back to indexDavid Sinclair: Extending the Human Lifespan Beyond 100 Years | Lex Fridman Podcast #189
link |
The following is a conversation with David Sinclair.
link |
He's a professor in the Department of Genetics at Harvard
link |
and co director of the Paul F. Glenn Center
link |
for the Biology of Aging at Harvard Medical School.
link |
He's the author of the book,
link |
Lifespan and co founder of several biotech companies.
link |
He works on turning age into an engineering problem
link |
Driven by a vision of a world
link |
where billions of people can live much longer
link |
and much healthier lives.
link |
Quick mention of our sponsors,
link |
Onnit, Clear, National Instruments,
link |
and I, SimpliSafe and Linode.
link |
Check them out in the description to support this podcast.
link |
As a side note, let me say that longevity research
link |
challenges us to think how science and engineering
link |
will change society.
link |
Imagine if we can live 100,000 years,
link |
even under controlled conditions,
link |
like in a spaceship say,
link |
then suddenly a trip to Alpha Centauri
link |
that is a 4.37 light years away
link |
takes a single human lifespan.
link |
And on the psychological, maybe even philosophical level,
link |
as the horizons of death drifts farther into the distance,
link |
how will our search for meaning change?
link |
Does meaning require death
link |
or does it merely require struggle?
link |
Reprogramming our biology will require us to delve deeper
link |
into understanding the human mind and the robot mind.
link |
Both of these efforts are as exciting of a journey
link |
This is the Lex Friedman Podcast
link |
and here is my conversation with David Sinclair.
link |
I usually feel like the same person when I was 12.
link |
Like when I, right now, as I think about myself,
link |
I feel like exactly the same person
link |
that I was when I was 12.
link |
And yet, I am getting older, both body and mind,
link |
and still feel like time hasn't passed at all.
link |
Do you feel this tension in yourself
link |
that you're the same person and yet you're aging?
link |
Yeah, I have this tension that I'm still a kid,
link |
but that helps in my career.
link |
Scientists need to have a wonder about the world
link |
and you don't wanna grow up at 12 year olds
link |
and even younger, I would say six, seven year olds.
link |
I've still got that boy in me and I can look at things.
link |
It's a gift, I think, that I can see things
link |
for the first time if I choose to,
link |
and then explain them as I would to a six year old
link |
because I am that mentally.
link |
But on the other hand, I'm getting older, right?
link |
I run a lab of 20 people at Harvard.
link |
I've got a book, I've got science to do, companies to run,
link |
and so I have to, on most days,
link |
just pretend to be a grownup and be mature,
link |
but I definitely don't feel that way.
link |
There's something I really appreciated
link |
in opening your book.
link |
You talked about your grandmother.
link |
And on this kind of theme, on this kind of topic,
link |
she, first of all, had a big influence on you.
link |
My grandmother had a big influence on me.
link |
And you also mentioned this poem
link |
by the author of Winnie the Pooh, Alan Alexander Milne.
link |
Maybe I can read it real quick
link |
because I love, on the topic of being children,
link |
when I was one, I had just begun.
link |
When I was two, I was nearly new.
link |
When I was three, I was hardly me.
link |
When I was four, I was not much more.
link |
When I was five, I was just alive, but now I am six.
link |
I am as clever, as clever, so I think I'll be six,
link |
now, forever and ever.
link |
So this idea of being six and staying six forever,
link |
being youthful, being curious,
link |
being childlike, this and other things,
link |
what influence has your grandmother had
link |
in your thinking about life, about death, about love?
link |
Yeah, I was getting misty eyed as you read that
link |
because that poem was read to me very often,
link |
if not every day, by my grandmother,
link |
who partially raised me.
link |
And she was as much a bohemian as an artist, philosopher.
link |
And she's one of those people
link |
that wouldn't talk about the little things.
link |
She said, I hate small talk.
link |
Don't talk to me about politics or the weather.
link |
Yeah, talk to me about human beings and culture.
link |
So I was raised on that,
link |
and this poem was one that she read to me often
link |
because she knew that the mind of a child is precious,
link |
it's honest, it's pure.
link |
And she grew up during the Second World War
link |
and in Hungary and Budapest witnessed the worst of humanity.
link |
She was trying to save a whole group of Jewish friends
link |
in her apartment, saw what happened after the World War,
link |
which was there was, the Russians were in control
link |
and locals weren't necessarily treated well
link |
if they were rebellious, which she was.
link |
And then there was the revolution in 56,
link |
which she was part of and had to escape the country.
link |
So she saw what can happen when humans do their worst.
link |
And her words to me, expressed in part through that poem
link |
was, David, always stay young and innocent
link |
and have wonder about the world,
link |
and then do your best to make humanity the best it can be.
link |
And that's who I am, that's what I live for,
link |
that's what I get up in the morning to do
link |
is to leave the world a better place
link |
and show to whoever's watching us,
link |
whether it's aliens or some future human historian,
link |
that we can do better than we did in the 20th century.
link |
You know, we mentioned offline this idea
link |
of bringing people back to life
link |
through artificial intelligence,
link |
sort of, I don't know if you've seen videos
link |
of basically animating people back to life,
link |
meaning whether it's, for me personally,
link |
I've been working on specifically about Albert Einstein,
link |
but also Alan Turing, Isaac Newton, and Richard Feynman.
link |
And it's an opportunity to bring people
link |
that meant a lot to others in the world
link |
and animate them and be able to have a conversation
link |
with them at first to try to visually,
link |
visually explore the full richness of character
link |
that they had as they struggle
link |
with the ideas of the modern age.
link |
Sort of, it's less about bringing back their mind
link |
and more bringing back the visual quirks
link |
that made them who they are.
link |
And then maybe in the future,
link |
it's using the textual, the visual,
link |
the video, the audio data to actually compress
link |
down the person for who they are
link |
and be able to generate text.
link |
There's a few companies, there's Replica,
link |
which is a chat engine that was born
link |
out of the idea of bringing,
link |
the founder lost her friend to,
link |
he got run over by a car.
link |
And the initial reason she founded the company
link |
was trying to just have a conversation with her friend.
link |
She trained machine learning, natural language system
link |
on the texts that they exchange with each other
link |
and try, she had a conversation with him
link |
sort of after he was gone.
link |
And it's very, the conversation was very trivial.
link |
It was obvious that it's AI agent,
link |
but it gave her solace.
link |
It made her actually feel really good.
link |
And that's the way I wonder if it's possible
link |
to bring back people that are,
link |
that mean something to us personally,
link |
not just Einstein, but people that we've lost
link |
and in that way achieve a kind of small
link |
artificial immortality.
link |
I don't know if you think about this kind of stuff.
link |
Well, I definitely think about a lot of things.
link |
That one's a really good one.
link |
There's a great Black Mirror episode
link |
about the wife who brings back the boyfriend or husband.
link |
I think one of the challenges
link |
with bringing back Richard Feynman
link |
would be to capture his sense of humor,
link |
but that would be awesome.
link |
But yeah, bringing back loved ones would be great,
link |
especially if they're young and they die early,
link |
though it may hold you back from moving on.
link |
That's another thing that could happen as a negative.
link |
But I think that's great.
link |
And I also think that it's gonna be possible,
link |
especially when we're recording some of us,
link |
every aspect of our lives,
link |
whether it's our face or things we see, right?
link |
Eventually one day, everything we see can be recorded.
link |
And then you can build somebody's experience
link |
and thoughts, speech,
link |
and you will have replicas of everybody,
link |
at least digitally,
link |
and physically you could do that too one day.
link |
But that's a good idea,
link |
especially because there are people that I'd like to meet,
link |
and I think it's easier than building a time machine.
link |
One person I'd love to meet is Benjamin Franklin.
link |
Well, I wouldn't go back in time.
link |
I would, but I'd prefer to bring him into the future
link |
and say, can you believe we have this thinking machine
link |
in our pockets now?
link |
And just see the look on his face
link |
as to where humanity has come.
link |
Because I think of him as a modern guy
link |
that just was before his time.
link |
Yeah, so you're thinking Benjamin Franklin the scientist,
link |
not Benjamin Franklin the political thing.
link |
Because he'd be very upset with Congress right now.
link |
So maybe talk to him about science and technology,
link |
Or maybe just don't get him on Twitter
link |
because he'll be very upset with human civilization.
link |
You know, I wonder what their personalities are like.
link |
Isaac Newton, it does seem complicated
link |
to figure out what their personality is like.
link |
Even Friedrich Nietzsche, who I also thought about.
link |
Feynman is, we just have enough video
link |
where we get the full kind of,
link |
I mean, it shows you how important it is
link |
to get not the official kind of book level presentation
link |
of a human, but the authentic,
link |
the full spectrum of humanity.
link |
You mentioned collecting data about a person,
link |
collecting the whole thing, the whole of life,
link |
the ups and downs, the embarrassing stuff,
link |
the beautiful stuff, not just the things
link |
that's condensed into a book.
link |
And then with Feynman, you start to see that a little bit.
link |
Through conversations, you start to see peaks
link |
of like that genius.
link |
And then through stories about him from others.
link |
And then certainly you, the sad thing
link |
about Alan Turing, for example,
link |
is there's very little, if any, recording of him.
link |
In fact, I haven't been able to find recording
link |
allegedly there's supposed to be a recording of him
link |
doing some kind of a radio broadcast,
link |
but I haven't been able to find anything.
link |
And so that's truly sad that it feels like
link |
it makes you realize how the upside,
link |
how nice it is to collect data about a person,
link |
to capture that person.
link |
That's the upside of the modern internet age,
link |
the digital age, that that information,
link |
yeah, creates a kind of immortality.
link |
And then you can choose to highlight
link |
the best parts of the person,
link |
maybe throw away the ugly parts
link |
and celebrate them even after they're gone.
link |
So that's a really interesting opportunity.
link |
You've also mentioned to me offline
link |
that you're really excited about all the different wearables
link |
and all the different ways we can collect information
link |
about our bodies, about the whole thing.
link |
What's most exciting to you in terms of collecting
link |
the biological data about a human being?
link |
Well, so I'm a biologist.
link |
I find animals and humans as machines very interesting.
link |
It's one of the reasons I didn't become an engineer
link |
I wanted to understand how we actually are built.
link |
And so I think a lot about machines merging with humans.
link |
And the first of that are the bio wearables.
link |
And so I talked a lot about this, I wrote about it
link |
in Lifespan, the book, and pictured a future
link |
where you would be monitored constantly
link |
so that you wouldn't suddenly have a heart attack,
link |
you'd know that was coming,
link |
or you wouldn't go to the doctor
link |
and they don't know if you need an antibiotic or not.
link |
Long term, how old are you, how to fix things,
link |
what should you eat, what should you take,
link |
what should your doctor do?
link |
These devices, I predicted, would be smarter,
link |
better educated than your physician
link |
and would augment them.
link |
And then there'd be a human that would just tick off
link |
to see if it's correct and they approve.
link |
I also was predicting in the book
link |
that we would have video conferences with our doctors
link |
and that medicines would be delivered,
link |
initially by courier, but eventually by drones
link |
and get it to you sometimes in an emergency.
link |
And that we could even have pills
link |
that were synthesized or delivered in your kitchen
link |
and combined certainly.
link |
What's amazing about that is that, what are we now,
link |
two years since the book came out, even less,
link |
and that future is basically here already.
link |
COVID 19 accelerated that incredibly.
link |
So where we're at now in society is,
link |
if you wanna pay for it, you can have a blood test
link |
that will detect cancer 10, 20 years earlier than it would
link |
before it forms a tumor.
