David Sinclair: Extending the Human Lifespan Beyond 100 Years
生物与进化AI 与机器学习音乐与艺术技术与编程心理与人性
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AI 智能总结
大卫·辛克莱谈将人类寿命延长至100岁以上
这是 Lex Fridman 与哈佛大学遗传学教授 David Sinclair 的深度对话。Sinclair 分享了他关于衰老的信息理论、长寿研究的最新进展、他个人的抗衰老实践，以及延长人类健康寿命的路径。
衰老长寿表观遗传学NAD+细胞重编程间歇性禁食生物技术
David Sinclair 是哈佛医学院遗传学教授、Paul F. Glenn 衰老生物学中心联合主任，著有《寿命》（Lifespan），是全球最重要的衰老研究科学家之一，也是多家长寿生物技术公司的联合创始人。
📌 核心观点
- 衰老的信息理论：Sinclair 提出衰老的根本原因是表观遗传信息的丢失——细胞逐渐「忘记」如何正确读取 DNA，导致细胞功能退化。这意味着衰老不是不可避免的，而是一种可以被逆转的信息损失。
- 长寿基因与 NAD+：Sinclair 的研究重点是 sirtuins（长寿蛋白）和 NAD+（烟酰胺腺嘌呤二核苷酸）。他发现通过补充 NMN 或 NR 来提高 NAD+ 水平，可以激活长寿基因，在动物实验中显著延长寿命。
- 热量限制与间歇性禁食：Sinclair 认为热量限制和间歇性禁食是目前最有效的长寿干预措施，它们通过激活 sirtuins 和 AMPK 等长寿通路发挥作用，他本人实践每天只吃一顿饭。
- 细胞重编程：Sinclair 最新的研究方向是通过 Yamanaka 因子（部分）重编程细胞，使其恢复年轻状态。他的团队已经在小鼠实验中成功逆转了视网膜细胞的衰老，恢复了视力。
- 对衰老的重新定义：Sinclair 认为衰老应该被定义为一种疾病，而非自然过程，这样才能获得医学研究资金和监管批准。他预测在未来 10-20 年内，我们将看到第一批真正的抗衰老药物。
✨ 金句摘录
Sinclair：衰老不是不可避免的——它是一种信息丢失，而信息是可以被恢复的。
Sinclair：我们正处于一场医学革命的边缘，在未来 10-20 年内，我们将能够显著延缓甚至逆转衰老。
Sinclair：衰老应该被定义为一种疾病——这不仅是语义问题，而是关乎我们是否认真对待它。
📋 章节目录
暂无章节信息
🔑 关键词
dondatagoingagingagehumanbrainsleepdoingeatstufflongevitygotcellscellpersonbiologygettinggenesbetter
💬 精彩语录
暂无语录
🎙️ 完整对话（2343 条）
Lex Fridman (00:00.000)
The following is a conversation with David Sinclair.
以下是与大卫·辛克莱的对话。
Lex Fridman (00:02.760)
He's a professor in the Department of Genetics at Harvard
他是哈佛大学遗传学系教授
Lex Fridman (00:06.200)
and co director of the Paul F. Glenn Center
保罗·F·格伦中心联合主任
Lex Fridman (00:08.920)
for the Biology of Aging at Harvard Medical School.
哈佛医学院衰老生物学。
Lex Fridman (00:12.280)
He's the author of the book,
他是这本书的作者，
David Sinclair (00:13.280)
Lifespan and co founder of several biotech companies.
Lifespan 是多家生物技术公司的联合创始人。
Lex Fridman (00:16.840)
He works on turning age into an engineering problem
他致力于将年龄变成一个工程问题
Lex Fridman (00:20.800)
and solving it.
并解决它。
Lex Fridman (00:22.160)
Driven by a vision of a world
由世界愿景驱动
David Sinclair (00:23.960)
where billions of people can live much longer
数十亿人可以活得更久
Lex Fridman (00:25.960)
and much healthier lives.
和更健康的生活。
David Sinclair (00:28.160)
Quick mention of our sponsors,
快速提及我们的赞助商，
Lex Fridman (00:30.360)
Onnit, Clear, National Instruments,
Onnit、Clear、国家仪器、
Lex Fridman (00:33.400)
and I, SimpliSafe and Linode.
我、SimpliSafe 和 Linode。
Lex Fridman (00:36.840)
Check them out in the description to support this podcast.
在说明中查看它们以支持此播客。
David Sinclair (00:40.040)
As a side note, let me say that longevity research
作为旁注，让我说一下长寿研究
Lex Fridman (00:42.780)
challenges us to think how science and engineering
挑战我们思考科学和工程如何
David Sinclair (00:45.880)
will change society.
将改变社会。
Lex Fridman (00:47.640)
Imagine if we can live 100,000 years,
想象一下，如果我们能活十万年，
David Sinclair (00:50.400)
even under controlled conditions,
即使在受控条件下，
Lex Fridman (00:51.920)
like in a spaceship say,
David Sinclair (00:53.720)
then suddenly a trip to Alpha Centauri
Lex Fridman (00:55.960)
that is a 4.37 light years away
David Sinclair (00:58.840)
takes a single human lifespan.
Lex Fridman (01:01.280)
And on the psychological, maybe even philosophical level,
David Sinclair (01:05.160)
as the horizons of death drifts farther into the distance,
Lex Fridman (01:08.720)
how will our search for meaning change?
David Sinclair (01:11.120)
Does meaning require death
Lex Fridman (01:13.080)
or does it merely require struggle?
David Sinclair (01:15.720)
Reprogramming our biology will require us to delve deeper
Lex Fridman (01:19.440)
into understanding the human mind and the robot mind.
David Sinclair (01:23.680)
Both of these efforts are as exciting of a journey
Lex Fridman (01:26.600)
as I can imagine.
David Sinclair (01:28.160)
This is the Lex Friedman Podcast
Lex Fridman (01:30.320)
and here is my conversation with David Sinclair.
David Sinclair (01:34.360)
I usually feel like the same person when I was 12.
Lex Fridman (01:38.320)
Like when I, right now, as I think about myself,
David Sinclair (01:42.460)
I feel like exactly the same person
Lex Fridman (01:45.040)
that I was when I was 12.
Lex Fridman (01:46.400)
And yet, I am getting older, both body and mind,
Lex Fridman (01:51.400)
and still feel like time hasn't passed at all.
Lex Fridman (01:54.240)
Do you feel this tension in yourself
Lex Fridman (01:56.880)
that you're the same person and yet you're aging?
David Sinclair (02:01.000)
Yeah, I have this tension that I'm still a kid,
Lex Fridman (02:04.640)
but that helps in my career.
David Sinclair (02:05.880)
Scientists need to have a wonder about the world
Lex Fridman (02:07.920)
and you don't wanna grow up at 12 year olds
Lex Fridman (02:10.520)
and even younger, I would say six, seven year olds.
Lex Fridman (02:13.380)
I've still got that boy in me and I can look at things.
David Sinclair (02:16.560)
It's a gift, I think, that I can see things
Lex Fridman (02:18.240)
for the first time if I choose to,
Lex Fridman (02:19.960)
and then explain them as I would to a six year old
Lex Fridman (02:23.160)
because I am that mentally.
Lex Fridman (02:24.960)
But on the other hand, I'm getting older, right?
Lex Fridman (02:26.720)
I run a lab of 20 people at Harvard.
David Sinclair (02:29.240)
I've got a book, I've got science to do, companies to run,
Lex Fridman (02:33.520)
and so I have to, on most days,
David Sinclair (02:35.680)
just pretend to be a grownup and be mature,
Lex Fridman (02:38.160)
but I definitely don't feel that way.
David Sinclair (02:40.640)
There's something I really appreciated
Lex Fridman (02:43.400)
in opening your book.
David Sinclair (02:44.920)
You talked about your grandmother.
Lex Fridman (02:46.920)
And on this kind of theme, on this kind of topic,
David Sinclair (02:51.240)
she, first of all, had a big influence on you.
Lex Fridman (02:53.720)
My grandmother had a big influence on me.
Lex Fridman (02:57.800)
And you also mentioned this poem
Lex Fridman (02:59.080)
by the author of Winnie the Pooh, Alan Alexander Milne.
David Sinclair (03:04.720)
Maybe I can read it real quick
Lex Fridman (03:06.120)
because I love, on the topic of being children,
David Sinclair (03:10.280)
when I was one, I had just begun.
Lex Fridman (03:12.560)
When I was two, I was nearly new.
David Sinclair (03:14.800)
When I was three, I was hardly me.
Lex Fridman (03:17.240)
When I was four, I was not much more.
David Sinclair (03:19.840)
When I was five, I was just alive, but now I am six.
Lex Fridman (03:24.320)
I am as clever, as clever, so I think I'll be six,
David Sinclair (03:27.480)
now, forever and ever.
Lex Fridman (03:31.440)
So this idea of being six and staying six forever,
David Sinclair (03:37.720)
being youthful, being curious,
Lex Fridman (03:39.320)
being childlike, this and other things,
Lex Fridman (03:43.360)
what influence has your grandmother had
Lex Fridman (03:46.760)
in your thinking about life, about death, about love?
David Sinclair (03:53.200)
Yeah, I was getting misty eyed as you read that
Lex Fridman (03:54.920)
because that poem was read to me very often,
David Sinclair (03:58.040)
if not every day, by my grandmother,
Lex Fridman (03:59.520)
who partially raised me.
Lex Fridman (04:02.300)
And she was as much a bohemian as an artist, philosopher.
Lex Fridman (04:06.420)
And she's one of those people
David Sinclair (04:08.120)
that wouldn't talk about the little things.
Lex Fridman (04:09.760)
She said, I hate small talk.
David Sinclair (04:11.560)
Don't talk to me about politics or the weather.
Lex Fridman (04:13.960)
Yeah, talk to me about human beings and culture.
Lex Fridman (04:16.920)
So I was raised on that,
Lex Fridman (04:18.040)
and this poem was one that she read to me often
David Sinclair (04:20.600)
because she knew that the mind of a child is precious,
Lex Fridman (04:26.040)
it's honest, it's pure.
Lex Fridman (04:28.520)
And she grew up during the Second World War
Lex Fridman (04:31.480)
and in Hungary and Budapest witnessed the worst of humanity.
David Sinclair (04:35.680)
She was trying to save a whole group of Jewish friends
Lex Fridman (04:40.060)
in her apartment, saw what happened after the World War,
David Sinclair (04:43.180)
which was there was, the Russians were in control
Lex Fridman (04:47.760)
and locals weren't necessarily treated well
David Sinclair (04:50.320)
if they were rebellious, which she was.
Lex Fridman (04:52.520)
And then there was the revolution in 56,
David Sinclair (04:54.440)
which she was part of and had to escape the country.
Lex Fridman (04:57.240)
So she saw what can happen when humans do their worst.
Lex Fridman (05:01.260)
And her words to me, expressed in part through that poem
Lex Fridman (05:05.240)
was, David, always stay young and innocent
Lex Fridman (05:09.560)
and have wonder about the world,
Lex Fridman (05:11.600)
and then do your best to make humanity the best it can be.
Lex Fridman (05:15.440)
And that's who I am, that's what I live for,
Lex Fridman (05:18.340)
that's what I get up in the morning to do
David Sinclair (05:19.800)
is to leave the world a better place
Lex Fridman (05:21.640)
and show to whoever's watching us,
David Sinclair (05:23.180)
whether it's aliens or some future human historian,
Lex Fridman (05:26.760)
that we can do better than we did in the 20th century.
David Sinclair (05:31.240)
You know, we mentioned offline this idea
Lex Fridman (05:33.200)
of bringing people back to life
David Sinclair (05:34.920)
through artificial intelligence,
Lex Fridman (05:38.240)
sort of, I don't know if you've seen videos
David Sinclair (05:40.880)
of basically animating people back to life,
Lex Fridman (05:45.200)
meaning whether it's, for me personally,
David Sinclair (05:47.960)
I've been working on specifically about Albert Einstein,
Lex Fridman (05:51.600)
but also Alan Turing, Isaac Newton, and Richard Feynman.
Lex Fridman (05:56.740)
And it's an opportunity to bring people
Lex Fridman (05:59.520)
that meant a lot to others in the world
Lex Fridman (06:02.360)
and animate them and be able to have a conversation
Lex Fridman (06:06.240)
with them at first to try to visually,
David Sinclair (06:12.740)
visually explore the full richness of character
Lex Fridman (06:17.200)
that they had as they struggle
David Sinclair (06:18.800)
with the ideas of the modern age.
Lex Fridman (06:20.880)
Sort of, it's less about bringing back their mind
Lex Fridman (06:24.120)
and more bringing back the visual quirks
Lex Fridman (06:27.440)
that made them who they are.
Lex Fridman (06:28.960)
And then maybe in the future,
Lex Fridman (06:30.960)
it's using the textual, the visual,
David Sinclair (06:33.200)
the video, the audio data to actually compress
Lex Fridman (06:38.600)
down the person for who they are
Lex Fridman (06:41.080)
and be able to generate text.
Lex Fridman (06:42.460)
There's a few companies, there's Replica,
David Sinclair (06:44.520)
which is a chat engine that was born
Lex Fridman (06:46.920)
out of the idea of bringing,
David Sinclair (06:48.460)
the founder lost her friend to,
Lex Fridman (06:53.440)
he got run over by a car.
Lex Fridman (06:55.840)
And the initial reason she founded the company
Lex Fridman (06:59.740)
was trying to just have a conversation with her friend.
David Sinclair (07:02.840)
She trained machine learning, natural language system
Lex Fridman (07:07.400)
on the texts that they exchange with each other
Lex Fridman (07:09.480)
and try, she had a conversation with him
Lex Fridman (07:11.880)
sort of after he was gone.
Lex Fridman (07:13.880)
And it's very, the conversation was very trivial.
Lex Fridman (07:16.880)
It was obvious that it's AI agent,
Lex Fridman (07:21.200)
but it gave her solace.
Lex Fridman (07:23.200)
It made her actually feel really good.
Lex Fridman (07:26.080)
And that's the way I wonder if it's possible
Lex Fridman (07:27.920)
to bring back people that are,
David Sinclair (07:30.840)
that mean something to us personally,
Lex Fridman (07:32.520)
not just Einstein, but people that we've lost
Lex Fridman (07:36.640)
and in that way achieve a kind of small
Lex Fridman (07:40.480)
artificial immortality.
David Sinclair (07:42.680)
I don't know if you think about this kind of stuff.
Lex Fridman (07:44.700)
Well, I definitely think about a lot of things.
David Sinclair (07:46.800)
That one's a really good one.
Lex Fridman (07:47.640)
There's a great Black Mirror episode
David Sinclair (07:49.160)
about the wife who brings back the boyfriend or husband.
Lex Fridman (07:52.840)
I think one of the challenges
David Sinclair (07:54.280)
with bringing back Richard Feynman
Lex Fridman (07:55.520)
would be to capture his sense of humor,
Lex Fridman (07:58.080)
but that would be awesome.
Lex Fridman (07:59.300)
But yeah, bringing back loved ones would be great,
David Sinclair (08:00.940)
especially if they're young and they die early,
Lex Fridman (08:07.680)
though it may hold you back from moving on.
David Sinclair (08:09.180)
That's another thing that could happen as a negative.
Lex Fridman (08:11.840)
But I think that's great.
Lex Fridman (08:12.680)
And I also think that it's gonna be possible,
Lex Fridman (08:14.680)
especially when we're recording some of us,
David Sinclair (08:17.260)
every aspect of our lives,
Lex Fridman (08:18.440)
whether it's our face or things we see, right?
David Sinclair (08:22.600)
Eventually one day, everything we see can be recorded.
Lex Fridman (08:26.040)
And then you can build somebody's experience
Lex Fridman (08:28.980)
and thoughts, speech,
Lex Fridman (08:31.840)
and you will have replicas of everybody,
David Sinclair (08:35.000)
at least digitally,
Lex Fridman (08:36.440)
and physically you could do that too one day.
Lex Fridman (08:38.740)
But that's a good idea,
Lex Fridman (08:40.360)
especially because there are people that I'd like to meet,
Lex Fridman (08:42.640)
and I think it's easier than building a time machine.
Lex Fridman (08:44.940)
One person I'd love to meet is Benjamin Franklin.
Lex Fridman (08:47.320)
Really?
Lex Fridman (08:48.160)
Well, I wouldn't go back in time.
David Sinclair (08:50.720)
I would, but I'd prefer to bring him into the future
Lex Fridman (08:53.140)
and say, can you believe we have this thinking machine
Lex Fridman (08:57.040)
in our pockets now?
Lex Fridman (08:58.420)
And just see the look on his face
David Sinclair (09:00.240)
as to where humanity has come.
Lex Fridman (09:01.320)
Because I think of him as a modern guy
David Sinclair (09:03.480)
that just was before his time.
Lex Fridman (09:05.480)
Yeah, so you're thinking Benjamin Franklin the scientist,
David Sinclair (09:08.520)
not Benjamin Franklin the political thing.
Lex Fridman (09:10.400)
Because he'd be very upset with Congress right now.
David Sinclair (09:13.040)
Right.
Lex Fridman (09:13.880)
So maybe talk to him about science and technology,
David Sinclair (09:16.160)
not politics.
Lex Fridman (09:18.160)
Or maybe just don't get him on Twitter
David Sinclair (09:19.600)
because he'll be very upset with human civilization.
Lex Fridman (09:22.400)
You know, I wonder what their personalities are like.
David Sinclair (09:25.360)
Isaac Newton, it does seem complicated
Lex Fridman (09:28.640)
to figure out what their personality is like.
David Sinclair (09:30.480)
Even Friedrich Nietzsche, who I also thought about.
Lex Fridman (09:33.320)
Feynman is, we just have enough video
David Sinclair (09:36.800)
where we get the full kind of,
Lex Fridman (09:39.360)
I mean, it shows you how important it is
David Sinclair (09:42.440)
to get not the official kind of book level presentation
Lex Fridman (09:47.560)
of a human, but the authentic,
David Sinclair (09:49.560)
the full spectrum of humanity.
Lex Fridman (09:51.960)
You mentioned collecting data about a person,
David Sinclair (09:54.420)
collecting the whole thing, the whole of life,
Lex Fridman (09:57.280)
the ups and downs, the embarrassing stuff,
David Sinclair (09:59.480)
the beautiful stuff, not just the things
Lex Fridman (10:01.600)
that's condensed into a book.
Lex Fridman (10:03.160)
And then with Feynman, you start to see that a little bit.
Lex Fridman (10:05.880)
Through conversations, you start to see peaks
David Sinclair (10:07.940)
of like that genius.
Lex Fridman (10:09.240)
And then through stories about him from others.
Lex Fridman (10:12.920)
And then certainly you, the sad thing
Lex Fridman (10:15.680)
about Alan Turing, for example,
David Sinclair (10:17.720)
is there's very little, if any, recording of him.
Lex Fridman (10:22.240)
In fact, I haven't been able to find recording
David Sinclair (10:24.160)
allegedly there's supposed to be a recording of him
Lex Fridman (10:27.440)
doing some kind of a radio broadcast,
Lex Fridman (10:29.720)
but I haven't been able to find anything.
Lex Fridman (10:32.120)
And so that's truly sad that it feels like
David Sinclair (10:35.680)
it makes you realize how the upside,
Lex Fridman (10:40.360)
how nice it is to collect data about a person,
David Sinclair (10:44.000)
to capture that person.
Lex Fridman (10:46.280)
That's the upside of the modern internet age,
David Sinclair (10:48.740)
the digital age, that that information,
Lex Fridman (10:51.340)
yeah, creates a kind of immortality.
Lex Fridman (10:55.700)
And then you can choose to highlight
Lex Fridman (10:57.100)
the best parts of the person,
David Sinclair (10:58.220)
maybe throw away the ugly parts
Lex Fridman (11:00.580)
and celebrate them even after they're gone.
Lex Fridman (11:03.460)
So that's a really interesting opportunity.
Lex Fridman (11:05.100)
You've also mentioned to me offline
David Sinclair (11:07.900)
that you're really excited about all the different wearables
Lex Fridman (11:11.060)
and all the different ways we can collect information
David Sinclair (11:14.020)
about our bodies, about the whole thing.
Lex Fridman (11:18.060)
What's most exciting to you in terms of collecting
Lex Fridman (11:21.180)
the biological data about a human being?
Lex Fridman (11:27.860)
Well, so I'm a biologist.
David Sinclair (11:29.300)
I find animals and humans as machines very interesting.
Lex Fridman (11:34.060)
It's one of the reasons I didn't become an engineer
David Sinclair (11:36.500)
or a surgeon.
Lex Fridman (11:37.340)
I wanted to understand how we actually are built.
Lex Fridman (11:40.580)
And so I think a lot about machines merging with humans.
Lex Fridman (11:46.020)
And the first of that are the bio wearables.
