live

Can we live to 150? The Cutting-Edge Science of Human Longevity



Sharing buttons:

good welcome everybody thank you so much

Lawrence Lawrence and his family have

been great friends of mine for the

area's great friends of mine for many

years and great friends of the 92y and

really great friends of the world

through your contributions not just here

but to Harvard and to research and all

kinds of great causes so thank you to

you and your family and thank you to

92nd Street Y I think many of us here

will agree that this is a very tense and

difficult time for our country and the

world but there are many big and very

important issues that we all need to be

exploring and the world keeps going and

this is a place an intellectual center

and ideas center and an action Center

where people can come together and try

to build through all of our actions the

kind of world that we would like to we

would like to see and part of what

thinking about the future involves

thinking about our own mortality

mortality and thinking about mortality

has been part of the human condition

since time since time immemorial there

are many philosophers who believe that

mortality defines our humanity and that

definition for most of our experience as

a species has been dictated in by the

trade-offs made in evolution and there

are different animal species that have

longer and shorter and there are all

these kinds of trade-offs but for as

long as we've been around as long as

we've been telling stories around

campfires our species has fantasized

about breaking through breaking out of

the cycle of mortality many of you had

know the story of Methuselah from the

Bible who lived to the ripe old age of

969 those of us who aren't literalists

think that maybe that didn't happen but

we've always imagined what it would

maybe David things that happen we've

always imagined what life would be like

if we could break out of mortality and

we've fought back and we've fought back

very successfully at the time of the

Roman Empire the average lifespan was

about 25 years old that doesn't mean

that everybody died when they were 25

but there was large infant mortality and

average lifespan was very low by the

time of the Middle Ages and it only

expanded to about 30 in 1990 in the

United States it was only 47 now as

everybody knows in the United States and

around the developed world it's roughly

80 life average lifespan has doubled

over the last 200 years and it's not

just that it's doubled but it's that our

expectation of what a normal lifespan is

has expanded and so this thing that we

feel is very natural now to live to

whatever age we feel is normal is set in

a cultural context and these changes I

see they they normalize over time and

that becomes what everybody's

expectation whatever a sense of normal

and we fought back using these tools

that everybody knows medicine public

health nutrition and lifestyle and along

the way we've also had some really crazy

ideas crazy potions crazy elixirs about

a hundred years ago the very popular

process for life extension was monkey

testicle grafting and I'm I was told in

the greenroom that this is how this

process is having a comeback so anybody

who would like to volunteer we're going

to have a monkey testicles grafting

booth in the back and please let us know

but we as you all know which is part of

why you are here we are in a new age of

Science and Technology and one of the

biggest transformations of this age is

that the sequencing of the human genome

has turned biology in many ways to an

information technology when computers

were first developed people didn't think

about hacking into computer systems

people didn't real hadn't internalized

this idea things like Moore's Law but

over time we've come to expect that our

technology expands the power of our

technology grows exponentially and that

all that IT systems are inherently

hackable now that we are turning biology

into code which is what sequencing of

the genome has done increasingly biology

is becoming information technology and

therefore it has the same qualities as

any information technology which is

exponential growth at least in some ways

and we've seen that with the cost of

sequencing the

hours and cost of sequencing the genome

decreasing at two times the rate of of

Moore's Law and hack ability and that's

very very important and so we are in

this age where all kinds of science are

becoming information alized

and they're on this exponential J curve

and what it means is that our sense of

timing of how how long innovation takes

for us as a species is going to change

because right now our brains are

designed for linear thinking if you're

living on the savanna and you have

exponential thinking if you're thinking

ten generations ahead and you're not

thinking about the tiger that's coming

to get you you're in trouble and that's

why our brains are designed for linear

thinking but right now this pace of

innovation is going to increasingly get

faster and faster so when we think of

maybe one unit of change is 2006 to 2016

it could be that 2016 to 2026 may be

three times that 3x and 2026 to 2036

could be ten X and then 50 X so this

speed of innovation is going to

increasingly expand and therefore our

thinking how we think about the world

how we understand the world and the

things that are fixed and the things

that are unfixed are going to change

they're going to be brought into these

challenges to the way that we think and

coming bringing that back to aging we

see these examples of Aging in nature

where there are a lot of and we're going

to talk about this a lot of disparities

and we don't fully understand why it is

that a mouse in captivity lives maybe

four years in a mouse in the wild lives

one we have some good ideas why average

Mouse on the street here that a bat can

live 30 or almost 40 years why there are

sharks that can live 500 years when

there are other sharks that are

genetically similar that live much less

and why there are jellyfish and this is

in my novel I talk about this as well

but jellyfish did seem to be immortal

that go back and forth between mature

age and ippolit stage and so we're at

this

phase in our evolution as a species

where we have a question and the

question is is our mortality fixed is

our biology fixed or are we hackable and

is mortality in one way or another or in

pieces along the way overcome a ball and

that and hackable and that's what we're

here to discuss tonight and we really

have the super all-star team of people

to talk about is we always do four

events at 92nd Street Y and so going

from my far left we have NIR Barzilai

who is the professor of medicine and

genetics and the director of the

Institute for aging research at Albert

Einstein called College of Medicine he

is a recipient of many prestigious

awards and serves on the board of the

American Federation for aging research

he's also a founder of Khobar which is a

biotech company that develops

mitochondrial derived peptides for

therapy for aging and it's diseases next

is dr. Anna Marie Cuervo

who is the Robert and renee Belfort

chair for the study of neurodegenerative

medicine and the professor in the

department of developmental and

molecular biology also at Albert

Einstein and co-director of the Albert

