Essentials: The Biology of Slowing & Reversing Aging | Dr. David Sinclair
Andrew Huberman: Welcome to Huberman Lab essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health, and performance.
安德鲁·胡伯曼（Andrew Huberman）：欢迎来到胡伯曼实验室要点，在这里我们回顾过去的剧集，寻找针对心理健康、身体健康和表现的最有效、最可操作的基于科学的工具。
Andrew Huberman: I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine.
安德鲁·胡伯曼：我是安德鲁·胡伯曼，我是斯坦福大学医学院的神经生物学和眼科教授。
And now, my conversation with Dr. David Sinclair.
现在，我与大卫·辛克莱博士的对话。
Andrew Huberman: Thanks for being here.
安德鲁·休伯曼：感谢您来到这里。
I have a ton of questions for you about aging, longevity, lifespan, actionable protocols to increase how long we live, et cetera.
我有很多关于衰老、长寿、寿命、延长寿命的可行方案等问题要问您。
Andrew Huberman: And I just want to start off with a very simple question: What is the difference between longevity, anti-aging, and aging as a disease?
安德鲁·休伯曼：我只想从一个非常简单的问题开始：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: Right.
大卫·辛克莱：对。
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.
所以，我真的不喜欢抗衰老这个词。
But aging as a disease and longevity are perfectly valid ways to talk about this subject.
但衰老作为一种疾病和长寿是谈论这个话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。
David Sinclair: When I started my research, disease, here at Harvard Medical School, it was considered, 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.
David Sinclair：当我在哈佛医学院开始研究疾病时，人们认为，如果你有什么问题，而且这种情况很罕见，必须少于人口的 50%，那绝对是一种疾病。
And then, people work their whole lives to try and cure that condition.
然后，人们毕生努力尝试治愈这种病症。
And 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, typically you do, something that sounds pretty much like a disease.
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，通常你会这样做，这听起来很像一种疾病。
David Sinclair: But the caveat is that if more than half the population gets this condition, aging, it's put in a different bucket, which is...
大卫·辛克莱：但需要注意的是，如果超过一半的人口出现这种情况，即衰老，那么它就会被放在一个不同的桶里，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.
衰老是心脏病、阿尔茨海默病 80% 至 90% 的病因。
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。
David Sinclair: And actually, what we're showing in my lab is if you turn the clock back in tissues, those diseases go away.
大卫·辛克莱：实际上，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，衰老是问题所在，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.
一是我们想要延缓衰老，这样我们就不会患上这些疾病，当它们确实发生时，不要只是贴上创可贴。
Reverse the age of the body, and then the diseases will go away.
逆转身体的年龄，疾病就会消失。
Andrew Huberman: That clarifies a lot for me.
Andrew Huberman：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: Fortunately, during the 2000s, we settled on eight or nine major causes of aging.
David Sinclair：幸运的是，在 2000 年代，我们确定了八九个衰老的主要原因。
These eight or nine causes, at least for the first time, allowed us to come around and talk together.
这八九个原因，至少是第一次，让我们能够聚在一起交谈。
We put them on a pizza, so everyone got equal slices, but I think that there's one slice of the pizza that is way larger than the others.
我们把它们放在披萨上，所以每个人都得到相同的切片，但我认为披萨中有一片比其他片大得多。
And we can get to that, but that's the information in the cell that we call the epigenome.
我们可以得到这一点，但这就是细胞中我们称之为表观基因组的信息。
Andrew Huberman: Well, tell us a little bit more about the epigenome, frame it for us, if you will, and then we'll get into ways that one can adjust the epigenome in positive ways.
Andrew Huberman：好吧，请告诉我们更多关于表观基因组的信息，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: Yeah, 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.
大卫·辛克莱：是的，所以在科学中，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丢失。
It's a hard thing to overcome the second law of thermodynamics, that's fair.
克服热力学第二定律是一件很难的事情，这是公平的。
David Sinclair: 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.
大卫·辛克莱：但这个等式确实代表了一个事实，即我认为衰老是一种信息丢失，就像当你将某个东西复印一千次时，你会丢失该信息，或者你尝试复制盒式磁带，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。
And there are two types of information in the body.