link |
You can, of course, do your genome very cheaply
link |
for less than $100 now.
link |
There are bio wearables already I wear,
link |
this ring from Aura that I have a number of years of data.
link |
I've been doing blood tests for the last 12 years
link |
with a company called Inside Tracker, which I consult for.
link |
And so I have all of that data as well.
link |
And there's 34 different parameters on my testosterone,
link |
my blood glucose, my inflammation.
link |
And I use all that data to, of course,
link |
I wear a watch that measures things as well.
link |
I use that data to keep my body in optimal shape.
link |
And according to those parameters,
link |
I'm at least as good as someone in their early 40s.
link |
And if I really work at it,
link |
I can get my biochemistry down to early to mid 30s,
link |
though I like to now eat a little dessert once in a while.
link |
So that's the future we're in right now.
link |
Anyone can do what I just said.
link |
But in the very near future, just in the next few years,
link |
you can be wearing wearables.
link |
So I'm currently wearing a little,
link |
what's called a bio sticker.
link |
This one I just put on last night.
link |
It's about an inch long, a few millimeters.
link |
Yeah, for people just listening, it's on David's chest.
link |
It's just, how does it attach?
link |
It's just kind of.
link |
It sticks on. Sticks on.
link |
Yeah, so on one side you have an on button that you press.
link |
The lights come on, flashes four times, it's good to go.
link |
It immediately syncs to your phone.
link |
And this one, it's called a bio button, a nice name.
link |
And there's another one that I have that I haven't tried yet
link |
that does EKG on your heart.
link |
This is mainly for doctors to monitor patients
link |
that go home after a heart attack or surgery.
link |
But that's medical grade FDA approved device.
link |
So there will be a day, in fact, it's already here,
link |
that doctors are using these to get patients to go home
link |
and save a week in hospital, $2,000 at least
link |
That's massive savings for the hospital.
link |
But ultimately what I'm excited about is a future
link |
that isn't that far off where everybody,
link |
certainly in developed countries,
link |
eventually these will cost a few cents and rechargeable.
link |
The only cost will be the software subscription
link |
that can be monitored constantly.
link |
And to give an idea what this is measuring me
link |
at a thousand times a second is my vibrations as I speak,
link |
my orientation, it already has told me this morning
link |
how I slept, where I slept, what side I slept on.
link |
We've got sneezing, coughing, body temperature,
link |
heart rate, heart of other parameters of the heart
link |
that would indicate heart health.
link |
These data are being used to now to predict sickness.
link |
So eventually we'll have just in the next year or so
link |
the ability to predict whether something
link |
or diagnose whether something is pneumonia
link |
or just a rhinovirus that can be treated or not.
link |
This is really going to not just revolutionize medicine,
link |
but I think extend lives dramatically.
link |
Because if I'm gonna have a heart attack next week
link |
and that's possible, this device should know that
link |
and I'll be in hospital before I even have it.
link |
Maybe you can talk a little bit about InsideTracker
link |
because I saw that there's some really cool things in there.
link |
Like it actually, so maybe you can talk about,
link |
I guess that you're collecting blood to give it the data.
link |
So, and it has like basic recommendations
link |
on how to improve your life.
link |
So we're not just talking about diseases, right?
link |
Like anticipating having a particular disease,
link |
but it's almost like guiding your trajectory to life,
link |
how to, whether it's extend your life
link |
or just live a more fulfilling,
link |
like improve the quality of life.
link |
I suppose this is the right way to say it.
link |
How does InsideTracker work?
link |
What the heck is it?
link |
Because I thought there was also pretty cool.
link |
Is it something other people can use?
link |
You can definitely use it.
link |
You can sign up, it's consumer.
link |
It's like a company consumer facing company.
link |
And I also want to democratize the ability
link |
to just take a mouth swab eventually.
link |
We don't need to have a blood test necessarily,
link |
but for now it's a blood test
link |
and you'd go to a lab core request in the US.
link |
It's also available overseas.
link |
You can upload your own data for a minimal cost
link |
and get the algorithms, the AI in the background
link |
to take that data,
link |
plot where you are against others in your age group
link |
in terms of health and longevity at bio age.
link |
They call it inner age,
link |
but also it provides recommendations.
link |
And this isn't just a bunch of BS.
link |
It sounds like it might be to say, I'll go eat this
link |
or go to that restaurant and order that,
link |
but it's actually based on the basic.
link |
This company has entered hundreds.
link |
Now it would be thousands of scientific papers
link |
into their database
link |
and hundreds of thousands of human data points.
link |
And they have tens of thousands of individuals
link |
that have been tracked over time
link |
and anonymously that data is used to say
link |
what works and what doesn't.
link |
If you eat that, what works?
link |
If you take that supplement, what works?
link |
And I was a coauthor on a paper that showed
link |
that the recommendations for food and supplements
link |
was better than the leading drug for type two diabetes.
link |
The idea that you can connect,
link |
like skipping the human having to do this work,
link |
you can connect the scientific papers,
link |
almost like meta analysis of the science
link |
connected to the individual data.
link |
And then based on that sort of connect your data
link |
to whatever the proper group is
link |
within the whatever the scientific paper is
link |
to make the suggestion of how like how that work
link |
applies to your life.
link |
And then that ultimately maps to like a recommendation
link |
of what you should do with your life.
link |
Like it all like this giant system
link |
that ultimately recommends
link |
you should drink more coffee or less.
link |
Right, and we'll have the genome in there as well.
link |
You can upload that.
link |
Yeah, it's awesome.
link |
So these programs will know us way better
link |
than we do and our doctors as well.
link |
The idea of going to a doctor once a year
link |
for an annual checkup and having males get a finger
link |
up their butt and you cough, that to me is a joke.
link |
That's medieval medicine.
link |
And that's very soon going to be seen as medieval.
link |
Yeah, to me as a computer science person,
link |
it's always upsetting to go to the doctor
link |
and just look at him and like realize
link |
you know nothing about me.
link |
Like you're making your like opinions based on like,
link |
it is very valuable, years of intuition building
link |
about basic symptoms, but you're just like it is medieval.
link |
They're very good at it.
link |
In fact, doctors in medieval times were probably damn good
link |
at working with very little.
link |
But the thing is, I'd rather prefer a doctor
link |
that doesn't really know what they're doing,
link |
but has a huge amount of data to work with.
link |
Well, you're right.
link |
And many of my good friends are doctors.
link |
I work at Harvard.
link |
So I'm not against the profession at all.
link |
But I think that they need just as much help
link |
as anyone else does.
link |
We wouldn't drive a car without a dashboard.
link |
We wouldn't think of it.
link |
So why would doctors do the same?
link |
If we could, could we step back to the big,
link |
profound, philosophical, both tragic
link |
and beautiful question about age?
link |
How and why do we age?
link |
Is it from an engineering perspective?
link |
You said you like the biological machine.
link |
Is that a feature or a bug of the biological machine?
link |
It is both a bug and a feature.
link |
Evolutionary speaking, we only live as long as we need to
link |
to replace ourselves efficiently.
link |
If you're a mouse, you're only gonna live two
link |
and a half years, three years.
link |
You're probably gonna die of starvation,
link |
predation, freezing in the winter.
link |
So they divert most of their resources
link |
to reproducing rapidly,
link |
but they don't put a lot of energy
link |
into preserving their soma, which is their body.
link |
Conversely, a baleen type of whale,
link |
a bowhead whale in particular will live hundreds of years
link |
because they're at the top of the food chain
link |
and they can live as long as they want.
link |
So they breed slowly and build a body that lasts.
link |
We're somewhere in between because we've, you know,
link |
we've really only just come out of the savannas
link |
where we could be picked off by a cat.
link |
We were pretty wimpy going back 6 million years ago.
link |
So we actually need to evolve quicker than evolution will.
link |
And that's why we can use our oversized brains
link |
and intuition to give us what evolution
link |
not only didn't give us, but took away from us.
link |
Now we're pathetic, look at our bodies.
link |
These arms, if any of us, even the strongest person
link |
in the world went in a cage with a chimpanzee,
link |
the chimp could knock that person's head off, no question.
link |
So we're pathetic.
link |
So we need to engineer ourselves to be healthier
link |
So getting to aging, we can do better, right?
link |
Whales do way better.
link |
We're trying to learn how whales do that.
link |
And if you ask really anybody in the field now, professor,
link |
they'll say there are eight or nine hallmarks of aging,
link |
which are really, it's a word for causes of aging.
link |
So that you probably have heard of some of these,
link |
your listeners will have loss of telomeres,
link |
the ends of the chromosomes, like the little ends
link |
of shoelaces, that kind of thing.
link |
They get too short, cells stop dividing, become senescent.
link |
They become, they put out what are called mitogens
link |
that cause cancer and inflammatory molecules.
link |
So that's another aspect of aging, cellular senescence.
link |
Another one is loss of the energetic.
link |
So mitochondria, the battery packs wind down.
link |
There's a whole bunch, stem cells, proteostasis.
link |
Well, these are our Achilles heels that I'm talking about.
link |
They're a common amongst all life forms, really.
link |
But if you want me to jump to the chases to where,
link |
what is the upstream defining factor?
link |
If we boil it down, what do we get?
link |
So most biologists would say, you can't boil it down.
link |
I would say you can boil it down to an equation,
link |
which is the preservation of information
link |
and loss due to entropy, i.e. noise.
link |
And that is the basis of my research.
link |
It originally came out of discoveries in yeast cells,
link |
where I went to MIT in the 1990s.
link |
You studied bread.
link |
I studied the makers of bread,
link |
a little yeast called Saccharomyces cerevisiae,
link |
which at the time was one of the hottest, excuse the pun,
link |
organisms to work on.
link |
But we figured out in the lab why yeast cells get old
link |
and found genes that control that process
link |
and made them live longer,
link |
which was an amazing four years of my life.
link |
One of those genes had a name with an acronym SIR2.
link |
Now the two is irrelevant.
link |
The SIR is important.
link |
And the most important letter out of all of those three
link |
is I, which stands for information.
link |
Silent information regulator number two,
link |
when you put more copies of that gene in,
link |
just put in one more copy,
link |
the yeast cells lived 30% longer
link |
and suppressed the cause of aging,
link |
which was the dysregulation of information in the cell.
link |
And then, so fast forward to now,
link |
I've been looking in humans and mice,
link |
because they live shorter and cheaper to study,
link |
where the loss of information in our bodies
link |
is a root cause of aging.
link |
And I think it is.
link |
Your boldness in doing biology in this way is fascinating
link |
because that also leads to a kind of,
link |
it's almost like allows for a theory of aging,
link |
like you could boil it down to a single equation
link |
and it leads to a, perhaps a metric
link |
that allows you to optimize aging,
link |
sort of in the fight against entropy.
link |
I had to figure out which mechanisms, like you said,
link |
the silent information regulator,
link |
which mechanisms allow you to preserve information
link |
without injecting noise, without creating entropy,
link |
without creating degradation of that information.
link |
For some reason, converting biology,
link |
which I thought was mostly impossible
link |
into an engineering problem,
link |
feels like it makes it amenable to optimization,
link |
to solving problems, to creating technology that can,
link |
whether that's genetic engineering or AI,
link |
it makes it possible to create the technology
link |
that would improve the degradation of information and aging.
link |
Is there more concrete ways you think
link |
about the kind of information you want to preserve?
link |
And also, is there good ideas about regulators
link |
of that information, about ways to prevent the distortion,
link |
the degradation of that information?
