ] >> QUESTIONS FOR DR. HODES. TIONZ--YOU'VE HEARD FROM STAFF, OBSERVED YOURSELF THE HEROIC EFFORTS THAT HAVE BEEN NEEDED THIS PAST YEAR TOWARDS THE END OF THE YEAR SUCH AS THIS TO COMPLETE THE PROCESS OF MAKING DECISIONS AND AWARDING GRANTS AND THAT'S BECAUSE WE DON'T KNOW OW BUDGET UNTIL THE SPRING AND WE THEREFORE HAVE TO DELAY THE FINAL PROCESS OF APPROVAL AND FUNDING. IF WE WERE THIS YEAR ABLE TO BEGIN THAT AT THE BEGINNING OF THE YEAR IN OCTOBER, THIS WOULD BE AN ENORMOUS DIFFERENCE PROVIDING DIFFERENCES TO INVESTIGATORS IN A TIMELY FASHION, PERHAPS MONTHS EARLIER THAN WOULD HAVE BEEN POSSIBLE AND BY THAT, LONE ACCELERATING THE PAYS OF RESEARCH AND PROVIDING A MORE PALLETTABLE LIFESTYLE FOR SOME OF OUR STAFF FOLK WHO IS ARE OTHERWISE SO STRESSED AT THE END OF THE FISCAL YEAR SO WE HOPE THIS HAPPENS. >> DR. HARDIN. >> MORNING AND THANK YOU. AS WE MOVE FORWARD IN ANTICIPATION OF WHAT MIGHT OCCUR IN TERMS OF THE PRESIDENT'S BUDGET AND PROJECTED DEVELOPMENTAL DEFICIT, WHAT ARE CURRENT THOUGHTS ON HOW WE MIGHT APPROACH THAT PROCESS OF MAKING UP THOSE FUNDS? >> IF YOU ARE ASKING ME TO COMMENTOT FEDERAL BUDGET DEFICIT, I THINK THAT'S BEYOND ME BUT AGAIN, I WOULD ONLY EMPHASIZE THAT AT A TIME WHEN THERE ARE FISCAL CONSTRAINTS OF NECESSARY BEING CONSIDERED AND APPLY INDEED SO MANY PLACES ACROSS THE FEDERAL GOVERNMENT, WE ARE ENORMOUS LOW GRATIFIED THAT THERE REMAINS THE EXTRAORDINARY SUPPORT FOR NIH THAT HAS EXISTED AND APPEARS TO BE MAINTAINING ITSELF THROUGH THE NEXT BUDGET. SO IN THE PAST PRIOR 3 YEARS THERE HAVE BEEN INCREASES OF NIH WIDE, 2 PLUS 3 PLUS 2 BILLION, THIS IS A RATE OF GROWTH THAT I THINK MANY OF US THINK IS PRECISELY WHAT'S NEEDED FOR A HEALTHY RESEARCH ENVIRONMENT IN WHICH INVESTIGATORS--POTENTIAL INVESTIGATORS, THE BRIGHTEST OF THE YOUNG PEOPLE WHO ARE DECIDING WHAT KIND OF CAREER TO FOLLOW MAY HAVE THE EXAMPLE NOW OF SEVERAL YEARS AGO AND CONTINUED GROWTH AND THE KIND OF STABILITY AND PROMISE AND RESEARCH SUPPORT THAT WE HOPE WILL MAKE A DIFFERENCE IN RECRUITING ALL THE MORE OF THE NEW PEOPLE INTO THE FIELD AS HAD AS RETAINING THE RESEARCH CAPACITIES OF THOSE ALREADY HERE. SO WE WISH WELL OF COURSE FOR THE WHOLE FEDERAL AND BUDGET PROCESS WE'RE ENORMOUSLY GRAT FIGHTIFIED AT THE PARTICULAR NIH AND MEDICAL RESEARCH HAVE RECEIVED THESE PAST YEARS. >> THANK YOU DR. HODES. GOING ON TO IF YOU LOOK AT FUTURE MEETING DATES YOU NOTICE WE BECOME WANDERERS NEXT YEAR AND THAT'S BECAUSE THE ROOM THAT WE'RE IN AND THE ROOM--THE OTHER SIDE OF THE HALL ARE GOING TO BE RENAL RENOVATED AND THEY'RE FOR WE'LL BE IN BUILDING 45 IN JANUARY, THAT'S STILL ON CAMPUS AND BUILDING 60 IN MAY WHICH IS STILL ALSO ON CAMPUS BUT IN SEPTEMBER WE TREK UP TO NORTH BETHESDA TO THE NEUROSCIENCE BUILDING THERE. SO WE WILL HAVE--VISITING DIFFERENT ROOMS OVER THE NEXT YEAR. I NOW NEED A MOTION TO CONSIDER THE MINUTES FROM OUR MAY MEETING. MOTION? ALL RIGHT. SECOND? ALL RIGHT. DO YOU TO BRING UP ANYTHING FROM THE MINUTES FROM THE LAST MEETING. OKAY, ALL THOSE IN FAVOR, RAISE YOUR HANDS. THANK YOU. ANYONE OPPOSED OR ANY COUNCIL MEMBER ON THE PHONE OPPOSED? ALL RIGHT. THE MINUTES ARE APPROVED. WELL, THEN, WE'LL MOVE ON TO THE NEXT ITEM ON THE AGENDA ALMOST AS YOU'RE GETTING READY TO PRESENT THE TASK FORCE ON MINORITY AGING RESEARCH AND DR. MARIA CARRILLO WILL INTRODUCE THAT. >> GREAT, THANK YOU VERY MUCH. AND I JUST WANT TO THANK DR. CARL HILL FOR ACTUALLY LEADING THIS TASK FORCE AND WORKING WITH MYSELF, MY PREDECESSOR DR. WUTAN WHO RETIRED FROM COUNCIL AND FOR DR. HARDIN WH O AGREED TO TAKE ON THIS ROLE AS CHAIR SINCE THIS IS MY LAST MEETING AND--I WON'T BE HERE ANYMORE, IT'S SAD FOR ME BUT IT'S BEEN A GREAT EXPERIENCE AND I WANT TO START OFF THAT WE KNOW AND RECOGNIZE THE FACT THAT CARL HILL MAKES THIS WORK AND BRINGS ALL OF THESE GREAT TOPICS AND IDEAS TO US AND WE WORK TOGETHER AS A TEAM BUT HE IS DEFINITELY THE MOVEMENT BEHIND THE WHEEL. SO THANK YOU VERY MUCH DR. HILL FOR ALL OF THAT SUPPORT. THIS IS A VERY QUICK OVERVIEW OF JUST WHAT I WILL TALK ABOUT OVER THE NEXT FEW MACHINEUES. I FEEL SHEEPISH GIVING DR. MARRY BERNARD'S TALK AS SHE GAVE A GREAT TALK THAT SHE'S BEEN A PART OF AND THEN, SO PARDON ME, DR. BERNARD IF I MAKE ANY ERRORS BECAUSE I'M CERTAINLY NOT GOING TO BE ABLE TO DO JUSTICE TO YOUR FABULOUS TALK. AND ALSO HEARD SOME--A REALLY GREAT TALK FROM DR. HECTOR GONZALEZ AT THE DEPARTMENT OF NEUROSCIENCES AT UCSD. SO THAT'S WAY WILL GO THROUGH AND I WILL START AGAIN, HOW EMBARRASSING TO GIVE MARIE BERNARD'S TALK BUT SHE TALKED TO US ABOUT THE RESTEPS THAT VILLAIN HAVE BEEN TAKEN TO THE REVIEW ENVIRONMENTS OF THE 21st SEBILITIRY ACT. SO THIS IS SOMETHING WHEN WE DO HAVE THE TEST FOR AGING AND RESEARCH, WE LEARN A LOT BECAUSE THERE'S A LOT THAT I THINK AS COUNCIL MEMBERS WE DON'T KNOW WHAT'S GOING ON ACROSS THE NIH AND THIS IS AN OPPORTUNITY FOR US AS COUNCIL MEMBERS TO RECOGNIZE THAT, LEARN FROM IT AND THEN BRING IT BACK TO COUNCIL AND SEE HOW WE CAN WORK WITH IT AND IMPLEMENT IT AND ASK GOOD QUESTIONS BECAUSE WE KNOW PROGRAM STAFF WILL THINK ABOUT IT AS WELL. SO THIS IS SOMETHING THAT ACTUALLY, I DID NOT KNOW ABOUT AND SO THE INCLUSION ACROSS THE LIFE SPAN AND SHE START WIDE A TIMELINE WHICH I THINK HELPED FRAME ALL OF THE ISSUES AND YOU WILL NOTICE IN THE BOLD FROM 1998 THE INCLUSION OF CHILDREN WAS A REQUIREMENT FROM NIH BROADLY. IN 2015 SHE NOTED THAT IT WOULD CHANGE THE DEFINITION OF CHILDREN TO INCLUDE INDIVIDUALS THAT WERE 18 AND UNDER 18 BECAUSE PEOPLE I THINK WERE USING THE 21 AS KIND OF AN EASIER WAY TO DEAL WITH THE REQUIREMENT. BUT I THINK IN 2016 NEW RIERPTS ON AGE CAME INTO PLAY AND SO DR. MARRY BUR N ARD TALKED TO US ABOUT HOW THAT WENT. THIS IS A SHOT OF THE ACT THAT WAS ENACTED BY CONGRESS AND THE REQUIREMENT THAT WITHIN 180 DAYS THERE WAS ACTUALLY A WORKSHOP AND PUBLISHED DATA ON WHAT WAS GOING ON THROUGH NIH, THROUGHOUT NIH INCLUDING PEDIATRIC SUBGROUPS AS WELL. SO THIS WAS ACTED UPON OF COURSE WITHIN THE TIMELINE BECAUSE IT IS A CONGRESSIONAL MANDATE AND DR. BERNARD TALKED TO US ABOUT THIS GREAT WORKSHOP WITH OVER 150 PEOPLE THAT TOOK PLACE AND IT WAS WITHIN THE TIME SPAN REQUIRED BY CONGRESS AND AWARE THAT WOULD DISCUSS THE CHALLENGES AND BARRIERS AND THE 2 SIDES OF THE AGING SPECTRUM AND CHILDREN AND OLDER ADULTS AND HOW TO MAKE SURE THAT CHILDS WERE INCLUSIVE. THERE WERE PROMINENT INDIVIDUALS THERE ARE THERE, THERE ARE PARTS OF MACHINERY, SUSTAIN, AND JOURNAL EDITORS AND FUNDERS, ET CETERA AND YOU CAN SEE THERE'S DR. HODESOT FRONT ROW THERE. SO A BASE LINE NIH ANALYSIS WAS DONE AND AGAIN, SOMETHING THAT IS NOT VERY EASY TO DO BUT IT GOT TURNED OUT BECAUSE THEY HAD EXAMINED TOP 10 DISEASES THAT CAUSED HOSPITALIZATIONS, ET CETERA FOR OLDER ADULTS AND ANALYZED INFORMATION ON WHAT IS INCLUSION AND EXCLUSION FOR THESE TYPES OF CLINICAL TRIALS THAT COULD ALSO BE IMPEDIMENTS FOR PARTICIPATION OF OLDER ADULTS AND LIKEWISE IN CHILDREN NIH FUNDED GRANTS AND ASSOCIATED PUBLICATIONS WERE REVIEWED. AND AGE WAS QUOTED ACCORDING TO ENROLLMENT BUT THEN ALSO FOLLOW UP STUDIES AND PUBLICATIONS BECAUSE THAT'S IMPORTANT, YOU MIGHT INCLUDE THEM IN YOUR CLINICAL TILE, AND THEN YOU DO YOU INCLUDE THEM INTO THE ANALYSIS THAT GOES INTO THE PUBLICATION. SO THIS WAS--I WILL INN CLUED THE SUMMARY OF THE ADULT FINDINGS IN HERE FOR US IS WHERE THE COUNCIL ON AGING BUT SO FOR DISEASE IS PROMINENT AMONG PEOPLE OF OLDER AGE MANY TRIALS OFTEN EXCLUDED PARTICIPANTS AND 27% OF STUDIES HAD ARBITRARY UPPER AGE GAPS. WE KNOW THERE ARE MANY GOOD REASONS TO HAVE AGE BRACKETS, BUT IN SOME CASES THOSE ARE ACTUALLY ARBITRARY AND FOR THOSE TYPES OF STUDIES, I THINK THAT IT IS GOING TO BE TALK TO THOSE INVESTIGATORS TO BE MORE ENCLUESIVE AND THERE WERE ALSO INDIRECT EXCLUSION FACTORS THAT APPLIED. WE ALL KNOW THAT FROM CLINAL STUDIES AND CO MORBID CONDITIONS WERE 1 AND POLYMORPHISMS WAS ANOTHER. WE THINK SOMETHING THAT FOLKS BROUGHTUP WAS THAT THESE PARTICIPANTS MAY NOT REPRESENT REAL WORLD POPULATIONS WITH THE DISEASE AND THAT IS AN ISSUE OF COURSE THESE ARE ESPECIALLY CLINICAL TRIALS AND FUNDED BY FEDERAL DOLLARS SO IT'S A LOT OF MONITOR THAT'S GOES TOWARD THESE THIS IS SOMETHING AN ISSUE THAT WE ALSO TALKED ABOUT AND THESE ARE INCLUSIVE UNDERREPRESENTED POPULATIONS AND LOWER SOCIAL ECONOMIC STATUS ET CETERA AND THAT WAS BROUGHT UP DURING OUR TASK FORCE DISCUSSION AND THE QUESTIONS AND ANSWERS, BUT I THINK THE BOTTOM LINE AND I THINK DR. TAYLOR HARDIN STRESSED THIS IS THAT THE BOTTOM LINE IS IF YOU CAN'T ACTUALLY DRAW GENERALIZABLE CONCLUSION SYSTEM YOUR INITIAL INVESTMENT WORTH WHILE ANYWAY. SO THE GOAL IS TO BE ABLE TO GENERALIZE THAT AND GENERAL POPULATION AND I THINK THAT'S WHAT NIH'S MANDATE AS A WHOLE IS FOR THE COUNTRY AND TO PROTECT OUR HEALTH. SO THAT MADE A LOT OF SENSE CAN IT WAS A GREAT DISCUSSION THAT WE H. SO THESE--THE WORKS GROUP, 4 WORKING GROUP DISCUSSED POPULATIONS, STUDY ISSUES, DESIGN AND COLLECTION AND REPORTING AND IDENTIFIED A NUMBER OF THEMES THAT I THINK WERE IMPORTANT FOR SCIENTIFIC COMMUNITY AS A WHOLE BUT ALSO FUNDERS AND OTHER GOVERNMENT AGENCIES AND OFFICES SO THERE WAS AN RFI THAT CAME OUT FROM IT, REQUESTING INFORMATION FOR INCLUSION ON CLINICAL TRIALS ACROSS THE LIFE SPAN AND THEN OF COURSE TURNED INTEREST A POLICY REVISION AND IT'S NICE TO SEE THAT THESE DO HAPPEN AND THAL CASE WE WERE IMPRESSED AT THE SPEED WITH WHICH THIS HAPPENED BECAUSE YOU KNOW WE ALWAYS--WE OFTEN THINK OF THE GOVERNMENT AS CHURNING FAIRLY SLOWLY BUT THEY'RE ACTUALLY OPPORTUNITIES TO NOTICE THAT THE GOVERNMENT WORKS VERY QUICKLY. SO THE DISSEMINATION OF THE ALZHEIMER'S RESEARCH FUND SYSTEM A GREAT EXAMPLE OF THAT BUT THIS IS ANOTHER--BECAUSE THAT HAPPENED VERY SHORTLY AFTER AND SO THIS IS JUST ANOTHER QUICK SNAPSHOT THAT DR. BERNARD SHOWED US ON WHAT APPLICATIONS WERE ENCOURAGED OR ACTUALLY REQUIRED TO INCLUDE BOY THAT MANDATE SO I WILL LET YOU TAKE A QUICK PEEK AT THIS BECAUSE A LOT OF YOU KNOW FROM OUR COUNCIL BECAUSE YOU HAVE TO ACTUALLY FILL THESE THINGS OUT NOW. SO AGAIN THIS IS SOMETHING I WAS NOT AWARE OF THAT THIS& DISCUSSION HAPPENED ON THIS FEDERAL LEVEL ABROAD, AND I AGROW THAT IT'S ABSOLUTELY APPLICABLE ACROSS MANY INSTITUTES BUT CERTAINLY SPECIFICALLY IMPORTANT TO THE NIA AND THANK YOU SO FCH THAT LEADERSHIP AND THE PRESENTATION, I HOME I DIDN'T EMBAR ATIONZ YOU TOO MUCH WITH TOO MANY ERRORS HERE BUT THANK YOU VERY MUCH. MOVING ON TO DR. HECTOR GONZALEZ, I WAS GRATEFUL WE WERE ABLE TO HAVE COMMON MEETINGS WITH THE TASK FORCE, AND DR. HILL REALLY CRITICAL TO ALL OF THAT ACTIVITY AND THE TOPICS I GET PRESENTED TO US ON THE TASK FORS FOR EVERY COUNCIL MEETING AND THIS OF COURSE A TOPIC NEAR AND DEAR TO MY HEART BECAUSE I AM A MEXICAN-AMERICAN RESEARCHER BUT DR. GONZALEZ TALKED ABOUT THE IMPORTANCE OF NOT ONLY THE WORKFORCE BEING DIVERSIFIED BUT ACTUALLY HAVING PEOPLE FROM DIVERSE BACKGROUNDS, BEING THE 1S THAT ARE PARICIPATING AND LEADING THAT RESEARCH AND SO DR. HECTOR GONZALEZ HAS DONE SO HIMSELF AND STRESSED HOW IMPORTANT IT WAS TO BUILD THE INSIGHTS AND COMMITMENT OF FUTURE GENERATIONS OF RESEARCHERS SO I THINK--I MEAN I'M BEHAVIORIAL NEUROSCIENTIST BY TRAINING AND TRAINED IN ANIMAL WORK AND AS MOLLY WELL KNOWS WHAT MY MENTOR DR. JOHN DISTERHOFF, WE WORK INDEED MICE AND RABBITS SO THIS WAS NOT A PART OF MY THINKING ORIGINALLY WHEN I WAS STARTING IN THE FIELD. BUT, I WILL TELL YOU THAT THERE IS DEFINITELY A DIFFERENT MIND SET WHEN YOU KNOW THAT YOU ARE DOING CLINICAL TRIALS FOR EPIDEMIOLOGY ON A POPULATION THAT YOU KNOW A LITTLE BIT MORE ABOUT BECAUSE HAVE YOU INFORMATION ABOUT THEIR HISTORY BECAUSE YOU YOURSELF HAVE HAD THAT EXPERIENCE. SO I THINK THAT WAS SOMETHING THAT REALLY RESONATED WITH ME. AND HE GAVE US A REALLY GREAT TIMELINE OF HIS CAREER PATH WHICH WE DO ASK OUR SPEAKERS TO DO WHEN THEY COME AND TALK TO US ON THE TASK FORCE. YOU WILL SEE DR. TAYLOR HARDIN IS RIGHT THERE UP THE TOP AND DR. GONZALEZ STRESSED THE FACT THAT SHE PUT HIM ON THE PATH. SHE STARTED HIM ON THE PATH IN THE VERY BEGINNING. AT AN NIA SUMMER INSTITUTE WHEN HE WAS JUST A BABY, A BABY RESEARCHER THINKING ABOUT WHAT TO DO. I THOUGHT THAT THAT WAS VERY IMPACTFUL TO HEAR BECAUSE IT JUST TAKES SOME ENCOURAGEMENT SOMETIMES AND YOU KNOW THAT--THAT ENCOURAGEMENT THAT TELLS YOU, YES, YOU CAN DO IT AND THERE ARE PEOPLE AROUND TO SUPPORT YOU AND THAT YOU CAN TALK TO AND I THINK THAT'S DR. HARDIN DID FOR DR. GOL SWRAL ZETAMIN, AND YOU WILL SEE THROUGHOUT THE PRESENTATION AND YOU WILL BE JUST AS PROUD OF WHAT THAT BROUGHT TO BEAR BECAUSE HE'S A GREAT RESEARCHER BUT AS CAN YOU SEE, HIS WHOLE CAREER TRAJECTORY, VERY MUCH WELL FUNDED THROUGH NIH PROJECTS AND NOW MOVING ALL THE WAY TO HAVING THE NEXT GENERATION COME IN A POST DOCTORAL DIVERSITY SUPPLEMENT THROUGH DR. PRISCILLA GAVETTA, AGAIN, THE NEXT GENERATION COMING AND IT'S NICE TO SEE THAT HAPPEN AND I KNOW DR. HARDIN WAS GRATIFIED TO SEE THAT AS WELL. BUT THE TOPIC OF HIS CONVERSATION WAS LATINO DEMOGRAPHY AND THIS IS A SNAPSHOT OF WHAT HE WAS TALKING ABOUT AND WE CERTAINLY KNOW THAT THE LATINO POPULATION IN THE UNITED STATES IS GROWING BUT DOES FACE VERY UNIQUE ISSUES AS EACH UNDERREPRESENTED POPULATION DOES. SO HE REALLY HIGHLIGHTED THIS QUITE A BIT AND I THINK WHAT STRUCK ME HERE IS THE LAST POINT THAT THERE'S A 3 YEAR OR LONGER AVERAGE LIFE EXPECTANCY FOR LATINOS AND IT'S THE LATINO HEALTH PARADOX BECAUSE THEY ARE VERY MUCH AFFECTED BY CO MORBIDITIES AND DEMENTIA, ET CETERA SO HE MADE A POINT OF SAYING WELL THEY MAY LIVE LONGER BUT WHAT DOES THAT QUALITY OF LIFE LOOK LIKE AND WE NEED TO THINK ABOUT THAT AS WE LOOK AT EPIDEMIOLOGY AS WE THINK ABOUT HOW WE IMPROVE THAT AS LATINOS AND ALL OTHERS AGE. SO THIS WAS A SNAPSHOT OF THE DYNAMIC AND SIGNIFICANCE OF THE POPULATION. CERTAINLY THE IMMIGRANTS SHARE, HE POINTED OUT IS DROPPING FOR LATINOS AS OPPOSE TO WHAT OTHER PEOPLE THINK BUT HE--THEY ARE GROWING AND OF COURSE THAT IT IS SUCH A DIVERSE POPULATION, THAT MIDDLE GRAPH TELLS YOU JUST HOW DIVERSE THE POPULATION IS. YOU CAN'T REALLY LUMP IT TOGETHER AND I THINK SOME OF THE THINGS HE'S DOING IN THIS THE STUDY, AND YOU WILL SEE IN A FEW SLIDES REALLY REALLY BRINGS HOME THE FACT THAT THEY ARE NOT A GROUP THAT YOU CAN HOMOGINIZE. BUT WHAT DO WE KNOW ABOUT DEMENTIA IN THE CIND, THERE ARE A COUPLE STUDIES THAT HAVE DISPARATE RESULTS ON THAT AND I THINK THAT'S WHY THIS WHOLE STUDY VERY IMPORTANT BECAUSE THESE ARE FOCUSED ON CERTAIN TYPES OF POPULATIONS WITHIN THE LATINO COMMUNITY AND THEY DO AS YOU CAN SEE AS A RESULT OF THESE 2 VERY EXCELLENT STUDIES HAVE DIFFERENT TRAJECTORIES AND LOOK DIFFERENT SO HE TALKS A BIT ABOUT EVEN, YOU KNOW WHAT IT MEANT AND WITHIN CELLS FOR EXAMPLE LOOK AT DEMENTIA, A LOT OF IS ALZHEIMERS AND MUCH OF IT IS VASCULAR COMBINATIONS AND THAT STRESSES THE FACT THAT LATINOS MAY HAVE A DIFFERENT PICTURE BUT LUMPING THEM TOGETHER IS NOT THE WAY TO G. >> MEXICAN INCIDENCE IS UNKNOWN. THERE IS A KISER STUDY HE TALKED ABOUT BUT THAT STUDY TELLS US THERE IS COMPARABLE PREVALENCE BETWEEN WHITES AND LATINOS BUT IT DOES EXCLUDE 56 PERCENT OF UNINSURED LATINOS. SO THIS IS 1 OF THE THINGS WE DO NEED TO THINK ABOUT IN THIS POPULATION THERE ARE UNIQUE ISSUES AND THAT IS THAT THEY ARE UNDERREPRESENT INDEED COHORTS THAT COULD BE FOLLOWED BY FORMAL ADMINISTRATIVE DATA AND THE SOLE STUDY IS A FABULOUS STUDY AND I KNOW JOHN KNOWS A LOT ABOUT THIS AND IT'S BEEN SUPPORTED AS AS OTHER INSTITUTES. THIS IS A SNAPSHOT OF WHAT IT LOOKS LIKE AND THEN THERE IS THE--THIS IS A SNAPSHOT OF THE HYPER TENSION RESULTS IT'S AGAIN 1 OF THE FIRST HINTS THAT YOU CAN SEE HERE FROM THIS STUDY THAT LATINO POPULATION VS VERY DIFFERENT TRAJECTORIES IN TERMS OF CO-MORBIDITIES AND WE DID MAKE A DISTINCTION BETWEEN WHAT IS CALLED SORT OF ISLAND LATINOS VERSUS MAIN LAND LATINOS AND YOU CAN SEE HERE THAT THE RED BOX IS MORE THE ISLAND VARIETY. I THINK IN THIS SLIDE, YOU CAN SEE THE DIFFERENCE FOR DIABETES AND BETWEEN MEN AND WOMEN AND AGAIN HAVING MEXICAN AMERICAN POPULATION AND DOMINICAN POPULATION HAVING AMONGST THE HIGHEST BUT ALSO PUERTO RICANS AND WE KNOW THEY HAVE A RELATIONSHIP TO DEMENTIA AND SO I THINK THAT'S SOMETHING THAT HE'S LOOKING AT NEXT WITH THE STUDY WITH THE WHOLE INCA STUDY. SNAPSHOT HERE OF THE METABOLIC SYNDROME, WE KNOW THIS IS PART OF LATINO AGING AND DIABETES AND OBESITY AND HYPER TENSION IN THAT POPULATION AND NOT SURPRISING IS RELATED TO LOWER COGNITIVE FUNCTION. IN MIDLIFE IT'S BEEN FOUND IN OTHER POPULATIONS AND THIS POPULATION IS NO DIFFERENT. SO AGAIN THIS WHOLE INCA STUDY FOCUSES ON COGNITIVE ASPECTS OF AGING AND MCI POPULATION AND THE GOAL WAS TO IDENTIFY 6500 INDIVIDUALS FROM THE INITIAL SOL STUDY, TO STUDY COGNITION, FACTORS, BACKGROUND OF FOLKS AND SOCIOECONOMIC FACT ORS, ET CETERA. WE GOT A NICE SNAPSHOT OF THAT BECAUSE THEY JUST CLOSED THE BOOKS ON IT AND JUST I THINK HE SAID WAS A COUPLE WEEKS AGO OR DAYS AGO SO WE GOT DATA HOT OFF THE PRESS YET. THE GOAL AGAIN AS YOU SEE HERE, WERE SLIGHTLY UNDER THEIR GOAL BUT ONLY BECAUSE AGAIN, THE SOL STUDY HAD STARTED SO THEY WERE CALLING BACK SOME FOLKS AND THAT SOMETIMES DOESN'T GIVE YOU AS HIGH OF AN ENROLLMENT WHEN YOU CALL FOLKS BACK. BUT THIS IS A QUICK SNAPSHOT I WOULD LIKE TO SEE AND THESE ARE THE CENTERS THEY WERE DRAWING FROM. THE AGE GROUP FERS WHICH WAS PRETTY WELL BALANCED DID HAVE MORE FEMALES THAN MALES AND THE EDUCATION WAS PRETTY WELL BALANCED AS WELL, BUT IN THIS WONDERFUL PLOT, YOU CAN SEE THE NICE DIVERSITY OF REPRESENTED POPULATIONS THAT THEY HAD AND AGAIN, VERY IMPRESSIVE, I THINK FOR THE SOL INCA TRIAL TO HAVE MANAGED TO GET THIS TYPE OF DIVERSITY. AND I THINK DOES A GOOD JOB OF REPRESENTING THE PERCENTAGES THAT ARE LIVING IN THE UNITED STATES ACTUALLY. >> VERY QUICK SNAPSHOTS OF DATA BECAUSE AGAIN IT WAS NOT ANALYZED FOR DEPTH OF MEANING QUITE YET. HE WAS JUST GIVING US SNAPSHOTS AND HERE'S A SNAPSHOT OF MCI PREVALENCE AND JUST OF THE FEMALE-MALE RATIO, YOU CAN SEE IT'S DIFFERENT. WE HAVE DIFFERENCES WITH AGE, OLDER AGE, A MORE PREVALENCE OF MCI, LOWER EDUCATION AGAIN IN THE BLUE, ALSO RELEVANT TO MCI PREVALENCE, NOTHING THAT'S THAT SURPRISING AND I THINK WHAT'S INTERESTING ALSO IS THAT THERE WAS A SLIGHT DIFFERENT BETWEEN ISLANDERS IN TERPS OF DOMINICAN AND PUERTO RICK AN BACKGROUNDS AND CUBANS SO THAT'S SOMETHING THAT NEEDS TO BE STUDIED A BIT FURTHER BUT THE MAIN LAND EROZANS AS HE CALLED IT ARE RIGHT IN THE MIDDLE OF THAT GREEN GRAPH THERE, VERY INTERESTING WORK ALSO FROM THE CARDIOVASCULAR RISK AND 6 YEAR COGNITIVE DECLINE, QUICK SNAPSHOT BECAUSE THIS IS DATA HOT OFF THE PRESS. AND IN A BASE LINE GLOBAL COGNITION AS IT RELATES TO HYPER TENSION AND ALL THESE THINGS THEY FOLLOWED VERSUS A 6 YEAR TIME FRAME AND YOU KNOW IT'S NOT SURPRISING THAT DIABETES WAS A STRONGER--I THINK WE'VE KNOWN THAT IN THE AFRICAN AMERICAN COMMUNITY--IT'S HYPER TENSION AND HIGH BLOOD PRESSURE. IF DRIVEN BY THE MAJORITY OF THE MEXICAN POPULATION WHO HAS DIABETES AS A VERY STRONG RISK FACTOR THAT THE DIABETES REALLY WAS THE 1 THAT WAS SORT OF MORE CORRELATED WITH THE GLOBAL COGNITION AND CHANGE. APOE SNAPSHOT WAS INTERESTING FOR THOSE OF US IN THE ROOM AND AGAIN THESE ARE THINGS THAT WE--THAT DEPARTMENT HAVE A LOT OF INFORMATION ABOUT BEFORE. WE CERTAINLY NEED MORE NUMBERS BUT THESE ARE DIFFERENT NUMBERS THAN Y-CAP AND SALSA HAS SEEN. SO IT'S HARD TO KNOW WHAT TO MAKE OF THESE SO THIS IS JUST A SNAPSHOT OF THAT DATA SO YOU CAN SEE THIS. IT'S VERY INTERESTING AND HOW IT RELATES TO MCI. AGAIN IT'S HARD TO UNDERSTAND WHEN YOU SEE THIS. BUT APOE 24 AND 3-4 ARE INTERESTING WITH RESULTS SO AGAIN ALL THIS IS THE A QUICK SNAPSHOT OF DATA HOT OFF THE PRESS SO IT NEEDS TO BE UNDERSTOOD A BIT MORE AND I'M SURE NEEDS TO BE ANALYZED QUITE A BIT MORE. SO THESE ARE SORT OF THE SUMMARIES JUST IMPORTANT THAT THE SUBBULLET HERE OF BUILDING INSIGHTS AMONG DIVERSE SCHOLARS THAT ARE DOING THIS RESEARCH WITH THE SENSITIVITY THAT IMPORTANT AND THE COGNITIVE TESTING THAT IS ALSO IMPORTANT. JENNIFER HAS BEEN A BIG PART OF THOSE CONVERSATIONS AND as a co investigator, and then the future directions is important just to share with you because there is an important need to highlight when atn might emerge and studies give us the possibility of caring that type of work out and when we do--I know we're all in the race for the cure but it's important that we're all in the race and right now, there are populations that are not. THEY ARE NOT INCLUDE INDEED CLINICAL STUDIES AND THEY'RE NONAPOPTOTIC THE RACE AND WE DON'T KNOW IF OUR TREATMENTS ARE GOING TO WORK IN THOSE POPULATIONS SO THAT'S WHY THESE TYPES OF STUDIES ENABLE US TO EVEN DEMONSTRATE THAT WILL COME PARTICIPATE CAN BE FOLLOWED FOR MULTIPLE YEARS AND PARTICIPATE IN EVEN HEAVILY BIOMARKER BASED STUDIES SO THAT COULD BE POTENTIALLY INSWRAISIVE. THIS IS A QUICK SNAPSHOT OF WHAT THEY WANT TO DO IN THE FUTURE BECAUSE IT IS A GREAT COHORT TO CONTINUE TO FOLLOW AND WE CERTAINLY AGREED AND THAT YOU KNOW DIVERSITY OF INCREASING THE SCIENTIFIC WORKFORCE AGAIN WAS A BIG PART OF THIS. THERE IS AN A. D. CENTER THAT HAS STARTED UP THERE THAT'S GREAT AND BEEN FUNDED AND SO, I THINK OVER ALL THAT CONVERSATION WAS VERY INFORMATIVE FOR ALL OF US ON THE COUNCIL. SO THANK YOU AGAIN, CARL FOR MAKING THAT HAPPEN BUT DR. GONZALEZ FOR BEING THERE AND LASTLY I WILL SHARE WITH YOU A COUPLE OF INFORMATIONAL UPDATES BECAUSE I'M RUNNING OUT OF TIME. BUT CERTAINLY YOU ALL HAVE HEARD ABOUT A HEALTH DISPARITIES PANEL AT AIC, THAT TALKED A LOT ABOUT THE WORK THAT'S HAMMING THROUGH RO-3 FUNDED INVESTIGATORS. AND AN INCLUSION PRESENTATION THAT WAS ALSO--ALSO TOOK PLACE. GREAT SUCCESSES, WITH GREAT PARTICIPATION. GSA ALSO COMING UP BUT LOTS OF GREAT THINGS HAPPENING THERE. THIS IS A QUICK SNAPSHOT OF WHAT THERE IS THERE FOR THOSE OF YOU WHO ARE GOING TO BE THERE, FOR THOSE WHO ARE NOT, JUST KNOW THERE IS A LOT OF WORK BEING DONE THROUGH GSA, REPRESENTATIONOT MINORITY TASK FORGS WORK AND REPRESENTATION OF HEALTH DISPARITIES AND RESEARCHERS AND THEN LASTLY, THERE IS AN R13 GIVEN TO DR. JOHN MORRIS AT WASH-U TO HOST A WORKSHOP AND THIS WORKSHOP IS ON AFRICAN AMERICAN PARTICIPATION IN RESEARCH SPECIFICALLY. IT'S HAPPENING, I THINK IT IS OPEN TO ANYONE WHO WANTS TO ATTEND AND WE COLLABORATED WITH DR. MORRIS ON THIS R13 TO FUND 11 TRAVEL FELLOWSHIPS SPECIFICALLY FOR AFRICAN AMERICAN SCHOLARS AND RESEARCHERS TO COME TO THAT MEETING AND TALK ABOUT THEIR EXPERIENCES AND LEARN FROM OTHERS. SO HAPPY TO HAVE PARTNERED WIDE THAT R13. SO THANK YOU VERY MUCH TO DR. HILL AGAIN FOR LEADING ALL OF THESE EFFORTS WITH THE MINORITY TASK FORCE. I HAVE HAD AN ABSOLUTELY FABULOUS TIME AND LEARNED A LOT IN MY TIME WORKING WITH THE TASK FORCE AND WORKING WITH DR. WUTAN, I KNOW DR. TAYLOR HARDIN WILL TAKE THIS CHALLENGE ON AND YOU ABOUT BE EVEN BETTER SO THANK YOU SO MUCH FOR THE TIME AND THE ABILITY TO WORK WITH YOU THROUGH THIS TASK FORCE. ONE THING WE HAVE SEEN THROUGH THE PAST 10 YEARS AND THAT THERE IS MORE AWARENESS AND MUCH MORE OF AN EFFORT TO TALK ABOUT DIVERSITY OF ALL KINDS, NOT ONLY OF RACIAL, ETHNIC BUT SOCIOECONOMIC DIVERSITY, ET CETERA BUT PERHAPS IN RECEIPT YEAR THERE IS IS MORE OF A NEED TO CONTINUE ON THAT ROAD AND TO BE VERY LOUD AND VOCAL ABOUT IT AND I THINK THAT WHAT THE NIAs DOING AND LEADERSHIP THROUGH THE TASK FORCE AND DR. HILL IS MAKING THAT HAPPEN AND AS A MEMBER OF THAT