Einstein Institute for aging studies we

also received many awards and is

co-editor-in-chief of aging cell and

associate of autophagy and to my

immediate left is David Sinclair who's a

professor of genetics at Harvard Medical

School and co-director of the Paul Glenn

laboratories for biological mechanisms

of aging at Harvard Medical School the

founding director of the Glenn Center

for aging research he's published 130

papers as many patents and his

co-founder and Co chief editor the

scientific journal aging and appeared in

Time magazine's list of the hundred most

influential people in the world and

that's very influential so why don't we

start with a question for everybody and

then I'll have some specific questions

because we have well we have a lot of

area that we'd like to cover and then

we'll open it up to questions from from

all of you so maybe starting with you

near just to get our baseline what is

aging

first of all thank you very much for

your introduction introductory comments

I have nothing to add and I'm just

delighted you know those are the best

scientists in the world for two reason

first because they are second because

they they understood that aging is

really the future of how we make health

better and not everybody's up to this

speed so I'm just delighted for this

panel and I would let them define aging

but I'll tell you what I say when I'm

asked not in an aging meeting I'm just

telling them about this couple Midwest

United States they live in a house and

the wife turns to the husband and says

honey why don't we go upstairs and make

love and the husband looks at her and

says sweetie

I cannot do both I have to tell you I

was I was in Israel last week and I told

his story and in a meeting

that wasn't an aging meeting and these

release immediately said we live in one

flat apartment we will have the same

Valerius so I think with that the

example probably need already summarized

at the main point of age you know at

least from our point of view that aging

is a loss a gradual loss of function and

I think that's why you know it's a

physiological condition but nobody is

also physiological to be a child and

nobody wants to cure childhood so why do

you want to cure aging so I think the

reason why we are all interested in

aging is because this loss of function

affect your quality of life and also

make you very vulnerable to a lot of

stressors that normally you are very

well protected during your life and as

you get all you are not protected

anymore and that increase your stability

to disease and that's the reason why we

want to tackle aging to really prevent

those age related disorders that you

have here the two major experts on that

so I think that the loss of function

damage so nicely

prefer is only being able to do one

thing and not to is the thing that

worries us yeah dude

Paul thanks Jamie for having us I

already disagree ok Maria good I mean

end it anywhere any anyone who's got a

teenage daughter knows that someone want

to cure a childhood and so we we aging

research have been struggling to define

aging for really for the last thirty

years and we're getting better at it the

good news is though that we don't need

to know actually what causes aging to be

able to do something about it as we'll

talk about I hope we found many of the

genetic pathways that control the pace

of aging from yeast cells through to

humans and the races now on to control

those although you if we're in them in

the mood for telling jokes what I say is

a aging is a lot like pornography you

know I don't know what it is but I know

it when I see it and that's that's

really true we know it when we see it

but just being able to describe it

doesn't do it do science justice we have

to understand the molecular pathways and

that's really where we've come over the

last twenty years so how did you

disagree with us about the child are you

oh the child oh yeah yeah yeah pay

attention exactly so let's start with

you and then go back this legs I was

just these foundational questions what

do you see based on what we know now

which you've just said is imperfect as

the mechanism of agent what is what is

happening well there's a lot that goes

wrong just as a machine falls apart as

it as it gets older but the good news is

if you use an analogy of a car we used

to think that our bodies were just like

cars that would wear out and break down

but so the idea of having a single pill

to slow down or even reverse aging was

ludicrous with that model or that

analogy because it would be like having

a magic wrench that you throw at the car

and suddenly all the paint's fixed and

the rust is fixed and the engines fixed

that's never going to happen but our

bodies are much more complicated than

cars we have self-healing repair systems

that we know

know how to control with small molecules

and that's really the important thing if

I was to put a bet on what actually is

very the upstream cause of Aging though

there's a lot that happens including

what Ana Maria works on I think it's

actually that our cells are what I call

losing their epigenetic resilience and

that's just a complicated way of saying

it's not the DNA information the code

that's being lost that was that's the

current idea I think it's the cells

inability to read the right genes at the

right time so that our cells eventually

forget their identity and so liver cells

start behaving more like other types of

cells and we get dysfunction that way

the good news is if we still have that

information like a DVD or a compact disc

that is just scratched we should be able

to reverse aging just by polishing it

and allowing ourselves to read the

information that's in our genome and

that's what one of the things we're

working on yeah I mean we're going to

come back to the responses but for the

the mechanism of aging what's your

thought in any way I mean Michael is

again the aging is multifactorial and

there are going to be many factors and I

think the advance that we have done in

the last I will say five years is that

we are starting to define what are those

processes so we know that there are

several of them that are there probably

many but if you start focusing in like

nine or ten you can start thinking how

they relate so you know David was

talking about epigenetics and we're

saying well this is upstream because

it's the one that is going to organize

the whole thing and for example in our

case we are the ones polishing and

cleaning his genes because we work in

the cleaning so of course we think we

are upstream of here and this is where

the whole game is there and that's the

beauty that every single mekinese of

aging that we can think of is really

interconnected that they donors as

they'd say that they don't function

completely independent but that's also

the good part that if you fix one and

there that's why there are so many

approaches right now of trying to fix

aging because if you a Don Juan they are

so interconnected that you are going to

have a positive effect in another one so

for example we my lab works in cleaning

of yourself and my mother always say you

know a clean house everything works

better so his jeans are gonna wear

better

his my token we are gonna go better and

this is how things are related and and I

think that you know it sends that these