link |
Right, so we have silent information regulator genes
link |
We have seven of them, SIRT1 through seven, they're called.
link |
And we found in mice, one way to slow down
link |
the loss of information is to just give more of these,
link |
to upregulate these genes.
link |
So we made a mouse that has more of this SIRT1 gene,
link |
turned it on, and that slowed down the aging of the brain
link |
and preserved their information.
link |
Now, what information am I talking about, you might ask?
link |
Well, again, you can simplify biology.
link |
There are two types of information in the cell primarily.
link |
The one we all read about and know about
link |
is the DNA, the genome.
link |
And that's base four information, ATCG,
link |
the four chemicals that make up the various sequences
link |
of the genome, billions of letters.
link |
And that also degrades over time.
link |
But what's been fascinating is that we find
link |
that that information is pretty much intact
link |
in old animals and people.
link |
You can clone a dog.
link |
One of my friends in LA just cloned his dog three times.
link |
So this is doable, right?
link |
It means that the genome can be intact.
link |
But what's the other type of information?
link |
It's the epigenome, the regulators
link |
of the genetic information.
link |
And physically, that's really just how the DNA is wrapped up
link |
or looped out for the cell to access it and read it.
link |
So it's similar to, and excuse this analogy,
link |
but it's a good one, a compact disc or a DVD.
link |
Those pits in the foil are the digital information.
link |
That's the genome.
link |
And the epigenome is the reader of that information.
link |
And in a different cell, you'd read different music,
link |
different songs, different symphonies.
link |
And that's what gets laid down when we're in the womb.
link |
And that makes a skin cell forever a skin cell
link |
and not a brain cell tomorrow.
link |
Thank God, otherwise our brains wouldn't work very well.
link |
But over time, what we see is that the brain cells
link |
start to look more like skin cells.
link |
And the kidney cells start to look more like liver cells.
link |
And what we call X differentiate.
link |
This is a term that we use in my lab,
link |
but isn't yet widely used.
link |
But we needed a term to explain this.
link |
And that process of X differentiation,
link |
the loss of the reader of the CD or the DVD,
link |
we liken that to scratches on the DVD
link |
so that the reader cannot fully access the information.
link |
Now we can slow down the scratches, as I mentioned.
link |
We can turn on these genes.
link |
We can even put in molecules into the cell
link |
or even eat them and turn on those pathways,
link |
which my father and I have been trying to do
link |
for about a decade to slow things down.
link |
But the question that I've had is,
link |
is there a repository of information still in the body?
link |
Because anyone who knows anything
link |
about the loss of information
link |
or even has tried to copy a cassette tape
link |
or photocopy or Xerox anything knows that over time,
link |
you lose that information irreparably.
link |
So I've been looking for a backup copy,
link |
inspired largely by Claude Shannon's work
link |
at MIT as well in the 1940s.
link |
His mathematical theory of communication is just brilliant.
link |
And so I've been looking for what he called the observer,
link |
which is the backup copy.
link |
We today might call that the TCPIP protocol of the internet
link |
that stores information in case it doesn't make it
link |
to your computer, it will fill in the gaps.
link |
And we've been spending about the last five years
link |
to try and find if there really is a backup copy in the body
link |
to reset the epigenome and polish those scratches away.
link |
That's incredible.
link |
So finding the backup, so whenever there are too many
link |
scratches pile up, you can just write a new version.
link |
Like write, not a new version,
link |
but go to the backup and restore it.
link |
Right, that's really all we're talking about.
link |
It's not that hard once you know the trick.
link |
And for people that actually remember like DVDs
link |
and scratches on them, how frustrating it is.
link |
That's a brilliant metaphor for aging.
link |
And then the reader is the thing that skips
link |
and then it could destroy your experience,
link |
the richness of the experience that is listening
link |
to your favorite song.
link |
Right, but in biology, it's even worse
link |
because you'll lose your memory, your kidneys will fail,
link |
you'll get diabetes, your heart will fail.
link |
And we call that aging and age related diseases.
link |
So most people forget that diseases that we get
link |
when we get old are 80 to 90% caused by aging.
link |
And we've been trying to fix things with band aids
link |
after they occur without even generally talking
link |
about the root cause of the problem.
link |
Is there the scratches, do those come from,
link |
are those programmed or are they failures?
link |
Meaning is it, so if it's by design,
link |
then there's like a encoded timeline schedule
link |
that the body's just on purpose,
link |
degrading the whole thing.
link |
And then there's the just the wear and tear
link |
of like the scratches on a disc that happen through time.
link |
Which one is it that's the source of aging?
link |
It's more akin to wear and tear, there isn't a program.
link |
Getting back to evolution, there's no selection for aging.
link |
We're not designed to age, we just live as long as we need
link |
to and then we're at the whim of entropy, basically.
link |
Second law of thermodynamics, stuff falls apart.
link |
We live a bit longer than age 40,
link |
only because there are robust, resilient systems,
link |
but eventually they fail as well.
link |
Current limit to the human lifespan
link |
where they completely fail is 122.
link |
But I don't like to think of it as wear and tear
link |
because there's two aspects to it.
link |
There's a system that's built to keep us alive
link |
when we're young, but actually goes,
link |
comes back to bite us as we get older.
link |
And we call this issue antagonistic pleiotropy.
link |
What's good for you when you're young
link |
can cause problems when you're older.
link |
So we've been looking, what is the main causes of the noise?
link |
And we've found two of them definitively.
link |
The first one is broken chromosomes.
link |
When a chromosome breaks, the cell has to panic
link |
because that's either gonna cause a cancer or kill the cell.
link |
There's only two outcomes, it's pretty much a problem.
link |
And so what the cell does is it reorganizes the epigenome
link |
What that leads to is, think of it as a tennis match
link |
or a ping pong game.
link |
The proteins are the balls
link |
and they now leave where they should be,
link |
which is regulating the genes that make the cell type,
link |
And they have a dual function,
link |
they actually go to the break,
link |
the chromosome will break and fix that.
link |
And then they come back.
link |
You might ask, well, why is it set up that way?
link |
Well, it's a beautiful system,
link |
it coordinates gene expression,
link |
the control systems with the repair.
link |
You want them coordinated.
link |
Problem is, as we get older, this ping pong game,
link |
some of the balls get lost.
link |
They don't come back to where they originally started.
link |
And that's what we think is the main noise for aging.
link |
And we've also, the other cause of aging that we found
link |
is cell stress, we damage nerves and they age rapidly.
link |
So that's the other issue.
link |
There's probably others, smoking chemicals, for example,
link |
we know accelerates biological age pretty dramatically.
link |
But the question is, can you slow that down
link |
or can you reset them to get those ping pong balls
link |
to go back to where they originally started in the game?
link |
And we think we've found a way to do that.
link |
Can you give me hints?
link |
Whose fault is it in the balls not coming back?
link |
Is it the proteins themselves?
link |
Like are they starting?
link |
Again, I've been obsessed with the protein folding problem
link |
from the AI perspective.
link |
So is it the proteins or is it something else?
link |
Well, we know who hits the balls and recruits them.
link |
So that the break is recognized by the cell.
link |
It's recognized by proteins who send out a signal
link |
through phosphorylation is typical way cells talk
link |
to other proteins.
link |
And that recruits those repair factors,
link |
those ping pong balls to the break.
link |
So the cells actively doing this to try and help itself,
link |
but we don't know who's to blame for them not coming back.
link |
That could just be a flaw in the quote unquote design.
link |
I don't think that there's something saying,
link |
well, 1% of you balls proteins never go back.
link |
I just think it's hard to reset a system
link |
that's constantly changing.
link |
We have in our bodies close to a trillion DNA breaks
link |
And imagine that over 80 years,
link |
what damage that does to our epigenomic information.
link |
Now we know that this is, well,
link |
we never know anything in biology,
link |
but we have strong evidence that this is true
link |
because we can mess with animals.
link |
We can create DNA breaks and tickle them
link |
with a few breaks, maybe raise it by threefold
link |
over background levels of normal breakage.
link |
And if we're right, those mice should get old.
link |
We can actually, we've created these breaks
link |
in a way that's titratable.
link |
We can, it's like a rheostat.
link |
We can send it to 11.
link |
I drove my Tesla here, I'm a big fan of a spinal tap too,
link |
If we go to 11, we can make a mouse old
link |
in a matter of months.
link |
We prefer to go to a level of about four
link |
and it gets old in 10 months.
link |
But it's definitely old.
link |
It's got all of the hallmarks of aging.
link |
It's got diseases.
link |
It's got gray hair.
link |
But importantly, we can now measure age
link |
by looking at the scratches.
link |
We can look at the epigenome, we can measure it
link |
and use machine learning to give us a number.
link |
And those mice are 50% older than normal.
link |
So you can replicate the aging process in a controlled way.
link |
You can, I mean, in a way that, I mean,
link |
you could accelerate it in a controlled way
link |
and measure how much exactly it's aging.
link |
And that gives you step one of a two step process
link |
to when you can then figure out,
link |
how can we reverse this?
link |
And now we're reversing those mice.
link |
Is there a good, I love what you said.
link |
I mean, in biology, you really don't know.
link |
It's such a beautiful mess.
link |
Is there ideas how to do that?
link |
Is that on the genetic engineering level?
link |
Is it like, what can you mess with?
link |
Is it going to the, trying to discover the backup copies
link |
and restoring from them?
link |
Like what's, if it's possible to convert it
link |
to natural language words, what are the ideas here?
link |
What is the observer and how do we contact it?
link |
What's the observer and how do you contact?
link |
Or if there's other ideas, how to reverse
link |
the balls getting lost process.
link |
Yeah, well, you can slow it down.
link |
But we found a reset switch recently.
link |
We just published this in the December 2020 issue of Nature.
link |
And what we found is that there were three embryonic genes
link |
that we could put into the adult animal
link |
to reset the age of the tissues.
link |
And it only takes four to eight weeks to work well.
link |
And we can take a blind mouse
link |
that's lost its vision due to aging.
link |
Neurons aren't working well towards the brain.
link |
Reset those neurons back to a younger age.
link |
And now the mice can see again.
link |
These three genes are famous actually
link |
because they're a set of four genes
link |
discovered by Shinya Yamanaka,
link |
who won the Nobel Prize in 2016
link |
for discovering that those four genes
link |
when turned on at high levels in adult cells
link |
can generate stem cells.
link |
And this is, I think, well known now
link |
that we can create stem cells from adult tissue.
link |
But what wasn't known is can you partially take age back
link |
without becoming a tumor
link |
or generating a stem cell in the eye,
link |
which would be a disaster?
link |
And the answer is yes.
link |
There is a system in the body
link |
that can take the age of a cell back to a certain point,
link |
but no further, safely, and reset the age.
link |
And we're now using that to reset the age of the brain
link |
of those mice that we aged prematurely.
link |
And they're getting their ability to learn back.
link |
This is really exciting, right?
link |
Like what's the downside of this?
link |
Well, the downside is if you overdo it
link |
and you don't get it right, you might cause tumors.
link |
But we do it very carefully.
link |
And we also know that in the eye, it's very safe.
link |
We also injected these, we deliver them by viruses.
link |
So we can control where and when they get turned on.
link |
And in this paper, we've published
link |
that if we put high levels in the mouse,
link |
into their veins, throughout the body,
link |
they don't get cancer for over a year.
link |
So I'm so optimistic that we're going into human studies
link |
in less than two years from now.
link |
Is there a place where AI can help?
link |
Sorry to inject one of the things
link |
I'm very excited about and passionate about.
