Lex Fridman Podcast - #189 - David Sinclair: Extending the Human Lifespan Beyond 100 Years

The following is a conversation with David Sinclair.

He’s a professor in the Department of Genetics at Harvard

and co director of the Paul F. Glenn Center

for the Biology of Aging at Harvard Medical School.

He’s the author of the book,

Lifespan and co founder of several biotech companies.

He works on turning age into an engineering problem

and solving it.

Driven by a vision of a world

where billions of people can live much longer

and much healthier lives.

Quick mention of our sponsors,

Onnit, Clear, National Instruments,

and I, SimpliSafe and Linode.

Check them out in the description to support this podcast.

As a side note, let me say that longevity research

challenges us to think how science and engineering

will change society.

Imagine if we can live 100,000 years,

even under controlled conditions,

like in a spaceship say,

then suddenly a trip to Alpha Centauri

that is a 4.37 light years away

takes a single human lifespan.

And on the psychological, maybe even philosophical level,

as the horizons of death drifts farther into the distance,

how will our search for meaning change?

Does meaning require death

or does it merely require struggle?

Reprogramming our biology will require us to delve deeper

into understanding the human mind and the robot mind.

Both of these efforts are as exciting of a journey

as I can imagine.

This is the Lex Friedman Podcast

and here is my conversation with David Sinclair.

I usually feel like the same person when I was 12.

Like when I, right now, as I think about myself,

I feel like exactly the same person

that I was when I was 12.

And yet, I am getting older, both body and mind,

and still feel like time hasn’t passed at all.

Do you feel this tension in yourself

that you’re the same person and yet you’re aging?

Yeah, I have this tension that I’m still a kid,

but that helps in my career.

Scientists need to have a wonder about the world

and you don’t wanna grow up at 12 year olds

and even younger, I would say six, seven year olds.

I’ve still got that boy in me and I can look at things.

It’s a gift, I think, that I can see things

for the first time if I choose to,

and then explain them as I would to a six year old

because I am that mentally.

But on the other hand, I’m getting older, right?

I run a lab of 20 people at Harvard.

I’ve got a book, I’ve got science to do, companies to run,

and so I have to, on most days,

just pretend to be a grownup and be mature,

but I definitely don’t feel that way.

There’s something I really appreciated

in opening your book.

You talked about your grandmother.

And on this kind of theme, on this kind of topic,

she, first of all, had a big influence on you.

My grandmother had a big influence on me.

And you also mentioned this poem

by the author of Winnie the Pooh, Alan Alexander Milne.

Maybe I can read it real quick

because I love, on the topic of being children,

when I was one, I had just begun.

When I was two, I was nearly new.

When I was three, I was hardly me.

When I was four, I was not much more.

When I was five, I was just alive, but now I am six.

I am as clever, as clever, so I think I’ll be six,

now, forever and ever.

So this idea of being six and staying six forever,

being youthful, being curious,

being childlike, this and other things,

what influence has your grandmother had

in your thinking about life, about death, about love?

Yeah, I was getting misty eyed as you read that

because that poem was read to me very often,

if not every day, by my grandmother,

who partially raised me.

And she was as much a bohemian as an artist, philosopher.

And she’s one of those people

that wouldn’t talk about the little things.

She said, I hate small talk.

Don’t talk to me about politics or the weather.

Yeah, talk to me about human beings and culture.

So I was raised on that,

and this poem was one that she read to me often

because she knew that the mind of a child is precious,

it’s honest, it’s pure.

And she grew up during the Second World War

and in Hungary and Budapest witnessed the worst of humanity.

She was trying to save a whole group of Jewish friends

in her apartment, saw what happened after the World War,

which was there was, the Russians were in control

and locals weren’t necessarily treated well

if they were rebellious, which she was.

And then there was the revolution in 56,

which she was part of and had to escape the country.

So she saw what can happen when humans do their worst.

And her words to me, expressed in part through that poem

was, David, always stay young and innocent

and have wonder about the world,

and then do your best to make humanity the best it can be.

And that’s who I am, that’s what I live for,

that’s what I get up in the morning to do

is to leave the world a better place

and show to whoever’s watching us,

whether it’s aliens or some future human historian,

that we can do better than we did in the 20th century.

You know, we mentioned offline this idea

of bringing people back to life

through artificial intelligence,

sort of, I don’t know if you’ve seen videos

of basically animating people back to life,

meaning whether it’s, for me personally,

I’ve been working on specifically about Albert Einstein,

but also Alan Turing, Isaac Newton, and Richard Feynman.

And it’s an opportunity to bring people

that meant a lot to others in the world

and animate them and be able to have a conversation

with them at first to try to visually,

visually explore the full richness of character

that they had as they struggle

with the ideas of the modern age.

Sort of, it’s less about bringing back their mind

and more bringing back the visual quirks

that made them who they are.

And then maybe in the future,

it’s using the textual, the visual,

the video, the audio data to actually compress

down the person for who they are

and be able to generate text.

There’s a few companies, there’s Replica,

which is a chat engine that was born

out of the idea of bringing,

the founder lost her friend to,

he got run over by a car.

And the initial reason she founded the company

was trying to just have a conversation with her friend.

She trained machine learning, natural language system

on the texts that they exchange with each other

and try, she had a conversation with him

sort of after he was gone.

And it’s very, the conversation was very trivial.

It was obvious that it’s AI agent,

but it gave her solace.

It made her actually feel really good.

And that’s the way I wonder if it’s possible

to bring back people that are,

that mean something to us personally,

not just Einstein, but people that we’ve lost

and in that way achieve a kind of small

artificial immortality.

I don’t know if you think about this kind of stuff.

Well, I definitely think about a lot of things.

That one’s a really good one.

There’s a great Black Mirror episode

about the wife who brings back the boyfriend or husband.

I think one of the challenges

with bringing back Richard Feynman

would be to capture his sense of humor,

but that would be awesome.

But yeah, bringing back loved ones would be great,

especially if they’re young and they die early,

though it may hold you back from moving on.

That’s another thing that could happen as a negative.

But I think that’s great.

And I also think that it’s gonna be possible,

especially when we’re recording some of us,

every aspect of our lives,

whether it’s our face or things we see, right?

Eventually one day, everything we see can be recorded.

And then you can build somebody’s experience

and thoughts, speech,

and you will have replicas of everybody,

at least digitally,

and physically you could do that too one day.

But that’s a good idea,

especially because there are people that I’d like to meet,

and I think it’s easier than building a time machine.

One person I’d love to meet is Benjamin Franklin.


Well, I wouldn’t go back in time.

I would, but I’d prefer to bring him into the future

and say, can you believe we have this thinking machine

in our pockets now?

And just see the look on his face

as to where humanity has come.

Because I think of him as a modern guy

that just was before his time.

Yeah, so you’re thinking Benjamin Franklin the scientist,

not Benjamin Franklin the political thing.

Because he’d be very upset with Congress right now.


So maybe talk to him about science and technology,

not politics.

Or maybe just don’t get him on Twitter

because he’ll be very upset with human civilization.

You know, I wonder what their personalities are like.

Isaac Newton, it does seem complicated

to figure out what their personality is like.

Even Friedrich Nietzsche, who I also thought about.

Feynman is, we just have enough video

where we get the full kind of,

I mean, it shows you how important it is

to get not the official kind of book level presentation

of a human, but the authentic,

the full spectrum of humanity.

You mentioned collecting data about a person,

collecting the whole thing, the whole of life,

the ups and downs, the embarrassing stuff,

the beautiful stuff, not just the things

that’s condensed into a book.

And then with Feynman, you start to see that a little bit.

Through conversations, you start to see peaks

of like that genius.

And then through stories about him from others.

And then certainly you, the sad thing

about Alan Turing, for example,

is there’s very little, if any, recording of him.

In fact, I haven’t been able to find recording

allegedly there’s supposed to be a recording of him

doing some kind of a radio broadcast,

but I haven’t been able to find anything.

And so that’s truly sad that it feels like

it makes you realize how the upside,

how nice it is to collect data about a person,

to capture that person.

That’s the upside of the modern internet age,

the digital age, that that information,

yeah, creates a kind of immortality.

And then you can choose to highlight

the best parts of the person,

maybe throw away the ugly parts

and celebrate them even after they’re gone.

So that’s a really interesting opportunity.

You’ve also mentioned to me offline

that you’re really excited about all the different wearables

and all the different ways we can collect information

about our bodies, about the whole thing.

What’s most exciting to you in terms of collecting

the biological data about a human being?

Well, so I’m a biologist.

I find animals and humans as machines very interesting.

It’s one of the reasons I didn’t become an engineer

or a surgeon.

I wanted to understand how we actually are built.

And so I think a lot about machines merging with humans.

And the first of that are the bio wearables.

And so I talked a lot about this, I wrote about it

in Lifespan, the book, and pictured a future

where you would be monitored constantly

so that you wouldn’t suddenly have a heart attack,

you’d know that was coming,

or you wouldn’t go to the doctor

and they don’t know if you need an antibiotic or not.

Long term, how old are you, how to fix things,

what should you eat, what should you take,

what should your doctor do?

These devices, I predicted, would be smarter,

better educated than your physician

and would augment them.

And then there’d be a human that would just tick off

to see if it’s correct and they approve.

I also was predicting in the book

that we would have video conferences with our doctors

and that medicines would be delivered,

initially by courier, but eventually by drones

and get it to you sometimes in an emergency.

And that we could even have pills

that were synthesized or delivered in your kitchen

and combined certainly.

What’s amazing about that is that, what are we now,

two years since the book came out, even less,

and that future is basically here already.

COVID 19 accelerated that incredibly.

So where we’re at now in society is,

if you wanna pay for it, you can have a blood test

that will detect cancer 10, 20 years earlier than it would

before it forms a tumor.

You can, of course, do your genome very cheaply

for less than $100 now.

