Dr. David Sinclair: The Biology of Slowing & Reversing Aging
Andrew Huberman:
安德鲁·休伯曼：
Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life.
欢迎来到休伯曼实验室播客，我们在这里讨论科学和基于科学的日常生活工具。
Andrew Huberman:
安德鲁·休伯曼：
I'm Andrew Huberman and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine.
我是安德鲁·胡伯曼，斯坦福大学医学院神经生物学和眼科教授。
Today my guest is Dr. David Sinclair, Professor of Genetics at Harvard Medical School and co-director of the Paul F.
今天我的嘉宾是哈佛医学院遗传学教授、Paul F.
Glenn Center for the Biology of Aging.
格伦衰老生物学中心。
Dr. Sinclair's work is focused on why we age and how to slow or reverse the effects of aging by focusing on the cellular and molecular pathways that exist in all cells of the body and that progress those cells over time from young cells to old cells.
辛克莱博士的工作重点是我们衰老的原因以及如何通过关注身体所有细胞中存在的细胞和分子途径来减缓或逆转衰老的影响，以及随着时间的推移这些细胞从年轻细胞发展到衰老细胞的过程。
By elucidating the biology of cellular maturation and aging, Dr. Sinclair's group has figured out intervention points by which any of us, indeed all of us, can slow or reverse the effects of aging.
通过阐明细胞成熟和衰老的生物学原理，辛克莱博士的研究小组找到了干预点，通过这些干预点，我们任何人，实际上是我们所有人，都可以减缓或逆转衰老的影响。
What is unique about his work is that it focuses on behavioral interventions, nutritional interventions, as well as supplementation and prescription drug interventions that can help us all age more slowly and reverse the effects of aging in all tissues of the body.
他的工作的独特之处在于，它侧重于行为干预、营养干预以及补充剂和处方药干预，这些干预可以帮助我们所有人延缓衰老并逆转身体所有组织衰老的影响。
Andrew Huberman:
安德鲁·休伯曼：
Dr. Sinclair holds a unique and revolutionary view of the aging process, which is that aging is not the normal and natural consequence that we all will suffer, but rather that aging is a disease that can be slowed or halted.
辛克莱博士对衰老过程持有独特且革命性的观点，即衰老不是我们所有人都会遭受的正常和自然的结果，而是衰老是一种可以减缓或停止的疾病。
Dr. Sinclair continually publishes original research articles in the most prestigious and competitive scientific journals.
辛克莱博士不断在最负盛名和最具竞争力的科学期刊上发表原创研究文章。
In addition to that, he's published a popular book that was a New York Times bestseller.
除此之外，他还出版了一本成为《纽约时报》畅销书的畅销书。
The title of that book is Lifespan: Why We Age and Why We Don't Have To.
这本书的书名是《寿命：为什么我们会变老，为什么我们不必变老》。
He is also very active in public facing efforts to educate people on the biology of aging and slowing the aging process.
他还非常积极地向公众宣传衰老生物学和延缓衰老过程。
Dr. Sinclair and I share a mutual interest and excitement in public education about science, and so I'm thrilled to share with you that we've partnered and Dr. David Sinclair is going to be launching the Lifespan podcast, which is all about the biology of aging and tools to intervene in the aging process.
辛克莱博士和我对科学公共教育有着共同的兴趣和兴奋，因此我很高兴与您分享我们的合作伙伴关系，大卫辛克莱博士将推出“寿命”播客，该播客全部涉及衰老生物学和干预衰老过程的工具。
Andrew Huberman:
安德鲁·休伯曼：
That podcast will launch Wednesday, January 5th.
该播客将于 1 月 5 日星期三推出。
You can find it at the link in the show notes to this episode today.
您可以在今天本集的节目说明中的链接中找到它。
As well, you can subscribe to that podcast on YouTube, Apple or Spotify or anywhere that you get your podcast.
此外，您还可以在 YouTube、Apple 或 Spotify 或任何可以获取播客的地方订阅该播客。
Again, the Lifespan podcast featuring Dr. David Sinclair begins Wednesday, January 5th, 2022.
David Sinclair 博士主持的 Lifespan 播客再次于 2022 年 1 月 5 日星期三开始。
Be sure to check it out.
一定要检查一下。
You're going to learn a tremendous amount of information and you're going to learn both the mechanistic science behind aging, the mechanistic science behind reversing the aging process and practical tools that you can apply in your everyday life.
你将学到大量的信息，你将学到衰老背后的机械科学、逆转衰老过程背后的机械科学以及可以在日常生活中应用的实用工具。
Andrew Huberman:
安德鲁·休伯曼：
In today's episode, Dr. Sinclair and I talk about the biology of aging and tools to intervene in that process, and so you might view today's episode as a primer for the Lifespan podcast because we delve deep into the behavioral tools, nutritional aspects, supplementation aspects of the biology of aging.
在今天的节目中，辛克莱博士和我讨论了衰老的生物学以及干预该过程的工具，因此您可能会将今天的节目视为寿命播客的入门读物，因为我们深入研究了衰老生物学的行为工具、营养方面和补充方面。
We also talk about David's important discoveries of the sirtuins, particular molecular components that influence what is called the epigenome.
我们还讨论了 David 对 Sirtuins 的重要发现，即影响表观基因组的特殊分子成分。
If you don't know what the epigenome is, you will soon learn in today's episode.
如果您不知道表观基因组是什么，您很快就会在今天的节目中了解到。
Coming away from today's episode, you will have in-depth knowledge about the biology of aging at the cellular, molecular and what we call the circuit level, meaning how the different organs and tissues of the bodies age independently and how they influence the aging of each other.
看完今天的节目，您将深入了解细胞、分子和我们所说的回路层面的衰老生物学，这意味着身体的不同器官和组织如何独立衰老以及它们如何相互影响衰老。
Andrew Huberman:
安德鲁·休伯曼：
Today's episode gets into discussion about many aspects of aging and tools to combat aging that have not been discussed on any other podcast or in the book Lifespan.
今天的节目讨论了衰老的许多方面以及对抗衰老的工具，这些内容在任何其他播客或《寿命》一书中都没有讨论过。
Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford.
在开始之前，我想强调一下，这个播客与我在斯坦福大学的教学和研究角色是分开的。
It is, however, part of my desire and effort to bring zero-cost-to-consumer information about science and science-related tools to the general public.
然而，我的愿望和努力的一部分是将有关科学和科学相关工具的零成本消费者信息带给公众。
In keeping with that theme, I'd like to thank the sponsors of today's podcast.
为了与这个主题保持一致，我要感谢今天播客的赞助商。
Now, my conversation with Dr. David Sinclair.
现在，我与大卫·辛克莱博士的对话。
Andrew Huberman:
安德鲁·休伯曼：
Thank you for coming.
谢谢您的光临。
David Sinclair:
大卫·辛克莱：
Thanks for having me here.
谢谢你让我来这里。
It's good to see you.
很高兴见到你。
Andrew Huberman:
安德鲁·休伯曼：
This is Monte, by the way, that we're toasting at 11:00 AM.Unlike other podcasts, we ...
顺便说一句，这是蒙特，我们在上午 11:00 举杯。与其他播客不同，我们...
Well, I don't drink alcohol, so I'm boring that way.
嗯，我不喝酒，所以我这样很无聊。
But truly thanks for being here.
但真的感谢你来到这里。
I have a ton of questions for you.
我有很多问题要问你。
We go way back in some sense, but that doesn't mean that I don't have many, many questions about aging, longevity, lifespan, actionable protocols to increase how long we live, etcetera.
从某种意义上说，我们可以追溯到很久以前，但这并不意味着我对衰老、长寿、寿命、延长寿命的可行方案等没有很多很多问题。
I just want to start off with a very simple question that I'm not even sure there's an answer to, but what is the difference between longevity, anti-aging and aging as a disease?
我只想从一个非常简单的问题开始，我什至不确定是否有答案，但长寿、抗衰老和衰老作为一种疾病之间有什么区别？
Because I associate you with this statement, aging is a disease.
因为我将你与这句话联系起来，衰老是一种疾病。
David Sinclair:
大卫·辛克莱：
Well, so longevity is the more academic way we describe what we research.
好吧，长寿是我们描述我们研究内容的更学术的方式。
Anti-aging is kind of the same thing, but it's got a bad rap because it's been used by a whole bunch of people that don't know what they're talking about.
抗衰老是同样的事情，但它的名声很差，因为它被一大群不知道自己在说什么的人使用。
So I really don't like that term anti-aging, but aging as a disease and longevity are perfectly valid ways to talk about this subject.
所以我真的不喜欢抗衰老这个词，但衰老作为一种疾病和长寿是谈论这个主题的完全有效的方式。
So let's talk about aging as a disease.
那么让我们来谈谈衰老作为一种疾病。
When I started my research, disease, here at Harvard Medical School, it was considered ...
当我在哈佛医学院开始我的疾病研究时，人们认为……
if there's something that's wrong with you and it's a rare thing, has to be less than 50% of the population, that's definitely a disease, and then people work their whole lives to try and cure that condition.
如果你身上有什么问题，而且这种情况很罕见，占人口的比例必须低于 50%，那么这绝对是一种疾病，然后人们会花费一生的时间来尝试治愈这种疾病。
So I looked up what's the definition of aging, and it says, "Well, it's a deterioration in health and sickness and you can die from it.
所以我查了一下衰老的定义，它说：“嗯，这是健康和疾病的恶化，你可能会因此而死亡。
Typically you do."
通常你会这样做。”
David Sinclair:
大卫·辛克莱：
So I'm thinking, "That sounds pretty much like a disease." But the caveat is that if more than half the population gets this condition, aging, it's put in a different bucket, which is ...
所以我在想，“这听起来很像一种疾病。”但需要注意的是，如果超过一半的人口出现这种情况，即老龄化，那么它就会被放在不同的桶中，那就是......
first of all, that's outrageous because it's just a totally arbitrary cutoff.
首先，这是令人愤慨的，因为这完全是任意的截止。
But think about this, that we're ignoring the major cause of all these diseases.
但想一想，我们忽视了所有这些疾病的主要原因。
Aging is 80 to 90% the cause of heart disease, Alzheimer's.
80% 到 90% 的心脏病、阿尔茨海默氏症是由衰老引起的。
If we didn't get old and our bodies stayed youthful, we would not get those diseases.
如果我们不变老，身体保持年轻，我们就不会患上这些疾病。
Actually, what we're showing in my lab is if you turn the clock back in tissues, those diseases go away.
事实上，我们在实验室中展示的是，如果你在组织中倒转时钟，这些疾病就会消失。
So aging is the problem and instead, through most of the last 200 years, we've been sticking band aids on diseases that have already occurred because of aging and then it's too late.
因此，衰老是一个问题，相反，在过去 200 年的大部分时间里，我们一直在因衰老而发生的疾病上贴创可贴，但为时已晚。
So there are a couple of things.
所以有几件事。
One is we want to slow aging down so we don't get those diseases, and when they do occur, don't just stick a band aid on, reverse the age of the body and then the diseases will go away.
一是我们想要延缓衰老，这样我们就不会得这些疾病，当它们真的发生时，不要只是贴上创可贴，逆转身体的年龄，然后疾病就会消失。
Andrew Huberman:
安德鲁·休伯曼：
That clarifies a lot for me.
这对我来说澄清了很多。
Thank you.
谢谢。
Can we point to one specific general phenomenon in the body that underlies aging?
我们能否指出导致衰老的体内一种特定的普遍现象？
David Sinclair:
大卫·辛克莱：
Yeah, well, that's contentious because scientists like to come up with new hypotheses, it's how they build their careers.
是的，这是有争议的，因为科学家喜欢提出新的假设，这就是他们建立职业生涯的方式。
But fortunately during the 2000s we settled on eight or nine major causes of aging.
但幸运的是，在 2000 年代，我们确定了八九个衰老的主要原因。
We call them hallmarks because causes was a little bit too strong, but these eight or nine causes, at least for the first time, allowed us to come around and talk together and we put them on a pizza so everyone got an equal weighting, equal slices.
我们称它们为标志，因为原因有点太强烈了，但这八个或九个原因，至少是第一次，让我们能够聚在一起交谈，我们把它们放在披萨上，这样每个人都得到相同的权重、相同的切片。
But before that, by the way, we were trying to kill each other in the field.
但顺便说一下，在此之前，我们曾试图在战场上互相残杀。
It was horrible.
太可怕了。
Andrew Huberman:
安德鲁·休伯曼：
Interesting that you guys work on aging and you're trying to kill each other.
有趣的是，你们致力于衰老，却试图互相残杀。
David Sinclair:
大卫·辛克莱：
Yeah, isn't it?
是啊，不是吗？
Well, kill each other's careers.
好吧，扼杀彼此的职业生涯。
We now like to think I was fairly generous, but I was one of the kids and the old guard really didn't like the new guard.
我们现在认为我相当慷慨，但我是孩子之一，老守卫真的不喜欢新守卫。
We just came along in the 1990s and said, "Free radicals don't do much." There were actually genes called longevity genes, and that caused a whole ruckus and there was this competition for what never happened, which was a Nobel Prize for this, and it just led to a lot of competition.
我们刚刚在 20 世纪 90 年代出现并说：“自由基没有多大作用。”实际上有一种叫做长寿基因的基因，这引起了一场轩然大波，人们对从未发生过的事情进行了竞争，这就是诺贝尔奖，这导致了很多竞争。
I would go to meetings and people would shout at each other and just backstab.
我去参加会议，人们会互相大喊大叫，甚至背后捅刀子。
It was horrible.
太可怕了。
But then fortunately in the 2000s we rallied around this new map of aging with these causes or hallmarks.
但幸运的是，在 2000 年代，我们围绕着这张新的老龄化地图与这些原因或标志团结在一起。
But I think that there's one slice of the pizza that is way larger than the others, and we can get to that.
但我认为有一片披萨比其他披萨大得多，我们可以做到这一点。
But that's the information in the cell that we call the epigenome.
但这就是细胞中我们称之为表观基因组的信息。
Andrew Huberman:
安德鲁·休伯曼：
Well, tell us a little bit more about the epigenome.
好吧，请告诉我们更多关于表观基因组的信息。
Frame it for us, if you will, and then we'll get into ways that one can adjust the epigenome in positive ways.
如果您愿意的话，请为我们构建它，然后我们将探讨如何以积极的方式调整表观基因组。
David Sinclair:
大卫·辛克莱：
So in science, what I like to do, I'm a reductionist, is to boil it down and I actually ended up boiling aging down to an equation, which is the loss of information due to entropy.
所以在科学上，我喜欢做的，我是一个还原论者，就是把它归结为一个方程，我实际上最终将衰老归结为一个方程，即由于熵而导致的信息损失。
It's a hard thing to overcome the second law of thermodynamics that's there, but this equation really represents the fact that I think aging is a loss of information in the same way that when you xerox something a thousand times, you'll lose that information, or you try to copy a cassette tape, or even if you send information across the internet, some of it will get lost.
克服热力学第二定律是一件很难的事情，但这个方程确实代表了一个事实，即我认为衰老是一种信息丢失，就像当你将某样东西复印一千次时，你会丢失该信息，或者你试图复制一盒磁带，或者即使你通过互联网发送信息，其中一些信息也会丢失。
That's what I think is aging.
我认为这就是衰老。
There are two types of information in the body.
正文中有两种类型的信息。
There is the genetic information, which is digital, ATCG, the chemical letters of DNA, but there's this other part of the information in the body that's just as important, it's essential, in fact, and that's the systems that control which genes are switched on and off in what cell, at what time in response to what we eat, etcetera.
有遗传信息，它是数字的、ATCG、DNA 的化学字母，但体内信息的其他部分同样重要，事实上，它是必不可少的，这就是控制哪些基因在哪个细胞中打开和关闭、在何时响应我们所吃的东西等的系统。
David Sinclair:
大卫·辛克莱：
It turns out that 80% of our future longevity and health is controlled by this second part, the epigenetic information, the control systems.
事实证明，我们未来 80% 的寿命和健康是由第二部分（表观遗传信息，即控制系统）控制的。
I liken the DNA to the music that's on a DVD or compact disc.
我将 DNA 比作 DVD 或光盘上的音乐。
For the younger people, we used to use these things.
对于年轻人来说，我们过去常常使用这些东西。
Andrew Huberman:
安德鲁·休伯曼：
I recall.
我记得。
David Sinclair:
大卫·辛克莱：
Then the epigenome is the reader that says, "Okay, in this cell we need to play that set of songs.
那么表观基因组就是读取器，它说：“好吧，在这个细胞中我们需要播放那组歌曲。
In this other cell we have to play a different set of songs." But over time, aging is the equivalent of scratching the CD and the DVD so that you're not playing the right songs.
在另一个牢房里，我们必须演奏一组不同的歌曲。”但随着时间的推移，老化就相当于 CD 和 DVD 被划伤，导致无法播放正确的歌曲。
Cells, when they don't hear the right songs, they get messed up and they don't function well, and that is what I'm saying is the main driver of aging and these other hallmarks are largely manifestations of that process.
细胞，当它们听不到正确的歌曲时，它们就会变得混乱并且无法正常运作，这就是我所说的衰老的主要驱动因素，而这些其他特征在很大程度上是这一过程的表现。
Andrew Huberman:
安德鲁·休伯曼：
Can we go a little deeper into what these scratches are?
我们可以更深入地了解这些划痕是什么吗？
Is it the way that the DNA are packed into a cell?
这是 DNA 被装入细胞的方式吗？
Is it the way that they're spaced?
他们的间隔是这样的吗？
What are the scratches that you're referring to?
你说的划痕是什么？
David Sinclair:
大卫·辛克莱：
So DNA is six foot long.
所以DNA有六英尺长。
If you join your chromosomes together, you get at six foot cell, so there's enough to go to the moon and back eight times in your body, and it has to be wrapped up to exist inside us.
如果你把你的染色体连接在一起，你就会得到六英尺的细胞，所以你体内的细胞足够往返月球八次，而且它必须被包裹起来才能存在于我们体内。
But it's not just wrapped up willy-nilly, it's not just a bundle of string.
但它不仅仅是随意地包裹起来，它不仅仅是一捆绳子。
It's wrapped up very carefully in ways that dictates which genes are switched on and off.
它以决定哪些基因打开和关闭的方式非常仔细地包裹起来。
When we're developing in the embryo, the cell marks the DNA with chemicals that says, "Okay, this gene is for a nerve cell.
当我们在胚胎中发育时，细胞会用化学物质标记 DNA，这些化学物质会说：“好吧，这个基因是针对神经细胞的。
You, cell, will stay a nerve cell for the next a hundred years, if you're lucky.
如果你幸运的话，你，细胞，在接下来的一百年里将一直是一个神经细胞。
Don't turn into a skin cell.
不要变成皮肤细胞。
That would be bad." Those chemicals, there are many different types of chemicals, but one's called methylation.
那会很糟糕。”这些化学物质有很多不同类型，但有一种叫做甲基化。
Those little methyls will mark which songs get played for the rest of your life, and there are other marks that change daily.
这些小甲基将标记哪些歌曲将在您的余生中播放，并且还有其他标记每天都会变化。
David Sinclair:
大卫·辛克莱：
But in total, what we're saying is that the body controls the genome through the ability to mark the DNA and then compact some parts of it, silence those genes, don't read those genes, and open others, keep others open that should stay open.
但总的来说，我们所说的是，身体通过标记 DNA 的能力来控制基因组，然后压缩 DNA 的某些部分，沉默这些基因，不读取这些基因，并打开其他基因，让其他应该保持打开状态的基因保持打开状态。
That pattern of genes that are silent and open, silent, open is what dictates the cell's type, the cell's function and then the scratches are the disruption of that.
这种沉默而开放的基因模式决定了细胞的类型、细胞的功能，而划痕则是对它们的破坏。
So genes that were once silent, and you could say it's a gene that is involved in skin, it's starting to come on in the brain, it shouldn't be there, but we see this happen, and vice versa, the gene might get shut off over time during aging, cells over time lose these structures, lose their identity, they forget what they're supposed to do and we get diseases.
所以曾经沉默的基因，你可以说它是一个与皮肤有关的基因，它开始在大脑中出现，它不应该在那里，但我们看到这种情况发生，反之亦然，随着时间的推移，基因可能会在衰老过程中关闭，随着时间的推移，细胞会失去这些结构，失去它们的身份，它们忘记了它们应该做什么，我们就会患上疾病。
We call that aging and we can measure that.
我们称之为衰老，我们可以对其进行测量。
In fact, we can measure it in such a way that we can predict when somebody's going to die based on the changes in those chemicals.
事实上，我们可以通过这样一种方式来测量它，即根据这些化学物质的变化来预测某人何时会死亡。
Andrew Huberman:
安德鲁·休伯曼：
Are these changes the same sorts of changes that underlie the outward body surface manifestations of aging that most of us are familiar with?
这些变化是否与我们大多数人所熟悉的衰老的外在体表表现的变化相同？
Graying of the hair, wrinkling of the skin, drooping of the face.
头发花白，皮肤起皱，脸下垂。
Walking around New York lately, it's amazing to me, there are certain people that seem to walk looking down at the sidewalk because their spine is essentially in a C-shape, right?
最近在纽约走来走去，令我惊讶的是，有些人走路时似乎会低头看着人行道，因为他们的脊柱基本上呈C形，对吧？
A hallmark, if you will, of aging that most of us are familiar with.
如果你愿意的话，这是我们大多数人都熟悉的衰老标志。
Are these same sorts of DNAs scratches associated with that?
这些相同类型的 DNA 划痕是否与之相关？
Or are we talking about people that potentially are going to look older but simply live longer?
或者我们谈论的是那些看起来可能会变老但实际上寿命更长的人？
David Sinclair:
大卫·辛克莱：
Well, it's actually you are as old as you look, if you want to generalize.
好吧，如果你想概括的话，实际上你就和你看起来一样老了。
So let's start with centenarian families.
让我们从百岁家庭开始吧。
These are families that tend to live over 100.
这些家庭的人口往往超过 100 人。
When they're 70, they still look 50 or less.
当他们70岁的时候，他们看起来仍然只有50岁或更少。
So it is a good indicator.
所以这是一个很好的指标。
It's not perfect because you can, like me, grow up in Australia and accelerate the aging of your skin.
它并不完美，因为你可以像我一样在澳大利亚长大并加速皮肤的老化。
But in general, how you look.
但总的来说，你的外表如何。
No one's ever died from gray hair, but overall you can get a sense just from the ability of skin to hold itself up, how thin it is, the number of wrinkles.
没有人因白发而死亡，但总体而言，您可以通过皮肤支撑自身的能力、皮肤的厚度和皱纹的数量来了解。
A great paper just came out that said that an AI system looking at the face could very accurately predict someone's age.
刚刚发表了一篇很棒的论文，称人工智能系统通过面部识别可以非常准确地预测某人的年龄。
Andrew Huberman:
安德鲁·休伯曼：
Very interesting.
非常有趣。
I started off in developmental neurobiology, so one of the things that I learned early on that I still believe wholeheartedly is that development doesn't stop at age 12 or 15 or even 25, that your entire life is one long developmental arc.
我开始研究发育神经生物学，所以我很早就学到的一件事我仍然全心全意地相信，发育不会在 12 岁、15 岁甚至 25 岁时停止，你的整个生命是一个漫长的发育弧。
So in thinking about different portions of that developmental arc, the early portion of infancy, and especially puberty, seem like especially rapid stages of aging.
因此，在考虑发育弧的不同部分时，婴儿期的早期部分，尤其是青春期，似乎是特别快速的衰老阶段。
I know we normally look at babies and children and kids in puberty and we think, "Oh, they're so vital, they're so young," and yet the way you describe these changes in the epigenome and the way you have framed aging as a disease leads me to ask are periods of immense vitality the same periods when we're aging faster?
我知道我们通常会看到青春期的婴儿、儿童和儿童，我们会想，“哦，他们是如此重要，他们如此年轻”，但你描述表观基因组这些变化的方式以及你将衰老视为一种疾病的方式让我不禁要问，生命力旺盛的时期是否与我们衰老得更快的时期相同？
David Sinclair:
大卫·辛克莱：
Yes, and this is something I've never talked about, at least not publicly.
是的，这是我从未谈论过的事情，至少没有公开谈论过。
This is a really good question.
这是一个非常好的问题。
Those chemicals we can measure, it's also known as the Horvath clock.
我们可以测量的那些化学物质，也称为霍瓦斯时钟。
It's the biological clock.
这就是生物钟。
It's separate from your chronological age.
它与您的实际年龄不同。
So actually what I didn't mention is that when the AI looked at the faces of those people, they could predict their biological age, their internal age.
所以实际上我没有提到的是，当人工智能观察那些人的面孔时，他们可以预测他们的生物年龄，他们的内在年龄。
Your skin represents the age of your organs as well and the people that look after themselves, we can talk about how to do that later, but there are some people that are 10, 20 years younger than other people biologically.
你的皮肤也代表了你器官的年龄以及照顾自己的人的年龄，我们可以稍后再讨论如何做到这一点，但有些人在生物学上比其他人年轻10、20岁。
It turns out if you measure that clock from birth or even before birth, if you look at animals, there's a massive increase in age based on that clock early in life.
事实证明，如果你从出生时甚至出生前测量这个时钟，如果你观察动物，就会发现根据生命早期的时钟，年龄会大幅增加。
David Sinclair:
大卫·辛克莱：
So you're right.
所以你是对的。
That's a really important point that you have accelerated aging during the first few years of life and then it goes linear towards the rest of your life.
这是非常重要的一点，你在生命的最初几年会加速衰老，然后在你的余生中会呈线性增长。
But there's another interesting thing you brought up, which is that we're finding that the genes that get messed up, that get scratched, that are leading to aging are those early developmental genes.
但你提到的另一件有趣的事情是，我们发现那些被弄乱、被划伤、导致衰老的基因是那些早期发育基因。
They come on late in life and just mess up the system and they seem to be particularly susceptible to those scratches.
它们出现得很晚，只会搞乱系统，而且它们似乎特别容易受到这些划痕的影响。
So what's causing the scratches?
那么是什么原因造成划痕呢？
Well, we know of a couple of things in my lab.
嗯，我们在我的实验室知道一些事情。
We figured out one is broken chromosomes, DNA damage, particularly cuts to the DNA breaks.
我们发现其中之一是染色体断裂、DNA 损伤，特别是 DNA 断裂的切割。
So if you have an x-ray or a cosmic ray, or even if you go out in the sun, you'll get your broken chromosomes.
因此，如果你有 X 射线或宇宙射线，或者即使你出去晒太阳，你也会得到断裂的染色体。
That accelerates the unwinding of those beautiful DNA loops that I mentioned.
这加速了我提到的那些美丽的 DNA 环的解开。
David Sinclair:
大卫·辛克莱：
We can actually do this to a mouse.
我们实际上可以对鼠标执行此操作。
We can accelerate that process and we get an old mouse, 50% older, and it has this bent spine kyphosis, that has gray hair, its organs are old.
我们可以加速这个过程，我们会得到一只老老鼠，老了50%，它有弯曲的脊柱后凸，有灰色的头发，它的器官很老。
So we now can control aging the forward direction.