link |
So Google DeepMind recently had a big breakthrough
link |
with AlphaFold2, but also AlphaFold two years ago,
link |
with achieving sort of a state of the art performance
link |
on the protein folding problem, single protein folding.
link |
But it also paints a hopeful picture
link |
of what's possible to do in terms of simulating
link |
the folding of proteins,
link |
but also simulating biological systems through AI.
link |
Is there something to you, combined with this brilliant work
link |
on the biology side that you're hopeful about
link |
where AI can be a tool to help?
link |
Where isn't it a tool?
link |
I mean, if you're not using AI right now in biology,
link |
you're getting less and less likely
link |
to be left behind in biology, you're getting left behind.
link |
We use it all the time.
link |
We're using it to generate these biological clocks
link |
to be able to read those scratches.
link |
We're using it to predict the folding of proteins
link |
so we can target molecules and modulate their activity.
link |
We're using it to assemble genomes of different species.
link |
We use it to predict the longevity of a mouse
link |
based on how it reacts to certain things,
link |
hearing, eyesight, generally frailty.
link |
We just put out a paper last year on that.
link |
The other thing we can use it for,
link |
which is a little off the track here,
link |
but we use it for predicting
link |
which microorganisms are in your body,
link |
actually not predicting, telling you.
link |
So our daughter, Natalie, was infected with Lyme disease
link |
a few years ago, almost went blind from it.
link |
And the test took four days.
link |
And I thought, just give me the DNA from her spinal fluid.
link |
I'll go tell you what's in it.
link |
If it's Lyme disease or not, they refused.
link |
And so at that point I said, this has to be done better.
link |
So I've started a company that now can take a sample
link |
of any part of your body.
link |
It's typically done now with liver transplant patients
link |
to detect viruses that come out of their organs.
link |
But that's another area that AI is extremely important for.
link |
I think if you're not, in five years,
link |
if you're not using deep learning, you've got a problem.
link |
Because the amount of data that we generate now
link |
as biologists is just terabytes.
link |
It can be terabytes per week.
link |
It'll eventually be terabytes per day.
link |
And then we just go from there.
link |
And I actually have trouble recruiting enough
link |
bioinformaticians.
link |
A lot of our work is now just number crunching.
link |
A part of that is collecting the data,
link |
which is kind of something we've talked a little bit about.
link |
But is there something you can say about
link |
how we can collect more and more data,
link |
not just on the one person level,
link |
like for you to understand your various markers,
link |
but to create huge datasets
link |
to understand how we can detect certain pathogens,
link |
detect certain properties, characteristics
link |
of whether it's aging or all the other ways
link |
that the human body can fail.
link |
It seems like with biology,
link |
there's a kind of privacy concerns that,
link |
well, actually not privacy concerns,
link |
it's almost like regulation that kind of prevents
link |
hospitals from sharing data.
link |
I'm not sure exactly how to say it,
link |
but it seems like when you look at autonomous vehicles,
link |
people are much more willing to share data.
link |
When you look at human biology system,
link |
people are much less willing to share data.
link |
Is there a hopeful path forward
link |
where we can share more and more data at a large scale
link |
that ultimately ends up helping us understand
link |
the human body and then treat problems with the human body?
link |
So we are right in the middle,
link |
we're living through what's gonna be seen
link |
as one of the biggest revolutions in human health,
link |
through the gathering of data about our bodies.
link |
And 20 years ago, people didn't wanna go on social media,
link |
they're worried about it, now you have to,
link |
if you're a kid, that's for sure.
link |
Same with medical records,
link |
these are becoming all digitized and expanded.
link |
Ultimately, we're going to, even if we don't want to,
link |
have to be monitored.
link |
There's gonna be a court case that,
link |
I bet two, three years from now, someone's gonna say,
link |
how come my father died from a heart attack?
link |
You had these biosensors, 20 bucks, and you didn't use it.
link |
Lawsuit right there, and suddenly,
link |
all hospitals have to give you one of these.
link |
There'll be a reversal, like to where,
link |
it's your fault if you don't collect the data,
link |
that's brilliant, and that's absolutely right.
link |
I mean, that's absolutely right.
link |
That's the frustration I feel on going to the doctor,
link |
is like, it's almost negligent to not collect the data,
link |
because you're making,
link |
there's something really wrong with me,
link |
and you're making decisions based on very few tests,
link |
that's almost negligent, when you have the opportunity
link |
to collect a huge amount more data.
link |
Well, let me tell you something.
link |
Like, I've got this inside tracker data
link |
for myself over a decade,
link |
and you'd think my doctor would roll his eyes at this,
link |
oh, he's gone to a consumer company, blah, blah, blah.
link |
I had my first checkup in a year with him
link |
through video conference, and he was running blind.
link |
He really didn't know what was going on with me.
link |
He asked the usual things.
link |
How am I sleeping?
link |
These kind of usual things.
link |
And I said, well, I've got new tests back
link |
from inside tracker, and he said, great,
link |
I'd love to see them.
link |
So I share screen, and we look at the graphs,
link |
look at the data, and he's loving it,
link |
because he cannot order these tests willy nilly.
link |
So I said, well, let's order a HbA1c blood glucose levels,
link |
because I'm very interested in that.
link |
That tracks with longevity.
link |
And he said, well, I have no reason to order that.
link |
Do you have a family history?
link |
Do you have any symptoms of diabetes?
link |
Well, I can't order the test.
link |
I almost wanted to reach through the computer
link |
and strangle him, but instead, I pay a little bit
link |
to get these tests done, and then he looks at them.
link |
So that's now the way consumer health is going,
link |
is that you can get better data than your doctor can,
link |
but they'd like you to do that.
link |
Quick human question, maybe you can educate me.
link |
I think doctors sometimes have a bit of an ego.
link |
I understand that the doctors super experience
link |
a lot of things, but this is a fundamental question
link |
of human variability.
link |
Like, I know a lot of specific details about like,
link |
I mean, it depends, of course, what we're talking about,
link |
but I bring a lot of knowledge, and if I have data with me,
link |
then I have like several orders of magnitude more knowledge.
link |
And I think there's an aspect to it where the doctor
link |
has to put their expert hat, like take it off
link |
and actually be a curious, open minded person
link |
and study and look at that data.
link |
Do you think it's possible to sort of change the culture
link |
of the medical system to where the doctors are almost,
link |
as you said, are excited to see the data?
link |
Or is that already happening?
link |
It's really happening.
link |
Now, we've probably lost the last generation.
link |
They're no hopers, but so I teach at Harvard Medical School
link |
and they're excited about this.
link |
They're excited about aging,
link |
which is a new aspect to medicine.
link |
Oh, wow, we can do something about that.
link |
And then, yeah, all this data, what do we do with it?
link |
There's still the traditional pathology and all that stuff,
link |
which they need to know, but time will change their mindset.
link |
I'm not worried about that.
link |
And like we were discussing, this isn't a question of if,
link |
it's just a matter of when.
link |
And I have a front row seat on all of this.
link |
I had breakfast with a CEO who is making this happen
link |
I can tell you for sure that most people have no idea
link |
that this revolution is occurring
link |
and is happening so quickly.
link |
If you're running a hospital and you can save $2,000
link |
per cardiac patient, what are you going to do?
link |
You have to use it.
link |
Otherwise, the hospital down the road
link |
is going to be beating you.
link |
And there are large hospital aggregations,
link |
so there's Ascension and others,
link |
that just have to go this way for budgetary reasons.
link |
And right now, the US spends 17% of their GDP on healthcare.
link |
Let's say one of these buttons on my chest costs $20.
link |
It's rechargeable.
link |
And it can predict people's health
link |
and save on antibiotics to prevent heart attacks.
link |
How many billions, if not trillions of dollars,
link |
will that save over the next decade?
link |
Yeah, so when the public wakes up to this,
link |
they'll almost demand it.
link |
Like, this should be accepted everywhere.
link |
It's going to save a lot of money.
link |
It's going to improve the quality of life.
link |
Well, and the CFOs of hospital groups will have to.
link |
And insurance companies are going to want to get in on this.
link |
So now that gets to privacy, right?
link |
Should an insurance company have access to your data?
link |
But you could voluntarily show them some of it
link |
if they give you a discount.
link |
And that's also being worked on right now.
link |
I hope we do create kind of systems
link |
where I can volunteer to share my data
link |
and I can also take the data back,
link |
meaning like delete the data, request deletion of data.
link |
And then maybe policy creates rules
link |
to where you can share data, you could delete the data.
link |
And I think if I have the option to delete all my data
link |
that a particular company has,
link |
then I'll share my data with everyone.
link |
I feel like if, because that gives me the tools
link |
to be a consumer, an intelligent consumer,
link |
of awarding my data to a company that deserves it
link |
and taking it back when the company is misbehaving.
link |
And in that way, encourage,
link |
as a consumer in the capitalist system,
link |
encourage the companies that are doing great work
link |
Well, yeah, healthcare data security is number one.
link |
On my mind, InsideTracker made sure that that was true.
link |
But these buttons on your chest,
link |
there's very private stuff they can probably tell
link |
if you're having sex one night, right?
link |
So this is not the kind of stuff you want leaked.
link |
So I don't know whether it's blockchain or something.
link |
Speak for yourself.
link |
I want this public.
link |
I guess it depends on how you go.
link |
But there's a lot of stuff you don't want out there.
link |
And this definitely has to be number one
link |
because it's one thing to have your credit card
link |
information stolen, it's another thing
link |
your health records are permanently out there.
link |
So there's, on the biology side,
link |
super exciting ways to slow aging.
link |
But there's also on the lifestyle side.
link |
I recently did a 72 hour fast.
link |
It's just an opportunity to take a pause
link |
and appreciate life.
link |
Think about, there's something about fasting
link |
that encourages you to reflect deeper
link |
than you otherwise might.
link |
The time kind of slows.
link |
And you also realize that you're human
link |
because your body needs food.
link |
And you start to see your body's almost as a machine
link |
that takes food and produces thoughts.
link |
And then ends briefly.
link |
I mean, you start to, depending who you are,
link |
if you're like engineering minded,
link |
you start to think of this whole thing
link |
as a kind of, yeah, as a machine.
link |
And then also feelings fill this machine.
link |
Feelings of gratitude, of love,
link |
but also the uglier things of jealousy
link |
and greed and hate and all those kinds of things.
link |
You start to think, okay, how do I manage this body
link |
to create a rich experience?
link |
All of that comes from fasting for me.
link |
Anyway, but there's also health benefits to fasting.
link |
I intermittent fast a lot.
link |
I eat just one meal a day most of the time.
link |
Is there something you could say
link |
about the benefits of fasting in your own life
link |
and in general the anti aging process?
link |
Well, you're a philosopher too.
link |
Sorry, I apologize.
link |
No, I'm impressed.
link |
True Renaissance man.
link |
It's a joy to be here.
link |
So when it comes to fasting, this is,
link |
being abstemious is one of the oldest ways
link |
to improve health.
link |
Probably they knew this 5,000 plus years ago.
link |
So that's not new.
link |
But what we're figuring out is what is optimal
link |
and how does it work?
link |
And one of the things we help contribute to,
link |
which I can speak to with some authority
link |
is that these longevity genes we work on,
link |
we showed back in the early 2000s
link |
are turned on by fasting.
link |
And at least in yeast, we were the first to show
link |
that how calorie restriction fasting works
link |
to extend lifespan.
link |
And that was the first for any species.
link |
Something similar happens in our bodies.