There are bio wearables already I wear,

this ring from Aura that I have a number of years of data.

I’ve been doing blood tests for the last 12 years

with a company called Inside Tracker, which I consult for.

And so I have all of that data as well.

And there’s 34 different parameters on my testosterone,

my blood glucose, my inflammation.

And I use all that data to, of course,

I wear a watch that measures things as well.

I use that data to keep my body in optimal shape.

So I’m now 51.

And according to those parameters,

I’m at least as good as someone in their early 40s.

And if I really work at it,

I can get my biochemistry down to early to mid 30s,

though I like to now eat a little dessert once in a while.

So that’s the future we’re in right now.

Anyone can do what I just said.

But in the very near future, just in the next few years,

you can be wearing wearables.

So I’m currently wearing a little,

what’s called a bio sticker.

This one I just put on last night.

It’s about an inch long, a few millimeters.

Yeah, for people just listening, it’s on David’s chest.

It’s just, how does it attach?

It’s just kind of.

It sticks on. Sticks on.

Yeah, so on one side you have an on button that you press.

The lights come on, flashes four times, it’s good to go.

It immediately syncs to your phone.

And this one, it’s called a bio button, a nice name.

And there’s another one that I have that I haven’t tried yet

that does EKG on your heart.

This is mainly for doctors to monitor patients

that go home after a heart attack or surgery.

But that’s medical grade FDA approved device.

So there will be a day, in fact, it’s already here,

that doctors are using these to get patients to go home

and save a week in hospital, $2,000 at least

for each patient.

That’s massive savings for the hospital.

But ultimately what I’m excited about is a future

that isn’t that far off where everybody,

certainly in developed countries,

eventually these will cost a few cents and rechargeable.

The only cost will be the software subscription

that can be monitored constantly.

And to give an idea what this is measuring me

at a thousand times a second is my vibrations as I speak,

my orientation, it already has told me this morning

how I slept, where I slept, what side I slept on.

We’ve got sneezing, coughing, body temperature,

heart rate, heart of other parameters of the heart

that would indicate heart health.

These data are being used to now to predict sickness.

So eventually we’ll have just in the next year or so

the ability to predict whether something

or diagnose whether something is pneumonia

or just a rhinovirus that can be treated or not.

This is really going to not just revolutionize medicine,

but I think extend lives dramatically.

Because if I’m gonna have a heart attack next week

and that’s possible, this device should know that

and I’ll be in hospital before I even have it.

Maybe you can talk a little bit about InsideTracker

because I saw that there’s some really cool things in there.

Like it actually, so maybe you can talk about,

I guess that you’re collecting blood to give it the data.

So, and it has like basic recommendations

on how to improve your life.

So we’re not just talking about diseases, right?

Like anticipating having a particular disease,

but it’s almost like guiding your trajectory to life,

how to, whether it’s extend your life

or just live a more fulfilling,

like improve the quality of life.

I suppose this is the right way to say it.

How does InsideTracker work?

What the heck is it?

Because I thought there was also pretty cool.


What is it?

Is it something other people can use?

You can definitely use it.

You can sign up, it’s consumer.

It’s like a company consumer facing company.

It is, yeah.

And I also want to democratize the ability

to just take a mouth swab eventually.

We don’t need to have a blood test necessarily,

but for now it’s a blood test

and you’d go to a lab core request in the US.

It’s also available overseas.

You can upload your own data for a minimal cost

and get the algorithms, the AI in the background

to take that data,

plot where you are against others in your age group

in terms of health and longevity at bio age.

They call it inner age,

but also it provides recommendations.

And this isn’t just a bunch of BS.

It sounds like it might be to say, I’ll go eat this

or go to that restaurant and order that,

but it’s actually based on the basic.

This company has entered hundreds.

Now it would be thousands of scientific papers

into their database

and hundreds of thousands of human data points.

And they have tens of thousands of individuals

that have been tracked over time

and anonymously that data is used to say

what works and what doesn’t.

If you eat that, what works?

If you take that supplement, what works?

And I was a coauthor on a paper that showed

that the recommendations for food and supplements

was better than the leading drug for type two diabetes.

That’s so cool.

The idea that you can connect,

like skipping the human having to do this work,

you can connect the scientific papers,

almost like meta analysis of the science

connected to the individual data.

And then based on that sort of connect your data

to whatever the proper group is

within the whatever the scientific paper is

to make the suggestion of how like how that work

applies to your life.

And then that ultimately maps to like a recommendation

of what you should do with your life.

Like it all like this giant system

that ultimately recommends

you should drink more coffee or less.

Right, and we’ll have the genome in there as well.

You can upload that.

Yeah, it’s awesome.

So these programs will know us way better

than we do and our doctors as well.

The idea of going to a doctor once a year

for an annual checkup and having males get a finger

up their butt and you cough, that to me is a joke.

That’s medieval medicine.

And that’s very soon going to be seen as medieval.

Yeah, to me as a computer science person,

it’s always upsetting to go to the doctor

and just look at him and like realize

you know nothing about me.

Like you’re making your like opinions based on like,

it is very valuable, years of intuition building

about basic symptoms, but you’re just like it is medieval.

They’re very good at it.

In fact, doctors in medieval times were probably damn good

at working with very little.

But the thing is, I’d rather prefer a doctor

that doesn’t really know what they’re doing,

but has a huge amount of data to work with.

Well, you’re right.

And many of my good friends are doctors.

I work at Harvard.

So I’m not against the profession at all.

But I think that they need just as much help

as anyone else does.

We wouldn’t drive a car without a dashboard.

We wouldn’t think of it.

So why would doctors do the same?

If we could, could we step back to the big,

profound, philosophical, both tragic

and beautiful question about age?

How and why do we age?

Is it from an engineering perspective?

You said you like the biological machine.

Is that a feature or a bug of the biological machine?

It is both a bug and a feature.

Evolutionary speaking, we only live as long as we need to

to replace ourselves efficiently.

If you’re a mouse, you’re only gonna live two

and a half years, three years.

You’re probably gonna die of starvation,

predation, freezing in the winter.

So they divert most of their resources

to reproducing rapidly,

but they don’t put a lot of energy

into preserving their soma, which is their body.

Conversely, a baleen type of whale,

a bowhead whale in particular will live hundreds of years

because they’re at the top of the food chain

and they can live as long as they want.

So they breed slowly and build a body that lasts.

We’re somewhere in between because we’ve, you know,

we’ve really only just come out of the savannas

where we could be picked off by a cat.

We were pretty wimpy going back 6 million years ago.

So we actually need to evolve quicker than evolution will.

And that’s why we can use our oversized brains

and intuition to give us what evolution

not only didn’t give us, but took away from us.

Now we’re pathetic, look at our bodies.

These arms, if any of us, even the strongest person

in the world went in a cage with a chimpanzee,

the chimp could knock that person’s head off, no question.

So we’re pathetic.

So we need to engineer ourselves to be healthier

and longer lived.

So getting to aging, we can do better, right?

Whales do way better.

We’re trying to learn how whales do that.

And if you ask really anybody in the field now, professor,

they’ll say there are eight or nine hallmarks of aging,

which are really, it’s a word for causes of aging.

So that you probably have heard of some of these,

your listeners will have loss of telomeres,

the ends of the chromosomes, like the little ends

of shoelaces, that kind of thing.

They get too short, cells stop dividing, become senescent.

They become, they put out what are called mitogens

that cause cancer and inflammatory molecules.

So that’s another aspect of aging, cellular senescence.

Another one is loss of the energetic.

So mitochondria, the battery packs wind down.

There’s a whole bunch, stem cells, proteostasis.

Well, these are our Achilles heels that I’m talking about.

They’re a common amongst all life forms, really.

But if you want me to jump to the chases to where,

what is the upstream defining factor?

If we boil it down, what do we get?

So most biologists would say, you can’t boil it down.

It’s too complex.

I would say you can boil it down to an equation,

which is the preservation of information

and loss due to entropy, i.e. noise.

And that is the basis of my research.

It originally came out of discoveries in yeast cells,

where I went to MIT in the 1990s.

You studied bread.

I kind of did.

I studied the makers of bread,

a little yeast called Saccharomyces cerevisiae,

which at the time was one of the hottest, excuse the pun,

organisms to work on.

But we figured out in the lab why yeast cells get old

and found genes that control that process

and made them live longer,

which was an amazing four years of my life.

One of those genes had a name with an acronym SIR2.

Now the two is irrelevant.

The SIR is important.

And the most important letter out of all of those three

is I, which stands for information.

Silent information regulator number two,

when you put more copies of that gene in,

just put in one more copy,

the yeast cells lived 30% longer

and suppressed the cause of aging,

which was the dysregulation of information in the cell.

And then, so fast forward to now,

I’ve been looking in humans and mice,

because they live shorter and cheaper to study,

where the loss of information in our bodies

is a root cause of aging.

And I think it is.

Your boldness in doing biology in this way is fascinating

because that also leads to a kind of,

it’s almost like allows for a theory of aging,

like you could boil it down to a single equation

and it leads to a, perhaps a metric

that allows you to optimize aging,

sort of in the fight against entropy.

I had to figure out which mechanisms, like you said,

the silent information regulator,

which mechanisms allow you to preserve information

without injecting noise, without creating entropy,

without creating degradation of that information.

For some reason, converting biology,

which I thought was mostly impossible

into an engineering problem,

feels like it makes it amenable to optimization,

to solving problems, to creating technology that can,

whether that’s genetic engineering or AI,

it makes it possible to create the technology

that would improve the degradation of information and aging.

Is there more concrete ways you think

about the kind of information you want to preserve?

And also, is there good ideas about regulators

of that information, about ways to prevent the distortion,

the degradation of that information?

Right, so we have silent information regulator genes

in our bodies.

We have seven of them, SIRT1 through seven, they’re called.