所以我们现在可以朝着控制衰老的方向前进。
The other thing that accelerates aging is massive cell damage or stress, so we pinched nerves and we saw that their aging process was accelerated as well.
另一件加速衰老的事情是大量的细胞损伤或压力，所以我们捏紧神经，我们发现它们的衰老过程也加速了。
Andrew Huberman:
安德鲁·休伯曼：
Incredible.
难以置信。
This is more of an anecdotal phenomenon.
这更多的是一个轶事现象。
It is an anecdotal phenomenon, but this experience of in junior high school going home for a summer and you come back, high school in the U.S. usually starts eighth or ninth grade, or grade eight or grade nine for you Canadians, and then some of the kids, they grew beards over the summer or they completely matured quickly over the summer.
这是一个轶事现象，但是初中放暑假回家然后回来的经历，美国的高中通常从八年级或九年级开始，或者对你们加拿大人来说是八年级或九年级，然后有些孩子，他们在夏天留了胡子，或者在夏天很快就完全成熟了。
Do you think there's any reason to believe that rates of entry into and through puberty can predict overall rates of aging?
您认为有什么理由相信进入青春期和度过青春期的比率可以预测总体衰老率吗？
In other words, if a kid is a slow burner, they basically acquire the traits of puberty slowly over many years, can we make some course prediction that they are going to live a long time versus a kid that goes home for the summer and comes back a completely different organism or appearing to be a completely different organism?
换句话说，如果一个孩子是一个缓慢燃烧的孩子，他们基本上会在很多年里慢慢地获得青春期的特征，我们是否可以做出一些课程预测，与一个回家过暑假回来时完全不同的有机体或看起来完全不同的有机体的孩子相比，他们会活得更久？
Like they basically age very quickly in the summer, does that mean they're aging very quickly overall?
就像他们在夏天基本上衰老得很快一样，这是否意味着他们总体上衰老得很快？
David Sinclair:
大卫·辛克莱：
Well, I don't want to scare anybody.
好吧，我不想吓到任何人。
Andrew Huberman:
安德鲁·休伯曼：
Sure.
当然。
David Sinclair:
大卫·辛克莱：
There are studies that show that the slower you take to develop, it also is predictive of having a longer, healthier life.
有研究表明，发育速度越慢，也预示着您的寿命会更长、更健康。
It may have something to do with growth hormone.
可能和生长激素有关系。
We know that growth hormone is pro-aging.
我们知道生长激素具有促进衰老的作用。
Anyone who's taking growth hormone, pay attention.
任何正在服用生长激素的人都要注意。
Andrew Huberman:
安德鲁·休伯曼：
Just look at someone who's taking growth hormone, they often will acquire these characteristics of vitality, like improved smoothness of skin, but their whole body shape changes often.
看看那些服用生长激素的人，他们往往会获得这些活力的特征，比如皮肤的光滑度提高，但他们的整个体型经常发生变化。
David Sinclair:
大卫·辛克莱：
I mean, you'll feel better for a short amount of time.
我的意思是，你会在短时间内感觉好一些。
You'll build up muscle, you'll feel great, but it's like burning your candle at both ends.
你会增强肌肉，你会感觉很棒，但这就像蜡烛两头烧一样。
Ultimately, if you want to live longer, you want less of that.
最终，如果你想活得更长，你想要的就更少。
The animals that have been generated and mutants that have low growth hormone, sometimes these are dwarfs, they live the longest by far.
已经产生的动物和生长激素低的突变体，有时是侏儒，它们是迄今为止寿命最长的。
A guy in my lab, Michael Bonkowski, he had the longest lived mouse.
我实验室里的一个人迈克尔·邦考斯基（Michael Bonkowski）拥有寿命最长的老鼠。
A mouse typically lives about two and a bit years.
老鼠的寿命通常约为两年半。
He had a mouse that lived five years and he gave it caloric restrictions with fasting, combined with one of these dwarf mutations, low growth hormone.
他有一只活了五年的老鼠，他通过禁食限制热量，并结合矮化突变之一，即低生长激素。
I think he called it Yoda.
我想他称之为尤达。
But you look at who lives the longest.
但你看看谁活得最长。
It's the really small people.
这才是真正的小人物。
This is a bit anecdotal, but it sounds like it might be true, is that the people who played the Munchkins in the Wizard of Oz, many of them went on to live into their 90s and beyond.
这有点轶事，但听起来可能是真的，在《绿野仙踪》中扮演芒奇金人的人，其中许多人都活到了 90 多岁甚至更久。
Andrew Huberman:
安德鲁·休伯曼：
Really?
真的吗？
David Sinclair:
大卫·辛克莱：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Amazing.
太棒了。
David Sinclair:
大卫·辛克莱：
Oh, there are some Laron dwarfs as well.
哦，还有一些拉伦矮人。
There are dwarf mutations in South America and they seem to be protected against many of the diseases of aging.
南美洲存在侏儒突变，它们似乎可以免受许多衰老疾病的侵害。
You barely ever see heart disease or cancer in these families.
在这些家庭中你几乎看不到心脏病或癌症。
Andrew Huberman:
安德鲁·休伯曼：
Having owned a very large dog breed, a bulldog Mastiff, who lived a long life for a bulldog, 11 years, but there are many dogs that will live 12, 16 years that are smaller dogs.
拥有一种非常大的狗品种，斗牛犬獒，对于斗牛犬来说，它的寿命很长，可以活11年，但也有很多狗可以活12年、16年，都是小型犬。
Can we say that there's a direct relationship between body size and longevity or duration of life?
我们可以说身体大小和寿命或寿命之间有直接关系吗？
David Sinclair:
大卫·辛克莱：
Well, there is, but that doesn't mean that you're a slave to your early epigenome nor to your genome.
嗯，确实有，但这并不意味着你是早期表观基因组或基因组的奴隶。
The good news is that the epigenome can change; those loops and structures can be modified by how you live your life.
好消息是表观基因组是可以改变的。这些循环和结构可以根据您的生活方式进行修改。
So if you're born tall, and I wasn't, I wished at the time I did grow, but no matter what size you are, you can have a bigger impact on your life than anything your genes give you.
所以，如果你生来很高，而我不是，我希望当时我能长高，但无论你有多大，你对你生活的影响比你的基因给你的任何影响都大。
80% is epigenetic, not genetic.
80%是表观遗传的，而不是遗传的。
Andrew Huberman:
安德鲁·休伯曼：
So let's talk about some of the things that people can do, and I've kind of batched these into categories rather than just diving right into actionable protocols.
因此，让我们来谈谈人们可以做的一些事情，我将这些事情分为几类，而不是直接深入到可操作的协议中。
So the first one relates to food, blood sugar, insulin.
第一个与食物、血糖、胰岛素有关。
This is something I hear a lot about that fasting is good for us, but rarely do I hear why it's good for us.
我经常听到关于禁食对我们有好处的说法，但我很少听到为什么它对我们有好处。
One of the reasons I'm excited to talk to you today is because I want to drill into the details of this because I think understanding the mechanism will allow people to make better choices and not simply to just decide whether or not they're going to fast or not fast or how long they're going fast, I think should be dictated by some understanding of the mechanism.
我今天很高兴与你们交谈的原因之一是因为我想深入研究这个细节，因为我认为理解这个机制将使人们做出更好的选择，而不仅仅是决定他们是否要禁食或禁食多久或禁食多久，我认为应该由对机制的一些理解决定。
So why is it that having elevated blood sugar, glucose and insulin ages us more quickly?
那么，为什么血糖、葡萄糖和胰岛素升高会使我们更快衰老呢？
And/or why is it that having periods of time each day or perhaps longer can extend our lifespan?
和/或为什么每天有一段时间或更长时间可以延长我们的寿命？
David Sinclair:
大卫·辛克莱：
Well, let's start with what I think was a big mistake, was the idea that people should never be hungry.
好吧，让我们从我认为一个很大的错误开始，那就是人们永远不应该挨饿的想法。
We live in a world now where there's at least three meals a day and then we've got companies selling bars and snacks in between.
我们现在生活在一个每天至少有三顿饭的世界，然后我们就有了在三顿饭之间出售能量棒和零食的公司。
So the feeling of hunger, some people never experience hunger in their whole lives.
所以饥饿的感觉，有的人一辈子都没有经历过饥饿。
It's really, really bad for them.
这对他们来说真的非常非常糟糕。
It was based, I believe, on the 20th century view that you don't want to stress out the pancreas and you try to keep insulin levels pretty steady and not have this fluctuation.
我相信，它是基于 20 世纪的观点，即你不想给胰腺带来压力，你会努力保持胰岛素水平相当稳定，不出现这种波动。
What we actually found, my colleagues and I across this field of longevity, is that when you look at, first of all animals, whether it's a dog or a mouse or a monkey, the ones that live the longest by far, 30% longer, and stay healthy are the ones that don't eat all the time.
我和我的同事们在长寿领域的实际发现是，首先观察所有动物，无论是狗、小鼠还是猴子，迄今为止寿命最长的动物，寿命延长了 30%，而且保持健康的是那些不一直吃东西的动物。
David Sinclair:
大卫·辛克莱：
Actually, it was first discovered back in the early 20th century, but people ignored it and then it was rediscovered in the 1930s.
事实上，它早在20世纪初就被发现了，但人们忽视了它，然后在20世纪30年代才被重新发现。
Clive McCay did caloric restriction.
克莱夫·麦凯进行了热量限制。
He put cellulose in the food of rats so they couldn't get as many calories even though they ate, and those rats lived 30% longer.
他在老鼠的食物中加入了纤维素，这样它们即使吃东西也无法获得那么多的热量，而这些老鼠的寿命延长了 30%。
But then it went away and then it came back in the 2000s in a big way when a couple of things happened.
但后来它就消失了，然后在 2000 年代发生了一些事情之后它又大规模地卷土重来。
One is that my lab and others showed that there are longevity genes in the body that come on and protect us from aging and disease.
一是我的实验室和其他实验室表明，体内存在长寿基因，可以保护我们免受衰老和疾病的侵害。
The group of genes that I work on are called sirtuins, there seven of them.
我研究的一组基因称为sirtuins，共有七个。
We showed in 2005 in a science paper that if you have low levels of insulin and another molecule called "insulin-like growth factor," those low levels turn on the longevity genes.
我们在 2005 年的一篇科学论文中表明，如果你的胰岛素和另一种称为“胰岛素样生长因子”的分子水平较低，这些低水平就会启动长寿基因。
David Sinclair:
大卫·辛克莱：
One of them that's really important is called CERT1, but by having high levels of insulin all day, being fed means your longevity genes are not switched on.
其中一个非常重要的因素称为 CERT1，但由于整天都处于高水平的胰岛素，进食意味着您的长寿基因不会开启。
So you're falling apart, your epigenome, your information that keeps your cells functioning over time just degrades quicker.
所以你正在分崩离析，你的表观基因组，以及让细胞保持功能的信息随着时间的推移会退化得更快。
Your clock is ticking faster by always being fed.
由于总是有饭吃，你的时钟会走得更快。
The other thing that I think might be happening by always having food around is that it's not allowing the cell to have periods of rest and reestablish the epigenome and so it also is accelerating in that direction.
我认为周围总是有食物可能会发生的另一件事是，它不允许细胞有休息时间并重建表观基因组，因此它也在朝着这个方向加速。
There's plenty of other reasons as well that are not as profound, such as having low levels of glucose in your body will trigger your major muscles in your brain to become more sensitive to insulin and suck the glucose out of your bloodstream, which is very good.
还有很多其他并不那么深刻的原因，例如体内葡萄糖水平较低会触发大脑中的主要肌肉对胰岛素变得更加敏感，并将葡萄糖从血液中吸出，这是非常好的。
You don't want to have glucose flowing around too much and that will ward off type 2 diabetes.
您不希望葡萄糖流动过多，这样可以预防 2 型糖尿病。
Andrew Huberman:
安德鲁·休伯曼：
So hunger, of course, is associated with low blood glucose and low insulin.
因此，饥饿当然与低血糖和低胰岛素有关。
Do you think there's anything about the subjective experience of hunger itself that could be beneficial for longevity?
您认为饥饿本身的主观体验是否有利于长寿？
David Sinclair:
大卫·辛克莱：
Yeah, I do, though you get used to the feeling of not eating, so I'm kind of screwed that way.
是的，我愿意，尽管你已经习惯了不吃东西的感觉，所以我有点搞砸了。
Andrew Huberman:
安德鲁·休伯曼：
It's like cold water, you eventually adapt.
就像冷水一样，你最终会适应。
David Sinclair:
大卫·辛克莱：
You get used to it, unfortunately.
不幸的是，你已经习惯了。
But there are some studies that are being done at the National Institutes of Health that are able to simulate the effect of hunger but still provide the calories.
但美国国立卫生研究院正在进行一些研究，这些研究能够模拟饥饿的影响，但仍然提供卡路里。
It's looking like there's a small component that's due to hunger, but most of it actually is because you've got these periods of not being fed and then the body turns on these defensive genes.
看起来有一小部分是由于饥饿造成的，但实际上大部分是因为你在没有进食的时期，然后身体启动了这些防御基因。
There's a really interesting experiment that was published maybe a couple of years ago by Rafael de Cabo down at the NIH.
美国国立卫生研究院的拉斐尔·德卡波（Rafael de Cabo）大约几年前发表了一项非常有趣的实验。
What he did was he took over 10,000 mice and gave them different combinations of fat, carbohydrate, protein and he was trying to figure out what was the best combination.
他所做的就是给 10,000 多只老鼠提供不同的脂肪、碳水化合物和蛋白质组合，他试图找出最好的组合。
David Sinclair:
大卫·辛克莱：
Then he also cleverly had a group ...
然后他还巧妙的组了一个团……
well, two groups.
嗯，分成两组。
One that was fed all the time, or ate as much as they wanted, and the other group was only given food for an hour a day.
一组一直喂食，或者想吃多少就吃多少，而另一组每天只吃一小时的食物。
It turns out they ate roughly the same amount of calories because, of course, in an hour they're stuffing their faces.
事实证明，他们摄入的热量大致相同，因为当然，一个小时后他们就吃饱了。
It turns out it didn't matter what diet he gave them, it was only the group that ate within that window that lived longer and dramatically longer.
事实证明，他给他们的饮食是什么并不重要，只有在那个窗口内进食的那组人的寿命更长，而且寿命显着延长。
So my conclusion is, and mice are very similar to us metabolically, I think that tells us that it's not as important what you eat, it's when you eat during the day.
所以我的结论是，老鼠的新陈代谢与我们非常相似，我认为这告诉我们，吃什么并不重要，重要的是白天什么时候吃。
Andrew Huberman:
安德鲁·休伯曼：
What is the protocol that people can extrapolate from that?
人们可以从中推断出什么协议？
Or maybe I should just ask you, what is your protocol for when to eat and when to avoid food?
或者也许我应该问你，你关于何时进食和何时禁食的规定是什么？
Do you ever fast longer than 24 hours?
您是否曾禁食超过 24 小时？
What do you do and what do you think is a good jumping off place if people want to explore this as a protocol?
如果人们想将其作为一个协议来探索，你会做什么？你认为什么是一个好的起点？
David Sinclair:
大卫·辛克莱：
Well, if there's one thing I could say, I would say definitely try to skip a meal a day.
好吧，如果我可以说一件事，我会说绝对尝试每天不吃一顿饭。
That's the best thing.
这是最好的事情。
Andrew Huberman:
安德鲁·休伯曼：
Does it matter which meal or are they essentially equivalent?
哪顿饭很重要，或者它们本质上是等价的吗？
David Sinclair:
大卫·辛克莱：
Well, as long as it's at the end or the beginning of the day because then you add that to this sleep period where you're hopefully not eating.
好吧，只要是在一天结束或开始的时候，因为这样你就可以将其添加到这个睡眠时间段中，在这个时间段内你希望不吃东西。
Andrew Huberman:
安德鲁·休伯曼：
I think that's an excellent point.
我认为这是一个很好的观点。
I realize it's a simple one, but I think it's an excellent one because I think one of the things that people struggle with the most is knowing when and how to initiate this so-called intermittent fasting.
我意识到这是一个简单的方法，但我认为这是一个很好的方法，因为我认为人们最困难的事情之一就是知道何时以及如何开始这种所谓的间歇性禁食。
The middle of the day obviously is not tacked to the sleep cycle in the same way so it's much harder as well for many people.
显然，中午的睡眠周期并不以同样的方式进行，因此对于许多人来说，这也更加困难。
David Sinclair:
大卫·辛克莱：
I'll tell you what I do.
我会告诉你我是做什么的。
I skip breakfast.
我不吃早餐。
I have a tiny bit of yogurt or olive oil because the supplements I have need to be dissolved in it and then I go throughout the whole day as I'm doing right now here with this glass of water here, I'm just keeping myself filled with liquids and so I don't feel hungry.
我有一点点酸奶或橄榄油，因为我需要将补充品溶解在其中，然后我一整天都像我现在在这里所做的那样，在这里喝这杯水，我只是让自己充满液体，所以我不会感到饥饿。
Beware that the first two to three weeks when you try that you will feel hungry and you also have a habit of wanting to chew on something, there's a lot of physical parts to it, but try to make it through the first three weeks and do without breakfast or do without dinner and you'll get through it.
请注意，前两到三周，当你尝试时，你会感到饥饿，并且你也有想咀嚼东西的习惯，其中有很多身体部分，但尝试度过前三周，不吃早餐或不吃晚餐，你就会度过难关。
I did that for most of my life actually, mainly because I wasn't hungry in the morning.
事实上，我一生中的大部分时间都是这样做的，主要是因为我早上不饿。
Some people are very hungry in the morning and they may want to consider skipping dinner instead.
有些人早上很饿，他们可能想考虑不吃晚餐。
David Sinclair:
大卫·辛克莱：
But I will go throughout the whole day.
但我会花一整天的时间。
I don't get the crashes of the high glucose and the low glucose.
我没有感受到高血糖和低血糖的崩溃。
Anyone who goes, "Oh, man, it's three o'clock, I'm going to need a sleep." If you do what I do, you will not experience that anymore.
任何人都会说：“哦，伙计，现在是三点了，我需要睡觉了。”如果你按照我的做法，你就不会再经历这样的事情了。
Because what my body does is it regulates blood sugar levels naturally.
因为我的身体会自然调节血糖水平。
My liver is putting out glucose when it needs to and it's very steady and gives me pure focus throughout the day and I don't even have to think about lunch.
我的肝脏在需要时会释放葡萄糖，而且非常稳定，让我全天都能集中注意力，我什至不必考虑午餐。
I'm just powering through.
我刚刚通电。
At dinner, I love food as much as anybody so I will eat a regular, pretty healthy meal.
晚餐时，我和其他人一样喜欢食物，所以我会吃一顿常规的、非常健康的饭菜。
I'll try to eat mostly vegetables.
我会尝试主要吃蔬菜。
I can eat some fish, some shrimp.
我可以吃一些鱼，一些虾。
I rarely will eat a steak.
我很少会吃牛排。
In fact, my microbiome is so adapted to my diet now, if I eat a steak, it will not get digested very well.
事实上，我的微生物群现在已经非常适应我的饮食，如果我吃牛排，它就不会被很好地消化。
I'll feel terrible.
我会感觉很糟糕。
Andrew Huberman:
安德鲁·休伯曼：
If I don't eat a steak, I feel terrible.
如果我不吃牛排，我会感觉很糟糕。
Argentine lineage, but we can talk about that some other time.
阿根廷血统，但我们可以改天再谈。
David Sinclair:
大卫·辛克莱：
Well, everybody's different.
嗯，每个人都不同。
I mean, that's the other thing.
我的意思是，那是另一回事。
What works for me may not be perfect for you and we do have to measure things to know what's working.
对我有用的方法可能对你来说并不完美，我们必须衡量一些事情才能知道什么是有效的。
I rarely eat dessert.
我很少吃甜点。
I gave up dessert and sugar when I turned 40 and occasionally I'll steal a bit of dessert because it doesn't hurt if you steal it.
当我40岁的时候，我放弃了甜点和糖，偶尔我会偷一点甜点，因为偷了也没什么坏处。
But other than that, I avoid sugar, which includes simple carbohydrates.
但除此之外，我避免吃糖，其中包括简单碳水化合物。
Bread, I try to avoid.
面包，我尽量避免。
I've actually noticed, this is just a side note.
我实际上注意到了，这只是一个旁注。
I used to build up of plaque pretty easily and every time I went to the dentist they'd have to scrape it off and I even bought tools to scrape it off because it was driving me nuts.
我以前很容易积聚牙菌斑，每次我去看牙医时，他们都必须把它刮掉，我什至买了工具来刮掉它，因为它让我发疯。
I don't get plaque anymore and I think it's because of my diet.
我不再出现牙菌斑了，我想这是因为我的饮食习惯。
I don't have those sugars in my mouth that the bacteria feed on and then form the biofilm on the teeth.
我的嘴里没有细菌赖以生存的糖，然后在牙齿上形成生物膜。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
David Sinclair:
大卫·辛克莱：
Much better breath by the way.
顺便说一句，呼吸好多了。
Andrew Huberman:
安德鲁·休伯曼：
That's a benefit it.
这算是一个好处吧。
So do you ever fast longer than this?
那么你禁食过比这更长的时间吗？
It sounds like if you go to bed at ...
听起来好像如果你在...睡觉
Well, you tend to stay up late.
嗯，你经常熬夜。
I know because I get texts from you at two in the morning, my time, which means you're up very late and up early as well.
我知道，因为我在凌晨两点（我的时间）收到你的短信，这意味着你起得很晚，也起得很早。
But assuming that people go to sleep sometime around 11:30 or 12:00, plus or minus an hour, and wake up sometime around 7:00 AM, plus or minus 90 minutes, you're eating more or less on a ...
但假设人们在 11:30 或 12:00 左右（前后一小时）入睡，并在上午 7:00 左右（前后 90 分钟）醒来，那么你吃的东西或多或少......
it sounds like something 20 hours of fasting, four hours of eating or 16 hours of fasting and eight hours of food intake, etcetera.
听起来像是禁食 20 小时，进食 4 小时，或者禁食 16 小时，进食 8 小时，等等。
But do you ever do longer fasts like 48 hours or 72 hours or weeklong fasts?
但您是否曾经进行过较长时间的禁食，例如 48 小时、72 小时或一周的禁食？
David Sinclair:
大卫·辛克莱：
Occasionally I do.
我偶尔会这样做。
My typical day I would only eat within a two-hour window.
我通常的一天只会在两小时内吃东西。
Just usually either eating out or-
通常要么出去吃饭，要么——
Andrew Huberman:
安德鲁·休伯曼：
So you're 22/2?
所以你是22/2？
David Sinclair:
大卫·辛克莱：
Yeah.
是的。
But I love ...
但我爱...
Well ...
嗯...
Andrew Huberman:
安德鲁·休伯曼：
And if you exercise, then you just power through and maintain that fasted state?
如果你锻炼，那么你就能通过并保持禁食状态吗？
David Sinclair:
大卫·辛克莱：
Absolutely.
绝对的。
I can exercise and now my body's so used to it, I don't feel like I need food after exercising.
我可以运动，现在我的身体已经习惯了，运动后我不觉得需要食物了。
I used to.
我以前也是这样
But have I gone longer?
但我走了更长的时间了吗？
Yes, but not very often.
是的，但不是很频繁。
I find it quite difficult to go more than 24 hours.
我觉得坚持24小时以上是很困难的。
But when I do it, maybe it's once a month, I'll go for two days.
但当我这样做的时候，也许每个月一次，我会去两天。
After two, and actually even better if you go for three days without eating, it kicks in even greater longevity benefits.
两天后，实际上，如果你三天不吃东西，效果会更好，它会带来更大的长寿益处。
There's a system called the autophagy system, which digests old and misfolded proteins in the body and there's a natural cleansing that happens when you're hungry.
有一个称为自噬系统的系统，它可以消化体内旧的和错误折叠的蛋白质，并且当你饥饿时会发生自然净化。
Macro autophagy, its name is.
宏观自噬，它的名字是。
David Sinclair:
大卫·辛克莱：
But a good friend of mine, Ana Maria Cuervo at Albert Einstein College of Medicine discovered a deep cleanse called the chaperone-mediated autophagy, which kicks in day two, day three, which really gets rid of the deep proteins.
但我的一个好朋友，阿尔伯特·爱因斯坦医学院的安娜·玛丽亚·库尔沃（Ana Maria Cuervo）发现了一种称为伴侣介导的自噬的深层净化，它在第二天、第三天开始，真正清除了深层蛋白质。
What excites me is she just put out a big paper that said if you trigger this process in an old mouse, it lives 35% longer.
让我兴奋的是她刚刚发表了一篇大论文，说如果你在一只老老鼠身上触发这个过程，它的寿命会延长 35%。
Andrew Huberman:
安德鲁·休伯曼：
Wow.
哇。
David Sinclair:
大卫·辛克莱：
So it's a big deal.
所以这是一件大事。
If I could go longer, I would, but I just find that with my lifestyle and I'm going always 110%, I need to eat at least once a day, unfortunately.
如果我能坚持更长时间，我会的，但不幸的是，我发现按照我的生活方式，而且我总是 110%，我每天至少需要吃一次。
Andrew Huberman:
安德鲁·休伯曼：
One more practical question than a mechanistic question related to this.
这是一个比与此相关的机械问题更实际的问题。
The practical question is when you are fasting, regardless of how long, I know you're ingesting fluids like water and presumably some caffeine.
实际的问题是，当你禁食时，无论禁食多久，我都知道你会摄入水等液体，可能还摄入一些咖啡因。
I heard you had several or more or more espresso today, which is impressive.
我听说你今天喝了几杯或更多或更多浓缩咖啡，令人印象深刻。
But are you also ingesting electrolytes?
但你也摄入电解质吗？
I know some people get lightheaded, they start to feel shaky when they fast and that the addition of sodium to their water or potassium, magnesium is something that's becoming a little more in vogue now.
我知道有些人会感到头晕，他们在禁食时开始感到摇摇欲坠，而在水中添加钠或钾、镁现在变得更加流行。
Is that something that you do or that you see a need for people to do?
这是您所做的事情还是您认为人们需要做的事情？
David Sinclair:
大卫·辛克莱：
Well, it makes sense, but I haven't had a need to do it, so I don't.
嗯，这是有道理的，但我没有必要这样做，所以我没有这样做。
I drink tea during the day and coffee when I'm first awake and I don't get the shakes.
我白天喝茶，醒来时喝咖啡，这样我就不会发抖。
I don't fix what's not broken.
我不会修复没有损坏的东西。
I do add things to my protocol that I think will improve me and avoid those things, of course, that won't.
我确实在我的协议中添加了一些东西，我认为这些东西会改善我并避免那些事情，当然，这不会。
But yeah, because I don't have a need for it, I don't try it.
但是，是的，因为我不需要它，所以我不会尝试。
But it does make sense.
但这确实有道理。
Especially if you've had a big night the night before, you probably want to supplement with that.
特别是如果您前一天晚上度过了一个愉快的夜晚，您可能需要补充一下。
But I think there's fair amount of good stuff in tea and coffee as it is.
但我认为茶和咖啡中确实有很多好东西。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
So then the mechanistic question is ...