Lex Fridman (11:49.020)
And so I talked a lot about this, I wrote about it
Lex Fridman (11:51.380)
in Lifespan, the book, and pictured a future
David Sinclair (11:54.120)
where you would be monitored constantly
Lex Fridman (11:56.860)
so that you wouldn't suddenly have a heart attack,
David Sinclair (11:59.280)
you'd know that was coming,
Lex Fridman (12:00.220)
or you wouldn't go to the doctor
Lex Fridman (12:02.620)
and they don't know if you need an antibiotic or not.
Lex Fridman (12:07.540)
Long term, how old are you, how to fix things,
Lex Fridman (12:09.980)
what should you eat, what should you take,
Lex Fridman (12:11.540)
what should your doctor do?
David Sinclair (12:12.980)
These devices, I predicted, would be smarter,
Lex Fridman (12:16.100)
better educated than your physician
Lex Fridman (12:18.100)
and would augment them.
Lex Fridman (12:19.700)
And then there'd be a human that would just tick off
David Sinclair (12:21.460)
to see if it's correct and they approve.
Lex Fridman (12:24.300)
I also was predicting in the book
David Sinclair (12:26.820)
that we would have video conferences with our doctors
Lex Fridman (12:30.180)
and that medicines would be delivered,
David Sinclair (12:32.020)
initially by courier, but eventually by drones
Lex Fridman (12:33.940)
and get it to you sometimes in an emergency.
Lex Fridman (12:36.220)
And that we could even have pills
Lex Fridman (12:37.980)
that were synthesized or delivered in your kitchen
Lex Fridman (12:41.820)
and combined certainly.
Lex Fridman (12:43.920)
What's amazing about that is that, what are we now,
David Sinclair (12:47.100)
two years since the book came out, even less,
Lex Fridman (12:50.180)
and that future is basically here already.
David Sinclair (12:52.380)
COVID 19 accelerated that incredibly.
Lex Fridman (12:56.860)
So where we're at now in society is,
David Sinclair (12:58.480)
if you wanna pay for it, you can have a blood test
Lex Fridman (13:00.620)
that will detect cancer 10, 20 years earlier than it would
David Sinclair (13:03.580)
before it forms a tumor.
Lex Fridman (13:05.340)
You can, of course, do your genome very cheaply
David Sinclair (13:07.940)
for less than $100 now.
Lex Fridman (13:10.840)
There are bio wearables already I wear,
David Sinclair (13:12.960)
this ring from Aura that I have a number of years of data.
Lex Fridman (13:17.180)
I've been doing blood tests for the last 12 years
David Sinclair (13:19.220)
with a company called Inside Tracker, which I consult for.
Lex Fridman (13:22.580)
And so I have all of that data as well.
Lex Fridman (13:24.220)
And there's 34 different parameters on my testosterone,
Lex Fridman (13:27.700)
my blood glucose, my inflammation.
Lex Fridman (13:30.020)
And I use all that data to, of course,
Lex Fridman (13:32.700)
I wear a watch that measures things as well.
David Sinclair (13:34.720)
I use that data to keep my body in optimal shape.
Lex Fridman (13:39.280)
So I'm now 51.
Lex Fridman (13:40.660)
And according to those parameters,
Lex Fridman (13:42.140)
I'm at least as good as someone in their early 40s.
Lex Fridman (13:45.740)
And if I really work at it,
Lex Fridman (13:47.200)
I can get my biochemistry down to early to mid 30s,
David Sinclair (13:52.020)
though I like to now eat a little dessert once in a while.
Lex Fridman (13:56.220)
So that's the future we're in right now.
David Sinclair (13:58.700)
Anyone can do what I just said.
Lex Fridman (14:00.900)
But in the very near future, just in the next few years,
David Sinclair (14:04.340)
you can be wearing wearables.
Lex Fridman (14:06.380)
So I'm currently wearing a little,
David Sinclair (14:08.540)
what's called a bio sticker.
Lex Fridman (14:10.960)
This one I just put on last night.
David Sinclair (14:14.100)
It's about an inch long, a few millimeters.
Lex Fridman (14:18.580)
Yeah, for people just listening, it's on David's chest.
Lex Fridman (14:21.660)
It's just, how does it attach?
Lex Fridman (14:23.180)
It's just kind of.
David Sinclair (14:24.300)
It sticks on. Sticks on.
Lex Fridman (14:25.380)
Yeah, so on one side you have an on button that you press.
David Sinclair (14:27.740)
The lights come on, flashes four times, it's good to go.
Lex Fridman (14:30.500)
It immediately syncs to your phone.
Lex Fridman (14:32.980)
And this one, it's called a bio button, a nice name.
Lex Fridman (14:37.260)
And there's another one that I have that I haven't tried yet
David Sinclair (14:39.460)
that does EKG on your heart.
Lex Fridman (14:41.500)
This is mainly for doctors to monitor patients
David Sinclair (14:43.380)
that go home after a heart attack or surgery.
Lex Fridman (14:45.620)
But that's medical grade FDA approved device.
Lex Fridman (14:48.940)
So there will be a day, in fact, it's already here,
Lex Fridman (14:51.260)
that doctors are using these to get patients to go home
Lex Fridman (14:55.260)
and save a week in hospital, $2,000 at least
Lex Fridman (14:59.460)
for each patient.
David Sinclair (15:00.940)
That's massive savings for the hospital.
Lex Fridman (15:04.460)
But ultimately what I'm excited about is a future
David Sinclair (15:06.580)
that isn't that far off where everybody,
Lex Fridman (15:10.760)
certainly in developed countries,
David Sinclair (15:11.780)
eventually these will cost a few cents and rechargeable.
Lex Fridman (15:14.340)
The only cost will be the software subscription
David Sinclair (15:16.620)
that can be monitored constantly.
Lex Fridman (15:19.220)
And to give an idea what this is measuring me
David Sinclair (15:21.020)
at a thousand times a second is my vibrations as I speak,
Lex Fridman (15:26.220)
my orientation, it already has told me this morning
Lex Fridman (15:29.580)
how I slept, where I slept, what side I slept on.
Lex Fridman (15:33.220)
We've got sneezing, coughing, body temperature,
David Sinclair (15:37.000)
heart rate, heart of other parameters of the heart
Lex Fridman (15:40.840)
that would indicate heart health.
David Sinclair (15:44.000)
These data are being used to now to predict sickness.
Lex Fridman (15:49.880)
So eventually we'll have just in the next year or so
David Sinclair (15:53.640)
the ability to predict whether something
Lex Fridman (15:55.520)
or diagnose whether something is pneumonia
David Sinclair (15:58.160)
or just a rhinovirus that can be treated or not.
Lex Fridman (16:02.840)
This is really going to not just revolutionize medicine,
Lex Fridman (16:06.360)
but I think extend lives dramatically.
Lex Fridman (16:08.480)
Because if I'm gonna have a heart attack next week
Lex Fridman (16:11.520)
and that's possible, this device should know that
Lex Fridman (16:14.440)
and I'll be in hospital before I even have it.
David Sinclair (16:16.960)
Maybe you can talk a little bit about InsideTracker
Lex Fridman (16:19.280)
because I saw that there's some really cool things in there.
David Sinclair (16:23.000)
Like it actually, so maybe you can talk about,
Lex Fridman (16:25.960)
I guess that you're collecting blood to give it the data.
David Sinclair (16:29.240)
So, and it has like basic recommendations
Lex Fridman (16:32.480)
on how to improve your life.
Lex Fridman (16:34.200)
So we're not just talking about diseases, right?
Lex Fridman (16:36.560)
Like anticipating having a particular disease,
Lex Fridman (16:39.080)
but it's almost like guiding your trajectory to life,
Lex Fridman (16:41.840)
how to, whether it's extend your life
David Sinclair (16:44.600)
or just live a more fulfilling,
Lex Fridman (16:46.680)
like improve the quality of life.
David Sinclair (16:48.160)
I suppose this is the right way to say it.
Lex Fridman (16:50.600)
How does InsideTracker work?
Lex Fridman (16:52.460)
What the heck is it?
Lex Fridman (16:53.300)
Because I thought there was also pretty cool.
David Sinclair (16:55.080)
Yeah.
Lex Fridman (16:55.920)
What is it?
Lex Fridman (16:56.760)
Is it something other people can use?
Lex Fridman (16:58.240)
You can definitely use it.
David Sinclair (16:59.720)
You can sign up, it's consumer.
Lex Fridman (17:02.040)
It's like a company consumer facing company.
David Sinclair (17:04.440)
It is, yeah.
Lex Fridman (17:06.040)
And I also want to democratize the ability
David Sinclair (17:08.960)
to just take a mouth swab eventually.
Lex Fridman (17:11.000)
We don't need to have a blood test necessarily,
Lex Fridman (17:13.560)
but for now it's a blood test
Lex Fridman (17:14.640)
and you'd go to a lab core request in the US.
David Sinclair (17:18.380)
It's also available overseas.
Lex Fridman (17:19.840)
You can upload your own data for a minimal cost
Lex Fridman (17:22.540)
and get the algorithms, the AI in the background
Lex Fridman (17:26.560)
to take that data,
David Sinclair (17:27.880)
plot where you are against others in your age group
Lex Fridman (17:31.560)
in terms of health and longevity at bio age.
David Sinclair (17:34.120)
They call it inner age,
Lex Fridman (17:36.000)
but also it provides recommendations.
Lex Fridman (17:38.120)
And this isn't just a bunch of BS.
Lex Fridman (17:39.640)
It sounds like it might be to say, I'll go eat this
David Sinclair (17:42.520)
or go to that restaurant and order that,
Lex Fridman (17:44.360)
but it's actually based on the basic.
David Sinclair (17:47.000)
This company has entered hundreds.
Lex Fridman (17:49.800)
Now it would be thousands of scientific papers
David Sinclair (17:51.760)
into their database
Lex Fridman (17:53.160)
and hundreds of thousands of human data points.
Lex Fridman (17:55.720)
And they have tens of thousands of individuals
Lex Fridman (17:59.040)
that have been tracked over time
Lex Fridman (18:00.360)
and anonymously that data is used to say
Lex Fridman (18:02.920)
what works and what doesn't.
Lex Fridman (18:04.240)
If you eat that, what works?
Lex Fridman (18:05.720)
If you take that supplement, what works?
Lex Fridman (18:07.600)
And I was a coauthor on a paper that showed
Lex Fridman (18:09.620)
that the recommendations for food and supplements
David Sinclair (18:15.040)
was better than the leading drug for type two diabetes.
Lex Fridman (18:18.920)
That's so cool.
David Sinclair (18:19.760)
The idea that you can connect,
Lex Fridman (18:21.660)
like skipping the human having to do this work,
David Sinclair (18:24.880)
you can connect the scientific papers,
Lex Fridman (18:27.380)
almost like meta analysis of the science
David Sinclair (18:30.080)
connected to the individual data.
Lex Fridman (18:32.480)
And then based on that sort of connect your data
David Sinclair (18:35.400)
to whatever the proper group is
Lex Fridman (18:37.880)
within the whatever the scientific paper is
David Sinclair (18:40.440)
to make the suggestion of how like how that work
Lex Fridman (18:44.840)
applies to your life.
Lex Fridman (18:47.120)
And then that ultimately maps to like a recommendation
Lex Fridman (18:49.640)
of what you should do with your life.
David Sinclair (18:51.240)
Like it all like this giant system
Lex Fridman (18:54.520)
that ultimately recommends
David Sinclair (18:55.700)
you should drink more coffee or less.
Lex Fridman (18:58.440)
Right, and we'll have the genome in there as well.
David Sinclair (19:00.280)
You can upload that.
Lex Fridman (19:01.200)
Yeah, it's awesome.
Lex Fridman (19:02.440)
So these programs will know us way better
Lex Fridman (19:04.640)
than we do and our doctors as well.
David Sinclair (19:07.480)
The idea of going to a doctor once a year
Lex Fridman (19:08.960)
for an annual checkup and having males get a finger
David Sinclair (19:11.940)
up their butt and you cough, that to me is a joke.
Lex Fridman (19:16.000)
That's medieval medicine.
Lex Fridman (19:18.140)
And that's very soon going to be seen as medieval.
Lex Fridman (19:21.440)
Yeah, to me as a computer science person,
David Sinclair (19:25.920)
it's always upsetting to go to the doctor
Lex Fridman (19:28.640)
and just look at him and like realize
David Sinclair (19:31.120)
you know nothing about me.
Lex Fridman (19:33.160)
Like you're making your like opinions based on like,
David Sinclair (19:38.560)
it is very valuable, years of intuition building
Lex Fridman (19:42.540)
about basic symptoms, but you're just like it is medieval.
David Sinclair (19:45.880)
They're very good at it.
Lex Fridman (19:47.200)
In fact, doctors in medieval times were probably damn good
David Sinclair (19:51.360)
at working with very little.
Lex Fridman (19:53.600)
But the thing is, I'd rather prefer a doctor
David Sinclair (19:58.520)
that doesn't really know what they're doing,
Lex Fridman (1:00:00.460)
in terms of longterm effects or the cost
David Sinclair (1:00:05.020)
in terms of longevity.
Lex Fridman (1:00:05.900)
It's very difficult to know how your choices
David Sinclair (1:00:08.060)
affect your longevity because the impact is down the line.
Lex Fridman (1:00:12.780)
Like just because something makes me feel good now,
David Sinclair (1:00:17.780)
like eating only meat makes me feel good now,
Lex Fridman (1:00:20.420)
I wonder what are the costs down the line.
David Sinclair (1:00:22.420)
Well, think about what I was saying about the trade offs
Lex Fridman (1:00:24.940)
between growth and reproduction,
David Sinclair (1:00:27.220)
which is what a mouse does and a whale
Lex Fridman (1:00:29.300)
that grows slowly, reproduces slowly, lives a long time.
David Sinclair (1:00:33.060)
It's called the disposable soma theory.
Lex Fridman (1:00:35.900)
Koch would just propose that in the 70s.
Lex Fridman (1:00:38.780)
What meat probably does is put you in the mouse category,
Lex Fridman (1:00:42.140)
super fertile, grow fast, heal fast.
Lex Fridman (1:00:44.780)
And then if you wanna be a whale,
Lex Fridman (1:00:46.660)
you should restrict meat and do things
David Sinclair (1:00:49.660)
that promote the preservation of your body.
Lex Fridman (1:00:53.380)
Is it difficult to eat a plant based diet
Lex Fridman (1:00:57.820)
that you perform well under?
Lex Fridman (1:01:00.020)
So mentally and physically, just almost,
David Sinclair (1:01:02.860)
I'm asking almost like an anecdotal question
Lex Fridman (1:01:06.860)
or unless you know the science.
David Sinclair (1:01:09.780)
Well, the science is still being worked out,
Lex Fridman (1:01:12.140)
but from the synthesis of everything that I've read,
David Sinclair (1:01:15.180)
I try to eat a diet that's definitely full of leafy greens,
Lex Fridman (1:01:21.180)
particularly spinach is great
David Sinclair (1:01:22.580)
because it's got the iron that we need, plenty of vitamins.
Lex Fridman (1:01:25.860)
I also try to avoid too much fruit and berries,
David Sinclair (1:01:32.420)
particularly fruit juice,
Lex Fridman (1:01:34.020)
definitely avoid that sugar high.
David Sinclair (1:01:35.900)
Spiking your sugar is not healthy in the long run.
Lex Fridman (1:01:39.900)
The other thing that's interesting
David Sinclair (1:01:40.940)
is we discovered what we called xenohormetic molecules.
Lex Fridman (1:01:45.500)
Let me unpack that because it's a terrible name
Lex Fridman (1:01:47.580)
and I take full responsibility
Lex Fridman (1:01:49.460)
with my friend, Conrad Howards.
David Sinclair (1:01:51.740)
The Xeno means cross species
Lex Fridman (1:01:53.900)
and hormesis is the term that what doesn't kill you
David Sinclair (1:01:57.380)
makes you live longer and be healthier.
Lex Fridman (1:02:01.180)
And so we're getting cross species health improvements
David Sinclair (1:02:04.620)
by molecules that plants make.
Lex Fridman (1:02:06.940)
And plants make these molecules
David Sinclair (1:02:08.220)
when they're also under adversity or perceived adversity.
Lex Fridman (1:02:11.780)
For instance, I understand
David Sinclair (1:02:14.140)
if you want really healthy, good oranges,
Lex Fridman (1:02:16.700)
you can drive nails into the bark of the tree
David Sinclair (1:02:19.340)
before you harvest.
Lex Fridman (1:02:20.380)
Same with wine, you typically want them to be dry
David Sinclair (1:02:23.220)
before you harvest or covered in fungus.
Lex Fridman (1:02:25.940)
And that's because these plants make these colorful
Lex Fridman (1:02:28.820)
and xenohormetic molecules
Lex Fridman (1:02:30.700)
that make themselves stress resistant,
David Sinclair (1:02:33.380)
turn on their sirtuin defenses, the serogenes remember.
Lex Fridman (1:02:37.700)
And when we eat them, we get those same benefits.
David Sinclair (1:02:40.300)
That's the idea and we've evolved to do so.
Lex Fridman (1:02:42.220)
This isn't a coincidence.
David Sinclair (1:02:43.700)
It's my theory, our theory that we want to know
Lex Fridman (1:02:47.020)
when our food supply is under adversity
David Sinclair (1:02:49.220)
because we need to get ready for a famine.
Lex Fridman (1:02:51.980)
And so we hunker down and preserve our body
Lex Fridman (1:02:54.580)
and by eating these colored foods,
Lex Fridman (1:02:55.860)
so practically speaking, if it's full of color
David Sinclair (1:02:58.780)
or if there's been some chewing by a caterpillar,
Lex Fridman (1:03:01.900)
organic, grown locally in local farms,
David Sinclair (1:03:04.980)
I'll eat that versus a watery, insipid, light colored lettuce
Lex Fridman (1:03:11.180)
that's been grown in California.
Lex Fridman (1:03:12.780)
So you want vegetables that have suffered.
Lex Fridman (1:03:14.540)
You want the David Goggins as a vegetables.
David Sinclair (1:03:16.700)
That's the xenohormetic molecules.
Lex Fridman (1:03:19.300)
I love that term.
David Sinclair (1:03:20.780)
I'm gonna take that one with me, thank you.
Lex Fridman (1:03:23.300)
Yeah.
David Sinclair (1:03:24.980)
Oh, I follow him on Instagram, he's always screaming.
Lex Fridman (1:03:27.380)
So you want that he's basically
David Sinclair (1:03:30.940)
the xenohormetic version of a human.
Lex Fridman (1:03:36.060)
I like it.
Lex Fridman (1:03:36.900)
So these are the molecules that are representative
Lex Fridman (1:03:38.980)
of the stress that a plant has been under.
David Sinclair (1:03:43.980)
Yeah, the best example of that is resveratrol,
Lex Fridman (1:03:46.660)
which many people, including myself,
David Sinclair (1:03:48.140)
take as a supplement.
Lex Fridman (1:03:49.660)
Grapes, grapevines produce that in abundance
David Sinclair (1:03:52.660)
when they're dried out or they have too much light
Lex Fridman (1:03:55.780)
or fungus and that we've shown activates
David Sinclair (1:03:59.060)
the Sertu enzyme in our bodies,
Lex Fridman (1:04:01.500)
which remember is what extends lifespan in yeast
Lex Fridman (1:04:03.780)
and slows down aging in the brain.
Lex Fridman (1:04:05.780)
That's beautiful.
David Sinclair (1:04:06.900)
Yeah, I tend to avoid fruit as well.
Lex Fridman (1:04:09.260)
So green, veggies, anything that's not very sweet.
Lex Fridman (1:04:12.660)
So I would just say you're relatively low,
Lex Fridman (1:04:15.420)
like you try to avoid sugary things as well.
David Sinclair (1:04:19.140)
Yeah, I'm fairly militant about that.
Lex Fridman (1:04:21.500)
I rarely would add sugar to anything.
David Sinclair (1:04:23.900)
Occasionally I would eat a slice of cheesecake,
Lex Fridman (1:04:27.820)
but that would be maybe once or twice a year.
David Sinclair (1:04:31.060)
You have to give in occasionally.
Lex Fridman (1:04:32.900)
But yeah, anything that's sweet,
David Sinclair (1:04:34.780)
I would rather substitute something like Stevia
Lex Fridman (1:04:37.460)
if I need a sugar hit.
Lex Fridman (1:04:40.820)
What about exercise?
Lex Fridman (1:04:42.420)
Your favorite topic.
Lex Fridman (1:04:45.260)
Is there a part?
Lex Fridman (1:04:46.660)
I don't mind talking about it.
David Sinclair (1:04:48.500)
Okay, great.
Lex Fridman (1:04:49.340)
Is there benefits to longevity from exercise?
David Sinclair (1:04:53.460)
Well, no doubt, that's proven.
Lex Fridman (1:04:55.940)
Just like fasting, it's pretty clear that that works.
David Sinclair (1:04:59.180)
For example, there are studies of cyclists.