link |
When we're hungry or put our bodies
link |
under any other perceived adversity,
link |
such as running, our bodies think,
link |
wow, we're getting chased by a saber tooth cat or something.
link |
If we're really hot or cold, these probably also work.
link |
To put our bodies in this defensive state,
link |
to activate these genes in the way that whales do
link |
And so hunger is the best way to do that.
link |
In fact, I don't think you have to feel hungry.
link |
You can get used to it.
link |
But if there was one thing I would recommend
link |
to anybody to slow down aging
link |
would be to skip a meal or two a day.
link |
Now it doesn't mean you don't have to live well.
link |
I go to restaurants, I eat regular food.
link |
I try to be as healthy as possible.
link |
But I've gone from skipping breakfast most of my life
link |
now just skipping lunch as well.
link |
And I have my physique back that I had when I was 20.
link |
I feel 20 mentally.
link |
I don't feel tired anymore.
link |
So I'm a huge fan of the one meal a day thing.
link |
Where I'm not good at is going beyond one day.
link |
But if you do three days.
link |
Have you ever fasted longer than 24 hours?
link |
I tried doing two days.
link |
I might have made it to the third and given up.
link |
I just find that I'm not very,
link |
I don't have a lot of willpower.
link |
I also hate exercise.
link |
So I'm not sure how long I'm gonna live.
link |
But I've managed to do one meal a day.
link |
So if I can do that, seriously, anybody can do that.
link |
To your listeners and viewers, I would say,
link |
don't try to do it all at once.
link |
You can't go from snacking and eating three meals a day
link |
to what I do easily.
link |
Work your way up to it, but also compensate with drinking.
link |
If you like tea, if you like coffee, put some milk in it.
link |
You can fill your stomach up with liquids,
link |
diet sodas, I get criticized for drinking,
link |
but I'm gonna continue to have those.
link |
But then I power through the day.
link |
I definitely don't feel tired.
link |
I don't have a lag anymore.
link |
But also give it at least two weeks
link |
because there's a habit as well.
link |
Having something in your mouth, chewing,
link |
feeling that fullness, you can break that habit.
link |
And within two, three weeks, you'll have done it.
link |
So I'm not actually even that strict about it.
link |
You said diet soda.
link |
Yeah, people are very kind of weirdly strict
link |
about fasting, the rules in fasting.
link |
Like for example, I drank Element electrolytes
link |
when I was fasting, and that has like five calories.
link |
And so technically it's not fasting.
link |
Or people will say like, if you drink coffee,
link |
there's caffeine, and they'll say
link |
that's technically not fasting
link |
because there's some kind of biological effects
link |
of caffeine, but whatever.
link |
Of course, there's like biological benefits
link |
that you can argue about,
link |
but there's also just experiential benefits.
link |
Just calorie restriction broadly has a certain experience
link |
to it that, like for me personally,
link |
just as you said, has made me feel really good.
link |
That said, especially, I've gained quite a bit of weight,
link |
maybe even like 15 pounds, something like that,
link |
since I moved to Austin, Texas.
link |
And I still keep the same diet,
link |
but I eat a lot of meat in that one,
link |
just because it's delicious,
link |
because it's also the amazing people I met in Texas.
link |
It's just there's like a camaraderie,
link |
a friendship, a love to the people
link |
that like makes you really enjoy
link |
the atmosphere of eating the brisket and the meat.
link |
Is this Joe Rogan insisting?
link |
Joe is, I mean, he's very different.
link |
Joe loves bread and pasta.
link |
Like he knows that his body feels best
link |
doing keto or carnivore.
link |
So that's what he usually tries to stick to,
link |
but he also does not hold back,
link |
and he'll just eat pasta when he eats pasta,
link |
and he sort of enjoys life in that way.
link |
I can't, I don't know how to enjoy life in that way.
link |
I also love pasta, but I'm just not going to enjoy it,
link |
because I know my body ultimately
link |
does not feel good with pasta.
link |
So it's a funny kind of dichotomies.
link |
I would like to cheat, I guess,
link |
by eating more meat than I, you know, like overeating
link |
on the things that I know my body feels good on
link |
as opposed to eating stuff I shouldn't,
link |
like cake and all those kinds of things.
link |
I tend to find happiness in overeating the good stuff
link |
versus eating the bad stuff.
link |
And that's the kind of balance.
link |
Him, he's like, fuck it.
link |
Every once in a while, you gotta enjoy it.
link |
And then also coupled with that for him
link |
is just exercise, like then face his demons the next day
link |
and just like burn a huge amount of calories,
link |
which is, I mean, whatever's up with that guy's mind,
link |
there's an, there's a ability to fully experience life,
link |
which is represented by the pasta,
link |
and the ability to just like fight the demons,
link |
which is represented by all the crazy kettle balls
link |
and running the hills and all this kind of stuff
link |
That takes a lot out of you doing
link |
that kind of insane exercise.
link |
And I think I'm more like you,
link |
or at least towards your direction is like,
link |
I really hate exercise.
link |
So I do it, but I really hate it.
link |
And so it's a balance that you have to strike.
link |
Is there something you could say about the diet side of that
link |
for you personally, but in general,
link |
in order to achieve calorie restriction,
link |
like for me, eating, I know it may not sound healthy,
link |
but eating carnivore, eating mostly meat
link |
has been, has made me feel really good,
link |
both mentally and physically.
link |
Is there something you could say about the kinds of diets
link |
that may improve longevity,
link |
but also enable calorie restriction?
link |
I mean, the first thing that's important to know
link |
is that while many people are interested slash obsessed
link |
with what they eat,
link |
the data that's come out of animal studies at least
link |
is it's far more important when you eat than what you eat.
link |
And this was a fantastic study a few years ago
link |
by my friend, Rafael de Cabo
link |
at the National Institutes of Health in Bethesda.
link |
And he had 10,000 mice on different diets,
link |
hoping to find the perfect mix of carbs, protein, and fat.
link |
And it turns out that the only ones that lived longer
link |
are the ones that only ate once a day.
link |
And so that, if we're not mice,
link |
but I think that we're close enough to mice
link |
that this tells us a lot.
link |
But okay, but I still think the best bang
link |
for the longevity buck is to do both well,
link |
eat less often and eat the right things.
link |
Now I'll preface this to say, I'm not a nut about this.
link |
I will eat occasional, very occasionally a dessert.
link |
Usually I steal from others, which doesn't count, right?
link |
But you gotta live life, right?
link |
What's a long life if it's not enjoyable anyway?
link |
But what I also found, and this is,
link |
I'll get to your question in a second,
link |
but my microbiome right now and stomach is at a point
link |
where if I try to overeat on a steak,
link |
which I did a couple of days ago,
link |
I actually had a chicken, a fried chicken specifically,
link |
for two days, I felt terrible.
link |
I couldn't sleep, it wouldn't go down.
link |
So I'm now at a point where even if I want to binge
link |
on meat and fried foods, I just can't, it just feels bad.
link |
But what do I recommend?
link |
Well, what the data says, which I try to follow,
link |
is that plant based foods will be better
link |
than meat based foods.
link |
And I know that there are a lot of people who disagree.
link |
But one of the facts is, well, there's a few facts.
link |
One is that people who live a long time
link |
tend to eat those type of diets.
link |
Mediterranean, Okinawa diet,
link |
they're eating mostly plants with a little bit of meat
link |
and not a lot of red meat.
link |
And the other fact is that in animals we know
link |
that there's a mechanism that's called mTOR,
link |
little m, capital TOR, that responds to certain amino acids
link |
that are found in more abundance in meat.
link |
And when it responds, it actually shortens lifespan.
link |
And the converse, if you starve it
link |
of those three amino acids, mostly in meat,
link |
then it extends lifespan.
link |
And there's a drug called rapamycin,
link |
which some people are experimenting with, that does that.
link |
So you might be able to, I'm just saying this here
link |
from all my colleagues, we don't know the results here,
link |
but you could potentially take a rapamycin like drug
link |
and counteract the effects of meat in the long run.
link |
Dono, we should try that actually,
link |
we could do that in the lab.
link |
But getting to the bottom of this,
link |
what I think is going on is that
link |
just like testosterone and growth hormone,
link |
you will get temporary, maybe not temporary,
link |
immediate health benefits.
link |
You'll feel great, you'll get more muscle energy.
link |
But the problem is I think it's at the expense
link |
of longterm health and longevity.
link |
Well, this is actually something I worry about
link |
in terms of longterm effects or the cost
link |
in terms of longevity.
link |
It's very difficult to know how your choices
link |
affect your longevity because the impact is down the line.
link |
Like just because something makes me feel good now,
link |
like eating only meat makes me feel good now,
link |
I wonder what are the costs down the line.
link |
Well, think about what I was saying about the trade offs
link |
between growth and reproduction,
link |
which is what a mouse does and a whale
link |
that grows slowly, reproduces slowly, lives a long time.
link |
It's called the disposable soma theory.
link |
Koch would just propose that in the 70s.
link |
What meat probably does is put you in the mouse category,
link |
super fertile, grow fast, heal fast.
link |
And then if you wanna be a whale,
link |
you should restrict meat and do things
link |
that promote the preservation of your body.
link |
Is it difficult to eat a plant based diet
link |
that you perform well under?
link |
So mentally and physically, just almost,
link |
I'm asking almost like an anecdotal question
link |
or unless you know the science.
link |
Well, the science is still being worked out,
link |
but from the synthesis of everything that I've read,
link |
I try to eat a diet that's definitely full of leafy greens,
link |
particularly spinach is great
link |
because it's got the iron that we need, plenty of vitamins.
link |
I also try to avoid too much fruit and berries,
link |
particularly fruit juice,
link |
definitely avoid that sugar high.
link |
Spiking your sugar is not healthy in the long run.
link |
The other thing that's interesting
link |
is we discovered what we called xenohormetic molecules.
link |
Let me unpack that because it's a terrible name
link |
and I take full responsibility
link |
with my friend, Conrad Howards.
link |
The Xeno means cross species
link |
and hormesis is the term that what doesn't kill you
link |
makes you live longer and be healthier.
link |
And so we're getting cross species health improvements
link |
by molecules that plants make.
link |
And plants make these molecules
link |
when they're also under adversity or perceived adversity.
link |
For instance, I understand
link |
if you want really healthy, good oranges,
link |
you can drive nails into the bark of the tree
link |
before you harvest.
link |
Same with wine, you typically want them to be dry
link |
before you harvest or covered in fungus.
link |
And that's because these plants make these colorful
link |
and xenohormetic molecules
link |
that make themselves stress resistant,
link |
turn on their sirtuin defenses, the serogenes remember.
link |
And when we eat them, we get those same benefits.
link |
That's the idea and we've evolved to do so.
link |
This isn't a coincidence.
link |
It's my theory, our theory that we want to know
link |
when our food supply is under adversity
link |
because we need to get ready for a famine.
link |
And so we hunker down and preserve our body
link |
and by eating these colored foods,
link |
so practically speaking, if it's full of color
link |
or if there's been some chewing by a caterpillar,
link |
organic, grown locally in local farms,
link |
I'll eat that versus a watery, insipid, light colored lettuce
link |
that's been grown in California.
link |
So you want vegetables that have suffered.
link |
You want the David Goggins as a vegetables.
link |
That's the xenohormetic molecules.
link |
I'm gonna take that one with me, thank you.
link |
Oh, I follow him on Instagram, he's always screaming.
link |
So you want that he's basically
link |
the xenohormetic version of a human.
link |
So these are the molecules that are representative
link |
of the stress that a plant has been under.