And we found in mice, one way to slow down

the loss of information is to just give more of these,

to upregulate these genes.

So we made a mouse that has more of this SIRT1 gene,

turned it on, and that slowed down the aging of the brain

and preserved their information.

Now, what information am I talking about, you might ask?

Well, again, you can simplify biology.

There are two types of information in the cell primarily.

The one we all read about and know about

is the DNA, the genome.

And that’s base four information, ATCG,

the four chemicals that make up the various sequences

of the genome, billions of letters.

And that also degrades over time.

But what’s been fascinating is that we find

that that information is pretty much intact

in old animals and people.

You can clone a dog.

One of my friends in LA just cloned his dog three times.

So this is doable, right?

It means that the genome can be intact.

But what’s the other type of information?

It’s the epigenome, the regulators

of the genetic information.

And physically, that’s really just how the DNA is wrapped up

or looped out for the cell to access it and read it.

So it’s similar to, and excuse this analogy,

but it’s a good one, a compact disc or a DVD.

Those pits in the foil are the digital information.

That’s the genome.

And the epigenome is the reader of that information.

And in a different cell, you’d read different music,

different songs, different symphonies.

And that’s what gets laid down when we’re in the womb.

And that makes a skin cell forever a skin cell

and not a brain cell tomorrow.

Thank God, otherwise our brains wouldn’t work very well.

But over time, what we see is that the brain cells

start to look more like skin cells.

And the kidney cells start to look more like liver cells.

And what we call X differentiate.

This is a term that we use in my lab,

but isn’t yet widely used.

But we needed a term to explain this.

And that process of X differentiation,

the loss of the reader of the CD or the DVD,

we liken that to scratches on the DVD

so that the reader cannot fully access the information.

Now we can slow down the scratches, as I mentioned.

We can turn on these genes.

We can even put in molecules into the cell

or even eat them and turn on those pathways,

which my father and I have been trying to do

for about a decade to slow things down.

But the question that I’ve had is,

is there a repository of information still in the body?

Because anyone who knows anything

about the loss of information

or even has tried to copy a cassette tape

or photocopy or Xerox anything knows that over time,

you lose that information irreparably.

So I’ve been looking for a backup copy,

inspired largely by Claude Shannon’s work

at MIT as well in the 1940s.

His mathematical theory of communication is just brilliant.

And so I’ve been looking for what he called the observer,

which is the backup copy.

We today might call that the TCPIP protocol of the internet

that stores information in case it doesn’t make it

to your computer, it will fill in the gaps.

And we’ve been spending about the last five years

to try and find if there really is a backup copy in the body

to reset the epigenome and polish those scratches away.

That’s incredible.

So finding the backup, so whenever there are too many

scratches pile up, you can just write a new version.

Like write, not a new version,

but go to the backup and restore it.

Right, that’s really all we’re talking about.

It’s not that hard once you know the trick.

And for people that actually remember like DVDs

and scratches on them, how frustrating it is.

That’s a brilliant metaphor for aging.

And then the reader is the thing that skips

and then it could destroy your experience,

the richness of the experience that is listening

to your favorite song.

Right, but in biology, it’s even worse

because you’ll lose your memory, your kidneys will fail,

you’ll get diabetes, your heart will fail.

And we call that aging and age related diseases.

So most people forget that diseases that we get

when we get old are 80 to 90% caused by aging.

And we’ve been trying to fix things with band aids

after they occur without even generally talking

about the root cause of the problem.

Is there the scratches, do those come from,

are those programmed or are they failures?

Meaning is it, so if it’s by design,

then there’s like a encoded timeline schedule

that the body’s just on purpose,

degrading the whole thing.

And then there’s the just the wear and tear

of like the scratches on a disc that happen through time.

Which one is it that’s the source of aging?

It’s more akin to wear and tear, there isn’t a program.

Getting back to evolution, there’s no selection for aging.

We’re not designed to age, we just live as long as we need

to and then we’re at the whim of entropy, basically.

Second law of thermodynamics, stuff falls apart.

We live a bit longer than age 40,

only because there are robust, resilient systems,

but eventually they fail as well.

Current limit to the human lifespan

where they completely fail is 122.

But I don’t like to think of it as wear and tear

because there’s two aspects to it.

There’s a system that’s built to keep us alive

when we’re young, but actually goes,

comes back to bite us as we get older.

And we call this issue antagonistic pleiotropy.

What’s good for you when you’re young

can cause problems when you’re older.

So we’ve been looking, what is the main causes of the noise?

And we’ve found two of them definitively.

The first one is broken chromosomes.

When a chromosome breaks, the cell has to panic

because that’s either gonna cause a cancer or kill the cell.

There’s only two outcomes, it’s pretty much a problem.

And so what the cell does is it reorganizes the epigenome

in a massive way.

What that leads to is, think of it as a tennis match

or a ping pong game.

The proteins are the balls

and they now leave where they should be,

which is regulating the genes that make the cell type,

whatever it is.

And they have a dual function,

they actually go to the break,

the chromosome will break and fix that.

And then they come back.

You might ask, well, why is it set up that way?

Well, it’s a beautiful system,

it coordinates gene expression,

the control systems with the repair.

You want them coordinated.

Problem is, as we get older, this ping pong game,

some of the balls get lost.

They don’t come back to where they originally started.

And that’s what we think is the main noise for aging.

And we’ve also, the other cause of aging that we found

is cell stress, we damage nerves and they age rapidly.

So that’s the other issue.

There’s probably others, smoking chemicals, for example,

we know accelerates biological age pretty dramatically.

But the question is, can you slow that down

or can you reset them to get those ping pong balls

to go back to where they originally started in the game?

And we think we’ve found a way to do that.

Can you give me hints?

Whose fault is it in the balls not coming back?

Is it the proteins themselves?

Like are they starting?

Again, I’ve been obsessed with the protein folding problem

from the AI perspective.

So is it the proteins or is it something else?

Well, we know who hits the balls and recruits them.

So that the break is recognized by the cell.

It’s recognized by proteins who send out a signal

through phosphorylation is typical way cells talk

to other proteins.

And that recruits those repair factors,

those ping pong balls to the break.

So the cells actively doing this to try and help itself,

but we don’t know who’s to blame for them not coming back.

That could just be a flaw in the quote unquote design.

I don’t think that there’s something saying,

well, 1% of you balls proteins never go back.

I just think it’s hard to reset a system

that’s constantly changing.

We have in our bodies close to a trillion DNA breaks

every day.

And imagine that over 80 years,

what damage that does to our epigenomic information.

Now we know that this is, well,

we never know anything in biology,

but we have strong evidence that this is true

because we can mess with animals.

We can create DNA breaks and tickle them

with a few breaks, maybe raise it by threefold

over background levels of normal breakage.

And if we’re right, those mice should get old.

And they do.

We can actually, we’ve created these breaks

in a way that’s titratable.

We can, it’s like a rheostat.

We can send it to 11.

I drove my Tesla here, I’m a big fan of a spinal tap too,

going to 11.

If we go to 11, we can make a mouse old

in a matter of months.

We prefer to go to a level of about four

and it gets old in 10 months.

But it’s definitely old.

It’s got all of the hallmarks of aging.

It’s got diseases.

It looks old.

Its skin is old.

It’s got gray hair.

But importantly, we can now measure age

by looking at the scratches.

We can look at the epigenome, we can measure it

and use machine learning to give us a number.

And those mice are 50% older than normal.

So you can replicate the aging process in a controlled way.

You can, I mean, in a way that, I mean,

you could accelerate it in a controlled way

and measure how much exactly it’s aging.

And that gives you step one of a two step process

to when you can then figure out,

how can we reverse this?

And now we’re reversing those mice.

Is there a good, I love what you said.

I mean, in biology, you really don’t know.

It’s such a beautiful mess.

Is there ideas how to do that?

Is that on the genetic engineering level?

Is it like, what can you mess with?

Is it going to the, trying to discover the backup copies

and restoring from them?

Like what’s, if it’s possible to convert it

to natural language words, what are the ideas here?

What is the observer and how do we contact it?


What’s the observer and how do you contact?

Or if there’s other ideas, how to reverse

the balls getting lost process.

Yeah, well, you can slow it down.

Slow it.

But we found a reset switch recently.

We just published this in the December 2020 issue of Nature.

And what we found is that there were three embryonic genes

that we could put into the adult animal

to reset the age of the tissues.

And it only takes four to eight weeks to work well.

And we can take a blind mouse

that’s lost its vision due to aging.

Neurons aren’t working well towards the brain.

Reset those neurons back to a younger age.

And now the mice can see again.

These three genes are famous actually

because they’re a set of four genes

discovered by Shinya Yamanaka,

who won the Nobel Prize in 2016

for discovering that those four genes

when turned on at high levels in adult cells

can generate stem cells.

And this is, I think, well known now

that we can create stem cells from adult tissue.

But what wasn’t known is can you partially take age back

without becoming a tumor

or generating a stem cell in the eye,

which would be a disaster?

And the answer is yes.

There is a system in the body

that can take the age of a cell back to a certain point,

but no further, safely, and reset the age.

And we’re now using that to reset the age of the brain

of those mice that we aged prematurely.

And they’re getting their ability to learn back.

This is really exciting, right?

Like what’s the downside of this?

Well, the downside is if you overdo it

and you don’t get it right, you might cause tumors.

But we do it very carefully.

And we also know that in the eye, it’s very safe.

We also injected these, we deliver them by viruses.

So we can control where and when they get turned on.

And in this paper, we’ve published

that if we put high levels in the mouse,

into their veins, throughout the body,

they don’t get cancer for over a year.

So I’m so optimistic that we’re going into human studies

in less than two years from now.

Is there a place where AI can help?

Sorry to inject one of the things

I’m very excited about and passionate about.

So Google DeepMind recently had a big breakthrough

with AlphaFold2, but also AlphaFold two years ago,

with achieving sort of a state of the art performance

on the protein folding problem, single protein folding.