那么机械问题是......
you've told us that-
你告诉过我们——
Andrew Huberman:
安德鲁·休伯曼：
Mechanistic question is you've told us that there's ample evidence that keeping your blood sugar low for a period of time each 24 hours can help trigger some of these longevity anti-aging mechanisms.
机制问题是，您告诉我们，有充分的证据表明，每 24 小时一段时间内保持低血糖有助于触发一些长寿抗衰老机制。
And that extending them out two or three days can trigger yet additional mechanisms of gobbling up of dead cells and things of that sort.
将它们延长两三天可能会触发吞噬死细胞和类似物质的额外机制。
How is it that blood glucose triggers these mechanisms?
血糖是如何触发这些机制的？
Because we've said, okay, remove glucose and things get better.
因为我们说过，好吧，去掉葡萄糖，情况就会好起来。
You've talked before, maybe we could talk more now about some of the underlying cell and genetic mechanisms, things like the sirtuins, but how are glucose and the sirtuins actually tethered to one another mechanistically?
您之前已经谈过，也许我们现在可以更多地讨论一些潜在的细胞和遗传机制，例如去乙酰化酶，但是葡萄糖和去乙酰化酶实际上是如何在机制上相互联系的？
David Sinclair:
大卫·辛克莱：
Yeah, there's a really good question that proves you're a scientist or world-leading one.
是的，有一个非常好的问题可以证明您是一名科学家或世界领先的科学家。
So what we now know is that these longevity pathways, we call them these longevity genes, talk to each other.
所以我们现在知道的是，这些长寿途径，我们称之为长寿基因，是相互交流的。
And we used to say, "Oh my longevity gene's more important than yours." It was ridiculous because they're all talking to each other.
我们常常说，“哦，我的长寿基因比你的更重要。”这很荒谬，因为他们都在互相交谈。
You pull one lever and the other one moves.
您拉动一根控制杆，另一根就会移动。
David Sinclair:
大卫·辛克莱：
And the way to think of it is that there are systems set up to detect what you're eating.
思考这个问题的方法是，设置一些系统来检测你正在吃什么。
So the sirtuins will mainly respond to sugar and insulin.
因此去乙酰化酶主要对糖和胰岛素做出反应。
And then there's this other system called mTOR, which is sensing how much protein or amino acids are coming into your body, and they talk to each other.
然后还有一个称为 mTOR 的系统，它可以感知有多少蛋白质或氨基酸进入您的身体，并且它们可以相互通信。
We can pull one and infect the other and vice versa.
我们可以拉出一个并感染另一个，反之亦然。
But together, when you're fasting, you'll get the sirtuin activation, which is good for you and you, you'll also, through lack of amino acids, particularly three of them, leucine, isoleucine, valine, the body will down-regulate mTOR and it's that up sirtuin and down mTOR that is hugely beneficial and turns on all of the body's defenses.
但同时，当你禁食时，你会激活sirtuin，这对你和你都有好处，而且，由于缺乏氨基酸，特别是其中三种氨基酸，亮氨酸、异亮氨酸、缬氨酸，身体会下调mTOR，正是sirtuin的上调和mTOR的下调非常有益，并开启身体的所有防御能力。
Chewing up the old proteins, improving insulin sensitivity, giving us more energy, repairing cells, all of that.
咀嚼旧蛋白质，提高胰岛素敏感性，给我们更多能量，修复细胞，所有这些。
And so these two pathways I think are the most important for longevity.
所以我认为这两条途径对于长寿来说是最重要的。
Andrew Huberman:
安德鲁·休伯曼：
So interesting.
太有趣了。
You mentioned leucine within the resistance training/body building/fitness community.
您在阻力训练/健美/健身社区中提到了亮氨酸。
Leucine gets a lot of attention because there are longstanding debates about how much protein one needs per day and how much one can assimilate at each meal.
亮氨酸之所以受到广泛关注，是因为关于一个人每天需要多少蛋白质以及每顿饭可以吸收多少蛋白质的争论由来已久。
It makes for many YouTube videos and not much else, frankly.
坦率地说，它可以制作很多 YouTube 视频，但除此之外就没有什么用了。
However, it's clear that because of leucine's effects on the mTOR pathway that there are many people, not just people in these particular fitness communities, that are actively trying to ingest more leucine on a regular basis in order to maximize their wellness and fitness and in some cases muscle growth, but also just wellness.
然而，很明显，由于亮氨酸对 mTOR 通路的影响，有很多人，不仅仅是这些特定健身社区的人，正在积极尝试定期摄入更多的亮氨酸，以最大限度地提高他们的健康和健身，在某些情况下，促进肌肉生长，但也只是保持健康。
But what I interpret your last statement to mean is that leucine because it triggers cellular growth is actually pro-aging in some sense.
但我对你最后一句话的解释是，亮氨酸因为它能触发细胞生长，所以在某种意义上实际上是促衰老的。
Is that right?
是这样吗？
David Sinclair:
大卫·辛克莱：
Well, it could be.
嗯，可能是这样。
That's what the evidence suggests.
这就是证据所表明的。
And again, it goes back to the debate, should you supplement with growth hormone or testosterone?
又回到了争论，你应该补充生长激素还是睾丸激素？
All of these activities will give you immediate benefits, you'll bulk up more, you'll feel better immediately.
所有这些活动都会给你带来立竿见影的好处，你会变得更强壮，你会立即感觉更好。
But based on the research, it's at the expense of long-term health.
但根据研究，这是以牺牲长期健康为代价的。
So my view of longevity, the way I treat my body is I don't burn both candles.
所以我对长寿的看法，我对待自己身体的方式是我不烧两根蜡烛。
I have one end of the candle lit.
我点燃了蜡烛的一端。
I'm very careful I don't blow on it, but I also do enough exercise that I'm building up my muscle.
我非常小心，不吹气，但我也做了足够的运动来增强肌肉。
But I'm not huge.
但我并不大。
Anyone who's seen me knows that I'm not a professional bodybuilder.
见过我的人都知道我不是专业健美运动员。
David Sinclair:
大卫·辛克莱：
But I try to actually, here's the key, and I haven't said this publicly that I can remember.
但实际上我尝试这样做，这就是关键，我记得我还没有公开说过这一点。
I pulse things so that I get periods of fasting and then I eat, then I take a supplement, then I fast, then I exercise and I'm taking the supplements and eating in the right timing to allow me to build up muscles sometimes because you can't just expect to take something constantly and do something constantly for it to work.
我会进行脉动，这样我会禁食一段时间，然后吃东西，然后服用补充剂，然后禁食，然后锻炼身体，我服用补充剂并在正确的时间进食，有时可以让我增强肌肉，因为你不能指望不断地服用某些东西并不断地做一些事情才能发挥作用。
And that's why it's taken me about 15 years to develop my protocol and there's a lot of subtlety to it.
这就是为什么我花了大约 15 年的时间来开发我的协议，其中有很多微妙之处。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, it sounds like a very rational protocol.
是的，这听起来是一个非常合理的协议。
Does the name Ori Hofmekler mean anything to you?
Ori Hofmekler 这个名字对你来说有什么意义吗？
David Sinclair:
大卫·辛克莱：
No.
不。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Just briefly.
只是简单地说。
I discovered Ori Hofmekler about 15 years ago.
大约 15 年前我发现了 Ori Hofmekler。
He was an Israeli Special Forces, he's now got to be close to 70, forgive me, Ori if that number is inflated.
他是一名以色列特种部队成员，现在已经接近 70 岁了，请原谅我，奥里，如果这个数字被夸大了。
He wrote a book called The Warrior Diet, which got very little attention at the time.
他写了一本名为《战士饮食》的书，当时很少受到关注。
But what he said was when he was in Israeli Special Forces, they rarely ate more than once per day and sometimes once every second or third day.
但他说，当他在以色列特种部队时，他们很少每天吃超过一次，有时每隔两天或三天吃一次。
And this is a guy who maintains an incredible physical stature.
这是一个保持着令人难以置信的身材的家伙。
He's very lean, very strong and very vital at, I wouldn't say an advanced age, but he's getting up there and he just seems to be getting better and better.
他非常瘦弱，非常强壮，而且非常有活力，我不会说他已经是高龄了，但他正在崛起，而且他似乎变得越来越好。
Andrew Huberman:
安德鲁·休伯曼：
Ori Hofmekler was the person who essentially founded, if you will, although our ancestors founded, to be completely fair, the so-called intermittent fasting diet.
如果你愿意的话，奥里·霍夫梅克勒（Ori Hofmekler）本质上是创立了所谓的间歇性禁食饮食的人，尽管我们的祖先创立了，完全公平。
He called it the Warrior Diet.
他称之为“战士饮食”。
And this book didn't get much attention, but one of the things that you just said really reminded me of Ori.
这本书并没有引起太多关注，但是你刚才说的一件事确实让我想起了奥里。
I sat down with him.
我和他一起坐下来。
I actually went to his home and sat down with him and he said, "Fasting is wonderful, but these pulses where you nourish the body or even slightly overnourish the body, provided they aren't too frequent, have a tremendous effect on vitality."
我实际上去了他的家，和他坐在一起，他说：“禁食是美妙的，但是这些滋养身体的脉搏，甚至稍微营养过剩的脉搏，只要它们不是太频繁，就会对活力产生巨大的影响。”
Andrew Huberman:
安德鲁·休伯曼：
And so I want to use that as kind of a segue to address this issue of vitality versus longevity.
所以我想用它作为一种延续来解决活力与长寿的问题。
Because here you're telling me, and certainly the evidence supports that growth hormone will make you feel better and younger, taking testosterone or estrogen, we should probably say there are right women who are take hormone therapies later in life who take estrogen.
因为你在这里告诉我，当然有证据支持生长激素会让你感觉更好、更年轻，服用睾酮或雌激素，我们可能应该说，有一些在晚年接受激素治疗的女性也服用雌激素。
They experience a strong increase in vitality if it's done correctly.
如果做得正确，他们的活力会大大增强。
But there is an effect of aging the body more rapidly.
但有使身体加速衰老的作用。
It's sort of a second puberty if you will.
如果你愿意的话，这有点像第二个青春期。
But this idea of restriction and then pulsing, not necessarily feast and famine, but certainly famine and feast and lowercase letters.
但这种限制然后脉动的想法，不一定是盛宴和饥荒，但肯定是饥荒和盛宴和小写字母。
There really seems to be something about that.
似乎确实有这方面的事情。
So at a cellular level, we kind of go back to mTOR and the sirtuins.
因此，在细胞水平上，我们有点回到 mTOR 和 Sirtuins。
How do you think that the cells might be reacting to this kind of lowercased feast and uppercase famine type protocol?
您认为细胞可能会对这种小写盛宴和大写饥荒类型的方案做出反应？
David Sinclair:
大卫·辛克莱：
Right.
对。
Well, the pulsing, I think is, what you want to do is to get the cells to be perceiving adversity.
嗯，我认为脉冲是，你想要做的是让细胞感知逆境。
Okay?
好的？
Because our modern life, we're sitting around, we're eating too much, we're not exercising.
因为我们的现代生活，我们坐着，吃得太多，没有锻炼。
Our cells respond, they go, "Hey, everything's cool.
我们的细胞做出反应，它们说：“嘿，一切都很好。
No problem." And they become relaxed and they turn on their defenses.
没问题。”他们变得放松并开启防御。
And we age rapidly.
我们衰老得很快。
We can see it in the clock.
我们可以在时钟上看到它。
People who exercise and eat less have a slower ticking clock.
运动量少、饮食少的人的生物钟走得更慢。
It's a fact.
这是事实。
But my protocol is different than most people's because I am pulsing it.
但我的协议与大多数人不同，因为我正在脉冲它。
Now first of all, let's get to why did I even think that might be possible?
现在首先，让我们来看看为什么我认为这是可能的？
Because I didn't read The Warrior Diet.
因为我没有读过《战士饮食》。
David Sinclair:
大卫·辛克莱：
What I found in my research was that if we gave resveratrol, this red wine molecule that became well known in the 2000s.
我在研究中发现，如果我们给予白藜芦醇，这种红酒分子在 2000 年代就广为人知。
If we gave it to mice their whole lifespan, they were protected against a high fat diet, which we call the Western diet.
如果我们在小鼠的整个生命周期中给予它，它们就可以免受高脂肪饮食（我们称之为西方饮食）的影响。
They had lean organs, they live slightly longer, but not a lot.
他们的器官很瘦，寿命稍长，但也不是很多。
And if we gave them a high fat diet without resveratrol, they actually lived a lot shorter.
如果我们给它们提供不含白藜芦醇的高脂肪饮食，它们的寿命实际上会短得多。
So resveratrol protected them against the high fat diet.
因此，白藜芦醇可以保护他们免受高脂肪饮食的影响。
We gave it to them on a normal diet.
我们以正常饮食的方式给他们服用。
They just ate it when they wanted and there wasn't much effect.
他们只是想吃的时候就吃，并没有太大的效果。
David Sinclair:
大卫·辛克莱：
This is what's not known though.
但这是未知的。
It's in a supplemental data of the paper that nobody ever reads.
它位于论文的补充数据中，但没有人读过。
The mice that we've given resveratrol every second day on a normal diet live dramatically longer than any other group.
在正常饮食下，我们每隔一天给予白藜芦醇的小鼠比任何其他组的寿命显着延长。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
David Sinclair:
大卫·辛克莱：
So people out there, my critics say, "Oh, resveratrol didn't extend the lifespan of mice on a normal diet, therefore it's not aging, it's just protecting against the high fat diet." Well look at the supplemental data, please.
所以人们，我的批评者说，“哦，白藜芦醇并没有延长正常饮食的老鼠的寿命，因此它不是衰老，它只是防止高脂肪饮食。”请看一下补充数据。
If you give it to the mice every other day, we had mice living over three years.
如果你每隔一天给老鼠喂一次，我们的老鼠就能活三年多。
Andrew Huberman:
安德鲁·休伯曼：
Wow.
哇。
That's a long time for, I have got many, many mice in my ownership at my lab at Stanford.
这已经是很长一段时间了，我在斯坦福大学的实验室里拥有很多很多的老鼠。
And that's a very long life for a mouse.
对于老鼠来说，这已经是很长的寿命了。
David Sinclair:
大卫·辛克莱：
It was by far.
到目前为止已经是这样了。
And so it was a long lifespan extension.
所以这是一个很长的寿命延长。
And what that told me is that probably you don't want to be taking a supplement every day.
这告诉我，您可能不想每天服用补充剂。
You can take it either every other day or give your body a rest.
您可以每隔一天服用一次，也可以让身体休息一下。
And I do the same with my meals.
我在吃饭时也这样做。
I rest during the day and then I give a nutritious dinner to my body and then give it a rest.
我白天休息，然后给身体吃一顿营养的晚餐，然后让它休息。
Same with exercise.
运动也一样。
And then I try to time it.
然后我尝试计时。
Because there are times when I'm taking the drug, metformin, which mimics low energy.
因为有时我会服用药物二甲双胍，它会模仿低能量。
For those of you don't know, metformin is a drug given to type 2 diabetics to bring down their blood sugar levels.
也许您不知道，二甲双胍是一种用于 2 型糖尿病患者降低血糖水平的药物。
David Sinclair:
大卫·辛克莱：
But it's been found that looking at tens of thousands of veterans and others, that those two type 2 diabetics live longer than people that don't even get type 2 diabetes.
但通过观察数以万计的退伍军人和其他人发现，这两种 2 型糖尿病患者比没有患 2 型糖尿病的人寿命更长。
So it's a longevity drug.
所以它是一种长寿药。
Right now you have to get it from your doctor in the U.S. and most other countries, you can just get it over the counter and you're protected, it looks like, based on epidemiological data, cancer, heart disease, frailty.
现在你必须从美国和大多数其他国家的医生那里得到它，你可以在柜台上买到它，你就受到了保护，看起来，基于流行病学数据，癌症、心脏病、虚弱。
What else?
还有什么？
Dementia.
痴呆。
So I take metformin.
所以我服用二甲双胍。
Andrew Huberman:
安德鲁·休伯曼：
In addition, you take metformin and you're fasting each day.
此外，您服用二甲双胍并且每天禁食。
So when do you take it relative to the fasting?
那么相对于禁食你什么时候服用呢？
David Sinclair:
大卫·辛克莱：
Yeah, I always take metformin in the morning along with the resveratrol because, for a number of reasons, but mainly because my body responds better.
是的，我总是在早上服用二甲双胍和白藜芦醇，因为有很多原因，但主要是因为我的身体反应更好。
And I've been measuring my body for 12, 13 years.
我测量自己的身体已经有十二、十三年了。
But here's the thing, if I'm going to exercise that day, I will skip the metformin.
但事情是这样的，如果我那天要锻炼，我会跳过二甲双胍。
And a lot of people who do pay attention to this kind of thing think that they should stop taking metformin because they're never going to get muscle or it's going to affect their ability to build up muscle, but that's not true.
许多关注此类事情的人认为他们应该停止服用二甲双胍，因为他们永远不会获得肌肉，或者会影响他们增强肌肉的能力，但事实并非如此。
What metformin does to you, it actually just reduces your ability to have stamina because it's inhibiting your body's ability to make energy.
二甲双胍对您的作用实际上只是降低您的耐力能力，因为它抑制您的身体产生能量的能力。
And so what happens is when you're on metformin, you do fewer reps.
因此，当您服用二甲双胍时，会发生的情况是，您的次数会减少。
But guess what?
但你猜怎么着？
Those muscles that you do build up on metformin have the same strength and have much lower inflammation and other markers of aging.
使用二甲双胍锻炼的肌肉具有相同的强度，并且炎症和其他衰老标志物的含量要低得多。
David Sinclair:
大卫·辛克莱：
You just won't have that extra 5% size of muscles.
你只是不会拥有额外 5% 的肌肉。
So if you want large muscles, don't take metformin and you'll be fine during your exercise.
因此，如果您想要大块肌肉，请不要服用二甲双胍，您在锻炼过程中会没事的。
But for me, I'm not trying to get giant, I want strong muscles and I want to live longer and healthier.
但对我来说，我并不是想变得巨人，我想要强壮的肌肉，我想要活得更长、更健康。
So I just try to time it so that I get the most reps out of my exercise regime.
所以我只是尝试计时，以便从我的锻炼计划中获得最多的重复次数。
But sometimes in scientific literature, it's worth bringing this up, if there's a 5% difference in a graph, then either the press release or some reporter will say, "Oh my goodness, big difference.
但有时在科学文献中，值得提出这一点，如果图表中有 5% 的差异，那么新闻稿或一些记者会说，“哦，天哪，差别很大。
Five percent can't take metformin during exercise." That's the headline.
百分之五的人不能在运动时服用二甲双胍。”这就是标题。
And then you go in and it's barely significant and the graph is distorted because they've changed the axes to make it look bigger.
然后你进去，发现它几乎不重要，而且图表扭曲了，因为他们改变了轴以使其看起来更大。
And now it's become a myth that metformin greatly inhibits your ability to exercise, which is not true.
现在，二甲双胍会极大地抑制您的运动能力已成为一个神话，但事实并非如此。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
David Sinclair:
大卫·辛克莱：
But in an abundance of caution, I skip my metformin on days I'm going to exercise.
但为了谨慎起见，我在要锻炼的日子里不服用二甲双胍。
And not only that, I'm one of the 20% of people that has a stomach sensitivity to it.
不仅如此，我是 20% 对其胃部敏感的人之一。
So if I'm not feeling great that day, I don't take it either.
所以如果那天我感觉不太好，我也不会接受。
Andrew Huberman:
安德鲁·休伯曼：
You mentioned metformin is available only by prescription from a doctor, at least in the U.S. Berberine is a substance that comes from tree bark, I also learned about many years ago from Ori.
你提到二甲双胍只能通过医生处方才能获得，至少在美国是这样。小檗碱是一种来自树皮的物质，我多年前也从Ori那里了解到。
He said, "If ever I'm going to overeat like a Thanksgiving meal or something, I take berberine." Those were his words and I tried it.
他说：“如果我要吃得过多，比如感恩节大餐之类的，我就会服用小檗碱。”这是他的话，我也尝试了。
And what's remarkable about berberine is that you can eat enormous quantities of food and not feel as if you've eaten enormous quantities of food.
小檗碱的非凡之处在于，您可以吃大量的食物，但不会感觉好像吃了大量的食物。
I'm not necessarily recommending people do this, but what I noticed was if I took berberine, which my understanding is it works very similarly to metformin, works on the AMPK pathway, in the mTOR pathway, etcetera, that if I didn't ingest food, in particular carbohydrates, I would feel a little dizzy and kind of get a headache, almost hypoglycemic.
我不一定建议人们这样做，但我注意到，如果我服用小檗碱，我的理解是它的作用与二甲双胍非常相似，作用于 AMPK 途径、mTOR 途径等，如果我不摄入食物，特别是碳水化合物，我会感到有点头晕，有点头痛，几乎是低血糖。
Andrew Huberman:
安德鲁·休伯曼：
What are your thoughts on berberine as an alternative to metformin?
您对小檗碱作为二甲双胍的替代品有何看法？
And are there any cautionary notes?
有什么注意事项吗？
I mean, obviously people should talk to their doctor before adding or subtracting anything from their life, including breathwork or anything, that one that comes up.
我的意思是，显然人们应该在生活中添加或减少任何东西之前先咨询医生，包括呼吸或任何出现的东西。
But with all that set aside, what are your thoughts about berberine and timing of low blood sugar and these sorts of things?
但抛开所有这些，您对小檗碱和低血糖发生时间以及诸如此类的事情有何看法？
David Sinclair:
大卫·辛克莱：
Right.
对。
Well, before I had access to metformin, I was taking berberine.
嗯，在我使用二甲双胍之前，我服用小檗碱。
It's often known as the poor man's metformin that-
它通常被称为穷人的二甲双胍——
Andrew Huberman:
安德鲁·休伯曼：
He just called me poor.
他只是说我可怜。
David Sinclair:
大卫·辛克莱：
Women can take it too.
女性也可以接受。
So the thing with berberine, we've studied it in my lab, it is effective at boosting energetics in the body just like AMPK and metformin does.
所以关于小檗碱的事情，我们在我的实验室里进行了研究，它可以有效地增强体内的能量，就像 AMPK 和二甲双胍一样。
And we've actually given it to rats and mice and seen that they're very healthy, especially on a high fat diet.
事实上，我们已经将其给予大鼠和小鼠，发现它们非常健康，尤其是在高脂肪饮食的情况下。
So I think it's likely to be good.
所以我认为这可能会很好。
There are some human studies that exist, clinical trials showing that it increases insulin sensitivity.
一些人体研究和临床试验表明它可以提高胰岛素敏感性。
You have to take high doses.
你必须服用高剂量。
Andrew Huberman:
安德鲁·休伯曼：
Which is a good thing, right?
这是一件好事，对吧？
David Sinclair:
大卫·辛克莱：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I think when people hear insulin sensitivity, sometimes people think, "Oh, well that's bad, right?" No, but you want your cells to be insulin sensitive.
我认为当人们听到胰岛素敏感性时，有时人们会想，“哦，这很糟糕，对吧？”不，但您希望您的细胞对胰岛素敏感。
You don't want a lot of blood sugar floating around that can't be sequestered into cells.
您不希望大量血糖无法被隔离在细胞中而漂浮在周围。
David Sinclair:
大卫·辛克莱：
Exactly.
正是如此。
So this is anti-type 2 diabetes.
所以这是抗2型糖尿病。
And so that this berberine does have wonderful effects on the metabolism of animals.
所以说这种小檗碱确实对动物的新陈代谢有奇妙的作用。
And in some clinical trials on dozens of people, that's been tested.
在对数十人进行的一些临床试验中，这一点已经得到了测试。
Now, there's one cautionary tale which just came up, Matt Kaeberlein's lab published that berberine reduced the lifespan of worms.
现在，刚刚出现了一个警示故事，马特·凯伯莱因 (Matt Kaeberlein) 的实验室发表了一篇文章，称小檗碱会缩短蠕虫的寿命。
But I'm not sure worms trump human clinical trials at this point.
但目前我不确定蠕虫是否能胜过人类临床试验。
So I would say-
所以我想说——
Andrew Huberman:
安德鲁·休伯曼：
Not in my opinion.
我认为不是。
David Sinclair:
大卫·辛克莱：
I wouldn't-
我不会-
Andrew Huberman:
安德鲁·休伯曼：
No disrespect to my C.
没有对我的C不尊重的意思。
elegans colleagues, or rather my colleagues that work on C.
elegans 的同事，或者更确切地说是我从事 C 工作的同事。
elegans.
线虫。
David Sinclair:
大卫·辛克莱：
Yeah.
是的。
Well, what I like to do is to give all the information.
嗯，我喜欢做的就是提供所有信息。
People can decide what they want.
人们可以决定他们想要什么。
But I would say if based on the worm data, I wouldn't panic just yet.
但我想说，如果基于蠕虫数据，我还不会惊慌。
I think berberine has been shown to be really safe in humans.
我认为小檗碱已被证明对人类非常安全。
Andrew Huberman:
安德鲁·休伯曼：
You mentioned resveratrol, I think now would be a great time to talk a little bit about protocols for resveratrol, grapeseed extract, etcetera.
你提到了白藜芦醇，我认为现在是谈论白藜芦醇、葡萄籽提取物等协议的好时机。
Let's start with the obvious one that, I know you get a lot, but for the record, can't I just drink red wine and get enough resveratrol, David?
让我们从一个明显的开始，我知道你会得到很多，但郑重声明，我不能只喝红酒并获得足够的白藜芦醇吗，大卫？
David Sinclair:
大卫·辛克莱：
You can try you.
你可以尝试一下。
You'd need to drink about 200 glasses a day.
你每天需要喝大约200杯。
So-
所以——
Andrew Huberman:
安德鲁·休伯曼：
I'm sure it's been tried.
我确信已经尝试过。
David Sinclair:
大卫·辛克莱：
There are some, And I drink a glass of red wine a day if I get the chance.
有一些，如果有机会的话，我每天都会喝一杯红酒。
But any more than that, it's a lot of calories.
但除此之外，它还含有大量卡路里。
And your liver will get fatty and it's all bad.
你的肝脏会变得肥胖，这一切都很糟糕。
So I mean, realistically, you can only get the thousand milligrams that I take a day from a supplement that's pure.
所以我的意思是，实际上，你只能从纯补充剂中获取我每天服用的一千毫克。
Now there are a lot of people selling resveratrol.
现在有很多人卖白藜芦醇。
If it's not light gray or white in color, throw it away.
如果颜色不是浅灰色或白色，请将其扔掉。
The brown stuff has gone bad or is contaminated and the contaminated stuff beware, it'll cause diarrhea.
棕色的东西已经变质或者被污染了，小心被污染的东西，会引起腹泻。
But regular resveratrol should not do that.
但普通白藜芦醇不应该这样做。
Andrew Huberman:
安德鲁·休伯曼：
So a thousand milligrams per day is what you do?
那么每天一千毫克就是你所做的吗？
David Sinclair:
大卫·辛克莱：
Yeah-
是啊-
Andrew Huberman:
安德鲁·休伯曼：
One gram?
一克？
David Sinclair:
大卫·辛克莱：
And I have for about 15 years now.