complex because you have so many things

going wrong but this idea that they are

interconnected make it very possible

that by acting in a couple of them you

can completely put a rheostat and bring

bad things back to normal

and that's the future near anything I

think that was a good discussion I want

to just for completion throw a buzz word

that's called mTOR mTOR is a sensing

mechanism of the cell and when you

inhibit that okay almost in every animal

they live longer and actually they've

lived the longest compared to other

animals that were intervene and I'm

saying just because emptor is there the

inhibitor is replacing is using clinical

setup and there are lots of papers who

are talking about it it's just an

example of identifying a pathway

modulated and showing that it increased

not only the lifespan but health span of

animals right and we will talk about

animals in in a moment so just following

up on that so mTOR is working and and

just people should Google later

rapamycin it's a great story of being

found in the in the dirt in Easter

Island but what does that say about

what's the mechanism of Aging based on

what the mTOR is doing well so the mTOR

sense nutrient and kind of decrease a

the nutrient flux in the cells are

really in a coordinated way around the

body and it just repairs kind of the the

aging all over and you know that's the

mechanism and one way to think of it now

Jamie is that I talked about those cars

that our bodies are like cars that get

older mTOR is one of those repair body

shop mechanics and what we're learning

to do is to get them out of bed earlier

in the morning and work harder to repair

our body and keep it pristine so we're

going to talk a little bit later about

inter

mentions and I think everybody has we've

already started to talk about that but

without even intervening when we just

look at the animal kingdom there are

just different differences in aging of

things that you think like a mouse and a

bat you think well they look pretty

similar you'd imagine that they would

have a different relatively similar

lifespan or different kinds of sharks

that look roughly the same or different

whales but but the actual life

expectancy is drastically different

David from looking at variations across

the animal kingdom what can that what

can we learn about the different

processes of aging well so for a start

we've been very fortunate to have these

lab organisms that we can as geneticists

find mutants that live longer and figure

out what are the genes that control

lifespan that's how we found jeans like

mTOR and others that control lifespan

but what's great about the whole

penélope of life on the planet is that

some organisms live a day or less and

some organisms live 300-400 even if you

talk about plants more than a thousand

years so what does that tell us that

tells us that first of all each species

has a certain range of life span that

must be encoded in the genome and if

you're if you're lucky and you live a

healthy life you can maximize that but

there seems to be a genetically encoded

limit saying for humans it's about 120

122 is the oldest yeah yeah and you can

exercise as much as you want and eat a

perfect diet and that's about as good as

you can get but what that doesn't mean

is that that's our actual limit it means

that sure we can we can live according

to our genes but if we have enough

technology we can fly it's not in our

genome to fly we can cure diseases with

antibiotics and we can intervene in

aging and get us maybe not

living forever but giving most of us a

chance to live in 290 up to 90 and 100

in a healthy way playing tennis and

raising the great grandkids and what it

actually tells us is the other animals

that live longer than us is that living

a long time is not against the laws of

physics

it's doable and we just need to figure

out what secrets are yeah and annamaria

one of things we talked about extending

lifespans and we've and I in my

introduction I talked about the progress

that we've made life span has extended

more quickly than health span why is

that

second it's prolly a combination of

factors but I think we are the ones

preventing our expansion of health span

and need already touched a little upon

that with mTOR and energetics and food

and eating and I think one of the things

is that the kind of things that our

society has adopted let's exercise it in

all these things that we should need

non-sleeping

all those things are going against the

natural course of healthy life and those

are the ones that are really probably

decreasing our resilience and that's

what make us vulnerable to all those

diseases so so I think it's like these

changes these new things that we are

adopting in our life are probably the

ones prevented so we're getting the

disease's but we're treating the

diseases so we're living longer but

having not be as healthy in our long

lives as we could but the other problem

is how we are treating the diseases and

and that I think that there are two

factors that as scientists we don't get

the whole picture of what happened in

the clinic when we develop models to

treat a disease in many many cases those

animals are not all and the people that

are going to have those diseases are

also you are treating diabetes in a

three-year-old kid in comparison to what

we do so we are not putting the things

in the right context and the other thing

is that we are treating or we are doing

models once at a time and something that

everybody knows is that you have

comorbidities when did you have somebody

in the clinic that came to you only with

Alzheimer probably that person is going

to have high blood pressure is going to

happen so so that's the thing that what

we are doing as treatments we are not

considering the most important

aggravating factor at least for the

people in this panel that will be aging

and the fact that you have several

things at once so if we go once at a

time we are never gonna

I think that's that's a great point

because we put so much emphasis on

cancer and if we just eliminated all of

cancer our life expectancy would only go

up an average of three years because if

you're if you're at the age when you're

going to get cancer even if you don't

have cancer likelihood you're going to

get something as and that's why there's

such a movement among some people I'd

imagine everybody on this stage to think

at least for regulatory purposes of

aging as a disease so we can have the

funding to try to understand addressing

dizzy as dressing aging and then

preventing disease rather than treating

diseases later in the stage but David

just talked about extending life beyond

122 and but in our internal email

exchange about what we should name this

topic David had said can we live to be

150 and near you responded about the the

upper limits of possible life expects

talk a little bit I'm older than he

meant to leave him a hundred years now

seems not so attractive um but but I

think David actually David you know said

that he'll provoke me but he said things

on sharks that I can say on humans too

we do have probably a maximal lifespan

as a specie which by the way maybe is

115 years you know the fact that

somebody leaves under 20 to 20 years ago

it's like their jumper in Mexico

Olympics that jumped so far as that