UNDERREPRESENTED POPULATION I'M REALLY GRATEFUL FOR IT BUT CERTAINLY AS A I ALSO AM GRATEFUL FOR THE OPPORTUNITY TO HAVE WORKED WITH THIS GROUP AND LEARNED A LOT. THANK YOU VERY MUCH. [ APPLAUSE ] >> THANK YOU DR. CARRILLO. ANY QUESTIONS FOR DR. CARRILLO? >> ALL RIGHT. SUE? >> I HAVE A QUESTION FOR MARIE? I WAS THRILLED ABOUT WHAT HAPPENED WITH THE INCLUSION ACROSS THE LIFE SPAN EFFORT AND I JUST WANTED TO KNOW IF IT WAS OVER OR IF THERE WERE GOING TO BE FURTHER ACTIVITIES GOING ON? >> SO THE NEXT STEP WITH THIS IS THAT AS OF JANUARY 25th OF 2019 ANY APPLICATION THAT'S SUBMITTED HAS TO ADDRESS THE AGES OF SUBJECTS THAT ARE INVOLVED AND ANY PROJECTS THAT ARE FUNDED FROM THAT DATE ON WARD IN THEIR PROJECT REPORTS WILL HAVE TO NOT ONLY INFORMATION ABOUT AGE AND ENROLLMENT IN HOURS, MONTHS OR YEARS BUT ALSO SEX GENDER, RACE, ETHNICITY WHICH WILL ENABLE LESS AT THE NIH TO REALLY HAVE A COMPREHENSIVE SENSE OF WHAT'S BROUGHT INTO FOR VARIOUS STUDIES AND MY EXPECTATION IS THAT 4 OR 5 YEARS OUT FROM THAT, WE ARE GOING TO SYSTEMATICALLY PROBABLY LOOK AT HOW WELL WE'RE DOING AND SEE WHETHER THERE ARE ANY ADDITIONAL MEASURES THAT NEED TO BE TAKEN OR WHATEVER. WE CERTAINLY AS ANOTHER PROVISION IN THE 21st CENTURY CURES ACT, WE ARE MANDATED TO REPORT INVOLVEMENT OF SUBJECTS BY DISEASE CATEGORY BASED UPON SEX GENDER AND RACE AND ETHNICITY SO THOSE ARE THE THINGS THAT WE'RE DOING. I'M AWARE THAT THERE ARE OUTSIDE ORGANIZATIONS THAT ARE VERY INTERESTED IN THIS ISSUE. MY UNDERSTANDING IS THAT THE AMERICAN GERIATRIC SOCIETY IS PLANNING TO HAVE I SPECIAL ISSUE AND THEY'RE PUTTING THEMSELVES FORWARD TO TRY TO HELP OTHER DISCIPLINES TO THINK ABOUT HOW TO BETTER INCLUDE OLDER ADULTS IN CLINICAL STUDIES. I'M AWARE THAT THE GERON TO LOGICAL SOCIETY OF AMERICA IS HAVING A WORKSHOP ON INCLUSION ACROSS THE LIFE SPAN BUT WE WOULD ENCOURAGE ALL WHO ARE INTERESTED IN THIS ISSUE TO HELP IN MAKING SURE THAT IT'S NOT JUST THOSE PEOPLE THAT ARE INTERESTED IN AGING RESEARCH WHO ARE FOCUSING ON THIS BUT AND IT'S REALLY THE BASE LINE ANALYSIS THAT WAS DONE WAS LOOKING AT THINGS LIKE HEART DISEASE AND STROKE AND LUNG CANCER AND PROSTATE CANCER, YOU KNOW THOSE RESEARCHERS DON'T NECESSARILY SEE THEMSELVES AS AGING RESEARCHERS, BUT THEY'RE ADDRESSING ISSUES OF OLDER ADULTS AND THEY REALLY NEED TO THINK ABOUT HOW THEY CAN INCLUDE OLDER ADULTS IN CLINICAL STUDIES. >> ASCO HAD A GREAT MEETING WITH THE FDA ON THIS ISSUE AND I JUST WANTED TO ENCOURAGE THE NIA, I KNOW THAT YOU DID, YOU KNOW SORT OF WHAT WAS CALLED 4 URNTD 21st CENTURY CURES ACT AND WE WERE REALLY EXCITED ABOUT THAT AS SORT OF LIKE A FITTER STEP IN SORT OF A SIDE WAY TO PUSH THE FDA BUT AS SIGNIFY SECOND STEP IF YOU WOULD BE OPEN TO IT WOULD BE INCREDIBLE TO TALK ABOUT MAYBE A CONVENING WITH FDA AND POTENTIALLY INVITING EMA--I KNOW FDA CAME TO THE NIH INCLUSION. BUT POTENTIALLY INCLUDING EAMERICASA SENSE THEY HAVE A GERIATRIC MEDICINE STRATEGY IN EUROPE AND THE CLINICAL TRIALS THAT NIH DOES--THIS IS A VERY IMPACTFUL BUT IT'S VERY SMALL PERCENTAGE OF CLINICAL TRIALS AND IT'S PRIMARILY INDUSTRY WHICH IS SOMETHING THAT'S GOING TO HAVE TO COME THROUGH FDA. AS A LEADER, IT WOULD BE INCREDIBLE IF YOU WOULD BE WILLING TO DISCUSS FURTHER POTENTIALLY THINKING ABOUT DOING A NEXT STEP TO, YOU KNOW BRING IN FDA AND TAKING A LOOK AT THIS GERIATRIC MEDICINE STRATEGY. >> I APPRECIATE THAT INPUT. I SHOULD SHOULD HAVE MENTIONED AS WELL THAT FDA HAD A LEGISLATE IEVER MANDATE TO LOOK AT THEIR INCLUSION ISSUES AND WE HAVE BEEN INCONVERSATIONS WITH THEM BOTH THE INCLUSION GOVERNMENT'S COMMITTEE THAT I CO-CHAIR AND BUILDING 1 WITH THE LEADERSHIP FOR NIH. FDA IMPACT HAD A WORKSHOP OF THEIR OWN IN APRIL OF 20--2018. I'M LOSING TRACK OF TIME BUT IT WAS A RECENT WORKSHOP WHERE I GOT A CHANCE TO PRESENT OUTCOMES FROM OUR WORKSHOP AND AND COLLEAGUES WHO LOOKED AT INCLUSION OF PRACTICINGINANT AND LACTATING WOMEN AND GOT AN OPPORTUNITY TO PROVIDE INPUT AND THE CONVERSATIONS CONTINUE AND I THINK THIS IS A WELL TAKEN POINT SO WE'LL STUDY IT MORE. APPRECIATE THAT. >> THANK YOU WE'LL MOVE ON TO THE REPORT OF THE WORKING GROUP AND I HAVE TO CHECK TO SEE IF DR. KRIMINS IS ON THE LINE. >> I AM AND I AM READY TO PRESENT WHAT WENT ON IN THE WORKING GROUP OF PROGRAM YESTERDAY. NORMALLY WE SPEND MOST OF OUR TIME REVIEWING CONCEPTS FOR FUTURE RFAs AND RFPs AND YESTERDAY WE DID NOT CONSIDER ANY CONCEPTS. THE REASON BEING THAT WE DID SO MUCH OF THIS OVER THE LAST FEW CYCLES OF THE NACA GROUP THAT WE ESSENTIALLY ALL THOSE THINGS ARE NOT REALLY CLEARING AND NOTHING WAS CONSIDERED YESTERDAY. SO THIS REPORT WILL BASICALLY SUPPORT OF PEOPLE OF THE THINGS THAT WE DID TALK ABOUT YESTERDAY IN THE WORKING GROUP ON PROGRAM. AND THE FIRST THING THAT WE CONSIDERED WAS THE INITIAL REVIEW OF THE DIVISION OF NEUROSCIENCE WHICH WAS PRESENTED TO US BY DR. REE SA SPERLING WHO IS THE CHAIR OF THAT COMMITTEE. THIS IS JUST A QUICK REVIEW OF THE MAJOR POINTS THAT WERE--WILL BE IN A FINAL REPORT THAT WE WILL ACTUALLY CONSIDER IN JANUARY BUT THE POINTS THAT WE WERE--THAT WE TALKED ABOUT YESTERDAY WOULD BE PRESENTED TO US TODAY BY A MEMBER OF THE COMMITTEE WHO IS ON THE COUNCIL AND THEIR DR. ERIC RHINEMAN. IS ERIC THERE? >> THANK YOU VERY MUCH, EILEEN. I APPRECIATE THAT SO I'M PLEASED TO GIVE YOU AN UPDATE ON OUR PRELIMINARY FINDINGS AND RECOMMENDATIONS, JUST A FEW POINTS WHILE DR. SPERLING WILL GIVE A FORMAL REPORT OF OUR FINDINGS AND RECOMMENDATIONS IN JANUARY. WORKING GROUP CONSISTED OF--HAS CONSISTED OF 6 COMMITTEES INCLUDING MORE THAN 30 MEMBERS AND 12 CO CHAIRS. IT'S BEEN LED BY DR. SPERLING, IT'S BEEN ABLY ASSISTED BY SERESE, AND ELLIOTT AND THE WORKING GROUP WANTS TO THANK DR. REESE FOR GIVING US ALL THE HELP WE CAN TO PROVIDE AND MAKE THE MOST INFORMED INPUT. WE HAVE BEEN STRUCK BY THE EXTRAORDINARY PROGRESS, PRODUCTIVITY AND RESPONSIVENESS OF THE DIVISION STAFF DURING THE LAST FEW YEARS AND THE FOUNDATION HAS PROVIDED TO HELP US ADVANCE THIS FIGHT AGAINST ALZHEIMER'S DISEASE AND OVER THE ENSUING MONTHS WE WANT TO CONGRATULATE THE DIVISION FOR ITS PROGRESS, EVEN AS WE ASK IT TO DO MORE. WE ARE STRUCK BY THE IMPACT THAT IT'S LEADER [INDISCERNIBLE] HAS ALREADY HAD ON PRODUCTIVITY, COMMUNICATIONS AND MORAL WITHIN THE DIVISION SENSE HIS ARRIVAL. WE'VE BEEN IMPRESSED BY THE QUALITY OF THE STAFF AND THE QUALITY OF NEW EDITIONS TO THIS STAFF. WE CAN ONLY IMAGINE HOW MUCH MORE 1 COULD DO WITH ADDITIONAL STAFF. THINKING ABOUT INCREASING THE STAFF AND STRATEGICALLY INFORMED WAYS TO ADVANCE OUR AMBITIOUS GOALS AND IT WAS A CONSENSUS AMONG EVERYONE IN THE WORKING GROUP THAT THERE WILL--THERE WILL OPPORTUNITIES TO DO THAT WITH THE NEW OPPORTUNITIES IN FUNDING THAT WE EXPECT IN THE NEXT FEW YEARS. THERE WAS ALSO A SHARED VIEW THAT THERE ARE MORE OPPORTUNITIES TO ADVANCE, TO VALUE NORMAL BRAIN AGING RESEARCH IN TERMS OF ITS RELEVANCE TO THE FIGHT AGAINST ALZHEIMER'S DISEASE AND IN ADDITION TO ITSELF INHERENT STRATEGIC VALUE AND THERE MAY BE WAYS TO LEVERAGE THOSE OPPORTUNITIES AND INCREASE IT, INCLUDE IT WITHIN THE FUNDING UNDER THE ALZHEIMER'S CATEGORY WHEN APPROPRIATELY JUSTIFIED. WE THINK THERE ARE ADDITIONAL OPPORTUNITIES THAT COULD BE TAKEN TO ATTRACT AND RETAKEN TRAINEES, OTHER NEW INVESTIGATORS AND SENIOR INVESTIGATORS FROM OTHER FIELDS. YOU THINK THERE ARE OPPORTUNITIES TO INCREASE FUNDING, SUPPORT AND THE OPPORTUNITIES ARE AND WHEN POSSIBLE TO REVIEW THOSE GRANTS THAT ARE CLOSE TO FUNDING, IMPROVE THEIR STRENGTH AND GET THEM APPROVED WITHOUT DELAY SO THAT WE DO NOT LOSE THESE INDIVIDUALS. WE THINK THERE ARE OPPORTUNITIES TO INCREASE THE DIVERSITY OF RESEARCHERS IN THIS AREA, NOT ONLY IN TERMS OF THEIR BACKGROUND BUT IN TERMS OF AREAS OF EXPERTISE, 1 EXAMPLE THAT WAS BROUGHT UP WAS ADDITIONAL EXPERTISE AND COMPUTATIONAL NEUROSCIENCE WE NEED TO BRING IN, BUT THERE ARE MANY RPGHT EXAMPLES. THERE WAS AIR SHARED VIEW WE COULD DRAMATICALLY IMPROVE THE VALUE OF OUR EXISTING COHORTS AND OTHER STUDIES BY FINDING WAYS TO EMBED MORE BIOMARKERS WHICH ARE INCREASINGLY IMPORTANT FOR ALZHEIMER'S DISEASE. WE NEED TO DEVELOP MORE SCALABLE BIOMARKERS, LESS EXPENSIVE, LESS INVASIVE BIOMARKERS FOR A. D. AS AS BIOMARKERS FOR OTHER CONDITIONS. WE NEED TO PROVIDE THE INFRASTRUCTURE, DATA, SPECIMENS, TECHNICAL SUPPORT, AND PARTNERSHIPS NEEDED TO MAKE THAT HAPPEN AS SOON AS POSSIBLE AND THERE'S A CONSENSUS THAT IF WE HAD AN AMYLOID BLOOD TEST WITHIN THE NEXT COUPLE OF YEARS IT WOULD BE GALVANIZING. WE ALSO SEE SIMILAR OPPORTUNITIES IN THE USE OF MOBILE AND DIGITAL TECHNOLOGIES IN THIS AREA. THERE ARE OTHER TECHNOLOGIES IN RELATIONSHIP TO ADVANCEING EVERYBODY'S AGENDA OVERALL AND WE WOULD LIKE TO FIND WAYS TO BRING IN THAT EXPERTISE. WE'VE BEEN IMPRESS BIDE THE PARTNERSHIPS THAT NIA HAS ESTABLISHED NOT ONLY AMONG OTHER AGENCIES AND OTHER STAKEHOLDERS OUTSIDE OF NIH, WE ANTICIPATE THERE WILL BE NEW OPPORTUNITIES TO ADVANCE THAT EFFORT. WE SUPPORT THE EXISTING EFFORTS AND WOULD LIKE TO SEE CONTINUED EFFORTS IN INCREASING DIVERSITY WITHIN ENROLLED RESEARCH PARTICIPANTS AND THE WORKFORCE. AND WE'RE STILL THINKING ABOUT WAYS WE'VE BEEN IMPRESSED WITH THE NUMBER OF FOAs THAT HAVE BEEN GENERATED TO ADVANCE AREAS OF PROGRAM RELEVANCE AND WE ARE--WOULD LIKE TO BE ABLE TO THINK ABOUT WAYS TO FIND THAT SWEET SPOT BETWEEN THE USE OF FOAs AND OTHER MECHANISMS TO ADVANCE STRATEGIC GOALS. WHEN A CENTURY AGO WHEN THE GREAT CARUSO GAVE A PERFORMANCE [INDISCERNIBLE] WAS ASKED GIVE THE NEXT PERFORMANCE AND HE--BEFORE HE BEGAN SINGING, HE SAID YOU AIN'T SEEN NOTHING YET. ONE CAN THINK OF THE DIVISION OF NEUROSCIENCE AS A COMBINATION OF THE GREAT CARUSO AND THE FOUNDATION IT PROVIDED AND THAT OVER THE NEXT FEW YEARS THAT HOPEFULLY WE AIN'T SEEN NOTHING YET AND WE LOOK FORWARD TO PROVIDING A FORMAL REPORT IN JANUARY. >> THANK YOU. ARE THERE QUESTIONS? THAT I OR DR. RIMER CAN ANSWER? >> THERE ARE APPEAR TO BE NO QUESTIONS, I THINK WE CAN MOVE ON. >> OKAY, SO THE NEXT TALK THAT WE ENVISION TO YESTERDAY SX HEAT NATIONAL-- >> THANKS DR. CREMEINS, I WILL DISCUSS WHAT WE WENT OVER YESTERDAY ON A WORKING GROUP INITIATIVE THAT NIA HAS BEEN CONVENING FOR THE LAST 2 YEARS WITH SIGNIFICANT HELP FROM THE ALZHEIMER'S ASSOCIATION DR. CARRILLO AND MEMBERS ON HER STAFF. MANY OF YOU IN THE ROOM KNOW ABOUT THIS. BUT TO ADDRESS SOME OF THESE CHALLENGES IN ALZHEIMEREE DISEASE AND ALDZ HYMER'S DISEASE RELATED DEMENTIAS, WE HAVE GOT TOGETHER A GROUP OF RESEARCHERS, ACADEMIC EXPERTS, FEDERAL OFFICIALS AND REALLY TRIED TO LOOK AT WHAT ARE THE TECHNOLOGY TRANSFERS WE KNOW ABOUT RECRUITMENT, WHAT ARE SOME OF THE SIGNIFICANT CHALLENGES AND WHAT CAN WE ALL DO AS A COLLECTIVE GROUP TO INSURE THAT FOR PARTICIPANTS AND AND I SAID I LIKE THE IDEA OF WE NEED TO ALL BE IN THE RACE TO FIND THE CURE AND I THINK THAT'S REALLY EYE GUIDING PRINCIPLE OF THE STRATEGY THAT WE'VE BEEN WORKING ON FOR THE LAST 2 YEARS. THE STRATEGY GOT ITS GENESIS AND IT'S START AT THE ALZHEIMER'S ASSOCIATION CONFERENCE IN TORONTO IN 2016 WHERE A SMALL GROUP GATHERED TO START THINK BEING THE CHALLENGES AND WHAT CAN WE DO TO START ADDRESSING THOSE AND FROM THERE, THE NIA WITH FACILITATION FROM THE ASSOCIATION AND WITH THE HELP OF OTHER GROUPS PULLED TOGETHER A STEERING COMMITTEE AND WORKING GROUPS TO REALLY START THINKING AND ADDRESSING THE CHALLENGES FOR RECRUITMENT AND RECRUITMENT IS NOT NOT A NEW ISSUE, IT'S SOMETHING THAT HAS BEEN INCLUDED IN THE NATIONAL PLAN FOR ALZHEIMER'S DISEASE SO THIS IS A WAY FOR US TO HELP ADDRESS THE--SOME OF THE PIECES OF THE NATIONAL PLAN AS WELL. WHEN WE GOT THE WORKING GROUPS TOGETHER WE WERE FOCUSING ON THESE AREAS. SO AT A NATIONAL LEVEL, HOW CAN WE INCREASE ENGAGEMENT AND AWARENESS AT A NATIONAL LEVEL SO THAT PEOPLE UNDERSTAND THE CHALLENGES AND THE NEED. THE SECOND AREA WAS CAPACITY, WHAT CAN WE DO AT THE SITE LEVEL TO REAL HE EXPAND CAPACITY. WHAT ARE THE THINGS WE MIGHT NEED TO DO AT THE ACADEMIC CENTERS TO REALLY UNDERSCORE THE NEED FOR THE WORK THAT NEEDS TO GO INTO REALLY MAKING SURE WE HAVE DIVERSE PARTICIPATION IN OUR CLINICAL STUDIES. AND THEN THE THIRD WORKING GROUP, FOCUSED ON THE LOCAL AND DIVERSE ASPECTS OF RECRUITMENT SO REALLY THINKING ABOUT ADDED COMMUNITY LEVEL, WHAT ARE THE THINGS WE NEED TO BE THINKING ABOUT TO ENHANCE THAT ENROLLMENT, WHAT ARE SOME OF THE THINGS THAT WE CAN DO COLLECTIVELY, TO GO OUT INTO COMMUNITIES WHO HAVE BEEN UNDERREPRESENTED IN OUR CLINICAL STUDIES AND WORK WITH THEM TO UNDERSTAND THEIR NEEDS AND TO CONVEY THE NEEDS AND THE IMPORTANCE OF PARTICIPATING IN CLINICAL STUDIES. SO FAR AN UPDATE ON WHERE WE ARE ON THE STRATEGY BACK THIS YEAR, WE TOOK ALL THE GREAT IDEAS AND STRATEGIES AND THOUGHTS FROM THE 3 WORKING GROUPS AND PUT THEM OUT FOR PUBLIC COMMENT THROUGH NIDS CROWD SCALE SOURCING PLATFORM. I HOPE MANY OF YOU WERE AWARE AND PARTICIPATED IN THAT. WE GOT OVER A THOUSAND PARTICIPANTS, 200 COMMENTS, 240 NEW YEARS SO WE WERE VERY APPRECIATIVE AND AND HAPPY TO GET ALL THAT INPUT. WE WERE PARTICULARLY GRATIFIED THAT MANY OF THE IDEAS IN THE COMMENTS ECHOED WHAT WAS ALREADY IN THE STRATEGIES, WHAT WAS IN THE IDEAS THAT THE WORKING GROUPS CAME UP WITH SO WE KNEW WE WERE HEADED ON THE RIGHT PATH. A COUPLE OF POINTS. WE ARE IN THE FINAL PROCESS OF REVIEWING THAT DOCUMENT WITH THE GOAL OF LAUNCHING IT AT THE NEXT NACA ADVISORY COUNCIL MEETING WHICH WILL BE IN OCTOBER OF THIS YEAR. SO WE'RE IN THE HOME STRETCH BUT THE STRATEGY IS FOR EVERYONE TO LOOK AT AND EXAMINE WHICH PIECES CAN WE TAKE AS OUR OWN AND WORK THROUGH AND HELP US ENHANCE RECRUITMENT IN CLINICAL STUDIES. I DO WANT TO ALSO NOTE THAT AS PART OF THE STRATEGY 1 OF THE THINGS WE HAVE BEEN THINKING INTERNALLY IS BUILDING UP THE SCIENCE OF RECRUITMENT AND DR. ELLIOTT HAS AN R24 OUT ADDRESSING THAT AND SHE CAN SPEAK TO THAT BUT REALLY HOW CAN WE BETTER EVALUATE, HOW CAN WE BETTER UNDERSTAND SOME OF THE SCIENCE BASE OF RECRUITMENT STRATEGIES? IMPLEMENTATION WAS STAL'RE START AS WELL, NIA IS STARTING THAT AND HAVE AN ONLINE DATABASES THAT MANY OF YOU AND COLLEAGUES HAVE BEEN USING FOR RECRUITMENT AND THAT'S SOMETHING WE'VE BEEN WORKING CLOSELY WITH DR. SILVER BERG AND THESE BEEN INTERESTED IN THAT FOR SEVERAL YEARS AND WE'RE HOPING TO GET THAT OFF THE GROUND OVER THE COURSE OF THE NEXT YEAR AND WE WILL CERTAINLY BE CONTINUING TO CONVENE EFFORTS IN THIS AREA FOR IMPLEMENTATION, IF THERE ARE NEW STRATEGIES THAT ARE TESTED, WE WILL CERTAINLY BE INCORPORATING THAT INTO THIS STRATEGY. WE SEE THIS AS--AS KIND OF THE BEGINNING OF A ROADMAP FOR ALL OF US AND IT WILL BE AN ONGOING AND ITERATIVE PROCESS, SO THAT'S THE NATIONAL STRATEGY. >> THANK YOU. THANK YOU. OTHER QUESTIONS FOR MELISSA? >> MELISSA THANK YOU VERY MUCH. AND I KNOW IT'S A LOT OF WORK, I KNOW IT'S NATIONAL STRATEGIC PLAN EDGE O ALZHEIMER'S BUT I'M WONDERING HOW DIRECTLY YOU SEE THIS APPLICABLE TO THE ISSUE OF SEEING RECRUITMENT OF OLDER ADULTS ACROSS THE BOARD IN CLINICAL TRIALS IN APPLICABILITY. >> WELL I CERTAINLY THINK THAT MANY OF THINGS WE WERE TALKING ABOUT PARTICULARLY AT THE LOCAL AND DIVERSE WORKING GROUP LEVEL BEING OUT IN THE COMMUNITY INVOLVING THE COMMUNITY GETTING THE WORD OUT, WE TALKED A BIT ABOUT THE NEED TO--TO GO OUT INTO THE COMMUNITY MULTIPLE TIMES. YOU NEED MULTITELETOUCH POINTS TO HELP THEM UNDERSTAND WHAT WE'RE TRYING TO DO WITH THE CLINICAL STUDIES, THE VALUE OF PARTICIPATING SO I CERTAINLY THINK THAT WHILE THE FOCUS IS ALZHEIMER'S DISEASE AND RELATED DEMENTIAS, THERE WILL BE MANY COMPONENTS OF IT THAT WILL BE ABLE TO BE USED ACROSS THE BOARD. >> I WOULD LIKE TO THANK YOU FOR MAKING ACCESS TO CLINICAL TRIALS .GOV MORE FRIENDLY SO I THINK IT WILL BE GREAT FOR RECRUITMENT. >> I THINK WE CAN GO ON TO THE NEXT-- >> ALL RIGHT, THANK YOU MELISSA. SO THE NEXT TALK IS GOING TO BE ABOUT OUTREACH EFFORTS AND PROMOTING ABRD FUNDING OPPORTUNITIES AND RON BAYRO IS GOING TO PRESENT. > DAWN IS COMING. >> GOOD MORNING EVERYONE. SO YESTERDAY THERE WAS ACTUALLY A TALK DELIVERED BY GENERATED VERWATSON FROM THE COMMUNICATIONS OFFICE AND MYSELF. TODAY I WILL REVIEW THE HIGH LEVEL POINTS WE DISCUSSED YESTERDAY. SO, AS WE HAVE ALL SEEN AND AS A LOT OF YOUR INTIMATE WORK HAS BEEN INVOFFED IN CLEARING CONCEPTS, YOU HAVE A REALLY GRIT UNDERSTANDING OF THE FACT THAT THERE HAVE BEEN A LARGE NUMBER OF FOAs RELEASED BY NIA. SO WE REALLY THOUGHT IT WOULD BE OUR DUE DILIGENCE TO GIVE OUTREACH TO THE COMMUNITY, LET PEOPLE KNOW WHAT WE'RE DOING, WHAT--WHAT FOAs THAT WE'RE FOCUSING ON, WHAT ARE ACTIVE AND REAL LOAMACY HOW THEY CAN PARTICIPATE AND APPLY FOR GRANTS. SO WE HAVE A NUMBER OF METHODS THAT WE'VE USED TO GET THE WORD OUT TO THE RESEARCH COMMUNITY TO LET THEM KNOW WHAT'S GOING ON HERE AT NIA. SO WE STARTED THE TALK ADDRESSING SOME OF THE ELECTRONIC FORMS OF OUTREACH THAT WE'VE DONE, THE COMMUNICATIONS OFFICE HAS DEN A GREAT JOB OF PUTTING UP SEVERAL DIFFERENT WEBPAGES THAT THE COMMUNITY CAN USE AS A RESOURCE TO FIND OUT EXACTLY WHAT FOAs ARE AVAILABLE. SO THERE ARE SITES THAT AGGREGATE ALL OF THE ADRD FOAs IN 1 PLACE. THERE ARE ALSO BLOGS THAT TOUCH ON THE SPECIFIC FOAs WHEN THEY ARE LAUNCHED AND TO GET PEOPLE INVOLVED AND TO REALLY UNDERSTAND WHAT'S CONTAINED IN THE FACTORIES OAs--FOAs. THERE'S A NEW E-MAIL LIST THAT GOES OUT PERIODIC LOAMACY AND THAT WILL INCLUDE ALL THE NEW FOAs THAT HAVE BEEN ROLLED OUT. WE ALSO USE SOCIAL MEDIA AS A WAY TO SPREAD THE WORD AND ALSO JENNIFER MENTIONED SOCIAL MEDIA AMPLIFICATION SO ACTUALLY BILL GATES WAS ABLE TO TWEET DR. HODES'S PRESENTATION AT AAIC AND THAT TOUCHED MILLIONS OF PEOPLE THAT WERE HIS FOLLOWERS SO JUST WAYS TO HAVE OUR OUTREACH ACTUALLY GO FURTHER THAN THE PEOPLE WE ALONE INTERACT WITH. THERE'S ALSO PRESS OUTREACH THAT WE ARE TRYING TO THINK HARD AND OFTEN ABOUT HOW WE CAN SPREAD THE WORD BECAUSE IT IS A BIT UNUSUAL TO HAVE SUCH A LARGE NUMBER OF FOAs BUT WE WANT THEM TO BE IMPACTFUL. I THEN ALSO REVIEWED ACTIVITIES TO ENGAGE OTHER ISCRRKSs AND ALSO STEPPING AWAY FROM THE ELECTRONIC COMMUNICATIONS BUT WHAT IS THE PERSONAL FACE-TO-FACE INTERACTION THAT WE CAN DO TO LET THAT OUTREACH FOR FOAs ALSO GO FURTHER. SO I REVIEWED SOME OF THE MEETINGS THAT WE HAVE WITH ADVOCACY GRUPS, WITH PROFESSIONAL SOCIETIES AND HOW THEY IN TURN USE OUR COMMUNICATIONS TO SHARE WITH THEIR STAKEHOLDERS ONER WHEN THEY COME FOR MEETINGS HERE AT NIH. SO, SORRY JUST TO GO BACK TO HOW WE INN GAUGE OTHER ICs WE HAD LITTLE BIT ABOUT A PILOT PROGRAM THAT WE TO GIVE ADRD SUPPLEMENTS TO NONA. D. GRANTS. AND WE STARTED THIS LAST YEAR WITH 1 IC ANDY DECIDED TO OPEN IT TO THE ICs THIS YEAR AND DR. ROBIN BAR OVERVIEWED HOW IT WAS AN OVERWHELMING RESPONSE. SO ALMOST ALL OF THE ICs AND SEVERAL OFFICES AT NIH ACTUALLY SIGNED ON FOR THIS PROGRAM AND WE CAN'T LET YOU KNOW YET BECAUSE IT'S NOT PUBLIC THE NUMBER OF APPLICATIONS WE RECEIVED BUT IT WAS DEFINITELY AN OVERWHELMING RESPONSE SO THE FIELD AND OTHER ASPECTS OF THE RESEARCH FIELD WHO AREN'T ACTUALLY DOING AGE RESEARCH FIND THAT IT'S REALLY USEFUL TO BE ABLE TO TO ADD A SUPPLEMENT TO THESE PROGRAMS SO DR. BAR REVIEWED SOME OF THE DIFFERENT AREAS WHERE THERE'S BEEN INTEREST SO LIKE FOR EXAMPLE IN THE CANCER EN--STRATEGIESITUTE THERE WILL BE A COUPLE OF SUPPLEMENTS ABOUT CHEMO BRAIN AND THEN WITH THE DIABETES, THERE'S A CLEAR INTERSECTION BETWEEN DIABETES AND DEMENTIA. SO POSSIBLY A FEW SUPPLEMENTS IN THAT AREA. SO IT'S DEFINITELY BEEN A LOT OF INTEREST FROM THE FIELD. SO WE'RE DEFINITELY GRATIFIED TO SEE THAT. BASIC LOW HOW CAN WE STRETCH THE DOLLARS FURTHER AND BRING NEW PEOPLE TO THE FIELD. SO WE THEN REVIEWED THE FINANCIAL SUPPORT THAT NIA HAS BEEN ABLE TO SHARE WITH OTHER ICs IN 2016 AND 17 AND WE'RE PROUD TO SAY THAT WE'VE MORE THAN DOUBLED THE SUPPORT IN THOSE YEARS AND IN 2017 WE'VE GIVEN ALMOST $58 MILLION TO OTHER ICs SO. SO IT'S REALLY IMPORTANT TO US THAT WE'RE FUNDING MERITORIOUS WORK SO EVEN IF IT'S NOT HAPPENING THROUGH OUR IC, IF THERE'S OTHER WORK HAPPENING AT OTHER ICs THAT THEY WOULD NOT BE ABLE TO FUND, WE'RE WORKING WITH THEM TO FUND PROJECTS THAT FALL WITHIN OUR PAY LINE. SO IN FY17 THAT WAS AROUND 58 MILLION-DOLLAR. AND THEN WE DID A LOOK TO SEE BETWEEN THE YEARS OF 2015 AND DWENT 17 WHEN WE'VE BEEN GETTING THESE EXTRA APPROPRIATIONS FROM CONGRESS HOW HAS THAT AFFECTED NEW INVESTIGATORS? BECAUSE WE'VE REALLY COMMITMENTED TO SUPPORTING NEW INVESTIGATORS AND WE WANTED TO TAKE A LOOK AND SEE HOW THAT HAS ACTUALLY EFFECTED THEM. SO IF YOU LOOK AT OUR PORTFOLIO FOR RO1S AND RF-1S IN THAT TIME SPAN, 1 QUARTER OF OUR ADRD GRANTS WERE GIVEN TO NEW AND EARLY STAGE INVESTIGATORS AND THEN IF YOU LOOK AT INVESTIGATORS IN THAT SAME TIME FRAME THAT HAD NEVER PREVIOUSLY HAD ANNALS HYMER'S CODED OR ALZHEIMER'S RELATED DEMENTIA CODED PROJECT. ONE-THIRD OF OUR RO1S AND RF-1S WERE GIVEN TO INVESTIGATORS THAT WERE NEW TO THE FIELD. SO WE HAVE BEEN ABLE TO SUCCESSFULLY PULL IN PEOPLE WHO HAVE NEVER PREVIOUSLY STUDIED ALZHEIMER'S RESEARCH AND WE THINK THAT'S IMPORTANT FOR INNOVATION AND ACTION AND BE ABLE TO WISELY USE THE FUNDS THAT CONGRESS IS TRUSTING US WITH. SO I ALSO THEN REVIEWED DIVISION OUTREACH SO OUR OFFICE AND THE COMMUNICATION OFFICE DID IS A GRAT JOB OF AT THE O. D. LEVEL OF GETTING THE WORD OUT BUT A LOT OF IT HAPPENS IN THE DIVISIONS AND THEY'RE THE 1S MEETING WITH RESEARCHERS AT CONFERENCES, AT WORKSHOPS HAVING ONE-ON-ONE PHONE CALLS AND MEETINGS WITH THE PEOPLE DOING THE RESEARCH. SO I JUST RELAYED A NUMBER OF DIFFERENT MEETINGS THAT A LOT OF OWEVER PROGRAM STAFF HAS BEEN ABLE TO ATTEND AND OTHER ACTIVITIES AND WORKSHOPS IN WHICH THEY USE AS A PLATFORM TO GET THE WORD OUT ON THE VARIOUS FOAs THAT WE HAVE. SO WE KNOW THAT IT'S SOMETIMES AN OVERWHELMING NUMBER OF FOAs, BUT WE USE THE TALK YESTERDAY TO JUST REALLY HIGHLIGHT, WE ARE WORKING HARD AND WE ARE USING MULTIPLE TOOLS TO GET THE WORD OUT TO THE COMMUNITY. THANK YOU. >> THANK YOU. QUESTIONS? >> NO QUESTIONS FOR DAWN. WE CAN MOVE ON. ALL RIGHT. THANK YOU DAWN AND WE ARE GOING TO MOVE ON TO A REPORT FROM THE OFFICE OF PLANNING ANALYSIS AND EVALUATION ON STRATEGIC DIRECTIONS FOR 2019 AND KATE NAGEE WILL PRESENT. >> GOOD MORNING EVERYONE, YESTERDAY I ADDRESSED THE WORKING GROUP ON PROGRAM ABOUT THE NIA STRATEGIC DIRECTIONS DOCUMENT WHICH IS A DOCUMENT THAT YOU'RE ALL VERY FAMILIAR WITH. AND IT'S TIME TO UPDATE IT. ACTUALLY IT'S A LITTLE BIT BEFORE TIME BUT SEVERAL THINGS HAVE BEEN HAPPENING THAT MAKE THIS A REALLY GOOD TIME TO LOOK AT CHANGING IT AND THE BIG THING IS THE 21st CENTURY CURES ACT WHICH MANDATES THAT STRATEGIC PLANS AT THE EN--STRATEGIESITUTE LEVEL CONTAIN CERTAIN INFORMATION THAT WASN'T NECESSARILY MANDATED BEFORE ALTHOUGH MANY STRATEGIC PLANS INCLUDED SOME OF THIS INFORMATION, THAT ENCLUEDS THINGS LIKE SPECIAL POPULATIONS, HEALTH DISPARITIES AND OUR PLAN TO REDUCE HEALTH DISPARITIES. THERE'S ALSO BEEN A TRANSNIH EFFORT TO DEVELOP A COMMON TEMPLATE AND THAT INCLUDES ITEMS LIKE MECHANICMENT AND RECRUITMENT AND RISK MANAGEMENT AND RETENTION AND A LOT OF THINGS THAT QUITE FRANKLY WE'VE NEVER INCLUDED BEFORE. SO WE HAVE BEGUN THE PROCESS OF THE NEW STRATEGIC PLAN AND THAT'S BEEN A MULTISTEP PROCESS THAT'S BEEN GOING ON ABOUT APRIL. WE STARTED OUT BY SURVEYING THE RESEARCH COMMUNITY THROUGH THE NIA BLOG REAL BEABOUT HOW THEY USE THE DOCUMENT AND WE RECEIVED A VERY ENCOURAGING AND ROBUST RESPONSE FROM THE COMMUNITY. WE HAVE AN TERNAL ANALYSIS GOING ON OF FOAs