我已经有大约 15 年了。
Andrew Huberman:
安德鲁·休伯曼：
And you ingest that with some fatty substance like olive oil or yogurt, is that right?
你将其与橄榄油或酸奶等脂肪物质一起摄入，对吗？
David Sinclair:
大卫·辛克莱：
Yeah, you have to.
是的，你必须这样做。
And other supplements, quercetin, curcumin, these are crunchy things.
还有其他补品，槲皮素，姜黄素，这些都是脆脆的东西。
There's not going to get through your gut.
不会通过你的直觉。
And I'm not just making this up, I always base my statements on human studies.
这并不是我编造的，我的陈述总是基于人类研究。
So we've done a lot of studies on resveratrol, as of others since.
因此，我们对白藜芦醇进行了大量研究，此后也进行了其他研究。
And we know that from, we found out earlier, I was one of the first people to take a high dose for resveratrol.
我们知道，我们早些时候发现，我是第一批服用高剂量白藜芦醇的人之一。
And when we included it with food, the levels in my blood went out fivefold.
当我们将其与食物一起食用时，我血液中的浓度下降了五倍。
And so you want to have something in there.
所以你想在里面放一些东西。
If you just drink it with water, it's not going to get through.
如果你只是用水喝的话，它是不会通过的。
And unfortunately, some people have done clinical trials without even thinking that they might need to dissolve it in something.
不幸的是，有些人在进行临床试验时甚至没有想到他们可能需要将其溶解在某种东西中。
Andrew Huberman:
安德鲁·休伯曼：
So are you taking this all at once in the morning and chasing it with some olive oil, or are you dissolving it in yogurt?
那么你是在早上一次性服用这些并用一些橄榄油来补充，还是将其溶解在酸奶中？
What's the specific protocol?
具体协议是什么？
David Sinclair:
大卫·辛克莱：
Yeah, I've been improving, perfecting what I do for about 10 years.
是的，大约十年来我一直在进步、完善我所做的事情。
I would take some Greek yogurt, couple of spoonfuls, put the resveratrol on there, mix it around, make sure it's dissolved and put that in my mouth and swallow that.
我会拿一些希腊酸奶，几勺，将白藜芦醇放在上面，混合，确保它溶解，然后放入嘴里吞下。
These days what I like to do, because I've realized that olive oil and particularly oleic acid, one of the monounsaturated fatty acids, is also an activator of the sirtuin defenses.
这些天我喜欢做的事，因为我意识到橄榄油，尤其是单不饱和脂肪酸之一的油酸，也是沉默调节蛋白防御的激活剂。
So I'm trying to ingest more of oleic acid.
所以我正在尝试摄入更多的油酸。
So I switched to olive oil.
所以我改用橄榄油。
What I do is I put a couple of teaspoons of olive oil in a glass, mix around the resveratrol and maybe some quercetin, a similar molecule, make sure it's dissolved.
我所做的是将几茶匙橄榄油放入玻璃杯中，与白藜芦醇和一些槲皮素（类似的分子）混合，确保其溶解。
I put a little bit of vinegar and if I have a basil leaf, I'll put that in and it's like drinking some salad dressing and it's great.
我放了一点醋，如果我有罗勒叶，我会把它放进去，就像喝一些沙拉酱一样，非常棒。
Andrew Huberman:
安德鲁·休伯曼：
Delicious.
好吃。
That raises a question that I want to ask before we get to NMN and NR and vitamin B3, which is by doing that, do you think that it breaks your fast?
这就提出了一个问题，在我们讨论 NMN、NR 和维生素 B3 之前我想问一下，你认为这样做会破坏你的禁食吗？
And I want to just frame this question of breaking the fast in a more general scientific theme.
我想用一个更普遍的科学主题来阐述打破斋戒的问题。
And I'd love your thoughts on this.
我很想听听你对此的想法。
One of the questions I get asked all the time is, does ingesting blank break the fast?
我经常被问到的问题之一是，摄入空白会破坏禁食吗？
Does eating this or drinking this coffee, if I walk in the room and someone else is eating a cracker, does it break my fast?
如果我走进房间而其他人正在吃饼干，吃这个或喝这个咖啡会破坏我的斋戒吗？
People get pretty extreme with this.
人们对此变得非常极端。
My sense, and please tell me if I'm wrong, but my sense is that it depends on the context of what you did the night before, whether or not you're diabetic, lots of things.
我的感觉，如果我错了，请告诉我，但我的感觉是，这取决于你前一天晚上所做的事情的背景，无论你是否患有糖尿病，很多事情。
Andrew Huberman:
安德鲁·休伯曼：
So for instance, if I eat an enormous meal at midnight, go to sleep, wake up at 6:00 AM I could imagine that black coffee or coffee with a little bit of cream might break my fast, but the body doesn't have a breaking the fast switch.
举例来说，如果我在半夜吃了一顿大餐，然后去睡觉，早上 6:00 醒来，我可以想象黑咖啡或加一点奶油的咖啡可能会打破我的禁食，但身体没有打破禁食的开关。
The body only speaks in the language of glucose, AMPK, mTOR, etcetera.
身体只用葡萄糖、AMPK、mTOR 等语言说话。
So do you worry that ingesting these calories is going to break your fast?
那么您是否担心摄入这些卡路里会破坏您的禁食？
And more generally, how do you think about the issue of whether or not you're fasting enough to get these positive effects?
更一般地说，您如何看待您的禁食是否足以获得这些积极效果的问题？
Because not everybody can manage on just water or just tea, or we should say not everybody is willing to manage on just water or just tea for a certain part of the day.
因为不是每个人都可以只喝水或只喝茶，或者我们应该说不是每个人都愿意在一天中的某个时间只喝水或只喝茶。
David Sinclair:
大卫·辛克莱：
Well, my first answer is not scientific, it's philosophical.
好吧，我的第一个答案不是科学的，而是哲学的。
If you don't enjoy life, what's the point?
如果你不享受生活，那还有什么意义呢？
And so I'd like a cup of coffee in the morning, little bit of milk.
所以我想早上喝杯咖啡，加一点牛奶。
Spoonful of yogurt's not going to kill me.
一勺酸奶不会要我的命。
Olive oil doesn't have protein or carbs in it, not many.
橄榄油中不含蛋白质或碳水化合物，数量也不多。
And so I'm probably not affecting those longevity pathways negatively.
所以我可能不会对这些长寿之路产生负面影响。
But without that, first of all, I wouldn't enjoy my life as much.
但如果没有这些，首先，我就不会那么享受我的生活。
Well the olive oil isn't, is not as great as the yogurt, but I'm trying to optimize and there's no perfect solution to what we're doing.
好吧，橄榄油不是，不如酸奶那么好，但我正在努力优化，但我们正在做的事情没有完美的解决方案。
And we're still learning.
我们仍在学习。
We don't know what's optimal for me, let alone everybody else.
我们不知道什么对我来说是最佳的，更不用说其他人了。
But I'm with you.
但我和你在一起。
I don't believe that taking a couple of spoonfuls of something, unless it's high fructose corn syrup, is going to hurt you.
我不认为吃几勺东西会对你造成伤害，除非是高果糖玉米糖浆。
Because I've now got the rest of the day till about 8:00/9:00 PM of not eating anything.
因为我现在一天中剩下的时间直到晚上 8:00/9:00 左右都不能吃任何东西。
I forgive myself for that.
我为此原谅自己。
David Sinclair:
大卫·辛克莱：
And that there's a really good point here.
这里有一个非常好的观点。
You and I were discussing this earlier.
你和我之前讨论过这个问题。
The point about doing this is that you try to do your best.
这样做的要点是你要尽力做到最好。
If you go from regular living to don't eat the whole day, you're going to fail like quitting smoking cold turkey.
如果你从有规律的生活变成一整天不吃东西，你就会像戒烟一样失败。
It's easier to chew gum and stick the patch on because your body has to get used to all sorts of habits.
咀嚼口香糖和粘贴贴片会更容易，因为您的身体必须习惯各种习惯。
And it's social.
而且它是社交的。
It's physical, putting stuff in your mouth, chewing, not just the low blood sugar levels.
这是身体上的，把东西放进嘴里咀嚼，而不仅仅是低血糖水平。
And your brain will fight it.
你的大脑会与之抗争。
Your limbic system is going to go, "Hey, do it, do it, do it." And you're going to have to fight it.
你的边缘系统会说：“嘿，做吧，做吧，做吧。”你将不得不与之抗争。
But once you get through it, you'll be better.
但一旦你熬过去了，你就会变得更好。
But you do it in stages.
但你要分阶段进行。
Do breakfast first, then do small lunch, and then eventually cut lunch out.
先吃早餐，然后吃小午餐，最后不吃午餐。
Don't go cold turkey.
不要突然冷火鸡。
Because everyone knows it's a fact that if you try to do a strict diet right out of the gates, you'll almost always fail.
因为每个人都知道事实是，如果你一开始就尝试严格节食，你几乎总是会失败。
Andrew Huberman:
安德鲁·休伯曼：
No, I think that captures the essence of fasting rationally and a rational approach to supplementation very well.
不，我认为这很好地抓住了理性禁食和理性补充方法的本质。
Along the lines of supplementation, what about NMN, NR, and B3?
补充方面，NMN、NR 和 B3 怎么样？
How does one, I want to know what you do.
一、我想知道你是做什么的。
I also want to know what I should do.
我也想知道我应该做什么。
And I think most people want to know what they should do.
我认为大多数人都想知道他们应该做什么。
I mean, these are molecules that impact the sertuin pathway, impact the pathways that control aging or rates of aging in the epigenome.
我的意思是，这些分子会影响丝氨酸途径，影响表观基因组中控制衰老或衰老速度的途径。
How do they do that and how does one incorporate that into a supplementation protocol, should they choose to do that?
他们如何做到这一点以及如何将其纳入补充方案中，他们应该选择这样做吗？
David Sinclair:
大卫·辛克莱：
All right.
好吧。
Well, disclaimer is I don't recommend anything, but I talk about what I do.
好吧，免责声明是我不推荐任何东西，但我谈论我所做的事情。
So a bit of scientific background.
所以有一点科学背景。
These sirtuin genes that we discovered first in yeast cells when I was at MIT and then in animals as I moved to Harvard in the 2000s.
当我在麻省理工学院时，我们首先在酵母细胞中发现了这些沉默调节蛋白基因，然后在 2000 年代我搬到哈佛大学时，我们在动物中发现了这些基因。
And one of my first postdocs, actually literally my first postdoc, Haim Cohen, published a great paper just a couple of months ago and found that turning on the sirtuin six gene, maybe the seven, number six gene is very potent.
我的第一个博士后之一，实际上是我的第一个博士后，Haim Cohen，几个月前发表了一篇很棒的论文，发现打开 Sirtuin 6 基因，也许是 7 号、6 号基因非常有效。
It extended the lifespan dramatically of mice that he engineered, both males and females, which is great.
它极大地延长了他改造的雄性和雌性小鼠的寿命，这非常棒。
So what you want to do is so naturally boost the activity of these sirtuins.
所以你要做的就是自然地提高这些去乙酰化酶的活性。
They are genes, but they also make proteins.
它们是基因，但它们也制造蛋白质。
That's what genes typically make or encode.
这就是基因通常制造或编码的东西。
And then those proteins take care of the body in many different ways as we've discussed.
然后，正如我们所讨论的，这些蛋白质以多种不同的方式照顾身体。
David Sinclair:
大卫·辛克莱：
So how do you turn on these genes and make the proteins they make even more active?
那么如何开启这些基因并使它们产生的蛋白质更加活跃呢？
You want to rev up that system.
你想加速这个系统。
So exercise will do it.
所以运动就可以了。
Fasting will do it.
禁食就能做到。
What about supplementation?
补充的话怎么办？
Well, the first activator of the sirtuins that we discovered that acts on the enzyme to make it do a better job of cleaning up the body and protecting was resveratrol.
嗯，我们发现的第一个作用于酶以使其更好地清理身体和保护身体的去乙酰化酶激活剂是白藜芦醇。
We looked at thousands of different molecules, eventually tens of thousands.
我们研究了数千种不同的分子，最终达到数万种。
And the one that was the best was resveratrol in the dish.
最好的是盘子里的白藜芦醇。
And then we gave it to little organisms, worms, and then flies and mice, eventually humans.
然后我们把它给小生物，蠕虫，然后是苍蝇和老鼠，最后是人类。
And we saw that it activated that enzyme.
我们看到它激活了这种酶。
So virtual is one way to activate it.
所以虚拟是激活它的一种方式。
And you can think of it as the accelerator pedal on a car.
您可以将其视为汽车上的加速踏板。
It revs it up.
它加快了速度。
David Sinclair:
大卫·辛克莱：
But there's something else that the sirtuins need to work, and that's NAD.
但 Sirtuins 还需要其他东西才能发挥作用，那就是 NAD。
NAD is a really small molecule, little chemical in the body that we need for life.
NAD 是一种非常小的分子，是我们生命所需的体内很少的化学物质。
It's used by the body for chemical reactions, 400 different reactions in the body.
它被身体用来进行化学反应，体内有 400 种不同的反应。
And without it you're dead within seconds.
如果没有它，你几秒钟内就会死亡。
You need NAD.
你需要 NAD。
The problem that we've seen is that NAD levels decline as you become obese, as you get older, if you don't ever get hungry, and the body not only doesn't make enough of it, it's chewing it up as well.
我们看到的问题是，NAD 水平会随着你变得肥胖、随着年龄的增长而下降，如果你从不感到饥饿，那么身体不仅无法制造足够的 NAD，还会将其消化掉。
There is an enzyme called CD38 that Eric Verdin over at UCSF showed chews up, (now he's now at the Buck Institute in California) chews up NAD as you get older.
有一种叫做 CD38 的酶，加州大学旧金山分校的埃里克·维尔丁 (Eric Verdin) 展示了它的作用，（现在他在加利福尼亚州的巴克研究所）随着年龄的增长，它会分解 NAD。
So it's a double whammy.
所以这是双重打击。
Don't make as much.
别赚那么多。
You chew it up, which is really bad because what we've shown in my lab and so of others is that NAD levels are really important for keeping those sirtuin defenses at a youthful level.
你把它嚼碎，这真的很糟糕，因为我们在我的实验室和其他人的实验室中证明，NAD 水平对于将这些 Sirtuin 防御保持在年轻水平非常重要。
David Sinclair:
大卫·辛克莱：
And you can give a lot of resveratrol, but if you don't have the fuel, you're basically accelerating a car that doesn't have enough gas.
你可以给予大量的白藜芦醇，但如果你没有燃料，你基本上就是在加速一辆没有足够汽油的汽车。
So you want to do both.
所以你想两者都做。
And that's what I do.
这就是我所做的。
I take a precursor to NAD called NMN, and the body uses that to make the NAD molecule in one step.
我采用一种称为 NMN 的 NAD 前体，身体利用它一步生成 NAD 分子。
And so I know from measuring dozens of human beings that if you take NMN for the time period that I do, I've been taking it for years.
因此，通过对数十个人的测量，我知道，如果你在我服用 NMN 的时间段内服用 NMN，那么我已经服用了很多年。
But if you take it for about two weeks, you'll double, on average double your NAD levels in the blood.
但如果你服用大约两周，你的血液中 NAD 水平就会翻倍，平均翻倍。
Okay?
好的？
That's not public information.
这不是公开信息。
That's from clinical trials that are not yet published over the last two years.
这是来自过去两年尚未发表的临床试验。
There are other ways to increase NAD levels in someone like me who's getting older, I'm 52 now.
对于像我这样年纪越来越大的人来说，还有其他方法可以提高 NAD 水平，我现在 52 岁了。
You can take NR, which is used to make NMN, which is used to make NAD and both NMN and NR are sold by companies in the U.S. NR lacks the phosphate.
你可以拿NR，它是用来制造NMN的，NMN是用来制造NAD的，NMN和NR都是由美国公司销售的。NR缺乏磷酸盐。
Phosphate's a small chemical the body needs.
磷酸盐是人体所需的一种小化学物质。
You've probably heard of the atom phosphorus.
您可能听说过磷原子。
David Sinclair:
大卫·辛克莱：
Let's go back one step.
让我们退一步。
How do you make NR?
怎么做NR？
NR gets made from vitamin B3.
NR 由维生素 B3 制成。
Often you can also find it in milk and other foods.
通常，您还可以在牛奶和其他食物中找到它。
But sometimes people ask me, "Why don't you just take vitamin B3 and won't that just force the body to make NAD?" And the answer is no, it doesn't work very well.
但有时人们会问我，“你为什么不直接服用维生素 B3，这不会迫使身体产生 NAD 吗？”答案是否定的，它的效果不是很好。
We know this just by doing the experiment.
我们只要通过实验就知道这一点。
But the reason I think is that NAD is, I said it's a small molecule, but relative to vitamin B3, it's big.
但我认为的原因是NAD是，我说它是一个小分子，但是相对于维生素B3来说，它是大分子。
It's got those phosphates on there, it's got a sugar, it's got the vitamin B attached.
它上面有磷酸盐、糖、维生素 B。
So you've got all these components that come together to make this very complicated little molecule called NAD.
因此，所有这些成分组合在一起就形成了这个非常复杂的小分子，称为 NAD。
And when you give NMN, it contains all three components that the body needs to make NAD.
当您给予 NMN 时，它包含身体制造 NAD 所需的全部三种成分。
If you give NR or just vitamin B3, which is an even smaller molecule, the body has to find these other components from somewhere else.
如果您给予 NR 或仅给予维生素 B3（分子更小），身体就必须从其他地方寻找这些其他成分。
David Sinclair:
大卫·辛克莱：
So where do you get phosphate?
那么从哪里获得磷酸盐呢？
Well, body needs it for DNA needs it for bones.
嗯，身体需要它，DNA 需要它，骨骼也需要它。
So high doses of something that requires additional phosphate makes me a little concerned.
如此高剂量的需要额外磷酸盐的东西让我有点担心。
And we have compared NMN and NR head-to-head in mouse studies.
我们在小鼠研究中对 NMN 和 NR 进行了头对头比较。
For instance, NMN, we've shown in a cell paper a few years ago, makes mice run further.
例如，几年前我们在一篇细胞论文中展示的 NMN 可以让小鼠跑得更远。
Old mice can run 50% further because they have better blood flow, better energy.
年老的老鼠可以跑多50%，因为它们有更好的血液流动和更好的能量。
NR at the same dose did not do that.
相同剂量的 NR 没有做到这一点。
In fact, it had no effect.
事实上，并没有什么效果。
Andrew Huberman:
安德鲁·休伯曼：
I see.
我明白了。
Dosage wise, if I were to elect to take NMN in supplement form to increase my NAD levels and presumably slow my aging, how much NMN should I take?
就剂量而言，如果我选择服用 NMN 补充剂来提高 NAD 水平并延缓衰老，我应该服用多少 NMN？
What's the protocol that you do and are the various forms that are out there, are some better or some worse?
你们采用的协议是什么？有哪些形式？有些更好，有些更差？
David Sinclair:
大卫·辛克莱：
Well, I'm always happy to tell you what I do and what my father does.
嗯，我总是很乐意告诉你我所做的事情和我父亲所做的事情。
My 82 -year-old father, we take a gram of NMN every day.
我82岁的父亲，我们每天服用一克NMN。
Andrew Huberman:
安德鲁·休伯曼：
So it's a gram of resveratrol and a gram of NMN.
所以它是一克白藜芦醇和一克 NMN。
David Sinclair:
大卫·辛克莱：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
A thousand milligrams.
一千毫克。
David Sinclair:
大卫·辛克莱：
Now another important point, which is I'm not the same as everybody else.
现在还有一个重要的点，那就是我和其他人不一样。
I have different microbiome, age, sex.
我有不同的微生物组、年龄、性别。
Andrew Huberman:
安德鲁·休伯曼：
Sure.
当然。
David Sinclair:
大卫·辛克莱：
Right.
对。
And so I've been measuring myself.
所以我一直在衡量自己。
And so I know if something's, or I know if something's making me better or worse based on measuring 45 different things.
因此，根据对 45 种不同事物的测量，我知道是否有某事，或者我知道某事是否使我变得更好或更差。
So I just want people to be aware that what I do may not perfectly, or work at all for others.
所以我只是想让人们意识到我所做的可能并不完美，或者对其他人来说根本不起作用。
But I have studied, as I said, dozens of people who take NMN at a gram, sometimes two grams.
但正如我所说，我研究了数十名服用一克（有时是两克）NMN 的人。
And I know by looking at all those people that without any exceptions, that if you do what I do, your NAD levels go up by about twofold or more.
通过观察所有这些人，我知道，无一例外，如果你按照我的做法，你的 NAD 水平会上升大约两倍或更多。
And so I do that every day.
所以我每天都这样做。
The thousand milligrams.
千毫克。
David Sinclair:
大卫·辛克莱：
Now, people sell it.
现在，人们出售它。
Now, I never get into brands and all that.
现在，我从不涉足品牌之类的事情。
First of all, I don't have the time to measure products.
首先，我没有时间测量产品。
I don't know though, I should say.
虽然我不知道，但我应该说。
I do want to say I'm working on a solution for people to know what's, what works and what's real and what isn't.
我确实想说，我正在研究一种解决方案，让人们知道什么是、什么是有效的、什么是真实的、什么不是。
But I'm not there yet.
但我还没到那儿。
And in the meantime I would say if you do want to buy this, let's say you want to buy NMN, look for a company that is well established that has high levels of quality control.
与此同时，我想说，如果你确实想买这个，比如说你想买 NMN，那就寻找一家信誉良好、质量控制水平高的公司。
Look for three letters, GMP, which is good manufacturing practices.
寻找三个字母：GMP，这是良好生产规范。
And so that means they make it under a certain level of quality control.
这意味着他们是在一定水平的质量控制下生产的。
You're not going to find iron filings in there and it probably has the stuff in it that they say it does.
你不会在那里找到铁屑，但里面可能有他们所说的东西。
So that's all I can say right now.
这就是我现在能说的。
Andrew Huberman:
安德鲁·休伯曼：
Sure.
当然。
David Sinclair:
大卫·辛克莱：
I'm working on something that's going to be much more helpful.
我正在做一些更有帮助的事情。
But overall, make sure it's white crystalline NMN.
但总体而言，请确保它是白色结晶 NMN。
And that, to me, it tastes like burnt popcorn.
对我来说，它尝起来就像烧焦的爆米花。
Andrew Huberman:
安德鲁·休伯曼：
You crack open the capsules and you'll take a little sample to make sure it tastes like burnt popcorn.
你打开胶囊，取出一点样品，确保它尝起来像烧焦的爆米花。
David Sinclair:
大卫·辛克莱：
Well, when I'm making my capsules, I'll taste it and I do a lot of quality control and the stuff that I take.
嗯，当我制作胶囊时，我会品尝它，并对我服用的东西进行大量的质量控制。
Andrew Huberman:
安德鲁·休伯曼：
Do you take that gram at once with the resveratrol or do you take it spread throughout the day?
您是立即将那克与白藜芦醇一起服用，还是全天服用？
David Sinclair:
大卫·辛克莱：
It's all in the morning for those things.
这些事情都在早上了。
So if I take metformin, it's NMN and the resveratrol altogether and there's a good reason for that.
因此，如果我服用二甲双胍，它就是 NMN 和白藜芦醇，这是有充分理由的。
It's all scientific.
这都是科学的。
I try to be.
我努力做到。
The levels of NAD go up in the morning in our bodies, naturally.
早晨，我们体内的 NAD 水平自然会上升。
Our bodies actually have a cycle of NAD.
我们的身体实际上有一个 NAD 循环。
It's not steady.
并不稳定。
Andrew Huberman:
安德鲁·休伯曼：
It's circadian?
这是昼夜节律吗？
David Sinclair:
大卫·辛克莱：
It's circadian.
这是昼夜节律。
In fact, NAD controls your clock.
事实上，NAD 控制着你的时钟。
This was shown by Shin Imai and colleagues in a nice science paper about a decade ago, that if you disrupt the NAD cycle, which is controlled by the sirtuin gene that we worked on, that is what's telling your body, "Oh, it's time to eat, it's time to go to sleep." And if you take these, the NMN late at night for example, you can disrupt your circadian rhythms.
Shin Imai 和他的同事在大约十年前的一篇不错的科学论文中证明了这一点，如果你破坏了 NAD 循环（它是由我们研究的 Sirtuin 基因控制的），那就会告诉你的身体，“哦，该吃饭了，该睡觉了。”如果你在深夜服用这些药物，例如 NMN，你可能会扰乱你的昼夜节律。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
David Sinclair:
大卫·辛克莱：
Conversely, when I travel and I want to reset my clock to the time zone, I will take a boost of NMN in the morning and I feel great.
相反，当我旅行并想将时钟重置为时区时，我会在早上服用 NMN，感觉很棒。
Andrew Huberman:
安德鲁·休伯曼：
Does this protocol for you, does it produce any immediate effects of increased energy, et cetera?
这个方案适合你吗？它是否会产生任何增加能量的立竿见影的效果等等？
You mentioned that one would, if it's right for them, would have to take it for at least two weeks to start to see the NAD levels increase.
您提到，如果适合他们，则必须服用至少两周才能开始看到 NAD 水平增加。
At that point when NAD levels increase, could one possibly expect an increase in overall energy focus, etcetera?
当 NAD 水平增加时，人们是否可能期望整体能量集中度增加等等？
I realize we're not making promises here, but I'm just wondering whether or not the only measure of whether or not this protocol is working is whether or not you die at age blank or blank plus 20.
我知道我们并不是在这里做出承诺，但我只是想知道衡量这个协议是否有效的唯一标准是否是你是否在空白年龄或空白加 20 岁时死亡。
And of course once you're dead, you can't really know if you would've lived longer if you'd done something differently and vice versa.
当然，一旦你死了，你就无法真正知道如果你做了不同的事情，你是否会活得更久，反之亦然。
David Sinclair:
大卫·辛克莱：
Sure.
当然。
Well there was a study again by Shin Imai, my good friend at Washington University in St. Louis, that showed that improves, remember this insulin sensitivity, which is a good thing, but you can't know your insulin sensitivity unless you're measuring glucose, have a glucose monitor on your own.
我在圣路易斯华盛顿大学的好朋友 Shin Imai 再次进行了一项研究，该研究表明胰岛素敏感性有所改善，这是一件好事，但除非您测量血糖，否则您无法知道自己的胰岛素敏感性，并且自己有一个血糖监测仪。
Andrew Huberman:
安德鲁·休伯曼：
Do you have one on right now?
你现在有一台吗？
David Sinclair:
大卫·辛克莱：
No, no. I used to.
不，不。我以前也是这样
I learned a lot.
我学到了很多。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Last time I saw you had this thing, it looks like a small leech, not a large leech.
上次我看到你有这个东西，看起来像是小水蛭，而不是大水蛭。
And it was measuring your blood glucose.
它正在测量你的血糖。
David Sinclair:
大卫·辛克莱：
They're very informative because you learn what your body reacts to.
它们提供的信息非常丰富，因为您可以了解自己的身体反应。
And grapes were really bad.
葡萄真的很糟糕。
Rhonda Patrick agrees with that.