Lex Fridman (1:05:01.860)
It was something like people that cycle
David Sinclair (1:05:04.180)
over 80 miles a week have a 40% reduction
Lex Fridman (1:05:07.660)
in a variety of diseases, certainly heart disease.
Lex Fridman (1:05:10.380)
So that's not even a question,
Lex Fridman (1:05:11.580)
but what's interesting is that we're learning
David Sinclair (1:05:13.460)
that you don't need much to have a big benefit.
Lex Fridman (1:05:15.620)
It's an asymptotic curve.
Lex Fridman (1:05:17.420)
And in fact, if you overdo it,
Lex Fridman (1:05:19.140)
you probably have reduced benefits,
David Sinclair (1:05:20.620)
particularly if you start to wear out joints,
Lex Fridman (1:05:22.140)
that kind of thing.
Lex Fridman (1:05:23.460)
But just 10 minutes on a treadmill a few times a week,
Lex Fridman (1:05:26.300)
lose your breath, get hypoxic, as it's called,
David Sinclair (1:05:28.540)
seems to be very beneficial for longterm health.
Lex Fridman (1:05:32.620)
And that's the kind of exercise that I like to do, aerobic.
David Sinclair (1:05:36.420)
Though I do enjoy lifting weights,
Lex Fridman (1:05:38.460)
so that is what I call my exercise,
David Sinclair (1:05:40.860)
which has other benefits,
Lex Fridman (1:05:41.820)
including maintaining hormone levels, male hormone levels.
Lex Fridman (1:05:46.180)
But also really why I do it is I want to be able
Lex Fridman (1:05:49.860)
to counteract the effects of sitting for most of the day.
Lex Fridman (1:05:53.460)
And as you get older, you lose muscle mass.
Lex Fridman (1:05:55.740)
It's a percent or so a year.
Lex Fridman (1:05:57.620)
And I don't wanna be frail when I'm older
Lex Fridman (1:05:59.420)
and fall over and break my hip,
David Sinclair (1:06:00.820)
which happens every 20 seconds in this country.
Lex Fridman (1:06:04.100)
So maintaining that strength,
Lex Fridman (1:06:05.460)
but also doing the cardio for the longevity,
Lex Fridman (1:06:07.900)
for avoiding the heart disease.
David Sinclair (1:06:10.100)
Yeah, I definitely, just like with fasting,
Lex Fridman (1:06:13.020)
have the philosophical benefit of running long
Lex Fridman (1:06:15.580)
and running slow.
Lex Fridman (1:06:17.060)
I enjoy it, because it kind of clears the mind
Lex Fridman (1:06:19.300)
and allows you to think,
Lex Fridman (1:06:20.540)
and actually listen to brown noise as I run.
David Sinclair (1:06:22.980)
It really helps remove myself from the world
Lex Fridman (1:06:26.340)
and just like zoom in on particular thoughts.
Lex Fridman (1:06:28.700)
What are these brown noise?
Lex Fridman (1:06:29.980)
It's like white noise, but deeper.
Lex Fridman (1:06:31.860)
So like the white noise is like shh,
Lex Fridman (1:06:35.060)
and then brown noise is more like,
David Sinclair (1:06:37.140)
shh, like ocean.
Lex Fridman (1:06:39.900)
That sounds great.
David Sinclair (1:06:40.780)
I might try that.
Lex Fridman (1:06:41.700)
Yeah, yeah, it's more soothing probably.
David Sinclair (1:06:44.900)
I'm not sure.
Lex Fridman (1:06:45.740)
There could be science to this.
David Sinclair (1:06:46.580)
I need to look this up.
Lex Fridman (1:06:47.580)
I've been meaning to.
Lex Fridman (1:06:48.820)
But when I started,
Lex Fridman (1:06:52.100)
this is maybe like five years ago,
David Sinclair (1:06:53.780)
I started listening to brown noise when I work.
Lex Fridman (1:06:56.020)
And the first time I listened to it,
David Sinclair (1:06:58.340)
something happened to my mind
Lex Fridman (1:07:00.220)
where it just went like zoomed in
David Sinclair (1:07:03.660)
to like, in a way that it felt like really weird.
Lex Fridman (1:07:07.780)
Like how precisely it was able to sort of
David Sinclair (1:07:11.540)
remove the distractions of the world
Lex Fridman (1:07:14.500)
and really help my mind.
David Sinclair (1:07:16.460)
Obviously, like the mind is trying to focus
Lex Fridman (1:07:19.540)
and then it just enabled that process
David Sinclair (1:07:21.700)
of trying to focus on a particular problem.
Lex Fridman (1:07:24.420)
I don't know if this is generalizable to others.
David Sinclair (1:07:26.220)
People should definitely try it
Lex Fridman (1:07:27.300)
if you're listening to this.
David Sinclair (1:07:28.980)
Maybe it's just my own mind,
Lex Fridman (1:07:30.180)
but it's funny, like it made me,
David Sinclair (1:07:34.420)
brown noise made me realize
Lex Fridman (1:07:35.780)
that there's probably hacks out there
David Sinclair (1:07:38.620)
that work for me
Lex Fridman (1:07:40.140)
that I should be constantly looking for.
David Sinclair (1:07:41.780)
It's almost like an encouraging
Lex Fridman (1:07:44.620)
and motivating event
David Sinclair (1:07:48.300)
that maybe there's other stuff out there.
Lex Fridman (1:07:49.900)
Maybe there's other brown noise like things out there
David Sinclair (1:07:52.780)
that truly like almost immediately make me feel better.
Lex Fridman (1:07:56.020)
I don't know if it's generalizable to others,
Lex Fridman (1:07:57.780)
but it does seem that it's the case
Lex Fridman (1:08:00.500)
that there's probably for many others,
David Sinclair (1:08:03.180)
things like that that could be discovered.
Lex Fridman (1:08:05.820)
And so it's always disappointing
David Sinclair (1:08:07.980)
when I find things in life
Lex Fridman (1:08:10.260)
that I wish I would have found earlier.
David Sinclair (1:08:12.860)
I got LASIK eye surgery a few years ago
Lex Fridman (1:08:17.260)
and the first thought I had like the next day
David Sinclair (1:08:19.340)
when I woke up is like,
Lex Fridman (1:08:21.260)
damn it, why didn't I do this way earlier?
David Sinclair (1:08:24.100)
There's all this stuff of that nature
Lex Fridman (1:08:27.220)
that are yet to be discovered.
Lex Fridman (1:08:29.540)
So it pays to explore.
Lex Fridman (1:08:31.620)
You have a different mind, you have quite a beautiful mind.
Lex Fridman (1:08:34.420)
So I suspect brown noise helps you focus
Lex Fridman (1:08:37.100)
and cause you're probably all over the place
David Sinclair (1:08:39.060)
if you don't control it.
Lex Fridman (1:08:40.140)
Yeah, exactly.
David Sinclair (1:08:40.980)
It means something about it.
Lex Fridman (1:08:42.260)
It's a programmer thing.
David Sinclair (1:08:43.340)
I don't, programming is a really difficult mental journey
Lex Fridman (1:08:50.140)
cause you have to keep a lot of things in mind.
David Sinclair (1:08:52.820)
You have to, so you're constantly designing things
Lex Fridman (1:08:56.460)
then you have to be extremely precise
David Sinclair (1:08:58.060)
by making those things concrete in code.
Lex Fridman (1:09:01.060)
You also have to look stuff up on the internet
David Sinclair (1:09:06.140)
to sort of feed like information
Lex Fridman (1:09:08.660)
and looking up stuff on the internet,
David Sinclair (1:09:10.420)
internet is full of like distracting things.
Lex Fridman (1:09:12.380)
So you have to be really focused
David Sinclair (1:09:13.780)
in the way you look stuff up in pulling that information in.
Lex Fridman (1:09:16.780)
So it requires a certain discipline and a certain focus
David Sinclair (1:09:20.100)
that I've been very much exploring how to do.
Lex Fridman (1:09:23.980)
Like I do it really well in the morning,
David Sinclair (1:09:26.340)
coffee is involved, all those kinds of things.
Lex Fridman (1:09:28.300)
You're trying to optimize, keeping very positive inspired,
David Sinclair (1:09:32.620)
no social media, all those kinds of things
Lex Fridman (1:09:34.580)
and trying to optimize for.
Lex Fridman (1:09:36.140)
And everybody has their own kind of little journey
Lex Fridman (1:09:38.660)
that they try to understand.
David Sinclair (1:09:40.540)
You get this from like writers
Lex Fridman (1:09:41.940)
when you read about the habits of writers,
David Sinclair (1:09:45.820)
like the habits they do in the morning,
Lex Fridman (1:09:47.860)
they usually write like two, three, four hours a day
Lex Fridman (1:09:49.820)
and that's it.
Lex Fridman (1:09:50.980)
It's like they optimize that ritual.
Lex Fridman (1:09:53.460)
And then there's always Hunter S. Thompson.
Lex Fridman (1:09:55.460)
So sometimes it pays off to be wild.
Lex Fridman (1:10:01.340)
What about sleep?
Lex Fridman (1:10:04.580)
How important is sleep for longevity?
David Sinclair (1:10:06.740)
I would guess based on the evidence
Lex Fridman (1:10:10.740)
that it's really important
Lex Fridman (1:10:12.180)
and because we don't know for sure.
Lex Fridman (1:10:15.060)
But what we know from animal studies is the following.
David Sinclair (1:10:17.580)
If you restrict sleep from a rat for just two weeks,
Lex Fridman (1:10:20.260)
it'll develop type two diabetes.
David Sinclair (1:10:22.180)
It's that important.
Lex Fridman (1:10:23.380)
So that's the main thing.
Lex Fridman (1:10:25.820)
What we also know is at the molecular level
Lex Fridman (1:10:28.460)
that if you disrupt your sleep wake cycle,
Lex Fridman (1:10:33.340)
so we actually have proteins that go up and down
Lex Fridman (1:10:35.100)
that control our sleep wake.
David Sinclair (1:10:36.700)
All of us, most of our cells do that.
Lex Fridman (1:10:39.220)
If you disrupt that, you'll get premature aging.
Lex Fridman (1:10:42.460)
And guess what?
Lex Fridman (1:10:43.300)
The opposite is true.
David Sinclair (1:10:44.140)
That as you get older, that cycle,
Lex Fridman (1:10:46.740)
the amplitude becomes diminished.
Lex Fridman (1:10:49.460)
And this is why it's harder to get to sleep
Lex Fridman (1:10:51.300)
as you get older
Lex Fridman (1:10:52.140)
and you've got all sorts of problems.
Lex Fridman (1:10:54.500)
And I think what's going on is this positive feedback loop,
David Sinclair (1:10:56.940)
which is a disaster in your old age,
Lex Fridman (1:10:59.420)
which is you're aging,
David Sinclair (1:11:02.060)
you can't at this moment totally prevent that.
Lex Fridman (1:11:05.780)
And then it's disrupting your sleep
Lex Fridman (1:11:06.900)
and you get not enough sleep
Lex Fridman (1:11:08.020)
and then that's gonna accelerate your aging process.
Lex Fridman (1:11:10.460)
And so it's known that the people who are shift workers
Lex Fridman (1:11:13.700)
are most susceptible to certain age related diseases.
Lex Fridman (1:11:17.540)
So your bottom line, you definitely wanna work on that.
Lex Fridman (1:11:19.940)
It's one of the reasons I have this ring on my finger,
David Sinclair (1:11:21.860)
which helps me optimize my sleep
Lex Fridman (1:11:23.300)
and learn what I do the day before,
David Sinclair (1:11:25.860)
if it was a bad idea and I'll stop doing that,
Lex Fridman (1:11:28.380)
like eating a fried chicken.
David Sinclair (1:11:31.740)
I see you're still carrying the burdens of that decision.
Lex Fridman (1:11:34.860)
But yeah, sleep is one of those things
David Sinclair (1:11:37.900)
that's making me wonder about the variability
Lex Fridman (1:11:41.580)
between humans a little bit
Lex Fridman (1:11:43.140)
and how science is often focused on,
Lex Fridman (1:11:47.540)
like it's not often focused on high performers
David Sinclair (1:11:51.500)
in a particular way.
Lex Fridman (1:11:53.620)
And it's looking at the aggregate
David Sinclair (1:11:55.220)
versus the individual cases.
Lex Fridman (1:11:57.820)
For example, like for me,
David Sinclair (1:11:59.340)
I don't know what the exact hours are,
Lex Fridman (1:12:00.940)
but like power naps are incredible.
David Sinclair (1:12:06.540)
I tend to look at the metric of stress and happiness and joy
Lex Fridman (1:12:11.740)
and try to optimize those.
Lex Fridman (1:12:13.100)
So decreasing stress, increasing happiness
Lex Fridman (1:12:16.020)
and using sleep as just one of the tools to do that.
David Sinclair (1:12:20.140)
Because like hitting the five, six, seven, eight,
Lex Fridman (1:12:23.700)
nine hour mark or whatever the correct mark is,
David Sinclair (1:12:27.180)
I find that to be stress inducing for me
Lex Fridman (1:12:29.980)
versus stress relieving.
David Sinclair (1:12:32.300)
Like thinking about that,
Lex Fridman (1:12:34.180)
I feel best if I sleep sometimes for eight hours,
David Sinclair (1:12:37.340)
sometimes for four hours and then power nap.
Lex Fridman (1:12:39.580)
And as long as I have a stupid private,
David Sinclair (1:12:42.580)
usually smile on my face,
Lex Fridman (1:12:44.460)
that's when I'm doing good,
David Sinclair (1:12:46.180)
as opposed to getting a perfect amount of sleep
Lex Fridman (1:12:49.460)
according to whatever the latest blog post is.
Lex Fridman (1:12:53.300)
And I also pull all nighters still.
Lex Fridman (1:12:56.500)
I also think there's something about the body,
David Sinclair (1:12:59.340)
like as long as you do it regularly,
Lex Fridman (1:13:02.860)
it's not as stress inducing.
David Sinclair (1:13:04.420)
Like you know what it is.
Lex Fridman (1:13:06.820)
The reason I pull all nighters isn't for like,
David Sinclair (1:13:08.980)
I'm playing Diablo three or something,
Lex Fridman (1:13:11.580)
is because I'm doing something I'm truly passionate about.
David Sinclair (1:13:13.980)
Well, like I'm also love video games,
Lex Fridman (1:13:15.820)
but I'm doing something I'm truly passionate about.
Lex Fridman (1:13:18.460)
And it's almost like there's the Jocko Willing feeling
Lex Fridman (1:13:21.420)
of when I'm up at 7 a.m. and I haven't slept all night
Lex Fridman (1:13:25.540)
and still I'm working on it.
Lex Fridman (1:13:27.140)
There's a kind of a celebration of the human spirit
David Sinclair (1:13:29.500)
that I really enjoy it.
Lex Fridman (1:13:31.020)
Like, and that's happiness.
Lex Fridman (1:13:33.700)
And to sort of then,
Lex Fridman (1:13:35.940)
and I usually don't tell that kind of stuff to people
David Sinclair (1:13:37.940)
because their first statement will be like,
Lex Fridman (1:13:40.820)
you should get more sleep.
David Sinclair (1:13:42.580)
It's like, no, I'm doing stuff I love.
Lex Fridman (1:13:46.180)
You should get more love in your life, bro.
David Sinclair (1:13:48.980)
That's right.
Lex Fridman (1:13:50.380)
So, but that said, in aggregate,
David Sinclair (1:13:52.500)
when you look at the full span of life,
Lex Fridman (1:13:55.340)
is probably you should be getting
David Sinclair (1:13:57.980)
a consistent amount of sleep.
Lex Fridman (1:14:00.700)
And it seems like it's in that seven, eight hour range.
David Sinclair (1:14:04.900)
Yeah, but it's similar to food.
Lex Fridman (1:14:06.700)
It's the quality, not the quantity, right?
Lex Fridman (1:14:09.300)
And when you get it.
Lex Fridman (1:14:10.700)
So I look at my data pretty often.
Lex Fridman (1:14:14.420)
And what makes a difference to me is not the amount of hours,
Lex Fridman (1:14:17.140)
but the quality, the depth and the deep sleep
David Sinclair (1:14:20.380)
is what will do it.
Lex Fridman (1:14:21.900)
So if I have a lot of alcohol before going to sleep
Lex Fridman (1:14:24.820)
and I can see my heart rate being different,
Lex Fridman (1:14:26.340)
but what really kills me is that I don't get a lot
David Sinclair (1:14:28.380)
of that deep sleep and I wake up barely remembering stuff.
Lex Fridman (1:14:32.420)
So that, like you say, if you're happy and contented
Lex Fridman (1:14:34.380)
and you don't have these cortisol chemicals
Lex Fridman (1:14:37.100)
going through your body,
David Sinclair (1:14:38.340)
you will more naturally get into that deep state.
Lex Fridman (1:14:40.660)
And even if you just get four hours,
David Sinclair (1:14:42.260)
way better than eight hours of none of that.
Lex Fridman (1:14:45.380)
Yeah, yeah, that's beautiful.
Lex Fridman (1:14:46.860)
And some of that could be genetic.
Lex Fridman (1:14:48.180)
For me, I just, I fall asleep like this.
David Sinclair (1:14:51.980)
If you want me to fall asleep right now, I can do it.
Lex Fridman (1:14:54.140)
It's no, I have no problem with it.
David Sinclair (1:14:57.300)
Combined with coffee, I just had two energy drinks.
Lex Fridman (1:14:59.300)
I can probably sleep.
Lex Fridman (1:15:01.420)
So that, I don't know if that's genetics
Lex Fridman (1:15:03.540)
or it's kind of, I don't know what it is.
David Sinclair (1:15:07.500)
Or maybe that I don't have kids and I'm single.
Lex Fridman (1:15:09.700)
So I don't have, I'm almost listening
David Sinclair (1:15:11.900)
to some kind of biological signal versus societal signal
Lex Fridman (1:15:15.340)
on when I'm supposed to go to sleep.
Lex Fridman (1:15:17.060)
So I just go to sleep whenever I feel like going to sleep.
Lex Fridman (1:15:20.660)
Well, that's because you're a self employed.
David Sinclair (1:15:22.460)
Self employed.
Lex Fridman (1:15:23.300)
Most people don't have that luxury,
Lex Fridman (1:15:24.620)
but we're lucky, the two of us,
Lex Fridman (1:15:26.100)
that we can make our own hours.
David Sinclair (1:15:27.580)
Yeah.
Lex Fridman (1:15:28.420)
But yeah, it's super important.
Lex Fridman (1:15:29.780)
And those people who have shift work,
Lex Fridman (1:15:32.340)
I mean, they really need to change the way that works
David Sinclair (1:15:35.460)
because they're literally killing those people.
Lex Fridman (1:15:38.900)
Is there something you could say about the,
Lex Fridman (1:15:41.740)
the mind and stress in terms of effect on longevity?
Lex Fridman (1:15:48.340)
Sort of, I don't know if you think about it this way,
Lex Fridman (1:15:52.460)
but when you talk about the biological machine,
Lex Fridman (1:15:55.060)
it's always these mechanisms that don't,
David Sinclair (1:15:57.780)
are not necessarily directly connected to the brain
Lex Fridman (1:16:00.860)
or the operation of the brain.
David Sinclair (1:16:02.620)
Like what's the role about stress and happiness
Lex Fridman (1:16:06.300)
and yeah, the sort of higher cognitive things
David Sinclair (1:16:10.700)
going on in the brain on longevity.
Lex Fridman (1:16:14.220)
Right.
David Sinclair (1:16:15.060)
Well, that's a great point that the brain
Lex Fridman (1:16:16.820)
is the center for longevity.
David Sinclair (1:16:18.300)
Actually, we do know that.
Lex Fridman (1:16:21.140)
For a start, when I'm stressed,
David Sinclair (1:16:22.780)
I can see mentally stressed,
Lex Fridman (1:16:24.620)
then I can see it in my body.
David Sinclair (1:16:27.060)
Heart rate, hormones, it's clear.
Lex Fridman (1:16:29.540)
That's no true surprise.
Lex Fridman (1:16:31.420)
So you've got to work on your brain first and foremost.
Lex Fridman (1:16:33.940)
If you are totally freaked out, agitated all the time,
David Sinclair (1:16:38.940)
you will live shorter.
Lex Fridman (1:16:40.300)
I'm certain of it.
David Sinclair (1:16:41.140)
You know, I keep fish.
Lex Fridman (1:16:42.540)
I'm a big aquarium guy.
Lex Fridman (1:16:46.460)
And you can see the difference
Lex Fridman (1:16:47.300)
between the fish that's having a good time and dominant
Lex Fridman (1:16:50.540)
and one that gets picked on.
Lex Fridman (1:16:52.180)
It just looks like crap.
David Sinclair (1:16:54.300)
You don't want to be that,
Lex Fridman (1:16:55.140)
the little fish getting picked on if you can help it.
Lex Fridman (1:16:57.740)
So I used to be extremely stressed as a kid.
Lex Fridman (1:17:00.100)
I was a perfectionist, very shy,
David Sinclair (1:17:02.540)
always worried about being a failure.