But it also paints a hopeful picture

of what’s possible to do in terms of simulating

the folding of proteins,

but also simulating biological systems through AI.

Is there something to you, combined with this brilliant work

on the biology side that you’re hopeful about

where AI can be a tool to help?

Where isn’t it a tool?

I mean, if you’re not using AI right now in biology,

you’re getting less and less likely

to be left behind in biology, you’re getting left behind.

We use it all the time.

We’re using it to generate these biological clocks

to be able to read those scratches.

We’re using it to predict the folding of proteins

so we can target molecules and modulate their activity.

We’re using it to assemble genomes of different species.

What else?

We use it to predict the longevity of a mouse

based on how it reacts to certain things,

hearing, eyesight, generally frailty.

We just put out a paper last year on that.

The other thing we can use it for,

which is a little off the track here,

but we use it for predicting

which microorganisms are in your body,

actually not predicting, telling you.

So our daughter, Natalie, was infected with Lyme disease

a few years ago, almost went blind from it.

And the test took four days.

And I thought, just give me the DNA from her spinal fluid.

I’ll go tell you what’s in it.

If it’s Lyme disease or not, they refused.

And so at that point I said, this has to be done better.

So I’ve started a company that now can take a sample

of any part of your body.

It’s typically done now with liver transplant patients

to detect viruses that come out of their organs.

But that’s another area that AI is extremely important for.

I think if you’re not, in five years,

if you’re not using deep learning, you’ve got a problem.

Because the amount of data that we generate now

as biologists is just terabytes.

It can be terabytes per week.

It’ll eventually be terabytes per day.

And then we just go from there.

And I actually have trouble recruiting enough


A lot of our work is now just number crunching.

A part of that is collecting the data,

which is kind of something we’ve talked a little bit about.

But is there something you can say about

how we can collect more and more data,

not just on the one person level,

like for you to understand your various markers,

but to create huge datasets

to understand how we can detect certain pathogens,

detect certain properties, characteristics

of whether it’s aging or all the other ways

that the human body can fail.

It seems like with biology,

there’s a kind of privacy concerns that,

well, actually not privacy concerns,

it’s almost like regulation that kind of prevents

hospitals from sharing data.

I’m not sure exactly how to say it,

but it seems like when you look at autonomous vehicles,

people are much more willing to share data.

When you look at human biology system,

people are much less willing to share data.

Is there a hopeful path forward

where we can share more and more data at a large scale

that ultimately ends up helping us understand

the human body and then treat problems with the human body?

So we are right in the middle,

we’re living through what’s gonna be seen

as one of the biggest revolutions in human health,

through the gathering of data about our bodies.

And 20 years ago, people didn’t wanna go on social media,

they’re worried about it, now you have to,

if you’re a kid, that’s for sure.

Same with medical records,

these are becoming all digitized and expanded.

Ultimately, we’re going to, even if we don’t want to,

have to be monitored.

There’s gonna be a court case that,

I bet two, three years from now, someone’s gonna say,

how come my father died from a heart attack?

You had these biosensors, 20 bucks, and you didn’t use it.

Lawsuit right there, and suddenly,

all hospitals have to give you one of these.

There’ll be a reversal, like to where,

it’s your fault if you don’t collect the data,

that’s brilliant, and that’s absolutely right.

I mean, that’s absolutely right.

That’s the frustration I feel on going to the doctor,

is like, it’s almost negligent to not collect the data,

because you’re making,

there’s something really wrong with me,

and you’re making decisions based on very few tests,

that’s almost negligent, when you have the opportunity

to collect a huge amount more data.

Well, let me tell you something.

Like, I’ve got this inside tracker data

for myself over a decade,

and you’d think my doctor would roll his eyes at this,

oh, he’s gone to a consumer company, blah, blah, blah.

I had my first checkup in a year with him

through video conference, and he was running blind.

He really didn’t know what was going on with me.

He asked the usual things.

How am I sleeping?

How am I eating?

These kind of usual things.

And I said, well, I’ve got new tests back

from inside tracker, and he said, great,

I’d love to see them.

So I share screen, and we look at the graphs,

look at the data, and he’s loving it,

because he cannot order these tests willy nilly.

So I said, well, let’s order a HbA1c blood glucose levels,

because I’m very interested in that.

That tracks with longevity.

And he said, well, I have no reason to order that.

Do you have a family history?


Do you have any symptoms of diabetes?


Well, I can’t order the test.

I almost wanted to reach through the computer

and strangle him, but instead, I pay a little bit

to get these tests done, and then he looks at them.

So that’s now the way consumer health is going,

is that you can get better data than your doctor can,

but they’d like you to do that.

Quick human question, maybe you can educate me.

I think doctors sometimes have a bit of an ego.

I understand that the doctors super experience

a lot of things, but this is a fundamental question

of human variability.

Like, I know a lot of specific details about like,

I mean, it depends, of course, what we’re talking about,

but I bring a lot of knowledge, and if I have data with me,

then I have like several orders of magnitude more knowledge.

And I think there’s an aspect to it where the doctor

has to put their expert hat, like take it off

and actually be a curious, open minded person

and study and look at that data.

Do you think it’s possible to sort of change the culture

of the medical system to where the doctors are almost,

as you said, are excited to see the data?

Or is that already happening?

It’s really happening.

Now, we’ve probably lost the last generation.

They’re no hopers, but so I teach at Harvard Medical School

and they’re excited about this.

They’re excited about aging,

which is a new aspect to medicine.

Oh, wow, we can do something about that.

And then, yeah, all this data, what do we do with it?

There’s still the traditional pathology and all that stuff,

which they need to know, but time will change their mindset.

I’m not worried about that.

And like we were discussing, this isn’t a question of if,

it’s just a matter of when.

And I have a front row seat on all of this.

I had breakfast with a CEO who is making this happen

just yesterday.

I can tell you for sure that most people have no idea

that this revolution is occurring

and is happening so quickly.

If you’re running a hospital and you can save $2,000

per cardiac patient, what are you going to do?

You have to use it.

Otherwise, the hospital down the road

is going to be beating you.

And there are large hospital aggregations,

so there’s Ascension and others,

that just have to go this way for budgetary reasons.

And right now, the US spends 17% of their GDP on healthcare.

Let’s say one of these buttons on my chest costs $20.

It’s rechargeable.

And it can predict people’s health

and save on antibiotics to prevent heart attacks.

How many billions, if not trillions of dollars,

will that save over the next decade?

Yeah, so when the public wakes up to this,

they’ll almost demand it.

Like, this should be accepted everywhere.

This is obvious.

It’s going to save a lot of money.

It’s going to improve the quality of life.

Well, and the CFOs of hospital groups will have to.

And insurance companies are going to want to get in on this.

So now that gets to privacy, right?

Should an insurance company have access to your data?

I would say no.

But you could voluntarily show them some of it

if they give you a discount.

And that’s also being worked on right now.

I hope we do create kind of systems

where I can volunteer to share my data

and I can also take the data back,

meaning like delete the data, request deletion of data.

And then maybe policy creates rules

to where you can share data, you could delete the data.

And I think if I have the option to delete all my data

that a particular company has,

then I’ll share my data with everyone.

I feel like if, because that gives me the tools

to be a consumer, an intelligent consumer,

of awarding my data to a company that deserves it

and taking it back when the company is misbehaving.

And in that way, encourage,

as a consumer in the capitalist system,

encourage the companies that are doing great work

with that data.

Well, yeah, healthcare data security is number one.

On my mind, InsideTracker made sure that that was true.

But these buttons on your chest,

there’s very private stuff they can probably tell

if you’re having sex one night, right?

So this is not the kind of stuff you want leaked.

So I don’t know whether it’s blockchain or something.

Speak for yourself.

I want this public.

The live stream.

I guess it depends on how you go.

But there’s a lot of stuff you don’t want out there.

And this definitely has to be number one

because it’s one thing to have your credit card

information stolen, it’s another thing

your health records are permanently out there.


So there’s, on the biology side,

super exciting ways to slow aging.

But there’s also on the lifestyle side.

I recently did a 72 hour fast.

It’s just an opportunity to take a pause

and appreciate life.

Think about, there’s something about fasting

that encourages you to reflect deeper

than you otherwise might.

The time kind of slows.

And you also realize that you’re human

because your body needs food.

And you start to see your body’s almost as a machine

that takes food and produces thoughts.

And then ends briefly.

I mean, you start to, depending who you are,

if you’re like engineering minded,

you start to think of this whole thing

as a kind of, yeah, as a machine.

And then also feelings fill this machine.

Feelings of gratitude, of love,

but also the uglier things of jealousy

and greed and hate and all those kinds of things.

You start to think, okay, how do I manage this body

to create a rich experience?

All of that comes from fasting for me.

Anyway, but there’s also health benefits to fasting.

I intermittent fast a lot.

I eat just one meal a day most of the time.

Is there something you could say

about the benefits of fasting in your own life

and in general the anti aging process?

Well, you’re a philosopher too.

Sorry, I apologize.

No, I’m impressed.

True Renaissance man.

It’s a joy to be here.

So when it comes to fasting, this is,

being abstemious is one of the oldest ways

to improve health.

Probably they knew this 5,000 plus years ago.

So that’s not new.

But what we’re figuring out is what is optimal

and how does it work?

And one of the things we help contribute to,

which I can speak to with some authority

is that these longevity genes we work on,

we showed back in the early 2000s

are turned on by fasting.

And at least in yeast, we were the first to show

that how calorie restriction fasting works

to extend lifespan.

And that was the first for any species.

Something similar happens in our bodies.

When we’re hungry or put our bodies

under any other perceived adversity,

such as running, our bodies think,

wow, we’re getting chased by a saber tooth cat or something.

If we’re really hot or cold, these probably also work.

