How young blood might help reverse aging. Yes, really

This is a painting from the 16th century
from Lucas Cranach the Elder.

It shows the famous Fountain of Youth.

If you drink its water or you bathe in it,
you will get health and youth.

Every culture, every civilization
has dreamed of finding eternal youth.

There's people like Alexander the Great
or Ponce de León, the explorer

who spent much of their life
chasing for the Fountain of Youth.

They didn't find it.

But what if there was
something to it?

What if there was something
to this Fountain of Youth?

I will share an absolutely amazing
development in aging research

that could revolutionize
the way we think about aging

and we may treat age-related
diseases in the future.

It started with experiments that
showed a recent number of studies

are but growing, that animals
-- old mice that share a blood

supply with young mice,
can get rejuvenated.

This is similar to what you might see
in humans in Siamese twins

and I know this sounds a bit creepy.

But what Tom Rando, a stem cell researcher
in 2007 reported, was that old muscle

from a mouse can be rejuvenated,
if it's exposed to young blood

through a common ciriculation.

This was reproduced by Amy Wagers
at Harvard, a few years later and others

then showed that similar rejuvenating
effects could be observed in the pancreas,

the liver and the heart.

But why I'm most excited about and several
other labs, is that this may even apply

to the brain.

So, what we found is that an old mouse
exposed to a young environment

in this model called parabiosis,
shows a younger brain and a brain

that functions better.

And I repeat, an old mouse that gets young
blood through the shared circulation looks

younger and functions
younger in its brain.

So, when we get older,
we can look different aspects

of human cognition and you can
see on the slide here, we can look

at reasoning, verbal
ability and so forth.

Around age 50 or 60, these functions
are all intact and as I look at the young

audience here in the room,
we're all still fine.

But it's scary to see how
all these curves go south.

And as we get older,
diseases such as Alzheimer's

and others may develop.

We know that with age, the connections
between neurons, the way neurons

talk to each other, the synapses start
to deteriorate, neurons die, the brain

starts to shrink and there's
an increased susceptibility

for neurodegenerative diseases.

One big problem we have, to try
to understand how this really works

at a molecular, mechanistic level
is that we can't study the brain's

in detail, in living people.

We can do cognitive tests,
we can do imaging.

All kinds of sophisticated testing.

But we usually have to wait
until the person dies to get

the brain and look how it really
changed through age or in a disease.

This is what neuropathologists
do, for example.

So, how about we think the brain
being part of the larger organism.

Could we potentially understand more
about what happens in the brain

at the molecular level, if we see
the brain as part of the entire body?

So, if the body ages or gets sick,
does that affect the brain?

And vice versa, as the brain gets older,
does that influence the rest of the body?

And what connects all the different tissue
in the body, is blood.

Blood is the tissue that not only carries
cells that transport oxygen, for example

to red blood cells or fight infectious
diseases, but it also carries messenger

molecules, hormone-like factors
that transport information from one

cell to another, from one
tissue to another.

Including the brain.

So, if we look at how the blood changes
in disease or age, can we learn something

about the brain?

We know that us, we get older.
The blood changes, as well.

So, these hormone like factors
change as we get older

and by in large, factors that we know
are required for development

of tissues for maintenance of tissues,
they start to decrease as we get older.

While factors involved in repair,
and injury, and inflammation

they increase, as we get older.

So there's this unbalance of good
and bad factors, if you will.

And to illustrated what we can do
potentially with that, I want to talk you

through an experiment that we did.

We had almost 300 blood samples
from healthy human beings

age 20 to 89 years of age,
and we measured over 100

of these communication factors,
These hormone-like proteins that

transport information between tissues.

And what we noticed first,
is that between the youngest

and the oldest group, there's about
half the factors changed significantly.

So our body lives in very different
environment as we get older,

when it comes to these factors.

And using phthisical or bioinformatics
programs, we could try to discover

those factors that best predict age,
in a way, back-calculate the relative

age of a person.

In the way this looks
is shown in this graph.

So, on the one axes you see the actual
age a person lived, the chronological age.

So, how many years
did they live?

And then we take these top factors
that I showed you and we calculate

what is their relative age,
what is their biological age.

And what you see, is that there is
a pretty good correlation,

so we can pretty well predict
the relative age of a person.

But what's really exciting
is the outliers, as so often in life.

You can see here, the person
I highlighted with the green dot

is about 70 years of age, but seems
to have a biological age, if that's really

true what we're doing here,
of only about 45.

So, is this a person that looks
actually much younger than their age.