nobody caught him you know it might be a

mistake but anyhow it doesn't matter we

have a maximum lifespan the the point is

the maximals lifespan which you said

also David is you know between dying at

80 average age now 115 we have a lot of

of place to move now and I think we're

we're able to move now and that doesn't

mean that in the future you're not going

to challenge the ceiling but I think we

have to realize that there is some

ceiling and there's a big opportunity so

if everybody who lives in the world

today what is the the oldest of everyone

alive today the oldest that somebody

will live like who's the longest lived

person of everybody what's your guess is

it is it a lifetime on record you

you see billboards they can quote me yes

the first person to live 150 is already

born

annamaria I guess hundred fifty cents

right 115 105 zero

one city yeah no 115 I say one one five

or one five zero in either 1 5 0 gram 1

15 1 1 5 so year 1 5 0 and your 1 1 5

and your 1 wildlife also very

interesting alright so we're gonna talk

about the fancy science but before we

get there and just to give everybody

here a game plan because I think

everyone is thinking like enough what am

I supposed to do

yeah there are there are mechanisms that

have nothing to do with science and just

how to we live our life and so we're

going to talk about them about them very

quickly one near exercise exercise is

the best advice that you can give anyone

at any age but certainly for aging ok

it's good for everything it's good for

people who are have diseases of aging

it's good for people who are afraid to

age exercise has been the right thing

and I just want to say it's a little

surprising because if you ask the public

what's the major thing that happens in

the body they they're saying orders

oxidative stress you know we have to

take antioxidants and the paradox with

exercise is that there's nothing to

increase your exiting oxidative stress

more than exercising and still it's the

most protective way to advanced aging

yeah and it's crazy what I say is that

if we had a pill that did everything

that aging does people would be

attacking the pharmacies to get it

they'd be killing one another it but if

you say but you have to wake up 20

minutes earlier and do a little jog or

go for a walk feels like I could never I

could never do that it well but if you

give them the choice of caloric

restriction or exercising or will will

be ready to exercise well let's get to

diet and caloric restriction so maybe

first on diet just because you come from

a country where people eat healthy food

naturally and then caloric restriction

which has led to a lot of other the more

scientific approaches yes so I think the

diet for us has been I think that there

is enough evidence of how

much it can impart aging in many aspects

but from the point of view of what we've

been discussing one of the things that

is very important is that your cells

have to clean themselves and I know that

I keep talking about cleaning but you

just care about free radicals oxidation

the damage that could happen somebody

has to clean that and our organist is so

well designed that the way that you

clean is when you need energy so if you

need to have energy and you don't have

food you're going to start breaking

things that you don't need anymore or

that there are damage and is this

recycling what gives you the energies

kind of getting like you know the trees

chop then and get the negative to the

fire to get the energy so you do that

and you do that every day for example in

between lunch and dinner

if you don't have snack in the middle

you're going to activate these cleaning

systems because it what they are going

to do is recycle to maintain your energy

so I think for the Talia the most

important thing is that the diet has to

be very balanced in addition of the

calorie restriction and we will talk

about that so if you reach a lot then

you don't have this need of using what

is already inside or what is damaged so

by eating too much you are preventing

this cleaning but also if your diet is

unbalanced if you have a lot of sewers

and lipids those are the the worst

things this clean insistence that also

get impact you have your mitochondria

your DNA everything gets modified so so

in a way is good your grandma always

tell you you exercise you sleep well and

you have a balanced diet and then you

will live forever it's not about them I

say yeah exactly we're talking over

myself I think this is a booming aiesec

crowd uhm so balanced diet what does it

mean like where do what are the rules if

you like three rules that people should

take away about what a balanced diet

means it's in the keys balanced balanced

in the sense that it's not all these

extremes that is like no fats and of

course you don't take fats your percent

of calories are gonna came from the

sugars so we have for example studies

going in the lab if you put an animal in

a low-fat diet the low-fat diet is also

got basically on a couple of protein and

they get like so fat and so bad so I

finished this idea of balance and you

know Mediterranean diet ooh I know I've

been a very balanced diet yeah keeps

people going so everyone's talking about

calorie restriction David why why does

it work what's the mechanism of calorie

restriction it's connected to it and

reducing yes or the old idea was that

calorie restriction just reduces your

body's metabolism and you just live

slower but that's not actually true it's

been disproved and what we think now is

that it's puts the body in a state of

what's known as hormesis I think any of

you heard of hormesis raise your hands

if you've heard of this word sort of yet

if you're as in Hanna he cannot see you

it yeah exactly so you may as well raise

your hand so anyway so so hormesis is a

concept that was actually first

discovered but when people were spraying

herbicides on plants and you if you

dilute it down very far the plants

actually grow better and another way to

think of hormesis it's a mild stress

that doesn't kill you makes you stronger

and by stress I don't mean the most

recent election I mean biological stress

putting your body in a state of

perceived adversity so running will tell

your body that there's adversity being

hungry puts your body in a state of

perceived adversity or her misses and

the body mounts a defense response it

starts the cleaning process it turns

this mTOR pathway on and other genes

that we work on and then they take care

of the fixing process so essentially

what you're doing is with this analogy

of this car repair shop what you're

doing is having a bullhorn and saying to

the mechanics get to work there's an

emergency we need to build this car and

and that's what being hungry and

exercising does and it's not that your

blood flows better or being hungry burns

the fat and that's what's good it's

actually the body gets into a defensive

state they can heal so you can I am can

I say something to prove this point from

by the way David is from Australia it's

also you know you don't have to just

pick on us with the but but in Australia

a a group of researcher gave food with

cellulose with high volume of something

else and the mice ate only 70 percent

the calories they were caloric

restricted but they didn't live longer

okay and the point here is we're not