To put our bodies in this defensive state,

to activate these genes in the way that whales do

and mice don’t.

And so hunger is the best way to do that.

In fact, I don’t think you have to feel hungry.

You can get used to it.

But if there was one thing I would recommend

to anybody to slow down aging

would be to skip a meal or two a day.

Now it doesn’t mean you don’t have to live well.

You can go out.

I go to restaurants, I eat regular food.

I try to be as healthy as possible.

But I’ve gone from skipping breakfast most of my life

now just skipping lunch as well.

And I have my physique back that I had when I was 20.

I feel 20 mentally.

I’m much sharper.

I don’t feel tired anymore.

I sleep well.

So I’m a huge fan of the one meal a day thing.

Where I’m not good at is going beyond one day.

But if you do three days.

Have you ever fasted longer than 24 hours?

I tried doing two days.

I might have made it to the third and given up.

I just find that I’m not very,

I don’t have a lot of willpower.

I also hate exercise.

So I’m not sure how long I’m gonna live.

But I’ve managed to do one meal a day.

So if I can do that, seriously, anybody can do that.

To your listeners and viewers, I would say,

don’t try to do it all at once.

You can’t go from snacking and eating three meals a day

to what I do easily.

Work your way up to it, but also compensate with drinking.

If you like tea, if you like coffee, put some milk in it.

That’s fine.

You can fill your stomach up with liquids,

diet sodas, I get criticized for drinking,

but I’m gonna continue to have those.

But then I power through the day.

I definitely don’t feel tired.

I don’t have a lag anymore.

But also give it at least two weeks

because there’s a habit as well.

Having something in your mouth, chewing,

feeling that fullness, you can break that habit.

And within two, three weeks, you’ll have done it.


So I’m not actually even that strict about it.

You said diet soda.

Yeah, people are very kind of weirdly strict

about fasting, the rules in fasting.

Like for example, I drank Element electrolytes

when I was fasting, and that has like five calories.

And so technically it’s not fasting.

Or people will say like, if you drink coffee,

there’s caffeine, and they’ll say

that’s technically not fasting

because there’s some kind of biological effects

of caffeine, but whatever.

Of course, there’s like biological benefits

that you can argue about,

but there’s also just experiential benefits.

Just calorie restriction broadly has a certain experience

to it that, like for me personally,

just as you said, has made me feel really good.

That said, especially, I’ve gained quite a bit of weight,

maybe even like 15 pounds, something like that,

since I moved to Austin, Texas.

And I still keep the same diet,

but I eat a lot of meat in that one,

just because it’s delicious,

because it’s also the amazing people I met in Texas.

It’s just there’s like a camaraderie,

a friendship, a love to the people

that like makes you really enjoy

the atmosphere of eating the brisket and the meat.

Is this Joe Rogan insisting?

Joe is, I mean, he’s very different.

Joe loves bread and pasta.

Like he knows that his body feels best

doing keto or carnivore.

So that’s what he usually tries to stick to,

but he also does not hold back,

and he’ll just eat pasta when he eats pasta,

and he sort of enjoys life in that way.

I can’t, I don’t know how to enjoy life in that way.

I also love pasta, but I’m just not going to enjoy it,

because I know my body ultimately

does not feel good with pasta.

So it’s a funny kind of dichotomies.

I would like to cheat, I guess,

by eating more meat than I, you know, like overeating

on the things that I know my body feels good on

as opposed to eating stuff I shouldn’t,

like cake and all those kinds of things.

I tend to find happiness in overeating the good stuff

versus eating the bad stuff.

And that’s the kind of balance.

Him, he’s like, fuck it.

Every once in a while, you gotta enjoy it.

And then also coupled with that for him

is just exercise, like then face his demons the next day

and just like burn a huge amount of calories,

which is, I mean, whatever’s up with that guy’s mind,

there’s an, there’s a ability to fully experience life,

which is represented by the pasta,

and the ability to just like fight the demons,

which is represented by all the crazy kettle balls

and running the hills and all this kind of stuff

that he does.

That takes a lot out of you doing

that kind of insane exercise.

And I think I’m more like you,

or at least towards your direction is like,

I really hate exercise.

So I do it, but I really hate it.

And so it’s a balance that you have to strike.

Is there something you could say about the diet side of that

for you personally, but in general,

in order to achieve calorie restriction,

like for me, eating, I know it may not sound healthy,

but eating carnivore, eating mostly meat

has been, has made me feel really good,

both mentally and physically.

Is there something you could say about the kinds of diets

that may improve longevity,

but also enable calorie restriction?

Well, sure.

I mean, the first thing that’s important to know

is that while many people are interested slash obsessed

with what they eat,

the data that’s come out of animal studies at least

is it’s far more important when you eat than what you eat.

And this was a fantastic study a few years ago

by my friend, Rafael de Cabo

at the National Institutes of Health in Bethesda.

And he had 10,000 mice on different diets,

hoping to find the perfect mix of carbs, protein, and fat.

And it turns out that the only ones that lived longer

are the ones that only ate once a day.

And so that, if we’re not mice,

but I think that we’re close enough to mice

that this tells us a lot.

But okay, but I still think the best bang

for the longevity buck is to do both well,

eat less often and eat the right things.

Now I’ll preface this to say, I’m not a nut about this.

I will eat occasional, very occasionally a dessert.

Usually I steal from others, which doesn’t count, right?


But you gotta live life, right?

What’s a long life if it’s not enjoyable anyway?

But what I also found, and this is,

I’ll get to your question in a second,

but my microbiome right now and stomach is at a point

where if I try to overeat on a steak,

which I did a couple of days ago,

I actually had a chicken, a fried chicken specifically,

for two days, I felt terrible.

I couldn’t sleep, it wouldn’t go down.

So I’m now at a point where even if I want to binge

on meat and fried foods, I just can’t, it just feels bad.

But what do I recommend?

Well, what the data says, which I try to follow,

is that plant based foods will be better

than meat based foods.

And I know that there are a lot of people who disagree.

But one of the facts is, well, there’s a few facts.

One is that people who live a long time

tend to eat those type of diets.

Mediterranean, Okinawa diet,

they’re eating mostly plants with a little bit of meat

and not a lot of red meat.

And the other fact is that in animals we know

that there’s a mechanism that’s called mTOR,

little m, capital TOR, that responds to certain amino acids

that are found in more abundance in meat.

And when it responds, it actually shortens lifespan.

And the converse, if you starve it

of those three amino acids, mostly in meat,

then it extends lifespan.

And there’s a drug called rapamycin,

which some people are experimenting with, that does that.

So you might be able to, I’m just saying this here

from all my colleagues, we don’t know the results here,

but you could potentially take a rapamycin like drug

and counteract the effects of meat in the long run.

Dono, we should try that actually,

we could do that in the lab.

But getting to the bottom of this,

what I think is going on is that

just like testosterone and growth hormone,

you will get temporary, maybe not temporary,

immediate health benefits.

You’ll feel great, you’ll get more muscle energy.

But the problem is I think it’s at the expense

of longterm health and longevity.

Well, this is actually something I worry about

in terms of longterm effects or the cost

in terms of longevity.

It’s very difficult to know how your choices

affect your longevity because the impact is down the line.

Like just because something makes me feel good now,

like eating only meat makes me feel good now,

I wonder what are the costs down the line.

Well, think about what I was saying about the trade offs

between growth and reproduction,

which is what a mouse does and a whale

that grows slowly, reproduces slowly, lives a long time.

It’s called the disposable soma theory.

Koch would just propose that in the 70s.

What meat probably does is put you in the mouse category,

super fertile, grow fast, heal fast.

And then if you wanna be a whale,

you should restrict meat and do things

that promote the preservation of your body.

Is it difficult to eat a plant based diet

that you perform well under?

So mentally and physically, just almost,

I’m asking almost like an anecdotal question

or unless you know the science.

Well, the science is still being worked out,

but from the synthesis of everything that I’ve read,

I try to eat a diet that’s definitely full of leafy greens,

particularly spinach is great

because it’s got the iron that we need, plenty of vitamins.

I also try to avoid too much fruit and berries,

particularly fruit juice,

definitely avoid that sugar high.

Spiking your sugar is not healthy in the long run.

The other thing that’s interesting

is we discovered what we called xenohormetic molecules.

Let me unpack that because it’s a terrible name

and I take full responsibility

with my friend, Conrad Howards.

The Xeno means cross species

and hormesis is the term that what doesn’t kill you

makes you live longer and be healthier.

And so we’re getting cross species health improvements

by molecules that plants make.

And plants make these molecules

when they’re also under adversity or perceived adversity.

For instance, I understand

if you want really healthy, good oranges,

you can drive nails into the bark of the tree

before you harvest.

Same with wine, you typically want them to be dry

before you harvest or covered in fungus.

And that’s because these plants make these colorful

and xenohormetic molecules

that make themselves stress resistant,

turn on their sirtuin defenses, the serogenes remember.

And when we eat them, we get those same benefits.

That’s the idea and we’ve evolved to do so.

This isn’t a coincidence.

It’s my theory, our theory that we want to know

when our food supply is under adversity

because we need to get ready for a famine.

And so we hunker down and preserve our body

and by eating these colored foods,

so practically speaking, if it’s full of color

or if there’s been some chewing by a caterpillar,

organic, grown locally in local farms,

I’ll eat that versus a watery, insipid, light colored lettuce

that’s been grown in California.

So you want vegetables that have suffered.

You want the David Goggins as a vegetables.

That’s the xenohormetic molecules.

I love that term.

I’m gonna take that one with me, thank you.


Oh, I follow him on Instagram, he’s always screaming.

So you want that he’s basically

the xenohormetic version of a human.

I like it.

So these are the molecules that are representative

of the stress that a plant has been under.

Yeah, the best example of that is resveratrol,

which many people, including myself,

take as a supplement.