AND NEW PROJECTS THAT WERE AWARDED SINCE THE PREVIOUS STRATEGIC DIRECTIONS DOCUMENT WAS RELEASED AROUND 2015 TO SEE HOW THEY MAP TO THE STRATEGIC DIRECTIONS AND OUR THOUGHT IS THAT THAT WILL INFORM THE DEVELOPMENT OF NEW--OF NEW OR--IT'LL INFORM THE DEVELOPMENT OF NEW STRATEGIC DIRECTIONS OR POINT TO WHERE OUR CHANGE MIGHT BE NECESSARY. WE'VE BEEN ALSO ALSO INTERVIEWING DIRECTORS AND STAFF AND RECEIVED VERY INTERESTING FEEDBACK FROM THEM. THE OVERWHELMING MESSAGE, 2 REALLY OVERWHELMING MESSAGES WE'VE RECEIVED FROM PROGRAM, FIRST IS THAT SINCE 2014-2015 THE MAJOR SCIENTIFIC GOALS AND OBJECTIVES REALLY WON'T HAVE CHANGED ALL THAT MUCH. WITH THAT SAID, WE DO NEED TO INCREASE THE VISIBILITY OF ALZHEIMER'S DISEASE AND RELATED DEMENTIAS WITHIN THE DOCUMENT. IT'S THERE, IT'S NOT EMPHASIZED AND THAT WAS A DELIBERATE DECISION BACK IN 2014. WE DECIDED THAT STRATEGIC PLANNING FOR ALZHEIMER'S DISEASE WAS ITS OWN THING. WE HAD THE NATIONAL PLAN, WE HAD THE BYPASS BUDGET, AND IT WOULD BE REFERENCED, IT WOULD BE REFERRED TO IN OUR--IN THE MAIN STRATEGIC PLAN BUT WE WOULDN'T--WE WOULDN'T GO INTO A GREAT DEAL OF DETAIL. THE MESSAGE WE'RE GETTING FROM PROGRAM RIGHT NOW IS THAT IT DOES NEED TO BE MUCH MORE VISIBLE THROUGHOUT THE DOCUMENT IN SUCH A WAY IT DOESN'T CONFLICT WITH THE GOALS OF THE NATIONAL PLAN SO THAT WILL BE A PARTICULAR CHALLENGE. WE'RE ALSO REQUIRED TO TO INCLUDE CERTAIN PERFORMTANCE METRICS, THAT'S SOMETHING WE'VE NEVER DONE BEFORE SO I'M LOOKING IF ORDER TO ANYBODY WHO WANTS TO WORK WITH ME ON HOW WE WILL DO THAT. SO THE TIMELINE IN NOVEMBER WE WILL BE RELEASING AN RNI TO GET THE FEEDBACK FROM THE ENTIRE SCIENTIFIC COMMUNITY AND ANYBODY ELSE WHO WISHES TO WEIGH IN. I WILL ALSO BE PRESENTING AT GSA. WRITING AFTER GATHERING ALL OF THIS INFORMATION AND WORKING WITH PROGRAM AND WORKING WITH YOU WILL BE WRIGHTING THROUGH APRIL, FINAL REVISION REVIEW IN APRIL, FINAL PRESENTATION TO COUNCIL OF MAY OF NEXT YEAR AND FINAL RELEASE IS TARGETED FOR JUNE 15th 2019. IT'S AN AMBITIOUS TIMELINE BUT IT'S DOABLE. ONE TECHNOLOGY TRANSFER THAT WAS BROUGHT UP YESTERDAY IS--IT WAS ASKED WHETHER COUNCIL WOULD BE INVOLVED A LITTLE BIT BEFORE MAY AND WOULD HAVE THE OPPORTUNITY TO WEIGH INTO A DOCUMENT BEFORE THEN. ABSOLUTELY. WE WILL WORK THAT INTO THE SCHEDULE AND I'LL WORK WITH DR. BAR TO TALK ABOUT WHAT THAT MIGHT LOOK LIKE. I WILL BE THE PRIMARY POINT OF CONTACT FOR THIS PROJECT. SO IF ANYBODY HAS ANY QUESTIONS, FEEDBACK, INPUT, PLEASE FEEL FREE TO CONTACT ME AT ANY TIME. THANK YOU. >> THANK YOU KATE. DOES ANYONE HAVE ANY QUESTIONS NOW? OR INPUT? >> NO QUESTIONS ARE APPEARING AT THE TABLE. ALL RIGHT. THEN I THINK I'LL HAND IT OVER TO YOU ROBIN. DO YOU WANT TO REPORT ON STATISTICAL DATA YOU PRESENTED YESTERDAY. >> I'LL MENTION IT BREFLY, THANK YOU, YES. SO AT EVERY COUNCIL WE HAVE A STATISTICAL PACKAGE WHICH SUMMARIZES THE APPLICATIONS THAT HAVE BEEN SUBMITTED TO US FOR THAT ROUND AND WE ALSO HAVE A TABLE THAT IT SHOWS HOW WELL THEY'RE PERFORMING IN REVIEW IN PEER REVIEW IN CSR. THE POINTS THAT I WAS MAKING YESTERDAY IS THAT WAS SEEN CONSIDERABLE GROWTH IN OUR APPLICATIONS, NOTICED JUST IN THOSE THAT GENERALLY COME IN THROUGH THE DOOR AT INVESTIGATOR INITIATED APPLICATIONS AND THAT THAT GROWTH IS PARTICULARLY CONCENTRATED IN ALZHEIMER'S DISEASE WHERE THE ALZHEIMER'S DISEASE APPLICATIONS ARE NOW WELL OVER 50% OFF THE APPLICATIONS COMING IN THE DOOR. BUT THAT GROWTH IS ITSELF NOT ON PARWITH THE BUDGET INCREASES WE'VE BEEN SEEING. WE HAVE IN ADDITION TO THAT THOUGH SUBSTANTIAL MEMBERS OF THE APPLICATIONS COMING IN ON INITIATIVES THAT WE DEVELOP THE FOAs THAT YOU HEARD ABOUT EARLIER THIS MORNING. AND WE RECEIVED AROUND ABOUT 500 OF THOSE APPLICATIONS FOR THE AUGUST ROUND WHICH IS PART OF THIS DISCUSSION SO IT'S A COMBINATION OF THE APPLICATIONS COMING IN FROM THE INITIATIVES AND THE INVESTIGATOR APPLICATIONS THAT COMES IN REGULARLY THAT GIVES US THE FULL NUMBER OF APPLICATIONS THAT DOES IN FACT USE THE EXTRA FUNDS THAT WE'VE BEEN GIVEN. THAT WAS THE SUMMARY. THE POINT I WAS MAKING ABOUT TABLING 2 THAT A LOT OF APPLICATIONS COMING IN ARE HAVING DIFFICULT NEUROECTODERMAL PEER REVIEW, THEY'RE NOT DOING SO WELL, NOT SURPRISING WHEN IT'S NEW APPLICATIONS ACTUALLY BUT IT SEEPS A LOT OF THE PROBLEM IS PRELIMINARY DATA, THEY DON'T HAVE SUFFICIENT PRELIMINARY DATA TO COMPETE WELL, AND SO THEY'RE LOOKING AT WAYS TO ALLOW APPLICATIONS TO ACQUIRE MORE PRELIMINARY DATA BEFORE THEY CAN--DO COMPETE FOR RO1S AND THE ADMINISTER THE SUPPLEMENT PROGRAM YOU HEARD EARLIER IS A WAY IN DID WE'RE DRYING TO GET PRELIMINARY DATA TO INVESTIGATORS. THANKS. >> ANY QUESTIONS FOR ROBIN? WELL HEARING NONE, I THINK THAT COMPLETES THE REPORT ON THE WORKING GROUP, ROBIN. >> THANK YOU. DR. HODES. >> AND DR. HODES? >> THANK YOU. AT THIS POINT I WANTED TO HAVE A CHANCE TO INTRODUCE PEOPLE WHO ARE NEW TO OUR STAFF OR FOR PEOPLE WHO ARE HERE VISITING, NOT PART OF OUR STAFF TO INTRODUCE THEMSELVES LET'S BEGENERATED WITH NEW STAFF. ANYONE WHO WE OUGHT TO BE GRIEWSING TO COUNCIL FOR THE FIRST TIME. NO, WE KNOW YOU. >> [LAUGHTER] >> I WILL INTRODUCE MYSELF ANYWAY, I'M MOLLY WAGS FROM THE DIVISION OF NEUROSCIENCE AND I WANT TO INTRODUCE A COUPLE OF INDIVIDUALS, 1 NEW STAFF MEMBER AND 1 PERSON WHO'S BEEN WORKING WITH US THIS SUMMER. FIRST OF ALL DR. MATT SUT EROZAN JOINED US LAST WEEK AS A HEALTH SPECIALIST IN OUR DIVISION OF NEUROSCIENCE AND THE BEHAVIORIAL AND SYSTEMS NEUROSCIENCE BRANCH AND MATT COMES TO US--WELL, ACTUALLY MOST RECEIPTLY HE JUST COMPLETED A TRIPLE AES FELLOWSHIP WORKING AT THE NATIONAL EN--STRATEGIESITUTE ON JUSTICE. HE RECEIVED HIS Ph.D. IN NEUROSCIENCE UNDER THE MENTORSHIP OF DR. DAN CHENLE KNOWN TO MANY OF US HERE AND DID A POST DOC ALSO AT THE UNIVERSITY OF IOWA UNDER CURRENT NIA GRANTEE DR. MICHELLE VOSS. SO WE'RE REALLY PLEASED. I'M VERY PLEASED TO HAVE MATT JOIN US. ALSO ON THE RIGHT SIDE OF THE ROOM, DR. CARMEN CASTRA, CARMEN HAS A DIRECT RAT IN PUBLIC HEALTH WITH SPECIALTY IN HEALTH SERVICES AND THIS PAST YEAR CARMEN HAS BEEN A HEALTH AND AGING POLARIZED FELLOW. THIS IS A FOLLOWSHIP PROGRAM SUPPORTED BY THE ATLANTIC PHILANTHROPIES AND THE HARVARD FOUNDATION AND CARMEN SPENT THE FIRST PART OF HER FELLOWSHIP WORKING IN THE OFFICE OF CONGRESSMAN GENE GREEN WHO REPRESENTS HER HOME DISTRICT IN HOUSTON, TEXAS. AND THIS SUMMER, THE PAST FEW MONTHS CARMEN CAME TO SPEND THE LATTER PART OF HER FELLOWSHIP HERE AT NIA IN OUR DIVISION OF NEUROSCIENCE HELPING WORK ON RECOMMENDATIONS FROM A PREVIOUS NATIONAL AKD--SALLY ME STUDIES ON PUBLIC HEALTH DIMENSIONS OF COGNITIVE AGING AND FOCUSED ON TECHNOLOGY AND COGNITIVE AGING. SO WE REALLY PREERKT THE HELP FROM CARMEN THIS SUMMER. >> WE JUST ADDED THESE ARE EXCELLENT EXAMPLES OF SOME OF THE PROGRAMS THAT ALLOW PEOPLE CAN WITH GREAT TALENTS AND BACKGROUNDS TO COME SPEND ROTATIONS AND FORTUNATE ENOUGH THAT OTHERS OF THEM ADD TO THE STRENGTHS OF THE INSTITUTE. >> [INDISCERNIBLE]. >> OH SORRY. BRAD WISE DISCIPLINARY VITIONZ OF NEUROSCIENCE, I WANT TO INTRODUCE AMANDA DEBAUDISTA AS A NEW PROGRAM OFFICER IN THE DISCIPLINARYRICIAN AND NEUROBIOLOGY AGING BRANCH. AMANDA GOT HER Ph.D. IN NEUROSCIENCE FROM GEORGETOWN UNIVERSITY AND AMANDATORY IS NOT NEW. MANY OF YOU KNOW HER, SHE'S BEEN HERE FOR A COUPLE YEARS WORKING AS A RESEARCH PROGRAM ANALYST WHERE SHE HAS DONE A FANTASTIC JOB IN HELPING US DO DATA AND GRANT ANALYSIS AND NOW SHE'S TURNING HER TALENTS TO DEVELOPING AND MANAGING A PORTFOLIO IN THE NEUROBIOLOGY OF AGING AND ALZHEIMER'S DISEASE. SO I REALLY AM HAPPY TO INTRODUCE HER IN THIS NEW ROLE AND SHE WILL BE A GREAT ASSET TO US. >> JOHN HAGUEIN FROM THE DIVISION OF BEHAVIORIAL AND SOCIAL RESEARCH AND I WOULD LIKE TO ACKNOWLEDGE DR. LORIE FRANK WHO'S ANOTHER HEALTH AND AGING POLICY FELLOW WHO'S BEEN WORKING WITH US THIS YEAR. LORIE COMES TO US FROM THE PC ORI, PATIENT CENTERED RESEARCH--OUTCOME RESEARCH INSTITUTE. SHE'S BEEN WORKING ON A BUNCH OF THINGS, ACTUALLY WITH 2 DIVISIONS, WITH DIVISION OF NEUROSCIENCES AS WELL AS PSR AND HEAD OF PRODUCTIVE FELLOWSHIP THERE. THANK YOU LORIE? HI [INDISCERNIBLE]. FROM THE DIVISION OF NEUROSCIENCE, EVERYBODY KNOWS SEREECE, ELLIOTT SO NO NEED FOR AN INTRODUCTION BUT I WANT ANNOUNCE SHE'S BEEN OFFICIALLY PROMOTED PROGRAM DIRECTORS AND IN HER NEW POSITION SHE'LL CONTINUE TO WORK WITH NINA ON THE ALZHEIMER'S DISEASE CENTERS AS WELL AS ON THE PROGRAMS THAT ACTUALLY WE HEARD SHE'S BEEN WORKING ON DIVERSITY, RECRUITMENT AND A NUMBER OF OTHER REALLY EXCITING IDEAS. SO GOOD TO HAVE YOU. ONE MORE. THANK YOU I'VE JUST BEEN REMINDED THAT WE HAVEN'T ANNOUNCED AT COUNCIL THAT DR. JOHN PHILLIPS WHO UNFORTUNATELY CAN'T BE HERE FOR A MEDICAL ISSUE TODAY HAS REJOINED NIA, HE CAME TO US MOST RECENTLY FROM A POST AS ASSOCIATE DIRECTOR OF THE SOCIAL SECURITY ADMINISTRATION. HE'S THE BRANCH CHIEF FOR THE POPULATION AND SOCIAL PROCESSES BRANCH. >> I THINK IT'S MY TURN NOW. HAVE A COUPLE OF INTRODUCTIONS TO MAKE, TOO. WE--WE AT N IA HAVE JUST--ARE JUST ESTABLISHING A NEW OFFICE SMALL BUSINESS RESEARCH AND THE INCOMING DIRECTOR OF THAT OFFICE IS WITH US TODAY HE'S DR. TODD HAIM. HE'S COMING FROM THE NATIONAL CANCER INSTITUTE WHERE HE'S BEEN PART OF THE SMALL BUSINESS INITIATIVE AND PROGRAM AT NCI. HE'S RIGHT BEHIND ME. AND WE ARE AWLTS VERY FORTUNATE TO BE ABLE RECRUIT DR. REPUBLICAN A [INDISCERNIBLE]. WE'VE STOLEN HIM FROM CSR, AND HE IS--I REALLY VERY MUCH APPRECIATE HIS EXPERIENCE AND EXPERTISE, NOT ONLY IN REVIEW WHERE HE HAS GREAT EXPERTISE BUT ALSO HIS BACK GROWBD IN ALZHEIMERER'S DISEASE RESEARCH AND THAT'S ALSO A VERY USEFUL ASSET FOR MY DIVISION. THE THIRD PERSON WE RECRUITED AND DR. [INDISCERNIBLE]. AND [INDISCERNIBLE] IS RIGHT ALL THE WAY DOWN THERE HIDING HE IS THE FIRST FULL-TIME TRAINING OFFICER THAT THE INSTITUTE HAS HAD IN ITS MORE THAN 40 YEARS OF EXISTENCE AND THAT'S BEEN 40 YEARS TOO ALONG WITHOUT A TRAINING OFFICER SO WE NOW HAVE 1. I AM VERY GLAD OF IT AND HE IS DOING A GREAT JOB ALREADY. >> AND DO WE HAVE VISITORS WHO WOULD LIKE TO INTRODUCE THEMSELVES? >> HI, I'M BRUCE LAMB, I WILL SPEAK LATER, I'MAD INDIANA UNIVERSITY AND LEADING THE MODEL A. D. CONSORTIA. ALL RIGHT THEN, FINAL BITTER SWEET MOMENT IS ACKNOWLEDGING OUR RETIRING MEMBERS. ONE RAYNARD KINGTON IS NOT ABLE TO BE HERE. HIS LEADERSHIP OF VERNELL COLLEGE HAS NOT ALLOWED HIM TO BE HERE AND HE HAD A REMARKABLE HISTORY IF WE WERE TO TRACK IT FROM YOU OF SUPPORT FROM THE EARLIEST TRAINING STAGES THROUGH SENIOR SUCCESS AT NIA AND DEPUTY DIRECTOR FOR ALL OF NIH BEFORE TAKING THESE CURRENT POSITION AND HE'S WAS A GREAT ASSET TO US HERE ON COUNCIL. AND THEN THERE ARE 3 MEMBERS WHO ARE ATTENDING AND HERE TO RECEIVE OUR THANKS AND GRATITUDE. USUALLY HAVE THE PLAQUES IN HAND FOR THIS BUT WE WILL HAVE TO DO IT-- >> [INDISCERNIBLE]. >> WE WILL GET THEM TO YOU. BUT EVEN WITHOUT THE CHERISHED PLAQUES, MARIA CARRILLO, MARIA AT NIA INCLUDING A PERSONAL RELATIONSHIP, I HAVE APPRECIATED GO BACK MANY YEARS BEFORE COINCIDENCE ILLEGALS SERVICE AND THAT IMPORTANT RELATIONSHIP AND COOPERATION BETWEEN THE ALZHEIMER O ASSOCIATION AND OUR INSTITUTION HAS BEEN TYPIFIED BY THE PERSONAL RELATIONSHIP I'VE VALUED WITH MARIA. HERE HER STAY ON COUNCIL HAS BEEN, NORMOUSLY USEFUL. SHE AS A SCIENTIFIC BACKGROUND. SHE HAS AN ADVOCACY BACKGROUND, SHE REPRESENTS THE EFFORTS OF NIA AND PARTNERSHIPS WITH PURSUING COMMON GOALS AND THERE'S NO WAY SHE WILL ESCAPE OUR CONTINUED RELATIONSHIP WITH HER BUT MARIA THANK YOU FOR YOUR TIME ON COUNSELS AND I WILL GIVE YOU A CHANCE IT SAY A FEW WORDS OR MORE? >> WELL THANK YOU VERY MUCH. IT'S BEEN A TBRAIT OPPORTUNITY FOR ME SO I REALLY APPRECIATE IT AND THE HONOR THAT WAS BESTOWED UPON ME WHEN I ASKED TO BE ON COUNCIL AND IT'S BEEN A GREAT PARTNERSHIP FOR ALMOST 15 YEARS NOW WITH YOUR TEAM, EXTRAORDINARILY IMPRESSED WITH THEIR LEADERSHIP AND IMPRESSED WITH THE--NOW THAT I'VE SEEN THE OTHER SIDE OF IT, THE OPERATIONS, AND ALL THE THOUGHT THAT GOES BEHIND EVERYTHING, CERTAINLY AS A REPRESENTATIVE FROM THE ALZHEIMER'S ASSOCIATION, WE'RE GRATIFIED TO SEE HOW EARNESTLY AND THOUGHTFULLY ALL THE DOLLARS ARE DEPLOYED SO HOW YOU THINK ABOUT ALL OF THAT FROM SOUP TO NUTS AND WE GOTTEN A DEEPER VIEW OF THAT ON COUNCIL, I THINK THAT WE DON'T GET WHEN WE'RE OUTSIDE WHETHER YOU'RE A RESEARCHER OR ADVOCACY REPRESENTATIVE SO THAT'S BEEN FABULOUS TO SEE, WE ARE LIVING ON A HISTORIC MOMENT, THERE'S NO DOUBT RELATED TO AGING AND DEMENTIAS AND NEUROGERONTOLOGYSTS GENRATIVE DISEASES AND THIS IS A HISTORIC MOMENT OF FUNDING AND THERE IS NO BETTER PLACE FOR THAT FUNDING TO BE LED THAN THROUGH YOU DR. HODES AND YOUR TEAM AND I'M IMPRESSED ABOUT THAT AND BRAG ABOUT ALL THE AMAZING THINGS THAT ARE HAPPENING ASKED BY OUR ADVOCATES AND ALL OF THOSE FEEL THE SAME WAY HERE ABOUT HOW THEY'RE ALL USED AND IF THEY'RE DEPLOYED IN THE RIGHT WAY SO WITH CONFIDENCE WE'RE ABLE TO SAY THAT WE KNOW WHICH WAY OUR PATH IS MOVING FORWARD BECAUSE THERE IS GREAT LEADERSHIP IS THAT MOVING THAT. WE KNOW THAT CERTAINLY THERE'S MORE MONEY COMING AND THERE WILL BE MORE WORK AND WE KNOW YOU NEED MORE STAFF AND MORE SUPPORT BUT THE HOUSE AND SENATE APPROPRIATIONS COMMITTEE APPROVED 425 MILLION AND SO, IF THE BILL GETS PASSED, SENATE WILL VOTE ON IT NEXT WEEK, THE HOUSE WHEN THEY COME BACK THEN THAT BILL CONTAINS 425 MILLION AS OF THIS MORNING OR YESTERDAY AFTERNOON. SO, MORE WILL COME AND THIS IS AGAIN AN HISTORIC MOMENT. IT'S BEEN A PRIVILEGE AND HONORER FOR ME TO BE PART OF THAT AS THAT MONEY HAS COME THROUGH AND I'M GRATEFUL FOR NOT ONLY EVERYTHING I LEARNED BUT EVERYTHING YOU DO EVERY DAY FOR ALL OF US HERE IN THE UNITED STATES. SO THANK YOU VERY MUCH DR. HODES,. >> THANK YOU AGAIN FOR ALL THE SUPPORT INCLUDING THE OCCASIONALLY PUBLISHED NUT BETTER AND JELLY SANDWICH WHICH WE TRAVEL TOGETHER AND NOW IT WILL BE UNCONSTRAINED 6 DAYS A YEAR WHEN YOU WERE PREVENTED FROM LOBBYING TO DO THAT AND 365 DAYS THROUGHOUT THE YEAR. NEXT JIM KIRKLAND WHO'S BEEN AN OUTSTANDING INVESTIGATOR IN THE AREA OF AGING RESEARCH AND THE BRIGHT STAR IN THAT AREA OF RESEARCH. SO HIS FOOT IN BOTH THE CLINICAL AND RESEARCH SIDE HAS BEEN EXTRAORDINARY THROUGH THE NEW EXCITING AREA OF AGING CELLS AND ANALYTICS HE'S EMBLEMATIC OF OUR TRANSLATION OF BASIC SCIENCE AND EXCITING POTENTIALS FOR TRANSLATION TO THE GOOD OF AN AGING AND OLDER GLOBAL POPULATION AND ALL THAT WE THANK AND YOU WITH THE PROMISE WE WILL CALL ON YOU TO DO SO MORE AND ASK IF YOU WOULDED LIKE TO SAY A FEW WORDS? >> THANK YOU VERY MUCH. I ECHO MARIA'S VERY ELOQUENT THOUGHTS. I TO HAVE LEARNED A LOT ON COUNCIL BUT WHAT'S REMARKABLE I THINK HAS BEEN TRANSFORMATION IN THE FIELD IN THE LAST FEW YEARS WHILE I'VE HAD THE PRIVILEGE OF BEING ON COUNCIL. HASN'T GONE UNNOTICED IN OUR TRAINEES. AND WE'RE FINDING THAT THE VERY BEST AND BRIGHTEST NOW WANT TO GO INTO RESEARCH ON THE BASIC BIOLOGY OF AGING AND NEUROCOGNITIVE DISEASE AND THE VERY BEST AND BRIGHTEST WANT TO BECOME GERIATRICIANS AND WE'RE FOR EXAMPLE GETTING OUR CHIEF RESIDENTS, WANTING TO GO INTO GERIATRICS. I'VE NEVER SEEN THAT HAPPEN BEFORE. SO I THINK THE INCREASE IN FUNDING THAT'S COMING IS GOING TO BE USED UP VERY QUICKLY AND IS GOING TO BE CAPITALIZED UPON THIS NEW WAY FOR PEOPLE COMING INTO THE SYSTEM. AND THEY'RE NOT COMING INTO THE SYSTEM JUST BECAUSE THERE'S MONEY THERE. THEY ARE COMING INTO THE SYSTEM BECAUSE WE'RE ACTUALLY AT THE POINT OF BEING ABLE TO DEVELOP INTERVENTIONS THAT COULD DELAY, PREVENT OR ALLEVIATE AGE RELATED DISEASES INSTEAD OF PICKING THEM OFF 1 AT A TIME AND THESE ARE THE CONDITIONS THAT CONTRIBUTE THE BULK OF MORBIDITY, MORTALITY AND EXPENDITURES NOT ONLY IN THE U.S. BUT AROUND THE WORLD AND ESPECIALLY IN DEVELOPING COUNTRIES AND I THINK OUR STUDENTS ARE SEEING THIS. SO WHAT'S HAPPENING IS INCREDIBLY IMPORTANT BECAUSE WE WILL HAVE A NEW WAVE OF BIG PEOPLE WHO ARE INCREDIBLY BRIGHT AND I THINK EVEN THOUGH WE'RE FINDING THAT PERCENTILES WHEN FUNDING IS ACCORDED HAVE GONE UP. THEY'RE GOING TO GO DOWN AGAIN BECAUSE WE'RE GETTING THIS HUGE RUSH OF VERY SMART PEOPLE MOVING INTO THE FIELD. SO I'VE BEEN VERY, VERY EXCITED TO BE HERE AND SEE THIS HAPPENING FROM THIS VANTAGE POINT I'D ALSO COMMEND ALL THE PEOPLE I'VE WORKED WITH AT THE NIA, YOU GUYS ARE DOING A FANTASTIC JOB, I NEVER REALIZED HOW DIFFICULT IT IS AND HOW MUCH OF AN IMPORTANT ROLE EVERYBODY HERE HAS AND I'VE BEEN TELLING OUR TRAINEES ABOUT THAT AS WELL. SO, AGAIN, THANK YOU FOR ALL THE HARD WORK THAT THE VERY BRIGHT PEOPLE OF THE NATIONAL EN--STRATEGIESITUTE ON AGING ARE DOING ACROSS THE NIH AND ALSO AT THE FDA, THE FDA NOW GETS IT AND I THINK THEY WILL BE A VERY IMPORTANT PARTNER GOING FORWARD. SO THANKS. >> THANK YOU FOR SUMMARIZING SO WELL THE VERY ASPECT OF THE TIME. I REMEMBER YOU USED TO QUOTE THE INCREDIBLY LOW NUMBER OF GERIATRICIANS ENGAGED IN RESEARCH AND I HEAR YOU NONAPOPTOTIC YOU TO BE SEEING SOME DRAMATIC CHANGES IN THIS AND IT'S EXTRAORDINARY, IT'S NOT JUST THE PAY LINE AND BUT THE FUNDING IN THE SOMETIME WHEN OPPORTUNITY IS SO EXCITING IT'S MAGNIFICENT AND IT'S THE PERFECT KIND OF APPROXIMATER FECT STORM IN THIS CASE AND THANK YOU FOR BEING HATTER OF IT. --PART OF. ANN E NEWMAN HAS BEEN WITH US IN CLINICAL EXPERTISE AND AGING TRANSLATIONAL ASPECTS. IN PARTICULAR ANNE KNOWS WE'RE NOT ABOUT TO LET HER GO WHEN WE'RE TRYING TO APPOINT HER TO HER VERY NEXT TERM OF SERVICE WHICH SHOULD BE A WARNING TO ALL OF YOU. [LAUGHTER] WITH THAT VERY CONDITIONAL THANKS AND FAREWELL, WOULD YOU LIKE TO TALK TO US A BIT? >> THANK YOU. I CAN ONLY ECHO THE STATEMENTS THAT HAVE BEEN MADE ABOUT THE WONDERFUL OPPORTUNITY TO WORK WITH SUCH A STELLAR GROUP OF STAFF AT THE NIA AND TO HAVE THE OPPORTUNITY TO WEIGH IN ON IMPORTANT OPPORTUNITIES AT A HIGH LEEFUL. SOME OF THOSE OPPORTUNITIES INCLUDED WORKING ON THE REVIEW OF THE ALZHEIMERY PROGRAM WITH NINA AND SEREECE, AND WORKING ON REVIEW OF THE GERIATRICS AND ONTOLOGY PROGRAM AND WE HAD AN OVERALL NIA REVIEW LED BY RICHARD MAYHUE WHICH GAVE ME A MULTIFACETED PERSPECTIVE ON WHAT GOES ON WITHIN NIA AND I HAD ALWAYS HEARD THAT THE COUNCIL WAS JUST A PLACE TO PUT YOUR FEET UP AND NOT HAVE TO REVIEW GRANTS. AND MY EXPERIENCE HAS BEEN ENTIRELY DIFFERENT. I'VE ALWAYS FELT THAT WE WERE REALLY WORKING TOGETHER WITH THE NIASTAFF AS A COUNCIL THAT WE WERE ALL--ALL HAD THE OPPORTUNITY TO SPEAK OUT AND WERE HEARD AND I FEEL WE'VE MADE A DIFFERENCE ON MANY IMPORTANT ISSUES THAT HAVE COME UP ALONG THE WAY. MOST STUNNING HAS BEEN THE OPPORTUNITY TO SHAPE THE--HELP SHAPE THE EXCELLENT WORK DONE BY THIS, IASTAFF ON DEVELOPING HALFWAYS--PATHWAYS TO MAKE USE OF THE TREMENDOUS INFLUX OF ALZHEIMER'S FUNDING AND THE CREATIVITY AND THE ENERGY AND ENTHAT'S ENTHUSIASM HAS IN SPITE OF THE VERY INTENSE WORK LOAD I'VE NEVER GOTTEN A SENSE OF ANYTHING BUT EXCITEMENT AND POSITIVITY ABOUT THAT WHICH I THINK IS WONDERFUL AND REFLECTS THE PASSION THAT YOU ALL HAVE FOR THE WORK THAT YOU ALL DO. I'VE ALSO LEARNED A LOT ABOUT THE NEED FOR ALL OF US TO ADVOCATE FOR US TO PARTICIPATE IN THE NEED FOR AGING AND FIND THERE WERE ASSESSMENTS FOR OLDER PEOPLE INCLUDED IPT GREATER I SHALY AND WINY ROSSY DID A LOT TO PUSH ON THAT AND WE ALL NEED TO CONTINUE TO BE STRONG ADVOCATES ACROSS THE INSTITUTE. I THINK SHARING THAT A. D. MONEY , I DO A LOT OF WORK WITH NHLBI, IT WAS INTERESTING TO SEE THEIR ACTION AS NOT BEING SO AWARE OF THOSE OPPORTUNITIES AT ANOTHER EN--STRATEGIESITUTE AND IT WAS SORT OF LIKE CHRISTMAS WITH EYES LIGHTING UP AND SUDDEN LY ALZHEIMER'S DISEASE BECAME, I THINK AN ISSUE FOR EVERYONE ACROSS THE NIH AND SO THAT'S BEEN VERY, VERY EXCITING TO SEE, BUT PROBABLY THE HOST EXCITING THING TO ME IS WHAT JIM TALKED ABOUT WHICH IS FOR THE FIRST TIME, WE'RE SEEING BIOLOGY OF AGING MEETING CLINICAL GERIATRICS AND I'VE BEEN THRILLED TO SEE THAT. I DO WANT TO LEAVE JUST A THOUGHT ABOUT AGING IN GENERAL THOUGH AND I THINK THAT WE HAVE TO APPRECIATE THAT I THINK THAT I THINK AGING IS CHANGING OVER TIME AND EVERYTHING WE'VE LEARNED IN PREVIOUS POPULATIONS IN THIS COUNTRY WHO HAVE SMOKED AND HAD OTHER EXPOSURES AND THINGS LIKE THAT ARE DIFFERENT THAN THE PEOPLE WHO ARE AGING INTO THE FUTURE, SO I THINK WE STILL HAVE TO BE VERY, VERY OPEN MINDED. WE'VE SEEN THE RATES OF ALZHEIMER'S DISEASE OR AT LEAST VASCULAR DEMENTIA SEEMS TO BE CHANGING IN A POSITIVE DIRECTION, THAT WE CAN'T REST ON WHAT WE KNOW AND ALWAYS HAVE TO BE VERY, VERY OPEN MINDED AS TO WHAT AGING IS AND WHAT IT CAN BE. I THINK THERE'S A LOT OF POSSIBILITY FOR THE FUTURE AND I'M REALLY, LEGAL EXCITED ABOUT WHAT'S GOING TO BE COMING NEXT. SO THANK YOU. >> WELL, THANK YOU, A MOMENTARY PAUSE BEFORE THE ROUND OF APPLAUSE ON THE DEPARTING MEMBERS ABOUT HOW FORTUNATE NIA HAS BEEN IN THE COMPOSITION AND QUALITY OF ITS ADVISORY COUNCILS FOR YEAR AFTER YEAR. WE HAVE SUPERB PEOPLE WHO KRIEWBED IN RELIEVING--WHO ARE LEAVING AND NEW GENERATIONS COME NOTHING TO TAKE THEIR PLACES AROUND THE TABLE I DON'T--OF COURSE KNOW WHAT WE WOULD DO WITHOUT YOU AS INFORMED GUIDES AND ADVISORS TO US DURING THE TIME YOU'RE HERE AND THEN AS CONTINUED AMBASSADORS WHO SERVE IN SO MANY WAYS AFTER YOU LEAVE SO TO THOSE WHO ARE DEPARTING FROM THOSE WHO WON'T BE DEPARTING QUITE YET. THANK YOU. [ APPLAUSE ] ALL RIGHT. SO WE WILL BREAK FOR 15 MINUTES NOW AND WE WILL COME BACK AT 10:00 O'CLOCK WHICH IS A BIT AHEAD OF SCHEDULE. >> IT IS MY GREAT PLEASURE AND HONOR TO INTRODUCE DR. BRUCE LAMB WHO IS EXECUTIVE DIRECTOR OF THE STARK NEUROSCIENCE RESEARCH AND HE CHAIRS THE ALZHEIMER RESEARCH AT THE INDIANA SCHOOL OF MEDICINE. DR. LAMB IS GRADUATE OF [INDISCERNIBLE] HE DID A MOLECULAR Ph.D. AT PENNSYLVANIA AND POST DOC AT JOHN HOPKINS AND LATER ON HE JOINED CASE WESTERN UNIVERSITY AS ASSIST ASSISTANT IS ASSOCIATE PROFESSOR AND THEN MOVED TO CLEVELAND CLINIC WHERE HE CONTINUED HIS HIS OUTSTANDING RESEARCH IN ALZHEIMER PATIENT HYM EROZAN'S DISEASE--ALWAYS HYMERA DISEASE AND MORE RECENTLY IN 2016 HE WAS RECRUITED BY AN INDIANA UNIVERSITY IN HIS NEW POSITION AS EXECUTIVE DIRECTOR OF THE NEUROSCIENCE RESEARCH ENTERPRISE. HE HAS RECEIVED NUMEROUS AWARDS INCLUDING THE JENNIFER B LANGSTON AWORD FOR THE CLEVELAND CHAPTER OF THE ALZHEIMER ASSOCIATION, NATIONAL CIVIC AWARD AND THE LIFETIME ACHIEVEMENT AWARD THAT IS GRANTED BY THE NATIONAL ALZHEIMER'S ASSOCIATION AND AS YOU WILL SEE MORE FROM HIS PRESENTATION DR. LAMB WORKS ON UNDERSTANDING THE BASIC MECHANISMS OF PATHOGENESIS IN ALZHEIMER'S DISEASE WITH SPECIAL INTERESTS ON THE GENETIC MODIFIERS, THE ROLE OF INFLAMMATION IN MICROGLEEL CELLSA AND MODELING ALZHEIMER'S DISEASE UTILIZING REALLY STATE-OF-THE-ART TOOLS. SO AS YOU ALSO WILL LEARN MORE WITH FRANK [INDISCERNIBLE] AT UCI HE'S A PI ON THE MODEL A. D. CONSORTIUM WHICH HAS THE MAIN OBJECTIVE OF PROVIDING NOVEL MODELS OF LATE AMS HYMERIER'S DISEASE SO BRUCE? >> THANK YOU VERY MUCH FOR THE INVITATION. IT'S GREAT TO BE HERE AND ALSO IT'S A GREAT OPPORTUNITY FOR ME TO HEAR THE CONVERSATIONS THAT ARE OCCURRING IN THIS ROOM AND I HAVE A LOT TO COVER AND I WANT TO SHOW YOU WHERE WE'RE AT BUT BEFORE WE DO I WANT TO ECHO SOME OF THE THOUGHTS THAT WE'RE SORT SPOKEN EARLIER. THE FIRST IS HOW DRAMATICALLY THE FIELD HAS CHANGED OVER THE PAST SEVERAL YEARS I THINK THANKS TO PUBLIC ASSOCIATION POLICY TEAM, LITTLERS, HOW DRAMATIC CHANGES AND SORT OF THE ADVOCACY OF CHANGED THE DIRECTIONS AND I THINK THE COURSE OF RESEARCH AND THE