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