Grapes, grapevines produce that in abundance

when they’re dried out or they have too much light

or fungus and that we’ve shown activates

the Sertu enzyme in our bodies,

which remember is what extends lifespan in yeast

and slows down aging in the brain.

That’s beautiful.

Yeah, I tend to avoid fruit as well.

So green, veggies, anything that’s not very sweet.

So I would just say you’re relatively low,

like you try to avoid sugary things as well.

Yeah, I’m fairly militant about that.

I rarely would add sugar to anything.

Occasionally I would eat a slice of cheesecake,

but that would be maybe once or twice a year.

You have to give in occasionally.

But yeah, anything that’s sweet,

I would rather substitute something like Stevia

if I need a sugar hit.

What about exercise?

Your favorite topic.

Is there a part?

I don’t mind talking about it.

Okay, great.

Is there benefits to longevity from exercise?

Well, no doubt, that’s proven.

Just like fasting, it’s pretty clear that that works.

For example, there are studies of cyclists.

It was something like people that cycle

over 80 miles a week have a 40% reduction

in a variety of diseases, certainly heart disease.

So that’s not even a question,

but what’s interesting is that we’re learning

that you don’t need much to have a big benefit.

It’s an asymptotic curve.

And in fact, if you overdo it,

you probably have reduced benefits,

particularly if you start to wear out joints,

that kind of thing.

But just 10 minutes on a treadmill a few times a week,

lose your breath, get hypoxic, as it’s called,

seems to be very beneficial for longterm health.

And that’s the kind of exercise that I like to do, aerobic.

Though I do enjoy lifting weights,

so that is what I call my exercise,

which has other benefits,

including maintaining hormone levels, male hormone levels.

But also really why I do it is I want to be able

to counteract the effects of sitting for most of the day.

And as you get older, you lose muscle mass.

It’s a percent or so a year.

And I don’t wanna be frail when I’m older

and fall over and break my hip,

which happens every 20 seconds in this country.

So maintaining that strength,

but also doing the cardio for the longevity,

for avoiding the heart disease.

Yeah, I definitely, just like with fasting,

have the philosophical benefit of running long

and running slow.

I enjoy it, because it kind of clears the mind

and allows you to think,

and actually listen to brown noise as I run.

It really helps remove myself from the world

and just like zoom in on particular thoughts.

What are these brown noise?

It’s like white noise, but deeper.

So like the white noise is like shh,

and then brown noise is more like,

shh, like ocean.

That sounds great.

I might try that.

Yeah, yeah, it’s more soothing probably.

I’m not sure.

There could be science to this.

I need to look this up.

I’ve been meaning to.

But when I started,

this is maybe like five years ago,

I started listening to brown noise when I work.

And the first time I listened to it,

something happened to my mind

where it just went like zoomed in

to like, in a way that it felt like really weird.

Like how precisely it was able to sort of

remove the distractions of the world

and really help my mind.

Obviously, like the mind is trying to focus

and then it just enabled that process

of trying to focus on a particular problem.

I don’t know if this is generalizable to others.

People should definitely try it

if you’re listening to this.

Maybe it’s just my own mind,

but it’s funny, like it made me,

brown noise made me realize

that there’s probably hacks out there

that work for me

that I should be constantly looking for.

It’s almost like an encouraging

and motivating event

that maybe there’s other stuff out there.

Maybe there’s other brown noise like things out there

that truly like almost immediately make me feel better.

I don’t know if it’s generalizable to others,

but it does seem that it’s the case

that there’s probably for many others,

things like that that could be discovered.

And so it’s always disappointing

when I find things in life

that I wish I would have found earlier.

I got LASIK eye surgery a few years ago

and the first thought I had like the next day

when I woke up is like,

damn it, why didn’t I do this way earlier?

There’s all this stuff of that nature

that are yet to be discovered.

So it pays to explore.

You have a different mind, you have quite a beautiful mind.

So I suspect brown noise helps you focus

and cause you’re probably all over the place

if you don’t control it.

Yeah, exactly.

It means something about it.

It’s a programmer thing.

I don’t, programming is a really difficult mental journey

cause you have to keep a lot of things in mind.

You have to, so you’re constantly designing things

then you have to be extremely precise

by making those things concrete in code.

You also have to look stuff up on the internet

to sort of feed like information

and looking up stuff on the internet,

internet is full of like distracting things.

So you have to be really focused

in the way you look stuff up in pulling that information in.

So it requires a certain discipline and a certain focus

that I’ve been very much exploring how to do.

Like I do it really well in the morning,

coffee is involved, all those kinds of things.

You’re trying to optimize, keeping very positive inspired,

no social media, all those kinds of things

and trying to optimize for.

And everybody has their own kind of little journey

that they try to understand.

You get this from like writers

when you read about the habits of writers,

like the habits they do in the morning,

they usually write like two, three, four hours a day

and that’s it.

It’s like they optimize that ritual.

And then there’s always Hunter S. Thompson.

So sometimes it pays off to be wild.

What about sleep?

How important is sleep for longevity?

I would guess based on the evidence

that it’s really important

and because we don’t know for sure.

But what we know from animal studies is the following.

If you restrict sleep from a rat for just two weeks,

it’ll develop type two diabetes.

It’s that important.

So that’s the main thing.

What we also know is at the molecular level

that if you disrupt your sleep wake cycle,

so we actually have proteins that go up and down

that control our sleep wake.

All of us, most of our cells do that.

If you disrupt that, you’ll get premature aging.

And guess what?

The opposite is true.

That as you get older, that cycle,

the amplitude becomes diminished.

And this is why it’s harder to get to sleep

as you get older

and you’ve got all sorts of problems.

And I think what’s going on is this positive feedback loop,

which is a disaster in your old age,

which is you’re aging,

you can’t at this moment totally prevent that.

And then it’s disrupting your sleep

and you get not enough sleep

and then that’s gonna accelerate your aging process.

And so it’s known that the people who are shift workers

are most susceptible to certain age related diseases.

So your bottom line, you definitely wanna work on that.

It’s one of the reasons I have this ring on my finger,

which helps me optimize my sleep

and learn what I do the day before,

if it was a bad idea and I’ll stop doing that,

like eating a fried chicken.

I see you’re still carrying the burdens of that decision.

But yeah, sleep is one of those things

that’s making me wonder about the variability

between humans a little bit

and how science is often focused on,

like it’s not often focused on high performers

in a particular way.

And it’s looking at the aggregate

versus the individual cases.

For example, like for me,

I don’t know what the exact hours are,

but like power naps are incredible.

I tend to look at the metric of stress and happiness and joy

and try to optimize those.

So decreasing stress, increasing happiness

and using sleep as just one of the tools to do that.

Because like hitting the five, six, seven, eight,

nine hour mark or whatever the correct mark is,

I find that to be stress inducing for me

versus stress relieving.

Like thinking about that,

I feel best if I sleep sometimes for eight hours,

sometimes for four hours and then power nap.

And as long as I have a stupid private,

usually smile on my face,

that’s when I’m doing good,

as opposed to getting a perfect amount of sleep

according to whatever the latest blog post is.

And I also pull all nighters still.

I also think there’s something about the body,

like as long as you do it regularly,

it’s not as stress inducing.

Like you know what it is.

The reason I pull all nighters isn’t for like,

I’m playing Diablo three or something,

is because I’m doing something I’m truly passionate about.

Well, like I’m also love video games,

but I’m doing something I’m truly passionate about.

And it’s almost like there’s the Jocko Willing feeling

of when I’m up at 7 a.m. and I haven’t slept all night

and still I’m working on it.

There’s a kind of a celebration of the human spirit

that I really enjoy it.

Like, and that’s happiness.

And to sort of then,

and I usually don’t tell that kind of stuff to people

because their first statement will be like,

you should get more sleep.

It’s like, no, I’m doing stuff I love.

You should get more love in your life, bro.

That’s right.

So, but that said, in aggregate,

when you look at the full span of life,

is probably you should be getting

a consistent amount of sleep.

And it seems like it’s in that seven, eight hour range.

Yeah, but it’s similar to food.

It’s the quality, not the quantity, right?

And when you get it.

So I look at my data pretty often.

And what makes a difference to me is not the amount of hours,

but the quality, the depth and the deep sleep

is what will do it.

So if I have a lot of alcohol before going to sleep

and I can see my heart rate being different,

but what really kills me is that I don’t get a lot

of that deep sleep and I wake up barely remembering stuff.

So that, like you say, if you’re happy and contented

and you don’t have these cortisol chemicals

going through your body,

you will more naturally get into that deep state.

And even if you just get four hours,

way better than eight hours of none of that.

Yeah, yeah, that’s beautiful.

And some of that could be genetic.

For me, I just, I fall asleep like this.

If you want me to fall asleep right now, I can do it.

It’s no, I have no problem with it.

Combined with coffee, I just had two energy drinks.

I can probably sleep.

So that, I don’t know if that’s genetics

or it’s kind of, I don’t know what it is.

Or maybe that I don’t have kids and I’m single.

So I don’t have, I’m almost listening

to some kind of biological signal versus societal signal

on when I’m supposed to go to sleep.

So I just go to sleep whenever I feel like going to sleep.

Well, that’s because you’re a self employed.

Self employed.

Most people don’t have that luxury,

but we’re lucky, the two of us,

that we can make our own hours.


But yeah, it’s super important.

And those people who have shift work,

I mean, they really need to change the way that works

because they’re literally killing those people.

Is there something you could say about the,

the mind and stress in terms of effect on longevity?

Sort of, I don’t know if you think about it this way,

but when you talk about the biological machine,

it’s always these mechanisms that don’t,

are not necessarily directly connected to the brain

or the operation of the brain.

Like what’s the role about stress and happiness

and yeah, the sort of higher cognitive things

going on in the brain on longevity.


Well, that’s a great point that the brain

is the center for longevity.

Actually, we do know that.