link |
Yeah, the best example of that is resveratrol,
link |
which many people, including myself,
link |
take as a supplement.
link |
Grapes, grapevines produce that in abundance
link |
when they're dried out or they have too much light
link |
or fungus and that we've shown activates
link |
the Sertu enzyme in our bodies,
link |
which remember is what extends lifespan in yeast
link |
and slows down aging in the brain.
link |
Yeah, I tend to avoid fruit as well.
link |
So green, veggies, anything that's not very sweet.
link |
So I would just say you're relatively low,
link |
like you try to avoid sugary things as well.
link |
Yeah, I'm fairly militant about that.
link |
I rarely would add sugar to anything.
link |
Occasionally I would eat a slice of cheesecake,
link |
but that would be maybe once or twice a year.
link |
You have to give in occasionally.
link |
But yeah, anything that's sweet,
link |
I would rather substitute something like Stevia
link |
if I need a sugar hit.
link |
What about exercise?
link |
Your favorite topic.
link |
I don't mind talking about it.
link |
Is there benefits to longevity from exercise?
link |
Well, no doubt, that's proven.
link |
Just like fasting, it's pretty clear that that works.
link |
For example, there are studies of cyclists.
link |
It was something like people that cycle
link |
over 80 miles a week have a 40% reduction
link |
in a variety of diseases, certainly heart disease.
link |
So that's not even a question,
link |
but what's interesting is that we're learning
link |
that you don't need much to have a big benefit.
link |
It's an asymptotic curve.
link |
And in fact, if you overdo it,
link |
you probably have reduced benefits,
link |
particularly if you start to wear out joints,
link |
that kind of thing.
link |
But just 10 minutes on a treadmill a few times a week,
link |
lose your breath, get hypoxic, as it's called,
link |
seems to be very beneficial for longterm health.
link |
And that's the kind of exercise that I like to do, aerobic.
link |
Though I do enjoy lifting weights,
link |
so that is what I call my exercise,
link |
which has other benefits,
link |
including maintaining hormone levels, male hormone levels.
link |
But also really why I do it is I want to be able
link |
to counteract the effects of sitting for most of the day.
link |
And as you get older, you lose muscle mass.
link |
It's a percent or so a year.
link |
And I don't wanna be frail when I'm older
link |
and fall over and break my hip,
link |
which happens every 20 seconds in this country.
link |
So maintaining that strength,
link |
but also doing the cardio for the longevity,
link |
for avoiding the heart disease.
link |
Yeah, I definitely, just like with fasting,
link |
have the philosophical benefit of running long
link |
I enjoy it, because it kind of clears the mind
link |
and allows you to think,
link |
and actually listen to brown noise as I run.
link |
It really helps remove myself from the world
link |
and just like zoom in on particular thoughts.
link |
What are these brown noise?
link |
It's like white noise, but deeper.
link |
So like the white noise is like shh,
link |
and then brown noise is more like,
link |
That sounds great.
link |
Yeah, yeah, it's more soothing probably.
link |
There could be science to this.
link |
I need to look this up.
link |
I've been meaning to.
link |
But when I started,
link |
this is maybe like five years ago,
link |
I started listening to brown noise when I work.
link |
And the first time I listened to it,
link |
something happened to my mind
link |
where it just went like zoomed in
link |
to like, in a way that it felt like really weird.
link |
Like how precisely it was able to sort of
link |
remove the distractions of the world
link |
and really help my mind.
link |
Obviously, like the mind is trying to focus
link |
and then it just enabled that process
link |
of trying to focus on a particular problem.
link |
I don't know if this is generalizable to others.
link |
People should definitely try it
link |
if you're listening to this.
link |
Maybe it's just my own mind,
link |
but it's funny, like it made me,
link |
brown noise made me realize
link |
that there's probably hacks out there
link |
that I should be constantly looking for.
link |
It's almost like an encouraging
link |
and motivating event
link |
that maybe there's other stuff out there.
link |
Maybe there's other brown noise like things out there
link |
that truly like almost immediately make me feel better.
link |
I don't know if it's generalizable to others,
link |
but it does seem that it's the case
link |
that there's probably for many others,
link |
things like that that could be discovered.
link |
And so it's always disappointing
link |
when I find things in life
link |
that I wish I would have found earlier.
link |
I got LASIK eye surgery a few years ago
link |
and the first thought I had like the next day
link |
when I woke up is like,
link |
damn it, why didn't I do this way earlier?
link |
There's all this stuff of that nature
link |
that are yet to be discovered.
link |
So it pays to explore.
link |
You have a different mind, you have quite a beautiful mind.
link |
So I suspect brown noise helps you focus
link |
and cause you're probably all over the place
link |
if you don't control it.
link |
It means something about it.
link |
It's a programmer thing.
link |
I don't, programming is a really difficult mental journey
link |
cause you have to keep a lot of things in mind.
link |
You have to, so you're constantly designing things
link |
then you have to be extremely precise
link |
by making those things concrete in code.
link |
You also have to look stuff up on the internet
link |
to sort of feed like information
link |
and looking up stuff on the internet,
link |
internet is full of like distracting things.
link |
So you have to be really focused
link |
in the way you look stuff up in pulling that information in.
link |
So it requires a certain discipline and a certain focus
link |
that I've been very much exploring how to do.
link |
Like I do it really well in the morning,
link |
coffee is involved, all those kinds of things.
link |
You're trying to optimize, keeping very positive inspired,
link |
no social media, all those kinds of things
link |
and trying to optimize for.
link |
And everybody has their own kind of little journey
link |
that they try to understand.
link |
You get this from like writers
link |
when you read about the habits of writers,
link |
like the habits they do in the morning,
link |
they usually write like two, three, four hours a day
link |
It's like they optimize that ritual.
link |
And then there's always Hunter S. Thompson.
link |
So sometimes it pays off to be wild.
link |
How important is sleep for longevity?
link |
I would guess based on the evidence
link |
that it's really important
link |
and because we don't know for sure.
link |
But what we know from animal studies is the following.
link |
If you restrict sleep from a rat for just two weeks,
link |
it'll develop type two diabetes.
link |
It's that important.
link |
So that's the main thing.
link |
What we also know is at the molecular level
link |
that if you disrupt your sleep wake cycle,
link |
so we actually have proteins that go up and down
link |
that control our sleep wake.
link |
All of us, most of our cells do that.
link |
If you disrupt that, you'll get premature aging.
link |
The opposite is true.
link |
That as you get older, that cycle,
link |
the amplitude becomes diminished.
link |
And this is why it's harder to get to sleep
link |
and you've got all sorts of problems.
link |
And I think what's going on is this positive feedback loop,
link |
which is a disaster in your old age,
link |
which is you're aging,
link |
you can't at this moment totally prevent that.
link |
And then it's disrupting your sleep
link |
and you get not enough sleep
link |
and then that's gonna accelerate your aging process.
link |
And so it's known that the people who are shift workers
link |
are most susceptible to certain age related diseases.
link |
So your bottom line, you definitely wanna work on that.
link |
It's one of the reasons I have this ring on my finger,
link |
which helps me optimize my sleep
link |
and learn what I do the day before,
link |
if it was a bad idea and I'll stop doing that,
link |
like eating a fried chicken.
link |
I see you're still carrying the burdens of that decision.
link |
But yeah, sleep is one of those things
link |
that's making me wonder about the variability
link |
between humans a little bit
link |
and how science is often focused on,
link |
like it's not often focused on high performers
link |
in a particular way.
link |
And it's looking at the aggregate
link |
versus the individual cases.
link |
For example, like for me,
link |
I don't know what the exact hours are,
link |
but like power naps are incredible.
link |
I tend to look at the metric of stress and happiness and joy
link |
and try to optimize those.
link |
So decreasing stress, increasing happiness
link |
and using sleep as just one of the tools to do that.
link |
Because like hitting the five, six, seven, eight,
link |
nine hour mark or whatever the correct mark is,
link |
I find that to be stress inducing for me
link |
versus stress relieving.
link |
Like thinking about that,
link |
I feel best if I sleep sometimes for eight hours,
link |
sometimes for four hours and then power nap.
link |
And as long as I have a stupid private,
link |
usually smile on my face,
link |
that's when I'm doing good,
link |
as opposed to getting a perfect amount of sleep
link |
according to whatever the latest blog post is.
link |
And I also pull all nighters still.
link |
I also think there's something about the body,
link |
like as long as you do it regularly,
link |
it's not as stress inducing.
link |
Like you know what it is.
link |
The reason I pull all nighters isn't for like,
link |
I'm playing Diablo three or something,
link |
is because I'm doing something I'm truly passionate about.
link |
Well, like I'm also love video games,
link |
but I'm doing something I'm truly passionate about.
link |
And it's almost like there's the Jocko Willing feeling
link |
of when I'm up at 7 a.m. and I haven't slept all night
link |
and still I'm working on it.
link |
There's a kind of a celebration of the human spirit
link |
that I really enjoy it.
link |
Like, and that's happiness.
link |
And to sort of then,
link |
and I usually don't tell that kind of stuff to people
link |
because their first statement will be like,
link |
you should get more sleep.
link |
It's like, no, I'm doing stuff I love.
link |
You should get more love in your life, bro.
link |
So, but that said, in aggregate,
link |
when you look at the full span of life,
link |
is probably you should be getting
link |
a consistent amount of sleep.
link |
And it seems like it's in that seven, eight hour range.
link |
Yeah, but it's similar to food.
link |
It's the quality, not the quantity, right?
link |
And when you get it.
link |
So I look at my data pretty often.
link |
And what makes a difference to me is not the amount of hours,
link |
but the quality, the depth and the deep sleep
link |
is what will do it.
link |
So if I have a lot of alcohol before going to sleep
link |
and I can see my heart rate being different,
link |
but what really kills me is that I don't get a lot
link |
of that deep sleep and I wake up barely remembering stuff.
link |
So that, like you say, if you're happy and contented
link |
and you don't have these cortisol chemicals
link |
going through your body,
link |
you will more naturally get into that deep state.
link |
And even if you just get four hours,
link |
way better than eight hours of none of that.
link |
Yeah, yeah, that's beautiful.
link |
And some of that could be genetic.
link |
For me, I just, I fall asleep like this.
link |
If you want me to fall asleep right now, I can do it.
link |
It's no, I have no problem with it.
link |
Combined with coffee, I just had two energy drinks.
link |
I can probably sleep.
link |
So that, I don't know if that's genetics
link |
or it's kind of, I don't know what it is.
link |
Or maybe that I don't have kids and I'm single.
link |
So I don't have, I'm almost listening
link |
to some kind of biological signal versus societal signal
link |
on when I'm supposed to go to sleep.
link |
So I just go to sleep whenever I feel like going to sleep.
link |
Well, that's because you're a self employed.
link |
Most people don't have that luxury,
link |
but we're lucky, the two of us,
link |
that we can make our own hours.
link |
But yeah, it's super important.
link |
And those people who have shift work,
link |
I mean, they really need to change the way that works
link |
because they're literally killing those people.
link |
Is there something you could say about the,
link |
the mind and stress in terms of effect on longevity?
link |
Sort of, I don't know if you think about it this way,
link |
but when you talk about the biological machine,
link |
it's always these mechanisms that don't,
link |
are not necessarily directly connected to the brain
link |
or the operation of the brain.
link |
Like what's the role about stress and happiness
link |
and yeah, the sort of higher cognitive things
link |
going on in the brain on longevity.
link |
Well, that's a great point that the brain
link |
is the center for longevity.