Lex Fridman (1:17:05.380)
If I didn't get an A+, you know,
David Sinclair (1:17:06.660)
I was crying in my bedroom, that kind of sad existence.
Lex Fridman (1:17:10.500)
I got into my twenties, then in my thirties,
Lex Fridman (1:17:12.860)
and realized that's not the way to live.
Lex Fridman (1:17:15.260)
So I've worked very hard to get to this point
David Sinclair (1:17:17.460)
where I almost never get stressed, never.
Lex Fridman (1:17:20.700)
There's nothing that, I've never gotten angry in my lab.
David Sinclair (1:17:23.100)
I've got 20 kids.
Lex Fridman (1:17:24.100)
Sometimes it's like a,
David Sinclair (1:17:25.580)
most of the time it's like a kindergarten.
Lex Fridman (1:17:28.300)
I haven't lost my temper.
David Sinclair (1:17:29.980)
I'm very calm, but that's intentional.
Lex Fridman (1:17:32.380)
And I don't worry about stuff.
David Sinclair (1:17:34.420)
Millions of dollars, billions of dollars at stake sometimes.
Lex Fridman (1:17:39.060)
Keep it cool.
David Sinclair (1:17:39.900)
It's only life.
Lex Fridman (1:17:40.740)
We're all headed to the same place anyway.
David Sinclair (1:17:42.740)
Don't worry about it.
Lex Fridman (1:17:44.260)
But to answer your question, I think in a better way,
David Sinclair (1:17:47.740)
if you manipulate the brain of an animal,
Lex Fridman (1:17:50.660)
I'll give you an example.
David Sinclair (1:17:51.500)
If we turn on this CERT gene that I mentioned,
Lex Fridman (1:17:53.780)
CERT1, we, a good friend of mine at WashU,
David Sinclair (1:17:56.660)
Sheena Mai did this.
Lex Fridman (1:17:58.060)
They upregulated that gene
David Sinclair (1:18:00.420)
just in the neurons of the animal.
Lex Fridman (1:18:03.180)
It lived longer.
Lex Fridman (1:18:04.740)
So that's sufficient to extend lifespan.
Lex Fridman (1:18:06.900)
We also know that you can manipulate the part of the brain
David Sinclair (1:18:09.980)
called the hypothalamus,
Lex Fridman (1:18:10.980)
which leeches a lot of chemicals into the body and proteins,
David Sinclair (1:18:15.060)
most of which we don't know yet,
Lex Fridman (1:18:17.060)
but just changing the inflammation of that little organ
David Sinclair (1:18:20.980)
or part of the brain is sufficient
Lex Fridman (1:18:22.860)
to make animals live longer as well.
Lex Fridman (1:18:24.900)
So get your brain in order first
Lex Fridman (1:18:26.460)
before you tackle anything else, I would say.
Lex Fridman (1:18:29.420)
So you kind of mentioned this,
Lex Fridman (1:18:31.660)
with the inside tracker, there's ability
David Sinclair (1:18:34.420)
to take blood measurement and then infer from that
Lex Fridman (1:18:39.420)
a bunch of different things about your body
Lex Fridman (1:18:40.980)
and how you can improve the longevity.
Lex Fridman (1:18:44.700)
And you've also mentioned saliva
Lex Fridman (1:18:47.060)
and more efficient ways to get data.
Lex Fridman (1:18:54.020)
What does that involve?
David Sinclair (1:18:55.420)
What's the future of data collection look like
Lex Fridman (1:18:57.380)
for the human biological system?
David Sinclair (1:18:59.220)
Right, well, yeah, the issue with blood is
Lex Fridman (1:19:01.740)
you need someone to take it.
David Sinclair (1:19:03.380)
I mean, or you prick your finger, which hurts.
Lex Fridman (1:19:06.060)
So you've got to have something better.
Lex Fridman (1:19:07.100)
So I think what the future looks like
Lex Fridman (1:19:08.980)
is that you'll spit onto a little piece of paper
Lex Fridman (1:19:12.380)
and stick it in a machine and it'll do that for you.
Lex Fridman (1:19:14.740)
But we're not there yet.
Lex Fridman (1:19:15.620)
So the intermediate future that I'm building right now
Lex Fridman (1:19:20.980)
is that you would take a swab of the inside of your mouth,
David Sinclair (1:19:24.180)
which is the easiest way to take cells out of your body
Lex Fridman (1:19:26.740)
and just ship them off.
David Sinclair (1:19:28.340)
Okay, so it's called a buckle swab.
Lex Fridman (1:19:30.780)
I think we became very used to that.
David Sinclair (1:19:32.900)
Right now, because of COVID,
Lex Fridman (1:19:34.340)
people don't like going to the doctor as much.
David Sinclair (1:19:36.100)
They don't like going out.
Lex Fridman (1:19:36.940)
They just want to have home tests.
Lex Fridman (1:19:38.700)
And so that I think is the next 10 years
Lex Fridman (1:19:40.780)
where you'll get a kit in the mail,
David Sinclair (1:19:43.140)
you'll swab your cheeks, stick it back in an envelope,
Lex Fridman (1:19:45.300)
send it off and a week later you have
David Sinclair (1:19:48.700)
either a doctor's report or a health recommendation.
Lex Fridman (1:19:52.900)
And what can you get off a cheek swab?
David Sinclair (1:19:54.980)
Well, you can get anything.
Lex Fridman (1:19:55.860)
You can get hormones, stress levels,
David Sinclair (1:19:58.380)
stress hormones, blood glucose levels.
Lex Fridman (1:20:00.900)
You can also tell your age reasonably accurately doing that,
David Sinclair (1:20:04.380)
actually quite accurately.
Lex Fridman (1:20:05.900)
And those clocks can not just tell you
Lex Fridman (1:20:08.260)
how you're doing over time,
Lex Fridman (1:20:10.220)
but can be used to give you recommendations
David Sinclair (1:20:12.220)
to slow that process down.
Lex Fridman (1:20:14.220)
Cause some people sometimes are 10 years older biologically
David Sinclair (1:20:16.620)
than their actual chronological age.
Lex Fridman (1:20:19.580)
I mean, why does it matter how many times
Lex Fridman (1:20:21.940)
the earth's gone around the sun seriously?
Lex Fridman (1:20:23.740)
Who cares about birthdays?
David Sinclair (1:20:24.940)
It's how long your body's clock has been ticking
Lex Fridman (1:20:27.260)
and how fast.
Lex Fridman (1:20:28.580)
So I could take a cheek swab from you today, Lex,
Lex Fridman (1:20:31.060)
take it back to my lab.
Lex Fridman (1:20:32.740)
And we then by tomorrow tell you
Lex Fridman (1:20:35.420)
how old you are biologically based on
Lex Fridman (1:20:37.740)
what we call the epigenetic clock.
Lex Fridman (1:20:40.940)
And you might be freaked out, you might be happy,
Lex Fridman (1:20:43.140)
but either way we can advise you
Lex Fridman (1:20:45.580)
on how to improve the trajectory.
David Sinclair (1:20:47.860)
Cause we know that smoking increases
Lex Fridman (1:20:49.420)
the speed of that clock.
David Sinclair (1:20:50.900)
We also know that fasting and people who eat the right foods
Lex Fridman (1:20:54.220)
have a slower clock.
David Sinclair (1:20:55.980)
Without that knowledge, you're flying blind.
Lex Fridman (1:20:58.340)
But I like the idea of a swab,
David Sinclair (1:20:59.820)
cause it's just so easy.
Lex Fridman (1:21:01.260)
A lot of us have done something like that for COVID tests.
David Sinclair (1:21:03.260)
It's not a big deal.
Lex Fridman (1:21:04.100)
I've been doing a nonstop rapid antigen test.
Lex Fridman (1:21:06.180)
So let me say that particular one rapid antigen test,
Lex Fridman (1:21:11.060)
they've been a source of frustration for me
David Sinclair (1:21:12.700)
because like everybody should be doing it.
Lex Fridman (1:21:14.860)
It's so easy.
David Sinclair (1:21:16.100)
We've also been working in my lab on democratizing
Lex Fridman (1:21:18.420)
these tests to bring them down from a few hundred bucks
David Sinclair (1:21:20.740)
to a dollar.
Lex Fridman (1:21:22.060)
So just to clarify,
David Sinclair (1:21:22.980)
you're talking about not research,
Lex Fridman (1:21:24.260)
you're talking about like company stuff,
Lex Fridman (1:21:25.820)
like actual consumer facing things?
Lex Fridman (1:21:28.620)
Well, right.
David Sinclair (1:21:29.460)
The research on bringing the price down
Lex Fridman (1:21:30.980)
has occurred in my lab at Harvard.
Lex Fridman (1:21:32.940)
And then that intellectual property is being licensed
Lex Fridman (1:21:35.100)
and has been licensed out to a company
David Sinclair (1:21:37.060)
that will be consumer facing.
Lex Fridman (1:21:40.300)
So anybody for a small amount of money can do this.
David Sinclair (1:21:43.340)
Well, you got subscriber number one obsessed.
Lex Fridman (1:21:46.420)
I think that's a beautiful, beautiful idea.
Lex Fridman (1:21:48.660)
So somebody who maybe I would have been more hesitant
Lex Fridman (1:21:51.460)
about it until COVID,
Lex Fridman (1:21:54.500)
but the home tests are super easy.
Lex Fridman (1:21:56.300)
I almost wanted to share that data with the world,
David Sinclair (1:21:59.340)
like in some way, not the entirety of the data,
Lex Fridman (1:22:01.820)
but like some visualization of like how I'm doing.
David Sinclair (1:22:05.740)
Like, it's almost like when you share,
Lex Fridman (1:22:09.380)
if you had like a long run or something like that,
David Sinclair (1:22:11.420)
I wish I could share because it inspires others.
Lex Fridman (1:22:14.540)
And then you can have a conversation about like,
David Sinclair (1:22:16.900)
well, what are the hacks that you've tried
Lex Fridman (1:22:18.780)
and have a conversation about like how to improve lifestyle
Lex Fridman (1:22:21.380)
and those kinds of things that's grounded in data.
Lex Fridman (1:22:23.660)
That's exactly, that's what's gonna happen.
David Sinclair (1:22:25.580)
Now, everything's anonymous, of course.
Lex Fridman (1:22:27.700)
We talked about security there,
Lex Fridman (1:22:29.620)
but once it's anonymized, you can then plot these numbers.
Lex Fridman (1:22:32.540)
And I've plotted my epigenetic age
David Sinclair (1:22:35.580)
versus hundreds of other people
Lex Fridman (1:22:37.300)
who have taken this test now.
Lex Fridman (1:22:39.060)
And I can tell you where I fit relative to others
Lex Fridman (1:22:41.460)
in terms of my biological age.
Lex Fridman (1:22:43.580)
And I'm happy to share that with you
Lex Fridman (1:22:44.980)
because it's pretty low.
David Sinclair (1:22:47.260)
You can choose to share it, of course,
Lex Fridman (1:22:48.500)
not everyone wants to share that.
Lex Fridman (1:22:50.460)
But when you go to the doctor,
Lex Fridman (1:22:52.220)
first of all, your doctor does treat you
David Sinclair (1:22:54.860)
as though you're an average person
Lex Fridman (1:22:55.940)
and none of us are average, there's no such thing.
Lex Fridman (1:22:58.620)
But second of all, we never know
Lex Fridman (1:23:00.300)
how we're doing relative to others
David Sinclair (1:23:01.740)
because we all, most of us, we don't share our information.
Lex Fridman (1:23:05.820)
So we might have this number and that number,
Lex Fridman (1:23:08.060)
but do you know that your numbers are good for your age
Lex Fridman (1:23:10.220)
or not?
David Sinclair (1:23:11.300)
You have no idea.
Lex Fridman (1:23:12.740)
Even your doctor probably doesn't even know.
Lex Fridman (1:23:14.540)
So this graph that I'm talking about
Lex Fridman (1:23:16.340)
is the beginning of a world where you can say,
Lex Fridman (1:23:18.020)
how am I doing?
Lex Fridman (1:23:18.940)
For the two of us, we're white and we're male
Lex Fridman (1:23:22.700)
and we're this age and we do this.
Lex Fridman (1:23:26.380)
Are we good?
Lex Fridman (1:23:27.220)
Are we doing the right things or the wrong things?
Lex Fridman (1:23:28.580)
Do we need to fix certain things?
Lex Fridman (1:23:30.420)
And this is what the future is.
Lex Fridman (1:23:32.100)
It's forget about just experimenting
Lex Fridman (1:23:35.340)
and not knowing the result.
Lex Fridman (1:23:36.260)
I mean, who doesn't experiment and doesn't look at the data?
David Sinclair (1:23:38.500)
No one, it makes no sense.
Lex Fridman (1:23:40.180)
So we're gonna enter a world
David Sinclair (1:23:41.180)
where we have a dashboard on our body,
Lex Fridman (1:23:43.460)
the swabs, the blood tests, the biosensors
David Sinclair (1:23:46.420)
where our doctors can look at that,
Lex Fridman (1:23:48.500)
but we can also look at it and they can recommend,
David Sinclair (1:23:51.580)
go to this restaurant down the road.
Lex Fridman (1:23:52.980)
They've got this great meal.
David Sinclair (1:23:54.380)
It's high in whatever you need today
Lex Fridman (1:23:56.300)
because you're lacking vitamin D and vitamin K2.
David Sinclair (1:23:58.460)
Go for it.
Lex Fridman (1:24:00.380)
Ridiculous question or perhaps not.
David Sinclair (1:24:03.260)
If you look maybe 50 years from now
Lex Fridman (1:24:05.100)
or 100 years from now, a person born then,
Lex Fridman (1:24:07.740)
what do you think is a good goal
Lex Fridman (1:24:09.260)
in terms of how long a person would live?
Lex Fridman (1:24:12.340)
What is the maximum longevity that we can achieve
Lex Fridman (1:24:16.020)
through the methods that we have today
David Sinclair (1:24:19.860)
or are developing some of the things
Lex Fridman (1:24:21.140)
we've been talking about in terms of genetics,
Lex Fridman (1:24:25.100)
in terms of biology?
Lex Fridman (1:24:27.140)
Is there a number?
David Sinclair (1:24:29.660)
Right, well, so it changes all the time
Lex Fridman (1:24:31.740)
because technology is changing so quickly.
David Sinclair (1:24:33.420)
I keep revising the number upward,
Lex Fridman (1:24:36.260)
but I would say that if you do the right things
David Sinclair (1:24:38.660)
during your life and start at an early age,
Lex Fridman (1:24:40.780)
let's say 25, we don't want malnutrition, starvation.
David Sinclair (1:24:43.260)
That's not what I'm talking about.
Lex Fridman (1:24:45.160)
But in your 20s, start eating the kind of diets
David Sinclair (1:24:48.860)
that I talked about, skipping meals.
Lex Fridman (1:24:51.880)
In animals, that gives you an extra 20 to 30%.
David Sinclair (1:24:55.940)
We don't know if that's true for humans
Lex Fridman (1:24:57.820)
and even 5% more would be a big deal for the planet.
David Sinclair (1:25:03.220)
I think that we should all aim to at least reach a century.
Lex Fridman (1:25:08.540)
I'm a little bit behind.
David Sinclair (1:25:09.380)
I was born too early to benefit the most
Lex Fridman (1:25:12.040)
from all of this discovery.
David Sinclair (1:25:13.820)
Those of you who are in your 20s,
Lex Fridman (1:25:16.000)
you should definitely aim to reach a hundred.
David Sinclair (1:25:18.700)
I don't see why not.
Lex Fridman (1:25:20.860)
Consider this, this is really important.
David Sinclair (1:25:23.140)
The average lifespan of a human
Lex Fridman (1:25:25.040)
that looks after themselves but doesn't pay attention
Lex Fridman (1:25:29.500)
is about 80, okay?
Lex Fridman (1:25:31.000)
Japan, that's the average age for a male, a bit higher.
David Sinclair (1:25:35.220)
If you do the right things in your life,
Lex Fridman (1:25:37.220)
which is eat healthy food, don't overeat,
David Sinclair (1:25:41.100)
don't become obese, do a bit of exercise,
Lex Fridman (1:25:42.900)
get good sleep and don't stress,
David Sinclair (1:25:44.720)
that gives you on average 14 extra years.
Lex Fridman (1:25:47.220)
That gets you to 94.
Lex Fridman (1:25:49.060)
So getting to a hundred,
Lex Fridman (1:25:50.260)
if you just focus on what I'm talking about,
David Sinclair (1:25:52.540)
it's not a big deal.
Lex Fridman (1:25:53.700)
So what's the maximum?
David Sinclair (1:25:54.620)
Well, we know that one human made it to 122
Lex Fridman (1:25:57.380)
and a number of them make it into their teens.
David Sinclair (1:26:00.360)
I think that's also the next level
Lex Fridman (1:26:02.140)
of where we can get to with the types of technologies
David Sinclair (1:26:06.300)
that I'm talking about.
Lex Fridman (1:26:07.580)
Medicines, like I mentioned rapamycin,
David Sinclair (1:26:09.980)
there's one called metformin, which is the diabetes drug,
Lex Fridman (1:26:12.840)
which I take.
David Sinclair (1:26:14.420)
That in combination with these lifestyle changes
Lex Fridman (1:26:16.460)
should get us beyond a hundred.
Lex Fridman (1:26:18.380)
How long can we ultimately live?
Lex Fridman (1:26:19.640)
Well, there's no maximum limit to human lifespan.
Lex Fridman (1:26:22.260)
Why can a whale live 300 years, but we cannot?
Lex Fridman (1:26:24.600)
We're basically the same structure.
David Sinclair (1:26:26.240)
We just need to learn from them.
Lex Fridman (1:26:27.980)
So anyone who says, oh, you max out at X,
David Sinclair (1:26:31.060)
I think is full of it.
Lex Fridman (1:26:33.300)
There's nothing that I've seen that says
David Sinclair (1:26:35.360)
biological organisms have to die.
Lex Fridman (1:26:37.520)
There are trees that live for thousands of years
Lex Fridman (1:26:39.500)
and their biochemistry is pretty close to ours.
Lex Fridman (1:26:42.480)
What do you think it means to live for a very long time?
David Sinclair (1:26:44.960)
Let's say if it's 200 years we're talking about
Lex Fridman (1:26:47.300)
or a thousand years.
David Sinclair (1:26:50.940)
There's some sense, you could argue,
Lex Fridman (1:26:54.580)
that there is immortal organisms already living on Earth,
David Sinclair (1:26:58.020)
like there's bacteria.
Lex Fridman (1:26:59.020)
So there's certain living organisms
David Sinclair (1:27:03.740)
that in some fundamental way do not die
Lex Fridman (1:27:07.940)
because they keep replicating their genetic,
David Sinclair (1:27:10.260)
they keep like cloning themselves.
Lex Fridman (1:27:12.660)
Is it the same human if we can somehow persist
David Sinclair (1:27:19.100)
the human mind, like copy, clone certain aspects
Lex Fridman (1:27:23.940)
and just keep replacing body parts?
Lex Fridman (1:27:27.380)
Do you think that's another way to achieve immortality?
Lex Fridman (1:27:30.460)
To achieve a prolonged sort of increased longevity
David Sinclair (1:27:33.780)
is to replace the parts that break easily
Lex Fridman (1:27:37.140)
and keep, because actually from your theory of aging
David Sinclair (1:27:42.220)
as a degradation of information,
Lex Fridman (1:27:44.460)
so an information theory view of aging,
Lex Fridman (1:27:48.260)
like what is the key information that makes a human?
Lex Fridman (1:27:51.480)
Can we persist that information
Lex Fridman (1:27:53.420)
and just replace the trivial parts?
Lex Fridman (1:27:57.300)
Yeah, I mean the short answer is yes.
David Sinclair (1:27:59.340)
We're already replacing body parts
Lex Fridman (1:28:01.340)
but what makes us human is our brain.
David Sinclair (1:28:03.820)
Everything else is suboptimal except our brain.
Lex Fridman (1:28:08.740)
The ability to replace actual neurons is really hard.
David Sinclair (1:28:13.660)
I think it might be easy to upload
Lex Fridman (1:28:16.220)
rather than replace neurons because they're so tight,
David Sinclair (1:28:19.180)
it's such a network and just perturbing the system.
Lex Fridman (1:28:24.380)
It's Roger and Gizcat.
David Sinclair (1:28:25.720)
You change everything once you get in there.
Lex Fridman (1:28:28.760)
The problem is, well, I guess the solution,
David Sinclair (1:28:31.800)
let me go to the solution that's more interesting.
Lex Fridman (1:28:34.180)
What we're learning is that if you reverse
David Sinclair (1:28:35.980)
the age of nerve cells,
Lex Fridman (1:28:38.660)
it looks like they get their memories back.
Lex Fridman (1:28:41.420)
So the memories are not lost.