For a start, when I’m stressed,

I can see mentally stressed,

then I can see it in my body.

Heart rate, hormones, it’s clear.

That’s no true surprise.

So you’ve got to work on your brain first and foremost.

If you are totally freaked out, agitated all the time,

you will live shorter.

I’m certain of it.

You know, I keep fish.

I’m a big aquarium guy.

And you can see the difference

between the fish that’s having a good time and dominant

and one that gets picked on.

It just looks like crap.

You don’t want to be that,

the little fish getting picked on if you can help it.

So I used to be extremely stressed as a kid.

I was a perfectionist, very shy,

always worried about being a failure.

If I didn’t get an A+, you know,

I was crying in my bedroom, that kind of sad existence.

I got into my twenties, then in my thirties,

and realized that’s not the way to live.

So I’ve worked very hard to get to this point

where I almost never get stressed, never.

There’s nothing that, I’ve never gotten angry in my lab.

I’ve got 20 kids.

Sometimes it’s like a,

most of the time it’s like a kindergarten.

I haven’t lost my temper.

I’m very calm, but that’s intentional.

And I don’t worry about stuff.

Millions of dollars, billions of dollars at stake sometimes.

Keep it cool.

It’s only life.

We’re all headed to the same place anyway.

Don’t worry about it.

But to answer your question, I think in a better way,

if you manipulate the brain of an animal,

I’ll give you an example.

If we turn on this CERT gene that I mentioned,

CERT1, we, a good friend of mine at WashU,

Sheena Mai did this.

They upregulated that gene

just in the neurons of the animal.

It lived longer.

So that’s sufficient to extend lifespan.

We also know that you can manipulate the part of the brain

called the hypothalamus,

which leeches a lot of chemicals into the body and proteins,

most of which we don’t know yet,

but just changing the inflammation of that little organ

or part of the brain is sufficient

to make animals live longer as well.

So get your brain in order first

before you tackle anything else, I would say.

So you kind of mentioned this,

with the inside tracker, there’s ability

to take blood measurement and then infer from that

a bunch of different things about your body

and how you can improve the longevity.

And you’ve also mentioned saliva

and more efficient ways to get data.

What does that involve?

What’s the future of data collection look like

for the human biological system?

Right, well, yeah, the issue with blood is

you need someone to take it.

I mean, or you prick your finger, which hurts.

So you’ve got to have something better.

So I think what the future looks like

is that you’ll spit onto a little piece of paper

and stick it in a machine and it’ll do that for you.

But we’re not there yet.

So the intermediate future that I’m building right now

is that you would take a swab of the inside of your mouth,

which is the easiest way to take cells out of your body

and just ship them off.

Okay, so it’s called a buckle swab.

I think we became very used to that.

Right now, because of COVID,

people don’t like going to the doctor as much.

They don’t like going out.

They just want to have home tests.

And so that I think is the next 10 years

where you’ll get a kit in the mail,

you’ll swab your cheeks, stick it back in an envelope,

send it off and a week later you have

either a doctor’s report or a health recommendation.

And what can you get off a cheek swab?

Well, you can get anything.

You can get hormones, stress levels,

stress hormones, blood glucose levels.

You can also tell your age reasonably accurately doing that,

actually quite accurately.

And those clocks can not just tell you

how you’re doing over time,

but can be used to give you recommendations

to slow that process down.

Cause some people sometimes are 10 years older biologically

than their actual chronological age.

I mean, why does it matter how many times

the earth’s gone around the sun seriously?

Who cares about birthdays?

It’s how long your body’s clock has been ticking

and how fast.

So I could take a cheek swab from you today, Lex,

take it back to my lab.

And we then by tomorrow tell you

how old you are biologically based on

what we call the epigenetic clock.

And you might be freaked out, you might be happy,

but either way we can advise you

on how to improve the trajectory.

Cause we know that smoking increases

the speed of that clock.

We also know that fasting and people who eat the right foods

have a slower clock.

Without that knowledge, you’re flying blind.

But I like the idea of a swab,

cause it’s just so easy.

A lot of us have done something like that for COVID tests.

It’s not a big deal.

I’ve been doing a nonstop rapid antigen test.

So let me say that particular one rapid antigen test,

they’ve been a source of frustration for me

because like everybody should be doing it.

It’s so easy.

We’ve also been working in my lab on democratizing

these tests to bring them down from a few hundred bucks

to a dollar.

So just to clarify,

you’re talking about not research,

you’re talking about like company stuff,

like actual consumer facing things?

Well, right.

The research on bringing the price down

has occurred in my lab at Harvard.

And then that intellectual property is being licensed

and has been licensed out to a company

that will be consumer facing.

So anybody for a small amount of money can do this.

Well, you got subscriber number one obsessed.

I think that’s a beautiful, beautiful idea.

So somebody who maybe I would have been more hesitant

about it until COVID,

but the home tests are super easy.

I almost wanted to share that data with the world,

like in some way, not the entirety of the data,

but like some visualization of like how I’m doing.

Like, it’s almost like when you share,

if you had like a long run or something like that,

I wish I could share because it inspires others.

And then you can have a conversation about like,

well, what are the hacks that you’ve tried

and have a conversation about like how to improve lifestyle

and those kinds of things that’s grounded in data.

That’s exactly, that’s what’s gonna happen.

Now, everything’s anonymous, of course.

We talked about security there,

but once it’s anonymized, you can then plot these numbers.

And I’ve plotted my epigenetic age

versus hundreds of other people

who have taken this test now.

And I can tell you where I fit relative to others

in terms of my biological age.

And I’m happy to share that with you

because it’s pretty low.

You can choose to share it, of course,

not everyone wants to share that.

But when you go to the doctor,

first of all, your doctor does treat you

as though you’re an average person

and none of us are average, there’s no such thing.

But second of all, we never know

how we’re doing relative to others

because we all, most of us, we don’t share our information.

So we might have this number and that number,

but do you know that your numbers are good for your age

or not?

You have no idea.

Even your doctor probably doesn’t even know.

So this graph that I’m talking about

is the beginning of a world where you can say,

how am I doing?

For the two of us, we’re white and we’re male

and we’re this age and we do this.

Are we good?

Are we doing the right things or the wrong things?

Do we need to fix certain things?

And this is what the future is.

It’s forget about just experimenting

and not knowing the result.

I mean, who doesn’t experiment and doesn’t look at the data?

No one, it makes no sense.

So we’re gonna enter a world

where we have a dashboard on our body,

the swabs, the blood tests, the biosensors

where our doctors can look at that,

but we can also look at it and they can recommend,

go to this restaurant down the road.

They’ve got this great meal.

It’s high in whatever you need today

because you’re lacking vitamin D and vitamin K2.

Go for it.

Ridiculous question or perhaps not.

If you look maybe 50 years from now

or 100 years from now, a person born then,

what do you think is a good goal

in terms of how long a person would live?

What is the maximum longevity that we can achieve

through the methods that we have today

or are developing some of the things

we’ve been talking about in terms of genetics,

in terms of biology?

Is there a number?

Right, well, so it changes all the time

because technology is changing so quickly.

I keep revising the number upward,

but I would say that if you do the right things

during your life and start at an early age,

let’s say 25, we don’t want malnutrition, starvation.

That’s not what I’m talking about.

But in your 20s, start eating the kind of diets

that I talked about, skipping meals.

In animals, that gives you an extra 20 to 30%.

We don’t know if that’s true for humans

and even 5% more would be a big deal for the planet.

I think that we should all aim to at least reach a century.

I’m a little bit behind.

I was born too early to benefit the most

from all of this discovery.

Those of you who are in your 20s,

you should definitely aim to reach a hundred.

I don’t see why not.

Consider this, this is really important.

The average lifespan of a human

that looks after themselves but doesn’t pay attention

is about 80, okay?

Japan, that’s the average age for a male, a bit higher.

If you do the right things in your life,

which is eat healthy food, don’t overeat,

don’t become obese, do a bit of exercise,

get good sleep and don’t stress,

that gives you on average 14 extra years.

That gets you to 94.

So getting to a hundred,

if you just focus on what I’m talking about,

it’s not a big deal.

So what’s the maximum?

Well, we know that one human made it to 122

and a number of them make it into their teens.

I think that’s also the next level

of where we can get to with the types of technologies

that I’m talking about.

Medicines, like I mentioned rapamycin,

there’s one called metformin, which is the diabetes drug,

which I take.

That in combination with these lifestyle changes

should get us beyond a hundred.

How long can we ultimately live?

Well, there’s no maximum limit to human lifespan.

Why can a whale live 300 years, but we cannot?

We’re basically the same structure.

We just need to learn from them.

So anyone who says, oh, you max out at X,

I think is full of it.

There’s nothing that I’ve seen that says

biological organisms have to die.

There are trees that live for thousands of years

and their biochemistry is pretty close to ours.

What do you think it means to live for a very long time?

Let’s say if it’s 200 years we’re talking about

or a thousand years.

There’s some sense, you could argue,

that there is immortal organisms already living on Earth,

like there’s bacteria.

So there’s certain living organisms

that in some fundamental way do not die

because they keep replicating their genetic,

they keep like cloning themselves.

Is it the same human if we can somehow persist

the human mind, like copy, clone certain aspects

and just keep replacing body parts?

Do you think that’s another way to achieve immortality?

To achieve a prolonged sort of increased longevity

is to replace the parts that break easily

and keep, because actually from your theory of aging

as a degradation of information,

so an information theory view of aging,

like what is the key information that makes a human?

Can we persist that information

and just replace the trivial parts?

Yeah, I mean the short answer is yes.

We’re already replacing body parts

but what makes us human is our brain.

Everything else is suboptimal except our brain.

The ability to replace actual neurons is really hard.

I think it might be easy to upload

rather than replace neurons because they’re so tight,

it’s such a network and just perturbing the system.

It’s Roger and Gizcat.

You change everything once you get in there.

