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 that 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..."

"...more garbage, more CO2. Where are 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' is that some people consider them immortal.

How can that be?

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 poor intercellular communication,

there's mitochondrial dysfunction, those are the powerhouses of the cell.

There are these 8 or 9 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 damage 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.

I mean, 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 are 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 epigenome.

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 read,

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 gotta say, there's some weird, hair patches, on my shoulder,

that have happened as I've gotten older.

Is that a cell... doing the wrong thing? Are those meant to be skin cells?

Are they're screwing up or is this just some... I don't know.

No, 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, the 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 in the epigenome

is DNA damage?

Yeah, so when you go out in the sun, 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,

note: 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 1% is the aging process.

So overtime, 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 gonna 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 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?" what we call the 'DNA methylation clock'.

And we measured it and those mice were actually 50% 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 are a little bit hot, or a little bit cold.

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.

There are the ones we work on called 'sirtuins' and they control the information in the cell.

In fact, 'sir' in sirtuin stands for 'silent information regulator' number two (SIR2).

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,

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,

that have 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?