doing really caloric restriction in

other words in the lab we're not giving

smaller meals we're just giving them

meal once at the end of the day that's

very different that's intermittent

fasting that's the stress rather than

the caloric restriction so let's talk

about fasting because I think everybody

hates caloric restriction it's like a

good there was a thing on the cover the

New York Times of these two monkeys and

the one monkey was the indulgence monkey

and one was the calorie restricted

monkey and the old the monkey that was

indulgent looked kind of like old but

kind of happy and the calorie restricted

monkey looked young and absolutely

miserable and so I think it's a bad it's

a bad choice so calorie restriction and

this is a originally Jewish organization

we're not good at calorie restriction

let's let's talk about the other options

um what about fasting if somebody said

well I hear you on that there's exercise

is beneficial but some period of fasting

could be useful is there a model of like

if you but let's say you wanted to do

that what would you do like what is

intermittent I'll take that one yeah

well there's plenty of different options

one that I know is called the five plus

two diet you can eat normally for five

days and then spend two days eating very

little or nothing what I do is I try to

skip at least one meal a day if I can

and go hungry for part of the day and

not snack in between and that seems to

work and especially if you if you can

eat an early dinner you see how long you

live well I'm 75 if you eat an early

dinner and skip breakfast then you are

basically fasting a vision and then I

also going into that there are some very

interesting studies now about this food

cloaking that you can gave the same

amount of calories but if you only gave

it at two times a day to the animals

specific times always this time then

they have this period of not food and I

think this is what David was referring

you get in this state of alert because

you know how food you activate this

whole process and they don't I mean they

don't live longer but they have much

better health span they have less lean

see that they don't lose weight so it

a way to lose weight because you're

taking the same calories that you had

this time to activate your outro for you

to be another and these animals they

have less incidence of cancer they have

less dementia so what's the easiest way

to do it would be like an early dinner

and have a cup of coffee for breakfast

and have lunch I mean is that if we're

looking how does this apply to me is

that is that a model yeah that's what

I'm doing

yeah well Anna Maria lives on diet cokes

I know I which is not everybody's

perfect um although she is I'm sure I'm

sure very close almost I'm watching

buddy so I so that's those these are

these kind of natural ish things that

that people can do we talked to in the

green room about swimming in freezing

cold water which apparently has some

some positive effects we won't go into

that but if you have freezing cold water

you'd like to go swimming in the morning

you should do it but can you each talk

about the most promising scientific

approaches to me you've met you've all

mentioned a little bit what is just

going from David Cross what do you think

are the just the most promising I know

you've worked on respiratory all and

some other things but do you think what

are the most promising scientific

approaches to life extension alright I

would put my money on these control

mechanisms these body shop repair

manages and they're really three main

contenders there there's a whole network

of them so of hundreds of them but

there's three main pathways that we like

to talk about one is we've talked about

mTOR near brought that up one is MP

kinase which near also works on and is

hoping to do a clinical trial to show

that that can extend lifespan or at

least reverse some aspects of Aging and

the third is a group of enzymes that I

work on cold sirtuins and there's seven

of those in the body and I I like

sirtuins but they're all equally

I think valid and if you tweak one the

others change so actually we're all

really holding the elephant just from

different ends if you're wondering what

the latest thing out of my lab is very

briefly we we know that these are - and

enzymes protect the cell and that they

need a little molecule that's got the

name

nad and we lose nad as we get older by

the time you're 50 and I'm almost 50 we

have about half the levels of nad that

we once had and without nad you're dead

within 30 seconds so we're developing

molecules that are going into human

trials next year that boost energy

levels back up to youthful levels and we

see at least in mice remarkable effects

that moving diet and exercise yeah so I

sent my mother a podcast of David and he

talked about your his own mother and

when my mother heard about this she went

on the internet and she ordered all

these nad boosters and all these kinds

of things so either thank you or you're

in big trouble otherwise virtual gave

millions of people an excuse to drink

red wine I know

exactly welcome in the in the case full

annamaria so for us out as we said the

beginning everybody's tackled for a

different point of view we are very

interested in this quality control and

this cleaning and the beauty is that

every single thing that they have

mentioned also activate this cleaning so

the cleaning is called out-of-body kind

of eating yourselves so entering heavy

sean

activates out of a team at four means

that we're here in a moment

activist Otto fudgy cr2 in such a way so

so in a way many of these drugs or

molecules that work is because they are

touching in very fundamental mechanics

and one of them is disk linen so in our

lab we have developed some compounds

that within activate this Auto fudgie

and we have evidence of that and at the

moment we are using in some of these

models of neurodegeneration Alzheimer

models and they seem to be doing the

cleaning and they seem to do an effect

so that's what we are but by no means

this is going to be the only thing so I

think that's the beauty that what could

you come here here is that there are

very different ways that we probably are

going to get this going back to balance

and that's what we do anyone yeah yeah

so a metformin

by the way 800 field 50 milligrams twice

a day if you're taking that don't come

to my study okay but we're launching a

big national study that's called Taymor

targeting or taming aging with metformin

and we want to work with the FDA and

show that aging can be targeted and

that's really the important thing that

we're doing now you heard that there are

many ways to tackle aging but

unfortunately the pharmaceuticals are

not going into this field because there

is no indication to target aging and

what we're trying to do now is to do a

study that will change that we're taking

this myth forming that is a drug that's

generic it's cheap it's very safe it's

been out for 60 years it's for trainer

of diabetes but it's not going to cause

any adverse effect to people who are not

diabetic and if we'll show that we can

delay a composite of age-related

diseases I think that the next decade

will be just healthspan is going to

increase and increase and we're going to

have a better and different quality life