But more importantly, is this a person
who is maybe at a reduced risk

to develop an age-related disease
and will have a long life

-- will live to 100 or more.

On the other hand, the person here
highlighted with the red dot,

is not even 40, but has
a biological age of 65.

Is this a person at increased risk
of developing an age-related disease?

So we're trying in our lab to understand
these factors better and many other groups

are trying to understand,
what are the true aging factors

and can we learn something
about them to possibly

predict age-relate diseases?

So, what I've shown you so far
is simply correlational, right?

You can just say, well these factors
change with age but you don't really know

if they do something about aging.

So, what I'm going to show you now
is very remarkable and it suggests

that these factors can actually
modulate the age of a tissue.

And that's where we come back
to this model called parabiosis.

So, parabiosis is done in mice
by surgically connecting

the two mice together and that leads
them to a shared blood system

where we can now ask
-- how does the old brain

get influenced by exposure
to the young blood?

And for this purpose we use young mice
that are equivalency of 20 year old people

and old mice that are roughly
65 years old in human years.

What we found is quite remarkable.

We find there is more neural
stem cells that make news neurons

in these old brains.

There's an increase activity
of the synapses, the connections

between neurons.

There's more genes expressed
that are known to be involved

in the formation
of new memories.

And there's less of this
bad inflammation.

But we observed that there's no cells
entering the brains of these animals.

So, when we connect them there's actually
no cells going into the old brain,

in this model.

Instead we've reasoned then,
that it must be the soluble factors,

so we could collect simply the soluble
fraction of blood which is called plasma,

and injected either young plasma
or old plasma in these mice

and we could reproduce these rejuvenating
effects, but what we could also do now,

is that we could do
memory tests with mice.

As mice get older, like us humans,
they have memory problems.

It's harder to detect them, but I'll show
you in a minute how we do that.

But we wanted to take this one
step further, one step closer

to potentially being relevant to humans.

What I'm showing, that you know,
is unpublished studies where we use

human plasma
-- young human plasma

and as a controlled saline
and injected it into old mice,

and asked, can we again
rejuvenate these old mice?

Can we make them smarter?

And to do this, we use
a test called a Barnes maze.

This is a big table that has lots of holes
in it, and there are guide marks around it

and there's a bright light
as on the stage here.

The mice hate this and they tried
to escape, and find the single hole

that you see, pointed at with an arrow,
where a tube is mounted underneath

where they can escape and feel
comfortable in a dark hole.

So we teach them over several days
to find this space on these cues

in the space and you can compare
this for humans, to find your car

in a parking lot after
a busy day of shopping.

(Laughter)

Many of us have probably had
some problems sometimes with that.

So, let's look at an old mouse here.

This is an old mouse that has memory
problems, as you notice in a moment.

It just looks into every hole,
but it didn't form this spacial map

that would remind itself where it was
the previous trial or the last state.

In stark contrast, this mouse here
is a sibling, has the the same age

but was treated with young human plasma
for three weeks with small injections

every three days.

And as you noticed, it's almost looks
around, "Where am I?"

and then walks straight
to the hole and escapes.

So, it could remember
where that hole was.

So, by all means, this old mouse
seems to be rejuvenated.

It functions more like
a younger mouse.

And it also suggests that there
is something, not only in young mouse

plasma, but in young human plasma that
has the capacity to help this old brain.

So, to summarize we find the old mouse
and its brain in particular are malleable.

They're not set in stone.
We can actually change them.

It can be rejuvenated.

Young blood factors can reverse aging
and what I didn't show you, in this model

the young mouse actually suffers
from exposure to the old.

So, there's old blood factors that
can accelerate aging and most importantly,

humans may have similar factors because
we can take young human blood

and have the similar effect.

Old human blood, I can show you,
does not have this effect.

It does not make the mice young.

So, is this magic
transferable to humans?

We're running a small clinical study
at Stanford, where we treat Alzheimer's

patients with mild disease,
with a pint of plasma

from young volunteers, 20 year olds,
and do this once a week for four weeks

and then we look
at their brains with imaging.

We test the cognitively and we ask their
caregivers for daily activities of living.

What we hope is that there are some signs
of improvement by this treatment.

And if that's the case, that could give us
hope that what I showed you

works in mice, might
also work in humans.

Now, I don't think we will live forever,
but maybe we discovered

that the Fountain of Youth is actually
within us and it has just dried out,

and if we can turn it back on,
a little bit, maybe we can find

the factors that are mediating
these effects, we can produce

these factors synthetically and we can
treat diseases of aging,

such as Alzheimer's disease
or other dementias.

Thank you very much.

(Applause)