my high school friends and I made a pact
where every prom
each other that we would dedicate our
careers to extending human lifespan
because this the Gilgamesh project which
was named after the ancient Sumerian
king who looked for a secret herb that
would extend his lifespan I've always
felt that human life is too short and I
was always fascinated by people who beat
the odds I present to you two former
smokers according to the Guinness Book
of World Records
Jean Coleman was the oldest woman who
ever lived
she reached an age of 122 but according
to a government ID an Indonesian man
reached an age of 146 now this age claim
is disputed these kinds of people give
rise to several questions one is can we
develop an aging test based on blood for
example so that we can verify age claims
but also what is the secret of these
exceptionally long lives what can we
learn to extend our lives to answer
these questions we need a very precise
way of measuring aging aging based on a
blood sample aging based on a skin
sample kidney sampled liver sample and
so on ideally we need an epigenetic
clock or an aging clock that allows us
to measure the age of every cell in your
body and this request leads to an idea
since most cells in the human body
contain DNA maybe we can track chemical
modifications of the DNA to measure
aging
basically look for rust on the DNA now
chemical modifications of the DNA
molecule are known as epigenetic
modifications
one important epigenetic modification is
DNA methylation you can think of it as a
rust in the context of Aging but DNA
methylation plays an essential
purposeful role during development I
stumbled across the first epigenetic
clock by accident a colleague gave me a
methylation data set because he was
interested in studying sexual
orientation and this methylation data
from saliva didn't lead to any signal
whatsoever for sexual orientation but
when I correlated the methylation data
to age I almost fell off my chair
because the signal was so strong and I
immediately decided that I will drop
everything else in my lab and will focus
on using methylation data to build aging
clocks
so the first epigenetic clock was based
on saliva samples and we published it in
2011 but we didn't stop there next I
built a clock for blood then an
epigenetic aging clock for post-mortem
brain tissue and so on and that led to
an idea why can't one build a single
aging clock that applies to all human
tissues and cells and this work
culminated in the so called pan tissue
clock you give me a DNA sample from any
cell of the body I can tell you your age
now it's 2020 and we are working on an
even more ambitious project we've
already built so-called universal
mammalian clock that applied to all
mammals all mammalian species
you give me a DNA sample from your dog
from a mouse from a horse from an
elephant from an beluga whale I can
estimate the age of that animal but
let's return to the species that we most
care about humans epigenetic clocks have
led to two profound discoveries first
there is no clear separation between
aging and development epigenetic clocks
apply to young children and they apply
to centenarians the second insight is
that people who have accelerated
epigenetic aging who are older than
expected based on their aging clock they
have a slightly elevated risk of death
and morbidity and we know that because
we have analyzed tens of thousands of
blood samples from large epidemiological
cohorts our latest epigenetic clocks are
called phenotypic age and grim age and
as indicated by the name grim age which
stands for the grim reaper age
these are mortality predictors so if you
are in the top 5% of fastest ages your
mortality risk is twice that of the
average person conversely is if your
grim age is in the bottom 5% your
mortality risk is only half that of the
average person when I turned 51 I
decided to measure my own dream age but
also the grim age of my identical twin
brother Marcus and to my great surprise
we had the identical grim age up to a
decimal point which was 48.9 the fact
that our ages were so similar clearly
reflects that we have the same genetic
background and also similar lifestyle
but what can we do to lower our
mortality risk well
after analyzing over 10,000 blood
samples I can state with full certainty
that your mother was right to eat your
vegetables get an education exercise
avoid smoking avoid obesity avoid
diabetes all of that so yes
pursue a healthy lifestyle however
unfortunately it will not be enough for
you to become 123 it's simply not strong
enough what we need to develop our aging
interventions that are much more
powerful and that brings me to the next
question can we use these epigenetic
clocks in order to identify or validate
anti-aging interventions and the answer
is yes for example we can apply certain
drugs or compounds to cells growing in
the dish and just evaluate whether these
drugs reversed or at least slowed the
aging of the cells so these studies have
already led to various compounds so if
this was 2018 I would now finish my talk
with two predictions I would say maybe
we will have an anti-aging intervention
that doubles the life span of a mouse by
2030 and if that happens maybe we are
lucky and we will have an anti-aging
intervention for humans by 2035 however
this is really a very lame prediction
because anybody who ever developed an
exciting technology or drug will say
give me 15 years you know the good news
is that last year we published an
epigenetic clock study of a small human
clinical trial it so-called phase one
trial but the results were stunning
because in that study we found that age
reversal was possible the participants
of that study showed an age reversal
effect of two and a half years some of
you weren't clapping because you
probably thought that's not good enough
you know give reverse it by 20 years
however you need to look at it this way
an age reversal effect of two and a half
years after twelve months means that we
stopped aging at least in blood tissue
now we will follow up on these results
we will carry out a larger validation
study and so maybe we or somebody else
will use the epigenetic clock method to
find an intervention that allows people
to live until age 123 however I can
easily imagine that I will at some point
then get a phone call and a person will
say you know Steve I just celebrated my
hundred 23rd birthday and I have a
problem I just enrolled in a new degree
program and it will take me five more
years to graduate so in other words this
person asks us to extend the lifespan of
the human species and I have to say
this is an ungrateful request because
because when you compare the human
species to other primates we are truly
blessed the oldest gorilla who ever
lived
reached the age of 60 the oldest
chimpanzee the age of 59 the oldest
rhesus macaque an age of 40 so we are
truly blessed as a species but what does
determine maximum lifespan or longevity
across species well on a superficial
levels is his size or more broadly the
ability to avoid predators a shrew lives
less than two years a bowhead whale can
live for over 200 years but there are
market exceptions to the rule that size
matters for example the naked mole rat
lives for over 30 years and brands pet
lives for over 40 years
although these animals have roughly a
similar size of a mouse they live
markedly longer lives so what's the
molecular secret this question has
occupied me for the last three years and
of course you can imagine its
methylation so we generated methylation
data from 10,000 tissues from over 140 5
different mammalian species and I'm
presenting to you a plot where I show
how longevity in the species depends on
the rate of change of methylation and
you don't need to be a statistician to
recognize there is a very strong
negative relationship so these studies
and others clearly demonstrate that
methylation explains at least 50% of the
differences in life span across species
I hope I managed to show you that
epigenetics is a very exciting new
frontier in anti-aging research it is of
course my greatest dream that epigenetic
clocks will be used to identify and to
validate anti-aging interventions that
benefit humans but taking a bird's-eye
view of the entire research field I'm
really happy to say that thousands if
not over 10,000 people biomedical
researchers are working on various
aspects of slowing aging and if only one
of them succeeds it will change the
world for the better to the older people
in the audience I want to say be brave
hang in there
exciting interventions are in the
pipeline thank you very much
[Applause]