LEADERSHIP HERE THAT HAS BEEN ENACTED IN THOSE CHANGES AND I CAN ALSO TELL YOU FROM THE FRONT LINE SIDE THAT THIS IS REALLY HAVING A DRAMATIC IMPACT AS WAS SUGGESTED BY DR. KIRKLAND ON ENTHUSIASM, THE COMMITMENT AND SORT OF JUST OVERALL EXCITEMENT IN THE FIELD IN TERMS OF THE FUTURE AND I THINK THAT'S A REALLY IMPORTANT THING GEAN WE NEED TO KNOW IT TO WORK ON BUT I REALLY COMMEND EVERYBODY FOR INVOLVEMENT IN THAT. SO WHAT I WANTED TO DO TODAY WAS TELL YOU ABOUT AN INITIATIVE THAT NOW WE'RE ABOUT 2 YEARS IN, IT'S CALLED THE MODEL ORGANISM DEVELOPMENT AND EVALUATION FOR LIFE ONSET A. D. CONSORTIA OR MODEL A. D. FOR SHORT AND THIS IS A CONSORTIA BETWEEN INDIANA UNIVERSITY, THE JACKSON LABORATORY, SAGE BY O NETWORKS AND ALSO THE UNIVERSITY OF CALIFORNIA IRVINE AS ELIASAR SUGGESTED. SO I WILL JUST GIVE A BIT OF BACKGROUND WITH THE ALDZ HYMER'S WE'VE HAD HAD CLINICAL FAILURES AND THESE ARE FOCUS ON PRIMARILY ON AMYLOID AND ANTITAU THERAPYINGS RIGHT HOW AND THIS IS NO SECRET TO ANYBODY IN THIS ROOM, BUT WHY DID THESE CLINICAL TRIALS FAIL IN AND THEN WHAT CAN WE LEARN FROM THAT AND WHAT DIRECTION WE NEED TO GO AND I THINK 1 IDEA OF CERTAINLY PUT OUT THERE IS THE STAGE OF DISEASE THAT'S TARGETED AND AGAIN THAT IS ONGOING RIGHT NOW TO SORT OF TRY TO CHANGE THAT I THINK THE MECHANISM OF DELIVERY HOW DRUGS ARE DELIVERED, I THINK THE SUITABILITY OF THE PATIENT AND ARE WE LOOKING FOR THE RIGHT DRUG THAT'S BEING FORWARDED. I THINK OTHER ISSUES ABOUT THE TARGET ITSELF, ARE WE LOOKING AT THE RIGHT TARGETS, HOW ARE THOSE TARGETS ENGAGED FOR BIOLOGY, ARE THERE OFFTARGET EFFECTS AND THEN FINALLY I THINK IN A LARGER LAST AREA THAT I THINK HAS BEEN RAISED AS SORT OF THE FACE AND CONSTRUCT VALIDITY OF THE MODELS THAT BEEN UTILIZED TO TAKE AND AND AND THERE'S MANY THERE'RE MANY REASONS THAT TO BE CONCERNED ABOUT THE EXISTING ANIMAL MODELS OF ALZHEIMER'S DISEASE, SOME OF THESE ARE LISTED HERE AND THERE ARE SEVERAL I THINK IN PARTICULAR THAT REALLY FELT LIKE NEEDED TO BE ADDRESSED AND THOSE ARE SORT OF CIRCLED HERE AND SO 1 IS THAT MANY OF THE MODELS THAT GENERATED OR MAINTAINED ON GENETIC BACKGROUND MAKE ITS DIFFICULT TO UNDERSTAND THE BIOLOGY, A LOT OF THESE MODELS ARE DUE TO LARGE OVER EXPRESSION OF FOREIGN TRANSGENES WHICH HAS THE OWN EFFECTS WHICH AGAIN IS A CONCERN. THERE'S BEEN A MAJOR EFFECT OF LEGAL RESTRICTIONS, SO THERE IS AGAIN I'M SURE THIS GROUP IS WELL AWARE, THE HISTORY HERE AS NOT BEEN GOOD. THAT THERE'S BEEN LEGAL RESTRICTIONS WHICH HAS MADE IT EXTREMELY DIFFICULT FOR PEOPLE IN THE FIELD TO OBTAIN ANIMAL MODELS AND DO THEIR WORK AND ALSO DO REPRODUCTION OF OTHER PEOPLE'S WORK. AND THERE'S AWLSZ BEEN I THINK NOTES A GREAT EFFORT TO DO REPRODUCIBILITY OF THE FINDINGS IN BOTH ANIMAL MODELS AND TRYING TO RELATE THOSE TO HUMAN RELEVANT BIOMARKER WHICH IS I THINK IS A REALLY IMPORTANT THING. AND THEN, 1 OF THE OTHERS HERE HAS BEEN THAT MOST OF THE MODELS HAVE BEEN GENERATED THUGS FAR HAVE FOCUSED ON EARLY ONSET ALZHEIMER'S DISEASE WHICH ARE FAIRLY RARE AND UNIQUE PRESENTATION OF THE DISEASE AND THEN FINALLY AND I CIRCLED IT THERE WITH A DOTTED LINE, YOU KNOW MOST OF THE MODELS ARE IN MICE AND AGAIN I'LL TELL YOU ABOUT THE WORK WE'RE DOING SO FAR IS IN MICE BUT WE'RE ALSO THINKING ABOUT WHAT OTHER SPECIES SHOULD WE BE THINKING ABOUT TO DEVELOP NEW MODELS. SO OUT OF THE 2015 NIA ALZHEIMER'S DISEASE SUMMIT CAME THESE RECOMMENDATIONS WHICH ARE REALLY FOCUSED AGAIN ON THAT ISSUE OF FACE AND CONSTRUCT VALIDITY FOR THE ANIMAL MODELS FOR THE PRECLINICAL TESTING AND YOU CAN SEE THEM HERE LISTED HERE AGAIN IN GENERATION AND NEXT GENERATION OF INVIVO MODELS, STANDARDIZATION AND RIGOROUS PROCESS FOR DEVELOPMENT AND CHARACTERIZATION OF THESE MODELS, TRANSLATABLE BIOMARKERS AND FINALLY RIGOROUS PRECLINICAL TESTING AND THAT'S SORT OF ALL PUT TOGETHER INTO THIS NIA INNERRISHIAATIVE THAT'S LISTED THERE, WHICH LED ULTIMATELY TO THE FUNDING OF 2 SEPARATE U54S WHICH TOGETHER ARE NOW PART OF THE MODELING DE-CONSORTIUM SO INDIANA UNIVERSITY AND THE JACKSON LABORATORY WAS THE FIRST 1 AWARDED LATER IN THE UNIVERSITY OF CALIFORNIA IEVER SIGN WAS ADD IN, SO WE'RE NOW WORKING TOGETHER AND REALLY THE IDEA IS TO EXPAND MODEL RESOURCES FOR CLINICAL RESEARCH AND TESTING OF CANDIDATE THERAPEUTICS AND WE HOPE OVER THERE PERIOD OF FUNDING TO DRAW 50 NEW MOUSE MODELS OF PATHOLOGIES, SO IT'S A PRETTY AGGRESSIVE GOAL. AND SO, THE IDEA HERE REALLY IS, AGAIN, MOVING AWAY FROM SORT OF THE EARLY ONSET ALZHEIMER'S DISEASE, HOW DO WE MODEL LATE ONSET DISEASE AND THIS IS A REALLY TRICKY QUESTION BECAUSE LATE ONSET DISEASE IS FAR MORE DIVERSE IN TERMS OF GENETICS AND CO MORBIDITIES AND IN TERPS OF ALL THE VARIOUS FACTORS THAT GO IN AND TRY TO MODEL THAT DIVERSITY AND PRIMATESSORITATING ONSET DISEASE GENE VARIANTS AS THEY'RE IDENTIFIED FOR ANIMAL MODELING AND CREATING NEW MOUSE MODELS WITH CRSPR AND THAT'S WHY WE'RE ABLE TO GENERATE THE LARGE NUMBER OF MODELS WE ARE AND HAS CHANGED HOW FAST AND HOW CHEAPLY WE CAN MOVE MODELS FORWARD. WE'RE CURRENTLY AND I WILL TELL YOU ABOUT THAT PILOTING RAT MODEL WHERE WE'RE DOING A HIGH CAPACITY SCREENING OF ALL THE MODELS AND DEEP PHENOTYPING OF THE MOST PROMISING MODELS THAT IS THEY MOVE THROUGH THE PHENOTYPING. AND REALLY CRITICAL PART OF THIS IS AS WE TRY TO ALINE THESE AS CLOSE AS WE CAN, EVERYTHING FROM NEUROPATHOLOGY BUTTA A LOT OF WORK ON OMICS AND ANIMAL IMAGING AND THEN FINALLY 1 OF THE OTHER--THE NCTS FINAL PIECE OF THE GOALS AND TO DO PRECLINICAL TESTING OF THE MOST PROMISING MODELS AND, THE DATA WILL ALL BE MADE AVAILABLE WITH UNRESTRICTED DISTRIBUTION OF ALL THE MODELS THROUGH THE JACKSON LABORATORIES AND ALL THE DATA THROUGH SAGE BIONETWORKS SO AGAIN WE HAVE MULTIPLE DIFFERENT COMPONENTS OF THIS, THE MODEL A. D. CENTER AND THE FIRST 1 WAS BIO-INFORMATICS AND DATA MANAGEMENT CORE WHICH AGAIN LOOKS AT ALL THE DATA AND TRIES TO DECIDE WHICH MODELS WE SHOULD GENERATE AS WELL AS COMPARE THE MOUSE FROM HUMAN COMPARISONS AND DISEASE MODELING PROJECT WHICH MAKES THE MODELS AND CHARACTERIZES THE MODELS, AND THEN FINALLY WE HAVE A PRECLINICAL TESTING CORE WHICH THEN TAKES THOSE MODELS INTO A PRECLINICAL TESTING PARADIGM. SO IN TERMS OF BIO-INFORMATICS AND DATA MANAGEMENT CORE WHAT WE'RE DOING IS UTILIZING ALL THE RESOURCES THAT HAVE BEEN FUNDED AND AND THE A. D. ET CETERA, TAKE ALL THAT INFORMATION THAT'S OUT THERE ABOUT HUMAN ALZHEIMER'S DISEASE AND IDENTIFY GENES AND VARIANTS THAT WE THINK WE WANT TO MOVE FORWARD WITH THESE, THEN WE PRIORITIZE THESE VARIANTS WHICH 1S WE WANT TO DO FIRST, WHICH 1S WE WANT TO DO SECOND. WE ALSO HAVE TO LOOK AT HOW WE CAN COMPARE THIS TO HUMAN TO MOUSE BECAUSE OBVIOUSLY SOME WE CAN MODEL AND SOME WE CAN'T JUST BASED ON THE FACT OF WHETHER HAVE A TRANSLATION FROM HUMAN TO MOUSE AND FINALLY WHAT WE HAVE THE DAILY BASIS AT ON THOSE MODEL SYSTEM TO MAP BACK, THE MOUSE PHENOTYPES TO THE HUMAN PHENOTYPES AND IN THE LAST PIECE IS DATA DISTRIBUTION, GIVING ALL THE DATA WE GENERATE TO SAFE BIONETWORKS TO THE COMMUNITY. SO IN TERMS OF THE GENE VALID AND RELIABLE YABT PRIORITIZATION, I AM JUST SHOWING YOU A SLIDE HERE WHICH HAS SOME OF THE GENES AND VARIANTS THAT THE TEAM HAS BEEN WORKING ON AND YOU CAN SORTED OF SEE THEY FIT INTO A NUMBER OF CATEGORIES OF LATE ONSET DISEASE WHICH IS INTERESTING, THIS IS VERY DIFFERENT THAN EARLY ONSET DISEASE O THIS AN IMPORTANT DISEASE, AND THE MITOCHONDRIA MEMBRANE BECAUSE OF SYNAPSES, AND HOW WE OOH DENTIFY THESE AS LOOKING AT SIGNIFICANCE OF GENE VARIANTS IN MULTIPLE STUDIES, SECOND DO THEY EVER PREDICT EFFECT ON FUNCTION, IS THERE HUMAN MOUSE SEQUENCE CONSERVATION WE CAN AGAIN MODEL THESE? IS THERE DIFREPRESENTIAL EXPRESSION IN DISEASE AND FINALLY ARE THERE NONCODING VARIANTS AND NIA IS LOOKING AT MODEL YAWN CODING VARIANTS BECAUSE THOSE ARE REALLY UNIQUE AND CHALLENGING FOR US TO MODEL. SO WE'VE MADE A LOT OF MODELS ALREADY. MOST OF THEM ARE LISTED UP HERE SO WE MADE 2 DIFFERENT HUMANIZED A. PSSMENTS P. MODELS WHERE IT'S BEEN IMMUNIZED TO CHANGE THE ASSAYS THAT ARE DIFFERENT BETWEEN MOUSE AND MUSEUM MAN BETA LLOYD. WE HAVE MADE A NEW APOE ALLELE SERIES WHICH IS A KNOCK IN OF 2 AND 34 ALLELESMENT THERE WERE OTHER MODELS AVAILABLE BUT THEY HAD RESTRICTIONS PLACED ON THEM IN TERMS OF WHAT I WAS TALKING ABOUT BEFORE, LEGAL RESTRICTIONS OF THESE ARE MADE AVAILABLE TO ANYBODY WHO UPONS TO USE THEM WE MADE A NUMBER OF CHEM 2, INCLUDES R47 H AND I WILL SHOW YOU DATA ON THAT LATER ON SO JUST--THAT'S WHY I HAVE IT HIGHLIGHTED HERE AND THEN FINALLY WE MADE A MODEL THAT COMBINES APOE 4 WHICH IS A RISK FACTOR FOR HUMAN RISK DISEASE WHICH IS ANOTHER BIG LATEON SET GENETIC RISK AND THOSE MICE ARE CURRENTLY BEING PHENOTYPED AND IN ARK DITION WE'RE GENERATING 8 NEW MODELS PER YEAR, AND SO THE MODELS, SOME OF THE MODELS THAT HAVE BEEN JUST BEEN MADE AVAILABLE THIS SUMMER, INCLUDING ANOTHER LATE ONSET GENE THAT'S BEEN IMPLICATED BOTH A KNOCK OUT AND A RISK ALLELE, CCAM 1 WHICH IS A IMK OUT IO1 RECEPTOR PROTEIN WHICH IS A ANOTHER IMMUNE MOLECULE, WE'VE MADE BOTH THE KNOCK OUT AND THE RISK ALLELE BY CRSPR. SO AGAIN ALL OF THOSE ARE CURRENTLY, CAN YOU GO ONLINE AND FIND THEM AVAILABLE. DAVID? >> MICROPHONE DAVID? >> ARE YOU GOING TO MAKE A TOM 40. >> WE HAD INITIAL DISCUSSIONS ABOUT THAT, WE WOULD LIKE TO GET INPUT FROM OUR EXTERNAL ADVISORY BOARD ON WHERE SHOULD WE GO WITH THAT. WE HAVEN'T COME UP WITH A GOOD STRATEGY YET WITH WHAT WE SHOULD DO BEWE WOULD LOVE TO HEAR MORE THOUGHTS ABOUT THAT. THE UC IRVINE GROUP IS ACTUALLY ALSO IN THE PROCESS OF DEVELOPING A HUMAN TAU KNOCK IN. SO THIS IS BASICALLY THE IDEA HERE IS TO COMPLETELY REPLACE MOUSE TAU WITH A FULL ENTIRE GENOMIC LOCUST OF HUMAN TAU. SO THIS PROCESS IS UNDERWAY AND WILL LEAD TO A MODEL THAT HAS ALL HUMAN TAU, ISOFORMS, PROTEINS THAT ARE PRODUCED IN THE APPROPRIATE LEVELS WITHIN THESE ANIMALS. AND THEN AGAIN 1 OF THESE AREAS WHERE THERE ARE NOT A LOT OF RESOURCES RIGHT NOW AND THIS WILL BE MADE AVAILABLE TO THE FIELD. AGAIN I MENTIONED 1 OF THE BIG THINGS WE'RE REALLY TRYING TO DO WITH THE MOUSE MODELS IS DO DEEP PHENOTYPING AND YOU SEE HOW CLOSE THEY GET TO HUMAN ALZHEIMER'S DISEASE AND THIS IS LOOKING ACROSS MULTIPLE DIFFERENT WAYS SO OMICS IS A BIG WAY, THERE'S INFORMATION FROM AMP-AD AND OTHERS, MOVE A. D. THAT THERE ARE IN FACT RNA SEQ, PROTEOMICS, METABOLOMICS AND ON THE HUMAN SIDE SO THE WHYED IS HOW MUCH CAN WE GENERATE IN THE MOUSE SIDE TO SEE HOW CLOSE WE'RE GETTING TO HUMAN DISEASE PATHWAYS. ANOTHER IS OBVIOUSLY LOOKING AT NEUROPATHOLOGY AND HOW CLOSELY THE NEUROPATHOLOGY REFLECTS AND THEN FINALLY WE ARE DOING ANIMAL IMAGINGLY AGAIN TO SORT OF SEE HOW CLOSELY TAKEN--THEY REFLECTS WHAT'S SEEN IN HUMANS. THIS JUST SHOWS OUR HUMAN PHENOTIPPING, THIS IS RAPID SCREENING TO ASSESS WHETHER WE WANT TO MOVE FORWARD WITH THE MODEL. INCLUDE EVERYTHING FROM PATHOLOGY AND NEUROINFLAMMATION, BUT ALSO DOING SOME TRANSCRIPTOMICS USING NANO STRING. THIS IS MOVED FORWARD. AND THEN IN,A DITION WE ARE DOING THE DEEP PHENOTYPING WE CAN SEE ON THE RIGHT COLUMN THERE, WE'RE DOING MUCH MORE DEEP PHENOTYPING IPT GREATER CLUING THEN EVERYTHING FROM TRANSCRIPTOMICS TO PROTEOMICS TO METABOLOMICS AND IMAGING AND BEHAVIOR. WE'VE HAD A COUPLE SUPPLEMENTS,& SO WE HAD A SUPPLEMENT THIS YEAR TO DEVELOP A NANO STRING PANEL WHICH WE RESEMBLE ALL THE AMP A. D. MODULES IN ALZHEIMER'S DISEASE, AND THAT'S UNDER DEVELOPMENT, WE HAVE 2 SUPPLEMENTS I WILL TELL YOU ABOUT THEA THE END TO WITH THE OTHER GROUPS IN AMP A. D. THAT DO THIS WORK. SO IN TERMS OF OUR INITIAL RESULTS, HERE ARE RESULTS WE'RE DOING LOOKING AT TRANSCRIPTOME LEVEL FINDINGS, AND COMPARING DIFFERENT MODELS, SO IN THIS PARTICULAR--WE'RE ELECTRICKING AT 5 X FAD, AND OUR APOE-4 KNOCK& IN AND THEN THE B66 HOT AND THEN THE TRIM 2 MUTANT ALLELE. THIS IS AT 6 MONTHS OF AGE WHOLE BRAIN 3 REPLICATES AND THEN BASICALLY THIS IS PRINCIPLE COMPONENT ANALYSIS WHERE WE COMPARE THE TRANSCRIPTOMES TO WHAT WE SEE IN THESE AMP A. D. MODMODDULES THESE GENE NETWORKS THAT ARE CHANGED IN ALZHEIMERY DISEASE, AND IT'S INTERESTING THAT CAN YOU SEE THE EXAMPLE FOR THE 5 X FAD TO THE 42 H SEEM TO CLUSTER WITH THE MODULES ON THE LEFT-HAND SIDE WHERE APOE CLUSTERS ON THE OTHER SIDE OF THE RIGHT HAND SIDE AND THERE'S A MODULE WE SEE REFLECT INDEED ANY OF THE MODELS WE'VE GENERATE THIS FAR. SO THIS HOPEFULLY GIVES YOU THE IDEA THE KINDS OF THINGS WE CAN DO TO LOOK AT HOW CLOSE ARE WE GETTING TO THE HUMAN DISEASE. AGAIN THESE ARE THE 1S, DIFFERENT AREAS HERE SO THE 1 THAT LOOKS LIKE THE TRIM 47 FH AND THE INFLAMMATION COMPLEMENT IN MICROGLEEL CELLSA WHICH IS NOT TERRIBLY SURPRISING AND THE TERM 2 IS THE 5 XFAD, THE SYNAPTIC SIGNALING AND, POE FALLS AND THE LAST GROUP THAT WE DON'T REALLY YET HAVE IDENTIFY INDEED AN MA MODELS IS DPLIEWK O GENESIS AND NEGATIVE EVALUATION OF NEURONAL APOPTOSIS. WE'RE ALSO CAPABLE SINCE WE'RE A LARGE CONSORTIA WE WILL ASSESS REPRODUCIBILITY ACROSS SEATS SITES SO WE CAN PHENOTYPE THESE ANIMALS FOR THE EXACT SAME TIME PLATFORMS AND MODALITY AND ASSESS HOW MUCH VARIATION THERE IS FROM SITE TO SITE WITH THE SAME ANIMALS. AND THIS WILL HELP US TO HARMONIZE ENVIRONMENT AND METHODOLOGY TO EXTENT AS MUCH AS POSSIBLE AND THEN ASSESS THE REPRODUCIBILITY AND WHAT I'M SHOWING YOU HERE IS TRANSCRIPTOME DATA GENERATED AND NOW LOOKING AT COMPONENT ANALYSIS BUT LOOKING AT ANIMALS THAT WERE HOUSED AND RAISE THE THE JACKSON LABORATORIES IN THE HARBOR AND AT INDIANA UNIVERSITY AND INDIANAPOLIS AND WHAT YOU CAN SORT OF SEE HERE IS THAT THE THESE 5 XFDJ, AND THE JAND IU WHERE THEY'RE HOUSED AND MORE OR LESS THEY ARE IN FACT, IT IS PRETTY MUCH CLUSTERING OF THE 5 X MODELS TOGETHER, THE V-6 MODELS TOGETHER AND THE APOE 4 MODELS TOGETHER SO THEY SUGGEST THERE'S GOOD REPRODUCIBILITY AND I WOULD POINT OUT THERE ARE SOME DIFFERENCES STILL IN THERE AS WELL. SO I THINK THAT WILL BE IN A REALLY IMPORTANT THING TO FOLLOW UP, WHAT IS THE DIFFERENCE BETWEEN THESE 2 DIFFERENT SITES AND AGAIN WE WILL NOW BE ADDING ALSO PHENOTYPING DATA FROM UC IRVINE AS THEY GET UP AND RUNNING. AND THEN FINALLY THE LAST PIECE OF THIS IS A PRETESTING CORE AND THE IDEA HERE IS TO TAKE THE MOST PROMISING MODELS THAT PASS THROUGH ALL OF THIS LEVEL OF PHENOTYPING ASK THEN WITH THE HELP OF OUR STEERING COMMITTEE AND EXTERNAL ADVISORY BOARD, DEVELOP A TRIAGE OF TEST COMPOWBDS THAT WILL MOVE INTO THOSE MODELS AND WE WILL LOOK AT ABOUT 1-2 MODELS, 1-2 THERAPIES A YEAR, AND TO A PARTICULAR MODEL AND REALLY THE EMPHASIS IS ON PRIORITIZING PHARMA KINETIC AND TRANSLATIONAL PHARMACODYNAMICS OVER BEHAVIOR, IT'S A RHYMEARY SCREEN FOR PRECLINICAL EFFICACY. SO WE HAVE A NUMBER OF SCREENS, FROM PK TO PD. AND AGAIN GO AND NO GO GATES. WE ARE USING ANIMAL IMAGING AND CONFIRMATION READIOG RAF EXPE IMMUNE O HISTOCHEMISTRY AS A SECONDARY SCREEN AND FINALLY THE TERTIARY SCREENS IN TERMS OF BEHAVIOR AS AS DEVELOPING A THERAPEUTIC INDEX AND THE PRECLINICAL TESTING CORES DEVELOPED SOPs FOR ALL OF THIS WHICH ARE USING THE ARRIVED GUIDELINES AND BEST PRACTICES, AGAIN, USING LARGE NUMBERS OF ANIMALS PER GROUP AND PER SEX, AGE MATCH VEHICLE CONTROLS, BLINDED TECH NIGDZS, BLAIND DATA ANALYSIS AND ORDER OF TESTING. AND IN ALL OF THE DATA, AND THE SOPs ARE GOING TO BE AT SAGE SYNAPSE AGAIN FOR EVERYBODY IN THE FIELD TO SEE THE DATA SO THAT WILL ALL BE AVAILABLE. >> SO 1 OF THE THINGS THAT THE GROUP FOR THE TESTING CORE DID SPEND A LOT OF TIME WORKING ON INITIALLY WAS HOW DO WE PRIORITIZE THERAPIES THAT ARE COMING IN THAT ARE RECOMMENDED TO US SO THEY HAVE DEVELOPED A SCREENING PROCESS BY WHICH THESE MOLECULES CAN BE SCREENED AND WE'RE NOW DEVELOPING A WEB-BASED PORTAL BASICALLY SWR INVESTIGATOR CANS COME TO THE WEB FORT, PUT IN INFORMATION ABOUT A PARTICULAR THERAPY OR DRUG AND AT THE END OF THIS WILL COME A SCORE WHICH UPON HELP US TO PRIORITIZE, YOU KNOW WHICH THERAPIES SHOULD WE MOVE FORWARD WITH IN A PARTICULAR ORDER. THIS IS IN A SUPPLEMENT THIS YEAR, WE HOPE TO RELEASE THIS SOON AS A WEB BASED PORTAL THAT ANYBODY CAN COME AND ENTER THIS INFORMATION. AND WE SPEBD A LOT OF TIME IN TERMS OF RESOURCE SHARING AND TRYING TO GET THE WORD OUT OF WHAT WE'RE DOING BECAUSE WE WANT PEOPLE TO TAKE UP THESE MODELS AND LET PEOPLE KNOW WHAT WE'RE DOING. AND WE WANT TO TRY TO HELP RESEARCHERS FIEBD THE RIGHT MODEL THEY WANT FOR THEIR STUDIES. SO AGAIN, ALL THE DATA THAT THIS INCLUDES MOUSE GENETIC INFORMATION, GENE VARIANTS, TRAIN BACKGROUND WILL BE AVAILABLE, MOUSE PHENOTYPING DATA ON ALL THE MODELS INCLUDES RNASEQ,IMEUNOLOGY, HISTOLOGY, ALL AVAILABLE THROUGH SAGE. PRECLINICAL DATA THROUGH STANDARDS, SOPs WILL BE AVAILABLE, AND ALSO THE FINALLY THE PRECLINICAL WILL BE AVAILABLE BY LARRY [INDISCERNIBLE]. AND THEN THE MICE WILL ALSO BE MADE AVAILABLE FROM THE JAX MOUSE REPOSITORY. AT LEAST ON OUR SIDE, WE CAN'T GUARANTEE WHAT ANYBODY ELSE, BUT THOSE ARE AVAILABLE AND A LOT OF THOSE MODELS I PUT UP ARE AVAILABLE TODAY AND YOU CAN GO ONLINE AND ORDER THEM. WE HAVE WHERE MOST OF OUR INFORMATION S&P AT A WEBSITE, MODEL A. D..ORGYOU CAN SORT OF SEE HERE AND SO AGAIN THAT HAS ALL THE INFORMATION ABOUT THE MODELS WHERE THEY ARE, YOU CAN LINK THEM TO ORDER THE MODELS. IT CAN ALSO LINK ULTIMATE GOAL MAILTLY TO THE DATA THAT WILL BE STORED AT SYNAPSE AND SAGE. WE ARE ALSO TRYING VERY HARD TO GET THE WORD OUT INTO THE COMMUNITY. WE ARE HAVING A SYMPOSIUM THAT I'M CHAIRING AT THE SOCIETY FOR NEUROSCIENCE ON ANIMAL MODELS. THERE'S ANOTHER MEETING THAT THE ALZHEIMER'S ASSOCIATION IS HOST NOTHING LATE NOVEMBER AS WELL HERE IN WASHINGTON TO TALK ABOUT ANIMAL MODELS. AND SO AGAIN, THIS IS PART OF OUR GOAL IS TO REALLY TO NOT ONLY DO THE WORK BUT ALSO GET THE WORD OUT OF WHAT WE'RE DOING. AND NOW I WANT TO SPEND A COUPLE MINUTES, I WILL BE AWARE OF TIME HERE, TOO, TO TALK ABOUT SOME VERY RECENT RESULTS. SO THIS IS STUFF REALLY THAT WE FOUND OUT ABOUT IT AT THE LAST MONTH. AND SO, AS WE'RE ANALYZING THIS R47 H KNOCK-IN MUTATION MADE BY CRISPR, WE NOTICED THERE WAS A CHANGE IN THE RNA THAT WAS PRODUCED FROM THIS ALLELE. AND THIS SHOWS INFORMATION FOR MODEL A. D. RNASEQ. FROM ANIMALS THIS 1 IS A 12 MONTHS OF AGE AND WHAT WE CAN SEE IS THAT WE HAVE A NOARMAL SLICE ISOFORM HERE AND THEN WE HAVE A NEW SPLICE JUNCTION IN THIS AXON, 2 WHICH IS REALLY UNUSUAL, AGAIN WITH SOMETHING THAT WAS TOTAL SURPRISE TO US AT THE TIME. WE ACTUALLY QUANTIFIED THE NUMBER OF THE DIFFERENT TRANSCRIPTS THAT EXIST, SO AT THE TOP HERE IS THE FULL LENGTH TRANSCRIPT OF TRIM 2 AND TAKEN--THEY FULL LENGTH TRANSCRIPT COMPARED TO WILD TYPE ANIMALS IS REDUCE BY ABOUT 50% MORE OR LESS, BUT WHAT'S INTERESTING IS THERE'S SEVERAL ISOFORMS THAT DON'T REALLY CHANGE THEIR EXPRESSION LEVELS AND FINALLY AT THE BOTTOM IS THIS NOVEL ISOFORM THAT'S NEW ONCE WE INTRODUCE THIS R47 H MUTATION. AND 1 OF THE FIRST THINGS WE ASKED OURSELVES WAS MAYBE, WELL COULD THIS BE WHAT THIS MUTATION IS DOING IN PEOPLE? AND OBVIOUSLY IT'S AN IMPORTANT QUESTION. SO THIS JUST SHOWS SOME DATA WE HAVE OTHER DATA NOW, BUT I DIDN'T HAVE TIME TO PUT IT TOGETHER. THIS SHOWS DATA FROM THE AMP AD GROUP WHERE WE LOOK AT TRANSCRIPT OHMS FROM THEIR 47 H MUTATIONS AND LOOK AT ALL THE TRANSCRIPTS THAT ARE DERIVED AND FROM THOSE PARTICULAR INDIVIDUALS THIS SHOWS THE SAMEAXON WHICH IS 2 OF TRIM 2 AND LET ME TELL YOU THERE'S NO EVIDENCE AT ALL OF ALTERNATIVE SMIES WITH ANY INDIVIDUALS THAT CARRY THAT PARTICULAR MUTATION. SO WHAT THIS APPEARS TO BE IS ACTUALLY THIS IS A NOVEL TRANSCRIPT WHICH IS SPECIFIC FOR THE MOUSE AS FOR AS WE CAN TELL. IT'S MISSING 119 BASE PAIRS FROM THE START OF AXON 2 AND THIS NEW ISOFORM AS 10% OF THE ABUNDANCE FOR ISOFORM AND WE THINK IT'S NONSENSE MEDIA DECAY AND THAT'S WHY IT'S REDUCED AND IT APPEARS TO BE SPECIES SPECIFIC AS FOR AS WE CAN TELL OF THE. THE PRIMARY TRANSCRIPT IS REDUCED 50% AND WE'RE EXAMINING HOW MUCH PROTEIN IS IN THOSE ANIMALS AND WE DON'T KNOW YET. AND THIS NOVEL ISOFORM IS ALSO AS JUST BEEN REPORTED LAST WEEK BY CHRISTIAN HAUS, AND COLLEAGUES BUT THEY USED OUR MODEL AS WELL AND THAT 1 OF THE ADVANTAGES WE HAD OUT THERE FOR PEOPLE TO DO THE STUDIES ON AND THEN ALSO FRANCIS EDWARDS FROM THE DIMENSION RESEARCH EN--STRATEGIESITUTE IN THE U. K. ALSO OBSERVED SOMETHING SIMILAR AS WELL. CHRISTIAN HAUS AND HIS COLLEAGUES PRODUCED THERE WERE LEVELS FROM MICROGLEEL CELLSA WHICH WAS SURPRISING BECAUSE WE ONLY AIAN 50% REDUCTION IN TRANSCRIPT SO THAT'S SOMETHING WE HAVE TO RESOLVE BUT AGAIN IT JUST SHOWS THE KIENTD OF INFORMATION WE WILL START TO GET ABOUT ALL DATA THAT'S COMING OUT. WE'RE CURRENTLY LOOKING AT OTHER STRATEGIES TO CHANGE HOW WE'RE LOOKING AT THAT MUTATION, WE DON'T WANT TO REDUCE HA IF IT'S NOT SEEN IN PEOPLE. SO WE'RE NOW INTRODUCING DENATIONAL LIBRARY OF MEDICINIC REASON YOJS SURRUNED THAGOREANA AXON 2, WITH THE R47 H ALLELE BY CRISPR AND GO TO THE LOCUST AND THAT'S SOMETHING WE'RE CURRENTLY TALKING ABOUT AND WE ARE CURRENTLY CONSULTING EXTERNAL ADVOICERY BOARD ON THIS. SO FIRSTLY ME FINISH UP WITH SUPPLEMENTS SO WE HAD A SUPPLEMENT THAT WAS FUNDED LAST YEAR ON METABOLOMICS AND I WON'T BORE YOU ON THE DETAILS HERE BUT WE LOOKED AT A NUMBER OF FIRST ANIMAL MODELS COMING THROUGH AND WE WORKED WITH THE DUKE GROUP TO SORT OF DO METRICS TAB O LOAM CLINICAL COMMUNITYS JUST LIKEOT HUMAN SIDE AND THIS IS IN THIS PRELIMINARY DATA AND IT'S INTERESTING IS THAT IT LOOKS LIKE THE APOE 4 ARE CLUSTERING THE ANALYSIS IN 1 GROUP AND 5 X AD ARE CLUSTER NOTHING 1 GROUP AND 6 ARE CLUSTERING IN YET A THIRD GROUP WHICH SUGGESTS WE MAY BE ABLE TO IDENT UNIQUE DIFFERENCES ACROSS THOSE PHENOTYPES. AND THEN SIMILARLY WITH FREED, THEY HAVE A PROJECT IN PROTEOMICS IN HUMANS, SO WE AGAIN PROCESS SAMPLES WITH THEM, TO LOOK AT PROTEINS AND THIS JUST SHOWING SOME OF THEIR PRELIMINARY DATA HERE AGAIN THIS IS BASICALLY LOOKING AT DIFFERENT MODULES IN THE PROTEOMICS SIDE AND WHAT CAN SEE AND THIS IS THE EARLY ONSET MODEL THAT SOME OF THE 5 XFAD MODELS ARE SHOWING THOSE IN THE SAME MODULES THAT ARE SEEN IN HUMAN DISEASE AND WE'RE CURRENTLY ANALYZING THE E-4 TRIM 2 MICE AS WE SPEAK. SX HEAT THEN FINALLY WE HAVE A RAT ONSET MODEL AND WE'RE JUST GENERATING DATA RIGHT NOW AND WE'LL HAVE DATA SOON. AND SO IN TERMS OF FUTURE DIRECTIONS WE HAVE A 2 SUPPLEMENTS THAT WERE WORDED FOR THIS YEAR. ON GENETIC DIVERSITY ASK THAT'S BACK TO MARIA'S PRESENTATION SO 1 OF THE THIJS WE'RE DOING IN THE INITIAL SETS OF STUDIES IS WE'RE GENERATING ON A COMLITE LE DEFINED GENERATED THETIC BACK GRUND AND WE DID THAT BECAUSE THAT'S THE BACKGROUND THE FIELD USES GENERALLY FOR ALMOST ALL THERE OTHER STUDIES BUT WE DON KNOW IS THAT THE RIGHT STRAIN OR COME BINNATION AND THERE IS DATA THAT THAT STRAIN MAY BE DISTANT TO THE PHENOTYPES OF SOME SORT SO WE'RE PROPOSING TO UTILIZE DIVERSITY AND EXISTING MOUSE RESOURCES TO START TO DIG INTO THAT. WHAT DOES GENETIC DIVERSITY LOOK LIKE AND HOW DOES IT IMPACT THE ANIMALS. AND THEN WE ARE ALSO PROPOSING TO EXPAND THE PROTEOMICS INTO SORT OF THE LARGER PHENOTYPING OF THE MODEL A. D. AND I THINK THE PRELIMINARY DATA LOOKS INTERESTING. WE ALSO WOULD LIKE TO EXPAND INTO RAT MODELS MORE WHERE WE DON'T HAVE THAT FUNDED TO YOU RIGHT NOW BUT TO DEVELOP LATE ONSET MODELS THAT PARALLEL THE MOUSE TO BE A POWERFUL TOOL TO AM CO PAIR ACROSS SEVERAL SPECIES. AND IN 1 OF THE OTHER THINGS WE ARE CURRENTLY THINK SUGGEST HOW DO WE MODEL THE CO MORBIDITIES AND BRAIN PATHOLOGIES THAT EXIST IF