Transcriber: Gia Linh Hoang Reviewer: David DeRuwe
“Life starts at 40.”
That’s what they say, right?
And I don’t know how you feel about this statement,
but definitely, science doesn’t agree with this.
Actually, in 2019, a group of Australian geneticists -
they actually developed a way to measure the maximum lifespan of a species.
And they determined that for humans, the maximum lifespan is 38 years.
We are talking about 38 years.
And the same number came also from studies done by anthropologists
that looking at remains of early humans and the Neanderthals,
they reached the same conclusion.
Of course, if we look at what’s happened in society,
the numbers are very different.
On average, males live a lifespan of 79 years
and females, they live 85 years,
and this is true in Europe as well as in the United States.
So we are talking double the lifespan that is expected from us
based on our genetic makeup.
And how is this possible?
So two main things happened that changed our lifespan.
From one side, the progress made in medicine,
especially in the last century,
and then also the change in lifestyles.
So these two things make the difference.
Are we OK for the lifespan as it is right now?
No, of course we want more,
but what we also want is to see our kids and grandkids grow up
and become adults themselves.
We want fertility, and we want to run a marathon when we are 60.
And we want sharp eyes, and we want a sharp brain, etc, etc.
So what we really care about is not really only the lifespan,
but the health span - how long we are healthy and fully functional.
This is really where the conversation is going.
And I’ve been now for a while very interested in the biology of aging,
and I spent the last decades trying to understand
if and how it’s possible to safely and effectively
extend our youth for longer.
I’m a stem cell| and developmental biologist by training,
so when I think about aging,
the thing that I think about is actually what happens to cells during time.
And what happens to cells involves especially two most important players:
From one side, we have the stem cells,
and on the other side, we have the senescent cells,
and you can think about them as a continuum on a spectrum
of differentiation and evolution.
On one side, stem cells are youthful and young and potent cells
that can divide and form other cells to regenerate a tissue.
And the senescent cells are actually older;
they can not divide anymore.
They are stuck in their nonfunctional state,
and they can’t produce any cell any more.
And what happens during time
is that actually when we get older, our stem cells stop working,
and so they don’t regenerate tissue anymore,
and that’s why we get the white hair,
that’s why our muscles become frail, etc., etc.
On the other side,
we have an accumulation of these senescent cells, these old cells,
and what we know now is that actually even a small percentage
of senescent cells in our tissue really stop the tissue from functioning properly,
and it has been proven in the last few years
that if we remove these senescent cells from an organ,
the organ will work much better.
So why do these two things happen?
Why do we end up with less stem cells and more senescent cells?
Is there some sort of punishment? Is this a mistake of evolution?
Is this a way to regulate the number of humans on this planet?
Now, actually, this is the basis of the yin and yang of aging.
These two things happen
because they control and limit the development of cancer.
So they protect us from cancer and tumors.
Remember that, by definition, an immortal cell is actually a cancer cell,
so definitely it’s not what we want.
We want to keep our cells in this perfect balance
between the self-renewal of the stem cells and the maintenance of a tissue,
and the process of senescence,
but we don’t want to unleash completely this regulation.
So what can we do to maintain this perfect balance in our tissues?
Well today, after decades and decades of studies worldwide,
I can finally unveil the big two secrets of how to live a long life:
Eat well
and exercise.
I know this is not surprising, but actually still remains in 2021.
This remains the two most important things
that we can do to live a healthy and longer and happy life.
So that, that’s for sure.
But I have to say that in the last few years in science,
there has been a lot of development and understanding
in what else we can do to extend the health span
and to stop, prevent, and cure age-associated diseases.
We are talking about Alzheimer’s, Parkinson’s, diabetes, osteoporosis, etc.,
and I was doing my research at Stanford University
with Michael Clarke and his team,
and by pure serendipity, we started studying something
that gave us very special insights into the biology of aging.
We started studying people with Down’s syndrome,
and as most of you know, people with Down’s syndrome,
they actually have an extra copy of chromosome 21.
This means that they have three copies instead of two
of a small chromosome in our genome.
What few people know is that actually people with Down’s syndrome,
they present signs of premature aging,
so they have early onset Alzheimer’s by age of 40.
They have osteoporosis. They have alopecia. They have skin aging.
And what happens at the cellular level is that, once again,
there are less stem cells and more senescent cells.
So we spent a lot of time trying to understand what’s really going on
in Down’s syndrome to cause the accelerated aging,
and we actually realized that there was an imbalance
of a protein called USP16 that caused this imbalance.
USP16 regulates actually the ratio between stem cells and senescent cells.
And if you reverted this imbalance that you see in Down’s syndrome,
you can actually cure
several of the age-associated diseases that can be observed.
So these open really a Pandora’s box on this space of signal blocker.
The signal blockers like USP16 are basically the gatekeepers of aging.
They’re able to control the perfect ratio between stem cell and senescent cells.
And actually, now we are using this signal blocker to develop treatments
for age-associated diseases.
For example, we are developing treatment for osteoarthritis,
and we should go into clinical trial in a couple of years from now.
So what we learned so far is that really, once again,
signal blockers show us that median states are the best that stay in the middle -
we want to maintain stem cell activity, not too many senescent cells,
but we want to keep a control on these processes so we don't get cancer.
And I just want to end with one of my favorite quotes from Seneca,
a Roman philosopher that 2000 years ago,
in his essay on the shortness of life,
he said, “It’s not that our life is short. It’s just that we waste a lot of it.”
We are very frugal with our personal property,
but when it comes to squandering time,
we are very wasteful of the one thing that is very important for us.
Seneca actually died at age 69,
healthy as a fish, just because he was forced to kill himself.
So I hope we can really live fully and healthy until our last breath.
Thank you.
(Applause)