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Language: en
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this is a video about research into
slowing
the rate of aging and extending the
human lifespan
so before i filmed this i wanted to know
what do you guys
generally think about such research and
i made a twitter poll
where i found the majority of people
were supportive and thought there should
be more of it
but there were some important concerns
and i want to address those here
at the beginning i mean the most
significant concern was
if we're looking to extend human
lifespan does that just mean we'll have
more sick years where we'll be in bed
with alzheimer's nobody wants that
and that was clear to me but the
professor that i was interviewing for
this video professor david sinclair
points out
that as you get older the risk of
horrible diseases things like diabetes
and
cancer and arthritis all those sorts of
things
it increases exponentially and so
if this research is successful the whole
point of it
will be to forestall those sorts of
diseases i mean if you really are
tackling aging then you should also see
that those age-related diseases do not
set in so quickly so
the point of slowing aging and extending
human lifespan
is to extend the healthy lifespan also
called
the health span the other concerns i saw
were that people were saying well this
could be used only for the wealthy and
increase inequality or it could increase
the population of the earth causing you
know garbage more co2
you know where the resources to feed all
these people i think these are valid
concerns
but they're not part of the scope of
this video so if you want to discuss
them in the comments feel free
but the point of this video is to
address can we slow aging in humans
can we extend the lifespan and the
health span
and what does that look like how do we
do it okay so for this video
i traveled up to the bodega marine lab
which is north of san francisco and
there i got to see
some moon jellyfish now what's
fascinating about these
moon jellyfishes some people consider
them immortal
how can that be right so all these
jellyfish have this
complex life cycle where they start off
as a polyp
which is basically like a small sea
anemone and then they'll go through a
metamorphosis and become a medusa
and the medusa stage is what we
generally think of when we think about a
jellyfish and in most of these species
the polyps are generally able to
asexually reproduce and they can
regenerate if
tissue is cut off of them or if they're
damaged and they
don't have any clear evidence of
senescence which is the
term for biological aging so they appear
to have some degree of immortality
no one had reported their ability to do
this until
i think this was 2015. so do moon
jellyfish hold the key to
slowing aging and extending our lifespan
could they
help us live forever before i got into
making this video
i would have put this sort of research
in the same category as
downloading your brain your
consciousness into a computer
like i can see how maybe that would work
but
i don't think we're anywhere near that
because we don't even understand how the
brain works or how memories are stored
so
that seems like serious science fiction
so i would have put say extending the
human lifespan to 120 150 and beyond
in the same category but after
reading professor sinclair's book and
doing an interview with him
i think it seems much more possible and
in fact
plausible that we'll make some progress
over controlling aging
in our lifetimes now if you want to slow
aging
the first question you need to answer is
why do we age in the first place i mean
what really
is aging i've made a video in the past
about
telomeres these are the end caps on your
chromosomes
and every time a cell divides the
telomere gets a bit shorter
so it was thought that these telomeres
are kind of like the
tips of your shoelaces and they prevent
the chromosome from fraying
but there are other signs in older
bodies
that you have old cells there are an
accumulation of things they're called
senescent
cells they're essentially these
zombie-like cells that just
go on living in your body and inflaming
the cells around them
there's uh poor intercellular
communication
there's mitochondrial dysfunction those
are the powerhouses of the cell
there are these eight or nine different
features
of older cells and they are the
hallmarks of aging
but the question is are they the cause
of aging
or are they kind of the result of a
deeper root cause
in the middle of the last century the
hypothesis
was that it was damaged to our dna
mutations to our dna that happened over
the course of our lives
that led us to be older but
evidence since then has suggested that
that is not really
the case you can take an adult cell
and you can clone it into a new
organism and that organism appears to
live
about as long as non-cloned organisms of
the same species
now the first sheep dolly the sheep had
a short lifespan
she died early but cloned animals you
can now clone a monkey
you can clone dogs in fact barbra
streisand the actress
she cloned her dogs and they're expected
to live a normal lifespan
so in that way it seems like all the
information is still there
in the dna so if we're not losing
information in our dna
then what is the reason for aging
well professor sinclair suspects that
it's a loss of information
but not the information in our dna in
our
genome no professor sinclair suspects
that the loss of information
is in our epi genome so
what is the epigenome every cell in your
body has
the same dna but different cell types
have different epigenomes they have
different ways of packaging that dna
coiling up you know a lot of it so that
it's not red
and leaving some parts of the dna
spooled out so it's easier to
transcribe and turn into proteins and
run that cell
so the epigenome is responsible for
turning on
or turning off different parts of the
dna
the way it does that is with proteins
called histones
that essentially the dna is wrapped on
and also things like methylation so
there's these
chemical signaling markers which are
placed on the dna in certain positions
so the idea is when your body is first
forming
the epigenome is what tells your cells