朗达帕特里克同意这一点。
But the issue was...
但问题是...
Where were we Andrew?
我们安德鲁在哪里？
Andrew Huberman:
安德鲁·休伯曼：
The issue is whether or not you can expect any immediate effects on energy, vitality, focus, just even subjectively.
问题是你是否可以预期对能量、活力、注意力、甚至主观上的任何直接影响。
David Sinclair:
大卫·辛克莱：
So what do you feel is the question?
那么你觉得问题是什么？
And anecdotally, because I've been taking this for a long time.
有趣的是，因为我已经服用这个很长时间了。
If I don't take it, I start to feel 50 years old.
如果我不服用它，我就会开始感觉自己已经50岁了。
It's horrible.
太可怕了。
I can't think straight.
我无法正常思考。
It may be placebo, but who knows.
它可能是安慰剂，但谁知道呢。
But what we're doing now are very careful clinical trials.
但我们现在正在做的是非常仔细的临床试验。
We've done the safety for two years and we're now treating elderly patients at Harvard Medical School with some wonderful colleagues.
我们已经做了两年的安全工作，现在正在哈佛医学院与一些优秀的同事一起治疗老年患者。
And those people are actually going to be, and currently in MRIs.
这些人实际上将会并且目前正在接受核磁共振检查。
So you can measure the energetics and the NAD levels in their legs as they exercise in real time and that will tell us if what we see in the mice, this increased endurance, actually works.
因此，您可以实时测量它们运动时腿部的能量和 NAD 水平，这将告诉我们在小鼠身上看到的这种增强的耐力是否真的有效。
In the meantime, it's fun to talk about anecdotes.
与此同时，谈论轶事也很有趣。
I have a number of athlete friends, some of whom have increased their, lowered their time in marathons, for example; there's a good friend of ours in our circle that is winning marathons at age 50 now.
我有很多运动员朋友，其中一些人增加或减少了马拉松时间，例如；我们圈子里有一个好朋友，他现在50岁了，正在赢得马拉松比赛。
And he attributes that to the protocol that he's on.
他将此归因于他所遵循的协议。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
I haven't started taking NMN, but I'm planning to do that when my next birthday arrives, which is in a couple months.
我还没有开始服用 NMN，但我计划在下一个生日到来时（几个月后）服用 NMN。
But I do experiments on my sister and have for years.
但我在我妹妹身上做了很多年的实验。
I have a sister who's three years older than I am, who is very enthusiastic about these protocols.
我有一个比我大三岁的姐姐，她对这些协议非常热衷。
Andrew Huberman:
安德鲁·休伯曼：
And I'll tell you that after reading your book, I started purchasing for her and giving her an NMN supplement.
我会告诉你，读完你的书后，我开始为她购买并给她服用 NMN 补充剂。
And she claims and I believe her, she has a quite sensitive system and she's very tuned into it.
她声称，我相信她，她有一个非常敏感的系统，而且她非常适应它。
She feels far and away better when she takes it as opposed to when she doesn't.
当她接受它时，她感觉比不接受时感觉好多了。
And I've done the control experiment of removing her supply and then giving it back to her and this kind of thing.
我做了对照实验，去掉她的供给，然后把它还给她，诸如此类的事情。
So that's my other laboratory.
这就是我的另一个实验室。
Andrew Huberman:
安德鲁·休伯曼：
This is what younger brothers do to older sisters.
这就是弟弟对姐姐所做的事。
I have a question about something that if it has no relevance, we can just treat it as a speed bump and then move right on.
我有一个问题，如果它没有相关性，我们可以将其视为减速带，然后继续前进。
The artificial sweeteners, these things that were, I should say non-glucose increasing sweeteners.
人工甜味剂，这些东西，我应该说是非葡萄糖增加甜味剂。
So you've got stevia, which is a plant basically, and then you've got sucralose and aspartame and all these things.
所以你有甜叶菊，它基本上是一种植物，然后你有三氯蔗糖和阿斯巴甜以及所有这些东西。
Andrew Huberman:
安德鲁·休伯曼：
There is some evidence that I know we're both aware of, that's been published in quite reputable journals showing that they can disrupt the gut microbiome in certain cases.
我知道我们都知道一些证据，这些证据已发表在相当有信誉的期刊上，表明它们在某些情况下可以破坏肠道微生物组。
In particular, saccharin, the one that basically nobody uses anymore, and it's questionable as to whether or not stevia has the same negative effects, etcetera.
特别是糖精，基本上已经没有人再使用了，而甜叶菊是否也有同样的负面影响，等等都是值得怀疑的。
That's not what this is about.
这不是重点。
Andrew Huberman:
安德鲁·休伯曼：
But in terms of the sensation of, or the perception of sweet taste, is that itself a possible detriment to these pro-longevity, forgive me for using the term, the pathways?
但就甜味的感觉或感知而言，这本身是否可能对这些长寿产生损害，请原谅我使用“途径”这个术语？
If I were to drink a Diet Coke during a fast, am I somehow disrupting this?
如果我在禁食期间喝健怡可乐，我是否会以某种方式扰乱这一切？
And I'm asking this question because I get asked this question a lot.
我问这个问题是因为我经常被问到这个问题。
David Sinclair:
大卫·辛克莱：
Well, there may be small effects.
嗯，可能会有一些小的影响。
I don't think they're worth worrying about.
我认为他们不值得担心。
Joe Rogan laughed at me because I was drinking a Diet Coke during the first interview I did with him.
乔·罗根嘲笑我，因为我第一次采访他时喝的是健怡可乐。
I will drink Diet Coke.
我会喝健怡可乐。
I've read those scientific literature and again, it's this 5% thing that I think is blown out of proportion.
我读过那些科学文献，我认为这 5% 的事情被夸大了。
David Sinclair:
大卫·辛克莱：
If I was to put a number on it, I would say if eating a high sugary meal or drinking a sugar-filled soda, what is that 30 grams of sugar?
如果要我写一个数字，我会说，如果吃一顿高糖餐或喝一杯含糖汽水，那30克糖是多少？
Let's say that's a 10 out of 10 bad for you.
假设这对您来说十分之十分不利。
A Diet Coke might be a one.
健怡可乐可能就是其中之一。
And if I'm, which am I going to do?
如果我是，我该怎么办？
I could have a 10 or a one or go without in my life, I'll do the one on occasion.
我一生中可以拥有 10 个或 1 个，也可以没有，有时我会做一个。
David Sinclair:
大卫·辛克莱：
I try to avoid them because I don't like the ones as much.
我尽量避开它们，因为我不太喜欢它们。
But you can't say that sucralose is equivalent to drinking a sugary soda.
但你不能说三氯蔗糖就相当于喝含糖苏打水。
There's just no comparison.
只是没有可比性。
And I think, what is it?
我想，这是什么？
Stevia?
甜叶菊？
I do use stevia whenever I can because it's a naturally sourced product and I haven't seen any good evidence yet that it's bad for you.
我会尽可能使用甜叶菊，因为它是一种天然来源的产品，而且我还没有看到任何好的证据表明它对你有害。
David Sinclair:
大卫·辛克莱：
But I think a lot of this is overblown and a lot of it's the media trying to give equal weight to stories.
但我认为很多事情都被夸大了，很多都是媒体试图对故事给予同等的重视。
As you know, as a scientist, it can be frustrating when something's a 10 and something's a one and they're equated.
如您所知，作为一名科学家，当某个值是 10、某个值是 1 并且它们相等时，可能会感到沮丧。
Andrew Huberman:
安德鲁·休伯曼：
How do I say this respectfully?
我该如何恭敬地说这句话？
I think if science journalists were required to post their credentials alongside their name and then the people would take the articles into, with an additional grain of salt, right?
我认为，如果科学记者被要求在名字旁边贴上他们的证件，那么人们就会对这些文章持怀疑态度，对吗？
Andrew Huberman:
安德鲁·休伯曼：
I mean in other words, that I think that most...
换句话说，我认为大多数...
The science media is mainly generated around two specific goals.
科学媒体主要围绕两个具体目标而产生。
One is to make people very, very afraid, or get people very, very excited and oftentimes, the get -people-excited part is sponsored content and I think that's overlooked.
一是让人们非常非常害怕，或者让人们非常非常兴奋，而通常，让人们兴奋的部分是赞助内容，我认为这一点被忽视了。
In any case, thank you for that.
无论如何，谢谢你。
Andrew Huberman:
安德鲁·休伯曼：
I want to talk about iron and iron load.
我想谈谈铁和铁负荷。
We were talking earlier about ferritin and of course, women menstruate and so their iron needs are greater than people, men, that don't menstruate or women that don't menstruate.
我们之前讨论过铁蛋白，当然，女性会来月经，因此她们对铁的需求比不来月经的男性或不来月经的女性更大。
Andrew Huberman:
安德鲁·休伯曼：
I don't think we can get right down into how much iron somebody needs because it'll vary person to person.
我认为我们无法直接确定一个人需要多少铁，因为每个人的铁含量都不同。
But I was surprised to learn that iron is actually going to accelerate the aging process in various contexts.
但我惊讶地发现铁实际上会在各种情况下加速衰老过程。
David Sinclair:
大卫·辛克莱：
Well, this is new finding, a new finding out of Spain.
嗯，这是新发现，来自西班牙的新发现。
Manuel Serrano's lab has found that excess iron will increase the number of senescent cells in the body.
曼努埃尔塞拉诺的实验室发现，过量的铁会增加体内衰老细胞的数量。
And senescent cells are the zombie cells that accumulate as you get older and they sit there and they cause inflammation mainly and also can cause cancer.
衰老细胞是随着年龄的增长而积累的僵尸细胞，它们坐在那里，主要引起炎症，也可能导致癌症。
David Sinclair:
大卫·辛克莱：
And it's found that if you get rid of these cells or never accumulate them, you stay younger.
研究发现，如果你摆脱这些细胞或从不积累它们，你就会保持年轻。
In animals, and there's some really interesting studies out of Mayo Clinic and humans as well.
在动物方面，梅奥诊所和人类也进行了一些非常有趣的研究。
So iron is a pro-senescent metal.
所以铁是一种促衰老金属。
And it's what, I think is that if you're taking excess iron as a supplement, you're probably accelerating your aging process.
我认为，如果您服用过量的铁作为补充剂，您可能会加速衰老过程。
David Sinclair:
大卫·辛克莱：
The other thing that I found really interesting is I've looked at hundreds of thousands of people's metabolism and their blood biomarkers.
我发现真正有趣的另一件事是我研究了数十万人的新陈代谢和他们的血液生物标志物。
I was one of the first people in InsideTracker as a board member and I'm still their scientific lead guy.
我是 InsideTracker 的第一批董事会成员之一，而且我仍然是他们的科学带头人。
David Sinclair:
大卫·辛克莱：
So I can look anonymously at hundreds of thousands of people's blood work, and we also know how fit they are, how old they are.
这样我就可以匿名查看数十万人的血液检查，我们也知道他们的健康状况和年龄。
Some of them are marathon runners, some of them are CrossFit.
他们中有些是马拉松运动员，有些是 CrossFit。
And there's a signature of health that actually is different than your average person.
而且健康的标志实际上与普通人不同。
David Sinclair:
大卫·辛克莱：
Now, I'm not going to say bad things about MDs because a lot of my best friends are MDs and I work with them at Harvard Medical School.
现在，我不会说医学博士的坏话，因为我的很多最好的朋友都是医学博士，而且我在哈佛医学院与他们一起工作。
The issue though is that with MD training, there's a scale of what's normal and if you're out of that normal range, something must be wrong.
但问题是，MD 培训有一个正常范围，如果超出正常范围，则一定有问题。
That's the paradigm that they work under, but first of all, everybody's different and you want to know their baseline and track people over years to know what's normal for them.
这就是他们工作的范式，但首先，每个人都是不同的，你想知道他们的基线并多年来跟踪人们以了解他们的正常情况。
David Sinclair:
大卫·辛克莱：
And what I find, for example, is people who are really healthy and live the way I do and have a diet that's fairly vegetarian but not strict, still have slightly low hemoglobin levels, slightly low iron, slightly low ferritin, but we have super amounts of energy.
例如，我发现，那些真正健康的人，按照我的方式生活，饮食相当素食但不严格，血红蛋白水平仍然略低，铁含量略低，铁蛋白略低，但我们有超强的能量。
We're not anemic and we're getting along great in life.
我们并不贫血，我们的生活也过得很好。
David Sinclair:
大卫·辛克莱：
But a doctor who just looks at that might say, "Oh we need to give you more iron." So what I'm getting at is an example of we need to personalize medicine and look at people over the long run to know what works for them and what's healthy for them and not just work towards the average human, but work towards what's optimal for human.
但医生看到这一点可能会说：“哦，我们需要给你更多的铁。”因此，我要举的例子是，我们需要个性化医疗，从长远来看，了解什么对他们有效，什么对他们健康，而不仅仅是针对普通人，而是针对对人类最有利的方式。
Andrew Huberman:
安德鲁·休伯曼：
I love that answer.
我喜欢这个答案。
You mentioned tracking and tracking over time, and this is a really interesting area that I know you have been focused on for a long time.
您提到了随着时间的推移进行跟踪和跟踪，这是一个非常有趣的领域，我知道您长期以来一直关注这一领域。
I've been getting blood work done about every six months since, frankly, since I was in college.
坦率地说，自从我上大学以来，我大约每六个月进行一次血液检查。
I like data and I got interested in supplementation and exercise because it made me feel better, but I also want to know what was going on under the hood.
我喜欢数据，我对补充和锻炼感兴趣，因为它让我感觉更好，但我也想知道幕后发生了什么。
Andrew Huberman:
安德鲁·休伯曼：
So you get numbers back.
这样你就可以得到数字了。
You get this hormone and that hormone, this blood glucose measure, etcetera.
你会得到这种激素和那种激素，这种血糖测量值，等等。
How do you make sense of the data?
您如何理解这些数据？
I mean, what InsideTracker is doing aside, how do you personally make sense of the data in ways that might differ from the way that a standard MD might look at one of these charts?
我的意思是，除了 InsideTracker 所做的事情之外，您个人如何以可能不同于标准 MD 查看这些图表的方式来理解数据？
Because the standard practice is to say, "Is it red, yellow, or green?" Right?
因为标准做法是说“它是红色、黄色还是绿色？”正确的？
Is it basically too high or too low?
基本上是太高还是太低？
Is it somewhere close to the margins or are you okay?
是在接近边缘的地方还是你还好吗？
Are you in these ranges?
您在这些范围内吗？
Andrew Huberman:
安德鲁·休伯曼：
Are there any things that you pay attention to that you think are particularly interesting for people to just take note of?
有没有您认为人们特别感兴趣且值得关注的事情？
I mean, we're not asking you to go against anybody's physician, but what sorts of things should people start to educate themselves about in terms of what these molecules are on their charts, if they choose to get them, and what do you look at?
我的意思是，我们并不是要求你反对任何人的医生，但是人们应该开始根据这些分子在他们的图表上的内容进行自我教育，如果他们选择得到它们，你会看什么？
David Sinclair:
大卫·辛克莱：
Yeah.
是的。
Wow, there's a lot there.
哇，那里有很多。
The first is that you should be tracking things because one measurement isn't enough.
首先，您应该跟踪事物，因为一次测量是不够的。
These things vary and over time, and if you can have a decade or more of data, it's super informative, as you well know, as you know.
这些事情会随着时间的推移而变化，如果你能拥有十年或更长时间的数据，正如你所知，它的信息量非常大。
David Sinclair:
大卫·辛克莱：
So the physician, interestingly, my physician, let's take him as an example.
所以医生，有趣的是，我的医生，让我们以他为例。
So he sees me, he says, "How you feeling?" "I'm feeling great." "Okay, see you next year." That's craziness.
所以他看到我，他说，“你感觉怎么样？” “我感觉很好。” “好吧，明年见。”这太疯狂了。
Anyway, so I say, "Okay, stop.
无论如何，所以我说：“好吧，停下来。
Let's talk a little bit about..."
我们来谈谈一些事情吧……”
Andrew Huberman:
安德鲁·休伯曼：
"Let me educate you." That's what David tells his physician.
“我来教育一下你吧。”这就是大卫告诉他的医生的。
I imagine that the 12-year-old David Sinclair says to his physician, "Listen.
我想象 12 岁的大卫·辛克莱 (David Sinclair) 对他的医生说：“听着。
Let's have a different discussion." Is that how it works?
让我们进行不同的讨论。”是这样的吗？
David Sinclair:
大卫·辛克莱：
It is.
是的。
He finds me pretty annoying, as does my dentist.
他觉得我很烦人，我的牙医也是如此。
But so I said, "Stop.
但我说：“停下来。
Hang on.
坚持住。
I've got this data.
我有这个数据。
I've got the InsideTracker data." So I pull that up on the screen and I'm showing him the changes in my cholesterol, in my CRP, which is an inflammatory marker, as you know.
我有 InsideTracker 数据。”所以我把它拉到屏幕上，向他展示我的胆固醇和 CRP 的变化，如你所知，CRP 是一种炎症标志物。
And we're going through it and you can see things change over time.
我们正在经历它，你可以看到事情随着时间的推移而变化。
And I've corrected them as they go slightly out of the optimal range for me, which is different than what he would do, of course.
我已经纠正了它们，因为它们稍微超出了我的最佳范围，这当然与他会做的不同。
David Sinclair:
大卫·辛克莱：
But what was funny is that he says, "This is great.
但有趣的是，他说：“这太棒了。
I love this data, but I'm not allowed to get this because of course the insurance companies won't pay for it." So again, you can pay out of pocket.
我喜欢这些数据，但我不被允许获得这些数据，因为保险公司当然不会为此付费。”同样，您可以自掏腰包付款。
It's not super expensive.
这不是超级贵。
I would say if you save a bit of money on a coffee, you can afford this kind of stuff.
我想说，如果你在咖啡上省点钱，你就买得起这种东西。
But the main point is that doctors do like this data.
但要点是医生确实喜欢这些数据。
It's just that they're unable to spend the money on every one of their patients to get it.
只是他们无法把钱花在每一位患者身上以获得它。
Andrew Huberman:
安德鲁·休伯曼：
Is there a code word that someone can use with their physician that will trigger a comprehensive blood test?
是否有人可以与医生一起使用密码来触发全面的血液检查？
I keep trying to figure out what's the code that one needs to ask or tell their doctor like, "I'm feeling blank" so that they get a full blood panel.
我一直试图找出人们需要询问或告诉医生的代码是什么，例如“我感觉一片空白”，以便他们获得完整的血液检查。
David Sinclair:
大卫·辛克莱：
Well-
嗯-
Andrew Huberman:
安德鲁·休伯曼：
Do you have to be hemorrhaging from the gut or something?
一定是肠道出血还是什么原因？
David Sinclair:
大卫·辛克莱：
Well, I usually use the WTH method, which is what the hell and then he says, "Okay, we'll do it."
嗯，我通常使用 WTH 方法，这就是见鬼的方法，然后他说：“好吧，我们就这么做。”
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
Because I think a lot of people out there are thinking, "Look, I'd love to have blood work repeatedly over time," but that's hard to get for financial reasons, but also a lot of people just don't know how to approach the conversation.
因为我认为很多人都在想，“听着，我希望随着时间的推移反复进行血液检查”，但由于经济原因很难做到这一点，而且很多人只是不知道如何进行对话。
Andrew Huberman:
安德鲁·休伯曼：
And this is one of the things that I hope that we can educate people on, that they deserve to know what's going on inside their body and that it makes a doctor's visit worthwhile, and that you don't have to feign illness in order to do it.
这是我希望我们能够教育人们的事情之一，他们应该知道自己体内发生了什么，这使得去看医生是值得的，而且你不必为了做到这一点而假装生病。
David Sinclair:
大卫·辛克莱：
Right and a lot of people do.
是的，很多人都这样做。
So I would say if you can afford these tests, there are increasing numbers of companies that offer these tests.
所以我想说，如果你能负担得起这些测试，就会有越来越多的公司提供这些测试。
InsideTracker is one of them and you just do it a couple of times a year at a minimum.
InsideTracker 就是其中之一，你每年至少要做几次。
And then you can share that with your doctor.
然后您可以与您的医生分享。
If you can't afford that, then I would say to your doctor, "Here are the main ones that Andrew and David do."
如果你负担不起，那么我会对你的医生说：“这是安德鲁和大卫做的主要手术。”
Andrew Huberman:
安德鲁·休伯曼：
Yeah, we must.
是的，我们必须。
And there's an email that is something like 5-5, or a phone number rather.
还有一封类似于 5-5 的电子邮件，或者更确切地说是电话号码。
It's 555-5555.
是555-5555。
I think if they have any complaints they can just call that number.
我认为如果他们有任何投诉，可以拨打该号码。
David will pick up on East Coast business hours and I'll pick up outside of those hours.
David 将在东海岸工作时间接听，我将在其他时间接听。
David Sinclair:
大卫·辛克莱：
Yeah, thank you.
是的，谢谢。
But there are some main ones.
但有一些主要的。
I would say, your blood sugar levels.
我会说，你的血糖水平。
You want to do your HbA1c which is your average glucose levels over the month.
您想要测量您的 HbA1c，这是您当月的平均血糖水平。
There's CRP, which I mentioned for inflammation.
CRP，我提到过它是针对炎症的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, let's talk about C-reactive protein for a second because I think it's been shown to be an early marker of macular degeneration, of heart disease or a variety of different things.
是的，让我们谈谈 C 反应蛋白，因为我认为它已被证明是黄斑变性、心脏病或各种不同疾病的早期标志物。
CRP is something that we don't hear enough about, I think.
我认为我们对 CRP 的了解还不够。
What do you know about CRP that I don't?
关于 CRP 你知道哪些是我不知道的？
I'm guessing a lot, but-
我猜测了很多，但是——
David Sinclair:
大卫·辛克莱：
Oh, it was originally picked up as something that was associated with heart disease and the Framingham study, I believe.
哦，我相信它最初被认为与心脏病和弗雷明汉研究有关。
It is the best marker for cardiovascular inflammation and is also, we use it as a predictor of longevity and its levels go up with mortality.
它是心血管炎症的最佳标志物，而且我们用它作为长寿的预测指标，其水平随着死亡率的升高而升高。
David Sinclair:
大卫·辛克莱：
And so this is an association, but there's enough data that I would say if you have high levels of CRP, you need to get your levels down quickly.
这是一个关联，但有足够的数据表明，如果您的 CRP 水平较高，您需要快速降低水平。
And the levels usually go up with age and with levels of inflammation.
而且这种水平通常会随着年龄和炎症程度的增加而上升。
So the ways to get it down would be to switch the diet, eat less, try to eat more vegetables.
所以降低它的方法就是改变饮食，少吃，多吃蔬菜。
You'll find it will come down.
你会发现它会下来。
There are also drugs that can do it.
也有药物可以做到这一点。
Anti-inflammatories can do it as well.
消炎药也可以做到这一点。
David Sinclair:
大卫·辛克莱：
But CRP is...
但CRP是...
It's actually hCRP.
它实际上是hCRP。
There's a high sensitive or hs-CRP.
有高敏或 hs-CRP。
Your doctor will know.
你的医生会知道的。
Get one of those readings because if you've got normal blood sugar levels, your doctor...
获取这些读数之一，因为如果您的血糖水平正常，您的医生...
Or fasting blood sugar levels, your doctor might say you're fine, but a lot of people have normal blood sugar but have high CRP, which is just as bad for you long term, and can predict a future heart attack.
或者空腹血糖水平，您的医生可能会说您没问题，但很多人的血糖正常，但 CRP 较高，这对您的长期健康同样不利，并且可以预测未来的心脏病发作。
Andrew Huberman:
安德鲁·休伯曼：
Along the lines of heart attack, I want your thoughts on cholesterol and serum cholesterol and dietary cholesterol.
沿着心脏病发作的思路，我想听听您对胆固醇、血清胆固醇和膳食胆固醇的看法。
I cannot, for the life of me, get my arms around this literature.
我一生都无法拥抱这些文学作品。
And even if I ignore all the, essentially, nonsense that's out there in various social media groups, as saying cholesterol is the worst thing in the world or cholesterol is not...
即使我忽略了各种社交媒体群组中的所有本质上的废话，比如说胆固醇是世界上最糟糕的东西，或者胆固醇不是……
Or dietary cholesterol has nothing to do with serum cholesterol and nothing to do with longevity.
或者说膳食胆固醇与血清胆固醇无关，与寿命无关。
Andrew Huberman:
安德鲁·休伯曼：
I can't seem to sort through the very basic data that essentially ask, is having high levels of LDL going to kill me earlier?
我似乎无法整理最基本的数据，这些数据本质上是在问：低密度脂蛋白水平高会提前杀死我吗？
Should I be striving to always reduce LDL and increase HDL?
我是否应该始终努力降低低密度脂蛋白并增加高密度脂蛋白？
Is that a reasonable goal?
这是一个合理的目标吗？
And if so, is dietary cholesterol the primary determinant of that?
如果是这样，膳食胆固醇是其主要决定因素吗？
Just as a final point about this, I am aware of quite good data that shows that anorexics, people that essentially eat no food unless you force them to, can often have very high LDL.
最后一点，我知道有相当好的数据表明，厌食症患者（除非强迫他们基本上不吃任何食物）的低密度脂蛋白通常非常高。
So their dietary cholesterol is essentially zero and so they're manufacturing a lot of their own.
因此，他们的膳食胆固醇基本上为零，因此他们自己生产大量胆固醇。
Andrew Huberman:
安德鲁·休伯曼：
Realize this isn't your primary area of expertise, but you're a smart guy.
意识到这不是您的主要专业领域，但您是一个聪明人。
You think about this kind of stuff a lot.
你经常思考这类事情。
What do you think is going on with the cholesterol literature and will we ever get to the bottom of this as a scientific and medical community?
您认为有关胆固醇的文献到底发生了什么？作为科学界和医学界，我们是否能弄清真相？
Because to me, it is rather perplexing.
因为对我来说，这是相当令人困惑的。
David Sinclair:
大卫·辛克莱：
It is.
是的。
But you can get through the politics.
但你可以通过政治。
I know a fair bit about cholesterol because it's in my family history and I was headed for an early death.
我对胆固醇有一定的了解，因为它是我的家族史，而我正走向早逝。
My grandmother had a stroke at 30.
我的祖母30岁时中风了。
That's how bad I am in terms of my genetics.
这就是我的基因有多糟糕。
So I went on a statin and I know there's a lot of people who say that statins, long term, are bad.
所以我开始服用他汀类药物，我知道很多人都说他汀类药物从长远来看是不好的。
It's associated with Alzheimer's disease.
它与阿尔茨海默病有关。
David Sinclair:
大卫·辛克莱：
I've been taking a statin since I was 29 and that's because I forced my same doctor to give me the statin.
我从 29 岁起就开始服用他汀类药物，那是因为我强迫我的同一位医生给我服用他汀类药物。
The conversation was something like this.
谈话内容是这样的。
"You're too young to be on a statin." I said, "What?
“你还太年轻，不适合服用他汀类药物。”我说：“什么？
You want me to have a heart attack before you give me something?
你想让我先心脏病发作再给我东西吗？
Give it to me now." So 29, I've been on a statin and my cholesterol was way up in, beyond 300, which is a massive mess.