LATE ONSET DISEASE. I THINK THIS IS A CHALLENGING TECHNOLOGY TRANSFER AND WE'RE TALKING RIGHT NOW AND HOW DO WE GO AFTER THIS. SO AGAIN THAT'S ANOTHER AREA THAT WE'RE TALKING ABOUT AND THEN FINALLY WE'RE INTERACTING AND POTENTIALLY COLLABORATING WITH A NUMBER OF THESE GROUPS THAT ARE PUT NOTHING APPLICATIONS FOR THE ALZHEIMERY CENTER FOR DISCOVERY OF NEW MEDICINE 54, IT WAS ANNOUNCED SEVERAL WEEKS AGO AND GIVEN THE GOALS, THE MODEL A. D. CONSORTIUM WILL PARTNER WITH A NUMBER OF TEAMS AT DIFFERENT INSTITUTIONS AND INCLUDING WO1 FROM INDIANA UNIVERSITY SO WITH THAT THANK YOU. I FORGOT TO TELL YOU THIS, THIS IS THE MOST IMPORTANT SLIDE ACTUALLY. I SHOULD HAVE SHOWN THIS IN THE BEGENERATED THANKSGIVING IS ALL THE GROUP. IT SHOWS THE COMPLEXITY OF THE GROUPS HERE, I JUST POINT OUT A COUPLE PEOPLE I'M AT INDIANA UNIVERSITY, PAUL IS HEAD OF THE PRECLINICAL TESTING AT THE UNIVERSITY, THE 2 HEADS OF THE PIs ARE GARRETT POWELL HEADING DISEASE MODELING PROJECT AND GREG CARTER HEADS THE BIO-INFORMATICS CORE, UC IRVINE AND COLLEAGUES LEAD THEIR U54, WE HAVE A GREAT EXTERNAL ADVISORY BOARD THAT'S THERE ON THE RIGHT HAND SIDE AND FINALLY THIS REALLY IS A GREAT PARTNERSHIP WITH SUZANNEA ASK LARRY TERMS OF REALLY MOVING THE FIELD FORWARD AND I WOULD LIKE TO THANK BOTH OF THEM FOR ALL OF THEIR EFFORTS AS WELL. SO THANK YOU. [ APPLAUSE ] >> JUST TIME FOR A COUPLE OF QUESTIONS. >> STARTING MORE SPECIFIC, YOUR CRISPR KNOCK-INS HAVE BEEN SHORT DELETIONS OR POOR MUTATIONS, SO YOU MENTIONED I THINK THAT THE IRVINE'S TAU WAS A WHOLE LOCUST PRESUMABLY JUST DISCREET CODING REGIONS IF NOT JUST INTRONS HOW LARGE--HOW LARGE HAVE YOU BEEN EXPERIMENTING WITH IN TERMS OF PUTTING MOUSE INTO HUMAN. >> YEAH SO THAT IS ABOUT--DOESN'T INCLUDE DISTANT REGULATORY REGIONS. >> DEPENDS HOW DISTANT YOU GO AND THAT'S 1 OF THE REQUESTIES THAT OUR MEGABASES ARE AWAY AND WE WON'T BE ABLE TO MODEL THAT IN A PRODUCTEDDIVE WAY. >> THE BALANCE BETWEEN CODING AND NONCODING? >> THE 1S WE FOCUSED ON ARE ARE CODING BECAUSE THEY ARE EASIER TO FIGURE OUT HOW TO DO. WE DO HAVE A MODEL A. D. SYMPOSIUM IN DECEMBER. WHICH IS REALLY TO GATHER FOLKS WHO WORK IN THE NONCODING--SORT OF WORLD TO ADVISE US AND HELP US FIGURE OUT HOW DO WE INTELLIGENTLY GO FOR NONCODING VARIANTS BECAUSE THOSE ARE THE LARGE MAJORITY OF THE GENES, CODING VARIANTS ARE NONCODING SO WE NEED TO COME UP WITH A STRATEGY SO WE HAD INITIAL DISCUSSIONS WITH ENCODE AND SOME OF THESE GROUPS WHICH ARE WORKING ON SORT OF CHROMATIN AND DOMAINS WITHIN THE CHROMATIN TO IDENTIFY LITTLER WAYS WE CAN USE THIS INFORMATION TO MAKE CHANGES AND WE DON'T KNOW YET. >> DOCTOR? >> YEAH, THANKS, THIS WAS VERY INTERESTING AND VERY IMPORTANT WORK. I THINK IT'S GOING--HELP US UNDERSTAND THE BASIC BIOLOGY OF THE DISEASE VERY MUCH. ONE OF MY QUESTIONS WAS GOING TO BE ABOUT GENETIC DIVERSITY AND I AM GLAD YOU ARE GOING TO BE DOING THAT. ARE YOU GOING TO USE THE DIVERSITY OUTCROSS FROM JACKSON OR-- >> THE PRIMARY FOCUS WILL USING THE CC-LINES WHICH ARE THE COLLABORATIVE CROSS LINES WHICH HAVE DRAMATIC DIVERSITY ACROSS THE DIFFERENT LINE SPECIALIZATION OF SPECIFIC ENDOTHELIAL WE'VE ALREADY STARTED, I MEAN JUST THIS WEEK WE'RE HAVING CONVERSATIONS SINCE THE SUPPLEMENT WAS AWARDED OF STARTING TO MOVE THOSE FORWARD SO THAT WILL BE HAPPEN THANKSGIVING YEAR. >> YEAH, THAT'S GREAT. SO FROM BASIC BIOLOGY SIDE, SO FAR YOU HAVE BEEN WORKING WITH C57 AND I'M CONCERNED THAT THE OLDEST AGE YOU'RE PLANNING TO TEST IS 18 MONTHS WHICH IS A ITH AGENTED MOUSE, AT THAT AGE HUMANS DON'T DEVELOP THE DISEASE YET AT LEAST IN THE LATE ONSET SO DO HAVE YOU ANY PLANS TO STUDY LATER? FOR THE PHENOTYPIC THINGS AND ESPECIALLY FOR TREATMENTS IF INTERVENTIONS? >> RIGHT. I THINK OUR GOAL WAS FIRST TO SHORT OF SEE WHAT AGAIN THE DATA LOOKS LIKE AT THESE TYPE POINTS WE'RE LOOKING AT AND THEN GO AGAIN USING THE OMICS AND EVERYTHING ELSE EXISTING ARE WE GETTING CLOSE OR NOT AND THEN WE CAN LOOK AT MORE. WE HAD TO DRAW A COUPLE LINES WHEN WE'RE LOOKING AT WHAT CAN WE DO, IS IT MORE IMPORTANT TO GENERATE A LOT OF MODELS AND PUSH THEM OUT OR, YOU KNOW--THEN ALSO HOW MANY AGENCIES DO WE LOOK AT SO THEREYA A NUMBER OF DECISION POINTS WE HAD TO MAKE BUT WE COULD CERTAINLY ADD ON OTHER TIME POINTS, THE--JACKS HAS AN NIA SHOCK CENTER SO THAT'S 1 POSSIBILITY OF WORKING WITH THEM TO SORT OF CONTINUE ON THAT SIDE BUT WE'RE KEENLY AWARE OF THAT AND THAT'S WHY WE WANT TO ELECTRIC AT MULTIPLE TIME POINTS AND 18 WAS 1 WE THOUGHT WE COULD GET TO REALISTICALLY WITH A NUMBER OF ANIMALS WE PROPOSED TO LOOK AT. >> DR. RYMAN. >> SO BRUCE, THAT'S FANTASTIC. THANK YOU FOR ALL YOUR EFFORTS. BRINGINGOT A CRYSTAL BALL, WHAT'S THE CHANCE WE WILL SEE AN ANIMAL MODEL, LATE ONSET MODEL THAT WILL RECAPITULATE AND NEURODEGENERATION? >> IT'S A GREAT QUESTION, I WISH I KNEW THE ANSWER, WE'RE JUST SCRATCHING THE SURFACE I THINK IN TERMS OF THE DIFFERENT STRATEGIES AND APPROACHES TO HOPEFULLY GET US THERE. I THINK, YOU KNOW INTRODUCING THE VARIOUS COMBINATIONS OF GENE VALID AND RELIABLE YABTS AS WELL AS LOOKING AT MAYBE--RISK CO MORBIDITIES AND RISK FACTORS WE MAY INTRODUCE INTO THE MODELS ARE THE WAY FORWARD BUT AGAIN, I THINK TIME WILL TELL. I'M ENCOURAGED BY AGAIN JUST THE FACT THAT EVEN SOME OF THESE MODELS, A FAIRLY EARLY TIME POINTS ARE BEGINNING TO SEE SOME OF THESE AMP A. D. MODULES SHOWING UP HAD IN THEM AND IT'S MEANINGFUL I THINK THAT SUGGESTS WE NEED TO KEEP FOLLOWING THOSE MODELS AND SEE WHAT HAPPENS WITH AGE. SO THEY DEVELOP AMYLOID PATHOLOGY AND TAU PATHOLOGY WHICH IS A BIG PROBLEM WE HAD THE FIELD IS WE DON'T HAVE A MODEL REALLY THAT ROBUST LE REFLECTS HUMAN BIOLOGY AMYLOID PATHOLOGY AND TAU PATHOLOGY LATE FOR EXAMPLE OR NEUROGERONTOLOGYSTS GENERATION AS WAS SUGGESTED AS WELL. SO THOSE ARE THINGS THAT--I'M ALSO COURAGED ABOUT THE CROSS IDEA BUZZ IF YOU LOOK AT THE BASIS OF JACKSON LAB AND THESE OTHER AREAS IS CARDIOVASCULAR DISEASE WHEN MODELS WERE LOOKED AT IN 1 OF THE GENETIC BACKGROUND OF THE DISEASE DOESN'T LOOK REALLY SORT OF THAT MUCH LIKE HUMAN DISEASE AND NOW AS THEY'VE BEEN INTRODUCED INTO THE DIVERSITY OF GENETIC BACKGROUND, YOU SEE A NUMBER OF THE FEATURES STARTING TO EVOLVE OUT OF THOSE MODEL WHICH IS ARE MUCH, MUCH MORE CLOSELY REFLECTIVE OF HUMAN BIOLOGY AND DISEASE AND SO THAT'S WHYIME EXCITED ABOUT THOSE GENETIC DIVERSITY APPROACHES. >> THANK YOU VERY MUCH. >> [ APPLAUSE ] >> NOW DR. LINDA JOSEPH WILL INTRODUCE DR. ELENA VOLPI. >> WHILE DANA IS DOING THAT IT'S MY GREAT PLEASURE TO INTRODUCE ELENA VOLPI, WITH THE DEPARTMENTS AGING, SHE COMES FROM THE UNIVERSITY OF GALVESTON SHE WEARS MULTIPLE HAT, SHE'S A CURRENT ENDOCRINOLOGYST AND GERIATRICIAN, AND GOING MORE TOWARDS GERIATRICS AND SHE DID EARLY TRAINING IN ITALY WITH HER M. D. AND Ph.D. WITH THE UNIVERSITY OF [INDISCERNIBLE] BUT THROUGH THE YEARS OF UNIVERSITY OF TEXAS SHE IS THE CHAIR OF GERIATRIC BRANCHES, DIRECTOR OF THE SEALY CENTER ON AGING, YOU ARE AUAR SHE IS AT THE YAWD CLEANUPPER CENTER AT UNIVERSITY OF TEXAS AND SHE IS ALSO ASSOCIATE DIRECTOR OF TRANSLATIONAL SCIENCE AND AS I SAID SHE WEARS MANY HATS AND SHE HAS APPOINTMENTS IN THE DEPARTMENT OF INTERNAL MEDICINE AND DEPARTMENT OF NEUROSCIENCE AND CELL BIOLOGY, AND METABOLISM AND PROFESSOR OF GRADUATE SCHOOL OF SCHOOL OF SCIENCES HER FOCUS IS ON PROTEIN SYNTHESIS, LOOKING AT LOSS OF FUNCTION AND METABOLISM AND TYPE 2 DIABETICS VERY MUCH INTERESTED IN EXERCISE OF VARIOUS INTERVENTIONS AND HOW IT EFFECTS MUSCLE GROWTH, INTERVENTIONS FROM EXERCISE, NUCLEOTIDESITRATION AND NOT JUST GLOBAL NUTRITION AND INDIVIDUAL AMINO ACIDS IN TERMS OF EXERCISE, SHE--HER GROUP LOCKS AT--USE BED REST AS A MODEL, THE ONLY MODEL WE HAVE TO LOOK AT CENTER BEHAVIOR AND MECHANISM MUSCLE GROWTH. FROM A [INDISCERNIBLE] PERSPECTIVE HER LAB IS INTERESTED IN USING SOME DRUGS FOR INSTANCE METAFORMIN AND HOW IT EFFECTS MUSCLE FUNCTION. SHE WEAR AS I LOT OF HATS AND GERIATRICS WE LIKE TO TALK ABOUT COLLABORATION AND MULTIDISCIPLINE APPROACH AND I WANT TO MENTION 3 MAJOR STUDIES THAT HER LAB IS A SITE FOR THESE 3 MAJOR STUDIES SPONSORED BY NIA, THE STRIVE TODAY WHICH A LOT OF YOU HEARD ABOUT IS THAT IT FALLS [INDISCERNIBLE]. THE [INDISCERNIBLE] STUDY LOOKING AT MOLECAR MECHANISM BEHIND EXERCISE AND MOST RECENTLY THE STEP HIGH STUDY LOOKING AT HIP FRACTURE AND USING TESTOSTERONE AND HOW IT HELPS WITH THE REHAB WITH THE HIP FRACTURE. DR. VOLPI HAS BEEN A PROLIFIC WRITER SHE HAS OVER 100-125 PAPERS THROUGH THE YEARS AND NOT ONLY THROUGH HER, SHE'S BEEN VERY SUCCESSFUL IN TRAINING UP AND COMING JUNIOR INVESTIGATORS. YESTERDAY WE TALK ABOUT THE PIPELINE AND A LOT OF HER POST DOCS HAVE GONE ON TO RECEIVE RO1S AND SO JUST TO KNOW SHE HAS BEEN CONSISTENTLY FUNDED FROM NIA SINCE ABOUT 2000 AND WITHOUT FURTHER ADO HERE IS DR. VOLPI. >> THANK YOU VERY MUCH FOR THIS INVITATION AND I'M REALLY HONORED TO BE HERE TODAY AND I WANT TO THANK THE LEADERSHIP OF NIA FOR HAVING SUPPORTED MY RESEARCH AND RESEARCH ON AGING FOR SO MANY YEARS SO TODAY I WILL TALK ABOUT IDENTIFYING THERAPEUTIC TARGETS OF SARK O PENIA, AND THE INVOLVEONATORY LSES OF MUSCLE-MUSCLE FUNCTION WITH AGING. IT'S AT THE CENTER OF--OH EOKAY. ALL RIGHT. --IS AT THE CENTER OF THE CYCLE OF FRAILTY AND DISABILITY AND DISABLEMENT AND MORTALITY IN THE OLDER ADULT. SO WHAT I WILL DO TODAY, I WILL GIVE YOU SOME SORT OF A PERSPECTIVE OF WHERE WE SPATTERED ABOUT 20 YEARS AGO AND WHERE WE'RE GOING AND HOW THE THE NIH FUNDING, IN PARTICULAR THE NIA HAS SUPPORTED ALL THESE VARIOUS STEPS SO WE CAN START WITH A HOW IS MUSCLE STASEIS CONTROLLED HOW MUSCLE MASS IS MAINTAINED AT THE MUSCLE LEVEL AND IT'S VERY SIMPLE. IT'S A PROCESS OF BALANCE WEAN MUSCLE GROWTH AND MUSCLE ATROPHY WHICH IS MAINLY DRIVEN BY THE BALANCE BETWEEN MUSCLE PROTEIN SYNTHESIS AND MUSCLE PROTEIN DEGRADATION FOR THE SIMPLE REASON THAT THE MUSCLE CAN ARK TRACT PROTEINS MAKE UP THE BULK OF THE WHOLE MUSCLE AND THERE ARE THOSE THAT PROVIDE THAT CONTRACT THEIR PROPERTIES OF MUSCLE IN THEIR MUSCLE FUNCTION. THERE'S 2 MAJOR FACTORS THAT CONTROL THIS BALANCE AND HOMEOSTASIS, THE FIRST 1,EUR NUTRIATIVE FACTORS ON THE 1 HAND THERE'S NUTRITION THAT ACTIVATES MUSCLE GENE SYNTHESIS AND GROWTH AND ON THE OTHER HAND THERE'S STARVATION WHICH PRODUCES ATROPHY AND ON THE OTHER FACTOR IS PHYSICAL ACTIVITY SO EXERCISE AS EEIVETS MUSCLE GROWTH AND UNLOADING IN ACTIVITY HAS ATROPHYING EFFECT SO AS ORIGINALLY BORN AS AN ENDOCRINOLOGY AND I WAS A METABOLISM EXPERT AND SO I--WE'VE--IN GALVESTON THERE'S ALWAYS BEEN THIS HISTORY SINCE THE EARLY 80S WHEN BOB WOLF WAS THERE TO ACTUALLY STUDY THE METABOLIC ASPECTS OF HEALTH AND DISEASE SO THERE'S A WAY TO LOOK AT THAT BOND BETWEEN MUSCLE PROTEIN SYNTHESIS AND BREAK DOWN BY USING STABLE ISOTOPE TRACERS IN HUMAN BEINGS WHEN ALLOW US TO ACTUALLY MEASURE THE RATES OF PROTEIN SYNTHESIS AND BREAK DOWN AS WELL AS WHEN WE USE MUSCLE BIOPSIES AND REGION FROM THE LEG REGION WE CAN ALSO MEASURE ALL THE GENETIC PARAMETERS THAT INVOLVE THE TRANSPORT OF AMINO ACIDS ACROSS THE MUSCLE BLOOD BARRIER AND THEN, WE CAN ALSO CALCULATE SYNTHESIS AND BREAK DOWN RATES OF THEICLETAL MUSCLE PROTEINS AND THE MEASURE OF THE NET BONDS. SO PHYSIOLOGICALLY IN HEALTHY YOUNG ADULTS, THE NET PROTEIN BALANCE SWINGS UP AND DOWN O A DAILY BASIS MANY TYPES I DAILY BASIS I BASED ON CONDITIONS, DURING THE RESTING, FASTING PERIOD, THE NET BOND SYSTEM NEGATIVE BECAUSE THE MUSCLE IS THE LARGEST RESERVOIR OF AMINO ACIDS IN THE BODY AND THEREFORE RELEASES THIS AMINO ACIDS FOR THE REST OF THE BODY TO UTILIZE ENCLUEDING THE NERVOUS SYSTEMS WHERE THE AMINO ACIDS ARE UTILIZED AS NEUROTRANSMITTERS NEAR THE LIVER WHERE THEY'RE ACUTE PHASE PROTEIN PRODUCTION, AND WE INTRODUCE FOOD IN OUR BODY PARTICULARLY EXOGENOUS, IT HAS ESSENTIAL AMINO ACIDS AND THE NET BONDS BECOMES POSITIVE AND EVEN AT REST AND THAT'S KNOW IMPORTANT TIME WHERE THE MUSCLE REPLENISHS ALL THOSE AMINO ACIDS LOST WITH THE CATABOLIC PROCESSES AND IF YOUNG ADULT EXERCISES IN THE FASTING PERIOD LIKE MANY PEOPLE DO, THE NET BALANCING PROVES A LITTLE BIT BUT IT NEVER REALLY BECOMES POSITIVE BECAUSE THERE'S NO--AMINO ACIDS ARE COMING IN EXOGENOUSLY TO PROVIDE THE SUBSTRATE FOR FOR INCREASED SYNTHESIS. BUT IF THIS IS FOLLOWED BY A FEEDING AND SO PARTICULARLY A PROTEIN MEAL THEN THERE IS A SYNERGY BETWEEN THE EXERCISE AND THE MEAL THAT THEN MAKES THE PROTEIN SYNTHESIS AND PROTEIN GROWTH IN THE MUSCLE MUCH LARMINGER. SO WHAT HAPPENS IN OLDER ADULT? S WE LOOKEDDA THE ALL THOSE COMPONENTS. WOE WE'VE LOOKED AT THE BASE LINE RESTING PERIOD IN THE HEALTHY OLDER ADULT. AND OVER THE PAST 20 YEARINGS, REALLY, THERE WAS NO EVIDENCE THAT THERE WAS ALTERATION AND NET MUSCLE PROTEIN BALANCE IF THE OLDER ADULT AND HEALTHY AND LIVING INDEPENDENTLY. THIS CONCEPT WHICH WE ORIGINALLY PUBLISHED IN 2001 WE REPAYSED IT IN A LARGE FREEZER TODAY WE'VE DONE THAT WE PUBLISHED NOT TOO LONG AGO AND WE ACTUALLY WERE ABLE IN THIS STUDY TO BREAK DOWN THE SYNTHETIC RATES IN--ACCORDING TO AGE AND SEX AND AGAIN THERE'S NO DIFFERENCES IN PROTEIN SYNTHESIS BETWEEN YOUNG AND HOLDER MEN AND WOMEN. ON THE OTHER HAND WHAT WE FOUND WAS SOMEWHAT OF AN INCREASED IF PHOSPHORYLATION IN THE OLDER ADULTS WHICH WAS ACTUALLY SIGNIFICANT THOSE STUDIES WERE A COLLECTION OF STUDIES OBVIOUSLY IN THE ROLE SUPPORTED BY OUR PEPPER CENTER FOR THE BOTH FOR RESEARCH CAREER DEVELOPMENT OF RESEARCH CAREER FACULTY AND FOR INFRASTRUCTURE. SO NOW LET'S MOVE TO THE--TO THE POTENTIAL TARGETS FOR TREATMENT OF SARCO PENIA, 1 OF THE FIRST THINGS WE'VE LOOKED AT WAS THE EFFECT OF FEEDING A MUSCLE PROTEIN TURNOVER IN NET BONDS IN PARTICULAR MUSCLE PROTEIN SYNTHESIS. IN YOUNG AND OLDER ADULTS AND WHAT WE FOUND IS THAT IN THE OLDER ADULTS, HEALTHY OLDER ADULTS, WE ACCOUNTED NOT SEE A SIGNIFICANT INCREASE OF MUSCLE PROTEIN SENTH SIS AND 1 PRESENTED WITH THE MEAL AND YOU CAN SEE HERE THERE'S A NICE INCREASE AND ALSO SERENDIPITOUSLY, WE FOUND OUT THAT LED BLOOD FLOW DIDN'T INCREASE IN THE THIS GROUP OF OLDER ADULTS FOLLOWING THE MEAL. AND SO WE STARTED LOOKING AT--ASKING OURSELVES WHY WOULD THAT HAPPEN AND SO, BY JUST PLOTTING DOWN THE MECHANISMS THAT LEAD TO MUSCLE GROWTH WITH NUTRIENT INTAKE THERE'S REALLY 2 PATHWAYS THAT LEAD TO THAT. ONE IS THE STIMULATION BY PROTEIN, DIETARY PROTEINS AND THE IMMUNE O ASIGNIFIES THAT COME TO IT, AND M-TOR SIGNALING AND THE ACID THAT LEADS TO SIGNALING AND LEADS PROTEIN SIPGHT SIS AND MUSCLE GROWTH AND ON THE OTHER HAND THERE IS A PATHWAY THAT IS SOMEWHAT MORE INDETECTED WHEREBY THE CARBOHYDRATES INTRODUCE WITH A MEAL STIMULATE INSULIN SECRETION WHICH INCREASED VASODILATION WITHIN THE MUSCLE TISSUE AND ALSO WITH SOME INDIRECT WAYS ALSO ACTIVATES MTOR SIGNALING AND ALTOGETHER THE VASODILATION WHICH IS NUTRIATIVE FLOW AND HORMONE FLOW TO THE MUSCLE WILL INCREASE MUSCLE GROWTH. SO WE LOOKED AT BOTH THESE ARMS OF THIS--THIS OF PATHWAYS. AND ON THE 1 HAND WE'VE LOOKED AT ENSURVEYS LYNN FIRST BECAUSE WE WERE SEEING THAT THE DECREASE IN VASODILATION AND SO WHAT WE FOUND IS THAT WHEN WE INFUSE INSULIN ALONE IN A HEALTHY YOUNG PERSON WE SEE A NICE INCREASE IN MUSCLE PROTEIN 60 KIG AND ALSO A INCREASE THIS BLOOD FLOW WHICH IS NORMAL. IF OLDER ADULT MASCULINIZED WERE DIABETIC WE COULD NOT REPLICATE THAT. A LOWER DOSE, A RAISE IN INSULIN TRONS KRAIGZS TO THE LEVEL THAT WOULD NORMALLY BE ACHIEVED WITH--AFTER A MEAL DIDN'T HAVE A POSITIVE EFFECT ON PROTEIN SYNTHESIS NOR ON PLOOD FLOW. BUT IF WE DOUBLE THAT DOSE SO WE GIVE A SUPER PHYSIOLOGICAL DOSE WE COULD HAVE A NICE INCREASE IN PROTEIN SYNTHESIS INDICATING THAT THE MUSCLE WAS RESISTANT TO THE ANTIBIOTIC ACTION OF INSULIN EVEN THOUGH THE SUBJECTS WERE NOT DIABETIC. THAT FACT WAS LINKED ALSO WITH AN INCREASE IN BLOOD FLOW TO THE END RESPONSE TO THE LARGE INSULIN DOSE. WE ALSO LOOKED AT INTRA CELLULAR SIGNALING USING MUSCLE BIOPSIES AND WE FOUND AND THIS IS ANABOLIC SIGNALING AND IGFINALLING ON THE LEFT AND ON THE RIGHT IS MTOR 1 SIGNALING 6 C 1 FOSTER NURSED FOCUSED ON AREALATION IS A DOWN STREAM ING RIEWLTOR FOR MOOR-1 AND WE FOUND THAT THE LARGER LOWER INSULIN DOSE WAS NORMALLY ACTIVATING NKT AND LARGER DOSE INCREASED PHOSPHORYLATION OF AKT SO INSULIN SIGNALING, WAS INTACT BUT ON THE OTHER HAND THE MTORQ 1 PHOSPHORYLATION WAS NOT SIMULATED BY THE NORMAL DOSE WHEREAS IT WAS INCREASED BY THE LARGER SUPER PHYSIOLOGICAL DOSE. THE LITTLER ARM OF THE NUTRIENT PATHWAY IS THE AMINO ACID ARM, AND THIS STUDIES THAT BOB WOLF HAD DONE IN GALVESTON USING A SMALL DOSE OF AMINO ACIDS, ABOUT 7-GRAMS THAT CONTAIN A RELATIVELY SMALL DOSE OF LUNG CANCER SEEN, ANY CHALLENGE THE MUSCLE OF OLDER ADULTS WITH THIS DOSE WAS ORAL DOSE AND THIS WERE ESSENTIAL AMINO ACIDS CORRESPOND TO 15-GRAMS OF HIGH QUALITY PROTEIN. LET'S SAY IT'S A OAT MEAL BREAKFAST, AND YOU KESEER THAT THE OAT MEAL BREAST FAST INCREASED THIS IN THE ELDERLY. WHEN IT MANIPULATED THE LOSING CONTENT OF THIS 7-GRAMS OF AMINO ACIDS BY INCREASING LUNG CANCER SEEN AND DECREASING THE OTHERS, IT COULD ACTUALLY OBTAIN A NORMAL AND LARGER PROTEIN SYNTH SIGN IN BOTH YOUNG AND OLDER ADULTS AND WHEN WE GAVE IT EVEN LARGER DOAGHT OF AMINO ACIDS, ABOUT 18-GRAMS WHICH CORSPONTS TO ABOUT 40-GRAMS OF HIGH QUALITY PROTEIN REALLY COULDN'T FIND ANY FURTHER IMPROVEMENT IN THE SYNTHETIC RESPONSE SUGGESTING THAT THERE'S SOME SORT OF A CEILING EFFECT OF DOSE OF PROTEIN AT EACH MEAL AFTER WHICH REALLY THERE'S NO BENEFIT IN GETTING MORE. ANOTHER STUDY THAT WAS INTERESTING FOR US IS WHEN WE PUT ASULTS AT 7 DAYS BED REST MIMICKING AN INFECTION, WE FOUND THAT THE RESISTANCE TO AMENO ACIDS WAS QUITE INCREASED BY THE BED REST. SO BEFORE BED REST WHEN WE GAVE A LARGER DOSE OF AMINO ACIDS CONTAINING QUOIT A BIT OF LE LEUCINE, WE HAD THE INCREASE IN THE MUSCLE BUT AFTER THE 7 DAYS BED REST THAT WAS COMPLETELY OBLITERATED AND WE FOUND THAT THIS EFFECT WAS ASSOCIATED WITH ALTASD RAITIONZS IN THE--ALTERATIONS IN THE EXPRESSION OF AMINO ACID TRANSPORTERS WHICH ARE NORMALLY ACTIVATED. SO THE EXPRESSION IS NORMALLY ACTIVATED BY AN AMINO ACID PROTEIN MEAL. AND WHEN YOU GET THE PROTEIN MEAL, ESSENTIALLY THE TRANSPORTERRED ARE ACTIVATED SOMEHOW PRIMING THE MUSCLE TO REPLENISH THAT TRANSPORT AND INCREASE THE LEVEL OF TRANSPORTERS FOR THE NEXT PEOPLE. THAT DISAPPEARS WITH 7 DAYS OF INACTIVITY AT BED REST. ANOTHER THING THAT COULD ACTUALLY AFFAIRS TEAM LEADERRER AND WORSEN ANABOLIC RESISTANT IS TYPE 2 DIABETES. OBSERVATIONAL STUDIES THAT'S SHOWN FROM SEVERAL LARGER--STUDIES HAVE SHOWN THAT TYPE 2 DIABETES TENDS TO INCREASE AND ACCELERATE THE LOSS OF MUSCLE MASS AND COHORTS OF OLDER ADULTS. AND WE ACTUALLY IN THIS PRELIMINARY DATA TO OUR LATEST RO-1 WE ACTUALLY FOUND THAT IN TYPE 2 DIABETICS THE AMINO ACID TRANSPORT IS DECREASED AND THERE'S AN ALTERATION IN TRAFFICKING AMINO ACIDS IN THE MUSCLE WITH THE DECREASED IN THE INTRA CELLULAR AMINO ACID CLEARANCE IN PROTEIN SYNTHESIS WHICH WE THINK COULD BE 1 OF THE MECHANISMS THAT CAN LEAD ALSO TO OVER THE LONG-TERM TO LOSS OF MUSCLE MAFUL AND FUNCTION. ANOTHER POINT OF RESISTANCE TO ANABOLIC ACTION IS THE RESISTANCE TO RESISTANCE EXERCISE IF YOU PARDON MY REPETITIONS. SO WHAT HAPPENS RESISTANCE EXERCISES, THAT AFTER AN EXERCISE--INTENSE EXERCISE BOUT WITH WEIGHT LIFTING IN THE LEGS THERE WAS AN INCREASE IN PROTEIN SYNTHESIS IN YOUNG ADULTS IN THE OLDER ADULTS IT'S BLUNTED IT DOESN'T DISAPPEAR BUT IT'S BLUNTED AND DATA OF RESISTANCE TRAINING INTERVENTIONS AND OLDER ADULTS ALSO CONFIRM THAT OVER TIME THAT GAINS IN MUSCLE MASS WITH RESISTANCE STRAINING ARE SOMEWHAT BLUNTED IN THE OLDER ADULT AND IN THIS CASE, WE FOUND THAT THE EXERCISE THAT THE AGING REALLY REDUCED THE MTOR ACTIVATION FOLLOWING THE EXERCISE, SO SO THE YOUNGER ADULTS AND THE BLACK AND ESSENTIALLY AND/OR THE NIGINALLING RIGHT AFTER THERE, AND COMPLETELY AFTER 6 AND 24 OR THE YOUNG SUBJECT IS STAYS UP FOR A LONG TIME AND. WHAT WE DID FIND IS THAT THE AMINO ACIDS AND IN THE MTOR IS SIGNALING PATHWAYS AND AND MUSCLE GROWTH AND AGING, REDUCES INSULIN INDUCED VASODILATION SO ESSENTIALLY JUST AS ENDOTHELIAL DYSFUNCTION AND MTOR SIGNALING WITH AMINO ACIDS AND EXERCISE, IN INACTIVITY AND POSSIBLE SEE DIABETES WHICH IS THE ACID TRANSPORT AS WELL. SO WHAT INTERVENTIONS CAN WE POTENTIALLY UTILIZE, WE CAN TRY TO HYPER ACTIVATE SO GIVE A LOT OF AMINO ACIDS TO ENHANCE THE ACTIVATION IN MTOR 1 SIGNALING AND SYNTHESIS AND THIS HAN BEEN SHOWN FOR WHAT CONCERNS RESISTANCE EXERCISE SO WHAT WE FOUND HERE WHILE THE RESPONSE OF RESISTANCE EXERCISE, IS YOUNGER ADULTS WHEN WE DO THE RESISTANCE EXERCISE AND ESSENTIAL AMINO ACIDS AFTER YOUR ASSISTANCE EXERCISE THERE IS A RECOVERY OF NORMAL RESPONSIVENESS OF THE MUSCLE WHICH IS COMPARABLE TO WHAT HAPPENS IN A YOUNGER ADULT GIVEN THE SAME TREATMENT. ANOTHER POINT THAT WE'VE BEEN LOOKING AT IS WHETHER WE CAN RESTORE VASODILATION AND THEN DURING HYPER DPLISEMIA AND THEN SEE IF THE INKREETIONED DILATION CAN LEAD TO IMPROVEMENT IN PROTEINS AND INSULIN AND SODIUM NIGHT ROUGH ATOM PROTEIN IN THE LEG AND THEN WE COMPARE THE 2 JUST A SIMPLE INFUSION OF INSULIN WITHOUT THE SODIUM PROCESSOR AND WE COULD RHETOR NORMAL MUSCLE PROFUSION AND INCREASE IN PROFUSION, AND PROTEIN SYNTHESIS SO IT SOUNDS LIKE THE DEFECT THAT INSULIN RESISTANCE OF MUSCLE PROTEIN SYNTHESIS IS REALLY DRIVEN BY THE DEFECTIVE CALCULATION. SO AND WE ALSO KNOW THAT STUDIES THAT DOUG SEALs GROUP HAS DONE THAT AEROBIC EXERCISE CAN RESTORE NOARMAL ENDOTHELIAL FUNCTION IN ADULTS HERE AND SO WE TESTED THAT AND WE TOOK OLDER ADULTS AND WE--WE DIVIDED THEM ESSENTIALLY IN A GROUP THAT WAS EXERCISE CHALLENGED THE NIGHT IN A CHALLENGE AND ANOTHER GROUP THAT WAS RESTING THE NIGHT BEFORE THE INSULIN CHALLENGE AND WHAT WE FOUND IS THAT THE ENDOTHELLIAN 1 DECLINED WITH THE EXERCISE WHICH IS GOOD NEWS BECAUSE ENDOTHELLIAN 1 IS A VASE O RESTRICTING FACTOR AND BLOOD FLOW IMPROVED WITH THE AEROBIC EXERCISE, AND IT VASEALATION IMPROVED AFTER THE EXERCISE AND PROTEIN MUSCLE SENTH SIS. ANOTHER THING WE DID THEN, WE TESTED THE APPROBIC EXERCISE, PRIOR TO A MEAL CHALLENGE TO SEE WHETHER THAT COULD RESTORE ALSO THE RESPONSE A MEAL AND SURENOUGH WE FOUNDLET SAME THING. SO INCREASE IN MUSCLE PROFUSION AFTER EXERCISE WITH THE MEAL AND THE MEAL AFTER THE EXERCISE WAS ABLE TO INCREASE A NORMAL PROTEIN SYNTHESIS SO IT LOOKS LIKE THE ANABOLIC RECESTANCE TO FEEDING MIGHT BE JUST LINKED AS MUCH TO INACTIVITY OR SEDENTARY LIFESTYLE IN OLDER ADULTS, SO WE THOUGHT THAT WE WANTED TO TEST THE COMBINATION OF ARE--ADMINISTRATIVE OABIC EXERCISE AND AMINO ACID SUPPLEMENTATION IN HEALTHY ADULTS TO SEE WHETHER THE CHRONIC TREATMENT FOR 6 MONTHS OF 3 DAYS A WEEK OF AEROBIC EXERCISE TRAINING PLUS DAILY 15-GRAMS ADISCIPLINARY OF AMINO ACID SUPPLEMENTATION COULD IMPROVE MUSCLE MASS AND FUNCTION AND THE RESULTS WERE NOT AS EXCITING AS WE WERE HOPING FOR ALTHOUGH WHAT WE FOUND IS THAT THE CHANGE IN TOTAL LEAN MASS REALLY WASN'T SIGNIFICANT. WE DID FIND WITH ANY OF THE TREATMENTS, AND WE DID FIND THE EXERCISE ALONE WITH PLACEBO ACTUALLY HAD A SIGNIFICANT EFFECT ON FAT MASS WHICH WAS NOT SURPRISING AND WITH FAT MASS AND OVER ALL WEIGHT. THE ADDITIONAL AMINO ACIDS WITH THE EXERCISE PREVENTED FAT LOSS AND THE ACININ O ACIDS INCREASE& FAT MASS, IT WAS ALMOST SIGNIFICANT IT WAS LIKE .06, .07. SO WE HAD A TREND SUGGESTING THAT IT HEALTHY OLDER ADULTS THAT ARE NOT MALNOURISHED, THE ADDITION OF ESSENTIAL AMINO ACIDS OF A DIETARYET IS NOT BENEFICIAL