what type of cell to be
but as you get older professor
sinclair's hypothesis is that we are
losing information in the epigenome and
that's important because if a skin cell
needs to remain a skin cell that's the
epigenome
and if you don't have the epigenome the
skin cell will forget what type of cell
it is
and it might turn into a brain cell
which may not be that bad but if your
brain turns into a skin cell
you've got a problem and i think that's
largely what aging is
i've got to say like there's some weird
like hair patches like on my shoulder
that have happened as i've gotten older
is that a cell
like doing the wrong thing are those
meant to be skin cells are they
screwing up or is this just some i don't
know no
weird stuff happens when you get older
right you start to get hair growing
where it shouldn't
ears nose back that's cells losing their
identity
cells go i can't remember what i'm
supposed to do i'm not reading the right
genes anymore
so the key to this sort of breakdown of
the epigenome
is dna damage
yeah so when you go out in the sun and
not like today but on a day where
there's a lot of sun
you'll break your chromosomes and in the
effort that the cells go to to
stick the chromosome back together you
know the dna isn't just flailing around
it's actually bundled up
the cell has to unwrap it recruit
proteins to help
join it together and then they have to
go back and reset the structures
and that resetting of the epigenome
happens about 99
that one percent is the aging process
so over time histones are not returned
to the right places
and dna methylation is added in places
where it shouldn't be
we can read that methylation pattern and
i could tell you
how old you are exactly and when you're
even going to die
how could you tell that well it's a
clock we call it the horvath clock
named after my good friend steve horvath
and so these little chemicals that
accumulate on the dna like a plaque on
the teeth
we can read that and the more you have
the older you are biologically
so you might only be 40 you're younger
than 40 of course but
you you know i'm 50 now but i might be
biologically 60
actually i was and i changed my life and
then the test said i was biologically
31.
i mean one of the things i found really
interesting was you found a way to make
mice age faster so how did you do that
well
the clock of aging is due to the loss of
the information in the cell
and one way to accelerate that is to go
break a chromosome
instead of going in the sun we
engineered a mouse where we could break
its chromosomes
not enough to cause mutations the cells
put the dna back together so we didn't
lose any genetic information but if
we're right about the epigenetic
information theory of aging those mice
should get old
and that's exactly what happened it's
gray it's got a hunchback it's got
dementia all its organs look old
but the real test was what if we
measured that dna clock
the what we call the dna methylation
clock and we
measured it and those mice were actually
50 percent older
than mice that we didn't treat so that
isn't just
a mouse that looks old that mouse
literally is older
what's interesting about this hypothesis
is that if it's true
if the noise accumulating the epigenome
is really what's causing aging
well then there are steps we can take
right now
to slow the rate of aging in our bodies
by trying to better maintain our
epigenomes
so how do we do that
there's this theory that billions of
years ago
early bacteria took an important
evolutionary step
they actually developed two different
modes of living
when times were good they used their
energy to grow and reproduce
but when conditions were tough they used
their energy to
protect and repair their cells they
evolved what professor sinclair calls
longevity genes these genes triggered by
adversity create enzymes which among
other things
maintain the epigenome and today those
same longevity genes can be found
in bacteria and us we have these
hormetic response genes or longevity
genes that are in all of our cells
and they sense when we've run a lot
we've lost our breath or we're hungry
we're a little bit hot but a little bit
cold but these genes are turning on
our general defenses against aging so
what is that so parts of our cells
fall apart they can put them back
together proteins misfold
they can get rid of them or put them
back together the ends of the
chromosomes get shorter they can
lengthen them a lot of processes that go
on but one of the most important i think
is maintaining the information the
epigenetic information in the cell
so that our cells don't forget what to
do
there are three types of longevity gene
they're the ones we work on called
sirtuins
and they control the information in the
cell in fact sir in the sirtuin stands
for
silent information regulator number two
there are other ones the other group is
called amp kinase or ampk
this group of genes senses how much
energy we're taking in
mostly in the form of sugar and then the
third group is called mtor
and these genes control and respond to
how much
amino acids we're taking in so if you
eat a giant steak
you've got a lot of amino acids coming
into your body
that'll actually prevent mtor from
hunkering down and keeping you
being longer lived so the mouse
experiments actually bear this out
the best way to make a mouse live longer
is to reduce
the amount of time it eats so periodic
fasting intermittent fasting
uh to keep it a little bit cool and to
restrict its amino acids
that's the recipe for long life for a
mouse and it's true for monkeys as well
they've been calorie restricted studies
where these monkeys for 15 years didn't
eat as much food as the ones that gorged
themselves whenever they wanted
and they were protected they didn't just
age slower they didn't get as much
diabetes and heart disease they were
actually fit and healthy when the
control group eating whatever they
wanted
aged and became sick quicker when some
people think about
eating less like calorie restriction as
a way to
extend their life that doesn't seem like
a very pleasant way
to extend life i mean to be hungry for
longer
so are there other ways to you know
mimic that effect or to simulate
that there are these molecules that turn