现在就给我吧。” 29 岁时，我一直在服用他汀类药物，但我的胆固醇却大幅上升，超过了 300，这真是一团糟。
Basically, my blood was creamy to look at.
基本上，我的血液看起来是奶油状的。
David Sinclair:
大卫·辛克莱：
So I've now got my cholesterol down to low, low levels to...
所以我现在已经把我的胆固醇降到很低很低的水平......
What would it be?
会是什么？
You could check on my InsideTracker, but...
你可以查看我的 InsideTracker，但是...
So my ratio of HDL to LDL, which you want to be less than five, is now two, and the LDL is below a 100.
因此，我的 HDL 与 LDL 比率（您希望低于 5）现在为 2，而 LDL 低于 100。
So it's all good.
所以一切都很好。
And my, I've measured my cardiovascular health with an MRI.
我的，我用核磁共振仪测量了我的心血管健康状况。
I've got a movie of my heart beating.
我有一部让我心跳的电影。
I've still got a heart of a 20-year-old.
我依然有一颗20岁的心。
So that's working.
这样就可以了。
David Sinclair:
大卫·辛克莱：
I'm willing to forego the risk that the statin is causing problems later because of my family history.
由于我的家族史，我愿意放弃他汀类药物日后引起问题的风险。
But other people, I would say, be aware that statins aren't perfect drugs.
但我想说，其他人要意识到他汀类药物并不是完美的药物。
There are some interesting new ones.
有一些有趣的新内容。
There's one called the PCSK9 inhibitor, which is a, I think, fortnightly or every two weeks injection that blocks the release of LDL from the liver.
有一种叫做 PCSK9 抑制剂，我认为每两周或每两周注射一次，可以阻止肝脏释放 LDL。
David Sinclair:
大卫·辛克莱：
That seems to be great for lowering cholesterol, but also has other benefits that might be prolongevity.
这似乎对降低胆固醇很有好处，但也有其他好处，可能是延长寿命。
And there are some people that I was just talking to who are on the cutting edge of this, and their doctors are trying them on this drug instead of the statin.
我刚刚与一些处于这方面最前沿的人交谈，他们的医生正在尝试用这种药物代替他汀类药物。
So you could talk to your doctor about...
所以你可以和你的医生谈谈...
Andrew Huberman:
安德鲁·休伯曼：
Do you avoid dietary cholesterol for that reason also?
您是否也因此而避免饮食中的胆固醇？
Red meat, butter.
红肉、黄油。
I mean, I happen to love butter.
我是说，我碰巧喜欢黄油。
I love red meat...
我喜欢红肉...
I realize there are some people who don't.
我意识到有些人不这么认为。
My cholesterol's a little bit high, but I'm working to bring that down a bit, although not by altering my food intake yet.
我的胆固醇有点高，但我正在努力将其降低一点，尽管还没有通过改变食物摄入量来实现。
Andrew Huberman:
安德鲁·休伯曼：
But what do you think is the relationship between dietary cholesterol and serum cholesterol and what's going on with the liver?
但您认为膳食胆固醇和血清胆固醇之间的关系以及肝脏发生了什么情况？
Why are anorexics...
为什么会厌食症...
Why is their serum cholesterol so high when they're eating nothing?
为什么他们不吃东西时血清胆固醇这么高？
David Sinclair:
大卫·辛克莱：
Yeah.
是的。
Well, there have been a number of papers over the years that have been ignored.
嗯，多年来有许多论文被忽视了。
And our friend Peter Attia brought to my attention recently a new study that I think definitively said that dietary cholesterol has almost zero impact on blood cholesterol levels.
我们的朋友彼得·阿提亚（Peter Attia）最近引起了我的注意，一项新的研究我认为明确表明膳食胆固醇对血液胆固醇水平的影响几乎为零。
Andrew Huberman:
安德鲁·休伯曼：
Good.
很好。
David Sinclair:
大卫·辛克莱：
Yeah.
是的。
I'm annoyed because I've been avoiding eggs and butter for most of my life and I didn't have to.
我很生气，因为我一生中的大部分时间都在避免吃鸡蛋和黄油，但我没有必要这样做。
So I have eggs-
所以我有鸡蛋-
Andrew Huberman:
安德鲁·休伯曼：
Plenty of time.
有充足的时间。
Or at least in your case.
或者至少就你而言。
David Sinclair:
大卫·辛克莱：
Yeah, yeah.
是啊，是啊。
So that's the thing.
就是这样。
You can eat these foods that were once banned because the...
你可以吃这些曾经被禁止的食物，因为......
It's very difficult to take cholesterol up into the body from the gut and most of it's being synthesized in the body.
胆固醇从肠道进入体内非常困难，而且大部分是在体内合成的。
Andrew Huberman:
安德鲁·休伯曼：
Wow.
哇。
I'm just pausing there for a second because I think that...
我只是在那里暂停了一秒钟，因为我认为......
What we've been told, six meals a day, eat a lot of grains and fruits, and this kind of thing.
我们被告知，一天六餐，吃很多谷物和水果，诸如此类的事情。
Avoid cholesterol.
避免胆固醇。
I mean, basically everything we learned in the 80s and 90s and early 2000s is getting flipped on its head now.
我的意思是，基本上我们在 80 年代、90 年代以及 2000 年代初学到的一切现在都被颠覆了。
Andrew Huberman:
安德鲁·休伯曼：
But, and I think this is a very strong caveat that's important to mention.
但是，我认为这是一个非常强烈的警告，值得一提。
Amino acids.
氨基酸。
In particular, the amino acids that come from animal products seem to have some pro-aging effect on them, right?
特别是来自动物产品的氨基酸似乎对它们有一些促衰老作用，对吧？
At least the way that I've heard you describe your diet.
至少是我听到你描述你的饮食的方式。
Andrew Huberman:
安德鲁·休伯曼：
And I'm somebody who enjoys meat.
而且我是一个喜欢吃肉的人。
I like it.
我喜欢它。
So I'm by no means a vegan at all.
所以我根本不是素食主义者。
But I've heard you say you eat mostly plants, but a little bit of fish or chicken or something of that sort...
但我听你说你主要吃植物，但也吃一点鱼或鸡肉之类的东西......
or eggs.
或鸡蛋。
But is that specifically to avoid excessive amino acid intake or is it something specific about plants that excites you with respect to...
但这是专门为了避免过量的氨基酸摄入，还是植物特有的东西让你兴奋……
Andrew Huberman:
安德鲁·休伯曼：
I mean, vegetables are delicious too, but what is it?
我的意思是，蔬菜也很好吃，但它是什么？
Is it something great about plants or is it something bad about...
植物有什么好处还是坏处...
When I think of meat, I guess the biologist in me thinks, amino acids, right?
当我想到肉时，我想我内心的生物学家会想，氨基酸，对吗？
I don't think, top sirloin, I think of amino acid.
我不认为，顶级牛腩，我想到的是氨基酸。
I think top sirloin as I'm eating it, but really what they are, are amino acids including lysine.
我认为我吃的牛腰肉是顶级的，但实际上它们是氨基酸，包括赖氨酸。
David Sinclair:
大卫·辛克莱：
Yeah.
是的。
Well, there are two good things about plants and neither of them is taste for me.
嗯，植物有两个好处，但我都不喜欢它们。
I would eat steak all the time if I could.
如果可以的话，我会一直吃牛排。
I did when I was a kid.
我小时候就这么做过。
I'm Australian.
我是澳大利亚人。
But plants have two benefits.
但植物有两个好处。
One is that they're highly nutritious and they'll give you a lot of the vitamins and nutrients that I need.
一是它们营养丰富，可以为您提供我需要的大量维生素和营养素。
David Sinclair:
大卫·辛克莱：
I don't take a multivitamin.
我不服用多种维生素。
I don't want to have the excess iron in my body.
我不想体内有多余的铁。
So there's that high-density nutrition.
所以就有了高密度的营养。
So those dark leaves.
所以那些深色的叶子。
If it's a spinach salad, great.
如果是菠菜沙拉那就太好了。
The second is that there is what's called xenohormetic molecules in plants.
第二个是植物中存在所谓的异种激素分子。
That term xenohormesis is a term that I came up with, with my friend Konrad Howitz, which means stressed plants make molecules that benefit your health.
“异毒效应”这个术语是我和我的朋友康拉德·霍维茨（Konrad Howitz）提出的，这意味着受压力的植物会产生有益于您健康的分子。
David Sinclair:
大卫·辛克莱：
I'll break it down.
我会把它分解。
Xeno means between species and hormesis is the term, whatever doesn't kill you makes you stronger and live longer.
异种意味着物种之间的关系，毒物兴奋效应是一个术语，任何杀不死你的东西都会让你变得更强大、活得更久。
And the idea is that when plants are stressed out — think of a grapevine that's dried out and they're starting to harvest the grapes, which is typically how it's done.
这个想法是，当植物承受压力时——想象一下干涸的葡萄藤，它们开始收获葡萄，这就是通常的做法。
They are full with resveratrol because resveratrol is a plant defense molecule that I think is made to activate those sort of sirtuin genes in a plant.
它们富含白藜芦醇，因为白藜芦醇是一种植物防御分子，我认为它是用来激活植物中的沉默调节蛋白基因的。
David Sinclair:
大卫·辛克莱：
So plants have sirtuins just like we do, but by purifying or at least concentrating in a lightproof bottle and keeping it out of the air, we stabilize the xenohormetic molecule or it's a cocktail, not just one.
因此，植物和我们一样也含有去乙酰化酶，但是通过纯化或至少浓缩在不透光的瓶子中并使其远离空气，我们可以稳定异种激素分子，或者它是一种鸡尾酒，而不仅仅是一种。
There's others in wine.
酒里还有其他东西。
We then ingest those and get the benefits of activating our own defenses because our food was getting stressed out.
然后，我们摄入这些物质，并获得激活自身防御的好处，因为我们的食物压力很大。
David Sinclair:
大卫·辛克莱：
And by stressed, I don't mean psychologically stressed, I mean biologically stressed.
我所说的压力不是指心理上的压力，而是指生物上的压力。
And so, I try to eat plants that have gone through a bit of stress.
因此，我尝试吃经历过一些压力的植物。
They might be brightly colored.
它们可能颜色鲜艳。
They've had too much sun or got nibbled on by a caterpillar.
它们受到了太多的阳光照射或者被毛毛虫啃咬了。
David Sinclair:
大卫·辛克莱：
So you go to places where it's organic or it's fresh, local, and those are the plants that aren't perfect and they probably have high concentrations of these molecules.
所以你去的地方都是有机的或者新鲜的，当地的，这些植物并不完美，它们可能含有高浓度的这些分子。
And in addition, I also buy the supplements to make sure I'm getting enough of those as well.
此外，我还购买补充剂以确保我摄入足够的补充剂。
Andrew Huberman:
安德鲁·休伯曼：
Which supplements mimic that?
哪些补充剂模仿了这一点？
David Sinclair:
大卫·辛克莱：
Well, resveratrol will...
那么，白藜芦醇会...
There's another one called quercetin or quercetin, some people call it, which you find in trace amount in apples and onions.
还有另一种叫做槲皮素或槲皮素，有些人称之为槲皮素，在苹果和洋葱中含有微量。
And we also showed back in 2003, that it activates sirtuins as well.
我们还在 2003 年证明，它也能激活去乙酰化酶。
But others have, 20 years later, found that it kills senescent cells or helps kill senescent cells.
但 20 年后，其他人发现它可以杀死衰老细胞或帮助杀死衰老细胞。
So it's a double whammy with that molecule.
所以这个分子是双重打击。
Andrew Huberman:
安德鲁·休伯曼：
And are you actively picking out the peaches that look like they were nibbled on by a caterpillar?
你是否正在积极地挑选那些看起来像被毛毛虫啃过的桃子？
David Sinclair:
大卫·辛克莱：
No, but I don't worry if they've been banged up a bit.
不，但我不担心它们是否被撞了一下。
Andrew Huberman:
安德鲁·休伯曼：
What's the story with antioxidants?
抗氧化剂有什么故事？
Are they of any value whatsoever, because the way that you described them at the beginning and what I've heard recently is that they are not all the rage for anti-aging?
它们有任何价值吗？因为你一开始描述它们的方式以及我最近听到的消息是它们并没有在抗衰老方面风靡一时？
What are they doing that's useful?
他们在做什么有用的事情？
Should we be seeking out antioxidants anyway, for other stellar health purposes?
为了其他重要的健康目的，我们是否应该寻找抗氧化剂？
David Sinclair:
大卫·辛克莱：
Well, yeah.
嗯，是的。
Antioxidants are not going to hurt you unless you take megadoses.
除非您服用大剂量，否则抗氧化剂不会伤害您。
We do need some oxidants for our immune system and there's even what's called mitohormesis, which is your mitochondria power packs need to have a little bit of these free radicals to be able to function.
我们的免疫系统确实需要一些氧化剂，甚至还有所谓的线粒体兴奋作用，即线粒体能量组需要有一点自由基才能发挥作用。
So you don't want to overdose on these antioxidants, Vitamin C, Vitamin E.
因此，您不想过量服用这些抗氧化剂、维生素 C、维生素 E。
Don't overdo it.
不要做得太过分。
Andrew Huberman:
安德鲁·休伯曼：
You don't take a multivitamin, correct?
你没有服用多种维生素，对吗？
David Sinclair:
大卫·辛克莱：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
I think I'm going to stop after this conversation because I've always just taken one for the kind of insurance purpose, which is a stupid purpose.
我想在这次谈话之后我会停下来，因为我一直只是出于保险目的而服用一个，这是一个愚蠢的目的。
Not actual insurance, but just thinking, "Oh, I'll top off on my A, C, B, D, E-
不是真正的保险，只是想，“哦，我会补充我的 A、C、B、D、E-
David Sinclair:
大卫·辛克莱：
Right and I'll pee out what I don't need.
好的，我会尿掉我不需要的东西。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
David Sinclair:
大卫·辛克莱：
Yeah, sure.
是的，当然。
Andrew Huberman:
安德鲁·休伯曼：
Well, that never bothered me.
嗯，这从来没有困扰过我。
The whole expensive pee thing never got...
整个昂贵的小便事情从来没有......
That argument never got me because of that...
那个争论从来没有让我感动过，因为……
A good vitamin is not that expensive.
好的维生素并不那么贵。
I just figured better safe than sorry, but it may be that it's detrimental.
我只是认为安全总比后悔好，但这可能是有害的。
David Sinclair:
大卫·辛克莱：
Well, it can in the case of iron, as we discussed, and the antioxidants.
嗯，正如我们所讨论的，对于铁和抗氧化剂来说，它可以。
So when I came into the aging field in the early 1990s, it was all about antioxidants and we thought that enzymes by the name of catalase and superoxide dismutase were going to be the key to longevity.
因此，当我在 20 世纪 90 年代初进入衰老领域时，一切都与抗氧化剂有关，我们认为过氧化氢酶和超氧化物歧化酶将成为长寿的关键。
David Sinclair:
大卫·辛克莱：
It turns out that it's largely been a failure, that giving animals and humans antioxidants hasn't had the longevity benefits that we dreamed of.
事实证明，这在很大程度上是失败的，给动物和人类提供抗氧化剂并没有带来我们梦想的长寿益处。
And the main reason is that there's a lot more going on than just free radical damage.
主要原因是，除了自由基损伤之外，还有更多的因素在发生。
The epigenome gets disrupted.
表观基因组被破坏。
We've got these proteins misfolding.
这些蛋白质发生了错误折叠。
David Sinclair:
大卫·辛克莱：
So the problem really has been that we didn't realize that you need to turn on the body's natural defenses against that plus a whole host of other things, to get the true benefits.
所以问题实际上是我们没有意识到你需要启动身体的自然防御能力以及其他许多东西才能获得真正的好处。
But I'm not going to say it's a problem taking an antioxidant drink.
但我不会说服用抗氧化饮料有问题。
Pomegranate juice for one, is full of good stuff including xenohormetic molecules.
其中之一的石榴汁富含包括异种激素分子在内的好东西。
David Sinclair:
大卫·辛克莱：
But resveratrol is a good case in point, which is, when I worked on resveratrol as a longevity molecule, first we showed it in yeast and worms and flies and mice.
但白藜芦醇是一个很好的例子，当我研究白藜芦醇作为一种长寿分子时，我们首先在酵母、蠕虫、苍蝇和小鼠中展示了它。
Before that, it was thought that resveratrol was good for your heart in red wine when you drank red wine because it's an antioxidant.
在此之前，人们认为喝红酒时，红酒中的白藜芦醇对心脏有益，因为它是一种抗氧化剂。
David Sinclair:
大卫·辛克莱：
So then we showed that it extended the lifespan of yeast cells through this genetic pathway, the sirtuins.
然后我们证明它通过这种遗传途径（sirtuins）延长了酵母细胞的寿命。
And we then tested whether resveratrol, if we changed one atom to make it not an antioxidant, guess what?
然后我们测试了白藜芦醇是否存在，如果我们改变一个原子使其不再是一种抗氧化剂，你猜怎么着？
It still worked fine.
它仍然工作得很好。
David Sinclair:
大卫·辛克莱：
So it wasn't its antioxidant activity that was extending lifespan, it was its ability to turn on the yeast's defenses against aging.
因此，延长寿命的并不是其抗氧化活性，而是其启动酵母抵御衰老的能力。
Conversely, when we gave the yeast antioxidants, they lived shorter.
相反，当我们给予酵母抗氧化剂时，它们的寿命会缩短。
So yeah, that was the beginning of my transformation into thinking, "Turn on the body's defenses.
是的，这就是我转变为思考的开始：“打开身体的防御系统。
Don't give it the antioxidants."
不要给它抗氧化剂。”
Andrew Huberman:
安德鲁·休伯曼：
This is an opportunity for me to say something I've been wanting to say for a long time, which is that what's so wonderful about science is that because the goal is mechanism, you can really start to understand, as you just described, what actually mediates a process is very different than what modulates a process.
这对我来说是一个机会，可以说出我长期以来一直想说的话，那就是科学的奇妙之处在于，因为目标是机制，所以你可以真正开始理解，正如你刚才所描述的，真正介导一个过程的东西与调节一个过程的东西非常不同。
Andrew Huberman:
安德鲁·休伯曼：
I mean, if a fire alarm goes off in the building right now, it's going to modulate our attention.
我的意思是，如果大楼里的火警警报现在响起，我们的注意力就会受到影响。
But that doesn't mean that it controls our attention.
但这并不意味着它控制了我们的注意力。
It's not mechanistically relevant.
这在机械上不相关。
And so I think this thing about antioxidants is one of these cases it sounds like where it's in the right ballpark, but until one really unveils the mechanism as you have, you can be...
所以我认为关于抗氧化剂的事情就是其中一种情况，听起来像是在正确的范围内，但直到有人真正揭开你所拥有的机制之前，你可以......
One can, or a field can be badly wrong for a very long period of time.
一个人或者一个领域可能会在很长一段时间内出现严重错误。
Andrew Huberman:
安德鲁·休伯曼：
It sounds like the sirtuins and really getting down to the guts of the machinery of what causes cells to age is really what it's about.
这听起来像sirtuins，真正深入了解导致细胞衰老的机制，这才是真正的意义所在。
Zooming way out, what are the behavioral tools that one can start to think about in terms of ways to modulate these, basically, the way that DNA is being expressed and functioning?
放远一点，人们可以开始考虑哪些行为工具来调节这些（基本上是 DNA 的表达和功能方式）？
Andrew Huberman:
安德鲁·休伯曼：
I've heard you talk before about hormesis of other sorts.
我以前听过你谈论过其他类型的毒物兴奋效应。
Cold exposure.
冷暴露。
We talked about fasting.
我们谈论了禁食。
We talked about exercise in broad terms, but what about any evidence, if it exists, as to whether or not aerobic training versus weight training?
我们从广义上讨论了锻炼，但是有任何证据（如果存在）可以证明有氧训练与重量训练之间的区别吗？
These sorts of things.
诸如此类的事情。
Andrew Huberman:
安德鲁·休伯曼：
In other words, what are the sorts of things that people can do to improve the sirtuin pathway?
换句话说，人们可以采取哪些措施来改善 Sirtuin 通路？
And I realized that there are caveats.
我意识到有一些警告。
We can't go directly from a behavior to sirtuins, but in the general theme, what can people do?
我们不能直接从行为转向sirtuins，但在总体主题中，人们能做什么？
What do you do?
你做什么？
David Sinclair:
大卫·辛克莱：
Right.
对。
Well, we know that that aerobic exercise in mice and rats raises their NAD levels and their levels of SIRT one of the genes goes up, two actually, number one and number three.
嗯，我们知道，小鼠和大鼠的有氧运动会提高其 NAD 水平，而 SIRT 水平会升高，其中一个基因会升高，实际上是两个，第一个和第三个基因都会升高。
David Sinclair:
大卫·辛克莱：
What we don't know yet is what type of exercise is optimal to get them to change.
我们还不知道什么类型的锻炼最适合让他们改变。
We will learn.
我们会学习的。
We're doing work.
我们正在做工作。
Now it's revealed that we're doing work with the military in the U.S. to try and understand that kind of thing.
现在有消息透露，我们正在与美国军方合作，试图了解这类事情。
David Sinclair:
大卫·辛克莱：
And I'll always tell you and the public when I don't know something.
当我不知道什么时，我总是会告诉你们和公众。
I'm not going to extrapolate, but what do I do?
我不打算推断，但我该怎么办？
I base my exercise on the scientific literature, which has shown that maintaining muscle mass is very important for a number of reasons.
我的锻炼基于科学文献，科学文献表明，出于多种原因，保持肌肉质量非常重要。
David Sinclair:
大卫·辛克莱：
The two main ones are, you want to maintain your hormone levels.
两个主要的问题是，您想要维持激素水平。
I'm an older male losing my testosterone and muscle mass over time.
我是一名老年男性，随着时间的推移，我的睾丸激素和肌肉质量正在丧失。
And by exercising, I will maintain that and have.
通过锻炼，我将保持这一点并拥有。
In fact, I probably haven't had a body like this since I was 20.
事实上，我大概从20岁起就没有过这样的身材了。
So that's one of the benefits of having this lifestyle.
这就是这种生活方式的好处之一。
Andrew Huberman:
安德鲁·休伯曼：
Sorry to interrupt.
抱歉打扰。
We did an episode on hormones and there are data in humans that show that there are some males in their 80s and 90s where their testosterone is equivalent to the average of 25- and 30-year-olds.
我们做了一期关于激素的节目，人类数据显示，一些 80 多岁和 90 多岁的男性，他们的睾酮水平相当于 25 岁和 30 岁的平均水平。
I can get you that information.
我可以给你这些信息。
It is really impressive studies.
这确实是令人印象深刻的研究。
Andrew Huberman:
安德鲁·休伯曼：
Unfortunately, they didn't include a lot of information about the lifestyle factors, etcetera, but this idea that testosterone goes down with age, it might be the trend but it's not necessarily a prerequisite.
不幸的是，他们没有包含很多有关生活方式因素等的信息，但睾丸激素随着年龄的增长而下降的想法可能是趋势，但不一定是先决条件。
David Sinclair:
大卫·辛克莱：
Right.
对。
I believe in naturally increasing and maintaining these hormone levels.
我相信自然地增加和维持这些激素水平。
And I've been measuring them for a long time and I could see for me, my testosterone levels steadily, levels were going down-
我已经测量它们很长一段时间了，我可以看到，我的睾丸激素水平稳步下降——
Andrew Huberman:
安德鲁·休伯曼：
And then you got tenure and they went back up again.
然后你获得了终身教职，他们的地位又恢复了。
David Sinclair:
大卫·辛克莱：
No. I actually became complacent and it was the worst, actually.
不，我实际上变得自满了，实际上这是最糟糕的。
My age changed in the wrong direction after that because I was relaxed.
从那以后我的年龄就朝着错误的方向变化了，因为我很放松。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
David Sinclair:
大卫·辛克莱：
And not worried about the future.
并且不担心未来。
But then I got serious and actually, according to the InsideTracker algorithm, got my age down from 58 to 31 in a matter of months.
但后来我认真起来，实际上，根据 InsideTracker 算法，我的年龄在几个月内从 58 岁降到了 31 岁。
That was a big drop.
那是一个很大的下降。
And I've been getting steadily younger over the last 10 years, according to that measurement, the blood test.
根据血液测试的测量结果，过去十年我一直在稳步年轻化。
Andrew Huberman:
安德鲁·休伯曼：
What about estrogen?
雌激素呢？
Because women are different in the sense that they do...
因为女性在某种程度上是不同的……
The number of eggs that they, and the ovaries change over time, right?
它们和卵巢的卵子数量会随着时间的推移而变化，对吗？
Do you think that they can maintain estrogen levels in, over longer periods of time using some of these same protocols?
您认为他们可以使用其中一些相同的方案在更长的时间内维持雌激素水平吗？
David Sinclair:
大卫·辛克莱：
Well.
好吧。
Yeah, I get into trouble from a certain university when I talk about this too much about.
是啊，如果我说太多的话，我就会被某所大学惹上麻烦。
Andrew Huberman:
安德鲁·休伯曼：
About estrogen?
关于雌激素？
David Sinclair:
大卫·辛克莱：
Just about fertility and...
只是关于生育能力和...
Long story.
很长的故事。
I don't want to get too much into the anecdotes, but I'll tell you the science, which is that if you take a mouse and put it on fasting or caloric restriction for, up until the point where it should be infertile — so that's about it — at a year of age, a mouse gets infertile.
我不想讲太多轶事，但我会告诉你科学，那就是，如果你拿一只老鼠禁食或限制热量，直到它应该不育的程度 - 就是这样 - 在一岁的时候，一只老鼠就会不育。
Female mouse-
母鼠-
Andrew Huberman:
安德鲁·休伯曼：
Due to fasting or due to simply to aging?
由于禁食还是仅仅由于衰老？
David Sinclair:
大卫·辛克莱：
No, due to aging.
不，是因为老化。
Due to aging.
由于老化。
The fasting, it's not extreme fast.
禁食，并不是极快。
It's just less calories.
只是卡路里较少。
Andrew Huberman:
安德鲁·休伯曼：
Got it.
明白了。
David Sinclair:
大卫·辛克莱：
Then you put them back on a regular food and they become fertile again for many, many months afterwards.
然后你让它们恢复正常的食物，它们会在很多很多个月后再次变得有生育能力。
So the effect on slowing down aging is also on the reproductive system.
所以延缓衰老的作用还在于生殖系统。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
David Sinclair:
大卫·辛克莱：
And so that...
所以...
I wouldn't say to any woman, I wouldn't think that they should become super skinny to try and preserve fertility.
我不会对任何女性说，我不认为她们应该变得超级瘦以试图保持生育能力。
That's not what I'm saying.
我不是这个意思。
But these pathways that we work on, these sirtuins, are known to delay infertility in female animals.
但我们研究的这些途径，即这些去乙酰化酶，已知可以延迟雌性动物的不孕。
David Sinclair:
大卫·辛克莱：
Case in point, I'm one of the lead authors on a paper where we used NMN.