IN TERMS OF A GAIN OF USCLE MASS AND IT MAY LEAD TO INCREASE IN FAT MASS DUE TO THE FACT THAT THERE'S AMINO ACIDS PROBABLY WENT INTO THE TCA CYCLE AND BEGAN LIPO GENIC. SO WHAT WE DID FIND WITH THE TRAINING IS INCREASING WALKING SPAIS AND WAS GOOD AND MOST GROUPS AND THEN THE INTERESTING PART WAS THAT THE COMBINATION OF XER--OF AEROBIC EXERCISE TRAINING WITH AMENOACIDS COULD INCREASE LEG STRENGTH MORE THAN ANY OF THE OTHER INTERVENTIONS WHICH WAS THE POSITIVE SIDE OF THIS. MORE RECEIPTLY WE'VE BESIDED TO LOOK AT THICKER MORE MALNOURISHED INDIVIDUALS AND THIS IS A PILOT STUDY THAT'S BEEN FUNDED BY THE NATIONAL DAIRY COUNCIL WITH SRMT FROM PREPPER CENTER FOR THE JUNIOR FACULTY WHO'S ACTUALLY RUNNING THIS STUDY. WHAT WE DID, WE TOOK OLDER ADULT WHO IS HAD BEEN ADMITTED TO THE HOSPITAL, WE RECRUITED THEM WHILE THEY WERE ADMITTED IN THE HOSPITAL FOR A MEDICAL ILLNESS, AND THEN WE RANDOMIZED TRIAL OHMIZED, WE TESTED THEIR PHYSICAL FUNCTIONING BY USING THE SBBB AND THEN WE RANDOMIZED THEM AFTER THE DISCHARGE TO 1 OF 5 GROUPS AND THIS IS A SMALL PILOT SO WE HAVE ONLY A HUNDRED PATIENTS IN HERE, A PLACEBO GROUP, 20-GRAMMINGS OF WEIGHT PROTEIN TWOIS A DAY, PLACEBO PLUS EXERCISE WHICH WAS INTENSIVE PHYSICAL THERAPY AND TEST OFTEN--DECISION OPENING REMARKS WHICH IS--TEST OFTEN--DECISION ROAN WHICH IS THE OTHER BRANCH OF THE STUDIES THAT I DON'T HAVE TIME TO TALK ABOUT AND WE JUST TESTED THIS POTENTIAL INTERVENTIONS AND WE FOUND AFTER 30 DAYS OF THIS INTERVENTIONS EXCEPT FOR TESTOSTERONE WAS ONLY A SINGLE INJECTION AT DISCHARGE WE COULD FIND AN IMPROVEMENT IN THE SBB STORE WHICH WAS BETTER IN THE POOLED INTERVENTION GROUPS AS COMPARED TO THE PLACEBO SO WE'VE BEEN DONE WITH THIS STUDY TO LOOK AT THE EFFECTS SIZE AND FEASIBILITY, FEASIBILITY PAPER HAS ALREADY BEEN PUBLISHED THE EFFECTS SIZE NOW WE'RE GETTING IN THE PROCESS OF PUSHLISHING IN AND AT THIS POINT WE THINK THAT WE HAVE GOOD PRELIMINARY DATA TO SCALE THIS UP TO A PHASE 2 TYPE OF TRIAL. AND SO IN CONCLUSION WE IDENTIFIED IN COLLABORATION WITH NCATS THROUGH CTSA FUNDING AND WITH NIAMS, FOR SOME OF THEIR R-01 FUNDING THAT THEY GAVE TO UTMB INVESTIGATORS THAT ENDOTHELIAL FUNCTION THROUGH MTOR SIGNALING AND ENABLISM THAT BECOME DYSFUNCTION AS WE'RE AGING AND MIGHT BE INVOLVED IN THE INVOFMENT OF SARCO PENIA, AND TARGETING KEY ELEMENTINGS OF THIS RESPONSE WHICH CAN ENCLUED INCREASED AMINO ACID VASE O DILATORS AND AEROBIC EXERCISE AND ARE READY FOR PRIME TIME. AND SO THIS INTERVENTIONS AWLINGS MAY BE MORE IMPACTFUL IN MALNOURISHED OR FRAIL OLDER ADULTS AND THAT SAID I WANT TO JUST ACKNOWLEDGE ALL THE OLDER COLLABORATORS AND SUPPORT STAFF WHO'VE BEEN WORKING ON THIS FOR THIS PAST 18 YEARS AND VUBSLY THE FUNDING SOURCES, THANK YOU VERY MUCH FOR ALLOWINGITOUS ACTUALLY DO THIS. THANKS A LOT. [ APPLAUSE ] QUESTIONS FOR DR. ROLPI, THIS IS GREAT FOR MANY OF US VERY RELEVANT INFORMATION BOTH PERSONALLY AND PROFESSIONALLY, PRACTICALLY. SO THE TIMING OF THE MAXIMAL EFFECT OF PROTEIN MEAL DURING OR POST EXERCISE ON MUSCLE SYNTHESIS IS, YOU WOULD SUMMARIZE HOW? >> SURE. IN YOUNG ADULTS, THE TIMING REALLY DOES NOT MATTER BECAUSE AS YOU'VE SEEN IN THE SLIDE WHERE PROTEIN SIPGHT SIS INCREASES WITH THE EXERCISE BOUT IMMEDIATELY AFTER THE EXERCISE BOUT AND THEN STAYS HIGH FOR ABOUT AT LEAST 24 HOURS. SO THERE'S A BROAD WINDOW OF OPPORTUNITY AND ACTUALLY REPEATED MEALS OVER THAT TIME FRAME CAN ACTUALLY BE VERY EFFECTIVE. IN THE OLDER ADULTS PROBABLY WITHIN THE FIRST THRESHOLD HOURS WOULD BE THE MAXIMAL EFFECT. WE HAVEN'T DONE YET THOSE STUDIES OF TIMES OF NUTRITIONAL INTERVENTIONS IN THE OLDER ADULT BUT BY LOOKING AT THE PROTEIN SYNTHETIC RESPONSE AND MTOR SIGNALING RESPONSE, REALLY THE TOP HAPPENS AROUND 3 HOURS AND AFTER THE 3 HOURS, THERE'S ESSENTIAL LE A RETURN TO BASE LINE. GIVEN THE RUNUTRITIONAL SUPPLEMENTATION DURING THE EXERCISE BOUT IS NOT REALLY EFFECTIVE AND WE'VE DONE THIS--OR BEFORE THE EXERCISE BUT WE'VE DONE THESE STUDIES IN YOUNG ADULTS AND THE REASON IS THE MTOR SIGNALING SHUTS DOWN DURING THE EXERCISE BOUGHT BECAUSE OF THE INCREASE OR MPK AND THE INCREASE ENERGY DEMANDS THAT THE EXERCISE REQUEST REQUIRES. AND THEREFORE, THE ENTHETIC PROCESSES ARE REALLY DORMANT AND UNTIL THE EXERCISE BOUT STOPS. AT THAT POINT, THERE'S MASSIVE REBOUND OF MTOR SIGNALING THAT THEN ACTIVATES ALL THE SYNTHETIC MACHINERY. >> AND FOR THOSE WHO CONSIDER INTERVENTIONS THAT HAVE TO DO WITH PROLONGED OR PERIODIC BOUTS OF CALORIE RESTRICTION OR FASTING IN OLDER ADULTS IT'S SORT OF A NARROW WINDOW TO TRY TO MINIMIZE LOSS OF MUSCLE MASS WHILE REGULARLY RESTRICTING CALORIE INTAKE, IT SEEPS QUITE CHALLENGING. SO THAT'S QUITE CHALLENGING AND I THINK WE OUGHT TO BE COGNIZANT OF THE FACT THAT OLDER ADULTS SEEM TO BE MORE SENSITIVE TO THINGS LIKE INACTIVITY SO IF WE PUT THEM IN THERE, IN THE DIET, THE LIKELY IT IS THAT THEY WANT TO KEEP THE SAME FISCAL ACTIVITY LEVEL. IT'S JUST A--YOU KNOW DEFENSE MECHANISM BECAUSE IF YOU'RE EATING LESS, PROBABLY YOU'RE FEELING MORE TIRED AND THEREFORE YOU MAY HAVE LESS FISCAL ACTIVITY, SO PHYSICAL AC50 NEEDS TO BE CONSIDER INDEED THIS STUDIES. AND THEN THE OTHER THING IS DEFINITELY, IF THERE IS CALORIE RESTRICTION, PARTICULARLY IN THOSE WHO ARE OBESE OR WITH OBESE SARCO PENIA OBESITY WHO MAY ACTUALLY BENEFIT IN TERMS OF PHYSICAL FUNCTION IT'S TIME FOR THE ADEQUATE AMOUNT OF PROTEIN INTAKE WITH THE INDIVIDUAL MEALS AND PROTEIN IS NOT REALLY VERY HIGH CALORIE TYPE OF FOOD AND SO YOU CAN ACTUALLY GET 30-GRAMS OF PROTEIN WITH 80-CALORIES. SO, IT'S REALLY A HUNDRED CALORIES MORE OR LESS. SO IT'S NOT A BIG, BIG PROBLEM BUT WE NEED TO REALLY MAKE SURE--AND MAKE SURE THAT THE INDIVIDUALS ARE NOT PROTEIN MALNOURISHED OVER TIME. >> THANK YOU. >> THANK YOU FOR THE PRESENTATION, YOU GBLIZED BETWEEN YOUNG ADULTS AND OLDER ADULTS. DO YOU HAVE SECONDARY DATA THAT BREAKS OUT SEX AND GENDER? AND IS THAT IMPORTANT GOING FORWARD IN STUDIES? >> I'VE SHOWN YOU DATA ON THE BASE LINE PROTEIN SYNTHESIS RATES ARE NOT DIFFERENT BETWEEN YOUNG AND OLDER MEN AND WOMEN AND THAT MORE OR LESS AT LEAST FOR THE MTOR SIGNALING WE HAVE MORE OR LESS THE SAME DIFFERENCES FOR--BETWEEN YOUNG MAN AND OLD MAN, YOUNG WOMEN, OLD WOMEN AND THERE'S NO DIFFERENCE BETWEEN OLD WOMEN AND YOUNG MEN AND WOMEN. THERE ARE SOME DIFFERENCES IN--HAVE BEEN REPORTED BY OTHER GROUPS IN PROTEIN TURNOVER FOLLOWING EXERCISE IN BETWEEN YOUNG MEN AND WOMEN AND SIEMS THE PROBLEM THERE IS THAT THE YOUNG WOMEN MIGHT HAVE BEEN STUDIED AT DIFFERENT MOMENTS OF THE OVARIAN CYCLE WHICH MIGHT EFFECT METABOLISM. AND THE CYCLE THERE'S LESS OF THAT TYPE OF PROBLEM. BUT DEFINITELY THAT'S 1 OF THE AREAS THAT IS IMPORTANT TO LOOK AT. ONE OF THE CAVEATS IS THAT AS WE FINDING NOW IN OUR XER SIETION STUDIES WE TEND TO HAVE MORE WOMEN ENROLLING IN THE STUDIES WHEN WE STUDY OLDER ADULTS JUST BECAUSE THERE ARE MORE INTERESTED AND THEY'RE HEALTHIER OR THEY'RE JUST WANT TO PARTICIPATE AND THAT'S A DIFFICULT--YOU KNOW PARADIGM WHEN YOU NEED TO GO OUT DISP LOOK FOR JUST MEN TO ENCLUED. YEAH BUT THAT'S A GOOD POINT AND WHEN WE DO THESE KINDS OF STUDIES I THINK TELL BE IMPORTANT ALSO AT LEAST FOR THE LARGER STUDY TO TRY AND MAYBE OVERSAMPLE EITHER OR GROUPS IF THERE IS AN IMBALANCE ON THOSE. >> DR. RYMAN, THANK? >> I THANK YOU. I WAS STRUCK BY THE DIFFERENT STAGES OF MUSCLE PROTEIN AND THINKING ABOUT WHAT IMPACT 1 WOULD HAVE--ABOUT STANFORD'S PARABIOSEIS STUDIES AND CONFUSIONS OF YOUNG BROOD AND EFFECTS ON MUSCLE MASS. IS THERE A DIFFERENTIAL EFFECT ON YOUNG BLOOD ON O. T. PRODUCTION IN THE FASTING VERSUS NOURISHED STATES AND HOW WOULD THESE DIFFERENT APPROACHES INFORM EACH OTHER. >> I DON'T KNOW ABOUT THE YOUNG BLOOD IN IT IS OLDER ADULTS. THESE ARE STUDIES IN HUMANS SO WE CAN'T DO THAT PARABIOSEIS TYPE OF STUDIES BUT ON THE OTHER HAND THERE ARE PEOPLE WHO ACTUALLY GET TRANSFUSIONS AND SO, THAT'S--YOU KNOW THAT WOULD BE AN INTERESTING THING TO LOOK AT MAYBE IN THE FUTURE. >> I THINK THEY EXTENDED TAKEN--THEY WORK FROM PARABIOSEIS TO INFUSION OF YOUNG BLOOD INDEPENDENT OF PARABIOSEIS WITH THE INDIVIDUAL DIFFUSIONS FOR YOUNG PEOPLE. I THINK TELL BE KEY IN THE PRECLINICAL STUDIES TO IDENTIFY WHAT'S IN THE YOUNG BLOOD IN THE YOUNG PLASMA THAT REALLY MAKES THE MUSCLE, THE OLDER MUSCLE GET BETTER BECAUSE THIS ARE ALL BIG QUESTIONS THAT I THINK THE BIOLOGY OF AGING SECTION OF THE NIA CAN REALLY ADDRESS AND FOR WHAT CONCERNS US WE'RE LOOKING REALLY AT SPECIFIC FACTORS AND WE'RE--AND THOSE GROUPS ARE DOING METABOLOMICS AND THE GROUPS ARE DOING PROTEOMICS. WE'RE NOT THIS TIME BUT WE MAY IN THE FUTURE AND--AND DEFINITELY THERE'S SOME FACTORS THAT MIGHT NEGATIVELY EFFECT THE MUSCLE MASS AND THOSE ARE, YOU KNOW INFLAMMATORY FACTORS AND SO THERE'S--WE HAD SOME OF OUR STUDIES ON THAT SHOWED THAT WHEN YOU PUT SOMEONE AT BED REST YOU HAVE AN INCREASE IN DLR 4 EXPRESSION IN THE MUSCLE MEANING THAT THE MUSCLE IS PRIMED WITH INACTIVITY TO REALLY RESPOND IN AN EXAGGERATED WAY TO ANY POTENTIAL BINDER THAT ANY COMPOUND THAT CAN BIND TO THE TLR 4 RECEPTOR WHICH WOULD THEN PRECIPITATE A DISASTER MUSCLE LOSS WITH FOR EXAMPLE INACTIVITY PLUS SAY PNEUMONIA, EVEN A SIMPLE PNEUMONIA, AND THAT'S WHY WE THINK A LOT OF THE PROBLEMS THAT OCCUR OF DEBILITATION THROUGHOUT HOSPITALIZATION EVEN IN THE 3-4 DAYS OF HOSPITAL STAY, OLDER PATE CANS LOSE A LOT OF MUSCLE AND A LOT OF FUNCTION. IT MIGHT BE TO A COMBINATION OF NOT JUST THE DISEASE, BUT ALSO THE INACTIVITY THAT COMES WITH THE HOSPITALIZATION. SO, WE HAVE MANY, MANY AREAS TO LOOK AT RIGHT NOW BUT I THINK AGAIN THE BASIC SCIENCES PROBABLY DID WORK A BIT MORE ON THIS BECAUSE I THINK IT'S GOING TO BE KEY FOR US TO UNDERSTAND AND TRY TO IDENTIFY NEW TREATMENTS FOR THOSE PATIENTS. >> RIGHT. LAST QUESTION DOCTOR? >> I HAVE A COMMENT AND A QUESTION. THE COMMENT IS GREAT, THAT LAST SLIDE NOT EVERYONE IN THIS ROOM MIGHT NOT KNOW HOW BIG AN SPB SCORE IS BUT IT'S IMPRESS AND I HAVE MUCH BIGGER THAN WE SEE FOR AEROBIC EXERCISE AND SEDENTARY COMMUNITY DWELLING IN OLDER ADULTS SOPHISTICATEDY THAT'S VERY ENCOURAGING BECAUSE THAT POST ACUTE PERIOD IS SUCH A PERIOD OF VULNERABILITY FOR OLDER ADULTS. MY QUESTION COMES FROM HEARING ABOUT THE INTERVENTIONS TESTING PROGRAM, GIVING RAPP A MYCIN TO MICE AND EXPANDING THEIR HEALTH AND LIFE SPAN BY BLOCKING MTOR AND DO YOU THINK THERE'S A ATTENTION HERE BETWEEN STIMULATING MTOR REGULARLY POTENTIALLY DOWN REGULATING IT AS A GERO-SCIENTIST SPAN IT'S INTERESTING TO THINK ABOUT. >> THAT'S A GOOD QUESTION. WE DID DO A STUDY IN YOUNG ADULTS RAPOMYCIN, AND MEASURED PROTEIN SYNTHESIS AFTER EXERCISE OR NUTRITION AND THERE WAS A COMPLETE BLUNTING ANABOLIC RESPONSE BUT THE RAT WAS HIGH, SO WE GAVE 16-MILLIGRAMS WHICH IS YOU KNOW, IT'S AT THE TOP OF THE DOSAGE THAT WAS GIVEN IN THE INITIAL STUDIES ON SEROLMIDS TO HEALTHY SUBJECTS AND WE THEN THINK THOUGH THAT IF WE ELECTRIC AT THE DATA IN THE MICE, THE DOSAGE OF RAPOMYCIN IS MUCH LOWER AND IF THE DOSAGE IS SLOWER IT MIGHT HAPPEN THAT IT REDUCES THE MTOR SIGNAL CHICAGO WE ACTUALLY FIND IN THE HEALTHY OLDER ADULT AT REST WHICH IS THE PAPER WE PUBLISH ON EXPERIMENTAL GERONTOLOGY ABOUT 3 YEARS AGO AND SO IF WE CAN RESET THAT HYPER STIMULATION AND MTOR SIGNALING WHILE LETTING MTOR STILL BE TABLE TO BE STIMULATED BY BY WHAT S&P A NORMAL ANTIBIOTIC EXERCISE OR AMINO ACID INTAKE OR MIXED MEAL INTAKE THEN I THINK WE'RE--WE MAY HAVE A REAL GOOD POTENTIAL FOR SEROLOMOUS, 1 WAY TO LOCK AT THIS COULD BE ON TO LOOK AT MAYBE INITIALLY DATA ADMINISTRATIVE DATA OF PATIENTS ON SEROLOMOUS AND IF THERE IS, CHRONIC LONG-TERM AND SEE IF THERE IS ANY EFFECTS ON THEIR PHYSICAL FUNCTIONING OR SAY ADMISSION TO REHAB FACILITY NURSING HOME, ET CETERA. NOW THIS HAS BEEN ON THE MARKET WHEN THERE'S A LOT OF PEOPLE WHO HAD A TRANSPLANT OR THEY'VE TAKEN IF FOR OTHER REASONS AND THAT MIGHT DO THAT OR THERE'S OPPORTUNITY TO DO STUDIES IN HEALTHIER OLDER ADULTS AND LOOKING AT DOSE RESPONSES BECAUSE THAT'S THE KEY. IF YOU SEE AEROBIC EXERCISE DOES, IT REDUCES MTOR SIGNALING AFTER THE EXERCISE ABOUT, SO IT RESETS. SO--AND THE EFFECT SOUNDS A BIT SIMILAR TO WHAT AEROBICKER EXERCISE DOES, SO THAT--THAT COULD BE ALSO A LINK BETWEEN THE 2. >> THANK YOU VERY MUCH, DR. VOLPI. [ APPLAUSE ] >> AND NOW WE WILL INTRODUCE DR. TERRI MOF FIT. >> THANKS. IT'S MY PLEASURE TO INTRODUCE DR. TERRIMOFFITT, WITH THE DEPARTMENTS OF PSYCHOLOGY AND NEUROSCIENCE AND PSYCHIATRY AND BI HAIEVERRIAL SCIENCES THE MPLET SHE'S WORKED ON THE IS ITED THAT FOLLOWED A THOUSAND PEOPLE THAT FOLLOWED A THOUSAND PEOPLE FROM BIRTH TO AGE 45. DR.MOFFITT'S INTEREST TAKE FOLLOW THE NATURAL HISTORY OF DISORDER EXPSES MEASUREMENT OF ABNORMAL BEHAVIOR AND LIFE COURSE DEVELOPMENTAL KRIMMOLOGY. SHE'S WELL KNOWN FOR HER THEORY OF ADOLESCENCE LIMITED AND LIFE COURSE PERSISTENT OFFENDER ANTISOCIAL BEHAVIOR AND HER WORK IN THIS AREA EXAMINES HOW GENETIC AND ENVIRONMENTAL RISKS WORK TOGETHER TO SHAPE THE COURSE OF ABNORMAL HUMAN BEHAVIORIORS AND HUMAN PSYCHIATRIC DISORDERS. FOR HER RESEARCH DR. MOFFIT RECEIVED NUMEROUS WAXER ARDS INCLUDING AMERICAN SOAK LOGICAL EARLY CAREER CONTRIBUTION AWARD IN 1993 AND MORE RECENTLY THE ASSOCIATION'S 2016 DISTINGUISHED CAREER RESEARCH AWARD WHICH SHE RECEIVED WITH HER HUSBAND AND COLLAB RETIREDDOR FOR THEIR INNOVATIVE RESEARCH AND THEOR O MENTAL HEALTH AND HUMAN DEVELOPMENT AND JUST THIS YEAR SHE WAS THE RECIPIENT OF THE 2018 NIH MATILDA WHITE RILEY DISTINGUISHED LECTURE AWARD WHO RECOGNIZES RESEARCHER WHO IS ADVANCED SCIENTIFIC KNOWLEDGE IN THE BEHAVIORIAL AND SOCIAL SCIENCES IN LINE WITH DR. RILEY'S VISION HIGHLIGHTING IMPORTANCE OF OF A LIFE COURSE PERSPECTIVE ON DEVELOPMENT HEGHT AND WELL BEING OF INDIVIDUALS AND SOCIETIES. NOW THE DUNEDIN CO HO--DR. HODESS AGE, THAT I HAVE CHARTED NEW TERRITORY IN AGING XESM--EXEMPLIFIED BY QUANTIFICATION AND BIOLOGICAL AGING IN YOUNG ADULTS WHICH IS SELECTED AS THE FOURTH MOST IMPORTANT SCIENTIFIC PAPER IN 2015. ADDITIONAL MAJOR CONTRIBUTIONS HAVE INCLUDED FOCUS ON EARLY LIFE PREDICTORS OF SOCIAL AND ECONOMIC OUTCOMES ENCLUEDING LONG-TERM IMPACTS OF EARLY LIFE ADVERSITY ON ADULT HEALTH AND COGNITION. I LEARNED WHILE REVIEWING DR. MOFETIS BIOSKETCH THAT IN ADDITION TO HER SCIENTIFIC ACCOMPLISHMENTS AND HONORS SHE HAS A HISTORY IN MOTION PICTURES HAVING HAD A SPEAKING ROLE IN THE SNEEN 73 FEATURE FILM 43 THE PETTY STORY ABOUT THE LIFE OF THE RICHARD PETTY THE KING OF NASCAR STOCK RACING SO I SUGGEST WE ALL ADD THIS TO OUR NETFLEX WATCH LIST THIS WEEKEND BUT TODAY'S PERFORMANCE WILL FOCUS ON HER DAY JOB AND FEATURE INN SIGHTS ON LIFE COURSE TRAJECTORIES OF DEVELOPMENT AND AGING AND ENTITLED STUDYING AGING IN YOUNG PEOPLE AND OPPORTUNITY FOR PREVENTION. PLEASE TO INTRODUCE DR. TERRI, MOFFITT. [ APPLAUSE ] >> SO HERE YOU ARE TO WATCH A FAILED MIEWFY STARLET, THANK YOU VERY MUCH 5 OR 6 YEARS AND DISCIPLINARY--TEACHING ME, WHAT I WANT TO TALK AND AND WHAT YOU MIGHT BE THINKING IS ISN'T IT DIFFICULT TO STUDY AGE NOTHING OLDER PEOPLE AND MUST WE NOW DO IT IN YOUNG PEOPLE TOO BUT WHAT I WOULD LIKE TO DO WITH THESE 20 MINUTES MINUTES AND CONVINCE THAT YOU STUDYING IN AGE NOTHING YOUNG PEOPLE IS ABOUT TO GET INTERESTING SO ABOUT A DOZEN YEARS AGO WHEN I MOO TEEM FIRST PROPOSED TO THE NATIONAL INNSITUTE OF AGING, THE IDEA OF STUDYING AGING IN A COHORT WHO WERE THEN IN THEIR--ONLY IN THEIR LATE 30S THE REVIEWERS SCOFFED AT OUR PROPOSAL. THE REVIEWS DID NOT BELIEVE WE SHOULD TAKE ISSUEMENTS RELEVANT TO THE STUDY OF AGING IN PEOPLE WHO ARE ONLY IN THEIR 30S AND THEY SAID SPECIFICALLY THERE WOULD NOT BE ANY VARIATION AND EVEN IF THERE WERE A LITTLE BIT OF VARIATION THE FIRST THING WE OBSERVED WAS THAT THERE IS DEFINITELY VARIATION IN AGING AMONG PEOPLE WHO ARE IN THEIR 30S. SO THIS SLIDE SHOWS YOU 3 COHORT MEMBERS FROM OUR BIRTH COHORT OF 1000 PARTICIPANTS. ALL 3 OF THESE WERE TAKEN AT THE SAME AGE WITHIN 60 DAYS OF THEIR 38th BIRTHDAY. SO JUST EXPLAIN THE BIG PICTURE OF WHAT WE WERE TRYING TO DO WITH OUR RESEARCH. I WANT TO CONTRACT 3 SIMPLE REALLY OVER SIMPLIFIED CONCEPTUAL MODELS AND ON THE TOP IS THE MODEL I LEARNED IN GERONTOLOGY COURSES I TOOK BACK IN GRADUATE SCHOOL AT THE UNIVERSITY OF SOUTH EVERYONE CALIFORNIA. I LEARNED THAT DISEASE IN FRAILTY AND INTENTS TO DEATH, AND DISEASE FRAILTY. THE MIDDLE BAR SHOWS A MODEL THAT GAINED TRACTION LATER IN MY CAREER, IT POINTE TO THE EARLIEST PERIOD OF LIFE FOR AGING FOR EXAMPLE THE THEORY OF THE DEVELOPMENT ORIGINS OF HEALTH AND DEC POINTED OUT THAT PRENATAL FACTORS PREDICTED LATE LIFE DECEASED AND MORETALLITY. IN ADDITION THERE WAS THE HUGE AGE RELATED RESEARCH BY HOW DISEASE AND GENETIC RESEARCH FROM THE POINT OF ENDOWMENT AND CONCEPTION AND CHILDHOOD RISK FACTORS SUCH AS DEPRIVATION AND ADVERSITY BUT THESE IMPERICAL FINDINGS ABOUT EARLY LIFE STILL LEFT A BLACK BOX AND SO IT'S TRULY REMARKABLE THAT RISK FACTORS THAT ARE PRESENT AT BIFGHT OR EARLY CHIDE HOOD CAN STATISTICALLY PREDICT LATE LIFE DISEASE AND MORTALITY. WHAT IS GOING ON THE SECOND, THIRD, AND FOURTH DECADES OF LIFE? THE PREDOMINANT NOTION WAS THAT EARLY RISK FACTORS ACCELERATE THE AGING PROCESS IN THOSE DECADES AND THIS IS SHOWN IN THE BOTTOM ON THAT YELLOW BAR. BUT THERE WAS A VIRTUALLY NO IMPERICAL WORK TESTING THIS TESTING OF YOUNG PEOPLE. SO WE DECIDED TO DO SOMETHING TO TEST THIS GAP. SO HERE'S MY OUTLINE IF YOU WANT TO FOLLOW ALONG AND THE FIRST THINK THIS I WANT TO DO BEFORE I SHOW YOU FINDINGS IS INTRODUCE YOU TO THE DUNEDIN HEALTH AND DEVELOPMENT STUDY. SO THIS STUDY IS WELL KNOWN IN THE--WELL I SHOULD JUST GO BACK. THIS STUDY IS WELL KNOWN IN THE PEDIATRIC LITERATURE AND IT'S GENERATED MORE THAN 1400 PUBLISHED FINDINGS ON CHILD HEALTH AND YOUNG ADULT DEVELOPMENT I WANT TO TELL YOU ABOUT THIS STUDY, IF YOU LOOK AT THE TOP OF THE CHART THERE WERE 137 BABIES ENROLLED AT THE TIME OF THEIR BIRTH IN 1972, 73, THIS WAS ALL BABIES BORN IN 1 CITY IN DUNEDIN NEW RELAND, NO EXCLUSIONARY RITERRIA, THIS AREA IS WHITE OF EUROPEAN DISSENT, IF YOU LOOK DOWN THE LEFT HAND COLUMN IT SHOWS YOU AGES OF DATA COLLECTION, THERE HAVE BEEN 14 ASSESS WANTS OF THIS COHORT, SO FAR, EACH TEEM TO ASSESS THE COHORT MANAGE MEMBERS EACH OF THEM IS BROUGHT IN A CLINICAL DAY FOR SETTING FOR DATA COLLECTION. AND OTHERS WITH THE UNIVERSITIES THAT TAKES PART. AND THEN DOWN AT THE BOTTOM YOU CAN SEE THAT THE LAST WAS AGE 38A IN 2012 WHEN 95% OF THE COHORT STILL TOOK PART AFTER ALL THIS TIME, I CAN TELL YOU THE COHORT'S STILL ACCURATELY REPRESENTS THE POPULATION OF THE SOUTH ISLAND OF NEW ZEALAND ON HEALTH AND SOCIOECONOMIC OUTCOMES. AND DOWN AT THE BOTTOM YOU SEE THE AGE 45 DATA COLLECTION WAVE IS NOW UNDER WAY AND EACH STUDY MEMBER IS SPENDING 1 AND HALF DAYS AT OUR RESEARCH UNIT BECAUSE WE ADDED A HALF DAY OF NEUROIMAGING THIS YEAR WITH FUNDING FROM NIA. NOW OBVIOUSLY THIS STUDY OF CHILD DEVELOPMENT WOULD BE CONVERTED INTEREST A PROPER STUDY OF AGING WE HAD TO START CLICKING AGING MEASURES THAT WOULD HARMONIZE WITH OTHER LEADING STUDIES OF AGING. AND THE BSR HAS REALLY HELPED ME PLAN FOR THAT AND I WILL SHOW YOU A FEW EFFORTS UNDER WAY IN THE DUNEDIN STUDY, THIS SPEECH IN NOISE ASSESSMENT THAT IS GIVEN, THERE'S HALF AN HOUR AUDIOLOGY MODULE THIS IS PART OF IT, THERE'S ALSO MEDICAL ASSESSMENTS INCLUDING POSTURAL HYPOTENSION NOW. BONE DENSITY, DEXA SCANNING, RETINAL IMAGING WITH SINGAPORE NATIONAL UNIVERSITY, THERE'S AN HOUR LONG OPTIC ASSESSMENT NOW WHICH INCLUDES THE OPTIC NERVE SCAN YOU SEE HERE, A DENTAL IMAGING ASSESSMENT USING MODERN ORAL EPIDEMIOLOGY TECHNIUES. AND RESPERATTORY TECHNIQUES WHICH GRAPHS TESTING OF LUNG FUNCTION. WE ARE DOING BRAINING IMAGING AND HERE I'M SHOWING YOU OUR NEWEST DISTRIBUTION OF WHITE MATTER HYPER INTENSITYS AND I'M SHOWING YOU THIS AGAIN TO ADDRESS THAT QUESTION OF WHETHER THERE WOULD BE ANY VARIATION AT THIS YOUNG AGE AND YOU CAN SEE THE DISTRIBUTION OF WHITE MATTER HYPER INTENSITIES OVER ON THE RIGHT HAND SIDE, APPARENTLY WHEN WE REVIEW THE WELLIT RATTURE, THESE THINGS WERE ONLY SUPPOSED TO BE OF INTEREST FOR STUDY FOR RESEARCH STUDY IN PEOPLE OVER 60. BUT WE ARE GETTING A VERY NICE DISTRIBUTION APPARENTLY BECAUSE OF THE VERY HIGH RESOLUTION OF OUR SCANNER. WE HAVE A PHYSICAL ASSESSMENT INCLUDING GRIP STRENGTH, CHAIR STANDS AND BALANCE TESTING AND THIS WAS DESIGNED BY OUR PEPPER CENTER, NOW 1 ASPECT OF THE DUNEDIN STUDY THAT MAKE THIS IS VALUABLE FOR THE AGE RELATED STUDY OF CHANGE WAS THAT IT WAS DESEENED TO BE A MULTIDISPLNARY STUDY FROM THE OUTSET SO WE HAVE MEASURED MANY OF THE CONSTRUCTS OF INTEREST TO AGING SCIENCE, REPEATEDLY SINCE THE PRESCHOOL AGES. AND THIS IS IN CENTERS IN HEARING, DENTAL, MOTOR FUNCTION, LUNG HEALTH, RESPERATTORY HEALTH AND COGNITIVE TESTING WHICH I WILL SHOW YOU IN A MEMORY CLONE WANT BUT HAVING THESE KINDS OF UNIQUE BASE LINE DATA IS HELPING US TO PUT THE MIDLIFE MEASURES IN THEIR LIFE LONG CONTEXT. WE CAN REALLY TELL IF PEOPLE HAVE CHANGED SENSE CHILDHOOD. SO AN OBVIOUS PLACE TO START HERE THEN IS TESTING HOW KEY MEASURES FROM GERONATOLOGY RESEARCH MIGHT BE RELATED TO EARLY LIFE BRAIN HEALTH. SO HERE YOU SLEEP APNEA AND OBESITYY HOW THE 1037 CHILDREN WERE INDIVIDUALLY TESTED WHEN THEY WERE 3 YEAR-OLDS. THEREYA A TEST EXAMINER AND THEN THEIR MRKT IS SITTING BY THEM AND FROM THE DATA THAT WERE COLLECTED AT AGE 3, WE KREACTED A COMPOSITE SUMMARY MODEL TO MEASURE EACH CHILD'S BRAIN HEALTH SO EACH CHILD WAS EXAMINED BY A PEDIATRIC NEUROLOGYST AT THE TIME IN 1975. THEY ALSO TOOK THE BAILEY MOTOR SKILLS TEST AND THEN THE RENEL TEST OF RECEPTIVE LANGUAGE, AND WE USED RECEPTIVE LANGUAGE INSTEAD OF EXPRESSIVE LANGUAGE BECAUSE LARGE NUMBERS OF 3 YEAR-OLDS ARE NOT ABLE TO SPEAK PLAINLY OR TO TALK WELL BUT APPARENTLY THAT HAS VERY LITTLE IMPLICATION FOR LATER LIFE. SO WHAT WE WANTED TO USE WAS COGNITIVE TESTS THAT DID NOT REQUIRE THE CHILD TO SPEAK. WE ALSO GAVE THE PEABODY PICTURE VOCABULARY TEST AT AGE WHICH DOES NOT REQUIRE SPOKEN LANGUAGE AND THEN AFTER THAT THE TESTING SESSION,--OH SORRY, GETTING A BIT AHEAD OF MYSELF HERE. AFTER THE TESTING SESSION, STAFF EXAM EARS RATED EACH CHILD'S BEHAVIOR AND FUNCTION OF THE BRAIN. WE MODEL THESE AS COMPOSITE INTERNATIONAL INDICATOR OF BRAIN HEALTH AND NOW I WANT TO SHOW YOU THE OWM COMES OF THAT. SO WE'VE BEEN LOOKING AT COG 95ATIVE PROCESSING SPEED BECAUSE IT'S KNOWN TO BE SENSITIVE MEASURE OF AGE RELATED COGNITIVE DECLINE. WE'VE TESTED PROPOSED DISCLOSURE SESESSING SPEED AT EVERY AGE SINCE CHILDHOOD RIGHT UP TO AGE 45 AND I'M SHOWING YOU NEW DATA FROM THE FIRST 500 COHORT MEMBERS WHO HAVE BEEN TESTED THIS YEAR AT AGE 45. SO IF YOU LOOK ACROSS THE BOTTOM WHAT YOU SEE IS AGE 3 BRAIN HEALTH, ON THE LEFT ARE THE CHILDREN WITH THE LEAST HEALTHY BRAIN FUNCTION AT AGE 3 AND ON THE RIGHT ARE THE CHILDREN WITH THE BEST HEALTHY BRAIN FUNCTION AT AGE 3. WHAT YOU SEE IS THAT THE 3 YEAR-OLDS WHO HAD THE POOREST BRAIN HEALTH HAVE PROCESSING SPEED ALMOST A STANDARD DEVIATION SLOWER AT AGE 45 THAN THERE COHORT PEER WHO IS HAVE THE BEST BRAIN HEALTH AS 3 YEAR-OLDS. WE'RE MEASURING THE CALIBER OF VENULES, THIS IS WIDELY USE INDEED BIOMARKER RESEARCH IN OLDER ADULTS ON RISK FOR STROKE AND DEMENTIA. AND YOU SEE HERE THAT THE 3 YEAR-OLDS WHO HAVE THE POOREST HEALTH HAVE HALF A STANDARD DEVIATION WIDER AT AGE 45 THAN THERE COHORT PEERS WHO HAD THE BEST BRAIN HEALTH AT AGE 3. AND THEN WALKING SPEED IS A HIGHLY SENSITIVE MARKER FOR AGE RELATED DECLINE