WEBVTT

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FROM ITALIAN OPERA.

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FIRST, IF YOU WOULD LIKE TO LIVE

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LONGER AND HEALTHIER IT APPEARS

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AN INDIANA AMISH FAMILY MAY HOLD

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SECRETS.

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A STUDY FINDS A GROUP OF AMISH

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PEOPLE WITH A GENETIC MUTATION

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LIVE 10% LONGER THAN RELATIVES

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WITHOUT THE MUTATION IT IS A

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MUTATION THAT SEEMS TO PROTECT

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AGAINST BIOLOGICAL AGING AND

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HUMAN TRIALS HAS BEGUN ON A DRUG

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THAT CREATES A KEY EFFECT ON

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THAT MUTATION.

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THE AUTHOR IS DR. DOUGLAS

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VAUGHAN, A CARDIOLOGIST AT THE

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FINEBURG SCHOOL OF MEDICINE.

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AND DR. DOUGLAS VAUGHAN JOINS US

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NOW.

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I UNDERSTAND THIS IS JUST A

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SINGLE LARGE EXTENDED FAMILY.

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TELL US MORE ABOUT THEM.

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>> THE FAMILY ORIGINALLY

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IMMIGRATED FROM SWITZERLAND IN

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THE MID-1800'S.

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AND WE CAN TRACE BACK THE

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MUTATION TO TWO ORIGINAL

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FOUNDERS THAT MOVED TO INDIANA

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AND AROUND 1850.

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AND SUBSEQUENTLY THIS MUTATION

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HAS BEEN HANDED DOWN THROUGH

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SEVEN GENERATIONS AND IT WAS

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DISCOVERED BY VIRTUE OF THE FACT

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THAT A SINGLE INDIVIDUAL

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PRESENTED IN THE EARLY 1990s

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WITH AN UNUSUAL BLEEDING

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DISORDER.

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AND THAT ALLOWED HEMOTOLOGISTS

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TO TAKE CARE OF THE GROUP TO

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APPRECIATE THE FACT THERE WAS

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SOMETHING UNUSUAL GOING ON.

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>> AND SOME MEMBERS OF THE

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FAMILY HAVE THIS MUTATION AND

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OTHERS DO NOT.

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HOW GOOD A CONTROL GROUP DOES IT

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GIVE YOU?

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>> AS GOOD AS YOU GET.

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THEY LIVE IN THE SAME AREA, THEY

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HAVE THE SIMILAR LIFESTYLE THEY

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LIVE AN 18TH CENTURY LIFESTYLE

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AND HAVE A SIMILAR DIET AND WEAR

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SIMILAR CLOTHES.

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THAT IS A GOOD CONTROL GROUP.

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>> SO THE PEOPLE WHO DO HAVE THE

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MUTATION, TELL US ABOUT HOW THAT

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MUTATION APPEARS TO BENEFIT

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THEM?

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>> THE MUTATION IS IN A FACTOR

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THAT APPEARS TO BE A MOLECULAR

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MARKER OF AGING.

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AND IT'S PRESENT IN CELLS OR

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TISSUES WHEN IN OTHER ANIMAL

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SPECIES THE PRESENCE OF THIS

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MUTATION BY CARRYING A SINGLE

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MUTANT COPY OF THE GENE PROVIDES

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A VARIETY OF BENEFITS FOR THE

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CARRIERS.

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TEAL MERES ARE THE CAPS OF YOUR

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CHROMOSOMES AND THEY SHORTEN AS

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WE AGE AND THEY PREDICT YOUR

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FLIGHT PATH INTO OBLIVIAN.

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>> IT IS A GENETIC HOURGLASS.

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>> IT IS AND SOME PEOPLE THINK

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IT IS A MARKER OF YOUR

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BIOLOGICAL AGE VERSUS YOUR

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CHRONOLOGICAL AGE.

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>> WHAT DOES THAT MEAN IN TERMS

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OF LONGEVITY?

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HOW MUCH LONGER DO THE PEOPLE

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LIVE THAN OTHER MEMBERS OF THE

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FAMILY THAT DO NOT HAVE THE

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MUTATION.

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>> THE CARRIERS HAVE 10% LONGER

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AND THAT PLAYS OUT INTO A

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LIFESPAN THAT IS 10 TO 13%

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LONGER AS WELCH.

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>> THAT IS DRAMATIC THAT CAN

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MEAN A DIFFERENCE OF SIX-8

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YEARS.

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>> ABSOLUTELY.

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AND 10 YEARS IN THIS POPULATION.

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MEDIAN LIFESPAN IN 75 IN THE

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UNAFFECTED KINDERRED, 85 IN THE

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CARRIERS OF THE MUTATION.