Lex Fridman (1:28:42.660)
They're just that the cells don't know how to interpret them
Lex Fridman (1:28:45.300)
and function correctly.
Lex Fridman (1:28:46.860)
And this is one of the things we're studying in my lab.
David Sinclair (1:28:48.860)
If you take an old mouse that has learned something
Lex Fridman (1:28:50.420)
when it was young but forgotten, does it get that back?
Lex Fridman (1:28:53.660)
And all evidence points to that being true.
Lex Fridman (1:28:56.460)
So I'd rather go in and rejuvenate the brain as it sits
David Sinclair (1:28:59.620)
rather than replace individual cells,
Lex Fridman (1:29:01.280)
which would be really hard.
Lex Fridman (1:29:03.120)
What do you think about like efforts like Neuralink,
Lex Fridman (1:29:06.700)
which basically you mentioned uploading,
David Sinclair (1:29:10.260)
are trying to figure out,
Lex Fridman (1:29:11.700)
so creating brain computer interfaces
David Sinclair (1:29:13.660)
that are trying to figure out
Lex Fridman (1:29:14.620)
how to communicate with the brain.
Lex Fridman (1:29:16.880)
But one of the features of that is trying to record
Lex Fridman (1:29:19.380)
the human brain more and more accurately.
Lex Fridman (1:29:22.740)
Do you have hope for that to,
Lex Fridman (1:29:27.220)
of course, it will lead to us better understanding
David Sinclair (1:29:30.780)
from a neuroscience perspective, the human mind,
Lex Fridman (1:29:33.260)
but do you have hope for it increasing longevity
Lex Fridman (1:29:36.060)
in terms of how it's used?
Lex Fridman (1:29:38.340)
I think that it can help with certain diseases.
Lex Fridman (1:29:41.180)
But I see, at least within our lifetime,
Lex Fridman (1:29:42.980)
that's the best use of it is to be able to replace
David Sinclair (1:29:45.300)
parts of the body that are not functioning,
Lex Fridman (1:29:47.620)
such as the retina and other parts,
David Sinclair (1:29:50.140)
the visual cortex back here.
Lex Fridman (1:29:51.840)
That's going to be doable.
David Sinclair (1:29:53.900)
In terms of longevity,
Lex Fridman (1:29:55.300)
maybe we could put something on the hypothalamus
Lex Fridman (1:29:58.040)
and start secreting those hormones and get that back.
Lex Fridman (1:30:02.300)
Ultimately, I think the best way to preserve the brain
David Sinclair (1:30:06.780)
is going to be to record it.
Lex Fridman (1:30:10.780)
But also, I think it's going to require death,
David Sinclair (1:30:12.700)
unfortunately, to then do very detailed scans,
Lex Fridman (1:30:16.980)
even if you have enough time and money, atomic microscopy,
Lex Fridman (1:30:20.580)
and rebuild the brain from scratch.
Lex Fridman (1:30:22.540)
Rebuild from scratch, yeah.
David Sinclair (1:30:24.500)
We are living more and more in a digital world.
Lex Fridman (1:30:28.860)
I wonder if the scanning is good enough
David Sinclair (1:30:31.500)
for the critical things in terms of memories,
Lex Fridman (1:30:34.420)
in terms of the particular quirks
David Sinclair (1:30:36.420)
of your cognitive processes.
Lex Fridman (1:30:38.120)
They're not, they're not, yeah.
David Sinclair (1:30:40.420)
We're not close, yes,
Lex Fridman (1:30:42.040)
but we've made quite a bit of progress,
Lex Fridman (1:30:44.580)
so if you're an exponential type of person.
Lex Fridman (1:30:50.220)
Yeah, well, let's dream a little here.
David Sinclair (1:30:52.140)
Yes, that's the point.
Lex Fridman (1:30:52.980)
The way it would work, that I could see it working is,
Lex Fridman (1:30:56.220)
so you take a single cell slice through your dead brain,
Lex Fridman (1:31:00.880)
and we can now,
David Sinclair (1:31:01.860)
the problem with the engineering aspect is that,
Lex Fridman (1:31:04.820)
the engineering is, the physical aspect of the brain
David Sinclair (1:31:07.420)
is not even half the problem.
Lex Fridman (1:31:09.700)
The problem is which genes are switched on and off.
David Sinclair (1:31:12.980)
This experience that we're having here
Lex Fridman (1:31:15.140)
is altering certain genes in neurons
David Sinclair (1:31:18.260)
that will be preserved, hopefully, for a number of decades,
Lex Fridman (1:31:22.060)
but you cannot see that with a microscope easily,
Lex Fridman (1:31:25.300)
but there are technologies invented,
Lex Fridman (1:31:27.780)
actually just down the hall in the building I'm at,
David Sinclair (1:31:30.740)
George Church invented a way, his lab invented a way,
Lex Fridman (1:31:33.520)
to look at which genes are switched on and off,
David Sinclair (1:31:36.840)
not only in a single cell, which any lab can do these days,
Lex Fridman (1:31:40.100)
but in situ, where it's situated in the brain.
Lex Fridman (1:31:42.980)
So you can say, okay, this nerve cell,
Lex Fridman (1:31:45.240)
had these genes switched on and these switched off,
David Sinclair (1:31:47.700)
we can recreate that,
Lex Fridman (1:31:49.740)
but just scanning the brain
Lex Fridman (1:31:50.980)
and looking how the nerves are touching each other
Lex Fridman (1:31:52.540)
is not gonna do it.
David Sinclair (1:31:54.820)
Wow, okay.
Lex Fridman (1:31:55.900)
So you have to scan the full biology, the full details.
Lex Fridman (1:31:59.260)
And look at the epigenome.
Lex Fridman (1:32:00.420)
And the epigenome too.
David Sinclair (1:32:01.580)
Yeah, which genes are on and off.
Lex Fridman (1:32:03.140)
It's just easier to reset the epigenome
Lex Fridman (1:32:05.080)
and get them to work like they used to.
Lex Fridman (1:32:06.500)
True, true.
David Sinclair (1:32:07.540)
We're doing that now.
Lex Fridman (1:32:08.380)
Use the hardware we already have,
David Sinclair (1:32:09.760)
just figure out how to make that hardware last longer.
Lex Fridman (1:32:13.860)
Right, ultimately information will be lost,
David Sinclair (1:32:15.700)
even genetic information degrades slowly through mutation.
Lex Fridman (1:32:19.380)
So immortality is not achievable through that means,
David Sinclair (1:32:22.540)
though I think we could potentially reset the body
Lex Fridman (1:32:25.280)
hundreds of times and live for thousands of years.
David Sinclair (1:32:28.480)
Okay, so we talked about biology.
Lex Fridman (1:32:31.540)
Let's, forgive me, but let's talk about philosophy
David Sinclair (1:32:34.620)
for just a brief moment.
Lex Fridman (1:32:36.740)
So somebody I've enjoyed reading,
David Sinclair (1:32:38.740)
Ernest Becker wrote The Denial of Death.
Lex Fridman (1:32:40.700)
There's also Martin Heidegger.
David Sinclair (1:32:42.980)
There's a bunch of philosophers who claim
Lex Fridman (1:32:47.820)
that most people live life in denial of death.
David Sinclair (1:32:51.980)
Sort of we don't fully internalize
Lex Fridman (1:32:58.400)
the idea that we're going to die.
David Sinclair (1:33:04.220)
Because if we did, as they say,
Lex Fridman (1:33:07.000)
there will be a kind of terror of,
David Sinclair (1:33:11.220)
I mean a deep fear of death.
Lex Fridman (1:33:15.380)
The fact that we don't know what's,
David Sinclair (1:33:17.280)
like we almost don't know what to do with non existence,
Lex Fridman (1:33:23.260)
with disappearing.
David Sinclair (1:33:24.860)
Like our, the way we draw meaning from life
Lex Fridman (1:33:28.300)
seems to be grounded in the fact that we exist
Lex Fridman (1:33:30.860)
and that we at some point will not exist is terrifying.
Lex Fridman (1:33:34.620)
And so we live in an illusion that we're not going to die
Lex Fridman (1:33:37.660)
and we run from that terror.
Lex Fridman (1:33:39.700)
That's what Ernest Becker would say.
Lex Fridman (1:33:41.740)
Do you think there's any truth to that?
Lex Fridman (1:33:44.260)
Oh, I know there's truth to that.
David Sinclair (1:33:45.460)
I experience it every day when I talk to people.
Lex Fridman (1:33:47.820)
We have to live that way.
David Sinclair (1:33:49.700)
Although unfortunately I can't,
Lex Fridman (1:33:51.420)
but for most people it's extremely distressing
David Sinclair (1:33:56.540)
to think about their own mortality.
Lex Fridman (1:33:59.380)
We think about it occasionally.
Lex Fridman (1:34:00.580)
And if we really thought about it every day,
Lex Fridman (1:34:02.300)
we'd probably be brought to tears.
Lex Fridman (1:34:04.020)
How much we not just miss ourselves,
Lex Fridman (1:34:05.780)
but miss our family, our friends.
David Sinclair (1:34:10.140)
All living life forms have evolved to not want to die.
Lex Fridman (1:34:14.420)
And when I mean want,
David Sinclair (1:34:15.680)
biochemically, genetically, physically.
Lex Fridman (1:34:18.220)
That yeast cell, the cells that I studied at MIT,
David Sinclair (1:34:21.660)
they were fighting for their lives.
Lex Fridman (1:34:23.700)
They didn't think,
Lex Fridman (1:34:25.260)
but our brain has evolved the same survival aspect.
Lex Fridman (1:34:28.980)
Of course, we don't want to die.
Lex Fridman (1:34:30.380)
But the problem for us, unfortunately,
Lex Fridman (1:34:32.540)
it's a curse and a blessing is that we're now conscious.
David Sinclair (1:34:34.960)
We know that we're going to die.
Lex Fridman (1:34:37.180)
Most species that have ever existed don't.
David Sinclair (1:34:40.300)
That's a burden, that's a curse.
Lex Fridman (1:34:42.300)
And so what I think has happened is
David Sinclair (1:34:43.660)
we've evolved certainly to want to live for a long time,
Lex Fridman (1:34:46.900)
perhaps never want to die.
Lex Fridman (1:34:49.140)
But the thought about dying is so traumatic
Lex Fridman (1:34:52.160)
that there is an innate part of our brains.
Lex Fridman (1:34:55.620)
And it's probably genetically wired to not think about it.
Lex Fridman (1:35:00.940)
I really think that's part of being human.
David Sinclair (1:35:03.180)
Because, think about tribes that obsessed
Lex Fridman (1:35:06.020)
with longevity every day and that we're going to die.
David Sinclair (1:35:09.620)
They probably didn't make much technological progress
Lex Fridman (1:35:12.300)
because they were just crying in their huts every day
David Sinclair (1:35:14.540)
or on the Savannah.
Lex Fridman (1:35:16.220)
So I really think that we've evolved
David Sinclair (1:35:18.060)
to naturally deny aging.
Lex Fridman (1:35:20.340)
And it's one of the problems that I face in my career.
Lex Fridman (1:35:23.180)
And when I speak publicly and on social media
Lex Fridman (1:35:26.780)
is that it's shocking.
David Sinclair (1:35:28.340)
People don't want to think about their age,
Lex Fridman (1:35:29.920)
but I think it's getting better.
David Sinclair (1:35:31.720)
I think my book has helped.
Lex Fridman (1:35:33.940)
These tests that we're developing
David Sinclair (1:35:35.220)
should help people understand it's not a problem
Lex Fridman (1:35:38.340)
to think about your longterm health.
David Sinclair (1:35:40.300)
In fact, if you don't,
Lex Fridman (1:35:41.820)
you're going to reach 80 and really regret it.
Lex Fridman (1:35:45.260)
And the other side of it, so again, Ernest Becker,
Lex Fridman (1:35:47.740)
but also Viktor Frankl recommended highly
David Sinclair (1:35:50.140)
Man's Search for Meaning.
Lex Fridman (1:35:52.300)
Bernard Williams is a moral philosopher.
David Sinclair (1:35:54.900)
They kind of argue that this knowledge of death,
Lex Fridman (1:35:58.620)
even if we often don't contemplate it, we do at times.
Lex Fridman (1:36:03.840)
And the very, what you call the curse,
Lex Fridman (1:36:06.960)
which I agree with you, it's a curse and a blessing
David Sinclair (1:36:10.620)
that we're able to contemplate our own mortality.
Lex Fridman (1:36:13.900)
That gives meaning to life.
Lex Fridman (1:36:16.580)
So death gives meaning to life,
Lex Fridman (1:36:18.860)
is what Viktor Frankl argues.
David Sinclair (1:36:21.140)
I would probably argue the same.
Lex Fridman (1:36:22.600)
There's something about the scarcity of life
Lex Fridman (1:36:25.180)
and contemplating that,
Lex Fridman (1:36:27.140)
that makes each moment that much sweeter.
Lex Fridman (1:36:30.180)
Is there something to that?
Lex Fridman (1:36:32.380)
I think it's individual.
David Sinclair (1:36:33.860)
In my case, it's completely wrong.
Lex Fridman (1:36:35.980)
I appreciate you saying that.
David Sinclair (1:36:39.820)
I don't get joy out of every day
Lex Fridman (1:36:41.860)
because I think I'm going to die.
David Sinclair (1:36:43.780)
I get joy out of every day because every day is joyous
Lex Fridman (1:36:46.060)
and I make it that way.
Lex Fridman (1:36:47.460)
And even if I thought I was going to live forever,
Lex Fridman (1:36:50.460)
I would still be enjoying this moment just as much.
Lex Fridman (1:36:54.580)
And I bet you would too.
Lex Fridman (1:36:56.340)
Well, I think about that a lot.
David Sinclair (1:36:59.900)
I think it's very difficult to know.
Lex Fridman (1:37:03.580)
I'm almost afraid that I wouldn't enjoy it as much
David Sinclair (1:37:06.740)
if I was immortal.
Lex Fridman (1:37:07.980)
I'm almost afraid to want to be immortal or to live longer
David Sinclair (1:37:11.900)
because it perhaps is a kind of justification
Lex Fridman (1:37:18.460)
for me to accept that I'm going to die.
David Sinclair (1:37:21.700)
It's saying like, oh, if I was immortal,
Lex Fridman (1:37:23.420)
I wouldn't be able to enjoy life as much as I do.
Lex Fridman (1:37:26.160)
But it's very possible that I would enjoy just as much.
Lex Fridman (1:37:30.260)
Of course, enjoying life, whether you're immortal or not,
David Sinclair (1:37:34.220)
takes work.
Lex Fridman (1:37:35.540)
Like it requires you to have the right kind
David Sinclair (1:37:38.580)
of frame of mind.
Lex Fridman (1:37:39.820)
You can discover, you can focus your mind
David Sinclair (1:37:42.460)
on the ugliness of life.
Lex Fridman (1:37:44.500)
There's plenty of ugly things in this world
Lex Fridman (1:37:46.900)
and you can focus on them.
Lex Fridman (1:37:47.960)
You can complain.
David Sinclair (1:37:49.340)
Whenever like, you know, if it's raining outside,
Lex Fridman (1:37:53.460)
you can focus on the fact that you have shelter
Lex Fridman (1:37:56.740)
and enjoy the hell out of it.
Lex Fridman (1:37:58.460)
Or you can enjoy running in the rain when it's warm
Lex Fridman (1:38:02.020)
and the beauty of nature, just being one with nature.
Lex Fridman (1:38:05.700)
Or you can just complain, it's fucking weather again
David Sinclair (1:38:07.920)
in Boston and then it's either always raining
Lex Fridman (1:38:10.420)
or freezing, damn it.
David Sinclair (1:38:13.920)
The same thing with like wifi going out on airplanes.
Lex Fridman (1:38:18.340)
You can either complain about stupid wifi
David Sinclair (1:38:23.340)
on JetBlue or something.
Lex Fridman (1:38:25.860)
Or you could say like, how incredible it is
David Sinclair (1:38:27.620)
that I can fly through the sky and in a matter of hours
Lex Fridman (1:38:30.180)
be anywhere else in the world.
Lex Fridman (1:38:31.700)
And then I could also on occasion watch like check email
Lex Fridman (1:38:35.700)
and even watch movies while connecting through satellites
David Sinclair (1:38:39.540)
that are flying through space.
Lex Fridman (1:38:40.500)
So it's a matter of perspective and perhaps
David Sinclair (1:38:42.780)
there's an extra level of work required
Lex Fridman (1:38:44.980)
when you're immortal because it's easier
David Sinclair (1:38:47.620)
when you're immortal or live longer to be lazy,
Lex Fridman (1:38:51.680)
to delay stuff.
Lex Fridman (1:38:52.980)
But if you're not, you can still derive
Lex Fridman (1:38:55.020)
the same amount of joy.
David Sinclair (1:38:56.460)
It's possible, it's possible.
Lex Fridman (1:38:59.060)
It's definitely possible.
David Sinclair (1:38:59.900)
In my life, I went from being the nothing's working
Lex Fridman (1:39:03.120)
to every day's great to wake up to.
Lex Fridman (1:39:06.660)
And I think even if you think you can live forever,
Lex Fridman (1:39:10.460)
you can enjoy every day.
Lex Fridman (1:39:12.180)
What I do is everything's relative.
Lex Fridman (1:39:14.940)
We can compare ourselves to our neighbor who has more money
David Sinclair (1:39:17.900)
or to the flight that should have had wifi
Lex Fridman (1:39:20.460)
or which is what I do, I'm still six years old remember.
Lex Fridman (1:39:23.580)
What a six year old does says, look, I can,
Lex Fridman (1:39:27.780)
when I tell my fingers to form a fist,
David Sinclair (1:39:29.940)
they actually do that.
Lex Fridman (1:39:31.300)
That's really cool.
David Sinclair (1:39:32.700)
That's how I live my life.
Lex Fridman (1:39:34.740)
I can pick up on your desk here, this metal object.
David Sinclair (1:39:36.840)
It's a metal cube, about an inch by an inch by an inch.
Lex Fridman (1:39:39.860)
And I tell myself not about cubes,
Lex Fridman (1:39:42.560)
but about inanimate objects.
Lex Fridman (1:39:44.920)
Probably once a day I'll say, I'm a living thing.
David Sinclair (1:39:48.260)
I can think, I can move, I can eat, I am full of energy.
Lex Fridman (1:39:51.880)
And there's that leaf or this cube here
David Sinclair (1:39:53.920)
that will never be alive.
Lex Fridman (1:39:55.840)
That's what I look at and compare myself to.
Lex Fridman (1:39:59.180)
And for as long as I live, if it's forever,
Lex Fridman (1:40:01.100)
of course it won't be, but even if it was forever,
David Sinclair (1:40:04.500)
relative to this lump of metal on this table here,
Lex Fridman (1:40:07.780)
we are wondrous things in the universe
Lex Fridman (1:40:10.860)
and probably the most wondrous things in the universe.
Lex Fridman (1:40:13.740)
Yeah, we're able to deeply appreciate the leaf or the cube
Lex Fridman (1:40:18.660)
and deeply appreciate ourselves,
Lex Fridman (1:40:20.540)
which is, it can be a curse, but it's mostly a gift,
David Sinclair (1:40:24.400)
especially when you're, it's such a beautiful poem.
Lex Fridman (1:40:29.040)
Now I'm six, I'm as clever as clever,
Lex Fridman (1:40:31.640)
so I think I'll be six now forever and ever.
Lex Fridman (1:40:35.380)
That's a good thing to aspire to.
David Sinclair (1:40:37.840)
Your grandmother was onto something.
Lex Fridman (1:40:40.600)
David, this is an incredible conversation.
David Sinclair (1:40:43.000)
I'm a huge fan of your work.
Lex Fridman (1:40:44.620)
So thank you for wasting your valuable time with me today.
David Sinclair (1:40:49.320)
I really, really appreciate it.
Lex Fridman (1:40:50.480)
This was awesome.
David Sinclair (1:40:51.320)
Thank you for having me on, Lex, appreciate it.
Lex Fridman (1:40:53.960)
Thanks for listening to this conversation
David Sinclair (1:40:55.480)
with David Sinclair, and thank you to Onnit, Clear,
Lex Fridman (1:40:59.720)
National Instruments, Simply Safe, and Linode.
David Sinclair (1:41:03.600)
Check them out in the description to support this podcast.
Lex Fridman (1:41:07.100)
And now let me leave you with some words
David Sinclair (1:41:08.680)
from Arthur Schopenhauer.
Lex Fridman (1:41:10.600)
All truth passes through three stages.
David Sinclair (1:41:13.660)
First, it is ridiculed.
Lex Fridman (1:41:15.460)
Second, it is violently opposed.
David Sinclair (1:41:18.200)
Third, it is accepted as being self evident.
Lex Fridman (1:41:22.240)
Thank you for listening, and hope to see you next time.
Lex Fridman (20:00.040)
but has a huge amount of data to work with.
Lex Fridman (20:03.080)
Well, you're right.
Lex Fridman (20:03.920)
And many of my good friends are doctors.