than what aging is associated with now

yeah it's fine I was saying before with

metformin which has been around since

the 1950s it's become this this wonder

drug thing a lot of people are excited

about it and I know certainly anybody

with type 2 diabetics diabetes taking

yes and when my dad started taking it my

mother I told her about the research

that you and others were doing she was

so jealous she went to her internist

five times and she was trying to figure

out how she could frame what her problem

was so that they would give her

metformin she kept doing research she

finally got it right and and then and

got it but in 10 years is everybody

going to be taking an aging pill every

day you know III I think you start a

detour or or somebody said it's right

this model that we have a disease and we

get to treatment and then we get you

know the number of people who are 60

years old that have three diseases

together and three treatments together

and every treatment as a side effect and

the combination of them are even it's

just the wrong model yeah we have to

really target aging and the effect not

only of course on the health of the

individual but on the economy I mean it

has been shown that this modest increase

inhale spam is a seven trillion dollar

saving until 2050 we just have to do it

that's that that's why I think they're

so special because that's what we need

to do not yeah yeah in my novel eternal

sonata and I the the mechanism that this

scientist uses is para biases blood

transfusion between and so the model

that that Tony Weiss Kure at Stamford is

using is you get an old mouse and a

young mouse and you connect their blood

stream and the old mouse starts to act

like he or she is younger and they're

smarter and in younger in every way and

the young mouse gets older what's your

thought about para by OSIS and as we are

talking about before self para biases

storing your own blood stem cells so

that you can get a transfusion later in

life of your own plasma and therefore

rejuvenate yourself who wants it so I I

have a one of our core at the aging

Center is a power bio z-score for $1,500

you can get to triplet a a young a young

connected to young and all too old and

then an a young and and all together

$1,500 a mouse or rat not a human know

we were either either a human human no

minute amount next to not connected is

getting em and and we observe of course

we have different projects which we

observe exactly the same in fact there

is something really interesting about

the intestine of the young getting old

by para biases and III think we're up to

something interesting so the parent by

Aziz there is an exchange there is a

flow of a lot of blood during a day you

know the circulation is at least hundred

times

your blood is circulating and and the

question is how much do you need a

plasma or blood in order to do any other

exchange and I'm a bit skeptical at this

age I think that from what I hear this

cannot be totally right by the way we're

taught

thing about stem cells but we're talking

about plasma - okay they both can can go

and maybe each one of them has a

different goes to a different place and

have a different component but I think

para para bios's is a very powerful tool

and the application of giving plasma to

human eye I think it has to be worked

out better yeah and in our earlier

sessions in this Homo sapiens 2.0 series

we've talked about the genomics

revolution and the last session we did

was on the future of fertility and in

vitro for fertilization and embryo

screening and so theoretically at least

as we learn more about the genetics of

aging it seems that we're going to be

able to predict based on the sequencing

of pre implanted embryos which embryos

have a greater likelihood to live longer

and not would you agree and do you think

that if we start selecting embryos to

eliminate disease we'll be able to

select based on estimated longevity

David all right so the interesting thing

about there's a lot of questions there

but the re yeah but on fertility what's

interesting is that what we've recently

discovered in science is that females

are not born with a set number of eggs

if you see that in high school textbooks

rip that page out it's wrong in many

mammals they produce eggs throughout

life and through stem cells and so where

we and others are growing stem cells

from women's ovaries and mouse ovaries

and we can isolate these grow them in

the lab we can genetically modify them

and we have the technology if we really

wanted to know we're not going to to

either modify or screen these cells for

different traits or remove diseases like

Huntington's and breast cancer that's

all in the future one of the other

things that's interesting though is that

the same molecules that that we're

talking about tonight that reverse aging

in adults also seem to work effectively

on the reproductive system and we have

some early results that we haven't yet

published but between friends

tell you now we can take an old mouse

the equivalent of a 78 year old human

female and make that Mouse fertile again

and reverse what we call Mouse opposed

yeah now think about what that'll be

like in a society where you can put off

having kids till after you've

established your career in your marriage

and present but that's the world where

we're headed and getting into questions

about selecting embryos for this and

that I'm not really into that part of it

but I do think being able to prevent

genetic diseases is something that's

going to be much more routine in the

future yeah

and but if we were doing that and we've

had other sessions on this and I write a

lot about this conceptually we would be

able to choose based on a genetic

fingerprint if you will of longevity of

course we could yeah that the technology

is almost there already yeah and you

know in I'm doing Studies on

centenarians and their families and

there are mutations that are associated

with longevity and we're looking at

strategies to develop drugs actually

there are two pharmaceuticals there are

developed drugs around that so we know

actually from the people who avoided the

consequence of health and got to in an

old age we learned a lot that is

relevant to a lifetime exposure to this

kind of genetics I just say whatever

think about fertility that I forgot to

mention which is people say oh how long

till this technology hits the

marketplace well in terms of fertility

you can already reverse aging in your

eggs if you want to this is not a plug

for a company but I did start a company

called over science which rejuvenates

eggs actually by isolating mitochondria

the the energy Power Packs of cells and

injecting those with the sperm into an

egg and women who failed IVF many times

are now having children and so there are

dozens of kids that exist now that

otherwise wouldn't have and that's one

application of aging technology that

we're talking about today yeah so why

don't we go to some of the of the

questions in the time that we have so

question one

is what is your dream research agenda

for extending lifespans the dream right

yeah my question what's the juice and

and what are the resources that you

think would need to be applied to really

make revolutionary change yes so I'm

very the first sort of this precision