link |
Actually, we do know that.
link |
For a start, when I'm stressed,
link |
I can see mentally stressed,
link |
then I can see it in my body.
link |
Heart rate, hormones, it's clear.
link |
That's no true surprise.
link |
So you've got to work on your brain first and foremost.
link |
If you are totally freaked out, agitated all the time,
link |
you will live shorter.
link |
I'm certain of it.
link |
You know, I keep fish.
link |
I'm a big aquarium guy.
link |
And you can see the difference
link |
between the fish that's having a good time and dominant
link |
and one that gets picked on.
link |
It just looks like crap.
link |
You don't want to be that,
link |
the little fish getting picked on if you can help it.
link |
So I used to be extremely stressed as a kid.
link |
I was a perfectionist, very shy,
link |
always worried about being a failure.
link |
If I didn't get an A+, you know,
link |
I was crying in my bedroom, that kind of sad existence.
link |
I got into my twenties, then in my thirties,
link |
and realized that's not the way to live.
link |
So I've worked very hard to get to this point
link |
where I almost never get stressed, never.
link |
There's nothing that, I've never gotten angry in my lab.
link |
Sometimes it's like a,
link |
most of the time it's like a kindergarten.
link |
I haven't lost my temper.
link |
I'm very calm, but that's intentional.
link |
And I don't worry about stuff.
link |
Millions of dollars, billions of dollars at stake sometimes.
link |
We're all headed to the same place anyway.
link |
Don't worry about it.
link |
But to answer your question, I think in a better way,
link |
if you manipulate the brain of an animal,
link |
I'll give you an example.
link |
If we turn on this CERT gene that I mentioned,
link |
CERT1, we, a good friend of mine at WashU,
link |
Sheena Mai did this.
link |
They upregulated that gene
link |
just in the neurons of the animal.
link |
So that's sufficient to extend lifespan.
link |
We also know that you can manipulate the part of the brain
link |
called the hypothalamus,
link |
which leeches a lot of chemicals into the body and proteins,
link |
most of which we don't know yet,
link |
but just changing the inflammation of that little organ
link |
or part of the brain is sufficient
link |
to make animals live longer as well.
link |
So get your brain in order first
link |
before you tackle anything else, I would say.
link |
So you kind of mentioned this,
link |
with the inside tracker, there's ability
link |
to take blood measurement and then infer from that
link |
a bunch of different things about your body
link |
and how you can improve the longevity.
link |
And you've also mentioned saliva
link |
and more efficient ways to get data.
link |
What does that involve?
link |
What's the future of data collection look like
link |
for the human biological system?
link |
Right, well, yeah, the issue with blood is
link |
you need someone to take it.
link |
I mean, or you prick your finger, which hurts.
link |
So you've got to have something better.
link |
So I think what the future looks like
link |
is that you'll spit onto a little piece of paper
link |
and stick it in a machine and it'll do that for you.
link |
But we're not there yet.
link |
So the intermediate future that I'm building right now
link |
is that you would take a swab of the inside of your mouth,
link |
which is the easiest way to take cells out of your body
link |
and just ship them off.
link |
Okay, so it's called a buckle swab.
link |
I think we became very used to that.
link |
Right now, because of COVID,
link |
people don't like going to the doctor as much.
link |
They don't like going out.
link |
They just want to have home tests.
link |
And so that I think is the next 10 years
link |
where you'll get a kit in the mail,
link |
you'll swab your cheeks, stick it back in an envelope,
link |
send it off and a week later you have
link |
either a doctor's report or a health recommendation.
link |
And what can you get off a cheek swab?
link |
Well, you can get anything.
link |
You can get hormones, stress levels,
link |
stress hormones, blood glucose levels.
link |
You can also tell your age reasonably accurately doing that,
link |
actually quite accurately.
link |
And those clocks can not just tell you
link |
how you're doing over time,
link |
but can be used to give you recommendations
link |
to slow that process down.
link |
Cause some people sometimes are 10 years older biologically
link |
than their actual chronological age.
link |
I mean, why does it matter how many times
link |
the earth's gone around the sun seriously?
link |
Who cares about birthdays?
link |
It's how long your body's clock has been ticking
link |
So I could take a cheek swab from you today, Lex,
link |
take it back to my lab.
link |
And we then by tomorrow tell you
link |
how old you are biologically based on
link |
what we call the epigenetic clock.
link |
And you might be freaked out, you might be happy,
link |
but either way we can advise you
link |
on how to improve the trajectory.
link |
Cause we know that smoking increases
link |
the speed of that clock.
link |
We also know that fasting and people who eat the right foods
link |
have a slower clock.
link |
Without that knowledge, you're flying blind.
link |
But I like the idea of a swab,
link |
cause it's just so easy.
link |
A lot of us have done something like that for COVID tests.
link |
It's not a big deal.
link |
I've been doing a nonstop rapid antigen test.
link |
So let me say that particular one rapid antigen test,
link |
they've been a source of frustration for me
link |
because like everybody should be doing it.
link |
We've also been working in my lab on democratizing
link |
these tests to bring them down from a few hundred bucks
link |
So just to clarify,
link |
you're talking about not research,
link |
you're talking about like company stuff,
link |
like actual consumer facing things?
link |
The research on bringing the price down
link |
has occurred in my lab at Harvard.
link |
And then that intellectual property is being licensed
link |
and has been licensed out to a company
link |
that will be consumer facing.
link |
So anybody for a small amount of money can do this.
link |
Well, you got subscriber number one obsessed.
link |
I think that's a beautiful, beautiful idea.
link |
So somebody who maybe I would have been more hesitant
link |
about it until COVID,
link |
but the home tests are super easy.
link |
I almost wanted to share that data with the world,
link |
like in some way, not the entirety of the data,
link |
but like some visualization of like how I'm doing.
link |
Like, it's almost like when you share,
link |
if you had like a long run or something like that,
link |
I wish I could share because it inspires others.
link |
And then you can have a conversation about like,
link |
well, what are the hacks that you've tried
link |
and have a conversation about like how to improve lifestyle
link |
and those kinds of things that's grounded in data.
link |
That's exactly, that's what's gonna happen.
link |
Now, everything's anonymous, of course.
link |
We talked about security there,
link |
but once it's anonymized, you can then plot these numbers.
link |
And I've plotted my epigenetic age
link |
versus hundreds of other people
link |
who have taken this test now.
link |
And I can tell you where I fit relative to others
link |
in terms of my biological age.
link |
And I'm happy to share that with you
link |
because it's pretty low.
link |
You can choose to share it, of course,
link |
not everyone wants to share that.
link |
But when you go to the doctor,
link |
first of all, your doctor does treat you
link |
as though you're an average person
link |
and none of us are average, there's no such thing.
link |
But second of all, we never know
link |
how we're doing relative to others
link |
because we all, most of us, we don't share our information.
link |
So we might have this number and that number,
link |
but do you know that your numbers are good for your age
link |
Even your doctor probably doesn't even know.
link |
So this graph that I'm talking about
link |
is the beginning of a world where you can say,
link |
For the two of us, we're white and we're male
link |
and we're this age and we do this.
link |
Are we doing the right things or the wrong things?
link |
Do we need to fix certain things?
link |
And this is what the future is.
link |
It's forget about just experimenting
link |
and not knowing the result.
link |
I mean, who doesn't experiment and doesn't look at the data?
link |
No one, it makes no sense.
link |
So we're gonna enter a world
link |
where we have a dashboard on our body,
link |
the swabs, the blood tests, the biosensors
link |
where our doctors can look at that,
link |
but we can also look at it and they can recommend,
link |
go to this restaurant down the road.
link |
They've got this great meal.
link |
It's high in whatever you need today
link |
because you're lacking vitamin D and vitamin K2.
link |
Ridiculous question or perhaps not.
link |
If you look maybe 50 years from now
link |
or 100 years from now, a person born then,
link |
what do you think is a good goal
link |
in terms of how long a person would live?
link |
What is the maximum longevity that we can achieve
link |
through the methods that we have today
link |
or are developing some of the things
link |
we've been talking about in terms of genetics,
link |
in terms of biology?
link |
Is there a number?
link |
Right, well, so it changes all the time
link |
because technology is changing so quickly.
link |
I keep revising the number upward,
link |
but I would say that if you do the right things
link |
during your life and start at an early age,
link |
let's say 25, we don't want malnutrition, starvation.
link |
That's not what I'm talking about.
link |
But in your 20s, start eating the kind of diets
link |
that I talked about, skipping meals.
link |
In animals, that gives you an extra 20 to 30%.
link |
We don't know if that's true for humans
link |
and even 5% more would be a big deal for the planet.
link |
I think that we should all aim to at least reach a century.
link |
I'm a little bit behind.
link |
I was born too early to benefit the most
link |
from all of this discovery.
link |
Those of you who are in your 20s,
link |
you should definitely aim to reach a hundred.
link |
I don't see why not.
link |
Consider this, this is really important.
link |
The average lifespan of a human
link |
that looks after themselves but doesn't pay attention
link |
is about 80, okay?
link |
Japan, that's the average age for a male, a bit higher.
link |
If you do the right things in your life,
link |
which is eat healthy food, don't overeat,
link |
don't become obese, do a bit of exercise,
link |
get good sleep and don't stress,
link |
that gives you on average 14 extra years.
link |
That gets you to 94.
link |
So getting to a hundred,
link |
if you just focus on what I'm talking about,
link |
it's not a big deal.
link |
So what's the maximum?
link |
Well, we know that one human made it to 122
link |
and a number of them make it into their teens.
link |
I think that's also the next level
link |
of where we can get to with the types of technologies
link |
that I'm talking about.
link |
Medicines, like I mentioned rapamycin,
link |
there's one called metformin, which is the diabetes drug,
link |
That in combination with these lifestyle changes
link |
should get us beyond a hundred.
link |
How long can we ultimately live?
link |
Well, there's no maximum limit to human lifespan.
link |
Why can a whale live 300 years, but we cannot?
link |
We're basically the same structure.
link |
We just need to learn from them.
link |
So anyone who says, oh, you max out at X,
link |
I think is full of it.
link |
There's nothing that I've seen that says
link |
biological organisms have to die.
link |
There are trees that live for thousands of years
link |
and their biochemistry is pretty close to ours.
link |
What do you think it means to live for a very long time?
link |
Let's say if it's 200 years we're talking about
link |
or a thousand years.
link |
There's some sense, you could argue,
link |
that there is immortal organisms already living on Earth,
link |
like there's bacteria.
link |
So there's certain living organisms
link |
that in some fundamental way do not die
link |
because they keep replicating their genetic,
link |
they keep like cloning themselves.
link |
Is it the same human if we can somehow persist
link |
the human mind, like copy, clone certain aspects
link |
and just keep replacing body parts?
link |
Do you think that's another way to achieve immortality?
link |
To achieve a prolonged sort of increased longevity
link |
is to replace the parts that break easily
link |
and keep, because actually from your theory of aging
link |
as a degradation of information,
link |
so an information theory view of aging,
link |
like what is the key information that makes a human?
link |
Can we persist that information
link |
and just replace the trivial parts?
link |
Yeah, I mean the short answer is yes.
link |
We're already replacing body parts
link |
but what makes us human is our brain.
link |
Everything else is suboptimal except our brain.
link |
The ability to replace actual neurons is really hard.
link |
I think it might be easy to upload
link |
rather than replace neurons because they're so tight,
link |
it's such a network and just perturbing the system.
link |
It's Roger and Gizcat.
link |
You change everything once you get in there.