Lex Fridman (20:05.600)
I work at Harvard.
Lex Fridman (20:06.520)
So I'm not against the profession at all.
Lex Fridman (20:09.640)
But I think that they need just as much help
David Sinclair (20:11.680)
as anyone else does.
Lex Fridman (20:13.480)
We wouldn't drive a car without a dashboard.
David Sinclair (20:15.320)
We wouldn't think of it.
Lex Fridman (20:16.140)
So why would doctors do the same?
David Sinclair (20:18.720)
If we could, could we step back to the big,
Lex Fridman (20:21.400)
profound, philosophical, both tragic
Lex Fridman (20:23.680)
and beautiful question about age?
Lex Fridman (20:26.360)
How and why do we age?
Lex Fridman (20:28.700)
Is it from an engineering perspective?
Lex Fridman (20:31.520)
You said you like the biological machine.
Lex Fridman (20:33.720)
Is that a feature or a bug of the biological machine?
Lex Fridman (20:37.760)
It is both a bug and a feature.
David Sinclair (20:40.720)
Evolutionary speaking, we only live as long as we need to
Lex Fridman (20:44.640)
to replace ourselves efficiently.
David Sinclair (20:47.360)
If you're a mouse, you're only gonna live two
Lex Fridman (20:49.320)
and a half years, three years.
David Sinclair (20:50.600)
You're probably gonna die of starvation,
Lex Fridman (20:51.880)
predation, freezing in the winter.
Lex Fridman (20:54.440)
So they divert most of their resources
Lex Fridman (20:57.120)
to reproducing rapidly,
Lex Fridman (20:59.320)
but they don't put a lot of energy
Lex Fridman (21:00.960)
into preserving their soma, which is their body.
David Sinclair (21:04.320)
Conversely, a baleen type of whale,
Lex Fridman (21:06.640)
a bowhead whale in particular will live hundreds of years
David Sinclair (21:09.320)
because they're at the top of the food chain
Lex Fridman (21:11.060)
and they can live as long as they want.
Lex Fridman (21:12.640)
So they breed slowly and build a body that lasts.
Lex Fridman (21:15.120)
We're somewhere in between because we've, you know,
David Sinclair (21:17.400)
we've really only just come out of the savannas
Lex Fridman (21:19.680)
where we could be picked off by a cat.
David Sinclair (21:22.080)
We were pretty wimpy going back 6 million years ago.
Lex Fridman (21:25.400)
So we actually need to evolve quicker than evolution will.
Lex Fridman (21:30.080)
And that's why we can use our oversized brains
Lex Fridman (21:33.560)
and intuition to give us what evolution
David Sinclair (21:36.140)
not only didn't give us, but took away from us.
Lex Fridman (21:38.280)
Now we're pathetic, look at our bodies.
David Sinclair (21:40.680)
These arms, if any of us, even the strongest person
Lex Fridman (21:42.920)
in the world went in a cage with a chimpanzee,
David Sinclair (21:45.000)
the chimp could knock that person's head off, no question.
Lex Fridman (21:47.400)
So we're pathetic.
Lex Fridman (21:48.240)
So we need to engineer ourselves to be healthier
Lex Fridman (21:50.280)
and longer lived.
Lex Fridman (21:51.580)
So getting to aging, we can do better, right?
Lex Fridman (21:55.680)
Whales do way better.
David Sinclair (21:57.260)
We're trying to learn how whales do that.
Lex Fridman (21:59.500)
And if you ask really anybody in the field now, professor,
David Sinclair (22:03.300)
they'll say there are eight or nine hallmarks of aging,
Lex Fridman (22:07.360)
which are really, it's a word for causes of aging.
Lex Fridman (22:11.520)
So that you probably have heard of some of these,
Lex Fridman (22:13.500)
your listeners will have loss of telomeres,
David Sinclair (22:16.600)
the ends of the chromosomes, like the little ends
Lex Fridman (22:19.600)
of shoelaces, that kind of thing.
David Sinclair (22:21.880)
They get too short, cells stop dividing, become senescent.
Lex Fridman (22:24.880)
They become, they put out what are called mitogens
David Sinclair (22:28.560)
that cause cancer and inflammatory molecules.
Lex Fridman (22:31.040)
So that's another aspect of aging, cellular senescence.
David Sinclair (22:34.280)
Another one is loss of the energetic.
Lex Fridman (22:35.880)
So mitochondria, the battery packs wind down.
David Sinclair (22:39.720)
There's a whole bunch, stem cells, proteostasis.
Lex Fridman (22:43.080)
Well, these are our Achilles heels that I'm talking about.
David Sinclair (22:45.440)
They're a common amongst all life forms, really.
Lex Fridman (22:48.400)
But if you want me to jump to the chases to where,
Lex Fridman (22:51.640)
what is the upstream defining factor?
Lex Fridman (22:54.400)
If we boil it down, what do we get?
Lex Fridman (22:57.300)
So most biologists would say, you can't boil it down.
Lex Fridman (22:59.700)
It's too complex.
David Sinclair (23:01.200)
I would say you can boil it down to an equation,
Lex Fridman (23:03.640)
which is the preservation of information
Lex Fridman (23:05.860)
and loss due to entropy, i.e. noise.
Lex Fridman (23:09.040)
And that is the basis of my research.
David Sinclair (23:12.380)
It originally came out of discoveries in yeast cells,
Lex Fridman (23:14.820)
where I went to MIT in the 1990s.
David Sinclair (23:17.240)
You studied bread.
Lex Fridman (23:18.760)
I kind of did.
David Sinclair (23:20.200)
I studied the makers of bread,
Lex Fridman (23:22.960)
a little yeast called Saccharomyces cerevisiae,
David Sinclair (23:25.480)
which at the time was one of the hottest, excuse the pun,
Lex Fridman (23:29.200)
organisms to work on.
Lex Fridman (23:30.920)
But we figured out in the lab why yeast cells get old
Lex Fridman (23:35.300)
and found genes that control that process
Lex Fridman (23:37.440)
and made them live longer,
Lex Fridman (23:39.000)
which was an amazing four years of my life.
David Sinclair (23:41.400)
One of those genes had a name with an acronym SIR2.
Lex Fridman (23:48.200)
Now the two is irrelevant.
David Sinclair (23:49.680)
The SIR is important.
Lex Fridman (23:51.800)
And the most important letter out of all of those three
David Sinclair (23:53.920)
is I, which stands for information.
Lex Fridman (23:56.960)
Silent information regulator number two,
David Sinclair (23:59.620)
when you put more copies of that gene in,
Lex Fridman (24:01.080)
just put in one more copy,
David Sinclair (24:02.760)
the yeast cells lived 30% longer
Lex Fridman (24:04.720)
and suppressed the cause of aging,
David Sinclair (24:06.080)
which was the dysregulation of information in the cell.
Lex Fridman (24:09.000)
And then, so fast forward to now,
David Sinclair (24:11.640)
I've been looking in humans and mice,
Lex Fridman (24:14.600)
because they live shorter and cheaper to study,
David Sinclair (24:17.760)
where the loss of information in our bodies
Lex Fridman (24:20.780)
is a root cause of aging.
Lex Fridman (24:22.580)
And I think it is.
Lex Fridman (24:24.040)
Your boldness in doing biology in this way is fascinating
David Sinclair (24:29.520)
because that also leads to a kind of,
Lex Fridman (24:31.840)
it's almost like allows for a theory of aging,
David Sinclair (24:40.280)
like you could boil it down to a single equation
Lex Fridman (24:43.080)
and it leads to a, perhaps a metric
David Sinclair (24:45.920)
that allows you to optimize aging,
Lex Fridman (24:48.620)
sort of in the fight against entropy.
David Sinclair (24:51.280)
I had to figure out which mechanisms, like you said,
Lex Fridman (24:53.820)
the silent information regulator,
David Sinclair (24:55.680)
which mechanisms allow you to preserve information
Lex Fridman (24:58.560)
without injecting noise, without creating entropy,
David Sinclair (25:03.760)
without creating degradation of that information.
Lex Fridman (25:07.000)
For some reason, converting biology,
David Sinclair (25:11.180)
which I thought was mostly impossible
Lex Fridman (25:13.520)
into an engineering problem,
David Sinclair (25:15.680)
feels like it makes it amenable to optimization,
Lex Fridman (25:19.400)
to solving problems, to creating technology that can,
David Sinclair (25:23.440)
whether that's genetic engineering or AI,
Lex Fridman (25:26.680)
it makes it possible to create the technology
David Sinclair (25:30.920)
that would improve the degradation of information and aging.
Lex Fridman (25:36.240)
Is there more concrete ways you think
Lex Fridman (25:38.160)
about the kind of information you want to preserve?
Lex Fridman (25:41.440)
And also, is there good ideas about regulators
David Sinclair (25:46.120)
of that information, about ways to prevent the distortion,
Lex Fridman (25:52.400)
the degradation of that information?
David Sinclair (25:54.020)
Right, so we have silent information regulator genes
Lex Fridman (25:56.580)
in our bodies.
David Sinclair (25:57.420)
We have seven of them, SIRT1 through seven, they're called.
Lex Fridman (26:00.360)
And we found in mice, one way to slow down
David Sinclair (26:03.200)
the loss of information is to just give more of these,
Lex Fridman (26:06.920)
to upregulate these genes.
Lex Fridman (26:08.440)
So we made a mouse that has more of this SIRT1 gene,
Lex Fridman (26:12.000)
turned it on, and that slowed down the aging of the brain
Lex Fridman (26:15.160)
and preserved their information.
Lex Fridman (26:16.520)
Now, what information am I talking about, you might ask?
David Sinclair (26:19.440)
Well, again, you can simplify biology.
Lex Fridman (26:22.000)
There are two types of information in the cell primarily.
David Sinclair (26:25.100)
The one we all read about and know about
Lex Fridman (26:27.200)
is the DNA, the genome.
Lex Fridman (26:29.040)
And that's base four information, ATCG,
Lex Fridman (26:32.440)
the four chemicals that make up the various sequences
David Sinclair (26:35.240)
of the genome, billions of letters.
Lex Fridman (26:37.880)
And that also degrades over time.
Lex Fridman (26:39.960)
But what's been fascinating is that we find
Lex Fridman (26:42.600)
that that information is pretty much intact
David Sinclair (26:45.120)
in old animals and people.
Lex Fridman (26:47.280)
You can clone a dog.
David Sinclair (26:48.240)
One of my friends in LA just cloned his dog three times.
Lex Fridman (26:50.980)
So this is doable, right?
David Sinclair (26:52.080)
It means that the genome can be intact.
Lex Fridman (26:53.800)
But what's the other type of information?
David Sinclair (26:56.200)
It's the epigenome, the regulators
Lex Fridman (26:58.480)
of the genetic information.
Lex Fridman (27:01.220)
And physically, that's really just how the DNA is wrapped up
Lex Fridman (27:04.380)
or looped out for the cell to access it and read it.
Lex Fridman (27:08.040)
So it's similar to, and excuse this analogy,
Lex Fridman (27:11.200)
but it's a good one, a compact disc or a DVD.
David Sinclair (27:15.200)
Those pits in the foil are the digital information.
Lex Fridman (27:18.480)
That's the genome.
Lex Fridman (27:19.560)
And the epigenome is the reader of that information.
Lex Fridman (27:22.240)
And in a different cell, you'd read different music,
David Sinclair (27:25.320)
different songs, different symphonies.
Lex Fridman (27:28.000)
And that's what gets laid down when we're in the womb.
Lex Fridman (27:31.600)
And that makes a skin cell forever a skin cell
Lex Fridman (27:34.600)
and not a brain cell tomorrow.
David Sinclair (27:36.360)
Thank God, otherwise our brains wouldn't work very well.
Lex Fridman (27:38.760)
But over time, what we see is that the brain cells
David Sinclair (27:41.200)
start to look more like skin cells.
Lex Fridman (27:42.880)
And the kidney cells start to look more like liver cells.
Lex Fridman (27:45.620)
And what we call X differentiate.
Lex Fridman (27:48.120)
This is a term that we use in my lab,
Lex Fridman (27:49.400)
but isn't yet widely used.
Lex Fridman (27:52.080)
But we needed a term to explain this.
Lex Fridman (27:53.400)
And that process of X differentiation,
Lex Fridman (27:55.840)
the loss of the reader of the CD or the DVD,
David Sinclair (28:01.160)
we liken that to scratches on the DVD
Lex Fridman (28:06.200)
so that the reader cannot fully access the information.
David Sinclair (28:09.440)
Now we can slow down the scratches, as I mentioned.
Lex Fridman (28:11.440)
We can turn on these genes.
David Sinclair (28:13.120)
We can even put in molecules into the cell
Lex Fridman (28:15.880)
or even eat them and turn on those pathways,
David Sinclair (28:18.960)
which my father and I have been trying to do
Lex Fridman (28:21.520)
for about a decade to slow things down.
Lex Fridman (28:24.400)
But the question that I've had is,
Lex Fridman (28:27.360)
is there a repository of information still in the body?
David Sinclair (28:30.840)
Because anyone who knows anything
Lex Fridman (28:32.240)
about the loss of information
David Sinclair (28:33.400)
or even has tried to copy a cassette tape
Lex Fridman (28:35.520)
or photocopy or Xerox anything knows that over time,
David Sinclair (28:38.720)
you lose that information irreparably.
Lex Fridman (28:41.760)
So I've been looking for a backup copy,
David Sinclair (28:43.940)
inspired largely by Claude Shannon's work
Lex Fridman (28:46.720)
at MIT as well in the 1940s.
David Sinclair (28:48.780)
His mathematical theory of communication is just brilliant.
Lex Fridman (28:53.060)
And so I've been looking for what he called the observer,
David Sinclair (28:55.500)
which is the backup copy.
Lex Fridman (28:57.200)
We today might call that the TCPIP protocol of the internet
David Sinclair (29:01.500)
that stores information in case it doesn't make it
Lex Fridman (29:04.020)
to your computer, it will fill in the gaps.
Lex Fridman (29:06.900)
And we've been spending about the last five years
Lex Fridman (29:09.380)
to try and find if there really is a backup copy in the body
David Sinclair (29:12.160)
to reset the epigenome and polish those scratches away.
Lex Fridman (29:15.960)
That's incredible.
Lex Fridman (29:16.940)
So finding the backup, so whenever there are too many
Lex Fridman (29:19.700)
scratches pile up, you can just write a new version.
David Sinclair (29:24.540)
Like write, not a new version,
Lex Fridman (29:26.540)
but go to the backup and restore it.
David Sinclair (29:29.120)
Right, that's really all we're talking about.
Lex Fridman (29:31.660)
It's not that hard once you know the trick.
Lex Fridman (29:34.420)
And for people that actually remember like DVDs
Lex Fridman (29:38.420)
and scratches on them, how frustrating it is.
David Sinclair (29:41.540)
That's a brilliant metaphor for aging.
Lex Fridman (29:44.200)
And then the reader is the thing that skips
Lex Fridman (29:51.000)
and then it could destroy your experience,
Lex Fridman (29:53.400)
the richness of the experience that is listening
David Sinclair (29:55.800)
to your favorite song.
Lex Fridman (29:57.160)
Right, but in biology, it's even worse
David Sinclair (29:59.000)
because you'll lose your memory, your kidneys will fail,
Lex Fridman (30:01.120)
you'll get diabetes, your heart will fail.
Lex Fridman (30:03.640)
And we call that aging and age related diseases.
Lex Fridman (30:06.880)
So most people forget that diseases that we get
David Sinclair (30:10.040)
when we get old are 80 to 90% caused by aging.
Lex Fridman (30:13.860)
And we've been trying to fix things with band aids
David Sinclair (30:15.960)
after they occur without even generally talking
Lex Fridman (30:19.040)
about the root cause of the problem.
David Sinclair (30:21.360)
Is there the scratches, do those come from,
Lex Fridman (30:28.260)
are those programmed or are they failures?
David Sinclair (30:31.880)
Meaning is it, so if it's by design,
Lex Fridman (30:36.440)
then there's like a encoded timeline schedule
David Sinclair (30:40.960)
that the body's just on purpose,
Lex Fridman (30:43.000)
degrading the whole thing.
Lex Fridman (30:44.560)
And then there's the just the wear and tear
Lex Fridman (30:47.100)
of like the scratches on a disc that happen through time.
Lex Fridman (30:50.400)
Which one is it that's the source of aging?
Lex Fridman (30:54.240)
It's more akin to wear and tear, there isn't a program.
David Sinclair (30:56.940)
Getting back to evolution, there's no selection for aging.
Lex Fridman (31:00.760)
We're not designed to age, we just live as long as we need
David Sinclair (31:03.600)
to and then we're at the whim of entropy, basically.
Lex Fridman (31:06.160)
Second law of thermodynamics, stuff falls apart.
David Sinclair (31:09.120)
We live a bit longer than age 40,
Lex Fridman (31:11.200)
only because there are robust, resilient systems,
Lex Fridman (31:13.420)
but eventually they fail as well.
Lex Fridman (31:15.320)
Current limit to the human lifespan
David Sinclair (31:16.940)
where they completely fail is 122.
Lex Fridman (31:21.480)
But I don't like to think of it as wear and tear
David Sinclair (31:23.240)
because there's two aspects to it.
Lex Fridman (31:25.880)
There's a system that's built to keep us alive
David Sinclair (31:28.080)
when we're young, but actually goes,
Lex Fridman (31:30.960)
comes back to bite us as we get older.
Lex Fridman (31:33.280)
And we call this issue antagonistic pleiotropy.
Lex Fridman (31:37.800)
What's good for you when you're young
David Sinclair (31:39.500)
can cause problems when you're older.
Lex Fridman (31:42.920)
So we've been looking, what is the main causes of the noise?
Lex Fridman (31:46.160)
And we've found two of them definitively.
Lex Fridman (31:49.320)
The first one is broken chromosomes.
David Sinclair (31:52.000)
When a chromosome breaks, the cell has to panic
Lex Fridman (31:55.000)
because that's either gonna cause a cancer or kill the cell.
David Sinclair (31:58.280)
There's only two outcomes, it's pretty much a problem.
Lex Fridman (32:01.180)
And so what the cell does is it reorganizes the epigenome
David Sinclair (32:05.100)
in a massive way.
Lex Fridman (32:06.100)
What that leads to is, think of it as a tennis match
David Sinclair (32:09.740)
or a ping pong game.
Lex Fridman (32:11.620)
The proteins are the balls
Lex Fridman (32:13.100)
and they now leave where they should be,
Lex Fridman (32:14.940)
which is regulating the genes that make the cell type,
David Sinclair (32:18.140)
whatever it is.
Lex Fridman (32:18.980)
And they have a dual function,
David Sinclair (32:20.540)
they actually go to the break,
Lex Fridman (32:22.100)
the chromosome will break and fix that.
Lex Fridman (32:24.620)
And then they come back.
Lex Fridman (32:26.900)
You might ask, well, why is it set up that way?
David Sinclair (32:28.460)
Well, it's a beautiful system,
Lex Fridman (32:29.300)
it coordinates gene expression,
David Sinclair (32:30.940)
the control systems with the repair.
Lex Fridman (32:32.860)
You want them coordinated.
David Sinclair (32:34.260)
Problem is, as we get older, this ping pong game,
Lex Fridman (32:36.580)
some of the balls get lost.
David Sinclair (32:37.700)
They don't come back to where they originally started.
Lex Fridman (32:40.660)
And that's what we think is the main noise for aging.
Lex Fridman (32:45.180)
And we've also, the other cause of aging that we found
Lex Fridman (32:47.660)
is cell stress, we damage nerves and they age rapidly.
Lex Fridman (32:51.140)
So that's the other issue.
Lex Fridman (32:52.860)
There's probably others, smoking chemicals, for example,
David Sinclair (32:56.420)
we know accelerates biological age pretty dramatically.
Lex Fridman (33:00.380)
But the question is, can you slow that down
David Sinclair (33:02.300)
or can you reset them to get those ping pong balls
Lex Fridman (33:04.420)
to go back to where they originally started in the game?
Lex Fridman (33:07.180)
And we think we've found a way to do that.
Lex Fridman (33:09.780)
Can you give me hints?
Lex Fridman (33:11.820)
Whose fault is it in the balls not coming back?
Lex Fridman (33:13.980)
Is it the proteins themselves?
Lex Fridman (33:15.780)
Like are they starting?
Lex Fridman (33:18.140)
Again, I've been obsessed with the protein folding problem
David Sinclair (33:20.300)
from the AI perspective.
Lex Fridman (33:21.140)
So is it the proteins or is it something else?
David Sinclair (33:23.700)
Well, we know who hits the balls and recruits them.
Lex Fridman (33:27.300)
So that the break is recognized by the cell.
David Sinclair (33:31.300)
It's recognized by proteins who send out a signal
Lex Fridman (33:35.140)
through phosphorylation is typical way cells talk
David Sinclair (33:38.940)
to other proteins.