The problem is, well, I guess the solution,

let me go to the solution that’s more interesting.

What we’re learning is that if you reverse

the age of nerve cells,

it looks like they get their memories back.

So the memories are not lost.

They’re just that the cells don’t know how to interpret them

and function correctly.

And this is one of the things we’re studying in my lab.

If you take an old mouse that has learned something

when it was young but forgotten, does it get that back?

And all evidence points to that being true.

So I’d rather go in and rejuvenate the brain as it sits

rather than replace individual cells,

which would be really hard.

What do you think about like efforts like Neuralink,

which basically you mentioned uploading,

are trying to figure out,

so creating brain computer interfaces

that are trying to figure out

how to communicate with the brain.

But one of the features of that is trying to record

the human brain more and more accurately.

Do you have hope for that to,

of course, it will lead to us better understanding

from a neuroscience perspective, the human mind,

but do you have hope for it increasing longevity

in terms of how it’s used?

I think that it can help with certain diseases.

But I see, at least within our lifetime,

that’s the best use of it is to be able to replace

parts of the body that are not functioning,

such as the retina and other parts,

the visual cortex back here.

That’s going to be doable.

In terms of longevity,

maybe we could put something on the hypothalamus

and start secreting those hormones and get that back.

Ultimately, I think the best way to preserve the brain

is going to be to record it.

But also, I think it’s going to require death,

unfortunately, to then do very detailed scans,

even if you have enough time and money, atomic microscopy,

and rebuild the brain from scratch.

Rebuild from scratch, yeah.

We are living more and more in a digital world.

I wonder if the scanning is good enough

for the critical things in terms of memories,

in terms of the particular quirks

of your cognitive processes.

They’re not, they’re not, yeah.

We’re not close, yes,

but we’ve made quite a bit of progress,

so if you’re an exponential type of person.

Yeah, well, let’s dream a little here.

Yes, that’s the point.

The way it would work, that I could see it working is,

so you take a single cell slice through your dead brain,

and we can now,

the problem with the engineering aspect is that,

the engineering is, the physical aspect of the brain

is not even half the problem.

The problem is which genes are switched on and off.

This experience that we’re having here

is altering certain genes in neurons

that will be preserved, hopefully, for a number of decades,

but you cannot see that with a microscope easily,

but there are technologies invented,

actually just down the hall in the building I’m at,

George Church invented a way, his lab invented a way,

to look at which genes are switched on and off,

not only in a single cell, which any lab can do these days,

but in situ, where it’s situated in the brain.

So you can say, okay, this nerve cell,

had these genes switched on and these switched off,

we can recreate that,

but just scanning the brain

and looking how the nerves are touching each other

is not gonna do it.

Wow, okay.

So you have to scan the full biology, the full details.

And look at the epigenome.

And the epigenome too.

Yeah, which genes are on and off.

It’s just easier to reset the epigenome

and get them to work like they used to.

True, true.

We’re doing that now.

Use the hardware we already have,

just figure out how to make that hardware last longer.

Right, ultimately information will be lost,

even genetic information degrades slowly through mutation.

So immortality is not achievable through that means,

though I think we could potentially reset the body

hundreds of times and live for thousands of years.

Okay, so we talked about biology.

Let’s, forgive me, but let’s talk about philosophy

for just a brief moment.

So somebody I’ve enjoyed reading,

Ernest Becker wrote The Denial of Death.

There’s also Martin Heidegger.

There’s a bunch of philosophers who claim

that most people live life in denial of death.

Sort of we don’t fully internalize

the idea that we’re going to die.

Because if we did, as they say,

there will be a kind of terror of,

I mean a deep fear of death.

The fact that we don’t know what’s,

like we almost don’t know what to do with non existence,

with disappearing.

Like our, the way we draw meaning from life

seems to be grounded in the fact that we exist

and that we at some point will not exist is terrifying.

And so we live in an illusion that we’re not going to die

and we run from that terror.

That’s what Ernest Becker would say.

Do you think there’s any truth to that?

Oh, I know there’s truth to that.

I experience it every day when I talk to people.

We have to live that way.

Although unfortunately I can’t,

but for most people it’s extremely distressing

to think about their own mortality.

We think about it occasionally.

And if we really thought about it every day,

we’d probably be brought to tears.

How much we not just miss ourselves,

but miss our family, our friends.

All living life forms have evolved to not want to die.

And when I mean want,

biochemically, genetically, physically.

That yeast cell, the cells that I studied at MIT,

they were fighting for their lives.

They didn’t think,

but our brain has evolved the same survival aspect.

Of course, we don’t want to die.

But the problem for us, unfortunately,

it’s a curse and a blessing is that we’re now conscious.

We know that we’re going to die.

Most species that have ever existed don’t.

That’s a burden, that’s a curse.

And so what I think has happened is

we’ve evolved certainly to want to live for a long time,

perhaps never want to die.

But the thought about dying is so traumatic

that there is an innate part of our brains.

And it’s probably genetically wired to not think about it.

I really think that’s part of being human.

Because, think about tribes that obsessed

with longevity every day and that we’re going to die.

They probably didn’t make much technological progress

because they were just crying in their huts every day

or on the Savannah.

So I really think that we’ve evolved

to naturally deny aging.

And it’s one of the problems that I face in my career.

And when I speak publicly and on social media

is that it’s shocking.

People don’t want to think about their age,

but I think it’s getting better.

I think my book has helped.

These tests that we’re developing

should help people understand it’s not a problem

to think about your longterm health.

In fact, if you don’t,

you’re going to reach 80 and really regret it.

And the other side of it, so again, Ernest Becker,

but also Viktor Frankl recommended highly

Man’s Search for Meaning.

Bernard Williams is a moral philosopher.

They kind of argue that this knowledge of death,

even if we often don’t contemplate it, we do at times.

And the very, what you call the curse,

which I agree with you, it’s a curse and a blessing

that we’re able to contemplate our own mortality.

That gives meaning to life.

So death gives meaning to life,

is what Viktor Frankl argues.

I would probably argue the same.

There’s something about the scarcity of life

and contemplating that,

that makes each moment that much sweeter.

Is there something to that?

I think it’s individual.

In my case, it’s completely wrong.

I appreciate you saying that.

I don’t get joy out of every day

because I think I’m going to die.

I get joy out of every day because every day is joyous

and I make it that way.

And even if I thought I was going to live forever,

I would still be enjoying this moment just as much.

And I bet you would too.

Well, I think about that a lot.

I think it’s very difficult to know.

I’m almost afraid that I wouldn’t enjoy it as much

if I was immortal.

I’m almost afraid to want to be immortal or to live longer

because it perhaps is a kind of justification

for me to accept that I’m going to die.

It’s saying like, oh, if I was immortal,

I wouldn’t be able to enjoy life as much as I do.

But it’s very possible that I would enjoy just as much.

Of course, enjoying life, whether you’re immortal or not,

takes work.

Like it requires you to have the right kind

of frame of mind.

You can discover, you can focus your mind

on the ugliness of life.

There’s plenty of ugly things in this world

and you can focus on them.

You can complain.

Whenever like, you know, if it’s raining outside,

you can focus on the fact that you have shelter

and enjoy the hell out of it.

Or you can enjoy running in the rain when it’s warm

and the beauty of nature, just being one with nature.

Or you can just complain, it’s fucking weather again

in Boston and then it’s either always raining

or freezing, damn it.

The same thing with like wifi going out on airplanes.

You can either complain about stupid wifi

on JetBlue or something.

Or you could say like, how incredible it is

that I can fly through the sky and in a matter of hours

be anywhere else in the world.

And then I could also on occasion watch like check email

and even watch movies while connecting through satellites

that are flying through space.

So it’s a matter of perspective and perhaps

there’s an extra level of work required

when you’re immortal because it’s easier

when you’re immortal or live longer to be lazy,

to delay stuff.

But if you’re not, you can still derive

the same amount of joy.

It’s possible, it’s possible.

It’s definitely possible.

In my life, I went from being the nothing’s working

to every day’s great to wake up to.

And I think even if you think you can live forever,

you can enjoy every day.

What I do is everything’s relative.

We can compare ourselves to our neighbor who has more money

or to the flight that should have had wifi

or which is what I do, I’m still six years old remember.

What a six year old does says, look, I can,

when I tell my fingers to form a fist,

they actually do that.

That’s really cool.

That’s how I live my life.

I can pick up on your desk here, this metal object.

It’s a metal cube, about an inch by an inch by an inch.

And I tell myself not about cubes,

but about inanimate objects.

Probably once a day I’ll say, I’m a living thing.

I can think, I can move, I can eat, I am full of energy.

And there’s that leaf or this cube here

that will never be alive.

That’s what I look at and compare myself to.

And for as long as I live, if it’s forever,

of course it won’t be, but even if it was forever,

relative to this lump of metal on this table here,

we are wondrous things in the universe

and probably the most wondrous things in the universe.

Yeah, we’re able to deeply appreciate the leaf or the cube

and deeply appreciate ourselves,

which is, it can be a curse, but it’s mostly a gift,

especially when you’re, it’s such a beautiful poem.

Now I’m six, I’m as clever as clever,

so I think I’ll be six now forever and ever.

That’s a good thing to aspire to.

Your grandmother was onto something.

David, this is an incredible conversation.

I’m a huge fan of your work.

So thank you for wasting your valuable time with me today.

I really, really appreciate it.

This was awesome.

Thank you for having me on, Lex, appreciate it.

Thanks for listening to this conversation

with David Sinclair, and thank you to Onnit, Clear,

National Instruments, Simply Safe, and Linode.

Check them out in the description to support this podcast.

And now let me leave you with some words

from Arthur Schopenhauer.

All truth passes through three stages.

First, it is ridiculed.

Second, it is violently opposed.

Third, it is accepted as being self evident.

Thank you for listening, and hope to see you next time.

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