link |
The problem is, well, I guess the solution,
link |
let me go to the solution that's more interesting.
link |
What we're learning is that if you reverse
link |
the age of nerve cells,
link |
it looks like they get their memories back.
link |
So the memories are not lost.
link |
They're just that the cells don't know how to interpret them
link |
and function correctly.
link |
And this is one of the things we're studying in my lab.
link |
If you take an old mouse that has learned something
link |
when it was young but forgotten, does it get that back?
link |
And all evidence points to that being true.
link |
So I'd rather go in and rejuvenate the brain as it sits
link |
rather than replace individual cells,
link |
which would be really hard.
link |
What do you think about like efforts like Neuralink,
link |
which basically you mentioned uploading,
link |
are trying to figure out,
link |
so creating brain computer interfaces
link |
that are trying to figure out
link |
how to communicate with the brain.
link |
But one of the features of that is trying to record
link |
the human brain more and more accurately.
link |
Do you have hope for that to,
link |
of course, it will lead to us better understanding
link |
from a neuroscience perspective, the human mind,
link |
but do you have hope for it increasing longevity
link |
in terms of how it's used?
link |
I think that it can help with certain diseases.
link |
But I see, at least within our lifetime,
link |
that's the best use of it is to be able to replace
link |
parts of the body that are not functioning,
link |
such as the retina and other parts,
link |
the visual cortex back here.
link |
That's going to be doable.
link |
In terms of longevity,
link |
maybe we could put something on the hypothalamus
link |
and start secreting those hormones and get that back.
link |
Ultimately, I think the best way to preserve the brain
link |
is going to be to record it.
link |
But also, I think it's going to require death,
link |
unfortunately, to then do very detailed scans,
link |
even if you have enough time and money, atomic microscopy,
link |
and rebuild the brain from scratch.
link |
Rebuild from scratch, yeah.
link |
We are living more and more in a digital world.
link |
I wonder if the scanning is good enough
link |
for the critical things in terms of memories,
link |
in terms of the particular quirks
link |
of your cognitive processes.
link |
They're not, they're not, yeah.
link |
We're not close, yes,
link |
but we've made quite a bit of progress,
link |
so if you're an exponential type of person.
link |
Yeah, well, let's dream a little here.
link |
Yes, that's the point.
link |
The way it would work, that I could see it working is,
link |
so you take a single cell slice through your dead brain,
link |
the problem with the engineering aspect is that,
link |
the engineering is, the physical aspect of the brain
link |
is not even half the problem.
link |
The problem is which genes are switched on and off.
link |
This experience that we're having here
link |
is altering certain genes in neurons
link |
that will be preserved, hopefully, for a number of decades,
link |
but you cannot see that with a microscope easily,
link |
but there are technologies invented,
link |
actually just down the hall in the building I'm at,
link |
George Church invented a way, his lab invented a way,
link |
to look at which genes are switched on and off,
link |
not only in a single cell, which any lab can do these days,
link |
but in situ, where it's situated in the brain.
link |
So you can say, okay, this nerve cell,
link |
had these genes switched on and these switched off,
link |
we can recreate that,
link |
but just scanning the brain
link |
and looking how the nerves are touching each other
link |
is not gonna do it.
link |
So you have to scan the full biology, the full details.
link |
And look at the epigenome.
link |
And the epigenome too.
link |
Yeah, which genes are on and off.
link |
It's just easier to reset the epigenome
link |
and get them to work like they used to.
link |
We're doing that now.
link |
Use the hardware we already have,
link |
just figure out how to make that hardware last longer.
link |
Right, ultimately information will be lost,
link |
even genetic information degrades slowly through mutation.
link |
So immortality is not achievable through that means,
link |
though I think we could potentially reset the body
link |
hundreds of times and live for thousands of years.
link |
Okay, so we talked about biology.
link |
Let's, forgive me, but let's talk about philosophy
link |
for just a brief moment.
link |
So somebody I've enjoyed reading,
link |
Ernest Becker wrote The Denial of Death.
link |
There's also Martin Heidegger.
link |
There's a bunch of philosophers who claim
link |
that most people live life in denial of death.
link |
Sort of we don't fully internalize
link |
the idea that we're going to die.
link |
Because if we did, as they say,
link |
there will be a kind of terror of,
link |
I mean a deep fear of death.
link |
The fact that we don't know what's,
link |
like we almost don't know what to do with non existence,
link |
with disappearing.
link |
Like our, the way we draw meaning from life
link |
seems to be grounded in the fact that we exist
link |
and that we at some point will not exist is terrifying.
link |
And so we live in an illusion that we're not going to die
link |
and we run from that terror.
link |
That's what Ernest Becker would say.
link |
Do you think there's any truth to that?
link |
Oh, I know there's truth to that.
link |
I experience it every day when I talk to people.
link |
We have to live that way.
link |
Although unfortunately I can't,
link |
but for most people it's extremely distressing
link |
to think about their own mortality.
link |
We think about it occasionally.
link |
And if we really thought about it every day,
link |
we'd probably be brought to tears.
link |
How much we not just miss ourselves,
link |
but miss our family, our friends.
link |
All living life forms have evolved to not want to die.
link |
And when I mean want,
link |
biochemically, genetically, physically.
link |
That yeast cell, the cells that I studied at MIT,
link |
they were fighting for their lives.
link |
They didn't think,
link |
but our brain has evolved the same survival aspect.
link |
Of course, we don't want to die.
link |
But the problem for us, unfortunately,
link |
it's a curse and a blessing is that we're now conscious.
link |
We know that we're going to die.
link |
Most species that have ever existed don't.
link |
That's a burden, that's a curse.
link |
And so what I think has happened is
link |
we've evolved certainly to want to live for a long time,
link |
perhaps never want to die.
link |
But the thought about dying is so traumatic
link |
that there is an innate part of our brains.
link |
And it's probably genetically wired to not think about it.
link |
I really think that's part of being human.
link |
Because, think about tribes that obsessed
link |
with longevity every day and that we're going to die.
link |
They probably didn't make much technological progress
link |
because they were just crying in their huts every day
link |
or on the Savannah.
link |
So I really think that we've evolved
link |
to naturally deny aging.
link |
And it's one of the problems that I face in my career.
link |
And when I speak publicly and on social media
link |
is that it's shocking.
link |
People don't want to think about their age,
link |
but I think it's getting better.
link |
I think my book has helped.
link |
These tests that we're developing
link |
should help people understand it's not a problem
link |
to think about your longterm health.
link |
In fact, if you don't,
link |
you're going to reach 80 and really regret it.
link |
And the other side of it, so again, Ernest Becker,
link |
but also Viktor Frankl recommended highly
link |
Man's Search for Meaning.
link |
Bernard Williams is a moral philosopher.
link |
They kind of argue that this knowledge of death,
link |
even if we often don't contemplate it, we do at times.
link |
And the very, what you call the curse,
link |
which I agree with you, it's a curse and a blessing
link |
that we're able to contemplate our own mortality.
link |
That gives meaning to life.
link |
So death gives meaning to life,
link |
is what Viktor Frankl argues.
link |
I would probably argue the same.
link |
There's something about the scarcity of life
link |
and contemplating that,
link |
that makes each moment that much sweeter.
link |
Is there something to that?
link |
I think it's individual.
link |
In my case, it's completely wrong.
link |
I appreciate you saying that.
link |
I don't get joy out of every day
link |
because I think I'm going to die.
link |
I get joy out of every day because every day is joyous
link |
and I make it that way.
link |
And even if I thought I was going to live forever,
link |
I would still be enjoying this moment just as much.
link |
And I bet you would too.
link |
Well, I think about that a lot.
link |
I think it's very difficult to know.
link |
I'm almost afraid that I wouldn't enjoy it as much
link |
if I was immortal.
link |
I'm almost afraid to want to be immortal or to live longer
link |
because it perhaps is a kind of justification
link |
for me to accept that I'm going to die.
link |
It's saying like, oh, if I was immortal,
link |
I wouldn't be able to enjoy life as much as I do.
link |
But it's very possible that I would enjoy just as much.
link |
Of course, enjoying life, whether you're immortal or not,
link |
Like it requires you to have the right kind
link |
You can discover, you can focus your mind
link |
on the ugliness of life.
link |
There's plenty of ugly things in this world
link |
and you can focus on them.
link |
Whenever like, you know, if it's raining outside,
link |
you can focus on the fact that you have shelter
link |
and enjoy the hell out of it.
link |
Or you can enjoy running in the rain when it's warm
link |
and the beauty of nature, just being one with nature.
link |
Or you can just complain, it's fucking weather again
link |
in Boston and then it's either always raining
link |
or freezing, damn it.
link |
The same thing with like wifi going out on airplanes.
link |
You can either complain about stupid wifi
link |
on JetBlue or something.
link |
Or you could say like, how incredible it is
link |
that I can fly through the sky and in a matter of hours
link |
be anywhere else in the world.
link |
And then I could also on occasion watch like check email
link |
and even watch movies while connecting through satellites
link |
that are flying through space.
link |
So it's a matter of perspective and perhaps
link |
there's an extra level of work required
link |
when you're immortal because it's easier
link |
when you're immortal or live longer to be lazy,
link |
But if you're not, you can still derive
link |
the same amount of joy.
link |
It's possible, it's possible.
link |
It's definitely possible.
link |
In my life, I went from being the nothing's working
link |
to every day's great to wake up to.
link |
And I think even if you think you can live forever,
link |
you can enjoy every day.
link |
What I do is everything's relative.
link |
We can compare ourselves to our neighbor who has more money
link |
or to the flight that should have had wifi
link |
or which is what I do, I'm still six years old remember.
link |
What a six year old does says, look, I can,
link |
when I tell my fingers to form a fist,
link |
they actually do that.
link |
That's really cool.
link |
That's how I live my life.
link |
I can pick up on your desk here, this metal object.
link |
It's a metal cube, about an inch by an inch by an inch.
link |
And I tell myself not about cubes,
link |
but about inanimate objects.
link |
Probably once a day I'll say, I'm a living thing.
link |
I can think, I can move, I can eat, I am full of energy.
link |
And there's that leaf or this cube here
link |
that will never be alive.
link |
That's what I look at and compare myself to.
link |
And for as long as I live, if it's forever,
link |
of course it won't be, but even if it was forever,
link |
relative to this lump of metal on this table here,
link |
we are wondrous things in the universe
link |
and probably the most wondrous things in the universe.
link |
Yeah, we're able to deeply appreciate the leaf or the cube
link |
and deeply appreciate ourselves,
link |
which is, it can be a curse, but it's mostly a gift,
link |
especially when you're, it's such a beautiful poem.
link |
Now I'm six, I'm as clever as clever,
link |
so I think I'll be six now forever and ever.
link |
That's a good thing to aspire to.
link |
Your grandmother was onto something.
link |
David, this is an incredible conversation.
link |
I'm a huge fan of your work.
link |
So thank you for wasting your valuable time with me today.
link |
I really, really appreciate it.
link |
Thank you for having me on, Lex, appreciate it.
link |
Thanks for listening to this conversation
link |
with David Sinclair, and thank you to Onnit, Clear,
link |
National Instruments, Simply Safe, and Linode.
link |
Check them out in the description to support this podcast.
link |
And now let me leave you with some words
link |
from Arthur Schopenhauer.
link |
All truth passes through three stages.
link |
First, it is ridiculed.
link |
Second, it is violently opposed.
link |
Third, it is accepted as being self evident.
link |
Thank you for listening, and hope to see you next time.