Lex Fridman (33:40.980)
And that recruits those repair factors,
David Sinclair (33:43.540)
those ping pong balls to the break.
Lex Fridman (33:45.100)
So the cells actively doing this to try and help itself,
Lex Fridman (33:49.100)
but we don't know who's to blame for them not coming back.
Lex Fridman (33:53.940)
That could just be a flaw in the quote unquote design.
David Sinclair (33:58.460)
I don't think that there's something saying,
Lex Fridman (34:00.300)
well, 1% of you balls proteins never go back.
David Sinclair (34:04.180)
I just think it's hard to reset a system
Lex Fridman (34:06.100)
that's constantly changing.
David Sinclair (34:07.660)
We have in our bodies close to a trillion DNA breaks
Lex Fridman (34:11.340)
every day.
Lex Fridman (34:12.740)
And imagine that over 80 years,
Lex Fridman (34:14.260)
what damage that does to our epigenomic information.
David Sinclair (34:17.540)
Now we know that this is, well,
Lex Fridman (34:20.260)
we never know anything in biology,
Lex Fridman (34:21.540)
but we have strong evidence that this is true
Lex Fridman (34:23.980)
because we can mess with animals.
David Sinclair (34:27.580)
We can create DNA breaks and tickle them
Lex Fridman (34:30.060)
with a few breaks, maybe raise it by threefold
David Sinclair (34:32.940)
over background levels of normal breakage.
Lex Fridman (34:35.780)
And if we're right, those mice should get old.
Lex Fridman (34:39.260)
And they do.
Lex Fridman (34:40.380)
We can actually, we've created these breaks
David Sinclair (34:42.420)
in a way that's titratable.
Lex Fridman (34:43.980)
We can, it's like a rheostat.
David Sinclair (34:45.260)
We can send it to 11.
Lex Fridman (34:47.380)
I drove my Tesla here, I'm a big fan of a spinal tap too,
David Sinclair (34:51.380)
going to 11.
Lex Fridman (34:52.420)
If we go to 11, we can make a mouse old
David Sinclair (34:54.180)
in a matter of months.
Lex Fridman (34:55.740)
We prefer to go to a level of about four
Lex Fridman (34:58.620)
and it gets old in 10 months.
Lex Fridman (35:00.220)
But it's definitely old.
David Sinclair (35:01.180)
It's got all of the hallmarks of aging.
Lex Fridman (35:03.740)
It's got diseases.
David Sinclair (35:05.220)
It looks old.
Lex Fridman (35:06.060)
Its skin is old.
David Sinclair (35:06.900)
It's got gray hair.
Lex Fridman (35:08.060)
But importantly, we can now measure age
David Sinclair (35:10.020)
by looking at the scratches.
Lex Fridman (35:11.420)
We can look at the epigenome, we can measure it
Lex Fridman (35:13.460)
and use machine learning to give us a number.
Lex Fridman (35:15.820)
And those mice are 50% older than normal.
Lex Fridman (35:19.180)
So you can replicate the aging process in a controlled way.
Lex Fridman (35:21.860)
You can, I mean, in a way that, I mean,
David Sinclair (35:24.460)
you could accelerate it in a controlled way
Lex Fridman (35:28.660)
and measure how much exactly it's aging.
Lex Fridman (35:31.620)
And that gives you step one of a two step process
Lex Fridman (35:35.020)
to when you can then figure out,
Lex Fridman (35:36.580)
how can we reverse this?
Lex Fridman (35:38.020)
And now we're reversing those mice.
David Sinclair (35:40.220)
Is there a good, I love what you said.
Lex Fridman (35:42.580)
I mean, in biology, you really don't know.
David Sinclair (35:45.380)
It's such a beautiful mess.
Lex Fridman (35:48.540)
Is there ideas how to do that?
Lex Fridman (35:51.500)
Is that on the genetic engineering level?
Lex Fridman (35:55.060)
Is it like, what can you mess with?
David Sinclair (35:57.620)
Is it going to the, trying to discover the backup copies
Lex Fridman (36:02.300)
and restoring from them?
David Sinclair (36:04.220)
Like what's, if it's possible to convert it
Lex Fridman (36:06.380)
to natural language words, what are the ideas here?
Lex Fridman (36:09.500)
What is the observer and how do we contact it?
Lex Fridman (36:11.500)
Exactly.
Lex Fridman (36:12.340)
What's the observer and how do you contact?
Lex Fridman (36:14.340)
Or if there's other ideas, how to reverse
David Sinclair (36:17.060)
the balls getting lost process.
Lex Fridman (36:20.620)
Yeah, well, you can slow it down.
David Sinclair (36:22.860)
Slow it.
Lex Fridman (36:23.700)
But we found a reset switch recently.
David Sinclair (36:26.260)
We just published this in the December 2020 issue of Nature.
Lex Fridman (36:33.060)
And what we found is that there were three embryonic genes
David Sinclair (36:36.900)
that we could put into the adult animal
Lex Fridman (36:39.780)
to reset the age of the tissues.
Lex Fridman (36:42.020)
And it only takes four to eight weeks to work well.
Lex Fridman (36:44.700)
And we can take a blind mouse
David Sinclair (36:46.060)
that's lost its vision due to aging.
Lex Fridman (36:48.340)
Neurons aren't working well towards the brain.
David Sinclair (36:50.460)
Reset those neurons back to a younger age.
Lex Fridman (36:52.660)
And now the mice can see again.
David Sinclair (36:55.140)
These three genes are famous actually
Lex Fridman (36:57.220)
because they're a set of four genes
David Sinclair (36:59.500)
discovered by Shinya Yamanaka,
Lex Fridman (37:01.700)
who won the Nobel Prize in 2016
David Sinclair (37:04.020)
for discovering that those four genes
Lex Fridman (37:05.900)
when turned on at high levels in adult cells
David Sinclair (37:09.620)
can generate stem cells.
Lex Fridman (37:11.900)
And this is, I think, well known now
David Sinclair (37:14.060)
that we can create stem cells from adult tissue.
Lex Fridman (37:16.900)
But what wasn't known is can you partially take age back
David Sinclair (37:19.460)
without becoming a tumor
Lex Fridman (37:20.820)
or generating a stem cell in the eye,
Lex Fridman (37:22.540)
which would be a disaster?
Lex Fridman (37:24.100)
And the answer is yes.
David Sinclair (37:24.940)
There is a system in the body
Lex Fridman (37:26.620)
that can take the age of a cell back to a certain point,
Lex Fridman (37:29.060)
but no further, safely, and reset the age.
Lex Fridman (37:33.100)
And we're now using that to reset the age of the brain
David Sinclair (37:36.580)
of those mice that we aged prematurely.
Lex Fridman (37:39.340)
And they're getting their ability to learn back.
Lex Fridman (37:42.580)
This is really exciting, right?
Lex Fridman (37:44.300)
Like what's the downside of this?
David Sinclair (37:46.860)
Well, the downside is if you overdo it
Lex Fridman (37:49.260)
and you don't get it right, you might cause tumors.
Lex Fridman (37:53.380)
But we do it very carefully.
Lex Fridman (37:54.980)
And we also know that in the eye, it's very safe.
David Sinclair (37:57.940)
We also injected these, we deliver them by viruses.
Lex Fridman (38:01.660)
So we can control where and when they get turned on.
Lex Fridman (38:07.020)
And in this paper, we've published
Lex Fridman (38:08.340)
that if we put high levels in the mouse,
David Sinclair (38:10.580)
into their veins, throughout the body,
Lex Fridman (38:12.420)
they don't get cancer for over a year.
Lex Fridman (38:14.740)
So I'm so optimistic that we're going into human studies
Lex Fridman (38:18.660)
in less than two years from now.
Lex Fridman (38:20.460)
Is there a place where AI can help?
Lex Fridman (38:23.980)
Sorry to inject one of the things
David Sinclair (38:27.740)
I'm very excited about and passionate about.
Lex Fridman (38:30.260)
So Google DeepMind recently had a big breakthrough
David Sinclair (38:35.100)
with AlphaFold2, but also AlphaFold two years ago,
Lex Fridman (38:39.140)
with achieving sort of a state of the art performance
David Sinclair (38:44.140)
on the protein folding problem, single protein folding.
Lex Fridman (38:47.260)
But it also paints a hopeful picture
David Sinclair (38:50.300)
of what's possible to do in terms of simulating
Lex Fridman (38:52.900)
the folding of proteins,
Lex Fridman (38:54.180)
but also simulating biological systems through AI.
Lex Fridman (38:58.700)
Is there something to you, combined with this brilliant work
David Sinclair (39:02.740)
on the biology side that you're hopeful about
Lex Fridman (39:05.940)
where AI can be a tool to help?
Lex Fridman (39:08.300)
Where isn't it a tool?
Lex Fridman (39:09.580)
I mean, if you're not using AI right now in biology,
David Sinclair (39:11.580)
you're getting less and less likely
Lex Fridman (39:13.100)
to be left behind in biology, you're getting left behind.
David Sinclair (39:15.540)
We use it all the time.
Lex Fridman (39:16.380)
We're using it to generate these biological clocks
David Sinclair (39:19.340)
to be able to read those scratches.
Lex Fridman (39:21.940)
We're using it to predict the folding of proteins
Lex Fridman (39:24.700)
so we can target molecules and modulate their activity.
Lex Fridman (39:28.220)
We're using it to assemble genomes of different species.
Lex Fridman (39:31.420)
What else?
Lex Fridman (39:32.740)
We use it to predict the longevity of a mouse
David Sinclair (39:36.540)
based on how it reacts to certain things,
Lex Fridman (39:39.180)
hearing, eyesight, generally frailty.
David Sinclair (39:41.860)
We just put out a paper last year on that.
Lex Fridman (39:45.660)
The other thing we can use it for,
David Sinclair (39:46.900)
which is a little off the track here,
Lex Fridman (39:49.100)
but we use it for predicting
David Sinclair (39:51.300)
which microorganisms are in your body,
Lex Fridman (39:53.300)
actually not predicting, telling you.
Lex Fridman (39:55.660)
So our daughter, Natalie, was infected with Lyme disease
Lex Fridman (39:59.660)
a few years ago, almost went blind from it.
Lex Fridman (40:02.380)
And the test took four days.
Lex Fridman (40:03.740)
And I thought, just give me the DNA from her spinal fluid.
David Sinclair (40:06.900)
I'll go tell you what's in it.
Lex Fridman (40:07.900)
If it's Lyme disease or not, they refused.
Lex Fridman (40:10.060)
And so at that point I said, this has to be done better.
Lex Fridman (40:12.580)
So I've started a company that now can take a sample
David Sinclair (40:15.740)
of any part of your body.
Lex Fridman (40:17.260)
It's typically done now with liver transplant patients
David Sinclair (40:21.620)
to detect viruses that come out of their organs.
Lex Fridman (40:24.900)
But that's another area that AI is extremely important for.
David Sinclair (40:29.340)
I think if you're not, in five years,
Lex Fridman (40:31.460)
if you're not using deep learning, you've got a problem.
David Sinclair (40:35.340)
Because the amount of data that we generate now
Lex Fridman (40:36.900)
as biologists is just terabytes.
David Sinclair (40:39.420)
It can be terabytes per week.
Lex Fridman (40:40.460)
It'll eventually be terabytes per day.
Lex Fridman (40:42.300)
And then we just go from there.
Lex Fridman (40:43.940)
And I actually have trouble recruiting enough
David Sinclair (40:46.300)
bioinformaticians.
Lex Fridman (40:49.020)
A lot of our work is now just number crunching.
David Sinclair (40:52.420)
A part of that is collecting the data,
Lex Fridman (40:55.140)
which is kind of something we've talked a little bit about.
Lex Fridman (40:57.580)
But is there something you can say about
Lex Fridman (41:00.540)
how we can collect more and more data,
David Sinclair (41:04.460)
not just on the one person level,
Lex Fridman (41:07.580)
like for you to understand your various markers,
Lex Fridman (41:13.220)
but to create huge datasets
Lex Fridman (41:16.620)
to understand how we can detect certain pathogens,
David Sinclair (41:20.460)
detect certain properties, characteristics
Lex Fridman (41:22.660)
of whether it's aging or all the other ways
David Sinclair (41:25.580)
that the human body can fail.
Lex Fridman (41:27.140)
It seems like with biology,
David Sinclair (41:29.740)
there's a kind of privacy concerns that,
Lex Fridman (41:33.420)
well, actually not privacy concerns,
David Sinclair (41:34.940)
it's almost like regulation that kind of prevents
Lex Fridman (41:38.420)
hospitals from sharing data.
David Sinclair (41:42.820)
I'm not sure exactly how to say it,
Lex Fridman (41:44.500)
but it seems like when you look at autonomous vehicles,
David Sinclair (41:48.260)
people are much more willing to share data.
Lex Fridman (41:50.220)
When you look at human biology system,
David Sinclair (41:52.580)
people are much less willing to share data.
Lex Fridman (41:54.380)
Is there a hopeful path forward
David Sinclair (41:56.860)
where we can share more and more data at a large scale
Lex Fridman (42:00.260)
that ultimately ends up helping us understand
Lex Fridman (42:03.060)
the human body and then treat problems with the human body?
Lex Fridman (42:06.780)
So we are right in the middle,
David Sinclair (42:08.300)
we're living through what's gonna be seen
Lex Fridman (42:10.140)
as one of the biggest revolutions in human health,
David Sinclair (42:12.620)
through the gathering of data about our bodies.
Lex Fridman (42:16.380)
And 20 years ago, people didn't wanna go on social media,
David Sinclair (42:19.500)
they're worried about it, now you have to,
Lex Fridman (42:21.300)
if you're a kid, that's for sure.
David Sinclair (42:23.660)
Same with medical records,
Lex Fridman (42:25.540)
these are becoming all digitized and expanded.
David Sinclair (42:29.420)
Ultimately, we're going to, even if we don't want to,
Lex Fridman (42:32.580)
have to be monitored.
David Sinclair (42:34.780)
There's gonna be a court case that,
Lex Fridman (42:36.980)
I bet two, three years from now, someone's gonna say,
Lex Fridman (42:39.740)
how come my father died from a heart attack?
Lex Fridman (42:42.380)
You had these biosensors, 20 bucks, and you didn't use it.
David Sinclair (42:45.740)
Lawsuit right there, and suddenly,
Lex Fridman (42:47.460)
all hospitals have to give you one of these.
David Sinclair (42:49.460)
There'll be a reversal, like to where,
Lex Fridman (42:52.820)
it's your fault if you don't collect the data,
David Sinclair (42:54.780)
that's brilliant, and that's absolutely right.
Lex Fridman (42:58.140)
I mean, that's absolutely right.
David Sinclair (43:00.780)
That's the frustration I feel on going to the doctor,
Lex Fridman (43:03.820)
is like, it's almost negligent to not collect the data,
David Sinclair (43:10.540)
because you're making,
Lex Fridman (43:11.900)
there's something really wrong with me,
Lex Fridman (43:13.980)
and you're making decisions based on very few tests,
Lex Fridman (43:17.900)
that's almost negligent, when you have the opportunity
David Sinclair (43:20.100)
to collect a huge amount more data.
Lex Fridman (43:21.980)
Well, let me tell you something.
David Sinclair (43:23.540)
Like, I've got this inside tracker data
Lex Fridman (43:26.780)
for myself over a decade,
Lex Fridman (43:29.020)
and you'd think my doctor would roll his eyes at this,
Lex Fridman (43:31.780)
oh, he's gone to a consumer company, blah, blah, blah.
David Sinclair (43:34.740)
I had my first checkup in a year with him
Lex Fridman (43:37.340)
through video conference, and he was running blind.
David Sinclair (43:42.620)
He really didn't know what was going on with me.
Lex Fridman (43:45.340)
He asked the usual things.
Lex Fridman (43:46.340)
How am I sleeping?
Lex Fridman (43:47.180)
How am I eating?
David Sinclair (43:48.540)
These kind of usual things.
Lex Fridman (43:50.020)
And I said, well, I've got new tests back
David Sinclair (43:52.300)
from inside tracker, and he said, great,
Lex Fridman (43:54.380)
I'd love to see them.
Lex Fridman (43:55.860)
So I share screen, and we look at the graphs,
Lex Fridman (43:58.100)
look at the data, and he's loving it,
David Sinclair (44:00.820)
because he cannot order these tests willy nilly.
Lex Fridman (44:04.460)
So I said, well, let's order a HbA1c blood glucose levels,
David Sinclair (44:08.940)
because I'm very interested in that.
Lex Fridman (44:10.100)
That tracks with longevity.
Lex Fridman (44:11.380)
And he said, well, I have no reason to order that.
Lex Fridman (44:13.900)
Do you have a family history?
David Sinclair (44:15.460)
No.
Lex Fridman (44:17.460)
Do you have any symptoms of diabetes?
David Sinclair (44:18.820)
No.
Lex Fridman (44:19.660)
Well, I can't order the test.
David Sinclair (44:20.620)
I almost wanted to reach through the computer
Lex Fridman (44:22.140)
and strangle him, but instead, I pay a little bit
David Sinclair (44:25.940)
to get these tests done, and then he looks at them.
Lex Fridman (44:28.260)
So that's now the way consumer health is going,
David Sinclair (44:30.580)
is that you can get better data than your doctor can,
Lex Fridman (44:32.780)
but they'd like you to do that.
David Sinclair (44:34.460)
Quick human question, maybe you can educate me.
Lex Fridman (44:39.100)
I think doctors sometimes have a bit of an ego.
David Sinclair (44:42.380)
I understand that the doctors super experience
Lex Fridman (44:44.660)
a lot of things, but this is a fundamental question
David Sinclair (44:47.580)
of human variability.
Lex Fridman (44:49.220)
Like, I know a lot of specific details about like,
David Sinclair (44:52.740)
I mean, it depends, of course, what we're talking about,
Lex Fridman (44:54.620)
but I bring a lot of knowledge, and if I have data with me,
David Sinclair (44:58.420)
then I have like several orders of magnitude more knowledge.
Lex Fridman (45:02.940)
And I think there's an aspect to it where the doctor
David Sinclair (45:05.460)
has to put their expert hat, like take it off
Lex Fridman (45:11.900)
and actually be a curious, open minded person
Lex Fridman (45:14.260)
and study and look at that data.
Lex Fridman (45:16.500)
Do you think it's possible to sort of change the culture
David Sinclair (45:19.980)
of the medical system to where the doctors are almost,
Lex Fridman (45:22.780)
as you said, are excited to see the data?
Lex Fridman (45:25.700)
Or is that already happening?
Lex Fridman (45:26.820)
It's really happening.
David Sinclair (45:27.660)
Now, we've probably lost the last generation.
Lex Fridman (45:30.620)
They're no hopers, but so I teach at Harvard Medical School
Lex Fridman (45:34.500)
and they're excited about this.
Lex Fridman (45:35.980)
They're excited about aging,
David Sinclair (45:37.140)
which is a new aspect to medicine.
Lex Fridman (45:39.580)
Oh, wow, we can do something about that.
Lex Fridman (45:41.660)
And then, yeah, all this data, what do we do with it?
Lex Fridman (45:43.900)
There's still the traditional pathology and all that stuff,
David Sinclair (45:45.900)
which they need to know, but time will change their mindset.
Lex Fridman (45:52.900)
I'm not worried about that.
Lex Fridman (45:54.300)
And like we were discussing, this isn't a question of if,
Lex Fridman (45:57.340)
it's just a matter of when.
Lex Fridman (45:58.980)
And I have a front row seat on all of this.
Lex Fridman (46:02.260)
I had breakfast with a CEO who is making this happen
David Sinclair (46:07.420)
just yesterday.
Lex Fridman (46:09.540)
I can tell you for sure that most people have no idea
David Sinclair (46:12.740)
that this revolution is occurring
Lex Fridman (46:14.580)
and is happening so quickly.
David Sinclair (46:17.220)
If you're running a hospital and you can save $2,000
Lex Fridman (46:19.780)
per cardiac patient, what are you going to do?
David Sinclair (46:22.380)
You have to use it.
Lex Fridman (46:23.340)
Otherwise, the hospital down the road
David Sinclair (46:25.540)
is going to be beating you.
Lex Fridman (46:28.380)
And there are large hospital aggregations,
Lex Fridman (46:30.820)
so there's Ascension and others,
Lex Fridman (46:32.860)
that just have to go this way for budgetary reasons.
Lex Fridman (46:37.500)
And right now, the US spends 17% of their GDP on healthcare.
Lex Fridman (46:43.660)
Let's say one of these buttons on my chest costs $20.
David Sinclair (46:45.860)
It's rechargeable.
Lex Fridman (46:47.220)
And it can predict people's health
Lex Fridman (46:48.620)
and save on antibiotics to prevent heart attacks.
Lex Fridman (46:52.820)
How many billions, if not trillions of dollars,
Lex Fridman (46:54.940)
will that save over the next decade?
Lex Fridman (46:58.380)
Yeah, so when the public wakes up to this,
David Sinclair (47:00.220)
they'll almost demand it.