举个例子，我是一篇使用 NMN 的论文的主要作者之一。
Remember, this is the gas, the fuel, the petrol for the sirtuins.
请记住，这是用于 Sirtuins 的气体、燃料、汽油。
We gave old mice...
我们给老老鼠...
One group of mice was 16 months old.
一组小鼠 16 个月大。
Remember, they came in fertile at 12.
请记住，他们 12 岁时就具有生育能力。
Gave them NMN, and I think it was only six weeks later, they had offspring.
给它们NMN，我想仅仅六周后，它们就有了后代。
David Sinclair:
大卫·辛克莱：
They became fertile again, which goes against biology, a textbook biology, which is that female mammals run out of eggs.
它们再次具有生育能力，这违背了生物学教科书上的观点：雌性哺乳动物没有卵子。
Turns out that's not true.
事实证明这不是真的。
You can rejuvenate the female reproductive system and even get them to come out of mouseopause, as we call it.
您可以使女性生殖系统恢复活力，甚至让它们摆脱我们所说的“小鼠更年期”。
So that's a whole new paradigm in biology as well.
所以这也是生物学的一个全新范式。
Andrew Huberman:
安德鲁·休伯曼：
That's super interesting.
这太有趣了。
Sorry to interrupt you, but I'm reminded by a set of studies that were done by your former colleagues cause they're no longer there.
很抱歉打扰您，但您的前同事所做的一系列研究提醒了我，因为他们已经不在了。
David Hubel and Torsten Wiesel, my scientific great-grandparents, won the Nobel Prize for discovering what are called critical periods.
我的科学曾祖父母大卫·休贝尔（David Hubel）和托斯顿·威塞尔（Torsten Wiesel）因发现所谓的关键期而获得诺贝尔奖。
This phase of early development when the brain is extremely plastic.
在早期发育的这个阶段，大脑的可塑性极强。
Andrew Huberman:
安德鲁·休伯曼：
And a big part of their work was to show that after a certain point, the critical period shuts down.
他们的工作的一个重要部分是表明，在某一点之后，关键期就会结束。
Essentially, the brain can't change or not nearly as much.
从本质上讲，大脑无法改变或几乎没有改变那么多。
And then people came along later and showed that you could open up these critical periods again, but very briefly and it takes a very specific stimulus, essentially.
后来人们出现并表明你可以再次打开这些关键时期，但非常短暂，并且本质上需要非常具体的刺激。
High degrees of focus, etcetera.
高度集中等等。
Andrew Huberman:
安德鲁·休伯曼：
However, there's a well-known phenomenon in this literature where if you take an animal, and to some degree this is being shown in humans as well, and you let them pass through the critical period, but then you essentially sensory deprive them.
然而，在这些文献中有一个众所周知的现象，如果你以一种动物为对象，并且在某种程度上这也表现在人类身上，你让它们度过了关键期，但你基本上剥夺了它们的感官。
You take away experience.
你带走了经验。
You close both eyes.
你闭上双眼。
You essentially reopen the critical period.
你基本上重新开启了关键时期。
So it seems like...
所以看起来...
Andrew Huberman:
安德鲁·休伯曼：
You essentially reopen the critical period.
你基本上重新开启了关键时期。
So it seems like, and I couldn't help but mention this, there's this parallel between what we're talking about here with fertility and neuroplasticity where yes, there's a timer where certain things are available to the organism early in life and then they tend to taper off.
所以，我忍不住要提到这一点，我们在这里讨论的生育力和神经可塑性之间存在这种相似之处，是的，有一个计时器，有机体在生命早期就可以使用某些东西，然后它们往往会逐渐减少。
It's not an open and shut, but they taper off.
这不是一个开放和关闭的过程，但它们会逐渐减弱。
But then a deprivation can actually reactivate the availability of that process.
但剥夺实际上可以重新激活该过程的可用性。
Forgive me, I just couldn't help but mention it, but to me, both of those things are associated with youth, fertility and neuroplasticity.
请原谅，我只是忍不住提一下，但对我来说，这两件事都与年轻、生育力和神经可塑性有关。
And so I think that it'd be so interesting, I'd love to collaborate with you on this, to explore how neuroplasticity might actually be regulated by these things like the sirtuins.
所以我认为这会很有趣，我很乐意与您合作，探索神经可塑性实际上如何受到这些东西（例如sirtuins）的调节。
David Sinclair:
大卫·辛克莱：
Right.
对。
And the sirtuins do control memory in neurons as well.
Sirtuins 确实也控制着神经元的记忆。
So what I think is really interesting is that what we are learning from work that you and your colleagues have done and in my lab as well, is that the body has remarkable powers of healing and recovering from illness and injury.
因此，我认为真正有趣的是，我们从您和您的同事以及我的实验室所做的工作中了解到，身体具有从疾病和伤害中治愈和恢复的非凡能力。
And what we once thought was a one-way street and you just can't repair, you can't get over these diseases, you can reset the system and the body can really get rejuvenated in ways that in the future, we'll wonder why didn't we work on this earlier?
我们曾经认为这是一条单行道，你无法修复，你无法克服这些疾病，你可以重置系统，身体可以真正以某种方式恢复活力，在未来，我们会想知道为什么我们不早点努力呢？
The future of humanity is more like us walking around like Deadpool.
人类的未来更像是我们像死侍一样四处走动。
We'll probably be cleaner and we won't smell as badly.
我们可能会变得更干净，而且气味也不会那么难闻。
But Deadpool, if you don't know, can get injured and just recover.
但如果你不知道的话，死侍可能会受伤并恢复。
It's very hard to injure this guy and we're going to be the same.
伤害这个家伙非常困难，我们也会一样。
There are many species you cut off the limb, the limb grows back.
有很多物种，你砍掉肢体，肢体又会长回来。
Andrew Huberman:
安德鲁·休伯曼：
Salamanders or ...
蝾螈或...
David Sinclair:
大卫·辛克莱：
Yeah.
是的。
We are now learning how to tap into that system and in part what we're doing is reversing the age of those cells and telling them how to read the genes correctly again, reversing the age of that epigenome.
我们现在正在学习如何利用该系统，我们正在做的部分工作是逆转这些细胞的年龄，并告诉它们如何再次正确读取基因，从而逆转表观基因组的年龄。
And we do that, the cells, the brain, for instance.
我们就是这样做的，例如细胞、大脑。
The skin.
皮肤。
We did the optic nerve.
我们做了视神经。
Andrew Huberman:
安德鲁·休伯曼：
Let's talk about those results for a second and then I want to make sure that we return to some of these behavioral protocols.
让我们先讨论一下这些结果，然后我想确保我们回到其中一些行为协议。
You had this amazing paper at the end of last year, cover article, full article in nature, showing that essentially a small menu of transcription factors, which control gene expression, etcetera, could essentially reverse the age of neurons in the eye and rescue those cells against damage.
去年年底，你发表了这篇令人惊叹的论文，封面文章，本质上的完整文章，表明本质上控制基因表达等的一小部分转录因子可以从根本上逆转眼睛神经元的年龄并拯救这些细胞免受损伤。
Essentially, allow blind mice to see again and offset degeneration of these retinal cells.
本质上，让失明的小鼠再次看见并抵消这些视网膜细胞的退化。
Incredible paper and such a boon to the field.
令人难以置信的论文，对这个领域来说是一个福音。
Where does that stand now in terms of human clinical trials?
就人体临床试验而言，现在的情况如何？
What are you envisioning in terms of the trajectory of those data from mice into human someday?
对于有一天这些数据从小鼠到人类的轨迹，您有何设想？
David Sinclair:
大卫·辛克莱：
Right.
对。
Well, to get to the point, immediately we're going to be testing the treatment on monkeys just for safety reasons.
好吧，言归正传，出于安全原因，我们将立即在猴子身上测试这种治疗方法。
And then the first patient should be done sometime in 2022, early 2023, and we're going to try to recover blindness.
然后第一个病人应该在 2022 年的某个时候、2023 年初完成手术，我们将尝试恢复失明。
Andrew Huberman:
安德鲁·休伯曼：
This involves making an injection of a virus into the eye?
这涉及将病毒注射到眼睛中？
Right now, there's no way that I am aware of to manipulate these transcription factors through a pill or some other-
目前，据我所知，还没有办法通过药物或其他方式来操纵这些转录因子——
David Sinclair:
大卫·辛克莱：
That's what we're working on in my lab at Harvard right now.
这就是我们现在在哈佛大学的实验室所做的工作。
So it will be-
所以会是——
Andrew Huberman:
安德鲁·休伯曼：
transcription-
转录-
David Sinclair:
大卫·辛克莱：
Well, yeah.
嗯，是的。
Pop a pill and the whole body gets rejuvenated by 20 years.
吃一颗药，整个身体就年轻了20岁。
That's what we're aiming for.
这就是我们的目标。
Now, we do it with gene therapy in the eye and other places.
现在，我们通过眼睛和其他部位的基因疗法来实现这一目标。
So in the eye, yes, it's single injection.
所以在眼睛上，是的，它是单次注射。
The genes go into the retina and we can turn it on with the drug called doxycycline.
这些基因进入视网膜，我们可以用强力霉素将其打开。
And we do that in the mice for four to eight weeks.
我们在小鼠身上进行了四到八周的实验。
The eye gets younger, we can measure that, so you can measure the clock.
眼睛变得更年轻，我们可以测量它，所以你可以测量时钟。
And then the vision comes back in those mice.
然后这些老鼠的视力又恢复了。
And I don't see any reason why it shouldn't work in people, because it's the same structures and mechanisms that are on in the human as well.
我不认为它有任何理由不适用于人类，因为它的结构和机制与人类相同。
Now these-
现在这些——
Andrew Huberman:
安德鲁·休伯曼：
And it's one injection.
而且是一针注射。
David Sinclair:
大卫·辛克莱：
It's one.
是一个。
Andrew Huberman:
安德鲁·休伯曼：
I should mention injections into the eye, obviously nobody should do this outside of an ophthalmology clinic, and they're definitely by an ophthalmologist.
我应该提到眼睛注射，显然没有人应该在眼科诊所之外进行这种注射，而且肯定是由眼科医生进行的。
But the injections into the eye are painless if done correctly by the right person.
但如果由正确的人正确完成，向眼睛注射是无痛的。
It sounds dreadful, but it's actually, I've seen it done hundreds of times.
这听起来很可怕，但实际上，我已经看过数百次了。
I've done it thousands of times.
我已经做过数千次了。
And it's not to myself, but to other creatures.
而且这不是针对我自己，而是针对其他生物。
And there's a way of doing this.
有一种方法可以做到这一点。
It's completely painless to the person.
这对人来说是完全无痛的。
David Sinclair:
大卫·辛克莱：
Oh, you don't feel it.
哦，你感觉不到。
It's a tiny needle too.
这也是一根小针。
But the great thing about this is that it's a one-time treatment.
但这的伟大之处在于它是一次性治疗。
Those genes go into the back of the eye and stay there forever and you can just turn them on whenever you want.
这些基因进入眼睛后部并永远留在那里，你可以随时打开它们。
So what we've found is you can turn them on in the mice, they get their vision back and then you turn it off again.
所以我们发现你可以在老鼠身上打开它们，它们恢复视力，然后你再次将其关闭。
And so far, many months out, the benefit has remained.
到目前为止，几个月过去了，这种好处仍然存在。
But if it does decline, we'll just turn it back on and reset the system, rinse and repeat.
但如果它确实下降，我们只需重新打开它并重置系统，冲洗并重复。
So one day, what's exciting is that we could potentially do this across the entire body and just take this antibiotic every five years and go back time and time again.
因此，有一天，令人兴奋的是，我们有可能在整个身体上做到这一点，只需每五年服用一次这种抗生素，然后一次又一次地服用。
Andrew Huberman:
安德鲁·休伯曼：
In thinking about the body and what's going on under the hood, I'm amazed still that there isn't a simple, affordable technology that would allow me to just look into my body and see whether or not there are any tumors growing anywhere.
在思考身体和幕后发生的事情时，我仍然感到惊讶，没有一种简单、负担得起的技术可以让我检查我的身体，看看是否有肿瘤在任何地方生长。
It's not that hard to look into the body.
观察身体并不难。
The technology exists.
这项技术是存在的。
Why hasn't anybody created an at-home or pseudo at-home solution like a clinic where you can go and pay 50 bucks or a hundred bucks and see if you have any tumors growing in your body?
为什么没有人创建一个家庭或伪家庭解决方案，例如诊所，您可以花 50 美元或 100 美元去诊所看看您体内是否有肿瘤生长？
David Sinclair:
大卫·辛克莱：
Yeah, it's still expensive.
是的，还是很贵。
You can get your doctor to try to get you in.
您可以让您的医生尝试让您进入。
There are some companies that offer blood tests that look at circulating DNA that'll measure it.
有些公司提供血液检测，检查循环 DNA 并对其进行测量。
We're getting there.
我们快到了。
We're still probably five to 10 years away from being really cheap.
我们距离真正便宜可能还需要五到十年的时间。
You can do things like a colon cancer test at home.
您可以在家做结肠癌检查等事情。
I think it's a hundred-something dollars.
我认为是一百多美元。
You ship off your shit, excuse my language, and they measure it.
你把你的狗屎运出去，请原谅我的语言，然后他们会衡量它。
And they tell you if you've got colon cancer with high probability.
他们会告诉您是否很有可能患有结肠癌。
I did that during the pandemic because I didn't want to get a colonoscopy.
我在大流行期间这样做是因为我不想接受结肠镜检查。
Andrew Huberman:
安德鲁·休伯曼：
Is it more accurate or as accurate as a colonoscopy?
它比结肠镜检查更准确还是一样准确？
David Sinclair:
大卫·辛克莱：
I believe it's close to being as accurate.
我相信它接近准确。
The downside is that during a colonoscopy, they can pinch off the polyps that are looking dangerous, whereas this obviously isn't that.
缺点是，在结肠镜检查期间，他们可以夹掉看起来很危险的息肉，而这显然不是那样。
But it's certainly easier to do.
但这确实更容易做到。
And my father, who's Australian, tells me that it's free for Australians.
我的澳大利亚父亲告诉我，这对澳大利亚人来说是免费的。
They get this test routinely.
他们定期进行这项测试。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
I want to return to the topic that I took us away from, so I apologize, which is behavioral protocols.
我想回到刚才让我们离开的话题，所以我很抱歉，这是行为协议。
Do you regularly do the cold-shower thing, ice baths, cold-water swims?
你经常洗冷水澡、冰浴、冷水游泳吗？
Are you into that whole biz?
你对整个行业感兴趣吗？
David Sinclair:
大卫·辛克莱：
Well, you do know that I've done it at least once, because we did it together.
嗯，你确实知道我至少做过一次，因为我们一起做过。
Andrew Huberman:
安德鲁·休伯曼：
That's right.
没错。
Not the same bath, just to be very clear.
不是同一个浴缸，只是要非常清楚。
Same sauna, different ice baths.
同样的桑拿，不同的冰浴。
The idea of Sinclair and Huberman taking an ice bath together is ...
辛克莱和胡伯曼一起洗冰浴的想法是……
It might warm some people's hearts, but just to be very clear, same ice bath, different times.
这可能会温暖一些人的心，但要非常明确的是，同样的冰浴，不同的时间。
David Sinclair:
大卫·辛克莱：
Yeah.
是的。
Thank you for clarifying.
谢谢你的澄清。
I don't do them regularly.
我不经常这样做。
I do try to sleep cool.
我确实尝试睡个好觉。
I sleep better anyway.
无论如何我睡得更好。
I try to dress without a lot of warm clothes.
我尽量穿不穿太多保暖衣服的衣服。
I'm here in a t-shirt and it's middle of summer, but in winter I'll try to wear a t-shirt too.
我穿着 T 恤来到这里，现在是仲夏，但冬天我也会尝试穿 T 恤。
Andrew Huberman:
安德鲁·休伯曼：
So you're challenging your system to thermal regulate?
那么您正在挑战您的系统的热调节能力吗？
David Sinclair:
大卫·辛克莱：
Right.
对。
I've got this hypothesis with Ray Cronise.
我和雷·克罗尼斯（Ray Cronise）得到了这个假设。
We published what's called the metabolic winter hypothesis, which is tens of thousands of years ago, we were either hungry or cold or both, and we rarely experience that now.
我们发表了所谓的新陈代谢冬季假说，即几万年前，我们要么饥饿，要么寒冷，要么两者兼而有之，而现在我们很少经历这种情况。
And so we try to give ourselves the metabolic winter.
所以我们试图给自己一个新陈代谢的冬天。
And part of the problem I think with the obesity epidemic is that we're never cold.
我认为肥胖流行的部分问题在于我们从来不冷。
And cold, when you're cold you have to burn energy.
而且冷，当你冷的时候你必须燃烧能量。
It may be only slightly.
可能只是轻微的。
But over the whole night, if you're a little bit cool, you'll actually expend more energy, so I try to do that.
但整个晚上，如果你冷静一点，你实际上会消耗更多的能量，所以我尝试这样做。
But I'm not a big fan of cold showers.
但我不太喜欢洗冷水澡。
The sauna, I don't have access to my gym as much as I did.
桑拿房，我不像以前那样经常去健身房。
But I do want to get back into it.
但我确实想重新投入其中。
I used to do it regularly with my son and I posted on Instagram once that he could stay in there for 15 minutes and I could only stay in for about three.
我以前经常和我儿子一起这样做，有一次我在 Instagram 上发帖说他可以在那里待 15 分钟，而我只能在那里呆大约 3 分钟。
Anyway, long story short, I try to compensate with changes in my diet and exercise until I get back into it.
不管怎样，长话短说，我尝试通过饮食和锻炼的改变来弥补，直到我重新开始。
Andrew Huberman:
安德鲁·休伯曼：
You reminded me of something that I meant to ask earlier, that obesity reduces NAD levels and accelerates aging.
你让我想起了我之前想问的一件事，肥胖会降低 NAD 水平并加速衰老。
How?
如何？
Okay, so again, this is the scientist in us.
好吧，再说一遍，这就是我们的科学家。
So someone's carrying a lot of excess adipose tissues, subcutaneous and visceral fat.
所以某人携带了大量多余的脂肪组织、皮下脂肪和内脏脂肪。
But why should that reduce NAD in any ways that are independent of effects on glucose and insulin?
但为什么会以任何独立于葡萄糖和胰岛素影响的方式减少 NAD 呢？
Is there something direct about white adipose tissue?
白色脂肪组织有直接关系吗？
And the reason I ask this is not simply to dig into mechanism alone, but I think there are really interesting data now that fat actually gets neural innervation.
我问这个问题的原因不仅仅是为了深入研究机制，而且我认为现在有非常有趣的数据表明脂肪实际上得到了神经支配。
It's not just a stored fuel.
它不仅仅是储存燃料。
It's stored fuel that's acting as an endocrine organ essentially.
它是储存的燃料，本质上充当内分泌器官。
So yeah, why would being fat make people age faster?
那么，为什么肥胖会让人衰老得更快呢？
David Sinclair:
大卫·辛克莱：
Yeah, that's a question that is so obvious, but so few people ask it.
是的，这是一个很明显的问题，但很少有人问。
That's what makes you a good scientist.
这就是让你成为一名优秀科学家的原因。
And so that, we don't know, but I'll give you my best answer, which is that obesity comes along with a lot of problems that include a lot of senescent cells in fat.
因此，我们不知道，但我会给你最好的答案，那就是肥胖会带来很多问题，其中包括脂肪中存在大量衰老细胞。
If you stain old fat for senescent cells, it lights up.
如果你对衰老细胞的旧脂肪进行染色，它就会发光。
And when you kill off those cells, at least in mice and maybe in humans, it looks like, the fat is less toxic to the body, because those senescent cells in the fat are secreting these inflammatory molecules that will accelerate aging as we now know.
当你杀死这些细胞时，至少在小鼠中，也许在人类中，脂肪看起来对身体的毒性较小，因为脂肪中的那些衰老细胞正在分泌这些炎症分子，正如我们现在所知，这些炎症分子会加速衰老。
David Sinclair:
大卫·辛克莱：
You talk about the sirtuins and NAD.
你谈到了 Sirtuins 和 NAD。
So if we just look philosophically at why this would be, the sirtuins only like to come on or get activated when the body needs, is under adversity.
因此，如果我们从哲学上看为什么会这样，sirtuins只喜欢在身体需要、处于逆境时出现或被激活。
And if a cell is surrounded by fat or contains a lot of fat, it's going to think times are good, doesn't need to switch on, so that's the evolutionary argument.
如果一个细胞被脂肪包围或含有大量脂肪，它就会认为时机成熟，不需要开启，这就是进化论。
Mechanistically, we don't know, but it could have something to do with the response to glucose, which then responds to the sirtuin gene.
从机制上讲，我们不知道，但它可能与对葡萄糖的反应有关，然后葡萄糖对去乙酰化酶基因做出反应。
But that hasn't been worked out very well.
但这还没有得到很好的解决。
Andrew Huberman:
安德鲁·休伯曼：
And is there any evidence that leptin, this hormone from fat, can actually interact with the sirtuin pathway?
是否有任何证据表明瘦素（这种来自脂肪的激素）实际上可以与沉默调节蛋白途径相互作用？
David Sinclair:
大卫·辛克莱：
I don't recall seeing that.
我不记得见过那个。
Andrew Huberman:
安德鲁·休伯曼：
Maybe I could do a sabbatical in your lab and that'd be a fun one.
也许我可以在你的实验室休假，那会很有趣。
David Sinclair:
大卫·辛克莱：
Definitely.
绝对是。
Andrew Huberman:
安德鲁·休伯曼：
Because leptin during development is what triggers the permission for the hypothalamus to enter puberty.
因为发育过程中的瘦素会触发下丘脑进入青春期的许可。
This is why kids that eat a lot when they're young and get overweight will also start to go and undergo puberty more quickly, although they have reproductive issues later.
这就是为什么年轻时吃得很多并且体重超标的孩子也会更快地进入青春期，尽管他们后来会出现生殖问题。
David Sinclair:
大卫·辛克莱：
Well yeah, we should study the hypothalamus together because the hypothalamus can control the aging of the body.
嗯，是的，我们应该一起研究下丘脑，因为下丘脑可以控制身体的衰老。
Andrew Huberman:
安德鲁·休伯曼：
The most interesting part of the brain.
大脑中最有趣的部分。
David Sinclair:
大卫·辛克莱：
For sure.
当然。
Andrew Huberman:
安德鲁·休伯曼：
Absolutely.
绝对的。
David Sinclair:
大卫·辛克莱：
If you turn on the one gene, the sirtuin gene that we work on in the hypothalamus, that actually will extend lifespan.
如果你打开一个基因，即我们在下丘脑中研究的沉默调节蛋白基因，实际上会延长寿命。
Also, it's been shown by Dongsheng Cai at Albert Einstein College of Medicine that if you inhibit inflammation in the hypothalamus in a mouse, it will increase or maintain the expression of what's called GnRH, which is the hormone that he found actually controls longevity in the mouse in part.
此外，阿尔伯特·爱因斯坦医学院的蔡东升还表明，如果抑制小鼠下丘脑的炎症，就会增加或维持促性腺激素释放激素（GnRH）的表达，他发现这种激素实际上在一定程度上控制小鼠的寿命。
And so keeping inflammation down in the hypothalamus is sufficient to extend the lifespan of animals.
因此，抑制下丘脑的炎症足以延长动物的寿命。
And I reviewed that paper for nature about seven years ago and that was the first demonstration that the hypothalamus is one of the leading regulators of the body's age.
大约七年前，我审阅了《自然》杂志上的那篇论文，这是第一次证明下丘脑是身体年龄的主要调节者之一。
Andrew Huberman:
安德鲁·休伯曼：
I find this fascinating.
我觉得这很有趣。
GnRH, for those of you that don't know, actually comes from neurons in the hypothalamus that then literally reach down into the pituitary and trigger the release of all the things that control fertility, luteinizing hormone, follicle-stimulating hormone, etcetera.
GnRH，对于那些不知道的人来说，实际上来自下丘脑的神经元，然后真正到达垂体并触发所有控制生育能力的物质的释放，如黄体生成素、卵泡刺激素等。
It's such a powerful set of neurons.
这是一组非常强大的神经元。
And it's never really been clear what, at a behavioral level, triggers the release of GnRH.
在行为层面上，什么触发了 GnRH 的释放，目前还不清楚。
There're all the stories about pheromones and timers and puberty, etcetera.
有所有关于信息素、计时器和青春期等等的故事。
But environmental conditions and dietary conditions and behaviors that can control GnRH release, I think, is an incredible area for exploration.
但我认为，可以控制 GnRH 释放的环境条件、饮食条件和行为是一个令人难以置信的探索领域。
I'd love to do that sabbatical by the way.
顺便说一句，我很想休假。
I have a couple seemingly random questions, but I can't help but ask because one thing I like to do is forage the internet for practices that at least more than a few people are doing and then wonder whether or not there's any basis for it.
我有几个看似随机的问题，但我忍不住要问，因为我喜欢做的一件事就是在互联网上寻找至少有不少人正在做的做法，然后想知道它是否有任何基础。
Andrew Huberman:
安德鲁·休伯曼：
You mentioned methylation as a detrimental process, the way it disrupts the epigenome and the CD reader, so to speak.
你提到甲基化是一个有害的过程，可以这么说，它会破坏表观基因组和 CD 读取器。
There are people out there who are ingesting methylene blue.
有些人正在摄入亚甲蓝。
And when I was a kid, I used methylene blue to clean my fish tank.
当我还是个孩子的时候，我用亚甲蓝来清洁我的鱼缸。
And I love fish tanks.
我喜欢鱼缸。
I know you're into aquaria also.
我知道你也喜欢水族馆。
A different podcast episode, talk about aquaria.
另一个播客节目，谈论水族馆。
But why in the world would people ingest methylene blue?
但为什么人们会摄入亚甲蓝呢？
Meaning, is their logic correct and or is that a dangerous practice?
意思是，他们的逻辑正确吗？或者这是一种危险的做法吗？
I'm not sure I'd want to ingest methylene blue.
我不确定我是否想摄入亚甲蓝。
Sounds like a bad thing to do.
听起来像是一件坏事。
David Sinclair:
大卫·辛克莱：
It stains your body.
它会弄脏你的身体。
You've seen these people can turn blue.
你已经看到这些人会变蓝。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Someone in my lab as a postdoc was using it to study a completely different process related to the blood brain barrier and used to inject into animals and they would turn blue.
我实验室里的一个博士后正在用它来研究与血脑屏障相关的完全不同的过程，并用它注射到动物体内，它们会变成蓝色。
But then again, people ingest colloid silver.
但话又说回来，人们摄入的是胶体银。
There's this ...
有这个...
Please people don't do this or if you do, don't tell me because I won't like it.
请人们不要这样做，或者如果你这样做了，请不要告诉我，因为我不会喜欢它。
People put it in their eyes and some people actually stain their skin.
人们把它放在眼睛里，有些人甚至弄脏了他们的皮肤。
They actually become this silver, purple brown color if they do it excessively.
如果做得过度，它们实际上会变成银色、紫棕色。
There's a lot of crazy stuff out there.
那里有很多疯狂的东西。
But what do you think they're thinking with this methylene blue thing or should we just get them to a good psychiatrist?