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AND IT PLACE OUT IN DIFFERENT

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WAYS.

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THEY HAVE LOWER INSULIN LEVELS.

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THEY ARE COMPLETELY PROTECTED

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FROM DIABETES AND THE

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CARDIOVASCULAR SYSTEM IS MORE

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JUVENILE.

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>> AND TELL US MORE WHAT THE

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MUTATION IS EXACTLY.

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>> THIS IS A LITTLE BIT

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COMPLICATED FOLLOW ALONG WITH

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ME.

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IT IS IN A PROTEIN WALLED PAI-1.

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CALLED PAI-1 AND THE GENE THAT

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CODES ISER IS OPINION E1 AND

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THIS IS ONE OF THE MUTATION IS A

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KNOWN MUTATION IN THE GENE.

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IF YOU HAVE THAT MUTATION THE

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GENE IS NOT TRANSCRIBED.

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SO YOU DO NOT MAKE THE PROTEIN

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RELATED TO THAT MUTATION.

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>> SO IT HAS TO DO WITH LOWER

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LEVELS OF THIS ONE PROTEIN AND

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AGAIN, MY UNDERSTANDING IS THAT

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IS A PROTEIN THAT IS ASSOCIATED

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THE LOWER LEVELS OF THE PROTEIN

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ARE ASSOCIATED WITH LONGEVITY IS

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THAT RIGHT?

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>> RIGHT.

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THE CARRIERS OF THE MUTATION

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HAVE LEVELS OF THE PROTEIN IN

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THEIR BLOOD THAT ARE HALF THAT

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OF THEIR UNAFFECTED KINDERRED.

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THE PROTEIN IS PART OF THE

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MOLECULAR SIGNATURE.

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>> SO THE QUESTION THAT COMES TO

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MIND IS CAN THIS BE REPLICATED?

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IN A WAY THAT WOULD BENEFIT

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PEOPLE WHO DO NOT HAVE THIS

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GENETIC MUTATION?

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>> WE THINK IT PROBABLY CAN.

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WE HAVE SEEN AN EXPERIMENTAL

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MODELS IN MY LABORATORY THAT

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GENETIC MANIPULATION OR

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DEFICIENCY IN MICE CAN PROLONG

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THEIR LIFESPAN AND PROTECT THEM

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FROM AGING.

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WE ARE COLLABORATING WITH A

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JAPANESE ACADEMIC GROUP IN

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DEVELOPING A DRUG THAT BLOCKS

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PAI-1 THAT HAS BENEFICIAL

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EFFECTS IN EXPERIMENTAL MODELS

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AND HOPEFULLY WE CAN BRING IT

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INTO HUMAN TESTING IN THE UNITED

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STATES SOON.

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>> IF ONE FOLLOWS WHAT YOUR

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RESEARCH HAS SHOWN AND THE FACT

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THAT YOU ARE DEVELOPING THIS

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POTENTIAL DRUG IT COULD BE OUT

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IN THE MARKET AT SOME POINT AS A

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WAY TO PROLONG LONGEVITY?

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>> I DO NOT THINK THE FDA IS

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GOING TO BE PREDISPOSED TO

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APPROVE A DRUG THAT ADDRESSES

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LONGEVITY BUT THERE ARE A LOT OF

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INDIVIDUALS IN OUR COMMUNITY AND

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OUR HOSPITALS THAT HAVE

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RELATIVELY EXPERIENCE RAPID

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AGING.

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PEOPLE WITH CHRONIC KIDNEY

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DISEASE AND DIABETES AND PEOPLE

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RECEIVED SOME FORMS OF SYSTEMIC

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CHEMOTHERAPY, PEOPLE WITH HIV

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INFECTIONS THEY ALL AGE RAPIDLY

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THEY MIGHT BE CANDIDATES FOR A

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DRUG LIKE THIS.

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>> DO YOU HAVE A HUNCH AS TO

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WHAT THE DRUG TRIALS WILL SHOW?

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>> YOU KNOW, I THINK WASTED ON

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EXPERIMENT --

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BASED ON EXPERIMENTAL MODELS

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IT'S LIKELY TO PROVIDE BENEFIT

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RELATING TO AGING RELATED

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PATHOLOGY LIKE HYPERTENSION AND

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DIABETES AND PERHAPS LUNG

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DISEASE AS WELL.

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IT WILL ALLOW US TO COMPRESS

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MORBIDITY LATER IN LIFE AND GIVE

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US A LONGER LIFESPAN.

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>> AND BACK TO THE ISSUE OF THE

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FDA APPROVAL ARE YOU SAYING THEY

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MIGHT APPROVE THE DRUG IN CASES

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WHERE SOMEBODY HAS A CONDITION

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THAT CAUSES THEM TO EXPERIENCE

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RAPID AGE SOMETHING THAT WHAT

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YOU ARE SAYING?