Lex Fridman (47:01.460)
Like, this should be accepted everywhere.
David Sinclair (47:04.020)
This is obvious.
Lex Fridman (47:04.980)
It's going to save a lot of money.
David Sinclair (47:05.980)
It's going to improve the quality of life.
Lex Fridman (47:07.620)
Well, and the CFOs of hospital groups will have to.
Lex Fridman (47:11.460)
And insurance companies are going to want to get in on this.
Lex Fridman (47:15.700)
So now that gets to privacy, right?
Lex Fridman (47:17.620)
Should an insurance company have access to your data?
Lex Fridman (47:20.460)
I would say no.
Lex Fridman (47:21.700)
But you could voluntarily show them some of it
Lex Fridman (47:24.100)
if they give you a discount.
Lex Fridman (47:25.500)
And that's also being worked on right now.
Lex Fridman (47:28.980)
I hope we do create kind of systems
David Sinclair (47:30.900)
where I can volunteer to share my data
Lex Fridman (47:33.180)
and I can also take the data back,
David Sinclair (47:35.780)
meaning like delete the data, request deletion of data.
Lex Fridman (47:39.060)
And then maybe policy creates rules
David Sinclair (47:41.460)
to where you can share data, you could delete the data.
Lex Fridman (47:45.020)
And I think if I have the option to delete all my data
David Sinclair (47:50.700)
that a particular company has,
Lex Fridman (47:52.700)
then I'll share my data with everyone.
David Sinclair (47:55.900)
I feel like if, because that gives me the tools
Lex Fridman (48:01.340)
to be a consumer, an intelligent consumer,
David Sinclair (48:04.580)
of awarding my data to a company that deserves it
Lex Fridman (48:08.700)
and taking it back when the company is misbehaving.
Lex Fridman (48:11.260)
And in that way, encourage,
Lex Fridman (48:13.460)
as a consumer in the capitalist system,
David Sinclair (48:15.780)
encourage the companies that are doing great work
Lex Fridman (48:18.740)
with that data.
David Sinclair (48:20.300)
Well, yeah, healthcare data security is number one.
Lex Fridman (48:24.220)
On my mind, InsideTracker made sure that that was true.
Lex Fridman (48:27.780)
But these buttons on your chest,
Lex Fridman (48:31.180)
there's very private stuff they can probably tell
Lex Fridman (48:33.740)
if you're having sex one night, right?
Lex Fridman (48:35.580)
So this is not the kind of stuff you want leaked.
Lex Fridman (48:37.860)
So I don't know whether it's blockchain or something.
Lex Fridman (48:39.580)
Speak for yourself.
David Sinclair (48:40.420)
I want this public.
Lex Fridman (48:41.580)
The live stream.
David Sinclair (48:43.540)
I guess it depends on how you go.
Lex Fridman (48:45.660)
But there's a lot of stuff you don't want out there.
Lex Fridman (48:48.980)
And this definitely has to be number one
Lex Fridman (48:51.620)
because it's one thing to have your credit card
David Sinclair (48:54.500)
information stolen, it's another thing
Lex Fridman (48:55.860)
your health records are permanently out there.
David Sinclair (48:57.740)
Yeah.
Lex Fridman (48:58.580)
So there's, on the biology side,
David Sinclair (48:59.860)
super exciting ways to slow aging.
Lex Fridman (49:03.620)
But there's also on the lifestyle side.
David Sinclair (49:05.580)
I recently did a 72 hour fast.
Lex Fridman (49:08.060)
It's just an opportunity to take a pause
Lex Fridman (49:09.420)
and appreciate life.
Lex Fridman (49:12.540)
Think about, there's something about fasting
David Sinclair (49:14.380)
that encourages you to reflect deeper
Lex Fridman (49:19.300)
than you otherwise might.
David Sinclair (49:22.060)
The time kind of slows.
Lex Fridman (49:24.060)
And you also realize that you're human
David Sinclair (49:25.980)
because your body needs food.
Lex Fridman (49:27.340)
And you start to see your body's almost as a machine
David Sinclair (49:30.580)
that takes food and produces thoughts.
Lex Fridman (49:33.660)
And then ends briefly.
David Sinclair (49:36.860)
I mean, you start to, depending who you are,
Lex Fridman (49:39.940)
if you're like engineering minded,
David Sinclair (49:41.700)
you start to think of this whole thing
Lex Fridman (49:43.580)
as a kind of, yeah, as a machine.
Lex Fridman (49:46.100)
And then also feelings fill this machine.
Lex Fridman (49:50.860)
Feelings of gratitude, of love,
Lex Fridman (49:52.460)
but also the uglier things of jealousy
Lex Fridman (49:56.580)
and greed and hate and all those kinds of things.
David Sinclair (49:59.660)
You start to think, okay, how do I manage this body
Lex Fridman (50:04.540)
to create a rich experience?
David Sinclair (50:06.140)
All of that comes from fasting for me.
Lex Fridman (50:07.740)
Anyway, but there's also health benefits to fasting.
David Sinclair (50:11.740)
I intermittent fast a lot.
Lex Fridman (50:13.340)
I eat just one meal a day most of the time.
David Sinclair (50:16.580)
Is there something you could say
Lex Fridman (50:18.180)
about the benefits of fasting in your own life
Lex Fridman (50:20.460)
and in general the anti aging process?
Lex Fridman (50:23.460)
Well, you're a philosopher too.
David Sinclair (50:25.540)
Sorry, I apologize.
Lex Fridman (50:26.860)
No, I'm impressed.
David Sinclair (50:28.420)
True Renaissance man.
Lex Fridman (50:30.340)
It's a joy to be here.
Lex Fridman (50:31.900)
So when it comes to fasting, this is,
Lex Fridman (50:34.060)
being abstemious is one of the oldest ways
David Sinclair (50:37.140)
to improve health.
Lex Fridman (50:38.420)
Probably they knew this 5,000 plus years ago.
Lex Fridman (50:41.540)
So that's not new.
Lex Fridman (50:43.100)
But what we're figuring out is what is optimal
Lex Fridman (50:45.580)
and how does it work?
Lex Fridman (50:47.020)
And one of the things we help contribute to,
David Sinclair (50:49.500)
which I can speak to with some authority
Lex Fridman (50:51.780)
is that these longevity genes we work on,
David Sinclair (50:54.380)
we showed back in the early 2000s
Lex Fridman (50:56.340)
are turned on by fasting.
Lex Fridman (50:58.580)
And at least in yeast, we were the first to show
Lex Fridman (51:01.140)
that how calorie restriction fasting works
David Sinclair (51:03.260)
to extend lifespan.
Lex Fridman (51:04.460)
And that was the first for any species.
David Sinclair (51:06.420)
Something similar happens in our bodies.
Lex Fridman (51:08.180)
When we're hungry or put our bodies
David Sinclair (51:10.500)
under any other perceived adversity,
Lex Fridman (51:12.620)
such as running, our bodies think,
David Sinclair (51:14.660)
wow, we're getting chased by a saber tooth cat or something.
Lex Fridman (51:19.500)
If we're really hot or cold, these probably also work.
David Sinclair (51:22.420)
To put our bodies in this defensive state,
Lex Fridman (51:24.740)
to activate these genes in the way that whales do
Lex Fridman (51:27.140)
and mice don't.
Lex Fridman (51:28.580)
And so hunger is the best way to do that.
David Sinclair (51:31.300)
In fact, I don't think you have to feel hungry.
Lex Fridman (51:33.700)
You can get used to it.
Lex Fridman (51:35.300)
But if there was one thing I would recommend
Lex Fridman (51:37.180)
to anybody to slow down aging
David Sinclair (51:39.500)
would be to skip a meal or two a day.
Lex Fridman (51:42.820)
Now it doesn't mean you don't have to live well.
David Sinclair (51:44.420)
You can go out.
Lex Fridman (51:45.260)
I go to restaurants, I eat regular food.
David Sinclair (51:47.660)
I try to be as healthy as possible.
Lex Fridman (51:49.980)
But I've gone from skipping breakfast most of my life
David Sinclair (51:53.340)
now just skipping lunch as well.
Lex Fridman (51:55.420)
And I have my physique back that I had when I was 20.
David Sinclair (51:59.260)
I feel 20 mentally.
Lex Fridman (52:01.220)
I'm much sharper.
David Sinclair (52:02.460)
I don't feel tired anymore.
Lex Fridman (52:03.460)
I sleep well.
Lex Fridman (52:04.620)
So I'm a huge fan of the one meal a day thing.
Lex Fridman (52:07.340)
Where I'm not good at is going beyond one day.
Lex Fridman (52:11.100)
But if you do three days.
Lex Fridman (52:11.940)
Have you ever fasted longer than 24 hours?
David Sinclair (52:15.580)
I tried doing two days.
Lex Fridman (52:17.100)
I might have made it to the third and given up.
David Sinclair (52:20.140)
I just find that I'm not very,
Lex Fridman (52:22.780)
I don't have a lot of willpower.
David Sinclair (52:23.820)
I also hate exercise.
Lex Fridman (52:24.900)
So I'm not sure how long I'm gonna live.
Lex Fridman (52:27.940)
But I've managed to do one meal a day.
Lex Fridman (52:29.140)
So if I can do that, seriously, anybody can do that.
David Sinclair (52:33.060)
To your listeners and viewers, I would say,
Lex Fridman (52:35.980)
don't try to do it all at once.
David Sinclair (52:38.100)
You can't go from snacking and eating three meals a day
Lex Fridman (52:40.700)
to what I do easily.
David Sinclair (52:42.820)
Work your way up to it, but also compensate with drinking.
Lex Fridman (52:45.580)
If you like tea, if you like coffee, put some milk in it.
David Sinclair (52:48.860)
That's fine.
Lex Fridman (52:49.700)
You can fill your stomach up with liquids,
David Sinclair (52:52.340)
diet sodas, I get criticized for drinking,
Lex Fridman (52:54.180)
but I'm gonna continue to have those.
Lex Fridman (52:56.540)
But then I power through the day.
Lex Fridman (52:58.260)
I definitely don't feel tired.
David Sinclair (52:59.740)
I don't have a lag anymore.
Lex Fridman (53:00.860)
But also give it at least two weeks
David Sinclair (53:02.660)
because there's a habit as well.
Lex Fridman (53:04.900)
Having something in your mouth, chewing,
David Sinclair (53:06.540)
feeling that fullness, you can break that habit.
Lex Fridman (53:09.500)
And within two, three weeks, you'll have done it.
David Sinclair (53:12.060)
Absolutely.
Lex Fridman (53:12.900)
So I'm not actually even that strict about it.
David Sinclair (53:14.500)
You said diet soda.
Lex Fridman (53:15.940)
Yeah, people are very kind of weirdly strict
David Sinclair (53:18.500)
about fasting, the rules in fasting.
Lex Fridman (53:20.860)
Like for example, I drank Element electrolytes
David Sinclair (53:25.620)
when I was fasting, and that has like five calories.
Lex Fridman (53:28.380)
And so technically it's not fasting.
David Sinclair (53:31.220)
Or people will say like, if you drink coffee,
Lex Fridman (53:33.700)
there's caffeine, and they'll say
David Sinclair (53:35.440)
that's technically not fasting
Lex Fridman (53:36.940)
because there's some kind of biological effects
David Sinclair (53:38.700)
of caffeine, but whatever.
Lex Fridman (53:40.300)
Of course, there's like biological benefits
David Sinclair (53:42.420)
that you can argue about,
Lex Fridman (53:43.540)
but there's also just experiential benefits.
David Sinclair (53:45.980)
Just calorie restriction broadly has a certain experience
Lex Fridman (53:49.980)
to it that, like for me personally,
David Sinclair (53:52.420)
just as you said, has made me feel really good.
Lex Fridman (53:55.180)
That said, especially, I've gained quite a bit of weight,
David Sinclair (54:01.380)
maybe even like 15 pounds, something like that,
Lex Fridman (54:03.340)
since I moved to Austin, Texas.
Lex Fridman (54:05.660)
And I still keep the same diet,
Lex Fridman (54:08.500)
but I eat a lot of meat in that one,
David Sinclair (54:12.840)
just because it's delicious,
Lex Fridman (54:14.060)
because it's also the amazing people I met in Texas.
David Sinclair (54:19.060)
It's just there's like a camaraderie,
Lex Fridman (54:21.700)
a friendship, a love to the people
David Sinclair (54:23.420)
that like makes you really enjoy
Lex Fridman (54:25.660)
the atmosphere of eating the brisket and the meat.
Lex Fridman (54:29.300)
Is this Joe Rogan insisting?
Lex Fridman (54:31.060)
Joe is, I mean, he's very different.
David Sinclair (54:34.660)
Joe loves bread and pasta.
Lex Fridman (54:38.660)
Like he knows that his body feels best
David Sinclair (54:42.180)
doing keto or carnivore.
Lex Fridman (54:44.220)
So that's what he usually tries to stick to,
Lex Fridman (54:47.420)
but he also does not hold back,
Lex Fridman (54:50.100)
and he'll just eat pasta when he eats pasta,
Lex Fridman (54:52.660)
and he sort of enjoys life in that way.
Lex Fridman (54:55.100)
I can't, I don't know how to enjoy life in that way.
David Sinclair (54:57.820)
I also love pasta, but I'm just not going to enjoy it,
Lex Fridman (55:01.780)
because I know my body ultimately
David Sinclair (55:05.740)
does not feel good with pasta.
Lex Fridman (55:06.980)
So it's a funny kind of dichotomies.
David Sinclair (55:09.340)
I would like to cheat, I guess,
Lex Fridman (55:13.740)
by eating more meat than I, you know, like overeating
David Sinclair (55:19.620)
on the things that I know my body feels good on
Lex Fridman (55:22.300)
as opposed to eating stuff I shouldn't,
David Sinclair (55:24.260)
like cake and all those kinds of things.
Lex Fridman (55:26.380)
I tend to find happiness in overeating the good stuff
David Sinclair (55:32.460)
versus eating the bad stuff.
Lex Fridman (55:35.940)
And that's the kind of balance.
David Sinclair (55:37.660)
Him, he's like, fuck it.
Lex Fridman (55:41.060)
Every once in a while, you gotta enjoy it.
Lex Fridman (55:43.380)
And then also coupled with that for him
Lex Fridman (55:47.060)
is just exercise, like then face his demons the next day
Lex Fridman (55:51.100)
and just like burn a huge amount of calories,
Lex Fridman (55:53.540)
which is, I mean, whatever's up with that guy's mind,
David Sinclair (55:58.860)
there's an, there's a ability to fully experience life,
Lex Fridman (56:03.780)
which is represented by the pasta,
Lex Fridman (56:05.980)
and the ability to just like fight the demons,
Lex Fridman (56:09.180)
which is represented by all the crazy kettle balls
Lex Fridman (56:11.380)
and running the hills and all this kind of stuff
Lex Fridman (56:13.900)
that he does.
David Sinclair (56:14.740)
That takes a lot out of you doing
Lex Fridman (56:16.260)
that kind of insane exercise.
Lex Fridman (56:17.540)
And I think I'm more like you,
Lex Fridman (56:20.420)
or at least towards your direction is like,
David Sinclair (56:22.500)
I really hate exercise.
Lex Fridman (56:24.420)
So I do it, but I really hate it.
Lex Fridman (56:26.820)
And so it's a balance that you have to strike.
Lex Fridman (56:29.620)
Is there something you could say about the diet side of that
David Sinclair (56:33.460)
for you personally, but in general,
Lex Fridman (56:36.980)
in order to achieve calorie restriction,
David Sinclair (56:39.780)
like for me, eating, I know it may not sound healthy,
Lex Fridman (56:43.940)
but eating carnivore, eating mostly meat
David Sinclair (56:47.820)
has been, has made me feel really good,
Lex Fridman (56:50.060)
both mentally and physically.
David Sinclair (56:52.820)
Is there something you could say about the kinds of diets
Lex Fridman (56:56.220)
that may improve longevity,
Lex Fridman (56:57.740)
but also enable calorie restriction?
Lex Fridman (57:01.140)
Well, sure.
David Sinclair (57:02.820)
I mean, the first thing that's important to know
Lex Fridman (57:04.540)
is that while many people are interested slash obsessed
David Sinclair (57:08.700)
with what they eat,
Lex Fridman (57:11.220)
the data that's come out of animal studies at least
David Sinclair (57:13.620)
is it's far more important when you eat than what you eat.
Lex Fridman (57:17.300)
And this was a fantastic study a few years ago
David Sinclair (57:20.140)
by my friend, Rafael de Cabo
Lex Fridman (57:22.020)
at the National Institutes of Health in Bethesda.
Lex Fridman (57:24.700)
And he had 10,000 mice on different diets,
Lex Fridman (57:26.900)
hoping to find the perfect mix of carbs, protein, and fat.
Lex Fridman (57:30.980)
And it turns out that the only ones that lived longer
Lex Fridman (57:33.260)
are the ones that only ate once a day.
Lex Fridman (57:35.860)
And so that, if we're not mice,
Lex Fridman (57:37.940)
but I think that we're close enough to mice
David Sinclair (57:40.300)
that this tells us a lot.
Lex Fridman (57:42.620)
But okay, but I still think the best bang
David Sinclair (57:44.900)
for the longevity buck is to do both well,
Lex Fridman (57:47.820)
eat less often and eat the right things.
David Sinclair (57:51.580)
Now I'll preface this to say, I'm not a nut about this.
Lex Fridman (57:54.340)
I will eat occasional, very occasionally a dessert.
Lex Fridman (57:57.940)
Usually I steal from others, which doesn't count, right?
Lex Fridman (58:00.860)
Exactly.
Lex Fridman (58:01.700)
But you gotta live life, right?
Lex Fridman (58:02.660)
What's a long life if it's not enjoyable anyway?
Lex Fridman (58:05.460)
But what I also found, and this is,
Lex Fridman (58:08.100)
I'll get to your question in a second,
Lex Fridman (58:09.220)
but my microbiome right now and stomach is at a point
Lex Fridman (58:12.540)
where if I try to overeat on a steak,
David Sinclair (58:15.700)
which I did a couple of days ago,
Lex Fridman (58:16.900)
I actually had a chicken, a fried chicken specifically,
David Sinclair (58:22.260)
for two days, I felt terrible.
Lex Fridman (58:23.860)
I couldn't sleep, it wouldn't go down.
Lex Fridman (58:26.020)
So I'm now at a point where even if I want to binge
Lex Fridman (58:28.260)
on meat and fried foods, I just can't, it just feels bad.
Lex Fridman (58:32.780)
But what do I recommend?
Lex Fridman (58:34.260)
Well, what the data says, which I try to follow,
David Sinclair (58:37.020)
is that plant based foods will be better
Lex Fridman (58:40.340)
than meat based foods.
Lex Fridman (58:41.300)
And I know that there are a lot of people who disagree.
Lex Fridman (58:43.900)
But one of the facts is, well, there's a few facts.
David Sinclair (58:46.220)
One is that people who live a long time
Lex Fridman (58:47.620)
tend to eat those type of diets.
David Sinclair (58:48.780)
Mediterranean, Okinawa diet,
Lex Fridman (58:51.020)
they're eating mostly plants with a little bit of meat
Lex Fridman (58:53.940)
and not a lot of red meat.
Lex Fridman (58:55.940)
And the other fact is that in animals we know
David Sinclair (58:58.580)
that there's a mechanism that's called mTOR,
Lex Fridman (59:01.340)
little m, capital TOR, that responds to certain amino acids
David Sinclair (59:05.420)
that are found in more abundance in meat.
Lex Fridman (59:07.620)
And when it responds, it actually shortens lifespan.
Lex Fridman (59:10.260)
And the converse, if you starve it
Lex Fridman (59:11.540)
of those three amino acids, mostly in meat,
David Sinclair (59:15.820)
then it extends lifespan.
Lex Fridman (59:17.540)
And there's a drug called rapamycin,
David Sinclair (59:19.460)
which some people are experimenting with, that does that.
Lex Fridman (59:22.740)
So you might be able to, I'm just saying this here
David Sinclair (59:25.540)
from all my colleagues, we don't know the results here,
Lex Fridman (59:27.660)
but you could potentially take a rapamycin like drug
Lex Fridman (59:30.660)
and counteract the effects of meat in the long run.
Lex Fridman (59:34.260)
Dono, we should try that actually,
David Sinclair (59:35.820)
we could do that in the lab.
Lex Fridman (59:37.300)
But getting to the bottom of this,
Lex Fridman (59:39.340)
what I think is going on is that
Lex Fridman (59:41.220)
just like testosterone and growth hormone,
David Sinclair (59:42.900)
you will get temporary, maybe not temporary,
Lex Fridman (59:47.100)
immediate health benefits.
David Sinclair (59:48.580)
You'll feel great, you'll get more muscle energy.
Lex Fridman (59:51.900)
But the problem is I think it's at the expense
David Sinclair (59:54.300)
of longterm health and longevity.
Lex Fridman (59:56.140)
Well, this is actually something I worry about
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