medicine and I know that there has been

a lot of talking about that but I think

what is right for one person is not

necessarily that the whole idea is the

same but I think you mentioned at some

point you say the signature of age you

know this so so I think we have to think

of aging a little of barcodes it's like

which combination of processes or which

level you have like for example I am a

meter and half and you are two meters

tall so obviously the same blood

pressure is not going to be the same

good for you than for me so I think the

same is with aging I mean and we've been

talking about calorie restriction and

there is a very nice study showing that

depending of your genetic background

even if there are mouse the percent of

calorie restriction that is beneficial

versus no is completely different so I

think in my my mind hopefully with this

precision medicine initiative that you

will start learning from healthy

individuals what is considered

successful aging and what is the

signature of non successful we just

should be able to identify what are the

tools that are going to make this non

successful signature to revert into

something that is going to help and I

think it has to be a combination and

requires a lot of information about

normal healthy individuals and

personalized medicine mm-hmm anything to

add on a dream research agenda well my

dream is that that we can accelerate

this research I know that it's it's a

matter of when not if now we have the

technology just a matter of translating

this and people like near it going as

fast as you can as we can

you'd be surprised I think most people

would be surprised at a fraction of 1%

of the research budget of the federal

government goes towards the basic

fundamental biology of Aging so we as

researchers are suffering you know we're

laying off people and given that

trillions of dollars could be saved in

the economy it's it's quite

and probably will just get worse over

the next four years at least but

research agenda I agree with that

annamaria that that being able to

measure yourself and optimize yourself

even before you get sick is important

for too long we doctors these two proper

doctors I'm just a Phe but we we

scientists have worried more about sick

people than preventing disease but we

have the technology now even from a

simple blood test to be able to say how

do you where would your optimal be not

just are you out of the range but let's

see if we can give you this or that and

tweak you so that you throughout your

whole lifespan your your optimal and we

can actually estimate your biological

age and through using this bio tracking

method and it's through right now a

blood test I was able to ostensibly

reduce my biological age from 58 to 31

hmm with a within a year and but i but i

but i you still look 75 there's still

some water in here yeah can i yeah i'll

also say something so i was invited

several months ago to the vatican okay

nice Jewish boy in the Vatican mm-hm

and they actually they invited me they

said there is a very small meeting we

want you to represent the field of Aging

and I said so I'm like the keynote

speaker and said no the keynote speaker

is the Pope and Joe Biden yeah was was a

little humbling a the Pope made it very

important so you know Joe Biden and the

scientists that he brought we're talking

about personalized medicine because

cancer is really you have your genome in

the cancer genome and actually five

different genomes I get it a but aging

is conserved actually among species I

think a to solve aging on principle is

easier to solve cancer in my mind but

what the Pope said is that he wish that

even for cancer there will be a single

simple cheap peel for everyone okay

because that's his view of the world he

won't cure for everyone and I think

that's kind of the hope that appeal like

metformin or other things are that we

can develop actually peels that maybe

will take us part way independent of the

personalized thing because I think we

have a I'm optimistic that we have we

are not like the concert people we

actually have real success I think and

would it help to classify aging as a

disease this is right now we have the

reimbursement codes and this whole

mechanism that when you have a disease

or you get some kind of procedure then

we have we open the floodgates of money

but if there's something that will

enhance individual health or public

health

we're very stingy with it should aging

be considered a disease I so you know

that my effort is to go to the FDA and

get indication mm-hmm

neither me representing the scientists

not the FDA wants to call aging a

disease first of all not everybody whose

ages it is disease and there's ageism

you don't want to end and so so what

we're trying to do is to say oh we want

to prevent the diseases of aging right

and that'll be a target i I don't think

we need to call aging a disease in order

to make progress that's what I feel

that's what the FDA is telling me yeah

yeah it's not to make progress it's just

to get money yeah unfortunately so a

question another question from the

audience how many years of excellent

dialate diet and daily exercise before

it increases your lifespan and I'll add

to that if you could talk a little bit

about the metformin with the mice where

you had the kind of the skinny healthy

exercising mice and you had the the fat

older non exercising mice but when they

started taking metformin the non

exercising mice actually live longer

than the healthy ones so what does it

say I mean if somebody is do you have to

exercise your whole life to get the

benefits of exercise how much exercise

do you need to do it by the way I don't

know what study you're talking about but

not mine but but yeah you wanna you

wanna answer no it might have been

rougher to Cabos studying metformin in

mice but he would it was with exercise

no no no with just with metformin

yeah a David you want to answer that no

you're the physician

look III again I think that exercise is

is kind of the or missus this kind of

distress that you need you know stress

when it's chronic is not good okay

Kress stress when it's acute or

sometimes or once a day it is good and

so I think about of exercise of forty

minutes five times a week I'm just

saying is is what what we're talking

about yeah and I think everybody in this

room should think of that as a doctor's

prescription that you should really just

did if you go to the doctor and the

doctor gives you a pill and says take

this pill because your life depends on

it I think you should everyone should

think about exercise as that pill and

whether your exercise is just a walk

around the block or something and I say

this a lot and my brother Jordan is a

sports medicine doctor and he says and

writes a talks about this but that a

skinny person who doesn't exercise is

less healthy than a fat person who

exercises and I just think that that's

if there's one takeaway from this it's

don't eat too much but exercise exercise

exercise so another question you're only

as old as you feel it's framed here true

or false but we will reframe it and in

the spirit of our converse is you're

only as old as you feel

boba mesa or not bola myself I think

biologically you can't overcome it but

you can certainly enjoy life the

converse is if you if your calorie