AND FOR EARLY MORTALITY AND IT'S A KEY MEASURE IN THE STUDY OF FUNCTIONAL AGING SO HERE YOU YOU SEE THAT THEY GATE SPEED ALMOST A STANDARD DEVIATION SLOWER THAN AGE 45 THAN COHORT PEERS THAN WHO HAD THE BEST BRAIN HEALTH AT AGE 3. SO WHAT DID THESE KINDS OF FINDINGS MEAN AND I CAN COULD GO ON WITH THESE BUT I DON'T HAVE TIME TO SHOW YOU ALL OF THEM. BUT THIS IS A GENERAL RULE THAT AGE 3 BRAIN HEALTH PREDICTS ALL OF OUR GERONATOLOGY MEASURES. SO WHEN RESEARCH TEEMS BEGAN TO DID A STUDY WITH OLDER ADULTS AND SOME OF THE PARTIC PANNEDS START TO SHOW SIGNS SUCH AS SLOW PROCESSING SPEED OR WIDE VENULES OR SLOW GAIT SPEED IT'S NOT AT ALL SAFE TO ASSUME THIS REFLECTSA A DECLINE OF RECENT ORIGIN. IT MIGHT BUT IT MIGHT NOT. INDIVIDUAL DIFFERENCES ON THESE KEY GERO NATOLOGY DIFFERENCES HAVE ROOTS EARLIER IN LIFE THAN WE MIGHT HAVE THOUGHT. --CAN THESE BE QUANTIFIED. SO I WANT TO VISIT OUR CONCEPTUAL MODEL AND OUR PROMISEOT WORK BEYOND THE PACE OF AGING AND FIRST THING IS EXPOSURES THAT CAUSE AGE RELATED DISEASES AKIEWMENTULATE STARTING FROM EARLY LIFE AND WE KNOW THAT CHANGES TO PHYSIOLOGY OCCUR MANY YEARS BEFORE DISEASE DIAGNOSIS. WE KNOW THAT ORGAN DAMAGE IS DIFFICULT TO REVERSE ONCE PHYSIOLOGICAL CHANGES ESTABLISH DAMAGE AND ALL OF THIS SUGGESTED TO US THAT PREVENTIVE--IN THIS SLIDE JUST SHOWS THAT INCREASING AGE IS ASSOCIATED WITH INCREASING PREVALENCE OF NONCOMMUNICABLE DISEASES. IF TD AIM OF PREVENTION IS TO TO DISRUPT THE PROCESSES OF AGING BEFORE THEY LEAVE FOR THE ONSET OF DISEASE, THEN THIS MAKES THE SECOND TO THE FIFTH DECADES OF LIFE A REASONABLE INTERVENTION POINT. WE WERE ALSO INTERESTED IN WHAT GERON-SCIENTISTS WERE SAYING ABOUT THE DEFINITION OF AGING, THEY DEFINED IT AS THE GRADUAL PROGRESSIVE COORDINATED DETERIORATION OF PHYSIOLOGICAL INTEGRITY ACROSS MULTIPLE BODILY SYSTEMS, IN OTHER WORDS A DECLINE ACROSS ORGAN SYSTEMS THAT'S HAPPENING SIM SIMULTANEOUSLY. NOW IN THE DUNEDIN STUDY WE HAVE BEEN TRACKING BIOMARKERS, 18 OF THEM SINCE THE STUDY MEMBERS WERE IN THEIR 20S AND YOU CAN SEE THE BIOMARKERS THAT WE'VE BEEN TRACKING HERE ON THIS SLIDE. WE ALREADY KNEW THERE WAS ENORMOUS VARIATION BETWEEN INDIVIDUALS ON THESE BIOMARKERS AT ANY GIVEN AGE BUT THE QUESTION REMAINING WAS WOULD THESE BIOMARKERS SHOW EVIDENCE OF MEAN LEVEL DECLINE ACROSS THE CO-HOTTERS 20S AND THIRDS AS REDICTED BY GERO SCIENCE. I'LL SHOW YOU 3 EXAMPLES. THIS IS MEAN VO-2 MAX WHICH IS A MEASURE OF CARDIO LOGICAL FITNESS AND WE DO IT ON AN EXERCISE BICYCLE, VO-2 MAX DECLINE STUDILY FROM AGE 26 TO AGE 32, TO AGE 38. LIKEWISE, BLOOD PRESSURE, ROSE ON AVERAGE FROM AGE 26 TO 32 TO 38. AND THE COHORTS MEAN LUNG FUNCTION DECLINED STUDILY FROM AGE 26 TO 32 TO 38. I'M NOT GOING TO SHOW THIS FOR ALL 18 BIOMARKERS BUT AGAIN THIS IS A GENERAL RULE. THIS SLIDE BEPATIENTS IN THE CLINICS AN EYEBALL LOOK AT THE DATA FOR THE BIOMARKERS VIRTUALLY ALL OF THEM DID SHOW GRADUAL PROGRESSIVE COORDINATED DECLINE OF PHYSIOLOGICAL INTEGRITY AND THIS WAS ACROSS MULTIPLE BODILY SYSTEMS. SO WHAT WE DID NEXT WAS WE CALCULATED A GROWTH CURVE FOR EACH OF THESE REPEATED BIOMARKER MEASURES AND THEN WE COMBINED THESE 18 GROWTH CURVES TO MODEL WHAT WE CALLED THE PACE OF AGING. THE IMPORTANT THING TO GET HERE IS THAT ANY TEMPORARY UPWARD BLIP ON A SINGLE BIOMARKER THAT WOULD REFLECT ACUTE ILLNESS IS EXCLUDED FROM OUR MODEL SO FOR EXAMPLE, C-REACTIVE PROTEIN, MEASURE OF INFLAMMATION MIGHT RISE BECAUSE MUCH AN ACUTE INFECTION BUT THIS KIND OF SHORT-TERM ACUTE CHANGE DOESN'T FEED INFORMATION INTO THE PACE OF AGING MEASURE. THE MEASURE REPRESENTS THE GRADUAL CHANGE ACROSS EACH OF THE 18 BIOMARKERS THAT IS COORDINATED TOGETHER WITH THE CHANGE IN THE OTHER 17 BIOMARKERS. THE HISTOGRAM SHOWS THE GRIEWKSZ OF THE PACE OF AGING IN THE DURKTS NEDIN COHORT, IT'S PLOTTED IN YEARS OF BIOLOGICAL CHAIN PER CHRONOLOGICAL YEAR. SO ON THE LEFT YOU SEE SOME INDIVIDUALS IN THE COHORT WHO SHOW ALMOST NO BIOLOGICAL AGING BETWEEN THE CHRONOLOGICAL AGES OF 26 AND 38. THESE PEOPLE ARE REMAINING YOUNG. ON THE RIGHT YOU SEE THAT SOME COHORT MEMBERS ARE AGED UP TO 2 YEARS PERCHRONOLOGICAL YIER BETWEEN AGE 36 AND 48 AND IN THAT STUDY THEY AGE NEARLY 24 YEARS BIOLOGICALLY. SO WE NEXT ASK WAS THIS PACE OF AGING MEASURE CAPTURING ANYTHING MEANINGFUL. SO HERE YOU SEE THAT THE FAST AGERS HAD POORER BALANCE ON 1 LEG AS YOUNG ADULTS, THE CIRCLE JUST REMINDS ME TO TELL YOU THAT EACH DATA POINT ON THE SLIDE REPRESENTS 20 OF THE 961 CO HO--DR. HODES MEMBERS WHO TOOK PART AT AGE 38. HERE YOU SLEEP APNEA AND OBESITYY THAT THE FAST AGERS HAD WEEKER GRIP STRENGTH ALREADY BY AGE 38. THE FAST AGER HIS TEST OF COGNITIVE DECLINE ON FUNCTION FROM CHILDHOOD TO AGE 38 SO THIS IS NOT CROSS SECTION AFRONS COGNITIVE FUNCTION BUT DOWNWARD CHANGE IT COGNITIVE FUNCTION FROM CHILDHOOD TO ADULTHOOD. AND THE FAST AGERS EVEN HAD FACES THAT WERE RATED AS LOOKING OLDER AT AGE 38. THERE FACES WERE RATED DUKE UNDERGRADUATES AGE 25-62. SO IN SUMMARY IT CAN BE MEASURED OVER TIME IN YOUNG PEOPLE AND IT DEPICTS COGNITIVE DECLINE AND FACIAL AGING. BUT WE'RE GOING TO CONTINUE TO MODEL THE PACE OF AGING INCLUDING OUR DATA AT AGE 45. BUT HERE YOU SEE THE PAPER THAT ALREADY APPEARED THAT LIZ REFERRED TO IN PNAS 2015. THE PACE OF AGING AND WE WUBLISHED MORE ABOUT AND AND JUST SHOWING AWE COUPLE OF AND THE MANY NEW MEASURES OF AGING THAT HAVE BEEN ANNOUNCED IN THE LITERATURE IN THE LAST 5 YEARS. AND SIMULTANEOUSLY THE EPIGENETIC CLOCKS THAT ARE BASED ON METHYLATION DATA AS CORRELAE WIDE CHRONOLOGICAL AGE SO WHAT THIS PAPER DID WAS TO REPORT HOW OUR LONGITUDINAL MANNER OF THE PACE OF AGING OVERTIME RELATED TO THESE OTHER CROSS SECTIONAL MEASURES AND ALSO HOW THAT THEY RELATED TO EACH OTHER. IF YOU LOOKOT THE RIGHT, PAPER SHOWS THERE THAT REPORTS CHARACTERISTICS FROM THE FIRST DECADE OF LIFE PREDICT THE COHORT MEMBERRINGS PACE OF AGING. FOR EXAMPLE, DUNEDIN STUDY MEMBERS WHO GRANT PARENTS HAD GREATER LONGEVITY ARE SHOWING A SLOW ARE PACE OF AGING DURING MIDLIFE AND THE COHORT MEMBER WHO IS SUFFER CHILDHOOD ADVERSITY ARE SHOWING A FASTER PACE OF AGING. SO OUR FIELDING IS NOW IN THE DAWN OF AGING THERAPEUTICS AND MY TEAM AIMS TO FORM BY OW AGING THERAPEUTIC CANS BE APPLIED IN A PREVENTIVE WAY TO YOUNG PEOPLE, WE SEE SEVERAL OPPORTUNITIES IF ARE THIS KIND OF PREVENTION ORIENTED WORK AND HERE'S WHAT WE'RE WORKING ON NOW. SO REGARDING RANDOMIZED CLINICAL TRIALS, THESE TRIALS ARE GOING TO NEED TO MEASURE THE PACE OF BIOLOGICAL AGING IN ORDER TO USE SUCH MEASURES AS OUTCOMES IN TRIALS OF ANTIAGING THERAPIES. SO WE'RE WORKING TO DEVELOP AN EPIGENETIC METHYLATION SIGNATURE THAT CAPTURES 3 DECADES OF BIOLOGICAL AGING IN YOUNG PEOPLE ON OUR 18 BIOMARKERS BUT DOING THIS IN A SINGLE BLOOD SAMPLE. SO A TEST THAT COULD BE EASILY IMPORTED INTO RANDOMIZED CLINICAL TRIALS. WE'RE APLOYING IT IN A CLINICAL TRIAL OF CALORIC RESTRICTION THAT WAS DONE AT DUKE WHICH WAS CALLED CALORIE. IN TERMS OF BASIC SCIENCE KNOWLEDGE, WE'RE WORKING ON INDIVIDUAL DIFFERENCES IN BIOLOGICAL AGING IN STILL HEALTHY YOUNG PEOPLE SO WE CAN UNDERSTAND HOW THAT AGING WORKS. IN TERMS OF SOCIAL INEQUALITIES WE'RE ASKING WHO'S GOING TO NEED ANTIAGING THERAPEUTICS MOST AND HINT HINT THE ANSWER IS THE POOR. WHICH I THINK IS REALLY INTERESTING BECAUSE AT PRESENT MOST OF THE INTEREST IN ANTIAGING THERAPIES IS DRIVEN BY WEALTHY INDIVIDUALS. IF REBARD TO TREATMENT RESPONSE WE WILL WONDER WHO WILL RESPOND FASTEST, FAST AGERS OR SLOW AGERS. YOU COULD MAKE A GOOD HYPOTHESIS BOTH WAYS. TELL BE INTERESTING SEE HOW IT TURNS OUT BUT THE RANDOMIZED CLINICAL TRIALS OF ANTIAGING THERAPEUTICS AND PREREGISTER THE MODERATORS OF EFFECTS. SO WHAT WE WANT TO DO IS GIVE THEM THAT THEY CAN USE TO DO THAT AND THEN IN REGARD TO NEW INTERVENGSZ TARGETS THERE'S A REAL OPPORTUNITY HERE TO IDENTIFY NEW EARLY LIFE TARGETS THAT MIGHT BE USED TO SLOW THE PACE OF BIOLOGICAL AGING. SPEAKING OF NOEVERLE PREVENTION TARGETS I WANTED TO SHOW YOU 3 MORE SLIDES ABOUT PSYCHIATRIC DISORDER MY HISTORY BEFORE BECOMING AN AGING RESEARCHER WAS WORKING ON MENTAL HEALTH SO IT'S STILL A FIRST LOVE. NOW THIS SLIDE SHOWS YOU THE WELL-KNOWN POPULATION PYRAMIDS AND THEY'RE HIELLY STYLIZED HERE. IF YOU LOOK AT THE LEFT 1, YOU SEE THE SITUATION IN THE PAST WHEN VERY FEW PEOPLE SURVIVE TO OLD AGE AND MOST OF THE POPULATION WERE CHILDREN AND YOUNG PEOPLE. AND IF YOU LOOK AT THE RIGHT, YOU SEE THE FUTURE WHERE THE POPULATION OF OLDER PEOPLE HAS DRAMATICALLY EXPANDED, SO YOU ALREADY KNOW ABOUT THIS. THESE POPULATION PYRAMIDS, WE SEE VERY PREQUENTLY. HOWEVER THE SLIDE ADDS NEW INFORMATION THAT YOU MIGHT NOT KNOW YET. FIRST PSYCHIATRIC DISORDERS HAVE L PEAK ONSET IN YOUNG AGE GROUPS. THIS IS SHOWN THERE IN ORANGE. SO YOU CAN SEE THE BULGES AT THE BOTTOM OF THE SLIDES ARE THE PEAK AGES OF PREVALENCE AND INCIDENTS AND PREVALENCE OF MENTAL HEALTH PROBLEMS. SECOND, SOMETHING YOU MIGHT NOT KNOW IS SOME THAT THE SAME PEOPLE WHO HAVE AGE RELATED DISEASES, AND NEURODEGENERATIVE CONDITIONS IN LATE LIFE, THEIR DATA ARE SHOWN IN BLUE AT THE TOP OF THE SLIDE. TEND TO HAVE HAD EARLY LIFE PSYCHIATRIC DISORDERS AND THESE--THEY'VE HAD THESE PSYCHIATRIC CONDITIONS AND THEIR YOUNGER LIFE. THE EVIDENCE FOR THIS DEVELOPMENTAL CONNECTION BETWEEN EARLY LIFE PSYCHIATRIC CONDITIONS AND LATE LIFE DISEASES IS GOOD AND IT'S GROWING. I'M LISTING A COUPLE OF PAPERS THERE FOR YOU BY SCOTT AND BY LAWRENCE ON THE SLIDE, THESE ARE EXAMPLES OF SOME OF THIS NEW EVIDENCE BASE. BUT THE LINK, I THINK IS TARTING TO RAISE THE INTERESTING QUESTION OF WHETHER MORE AGGRESSIVE AND EFFECTIVE TREATMENT OF PSYCHIATRIC CONDITIONS IN YOUNG PEOPLE MIGHT HELP TO PREVENT OR DELAY LATE LIFE DISEASE ONSET. NOW THE DUNEDIN STUDY IS THE LONGEST RUNNING STUDY OF DISORDERS WORLD WIDE IS HAS OUTLIVES 4 EDITION OF THE AMERICAN PSYCHEIAT ASSOCIATIONS DMS 5. THE DIAGNOSE MEASURE MEASUREMENT MANUEL. WE FOLLOWED THIS FORWARD IN LIFE WHILE REPEATEDLY ASSESSING THE STUDY FOR MENTAL DISORDERS AT EVERY AGE AND BY DOING THIS WE REVEALED THAT 35% OF THE POPULATION HAS A DIAGNOSEABLE BEHAVIORIAL OR EMOALINGSAL DEHAIEVERAISE CHILD OR ADOLESCENT. THIS IS KIND OF A SHOCKING STATISTIC BUT THIS RATE OF AAPPROXIMATELY ONE-THIRD OF YOUNG PEOPLE WITH A MENTAL DISORDER HAS BEEN CONFIRMED BY EPIDEMIOLOGICAL STUDIES NONAPOPTOTIC NUCLEOTIDES NORTH CAROLINA AND OREGON AND--IN NORTH CAROLINA, OREGON, BRITAIN AND SWITZERLAND SO THEREY A CRITICAL MASS OF LITERATURE ON THIS. THIS SLIDE SHOWS THE AGING AMONG THE DUNEDIN COHORT BUT THIS TIME STRATIFIED ACCORDING TO PSYCHIATRIC HISTORY IN EARLY LIFE. ON THE LEFT YOU SAW ONSET MENTAL DISORDER AS YOU'VE NILE. BIOLOGICALLY AGE 39 WHEN WE SAW THEM ATAIN 38. THEY HAD AGED ON AVERAGE 13 YEARS IN THE PAST 12 YEARS FROM AGE 26-38. IF YOU LOOKOT FAR RIGHT YOU SEE COHORT MEMBERS WHO NEVER HAD A MENTAL DISORDER, THEY AGED ONLY 10 YEARS ON AVERAGE DURING THIS 12 YEAR PERIOD SO THEY'RE AGING MORE SLOWLY THAN EXPECTED ON THE 18 BIOMARKERS THAT WE'RE TRACKING. SO THIS IS A SLIDE I TOOK AT A HOSPITAL IN BANGKOK AND I THINK IT CAPTURED MY NEW HYPOTHESIS NICELY. SOPHISTICATED I WANT TO GIVE YOU A THANK YOU TO RESEARCH TEAM MEMBERS AT DUKE UNIVERSITY, KINGS COLLEGE LONDON AND THE UNIVERSITY OF OIT, AGO WHO WORK ON THIS PROG EXPECT OUR SISTER STUDY WHO IS THE BIRTH COHORT OF TWINS IN THE U. K. AND WE'RE REPEATING THE DUNEDIN STUDY WITH THE 19 BIRTH COHORT OF TWINS. AND FOR THOSE WHO WANT TO KNOW MORE ABOUT THE ADVANTAGES OF STUDYING AGING IN YOUNG PEOPLE, THERE'S SUMMARIZED IN THIS PAPER. THANK YOU VERY MUCH. [ APPLAUSE ] NTHANK YOU VERY MUCH DR. IN, OFFI--DR. MOFFITT, AND PLEASE COME TO THE TABLE WITH THE MICROPHONES DOCTOR? >> BEAUTIFUL WORK. QUICK QUESTION TO YOU HAVE ANY INFORMATION ABOUT THE RELATIONSHIP BETWEEN THOSE EARLY MEASURES OF COGNITIVE CO PASTY AND SOCIOLOGICAL ECONOMEC STATUS? SO THE RELATIONSHIP BETWEEN THE BRAIN HEALTH IN ISSUE AND CHILD'S FAMILIES SOCIAL CLASS OF ORIGIN. YES. THEE IS A CORRELATION THERE, IT'S ABOUT SMALLER THAN YOU MIGHT THINK ABOUT .15, .12, BUT ALL THE ANALYSIS THAT WE'RE DOING CONTROL FOR SOCIOECONOMIC STATUS AND LOOK WITHIN STRATIFIED SOCIOECONOMIC STATUS GROUPS. THERE'S ALSO IN A STUDY LIKE THIS, A LITTLE COMPLICATED STUDYING SOCIOECONOMIC STATUS BECAUSE IT CHANGES SO FAMILIES MOVE UP AND DOWN THE SOCIAL CLASS LADDER PARTICULARLY WHEN MARRIAGES BREAK UP AND YOU HAVE SUDDENLY A SINGLE MOM WHERE AS YOU USED TO HAVE A MORE WELL-TO DO FATHER AND WE CAN LOOK AT SOCIAL AGE AND LIFE POINTS WHEN IT'S MORE OR LESS IMPORTANT AND WE CAN ALSO LOOK AT PEOPLE'S SOCIAL CLASS OF DESTINATION ACCORDING TO THE OCCUPATIONS AND INCOME AND WEALTH ACCRUAL THEY HAVE NOW AND ASK WHETHER THEIR HEALTH HISTORY IS RELATED TO THAT. ONE OF THE THINGS WE HAVE BEEN ABLE TO REPORT IN THE LANCEET WAS THAT CHILDREN WHO STARTED WITH LOW SOCIAL CLASS AND ACHIEVED HIGHER SOCIAL AND AND THE STATES THAT THIS IS A PRIMARILY WHITE SAMPLE IN AN ADVANTAGE. >> TERRY THANK YOU VERY MUCH, THAT IS A TOUR DEFORCE. >> YEAH. >> ONE COMMENT, 1 QUESTION. SO HOW DO WE BOTTLE A 4% ATTRITION RATE BETWEEN AGE 3 AND 38 OTHER THAN FOR PEOPLE WHO LIVE OUTSIDE OF NEW ZEALAND, IS THERE A PAPER ON LESSONS LEARN OFFICE OF DIVERSITY IN TERMS OF MINIMIZING ATTRITION ON STUDIES LIKE THAT. IT'S NOT AN INEXTENSIVE BATTERY, AND DOES 1 DO THAT. WE HAVE ENORMOUS GOOD WILL WITH THESE PEOPLE AND THERE'S SOMETHING ABOUT BEING I THINK FROM A SMALL COUNTRY VERY, VERY FAR AWAY THAT THERE'S--AND REPRESENTING THEIR COUNTRY ABROAD BRINGING MEDICAL KNOWLEDGE TO THE WORLD SO THERE'S A FEELING OF PRIDE OF TAKING PART IN THE STUDY IT ALSO HELPS THAT TELEVISION NEW ZEALAND MADE A 4 AND ON TELEVISION AROUND THE WORLD IS SHOW NOTHING CANADA AND SOUTH AFRICA RIGHT NOW AND SO THE STUDY MEMBERS SEE THEMSELVES ALSO AS SUCCESSFUL MOVIE STARS UNLIKE ME A FAILED MOVIE STAR. THE OTHER THING THAT WE DO IS THAT ANYTIME THAT ANY STUDY MEMBER HAS MOVED AWAY FROM THEIR HOME TOWN AND OVER 2/3RDS OF THEM HAVE DONE SO SO THEY MOVE TO THE NORTH ISLAND OVER TO AUSTRALIA SOMETIMES TO BRITAIN, UNITED STATES, CANADA AND LIVE ALL AROUND THE WORLD NOW, AND AIR NUCLEOTIDES ZEALAND HELPS US FLY THEM BACK TO TAKE PART SO WE WANT IN THE CLINIC, IN PERSON AND THEY GET A TRIP HOME SO IT'S NOT THE OF WHAT'S FURTHEST AWAY TEND TO BE LOST TO STUDY, SO THE WHOLE COUNTRY HELPS FOR EXAMPLE, THE PRISON SYSTEM HELPS US WHEN IT'S TIME TO ASSESS SOMEONE WHO IS CURRENTLY IN JAIL, THEY WILL BRING PRISON STAFF AND CONVERT OUR CLINIC INTO A MINIMUM SECURITY UNIT FOR THE DAY SO THAT WE CAN BRING THE INMATES AND PUT THEM THROUGH THE WHOLE PROTOCOL. SO WE GET A LOT OF COOPERATION FROM A LOT OF DIFFERENT LEVELS. >> AMAZING AND BESIDES THE EPIGENETIC FACTORS WHAT ABOUT INHERITED GENES LIKE APO3 VERSUS APOE 4? >> APOE IS SOMETHING WE HAVE GENOTYPED THOSE BUT WE HAVEN'T GOT ANY PAPERS ON THAT AND IN PART THAT'S BECAUSE OF THE I THINK THE SMALLISH SIZE OF THE STUDY, I'M NOT SURE WE WOULD HAVE THE PREVALENCE RATES TO DO POWERFUL WORK BUT AS I HAVE SERVED ON COUNCIL AND SEE WHAT OTHER PEOPLE ARE DOING, I THINK WE CAN DEVELOP SOMETHING THERE. WE'LL NEED SOME MORE EXPERTISE SO AS YOU SEE WITH A LOT OF THESE KINDS OF MEASUREMENTS WE'RE COLLECTING WE'RE BARGING AHEAD BUT WE HOPE IF WE BUILD IT POST DOCS WILL COME SO APOE RESEARCHERS PLEASE GET IN TOUCH. >> WE ARE HAVING TO GO TO LUNCH, I HAVE A NOTE HERE SAYING LUNCH IS HERE DRIVING ME AT THE MOMENT. >> SO THANK YOU VERY MUCH, DR. MOFFITT. GOOD AFTERNOON. LAST SPEAKER OF THE DAY, OF THE PROGRAM, I AM DELIGHTED TO INTRODUCE TO YOU DR. DANIEL PROMISLOW, WHO IS COMING TO US FROM THE UNIVERSITY OF WASHINGTON SEATTLE WHERE HE IS THE PROFESSOR IN THE DEPARTMENTS BOTH OF ABNORMAL GLUCOSE TOLERANCOLOGY AND THE DEPARTMENT OF BIOLOGY. HE'S ALSO THE CO-PI OF THE PROTEOMICS AND METABOLOMICS COURSE OF THE UNIVERSITY OF WASHINGTON OF THE CENTER, HE'S A GERONATOLOGYST BY TRAINING AND TRAIT, HE'S BEEN WORKING IN THIS FIELD SINCE HIS EARLY DAYS AS A ROAD SCHOLAR AT OXFORD UNIVERSITY WHERE HE STUDIED AGING AND NATURAL POPULATIONS OF MAMMALS. AND HE HAS REALLY DEVELOPED THE FIELD OF SYSTEM SYSTEM BIOLOGY AND METABOLOMICS AND THE STUDY OF AGING AND OVER A HUNDRED ARTICLES AND A NUMBER OF BOOKS, AND HE IS INTERNATIONALLY RECOGNIZED FOR HIS WORK FOR AGING ACROSS DIFFERENT SPECIES. HE'S ALSO RECOGNIZED BY WORDS TO NAME A FEW THE ELLISON SENIOR AGING AWARD AND THE BREAK THROUGH IN GERONATOLOGY AWARDS AND--HE IS THE CORRECTOR OF CANINE LONGEVITY CONSORTIUM HAD IS A COLLABORATIVE IRPT DISCIPLINARY NETWORK OF RESEARCHERS AND CLINICIANS THAT HAVE DESIGNED AND IMPLEMENTED THE FIRST NATIONWIDE CANINE LONGITUDINAL AGING STUDY AND THIS HAS BEEN FUNDED BY THE NATIONAL EN--STRATEGIESITUTES OF HEALTH AND IS DEDICATED TO UNDERSTANDING THE CAUSES OF AGING IN COMPANION DOGS. VERY RECENTLY DR. PROMISLOW AND HIS TEAM HAVE BEEN AWARDED BY NIEA TO CARRY OUT THE DOG AGING PROG EXPECT THAT WILL BE THE TOPIC OF TODAY'S TALK. THANK YOU VERY MUCH AND WELCOME DR. PROMISLOW. DID EMPLOY [ APPLAUSE ] >> THANK YOU VERY MUCH. IT'S AN HONOR TO HAVE THE OPPORTUNITY TO TALK TO ABOUT THE WORK WE ARE JUDGE UOF THE BEGINNING ON THE DOG AGING PROJECT. I WANT START WITH A DISCLOSURE THAT MATT AND KATE AND I ARE CONFOUNDERS OF A COMPANY CALLED FIDOGEN. SO I SEE THE FIELD OF GERO-SCIENCE IS BUILT ON 3 VERY BROAD KES, FIRST WHY IS IT THAT ORGANISMS AGE, WHAT ARE THE UNDERLYING BIOLOGICAL MECHANISMS AND EVOLUTIONARY EXPLANATIONS FOR AGING AND WHY IS IT THAT WITHIN A POPULATION THERE ARE INDIVIDUALS AS WE HEARD JUST NOW, SO BEAUTIFULLY WHO ARE FAST AGERS AND SLOW AGERS AND THIRD CAN WE DO ANYTHING ABOUT IT. AND 1 WAY TO KIND OF INCAPSULATE THESE QUESTION SYSTEM WITH A FIGURE THAT WE DESIGNED AS PART OF OUR GRANT PROPOSAL FOR THE DOG AGING PROJECT. IN TRYING TO UNDERSTAND--AND I DON'T KNOW IF I HAVE--THERE WE ARE, TRYING TO UNDERSTAND VARIATION AND AGE RELATED DISEASE ULTIMATELY IT COMES DOWN TO GENETIC VARIATION AND ENVIRONMENTAL VARIATION, AND THE MECHANISMS BY WHICH THESE RELATED DISEASES AND AGING ARE THE ENDOPHENOTYPES AND THE SYSTEMS BIOLOGICAL OMICs, THE PROTEIN COMPLEX I DON'T MEAN, EPIGENOME METRICS TAB O LOAM AND SO ON AND THE DOG AGING PROJECT IS AN ATTEMPT TO UNPACK THIS PATHWAY. SO WHY STUDY AGING IN DOGS, WELL FOR ANY OF YOU HAVE HAD 1 OR MORE DOGS IN YOUR LIFE, YOU'VE SEEN THAT DOG AGE. HERE'S A PHOTOGRAPH OF A DOG NAMED MADDIE AND THE SAME DOG AT AGE 5 AND 10 AND SHE AS A COUPLE OF YEARS OF LIFE LEFT HERE PROBABLY ON OFERAGE. HERE'S LILLY AT 8 MONTHS AND 15 YEARS AND SHE HAS A FEW GOOD YEARS LEFT. SO CLEARLY THERE ARE DRAMATIC DIFFERENCES IN YOUNG BREEDS IN LIFE SPAN AND THAT'S NOT ALL. AS ALL OF YOU KNOW THERE'S TREMENDOUS GENETIC VARIATION IN SIZE AND SHAPE AND COAT COLOR. THIS PAPER WHICH CAME OUT FROM ELAINE OSTRABDER, DR. OSTRANDOMIZED TRIALER IS HERE AT NIH, AND WHAT IS INSPIRED ME TO START THINKING ABOUT DOG SAYSS AS A GREAT MODEL FOR AGING. THIS PAPER WHICH GOT THE COVER OF SCIENCE FOCUSED ON GENETICS SIZE OF DOGS AND FOUND A SINGLE LOCUST THAT EXPLAINED ABOUT HALF OF ALL THE VARIATION AND SIZE IGF 1 AND AS ALL OF YOU KNOW, THERE'S A LENGTHY LITERATUREOT RELATIONSHIP BETWEEN IGF 1 AND AGING AND THAT GOT ME EXCITED ABOUT WHETHER IGF 1 MIGHT PLAY A ROLE IN CANINE AGING, WE DON'T YET KNOW THE ANSWER BUT IT CERTAINLY GOT ME GOING IN THIS FIELD AND OF COURSE THERE ARE LOTS OF LITTLER AREAS, LOTS OF OTHER PHENOTYPES WHERE WE CAN LOOK AT WHERE WE SEE GENETIC VARIATION IN BEHAVIOR FOR EXAMPLE, THERE ARE DOINGS THAT ARE HERDING DOGS BY GENETIC NATURE, THERE ARE DOINGS THAT LOVE TO JUMP. UNFORTUNATELY LIKE MY DOG, THERE ARE DOINGS THAT LIKE TO DIG, JUST LOOK AT MY BACKYARD. AND THEN IMPORTANTLY, THERE'S TREMENDOUS VARIATION IN AGING AND AGE RELATED DISEASE AND THAT'S WHAT WE STARTED LOOKING AT USING EXISTING DATA SETS. SO MY COLLEAGUE KATE KREAVY WHO WILL TELL YOU ABOUT MORE LATER REACHED OUT TO STEVE AUSSTAT WHO OBTAINED A DATA SET OF CAUSES OF MORTALITY FOR 80,000 DOG DISS 1 OF THE FIRST THINGS WE DID ON A PAPER IN 2011 WAS TO DEMONSTRATE A CROSS OF 70 BREEDS, TREMENDOUS VARIATION AND A SPECTRUM OF THE PRIMARY CAUSE OF MORTALITY. WAWE'RE LOOKING AT HERE ARE 4 BROAD CAUSES OF MORTALITY, RESPIRATORY, CARDIOVASCULAR, HEMEATOLOGICAL NGI, AS MANY OF YOU KNOW BULLDOGS HAVE GREAT RESPIRATORY PROBLEMS, THE MOST COMMON CAUSE OF MORTALITY AND RELATED TO RESPIRATORY DISEASE. IN KHIHIGH WASSAS IT'S HEART DISEASE AND IN THE SHARP A I THE MOST COMMON IS GI DISEASE, FOR THOSE WHO KNOW THE NAKED MOLE RAT STORY YOU MIGHT KNOW THAT THE WRINKLEY COATINGS CAUSE BY HIGH LEVELS OF HYURONIC ACID, PEEP USING THOSE IN AGE RELATED DISEASES. HERE FOR EXAMPLE IS A STUDY FROM [INDISCERNIBLE] 1 OF THE CO AUTHORS IS ELENNOR CARLSON COMO IS A LEAD GENETICIST IN OUR DOG AGING PROJECT AND THIS WAS A STUDY OF 2 COMMON CANCERS IN RETRIEVERS, HEMAGEIO SARCOMA AND B-CELL LYMPHOMA BOTH OF WHICH SHOWED A STRONG SIGNATURE IN CHROMOSOME 5. DOGS HAVE 39 CHROMOSOMES UNLIKE R23. IN ADDITION TO THE GENETIC VARIATION, THERE'S ALSO ENORMOUS ENVIRONMENTAL VARIATION. DOGS ARE FOUND COMMONLY IN THE UNITED STATES IN ABOUT 60 MILLION HOUSEHOLDS. THERE ARE ABOUT 90 MILLION DOGS TODAY IN THE U.S. AND NOT SURPRISINGLY, THEY ARE FOUND ACROSS DIVERSE ENVIRONMENTS. IT'S A LITTLE BIT HARD TO SEE FROM WHERE YOU ARE BUT THIS IS ACTUALLY A DOG HOUSE WITH A DOG IN FRONT OF IT AND THEN THERE ARE OTHER DOGS IN OBVIOUSLY POOR ENVIRONMENTS. THERE ARE HEALTHY DOGS AND NOT SO HEALTHY DOGS, THIS IS A DOG SMOKING A CIGARETTE. DOGS ALSO ARE FOUND ACROSS RACIAL AND ETHNIC DIVERSITY IN THE U.S., WE SEE A HIGH LEVEL OF DOG OWNERSHIP AMONG DIVERSE RACIAL GROUPS AND INTERESTINGLY IF YOU LOCK AT THE DISTRIBUTION OF INCOME FROM LESS THAN 20,000 TO OVER 85,000 ACROSS ALL HOUSEHOLDS AND THEN LOOK AT PET OWNING HOUSEHOLDS, THERE'S' A PRETTY GOOD MATCH SO WE CAN FIND DOGS IN LSEC ENVIRONMENTS AND DOGS IN IS. E. S. ENVIRONMENTS SO WE HAVE THE OPPORTUNITY TO IDENTIFY HOW GENETIC VARIATION AND ENVIRONMENTAL VARIATION AND IMPORTANTLY THE INTERACTION BETWEEN THE 2 SHAPE HEALTHY AGING IN DOGS. AND MOST IMPORTANTLY PEOPLE LOVE DOGS, NO 1 EVER COME UP TO ME AFTER GIVING A TALK ABOUT FRUIT FLIES AND SAID OH MY GODNESS I LOVE FRUIT FLIES BUT PEOPLE DO LOVE DOGS AND THAT'S A REALLY IMPORTANT MOTIVATING FACTOR. [LAUGHTER] SO TO RECAP WHY DOING? WELL THERE'S TREMENDOUS GENETIC VARIATION FOR AGE AND AGE RELATED DISEASE, THEY LIVE IN OUR ENVIRONMENT SO NOT ONLY IS THERE ENVIRONMENTAL VARIATION BUT THERE'S ENVIRONMENTAL VARIATION THAT'S A REFLECTION OF OUR ENVIRONMENTAL VARIATION. SPAN ON AVERAGE ABOUT 17th OF OUR OWN LIFE SPAN SO WHARF WE LEARN IN DOGS WE'LL TAKE 5-10 YEARS WHAT WOULD TAKE MANY DECADES IN HUMANS. THEY SHOW ROUGHLY THE SAME SPECTRUM OF DISEASES THAT WE HAVE, I'LL SHOW YOU A COUNTER EXAMPLE SHORTLY THOUGH. THE HEALTHCARE SYSTEM OF DOGS IS SECOND ONLY IN ITS LEVEL OF SOPHISTICATION TO OUR OWN SYSTEM AND AND OWNERS ARE PASSIONATE ABOUT HEALTHCARE AS WE HEARD FROM THE DUNEDIN STUDY, THIS IS ONLY IMPORTANT WHEN IT COMES TO RECRUITMENT AND RETENTION. SO WHAT DO WE KNOW ABOUT AGING AND DOGS. A BRIEF RECAP, THE BIGGEST PATTERN WE'RE AWARE OF IS THE RELATIONSHIP BETWEEN SIZE AND LIFE SPAN. SO EACH 1 OF THESE POINLTS REPRESENTS A DIFFERENT BREED, THERE'S A STRONG AND NEGATIVE CORRELATION BETWEEN LONGEVITY AND SIZE AND LARGER DOGS TEND TO BE SHORTER LIVED. THE COLORATION JUST REPRESENTS THE SOURCE OF DATA DIFFERENT STUDIES. THIS