但你认为他们对亚甲基蓝的事情有什么想法，还是我们应该把他们带到一位好的精神科医生那里？
David Sinclair:
大卫·辛克莱：
I don't know for sure.
我不确定。
I think methylene blue was found to extend the lifespan of some lower organism and that's where it came from.
我认为亚甲蓝被发现可以延长某些低等生物的寿命，这就是它的来源。
My recollection-
我的回忆——
Andrew Huberman:
安德鲁·休伯曼：
With the emphasis on lower organisms.
重点是低等生物。
David Sinclair:
大卫·辛克莱：
Yes.
是的。
Smaller organisms.
较小的生物体。
I think ...
我认为...
Do you remember, Andrew?
你还记得吗，安德鲁？
Does it interrupt or interfere with mitochondrial activity?
它会中断或干扰线粒体活动吗？
And that's-
那就是——
Andrew Huberman:
安德鲁·休伯曼：
Maybe that's why they're doing it.
也许这就是他们这样做的原因。
David Sinclair:
大卫·辛克莱：
Yeah, we need to look this up and post it.
是的，我们需要查找并发布它。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
David Sinclair:
大卫·辛克莱：
We'll get to the bottom of this.
我们会追查到底。
But those methyls, let's talk about those.
但是那些甲基，我们来谈谈那些。
Those methyls have to be placed on the right part of the genome.
这些甲基必须放置在基因组的正确部分。
They get attached to the right genes and the wrong genes.
它们会依附于正确的基因和错误的基因。
And if you have a lot of methylation, it's going to mess up the epigenome.
如果有大量甲基化，就会扰乱表观基因组。
Smoking will do that.
抽烟就会有这样的效果。
Lack of exercise, all that good stuff.
缺乏锻炼，都是好事。
So what you actually want to do is you want to measure it and make sure what you are doing with your body is working.
所以你真正想做的是测量它并确保你对身体所做的事情有效。
How do you know that if you do this or that is actually helping?
你怎么知道你这样做或那样做确实有帮助？
And so you can test your age.
这样你就可以测试你的年龄了。
David Sinclair:
大卫·辛克莱：
I could take a swab from your mouth and tell you how old you are biologically.
我可以从你嘴里取出一根棉签，告诉你你的生物学年龄。
And then we could work on trying to bring that down.
然后我们就可以努力降低这种情况。
And actually there are anecdotes now that people are reversing their age by a decade or more, just by doing some of the things that we've talked about and some other cutting edge stuff that I'm going to write about.
实际上，现在有一些轶事表明，人们只需做一些我们已经讨论过的事情以及我将要写的其他一些前沿的事情，就可以将年龄逆转十年或更长时间。
But you have to measure stuff.
但你必须衡量一些东西。
I didn't want to forget to bring that up.
我不想忘记提起这一点。
I'm measuring stuff all the time.
我一直在测量东西。
I have blood tests like you; I've got this monitor that's stuck to my chest right now that's measuring myself a thousand times a second, and I measure my biological age.
我和你一样也做了血液检查；我现在把这个监视器贴在我的胸口，它每秒测量我自己一千次，我测量我的生物年龄。
Andrew Huberman:
安德鲁·休伯曼：
What's it measuring a thousand times a second?
它每秒测量一千次是什么？
A huge host of things?
一大堆东西？
David Sinclair:
大卫·辛克莱：
Yeah, so this little device is stuck here and it's for two weeks.
是的，所以这个小设备被困在这里已经两周了。
You just recharge it or send it back and get a new one.
您只需为其充电或将其寄回并获得一个新的。
It's got body temperature movement, heartrate variability.
它有体温运动、心率变异性。
It's an FDA-approved device.
这是 FDA 批准的设备。
It's not a toy.
这不是一个玩具。
It's not one of these recreational things.
这不是这些娱乐活动之一。
It also listens to my voice.
它还会听我的声音。
Eventually it will tell me if I need a psychiatrist or if I'm depressed.
最终它会告诉我是否需要精神科医生或者我是否患有抑郁症。
It will tell me how I sleep, obviously.
显然，它会告诉我我的睡眠情况。
But when you put all that data together and it's individualized and anonymized, it can now tell my doctor in real time if I've got a cold that needs an antibiotic or it's just a virus, if I am suffering from COVID-19, or even if I'm going to have a heart attack next week.
但是，当你将所有这些数据放在一起并且进行个性化和匿名化时，它现在可以实时告诉我的医生我是否得了需要抗生素的感冒，或者只是病毒，我是否患有 COVID-19，甚至我下周是否会心脏病发作。
And so these little devices are going to be with us all the time instead of going to your doctor once a year, which is ludicrous.
因此，这些小设备将一直伴随着我们，而不是每年去看一次医生，这是可笑的。
Andrew Huberman:
安德鲁·休伯曼：
I have to ask you about x-rays because every time I go through the scanner at the airport, I think Sinclair would never do this.
我必须向你询问有关 X 光检查的问题，因为每次我在机场通过扫描仪时，我认为辛克莱永远不会这样做。
And the argument I heard you give about this before was a really excellent one, which is that it's a low level amount of radiation going through at the airport.
我之前听到你对此提出的论点非常出色，那就是机场中的辐射量很低。
But the argument is always, well it's just as much as on the plane.
但争论始终是，嗯，就像在飞机上一样。
And your counter argument I should say was ,well then why would I want to do both?
我应该说你的反驳观点是，那么我为什么要两者都做呢？
So when you go to the airport, assuming you're not running late and you have to go through the standard line, what do you say to them and do you say, "I'm David Sinclair," and then they shuttle you to your own line.
因此，当你去机场时，假设你没有迟到并且必须走标准线路，你会对他们说什么，你会说“我是大卫·辛克莱”，然后他们会把你送到你自己的线路。
What do you say?
你怎么说？
You do say, "I don't like this thing"?
你确实会说“我不喜欢这个东西”？
Do you have to give them a reason?
你需要给他们一个理由吗？
David Sinclair:
大卫·辛克莱：
No, you don't.
不，你不知道。
You can say I don't want this and they'll get annoyed because it's hard for them to pat you down.
你可以说我不想要这个，他们会生气，因为他们很难拍到你。
But you get a pat down and you're done.
但你拍拍一下就完成了。
As long as you're not in a hurry, it's fine.
只要你不着急，就没有问题。
If you want to pay for the TSA pre in America or the way to get around those scanners, you can do that.
如果您想在美国支付 TSA pre 费用或绕过这些扫描仪的费用，您可以这样做。
So I travel a lot, so it's worth it anyway.
所以我经常旅行，所以无论如何都是值得的。
But I just go through the metal detector.
但我只是通过金属探测器。
I don't get scanned.
我没有被扫描。
Andrew Huberman:
安德鲁·休伯曼：
And the metal detector doesn't have the same problem.
而金属探测器则不存在同样的问题。
And what about x-rays at the dentist?
去看牙医时的 X 光检查又如何呢？
David Sinclair:
大卫·辛克莱：
Yeah, well one x-ray's not going to kill you.
是的，一张 X 光检查不会杀死你。
Two's not going to kill you.
二人不会杀你。
But I'd rather-
但我宁愿——
Andrew Huberman:
安德鲁·休伯曼：
Three will kill you.
三个人会杀了你。
No, I'm just kidding.
不，我只是开玩笑。
David Sinclair:
大卫·辛克莱：
I try to limit it because it's cumulative.
我尝试限制它，因为它是累积的。
And I went for six years without having a dental x-ray.
我已经六年没有做过牙科X光检查了。
And then my last visit, I just gave up.
然后我最后一次访问，我就放弃了。
I was tired of arguing with my dentist, so they gave me one.
我厌倦了与牙医争论，所以他们给了我一个。
But they've got lead coats on and they put lead over your body.
但他们穿上了铅衣，他们把铅放在你的身上。
That's telling you something right there.
这就是告诉你一些事情。
And funnily enough, my teeth hadn't changed.
有趣的是，我的牙齿没有改变。
Now you could balance that by saying, well one x-ray, two x-rays, three x-rays is worth it if I have cavities.
现在你可以平衡一下，如果我有蛀牙，那么一次 X 光检查、两次 X 光检查、三张 X 光检查是值得的。
And that's true, you want to know what's in there.
确实如此，您想知道里面有什么。
But doing it regularly, for me, I don't think was worth it because my teeth are in perfect health and have always been.
但对我来说，定期这样做并不值得，因为我的牙齿一直都很健康。
Don't have any cavities.
不要有任何空洞。
Didn't have braces.
没有带牙套。
They're fine, so stop scanning me.
他们很好，所以别再扫描我了。
I know you have to pay for the machine, but do I have a choice?
我知道你必须支付机器费用，但我有选择吗？
Yes, so stop pressuring me.
是的，所以别再给我压力了。
Andrew Huberman:
安德鲁·休伯曼：
Who shared your sentiments about x-rays and the dentist in general, my apologies to the dentists out there, was the great physicist Richard Feynman.
伟大的物理学家理查德·费曼（Richard Feynman）与您分享了对 X 射线和牙医的看法，我向那里的牙医表示歉意。
This is a story about him that's not especially well known, but he had very serious concerns, health concerns, about x-rays because he understood the physics and he understood enough biology that he was actually quite vocal about his dislike of dental technology and its dangers.
这是一个关于他的故事，虽然不太为人所知，但他对 X 射线有非常严重的担忧，健康问题，因为他了解物理学，也了解足够的生物学，以至于他实际上非常直言不讳地表达了他对牙科技术及其危险的厌恶。
And he talked about some of that, and people can find that on the internet if they like.
他谈到了其中的一些内容，如果人们愿意的话，可以在互联网上找到这些内容。
Speaking of people who are like Feynman who've been engaged in public discourse about science, one of the things that I appreciate about you, in fact the way that you and I initially came to know one another, is through your public health education efforts.
说到像费曼这样从事科学公共讨论的人，我欣赏你的一件事，事实上，你和我最初相互认识的方式，就是通过你的公共卫生教育努力。
So obviously we're doing this podcast.
显然我们正在做这个播客。
You've done the Joe Rogan podcast, Lex Fridman podcast, many other podcasts.
您已经完成了 Joe Rogan 播客、Lex Fridman 播客以及许多其他播客。
You've written an amazing book.
你写了一本很棒的书。
Andrew Huberman:
安德鲁·休伯曼：
What are you thinking these days in terms of what the world needs in terms of education from scientists, education from MDs, education in general, as it relates to these things?
如今，您对世界对科学家教育、医学博士教育以及与这些事物相关的一般教育的需求有何看法？
Because I think if nothing else, 2020 revealed to us that there's a gap.
因为我认为，如果不出意外的话，2020 年就向我们揭示了差距。
There's a gap in understanding and that the scientists too are guilty of not knowing what to do with all the information that's out there on PubMed or elsewhere.
理解上存在差距，科学家们也因不知道如何处理 PubMed 或其他地方的所有信息而感到内疚。
Just what are you thinking for yourself, and in general, I'd like to just know what do you think the world needs there?
您自己在想什么？总的来说，我想知道您认为世界需要什么？
Maybe we can recruit some more public educators.
也许我们可以招募更多的公共教育工作者。
David Sinclair:
大卫·辛克莱：
Yeah.
是的。
Well, we've gone from a time when you and I were in college and young professors, where the only way to get our voice out to the public was either through a newspaper or a very short radio interview, which for me was extremely frustrating, because, particularly, the newspapers and my topic every time was twisted into something that was not just embarrassing.
好吧，我们已经离开了你我在大学和年轻教授的时代，那时向公众表达我们的声音的唯一方法是通过报纸或非常短的广播采访，这对我来说非常令人沮丧，因为，特别是，报纸和我的话题每次都被扭曲成不仅仅是令人尴尬的东西。
But Harvard University used to bring me into the back office and say-
但哈佛大学过去常常带我到后台办公室并说——
Andrew Huberman:
安德鲁·休伯曼：
Frankenstein!
弗兰肯斯坦！
David Sinclair:
大卫·辛克莱：
"How did you say such a thing?
“你怎么说出这样的话？
'We're all going to live to a hundred.'" I didn't say that.
‘我们都会活到一百岁。’”我没有这么说。
So we are now also in a world where we're overwhelmed with information and most of it is wrong and anyone can pretend to be an expert.
因此，我们现在也处于一个信息泛滥的世界，其中大部分都是错误的，任何人都可以冒充专家。
So we've gone from early days to now, the future, and we're experiencing it right now, thanks to guys, people like you, is that the experts, some experts, a small number who are brilliant and good communicators, are talking directly to the public.
所以我们已经从早期到现在，未来，我们现在正在经历它，感谢像你们这样的人，是专家，一些专家，一小部分才华横溢、善于沟通的人，正在直接与公众交谈。
David Sinclair:
大卫·辛克莱：
This has never been able to be possible until this time right now.
直到现在，这都是不可能的。
So another five years from now and certainly by 10 years, I would hope that there are trusted sources of information, of people who cannot just communicate the ideas directly, but are able to talk about things that are going on that aren't even published yet, to say, "Here's what's really going on and this is what the future looks like." But this is somebody like yourself who's spent their whole life studying a particular topic and knows what they're talking about.
因此，再过五年，当然是十年后，我希望有值得信赖的信息来源，人们不能直接传达想法，但能够谈论正在发生的事情，甚至尚未发表，说，“这就是真正发生的事情，这就是未来的样子。”但这是像你一样一生都在研究某个特定主题并且知道他们在谈论什么的人。
And this is also something that I think most people don't know: That we scientists, if we tell a lie, we burst into flames.
这也是我认为大多数人不知道的事情：我们科学家，如果我们说谎，我们就会起火。
We absolutely cannot tell something that's untrue.
我们绝对不能说不真实的事情。
And to the best of our knowledge, we say it as it is, because if we don't, we're beaten up or we kicked out of the university.
据我们所知，我们照原样说，因为如果我们不这样做，我们就会被殴打或被赶出大学。
So the people who survived to our age, and I'm a little older than you, so I've survived a bit longer-
所以活到我们这个年纪的人，我比你们大一点，所以我活得更久一点——
Andrew Huberman:
安德鲁·休伯曼：
But a lot younger inside.
但内心却年轻了许多。
David Sinclair:
大卫·辛克莱：
No, but we have to measure you with my swab test.
不，但我们必须用我的拭子测试来测量你的情况。
Andrew Huberman:
安德鲁·休伯曼：
I probably need a little help.
我可能需要一点帮助。
Hopefully not too much.
希望不要太多。
David Sinclair:
大卫·辛克莱：
We'll measure that and we'll work on your eating.
我们会衡量这一点，并会改善您的饮食。
But this is really important, is that finally people like you are allowed by our universities to talk to the public.
但这真的很重要，最终像你这样的人被我们的大学允许与公众交谈。
I used to do it with a real threat to my survival.
我以前这样做确实对我的生存构成威胁。
People would look at me.
人们会看着我。
"Oh he's a salesman, he's promoting this and that." It was seen as a real negative.
“哦，他是一名推销员，他在推销这个那个。”这被视为真正的负面影响。
But finally, I think we're in a world where it's not negative anymore.
但最后，我认为我们所处的世界不再是消极的。
And the pandemic showed that we need voices of reason and voices of fact that you could trust.
此次疫情表明，我们需要值得信赖的理性声音和事实声音。
And you can see the popularity of your podcast shows that the public, they're desperate for facts that they can trust because they don't know what to believe anymore.
你可以看到你的播客的受欢迎程度表明，公众迫切需要他们可以信任的事实，因为他们不知道该相信什么。
Andrew Huberman:
安德鲁·休伯曼：
Well, I am being completely honest when I say this that I followed your lead.
好吧，当我说我遵循你的领导时，我是完全诚实的。
I saw you on the Joe Rogan podcast and my jaw dropped.
我在乔·罗根播客上看到你，我的下巴都惊掉了。
I was like, "This is amazing," because he had had other good scientists on before.
我当时想，“这太棒了”，因为他之前也有过其他优秀的科学家。
But you're tenured professor of Harvard Department of Genetics.
但你是哈佛大学遗传学系的终身教授。
And for those of you don't know, there's the Harvard and, of course, Harvard Medical School, and they're both excellent of course.
对于那些不知道的人来说，还有哈佛大学，当然还有哈佛医学院，当然它们都很优秀。
But these are the top tiers of academia, and I certainly understand what it takes to get there and survive there and to thrive there.
但这些都是学术界的顶层，我当然明白如何才能到达那里并在那里生存并在那里蓬勃发展。
It's like a game of pinball.
这就像弹球游戏。
You never win.
你永远不会赢。
You just get to ...
你只需要去...
If you're doing really well, you get to keep playing.
如果你表现得很好，你就可以继续比赛。
That's the truth in academia.
这就是学术界的真理。
And if you're not, you stop playing basically.
如果你不这样做，你基本上就不再玩了。
Andrew Huberman:
安德鲁·休伯曼：
But when I saw you explain what you were doing in a way that was accessible to people and also talking about possible protocols that they might explore for themselves to see if those were right for them, I was just dazzled and excited and I made every effort to get in contact with you and the rest is history.
但当我看到你以一种人们可以理解的方式解释你在做什么，并谈论他们可能会自己探索的可能协议，看看这些协议是否适合他们时，我感到眼花缭乱和兴奋，我尽一切努力与你取得联系，剩下的就是历史了。
But I think what's really exciting to me these days is because of 2020 and what, everything that's happened, and it continues to happen, there's a thirst for knowledge.
但我认为这些天真正让我兴奋的是因为 2020 年以及所发生的一切，而且还在继续发生，人们对知识的渴望。
There's also this direct-to-the-public route that you mentioned.
还有您提到的直接面向公众的路线。
And I think there's also an openness.
我认为还有一种开放性。
And I love your thoughts on this, but it seems to me that there's an openness from the general public about health practices.
我喜欢你对此的想法，但在我看来，公众对健康实践持开放态度。
That there are actually things that people can do to control their stress level, sleep, cholesterol, if that's what they need to do — maybe they don't.
事实上，人们可以采取一些措施来控制压力水平、睡眠、胆固醇，如果这是他们需要做的——也许他们不需要。
And to even control their lifespan, which I think is remarkable.
甚至可以控制它们的寿命，我认为这是了不起的。
Andrew Huberman:
安德鲁·休伯曼：
And I know I speak on behalf of so many people when I just want to say thank you.
我知道当我只想说谢谢时，我代表了很多人。
You've truly changed the course of my life.
你确实改变了我的人生轨迹。
I would not be sitting here doing this were it not for your example.
如果没有你的例子，我就不会坐在这里做这件事。
And I always say, Sinclair, many people have written books, many academics have written books as you have.
我总是说，辛克莱，很多人都写过书，很多学者也像你一样写过书。
But in terms of doing podcasts and really getting out there with your message in a way that I have to assume raised your cortisol level and heart rate just a little bit, but you did it nonetheless.
但就做播客和真正以某种方式传达你的信息而言，我不得不假设稍微提高了你的皮质醇水平和心率，但你仍然做到了。
You were truly first man in and that deserves a nod and I have a great debt of gratitude to you for that, so thank you so much.
你确实是第一个进来的人，这值得赞扬，为此我非常感谢你，所以非常感谢你。
David Sinclair:
大卫·辛克莱：
Oh, thanks Andrew.
哦，谢谢安德鲁。
You've become a good friend and I'm super proud of what you've done and I know what you will do.
你已经成为我的好朋友，我为你所做的事情感到非常自豪，我知道你会做什么。
Andrew Huberman:
安德鲁·休伯曼：
So in addition to your book and your presence on social media, Instagram and Twitter, and appearances on podcasts recently, I've noticed that you've opened up a sort of email/website that people can ask, access, to get some information about their own health and rates of aging.
因此，除了你的书、你在社交媒体、Instagram 和 Twitter 上的出现，以及最近在播客上的露面之外，我注意到你还开设了一种电子邮件/网站，人们可以询问、访问，以获得一些有关他们自己的健康和衰老速度的信息。
Tell us about that and what's being measured and what is this test that you've been working on, secretly and now, soon, not so secretly?
告诉我们这件事以及正在测量的内容以及您一直在秘密进行的测试是什么，现在，很快，不那么秘密地进行的测试是什么？
David Sinclair:
大卫·辛克莱：
Yeah.
是的。
Well, what I want is a credit score for the body to make it easy for people to follow their health.
嗯，我想要的是身体的信用评分，以便人们可以轻松地跟踪自己的健康状况。
And there is a number, there's a biological age that you can measure.
有一个数字，有一个可以测量的生物年龄。
Unfortunately, the test is many hundreds of dollars right now.
不幸的是，目前的测试费用高达数百美元。
But in my lab, we've been able to bring that down a lot.
但在我的实验室，我们已经能够将其降低很多。
And so I want to democratize this test so that everybody has access to a score for their health that can predict not just their future health and time of death, but to change it.
因此，我希望使这项测试民主化，以便每个人都可以获得自己的健康评分，不仅可以预测他们未来的健康状况和死亡时间，还可以改变它们。
And I'm building a system that will point people in the right direction and give them discounts for certain things that will improve not just their health now, but 10, 20, 30 years into the future.
我正在建立一个系统，为人们指明正确的方向，并为他们提供某些事情的折扣，这不仅会改善他们现在的健康，而且会改善他们未来 10 年、20 年、30 年的健康。
David Sinclair:
大卫·辛克莱：
And we can measure that and very cheaply keep measuring it to know that you're on the right track, because if you don't measure something, you can't optimize it.
我们可以衡量这一点，并且非常便宜地继续衡量它，以了解您是否走在正确的轨道上，因为如果您不衡量某些东西，就无法优化它。
And so this is the biological age test.
这就是生物年龄测试。
We've developed it.
我们已经开发出来了。
It's a simple mouth swab.
这是一个简单的口腔拭子。
We're rolling it out.
我们正在推出它。
We're building the system right now and there is a signup sheet because a lot of people want to get in line.
我们现在正在构建系统，并且有一张注册表，因为很多人想要排队。
Go to doctorsinclair.com.
访问 doctorsinclair.com。
You can get on that and you'll be one of the first people in the world to get this test and see what we're doing.
你可以接受这个测试，你将成为世界上第一批接受这项测试并了解我们在做什么的人之一。
Andrew Huberman:
安德鲁·休伯曼：
Oh, fantastic.
哦，太棒了。
Will people be celebrating their biological age birthdays?
人们会庆祝他们的生理年龄生日吗？
In other words, if I'm minus ...
换句话说，如果我是负数...
If I could imagine, so I'm 45 right now, soon to be 46.
如果我能想象的话，我现在 45 岁，很快就 46 岁了。
But if I were to be so lucky as to get my biological age to 35 within 12 months, maybe you can help me do that, do I get to celebrate a negative birthday?
但如果我很幸运能够在 12 个月内将我的生物学年龄提高到 35 岁，也许你可以帮助我做到这一点，我可以庆祝负数生日吗？
David Sinclair:
大卫·辛克莱：
Absolutely.
绝对的。
And my plan is that those people who take their age back a year or more, we think we can go back 20 years eventually, they'll get a birthday card from me and it's a negative birthday card.
我的计划是，那些将年龄拉回一年或更长时间的人，我们认为我们最终可以回到 20 年前，他们会从我那里得到一张生日贺卡，这是一张负面的生日贺卡。
Andrew Huberman:
安德鲁·休伯曼：
I love it.
我喜欢它。
And probably a very little actual birthday cake being ingested.
可能吞下的实际生日蛋糕也很少。
But who cares, because you're living that much longer.
但谁在乎呢，因为你的寿命更长。
David Sinclair:
大卫·辛克莱：
Well, it's full of stevia.
嗯，里面充满了甜叶菊。
They'll be fine.
他们会没事的。
Andrew Huberman:
安德鲁·休伯曼：
And thank you for talking to us today.
感谢您今天接受我们的采访。
I realized I took us down deep into the guts of mechanism and, as well, talking about global protocols.
我意识到我带我们深入了解了机制的内部，并且还讨论了全球协议。
Everything from what one can do and take if they choose that's right for them, to how to think about this whole process that we talk about when we talk about lifespan.
从人们可以做什么和采取什么（如果他们选择适合自己的），到如何思考我们在谈论寿命时谈论的整个过程。
As always, incredibly illuminating.
一如既往，令人难以置信的启发。
Thank you, David.
谢谢你，大卫。
David Sinclair:
大卫·辛克莱：
Thanks Andrew.
谢谢安德鲁。
Andrew Huberman:
安德鲁·休伯曼：
Thank you for joining me for my conversation with Dr. David Sinclair.
感谢您参加我与大卫·辛克莱博士的对话。
If you're enjoying and or learning from this podcast, please subscribe to our YouTube channel.
如果您喜欢此播客或从中学习，请订阅我们的 YouTube 频道。
In addition, please subscribe on Apple and or Spotify.
此外，请在 Apple 和/或 Spotify 上订阅。
And on YouTube, you can leave us comments and you can leave us suggestions for future podcast guests that you would like us to feature.
在 YouTube 上，您可以给我们留下评论，也可以给我们留下您希望我们推荐的未来播客嘉宾的建议。
In addition, on Apple, you can leave us up to a five-star review and you can leave us a comment.
另外，在苹果上，您可以给我们留下五星级的评价，也可以给我们留言。
Please also check out the sponsors mentioned at the beginning of this episode.
另请查看本集开头提到的赞助商。
That's the best way to support this podcast.
这是支持这个播客的最佳方式。
Also, I teach science and science-related tools on Instagram.
此外，我还在 Instagram 上教授科学和科学相关工具。
It's Huberman Lab on Instagram.
这是 Instagram 上的 Huberman Lab。
I also have a Twitter, which is also Huberman Lab, so be sure to check those out.
我还有一个 Twitter，也是 Huberman Lab，所以一定要查看一下。
A lot of the material covers things similar to the podcast, but oftentimes I'll cover unique material not featured at all on the podcast.
很多材料涵盖了与播客类似的内容，但通常我会涵盖播客中根本没有的独特材料。
Andrew Huberman:
安德鲁·休伯曼：
So that's Huberman Lab on Instagram and on Twitter.
这就是 Instagram 和 Twitter 上的 Huberman Lab。
Also, take note that the Lifespan podcast, featuring Dr. David Sinclair as a host, launches Wednesday, January 5th.
另请注意，由 David Sinclair 博士担任主持人的 Lifespan 播客将于 1 月 5 日星期三推出。
You can find the first episode here on the Huberman Lab podcast channel.
您可以在 Huberman Lab 播客频道上找到第一集。
They also have their own independent channel.
他们也有自己独立的频道。
You can find the link to that channel in the show notes.
您可以在节目注释中找到该频道的链接。
So please go there, subscribe on YouTube.
所以请去那里，在 YouTube 上订阅。
Also on Apple and Spotify.
也在 Apple 和 Spotify 上。
I've seen these episodes.
我看过这些情节。
They are phenomenal and you're going to learn a tremendous amount about aging and how to slow and reverse aging from the world expert himself, Dr. David Sinclair.
它们是非凡的，您将从世界专家大卫·辛克莱博士那里学到大量有关衰老以及如何减缓和逆转衰老的知识。
And last but certainly not least, thank you for your interest in science.
最后但并非最不重要的一点是，感谢您对科学的兴趣。