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>> YES.

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FOR EXAMPLE, IN THE CARRIERS OF

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THE MUTATION IN THE AMISH THEY

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ARE PROTECTED FROM DIABETES.

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SO YOU COULD THINK OF A DRUG

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THAT WOULD PREVENT DIABETES I

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THINK THE FDA WOULD BE

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INTERESTED.

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>> IF THIS DRUG WERE AVAILABLE

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NOW WOULD YOU TAKE IT?

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>> YES, PROBABLY I WOULD.

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YOU KNOW, THE AMISH TELLS US A

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LOT.

06:46.333 --> 06:49.400 align:start position:10% line:74% size:35%
>> THE FAMILY.

06:47.100 --> 06:50.633 align:start position:10% line:74% size:80%
>> AND PARTICULARLY THE CARRIERS

06:48.300 --> 06:52.866 align:start position:10% line:74% size:40%
OF THE MUTATION.

06:49.400 --> 06:55.233 align:start position:10% line:74% size:77.5%
WE SAW INDIVIDUALS THAT THE ARE

06:50.633 --> 06:56.433 align:start position:10% line:74% size:77.5%
ALMOST 90 YEARS OF AGE AND THEY

06:52.866 --> 06:57.433 align:start position:10% line:74% size:72.5%
LIVED THEIR WHOLE LIFE WITH A

06:55.233 --> 06:59.433 align:start position:10% line:74% size:75%
LOWER PAI-1 LEVEL AND THEY ARE

06:56.433 --> 07:01.866 align:start position:10% line:74% size:12.5%
FINE.

06:57.433 --> 07:02.933 align:start position:10% line:74% size:75%
>> LOWER LEVEL OF THE PROTEIN.

06:59.433 --> 07:04.666 align:start position:10% line:74% size:77.5%
SO WE KNOW THAT THAT IS A GREAT

07:01.866 --> 07:06.100 align:start position:10% line:74% size:47.5%
NATURAL EXPERIMENT.

07:02.933 --> 07:07.500 align:start position:10% line:74% size:70%
IT'S SAFE TO HAVE YOUR LEVEL

07:04.666 --> 07:07.833 align:start position:10% line:74% size:65%
LOWERED FOR YOUR LIFETIME.

07:06.100 --> 07:09.466 align:start position:10% line:74% size:77.5%
>> AND BACK TO THE ISSUE OF THE

07:07.500 --> 07:11.100 align:start position:10% line:74% size:17.5%
FAMILY.

07:07.833 --> 07:13.266 align:start position:10% line:74% size:62.5%
HOW COOPERATIVE ARE THEY?

07:09.466 --> 07:15.200 align:start position:10% line:74% size:62.5%
>> EXTREMELY COOPERATIVE.

07:11.100 --> 07:16.766 align:start position:10% line:74% size:72.5%
THEY ARE CURIOUS ABOUT IT AND

07:13.266 --> 07:19.500 align:start position:10% line:74% size:75%
KNOW THERE ARE A FEW VERY RARE

07:15.200 --> 07:21.166 align:start position:10% line:74% size:70%
INDIVIDUALS IN THE COMMUNITY

07:16.766 --> 07:23.233 align:start position:10% line:74% size:72.5%
THAT HAVE THIS THAT HAVE THIS

07:19.500 --> 07:24.666 align:start position:10% line:74% size:77.5%
UNUSUAL BLEEDING DISORDER THERE

07:21.166 --> 07:26.900 align:start position:10% line:74% size:62.5%
ARE A HANDFUL BUT LOTS OF

07:23.233 --> 07:29.366 align:start position:10% line:74% size:70%
INDIVIDUALS IN THE COMMUNITY

07:24.666 --> 07:29.733 align:start position:10% line:74% size:72.5%
MAYBE 5% OUT OF 10,000 PEOPLE

07:26.900 --> 07:31.200 align:start position:10% line:74% size:62.5%
THAT ARE CARRIERS FOR THE

07:29.366 --> 07:33.266 align:start position:10% line:74% size:22.5%
MUTATION.

07:29.733 --> 07:34.566 align:start position:10% line:74% size:72.5%
AND THEY ARE CURIOUS ABOUT IT

07:31.200 --> 07:36.333 align:start position:10% line:74% size:75%
AND THEY WERE VERY COOPERATIVE

07:33.266 --> 07:37.133 align:start position:10% line:74% size:80%
AND GRACIOUS IN PARTICIPATING IN

07:34.566 --> 07:37.600 align:start position:10% line:74% size:30%
THE STUDIES.