restrict and you're always hungry

life may not be longer but it will

certainly feel that way Henry so thin I

mean one of the factors because we are

basic cell biology so so we always burn

the fat but there is a growing component

of how these different aspects that we

say of aging these different cellular

processes can be

is this psychological component and I

think we study it less because we don't

have good ways to measure it in animals

we don't know if the animal is happy we

sound happy but there is very clear

studies now in population or how your

mental state your anemic state is

influencing us your your way that you

respond to a stress your differences so

I think in a way and I think that's

example my father I think he's you know

the happiest person there the most

optimistic and you look at him and he

looks quite younger than me so I think

there is something about how do you feel

and how you take it they might be a

biological limit but I think that

component is also important to modulate

this stress that we talked about you

know Woody Allen said I'm not afraid of

dying I just don't want to be there when

it happens and I I think really that's

not the issue I think what people are

fearing is the diseases of aging that's

what they are fearing and from saying

centenarians and you can see in super

ages calm in my web you can see some

healthy centenarians

some of them are working at hundred and

six years old if you're healthy at any

age life is really good I think it's the

diseases of aging that are giving aging

such a bad name and you know we should

stop it yeah and so that that raises an

interesting point which is there's a

misconception that our research is about

making people live longer in an old

state right it's it's actually it's not

about keeping people in nursing homes

for longer it's keeping them out of

nursing homes for longer and compressing

that last period of life where people

are morbid into hopefully just a matter

of weeks and so imagine that future

where you can have a healthy happy life

and then just very quickly pass away and

pass on the baton centenarians leave 20

to 30 years healthier than a control

group but the most incredible thing they

have a contraction of morbidity they are

sick for very small time at the end of

life when the CDC calculated the economy

of that they showed that the health care

in the last two years of life of

somebody who dies 800 is third of that

who dies at 70

so it's not only that they live

healthier they die sooner they cost less

and this is kind of yeah anything my

friend Dan Buettner I don't know if

you're familiar Dan's work about Blue

Zones

so he Dan went around the world and

found all these places where people live

longer as a group than others and there

were some one was in Okinawa and in

different places and he was looking what

were the commonalities of all of those

and it's a lot of the things that we've

said one is people have active

lifestyles so you just have to get

around to go to the market just daily

life requires moving around

everybody ate moderate diets everybody

had a strong built-in social community

so one was the Jehovah's Witnesses I

mean this is where there was a community

I think called a key guy which he talks

to the Okinawan word for a reason for

living

and strangely everybody ate a lot of

beans I don't know what to what to make

of that but the interesting thing was

that in all of these places there was an

integration of the older people into the

communities and I think that's one of

the greatest tragedies of the way at

least we in the United States see aging

as a diminishment whereas I think that

it's not just I mean even if we didn't

change the nature of Aging at all I mean

there's so much wisdom that older people

have and I think that we in our

societies we don't absorb that to our

own to our own cost but I my last

question for all of you is how can we

enact the kind of cultural change that

on one hand were fighting against aging

because people would like to at least

live healthy as as long as possible but

we need to change the culture of of

aging how people think about aging how

people that have the role that older

people play in society for the last

question I'd like to each ask if you ask

each of you how can we think about

changing our overall societal framework

of aging if we start with you David well

we have been changing our view of what

it is to be old

fifty years ago being 70 was old you

know being 70 now is it's not surprising

if you can still run triathlons I know a

few people that do that so I think we're

putting the cut your argument is putting

the cart before the horse

I think that if we are able to allow

people to be healthier for longer

imagine your great grandmother or

grandfather getting on the floor playing

with the kids and with the toys then old

people aren't as scary anymore it's when

they're smelly and they can barely move

that then things get scary for little

kids and that's that's really what I

think is going to change where someone

who's 80 or 90 is just as vivacious

healthy and happy as they were when elf

in their 40s that's really late

annamaria so thin I agree that it has

really chance I mean when I was doing

when I was in medical school in Spain

many years ago the aging I mean as a

geriatrician is well you know this is

life and that was kind of like there is

nothing that can be done you are going

to get all and that's it and you have

now this kind of moment turning which is

very clear that there are things that

can be done that there are things that

are being done and you have two examples

of two companies developing this drug

and I think this is already changing so

it's just a matter of time and as David

said you know older people gets more

active and healthier they are going to

be integrated hopefully in this society

and there are many societies that are

talking now okay what are we going to do

with these people that that is still so

active and they are doing all this

volunteer so I thin it is already

changing so so we are giving you a

vision that in the next decade maybe

we'll spend 80 years in order to get to

the biological age of 60 right so now

you're biologically 60 chronologically

80 what does it mean to your retirement

age what does it mean to the Social

Security you know what advice do you

need you need more economical advice

than health advice by then right you

need to plan your future so I think and

we're not the experts on that but I

think it's true that if we're achieving

what we're achieving there's social

consequence to that and you know at the

end we want a

instead of taking care of our parents

for our parents to take care of our

grandchildren pretty much right and so

how do we form a society like that but

this is not science fiction this is

science now and it's science now and

that's why we're having these kinds of

conversations because these are

questions for all of us and that's also

why having this forum of the 92nd Street

Y where we can all come together with

incredible panelists and incredible

audience and think about these things

and take these conversations home is

really what we're all about so I hope

you'll join me in thanking our

incredible panelists for this wonderful

okay thanks everybody

you