FIGURE ALSO ILLUSTRATES THE VERY GREAT DISPARITY BETWEEN THE SHORTEST LIVED BREED, THIS [INDISCERNIBLE] IS 1 OF THE SHORTEST LIVED BREEDS ON AVERAGE OF 5 YEARS AND A SKIPPER TEE HAS A LIFE SPAN OF MORE THAN 17, MORE THAN MEAN VARIATION IN LIFE SPAN. INTEREST INTERESTING PARALENS LENS LENS LENSS BETWEEN DOGS AND HUMANS, IF WE LOOK AT LOG OF MORTALITY VERSUS AGE FOR MODERN HUMANS, DOGS, FEMALES IN RED, MALE IN BLUE, THE HIGH EARLY MORTALITY WOULD BE LOOKED IN HUMANS IF WE LOOKED AT DEVELOPING COUNTRIES OR 150 YEARS AGO IN THE U.S., SO CERTAINLY THE ANCESTRAL HUMAN PATTERN LOOKS VERY MUCH LIKE THAT OF DOGS. WE ALSO SEE INTERESTING PATTERNS OF CANINE CO MORBIDITY. THIS IS OBVIOUS LELY OF GREAT--OBVIOUSLY GREAT INTEREST OF NIA HOW DOES AGE EFFECT CO MORBIDITY AND OW DO CO-MORBIDITIES IN TERN EFFECT RISK OF AGING? IN DOGS ISSUES AS IN YOU HAD HUMANS WE SEE AN INCREASE COCOITY WITH AGE THESE ARE DATA FROM THE VETERINARY MEDICAL DATABASE ABOUT 80,000 DOGS AND YOU CAN SEE THAT THE AVERAGE NUMBER OF DIAGNOSIS OF DEATH IS HIGHEST IN THE OLDEST DOGS. WE CAN ALSO LOOK AT INDIVIDUAL DISEASES, SO THESE ARE DATA SHOWING THE AVERAGE NUMBER OF DIAGNOSIS OF DEATH FOR DOGS THAT ENCLUEDED A PARTICULAR DIAGNOSIS. SO THE AVERAGE ACROSS ALL DOGS IS 3. DOGS WITH DIABETES HAVE AN AVERAGE DIAGNOSIS OF 4 AND THESE DOG VS AN AVERAGE NUMBER OF DIAGNOSIS OF 6, SO PEOPLE WOCOME UP TO YOU AND SAY, WELL, I DON'T REALLY NEED TO WORRY ABOUT OBESITY IN DOGS BECAUSE FOR EXAMPLE, THERE'S NO INCREASED RISK OF TYPE 2 DIABETES AS A FUNCTION OF OBESITY, THAT MIGHT BE TRUE BUT THERE ARE ALL SORTS OF MUCH BIG RISKS. FOCUSING ON JOB DISEASES WE SEE SIMILARITIES AND DIFFERENCES. UP HERE WE HAVE THE PROPORTION OF DOGS OR HUMAN THAT DIE OF A PARTICULAR DISEASE AT AN INDIVIDUAL AGE SO FOR EXAMPLE, AT AGE 50 ABOUT 35% OF ALL DEATHS IN HUMANS ARE DUE TO CANCER AND O THIS PATTERN THAT AS IT INCREASES WITH AGE AND GOES DOWN SIMILARLY IN DOGS AS AN INCREASE IN THE PROPORTION OF DOGS OF ANY AGE DYING IN THE DISPLASSIA, DEATHS DUE TO INGESTION OF DRUGS OR POISONS STARTS HIGH AND GOES DOWN IN HUMANS, STARTS HIGH AND GOES DOWN IN DOGS BUT THEY'RE IMPORTANT DIFFERENCES AS WELL. SO WE SEE THE STUDY INCREASE IN DEATH DUE TO CARDIOVASCULAR DISEASE AND BY THE END OF LIFE, BY AGES OF 90 OR SO ABOUT HALF OF ALL HUMAN DEATHS ARE CARD QUO VASCULAR DISEASE, IN DOGS WE SEE HEART FAILURE MIGHT ROUGH ATOM VALVE DISEASE, CARDIOMYOPATHY, CARDIOVASCULAR DISEASE AND RELATIVELY RARE AND NOT EFFECTED BY AGE. SOME PEOPLE MIGHT ARGUE THAT THAT MAKES IT A POOR MODEL FOR CARDIOVASCULAR DISEASE, OTHERS WOULD ARGUE IT MAKES IT AN INTERESTING MODEL TRYING TO UNDERSTAND WHY IT IS THAT DOGS ARE PROTECTED FROM CARDIOVASCULAR DISEASE. THERE ARE SOME NICE DATA POINTING TO THE POSSIBILITY THAT DOGS MIGHT BE A VALUABLE MODEL FOR ALZHEIMER HYM HEREY DISEASE AND THERE'S PEOPLE WORKING ON THIS AND PICTURES AT LEFT SHOW 2 DEGRADATIONS SUFFERING FROM CANINE COGNITIVE DYSFUNCTION. THE DOG ON THE LEFT IS TRYING TO GET IN THE WRONG SIDE OF A DOOR, AS MANY OF YOU WHO KNOW, DOGS KNOW WHAT SIDE THE DOOR WILL OPEN FOR THEM, THE DOG ON THE RIGHT IS LOST, STUCK UNDER A CHAIR AND CAN'T FIND HIS WAY OUT. WHEN WE ELECTRIC AT THESE DOGS POST PORT UMKC WE SEE A BETA 42 PLAQUES AND THERE'S RECENT DATA POINTING TO THE POSSIBILITY THAT WE ALL SEE--ALSO SEE INCREASED LEVELS OF PHOSPHORALATESSED TAU. THERE'S GREAT INTEREST IN BIOMARKERS IN THE VET FIELD BUT IT ILLUSTRATES A REAL PROBLEM THAT EXISTS IN THE VETERINARY FIELD UNTIL NOW. TYPICAL VET STUDIES ARE SMALL. THESE VET STUDIES ARE LOOKING AT LESS THAN 50 DOGS TO RIERKS DENTIFY BIOMARKERS, MY CLOSE COLLABORATOR, KATE KREEFY LIKES TO SAY THAT THE PROBLEM IS ILLUSTRATED BY THE PAPER THAT COMES OUT THAT INCLUDES 5 DOGS, 2 GOATS AND A FERRET BECAUSE THOSE ARE THE 8 SPECIES THAT THE INDIVIDUALS THAT HAPPEN TO COME INTO THE CLINIC WITH SOME UNUSUAL DISORDER. SO WE NEED TO CHANGE THAT AND THAT'S PARTLY WHAT WE'RE TRYING TO DO HERE. SO THE WORK WAS INSPIRED WHEN [INDISCERNIBLE] CAME OUT IN A PAPER AT THE 2007, I WAS AT THE UNIVERSITY OF GEORGIA AT THE TIME. I TURN TO DR. KATE KREEFY, AND SHE WAS THERE AND IS NOW AT TEXAS A&M. WE STARTED TALKING ABOUT CREATING STUDIES BASED ON 10S OF THOUSANDS OF DOGS. WHEN I MOVED TO THE UNIVERSITY OF WASHINGTON IN 2013 EVEN BUYER I GOT THERE, MATT AND I STARTED TALKING ABOUT THE POSSIBILITY OF CARRYING OUT HEALTH SPAN INTERVENTION STUDIES IN DOGS AND SO WE--WORKING WITH ESPECIALLY WITH KATIE AND MATT AND MANY OTHER COLLEAGUES AND PEOPLE AT NIA, WE'VE BEEN DEVELOPING THE DOG AGING PROJECT. OUR EARLY INSPIRATIONS HAVE BEEN THE LONG-TERM LONGITUDINAL STUDIES YOU HEARD ABOUT THE DUNEDIN STUDY AND THE BALTIMORE STUDY GO BACK 60 AND 70 YEARS AND THE BRITISH BIRTH COHORT IS GOING BACK A HUNDRED YEARS AND MORE RECENTLY THE MORRIS ANIMAL FOUNDATION IN DENVER STARTED THE GOLDEN RETRIEVER LIFETIME STUDY. THAT'S THE FIRST LONG-TERM LONGITUDINAL STUDY IN DOGS ABOUT YOU IT'S ONLY 1 BREED SO THERE'S LITTLE GENETIC VARIATION AND IT'S FOCUSED ON THE 5 COMMON CAUSES OF CANCER RATHER THAN AGE NOTHING GENERAL AND IT'S A BEAUTIFUL STUDY AND ALL OF THESE ARE SORT OF THE GIANTS ON WHOSE SHOULDERS WE'RE STANDING. SO THE DOG AGING PROJECT INCLUDES 4 CORES WHICH I WILL TELL YOU ABOUT SHORTLY AND 4 PROJECTS. THE FIRST PROJECT IS REALLY AN ATTEMPT TO DEFINE AGING. WE HEARD ABOUT SIMPLE MEASURES THAT ALL OF YOU ARE FAMILIAR WITH LIKE GRIP STRENGTH AND WALKING SPEED AND THE TIME IT TAKES TO STAND UP OUT OF A CHAIR, WEEZ DON'T HAVE THOSE SIMPLE MEASURES THAT WILL ALLOW US TO CHARACTERIZE WHETHER AN OLDER DOG IS A HEALTHY AGER OR NOT. OUR FIRST PROJECT IS DEFINED AND AIMED TO SIMPLY DEFINE THAT AND THIS, IF SUCCESSFUL WILL BE A REAL GAME CHANGER FOR THE ENTIRE FIELD OF VETERINARY MEDICINE WHICH DOESN'T HAVE A GERIATRIC SPECIALTY DESPITE HAVING A COUPLE OF DOZEN OTHER SPECIALTIES. THE SECOND PROJECT IS GOING TO IDENTIFY THE GENETIC FACTORS THAT SHAPE AGING AND AGE RELATED DISEASE THAT INFLUENCE THE HEALTHY AGERS. THE THIRD PROJECT AND GENOMICS WILL TRY AND GET THE MECHANISMS THAT ARE THE TIE BETWEEN GENO TYPE AND PHENOTYPE AND ALSO TO IDENTIFY BIOMARKERS OF HEALTHY AGING AND THEN PROJECT 4 IS OUR INTERVENTION PROJECT LOOKING AT WHETHER WE CAN USE RAPOMYCIN TO INCREASE LEFT VENTRICULAR HEART FUNCTION AND HEALTH SPAN IN GENERAL IN AGING DOGS. IMPORTANTLY THE WHOLE IS THE MUCH GREATER THAN THE SUM OF THE PARTS. ALL THESE ISHT ACT CLOSELY WITH EACH OTHER AND SO TO GIVE YOU 1 EXAMPLE, INTERACTIONS BETWEEN PROJECT 2, GENETICS AND PROJECT 3 THE OMICS WILL GIVE US THE OPPORTUNITY TO ACTUALLY IDENTIFY THE GENERATEDET AND I CAN ENVIRONMENTAL DEFERMINANTS OF VARIATION IN METRICS TAB O LOAM OR THE EPIGENOME. THE ENTIRE COHORT CONSISTS OF 10,000 DOGS, ALL OF THESE DOGS WERE HAVE DNA SEQUENCING AND ANNUAL ELECTRONIC MEDICAL RECORDS AS WELL AS BASIC INFORMATION WE'LL COLLECT FROM THE OWNERS IN THE HOUSEHOLD. NESTED WITHIN THIS FOUNDATION COHORT IS THE PRECISION COHORT AND 1200 DOGS. THIS IS THE SYSTEM SYSTEM BIOLOGY COHORT FOR WHICH WE'LL HAVE OMIC MEASURES AND OTHER MEASURES AND THEN OVERLAPPING WITH THE PRECISION COHORT IS THE INTERVENTION COHORT. 500 DOGS WILL INITIALY BE ENROLLED. OUR GOAL IS TO HAVE 300 DOGS THAT COMPLETE THE RAPOMYCIN STUDY. THE PLACEBO DOGS WILL BE PART OF THE PRECISION COHORT BUT ONLY AFTER THE COHORT IS UNPLIENDED AFTER THE 3 YEARS OF TREATMENT. SO IT'S A DOUBLE BLINDED STUDY, ALTASD TOGETHER WE WILL COVER LOW DNA SEQUENCING FOR WHAT WE CALL OUR CENTENARIAN DOGS, WE WILL HAVE HIGH COVERAGE SEQUENCING, CLINICAL CHEMISTRY ATTACK SEQ TO LOOK AT THE GENOME, FECAL MIC ROW BIOME, ELECTRONIC MEDICAL RECORDS ACTIVITY MONITORS LIKE DOG FIT BITS. ENVIRONMENTAL DATA, AIR QUALITY, WATER QUALITY AND THEN A GREAT DEAL OF OWNER PROVIDED DATA THROUGH REGULAR SURVEYS. THE LOGISTICS FOR A PROJECT LEAK THIS IS CHALLENGING. THIS BRIEFLY LAYS OUT HOW WE ENVISION THE LOGISTICS. I WANT TO STARLIGHT BY JUST TELLING YOU A BIT ABOUT THE CORES. SO CORE A IS THE ADMEN ADMINISTRATIVE CORE THAT I WILL BE RUNNING AT THE UNIVERSITY OF WASHINGTON THAT OVER SEES THE ENTIRE PROJECT. AND I SHOULD MENTION THE PROJECT IS GOING TO--IS BEING FUNDED BY A U-19 FROM NIA. WE HAVE JUST RECEIVED NOTICE OF AWARD SO FUNDING WILL BE STARTING IN THE NEW FISCAL YEAR. SO CORE B IS THE DATA CORE. IT'S BASED AT THE UNIVERSITY OF WASHINGTON AND THAT WILL BE RESPONSIBLE FOR THE DATA COLLECTION, CURATION, DISSEMINATION AND ASSISTANCE WITH DATA ANALYSIS AND I SHOULD POINT OUT THIS IS AN OPEN DATA SCIENCE PROJECT. ALL THE DAILY BASIS AT THAT WE, ARNG LOWED TO MAKE PUBLIC WILL BE MADE PUBLIC WITHIN 18 MONTHS OF DATA CAPTURE THROUGH CORE B. CORE C AND LED BY DR. KATE KREEFY AT THE UNIVERSITY AT TEXAS A&M UNIVERSITY VET SCHOOL AND THIS IS THE RECRUITMENT AND RETENTION CORE. IT WILL CAPTURE OUR AUDIENCE OF SCIENCE SCIENTISTS AND VETERINARIANS AND WILL BE RESPONSIBLE FOR COMMUNICATION WITH THOSE DOG OWNERS AND VETINARS AND ALSO FOR SAMPLE COLLECTION. THE RED ARROWS ARE PHYSICAL SAMPLES. THE BLUE ARROWS ARE DATA SO OF CORE C WILL BE AVAILABLE FOR INSURING THESE KIDS ARE SENT TO OWNERS OR VETS FOR DATA COLLECTION AND SAMPLE COLLECTION AND THEN TO A REFERENCE LAB FACAS FOR PROCESSING AND THEN EITHER UPLOADED TO THE CORE AND SENT FOR FURTHER PROCESSING FOR MASS SPEC FOR EXAMPLE OR SEQUENCING. CORE D WILL BE RESPONSIBLE FOR COLLECTING THE ENVIRONMENT DATA AND I SHOULD SAY THAT THE DATA WILL BE AVAILABLE NOT JUST FOR SCIENTISTS AND PROJECTS FOR EXAMPLE AND OTHER SCIENTISTS WHO ARE INTERESTED BUT ALSO WE HOPE TO CREATE A PORTAL THAT PROVIDES USER FRIENDLY ACCESS FOR OWNERS AND FOR THE PUBLIC IN GENERAL. SO THE TEAM JUST BRIEFLY INCLUDES AT THE ADMINISTRATIVE TEAM AT THE UNIVERSITY OF WASHINGTON AND ABOUT WOTHIRDS OF SCIENTISTS ARE AT U-DUB, SO WE HAVE THE CORE AT TEXAS A&M AND ADVISELY PANELS, LEADERSHIP COMMITTEE AND LEADERSHIP CORE AND INDEPENDENT SCIENTIFIC ADVISORY BOARD CHAIRED BY BRIAN KENNED EXPE ANIMAL WELFARE ADVISORY BOARD CHAIRED BY PATTY OLSON WHO HAS A DVM AND BOARD CERTIFICATION IN ANIMAL WELFARE AND THE A DSMB FOR THE RAPOMYCIN THAT IS YET TO BE CONSITUTED. IT'S A HIGHLY DISCIPLINARY STUDY IN ADDITION TO OUR GERONATOLOGY STUDY, WE HAVE EXPERTISE AT THE TABLE IN ANIMAL WELFARE TO BIOETHICS FROM STATISTICS TO SYSTEMS BIOLOGY, DIVERSE EXPERTISE EEVERY TIME I TALK TO PEOPLE WHO AREN'T INVOLVED WITH THIS, THEY ASK IF THEY CAN COME UNDER THE UMBRELLA OR UNDER THE TENT. WE HAVE A BIG TENT, WE WELCOME INTERACTORS. IN TERMS OF TRANSLATIONAL POTENTIAL, WE BELIEVE THAT WHAT WE LEARN ABOUT BEN GETTICSTICS AND ENVIRONMENT EFFECTING HEALTH SPAN AND DOGS WILL BE TRANSLATABLE TO HUMANS, BUT ALSO DOINGS CONNECT AS SENTINALS. THERE'S ALREADY A LARGE LITERATURE LOOKING AT DOGS AS SENTINALS IN THE HUMAN ENVIRONMENT BECAUSE DOGS AGE SO MUCH MORE QUICKLY, IF THERE'S AN ENVIRONMENTAL RISK FACTOR THAT EFFECTS THE RISK OF DISEASE IN DOGS, WE EXPECT ON TO SEE IT IN 3 TO 5 YEARS AND THEN WE CAN ASK WHETHER SIGNS OF THOSE DISEASES ARE ALSO SHOWING UP IN THE HUMAN OWNERS. WE'RE ALSO VERY EXCITED ABOUT THE POSSIBILITY OF STUDYING DOG OWNERSHIP AS IT IMPACKS AND I'VE ALREADY HAD CONVERSATIONS WITH LOUIGI FARROUCI, AND JOANNE THE HEART STUDY, I'VE BEEN E-MAILING WITH EILEEN CRIMMINS, AT THE HEALTH AND RETIREMENT STUDY AND WEAR EXCITED ABOUT THESE INTERACTIONS. THERE ARE BROADER IMPACTS IN ADDITION TO PARTNERSHIP WITH HUMAN STUDIES WE'RE INTERESTED IN ANCILLARY STUDIES. WE WELCOME OTHER PEOPLE ONCE THE COHORT IS CREATED WHO ARE INTERESTED IN RARE DISEASES OR NEW BIOMARKERS OF THE TECHNOLOGY DEVELOPS, SOCIAL SCIENTISTS AND HUMANITIES RESEARCHERS WE'RE EXCITED ABOUT INVOLVING CITIZEN AND GIVING DOG OWNERS IN THE GENERAL PUBLIC AN EXCITEMENT FOR GE RO-SCIENCE AND GERO-SCIENCE RESEARCH AND AS A MENTIONED THE IMPACT OF DOGS ON HUMAN HEALTH. CURRENT STATUS, WE ARE CURRENTLY DEVELOPING THE INFRASTRUCTURE, THE WEBSITE BOTH FRONT END AND BACK END OF DATA MANAGEMENT AND WE'RE IN DISCUSSIONS WITH SAGE BIONETWORKS. EE ALREADY HEARD ABOUT THEM TODAY AND THE ALZHEIMER'S TALK TO HELP US DEVELOP A PHONE APP. WE HOPE TO TBE BEGIN RECRUITMENT IN FEBRUARY OR MARCH OF 2019. THE GOAL IS TO BRING IN AT LEAST 50,000 APPLICANTS AND THEN CHOOSE 10,000 TO CREATE A DIVERSITY OF BREED BOTH PURE BRED AND MIXED BREED, ALL AGES, SEXES, GEOGRAPHIC VARIATION AND SOCIOECONOMIC STATUS. IN THE INTEREST OF TIME I WILL JUST SKIP VERY BRIEFLY THROUGH THIS AND I WILL MENTION WE'RE ALREADY CARRYING OUT A NOW A PHASE 2 RAPP A MYCIN PHASE 12 STUDY IN TEXAS, PHASE 1 IS COMPLETE. WE FOUND A LOW DOSE AMOUNT ON LEFT VENTRICULAR HEART COMPOUND AND INTERESTINGLY, BUT NOT SIGNIFICANT WE'RE ALSO LOOKING AT AN EPIGENETIC CLOCK AND LOOKING THE AN ETAXIC CLOCK AND LOOKING AT PRESENCE OF PEEK AND TRANSCRIPTION SITES THAT INDICATE OPEN OR CLOSED CHROMATIN AND VERY PRELIMINARY DATA, LOOKING AT PERRIFFERAL OR CORPORATE CELLS SUGGEST THERE ARE SITES THAT ARE ASSOCIATED EITHER INCREASING CHROMATIN AVAILABILITY WITH AGE OR DECREASING WITH AGE OR INTERESTED IN MOVING FORWARD TO DEVELOP THAT CLOCK. I JUST WANT TO FINISH OUT WITH MY ACKNOWLEDGMENTS AND THE MOST IMPORTANT ACKNOWLEDGMENTS THAT I REALLY HAVE TODAY ARE TO NIA. WHEN I FIRST STARTED WORKING ON DOGS, I DIDN'T REALLY KNOW WHERE I WAS GOING AND I HAVE TO SAY THAT RON KOHANSKI CONTACTED ME AND SAID YOU HAVE TO DO THIS BIG. WE ARE EXCITED, GO BIG AND THINK ABOUT ANYTHING YOU COULD POSSIBLY DO. HE REALLY INSPIRED US, FETAL FELIPE, HAS PROMOTED OUR WORK AND FRAN CHESK KACCT HAS MADE EVERYTHING POSSIBLE, HELPED US ALONG THE WAY, MADE SURE THAT WE'RE DOING THIS IN THE BEST POSSIBLE WAY THAT WE CAN AND OF COURSE THIS ENORMOUS TEAM OF RESEARCHERS WHO ARE WORKING TOGETHER EVERY TIME I ASK SOMEONE TO JOIN US AND LEND THEIR EXPERTISE THEY'VE ALWAYS SAID YES I'VE NOT YET HAD ANYBODY SAY NO I'M NOT INTERESTED. SO THIS REALLY BEEN EXCITING WORK. WE'RE JUST ABOUT TO KICK THIS OFF AND I THINK THIS IS A GAME CHANGER FOR GERO SCIENCE, FOR VETERINARY SCIENCES, CERTAINLY BEEN A GAME CHANGER FOR ME IN MY OWN CAREER, IT'S REALLY EXCITING, THE WHOLE TEAM IS EXCITED AND I HOPE HAVE YOU PICKED UP A LITTLE BIT OF THAT EXCITEMENT. I WANT TO THANK YOU FOR INVITING MOOY TO SPEAK TO YOU TODAY AND THANK YOU IF ARE YOUR ATTENTION. [ APPLAUSE ] >> QUESTIONS? >> YES, THANK YOU ANYONE HAS HAS A DOG IS FASCINATED BY YOUR WORK BUT MY QUESTION HAVE YOU CONSIDERED THE OWNERS AS DATA COLLECTORS AND WHAT WOULD THAT ROLL LIKE LOOK IF YOU ARE ENGAGING DATA SCIENTISTS? >> SO REALLY IMPORTANT QUESTION, I WANT TO BRIEFLY ADDRESS 2 THINGS SO, AND THE OWNERS ARE VERY MUCH DATA COLLECTORS THAT'S PART OF THE REASON THAT'S CREATING A RELATIVELY PHONE APPLICATION THAT WILL ALLOW US TO SEND OUT REGULAR PUSH NOTIFICATIONS PERHAPS MONTHLY WITH SIMPLE QUESTIONS AS WELL AS QUESTIONNAIRES WE'RE GOING TO FILL OUT, VIDEO SO THAT THEY CAN SEND US VIDEOS OF GATE FOR EXAMPLE, THINGS LIKE THAT. ACTIVITY LEVELS. THERE ARE ALSO VERY IMPORTANT QUESTIONS THAT WE NEED TO ADDRESS ABOUT RELIABILITY, ABOUT OWNER FATIGUE, ABOUT WHO OWNS THOSE DATA. EDITORIAL THIS YEAR IN SCIENCE, ABOUT INTELLECTUAL PROPERTY. SO THESE ARE ALL IMPORTANT QUESTIONS THAT WE WILL BE ASKING AND TRYING TO ANSWER. CERTAINLY THE RELIABILITY PIECE IS CRITICAL. WE WILL ALSO HAVE A BLANKET IRB APPROVAL THAT ALLOWS US TO ASK THE OWNERS ABOUT THEIR OWN BEHAVIOR, DO THEY SMOKE OR NOT FOR EXAMPLE, ABOUT THEIR HEALTH TO OBTAIN THEIR OWN MEDICAL RECORDS SOPHISTICATEDY WE CAN LOOK AT THE RELATIONSHIP BETWEEN VETERINARY ELECTRONIC MEDICAL RECORDS AND THE HUMAN ELECTRONIC MEDICAL RECORDS AND THOSE ARE CHALLENGES AND IMPORTANT AND I'M ALSO REALLY EXCITED ABOUT THE IDEA OF HAVING PEOPLE PARTICIPATING IN SCIENCE WITHOUT REALIZING THAT THEY'RE DOING SCIENCE AND THEN AFTER 3 OR 4 YEARS SAYING LOOK AT WHAT YOU'VE BEEN DOING SCIENCE IS NOT SOMETHING TO BE AFRAID OF, - IT IS A COOL, FUN, THING THAT WILL ALLOW YOU TO LEARN ABOUT A LOT ABOUT AGING AND ABOUT YOUR DOG. >> THAT WAS A GREAT PRESENT AITIONZ, AAH-INSPIRING JUST AWESOME I WANT TO TOSS BACK TO YOU THE SAME QUESTION YOU ASKED ME WHICH IS ABOUT SOCIAL CLASS EFFECTS, I KNOW YOU HAVE SNYDER MECHLER ON YOUR TEEM AND HE'S 1 OF OURS AND NOAH USED TO SAY TO ME THE REASON IS FOR STUDYING MONKEYS IS BECAUSE THEY DON'T HAVE SOCIAL CLASS AND ALL THAT GOES WITH THAT, BUT WITH DOGS THEY SORT OF DO HAVE SOCIAL CLASS. SO CAN YOU SAY A BIT ABOUT THAT. >> SO THERE'S REALLY--NOT A LOT HAS BEEN DONE, VERY LITTLE HAS BEEN DONE ON SOCIAL CLASS AND DOGS THERE ARE A FEW THINGS THAT I'M REALLY INTERESTED IN. ONE I'M INTERESTED IN THE SENTINAL PIECE. SO PEOPLE HAVE LOOKED AT DOGS AS SENTINALS AND BOTH FOR PATHOGENS, BEAUTIFUL STUDY CAME OUT THIS YEAR, SHOWING EVIDENCE OF THE SPREAD OF LYME'S DISEASE BASED ON TITERS OF ANTIBODIES IN DOGS BEFORE THEY SHOW UP IN HUMANS. SO THATIA A POWERFUL PIECE, THERE'S EVIDENCE FOR EXAMPLE OF LED SO THOSE RISK FACTORS WE SO THE FINES--THIS MIGHT BE A GREATER CHALLENGE THOSE PEOPLE MOVE AROUND MORE, SO WE'RE EXCITED ABOUT THAT, AND THERE ARE OBVIOUSLY AND THERE ARE CHALLENGES TO THAT, TO THE RECRUITMENT YEAH, SO REALLY INTERESTED AND WE'RE EXCITED IN THAT WE WILL RECRUIT DOGS AND SO 1 THINK THIS I WANTED TO ADD DOGS IN THE LOWEST OF LOW SES ENVIRONMENTS THE DOGS OF OF HOMELESS PEOPLE TEND TO BE VERY HEALTHY. THERE ARE VET LYNNICS AROUND THE COUNTRY THAT CATER TO DOGS OF HOMELESS PEOPLE AND THOSE DOGS TEND TO BE WELL FED AND ARE REALLY IMPORTANT ASPECT OF DOGS SOCIAL LIFE IS INTERACTION WITH PEOPLE AND HOMELESS--DOGS, BELONG TO HOMELESS PEOPLE TEND TO BE WITH PEOPLE MORE OFTEN THAN MY DOG FOR EXAMPLE, AND THAT IS A REALLY POSITIVE ASPECT OF THEIR LIFE SO THERE ARE INTERESTING ASPECTS OF CANINE HEALTH AT THE LOWEST END OF THE SOCIOECONOMIC SPECTRUM. >> HOW DO I ENROLL MY WHEATON TERRIER AND I LIVE IN LEISURE WORLD WHERE EVERYBODY HAS A DIFFERENT KIND OF DOG AND IS ALWAYS OUT WALKING THEM AND THAT'S IN THE RECRUITMENT ARENA. >> THIS IS A REMINDER FOR ME TO SAY 2 THINGS, FIRST OF ALL DOG AGING PROJECT.COM. ALL 1 WORD, DOGAGINGPROJECT.COM. WE WON'T BEGIN RECRUITMENT UNTIL 2019, AND WE'RE TRYING TO GO INTO THE RADAR, AND THE SECOND TECHNOLOGY TRANSFER I WANT TO POINT OUT AND THE REASON WE ARE GOING TO INVEST IN IS WHAT THE GOLDEN RETRIEVER LIFETIME STUDY TELLS US IT'S A BEAUTIFUL STUDY, I ENCOURAGE YOU TO LOOK IT UP IS THAT THIS IS AN OPPORTUNITY TO BUILD A COMMUNITY, THE GOLDEN RETRIEVER AND GET RETENTION AFTER 5 YEARS AND ALL THE DOGS ARE KNOWN BY NUMBERS AND THEY TELL ME THEY SEE THINGS LIKE ON FACEBOOK, SOMEONE WILL SAY THIS IS 192, I'M GOING TO BE IN LAWRENCE KANSAS NEXT WEEK DOES ANYBODY LIVE THERE, WOULD YOU LIKE TO GO FOR A WALK? SO THIS IS AN OPPORTUNITY THAT BUILD COMMUNITY AND WE KNOW THAT THAT'S A REAL CHALLENGE IN OUR SOCIETY. >> I CONGRATULATE YOU ON THIS EXCITING INDEED. I WAS WONDERING MAY BE I MISS IT FOR HOW LONG WILL YOU BE FOLLOWING THE DOGS AND I IMAGINE THAT SOME DOGS WILL PASS AWAY ALONG THE WAY, IS THERE A PATHOLOGY COMPONENT. >> YES, THANK YOU FOR THOSE QUESTIONS. THE U19 IS FOR 5 YEARS AND I FULLY INTEND TO RENEW AND MAKE THAT 10 YEARS. WE WILL ALSO BE PURSUING OTHER FUNDING SOURCES TO ALLOW US TO DO MORE THAN AS IN THE U19 EVEN THOUGH IT'S A SUBSTANTIAL GRANT. WE ANTICIPATE--I SHOULD NOTE FOR THE RAPP A MOCYN THOSE WILL BE MIDDLE AGED LARGE BREED DOGS AND WE ANTICIPATE 30% OF THOSE WILL DIE IN THE 5 YEAR PERIOD BUT ALL BREEDS, ALLIGES ALL SIZES WILL BE ENROLLED AND WE HOPE TO DO NECROPSY ON AT LEAST 20% OF THE DOGS AND HOPEFULLY MORE, IT'S UP TO THE OWNERS. MANY OWNERS WON'T WANT TO NECROPSY THEIR DOG, WE WILL ASK THAT AT INTAKE BUT THAT WON'T BE A CRITERION FOR ENTERING INTO THE STUDY. THE ETHICAL BAR HERE FOR WHAT WE CAN DO IS EXTREMELY HIGH. WE CAN'T DO ANYTHING TO THESE DOGS THAT ISN'T PART OF THEIR REGULAR CARE, BUT OVER ALL WE CAN TAKE SKIN BIOPSIES BUT WE MIGHT LOOK INTO DOING THAT IN THE FUTURE. >> FABULOUS WORK, I AM EXCITED TO SEE THIS UNFOLD AND APPRECIATE THE WAY YOU ARE ENGAGING THE PUBLIC AND I HOPE THAT AS A RESULT OF THIS DEALING WITH THE PUBLIC COME TO APPRECIATE THAT DOG AGING RESEARCH IT REALLY COOL AND REALLY IMPORTANT BUT MAYBE THEY'LL SHORTEN THAT TO SAY THAT AGING RESEARCH IS REALLY COOL AND REALLY IMPORTANT SO THERE ARE WAYS TO SORT OF CARRY THE MOMENTUM FROM THIS, TO HAVE A SIDE BENEFIT TO RAISE AWARENESS AND THE VALUE OF AGING RESEARCH AMONG THE GENERAL PUBLIC SO CONGRATULATIONS. >> THANK YOU. >> DR., YOU DON'T HAVE A QUESTION, IT IT'S LATE I WAS HOLDING OFF BUT NOW THAT YOU'VE INVITED ME. [LAUGHTER] IT WOULD BE NICE TO SEE A LARGER NUMBER OF BEAGLES AND RELATE THIS TO ALZHEIMER'S I HEAR THAT'S ALZHEIMER'S FUNDING AVAILABLE THESE DAYS BUT JUST A QUESTION I HAVE, AND YOU GAVE A GREAT EXAMPLE OF THAT WHAT ARE THE PROS AND CONS OF METHOD LOGICALLY OF TRYING TO FIND INHERITED GENES THAT IS HIGHLY INBRED LIMITED GENE POOL SPECIES ABOUT GOING ACROSS SPECIES AND INDIVIDUAL VARIATION WITHIN SPECIES AND COMPLEMENT EACH OTHER AND OTHERS. >> SO FIRST OF ALL AMONG--THERE'S RELATIVELY LITTLE VARIATION DEGREE BUT ENOUGH TO MAP TRAITS LIKE THE OTHER STUDY, THE AWESOME POWER GENETIC POWER OF DOGS LIES IN ITS BREED STRUCTURE, AND WE KNOW A LOT ABOUT THE HISTORY OF THE BREEDS AND IF YOU THINK ABOUT US OTHER THAN TWIN STUDIES EACH OF US AND A UNIQUE EXEMPLAR OF OUR OWN GENOTYPE AND THE PROBLEM IS THAT WE ONLY HAVE 1 MEASURE. SO MY FATHER'S 6-FOOT 2 AND MY BROTHER IS 6-FOOT 3 AND ON A GOOD DAY I'M FINE FOOT 10 AND GENETICALLY MY BREEDING VALUE MIGHT BE CLOSER TO 6-FOOT OR 61. BUT FOR WHATEVER ENVIRONMENTAL REASONS I DIDN'T GET THERE. IF THERE WERE A HUNDRED OF ME, WE WOULD KNOW EXACTLY WHEN MY GENETIC HEIGHT IS. SO THATIA I BIG PROBLEM IN HUMAN STUDIES IN THE DOG STUDY, WE KNOW EXACTLY WHAT THE GENETIC SIZE IS FOR A WHEATEN TERIOR OR A BEAGLE OR A GREAT DANE. SO THERE'S TREMENDOUS POWER IN MAPPING COMPLEX TRAITS IN DOGS. THERE ARE BIG LINKAGE GROUPS THAT RAISES A CHALLENGE BUT WITH THE MIXED BREED DOGS WITH ALL THE RECOMBINATION, WE CAN THEN HONE IN ON INDIVIDUAL GENES. I ACTUALLY THINK WE'RE NOW AT A POINT WHERE WE ARE ALSO BEGENERATEDDING TO REALLY POWER AT IRPT SPECIFIC MAPPING AND THAT WORK THAT RELATIVELY JUNIOR GUIN AT PITTSBURGH NAMED NATHAN CLARK WHO'S BEEN IDENTIFYING USING SPECIES WIDE COMPARISONS OF WHOLE GENOMES LOOKING AT HOW RATES OF PRINTING EVOLUTION CORRELATE WITH COMPLEX TRAITS ACROSS SPECIES. A POST DOC IN HIS LAB IS WRITING A PAPER RIGHT NOW SHOWING THAT THERE ARE PARTICULAR PROTEINS ACROSS ALL MAMMALS, THERE ARE FEW PROTEINS THAT SHOW VERY RAPID EVOLUTION OF HISTORY AND HOW ASSOCIATED WITH LIFE SPAN. SO YOU TAKE THOSE SPECIES THAT HAVE LONG LIFE SPAN AND THEY HELP TO HAVE A FEW PROTEINS THAT EVOLVE VERY QUICKLY. SO I--I THINK BECAUSE OF BEING IN A--A NEXT GEN SEQUENCING ERA THAT THE ALL OF THESE APPROACHES ARE WITHIN HUMAN GWAS, THE BREED STRUCTURE DOG STUDIES INTERSPECIFIC GENOMIC STUDIES ARE ALL GOING TO COMPLEMENT EACH OTHER AND THE FINAL THING I'LL SAY IS, ALL 3 OF THOSE ARE CRITICAL AND ANSWERING THE BASIC QUESTION OF WHETHER THE GENES THAT WE IDENTIFIED IN YEAST WORMS FLIES AND MICE IN THE LAB HAVE ANYTHING TO DO WITH THE VARIATION IN THIS ROOM AND I THINK THAT'S AN OPEN QUESTION. DOGS IN SPECIFIC STUDIES AND GWAS IN HUMANS ARE THE ONLY WAY TO ANSWER THAT QUESTION. >> THANK YOU VERY MUCH DR. PROMISLOW. >> THANK YOU. >> [ APPLAUSE ] >> WE ARE ADJOURNED, THANK YOU