on the sirtuin pathway
and trick the body and so for example in
the lab
if i give some of our mice a molecule
called nmn
which raises the level of a chemical
called nad
you get hyperactive defenses in the body
and what did you see in these
you know senescent mice that you gave
animento
uh well we had a bit of an incident
these mice that we gave animento ran
50 further but actually some of them ran
so far
that the machine the little treadmill
stopped working and we had to reprogram
the software
because this program had never seen a
mouse that ran more than three
kilometers
three kilometers for a mouse for an old
mouse they outran the young mice
and that's like an ultra marathon for us
that would be
probably like taking a 70 year old and
making them
run faster than a 20 year old further
yeah so these are ultra marathoners and
if we did that to humans imagine you
could have 90 year olds
winning olympic medals so to sum up
there are six things that you can do
right now to slow the rate of your aging
starting with zero
avoid dna damage wear sunscreen avoid
x-rays and all that sort of stuff
number one eat less caloric restriction
number two eat less protein because your
body has ways of detecting how much of
that you're taking in
number three do some exercise high
intensity interval training
get your heart rate up to 85 make your
body feel like you're running from
a lion or something number four be
uncomfortably cold
or number five be uncomfortably hot
all of these things will trigger your
body's longevity genes
into maintaining your epigenome going
into
repair and protect mode rather than grow
and reproduce
if you think about those things those
are generally all the things that we
don't do
but what if slowing aging isn't enough
for you
well this is where my interview with
professor sinclair took an interesting
turn
because he's actually done some research
on reversing
aging so how would you do that well
effectively
you would need to take the epigenome and
reset it back to
an earlier time but how is that possible
back in 2012 a scientist named yamanaka
received the nobel prize for discovering
four
factors which when applied in a gene
therapy to an adult
cell would reset the whole epigenome
back to
how that cell was when it was an embryo
so it is what is called a pluripotent
stem cell now you wouldn't want to apply
that to your entire body because
well then you would turn into a giant
tumor because your cells wouldn't know
how to differentiate but it does suggest
that there are ways
of resetting your epigenome and they
could be the key
to reversing aging the big breakthrough
that we just had in my lab
only you know about a year or so ago was
to reprogram
the eye of a mouse and the eye we chose
the eye because that's a very hard thing
to fix right if you go blind when you're
older we think that's a one-way thing
you're never going to recover your
vision but we decided let's try it
anyway let's let's go for broke
so we put a gene therapy in the eye of
old mice
turned their retinas to be young again
reversed aging in their retinas
so those one-year-old mice went back to
about two months
and guess what those mice could see
again just like they were young again
how do you reset one of these eye cells
without resetting it to just a stem cell
well we have to be very careful not to
reset these cells to be
basically a stem cell otherwise we
wouldn't have
mice that can see we'd have mice with a
giant tumor in the back of their eyes
so what we do is a couple of things we
didn't use all of the four reprogramming
factors that won the nobel prize we use
just
three we leave off one called mic which
causes cancer
and those three seem to be just the
right recipe
for taking the age of the eye backwards
but not too far
then the second thing we do is we turn
it off we can actually turn
this system on when we want and off
again so that we don't take them too far
back in age
can you do that with any cell we think
we can do this in any tissue
where we've now given it to the whole
mouse and those mice are fine
no evidence of cancer they seem to be
really quite healthy
so the big question is can you take a
mouse way back the whole body
and be totally young again maybe back
from two years back to two months
and that's what we're doing right now
that's pretty exciting
it's it's freakishly exciting actually i
thought we'd just slow down aging now
we're talking about an aging reset
you know what we've only reset the age
of the eye once
but how many times can we do this maybe
it's twice maybe it's a hundred times
so professor sinclair claims that his
gene therapy
reversed aging in the mouse's eye and
allowed it to see
again but applying a gene therapy to
every one of your trillion cells is
pretty
impossible so in order for this to
actually work and reset an entire body
you would need another way and this is
where the jellyfish come in
because moon jellyfish any cell in an
adult jellyfish can actually
be reset into an earlier stage of its
life cycle it can become a polyp
again so it seems like the jellyfish are
actually
capable of activating something like the
yamanaka factors
and resetting their epigenomes to an
earlier time
in their lives if we're able to figure
out how they do that
well then maybe we could do the same
with our own cells
we do have the ability to reset our
epigenomes
but that is typically only used when
we're in the embryonic stage when we
need to maintain
all our cells as stem cells as we age
most mammals including humans we lose
stem cells over time and the stem cells
we do have become more and more
restricted
over time to the types of cells they can
make so if we can understand how
the moon jellyfish can take presumably
many different kinds of cells
and reverse engineer them into the cells
it needs during regeneration
that might give us an idea of how to do
it in ourselves as well
so i still think we're a fair ways off
from
reversing aging in the entire human body
but what i found interesting from
talking to professor sinclair was that
there's at least a road map
at least a path ahead where you can see
that it could be possible
to slow and even reverse aging
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