体内有两种信息。
David Sinclair: There is the genetic information, which is digital, A, T, C, G, 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, et cetera.
David Sinclair：有遗传信息，即数字、A、T、C、G、DNA 的化学字母，但身体中的信息的其他部分同样重要，实际上是必不可少的，这就是控制哪些基因打开和关闭、在什么细胞中、在什么时间、对我们吃的东西做出反应的系统，等等。
And 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——控制系统控制的。
David Sinclair: I liken the DNA to the music that's on a DVD or a compact disc, for the younger people, we used to use these things.
David Sinclair：我将 DNA 比作 DVD 或光盘上的音乐，对于年轻人来说，我们过去常常使用这些东西。
Andrew Huberman: I recall.
安德鲁·休伯曼：我记得。
Yeah.
是的。
David Sinclair: Yeah.
大卫·辛克莱：是的。
And then the epigenome is the reader that says, "Okay, in this cell, we need to play that set of songs, and 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, and cells, when they don't hear the right songs, they get messed up and they don't function well.
然后表观基因组是读取器，它说：“好吧，在这个单元格中，我们需要播放那组歌曲，而在另一个单元格中，我们必须播放一组不同的歌曲。”但随着时间的推移，衰老就相当于 CD 和 DVD 被划伤，无法播放正确的歌曲，而细胞如果听不到正确的歌曲，就会变得混乱，无法正常运作。
And that is what I'm saying is the main driver of aging, and these other hallmarks are largely manifestations of that process.
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: What are the scratches that you're referring to?
Andrew Huberman：你指的划痕是什么？
David Sinclair: So, DNA is six foot long, so if you join your chromosomes together, you get a six foot per 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, but it's not just wrapped up willy-nilly, it's not just a bundle of string.
大卫·辛克莱：所以，DNA 有六英尺长，所以如果你把染色体连接在一起，每个细胞就有六英尺长，所以它足够在你的身体里往返月球八次，而且它必须被包裹起来才能存在于我们体内，但它不仅仅是随意地包裹起来，它不仅仅是一束绳子。
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。
And 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 100 years, if you're lucky.
如果你幸运的话，你的细胞在接下来的 100 年里仍将是神经细胞。
Don't turn into a skin cell.
不要变成皮肤细胞。
That would be bad." And those chemicals, there are many different types of chemicals, but one's called methylation, those little methyls will mark which songs get played for the rest of your life.
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，这些小甲基将标记哪些歌曲会在你的余生中播放。
And there are other marks that change daily.
还有其他每天都在变化的标记。
David Sinclair: 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.
David Sinclair：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，保持其他基因打开，这应该保持打开状态。
David Sinclair: And that pattern of genes that are silent and open, silent, open, is what dictates the cell's type, the cell's function.
大卫·辛克莱：这种沉默又开放的基因模式决定了细胞的类型和细胞的功能。
And then the scratches are the disruption of that, 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, shouldn't be there, but we see this happen, and vice versa, the gene might get shut off over time during aging.
然后划痕就是对这种情况的破坏，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，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，该基因可能会在衰老过程中被关闭。
David Sinclair: Cells, over time, lose these structures, lose their identity, they forget what they're supposed to do, and we get diseases.
大卫·辛克莱：随着时间的推移，细胞会失去这些结构，失去自己的身份，忘记自己应该做什么，然后我们就会患上疾病。
We call that aging, and we can measure that.
我们称之为衰老，我们可以衡量它。
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: Are these changes the same sorts of changes that underlie the outward body surface manifestations of aging that most of us are familiar with, graying of the hair, wrinkling of the skin, drooping of the face?
安德鲁·休伯曼：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（头发变灰、皮肤起皱、脸部下垂）相同？
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: Well, it's actually, you are as old as you look, if you want to generalize.
大卫·辛克莱：嗯，事实上，如果你想概括的话，你就和你看起来一样老了。
So, let's start with centenarian families.
那么，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，或者更少。
So, it is a good indicator, it's not perfect because you can, like me, grow up in Australia and accelerate the aging of your skin, but in general, how you look.
所以，这是一个很好的指标，它并不完美，因为你可以像我一样在澳大利亚长大并加速你的皮肤老化，但总的来说，你的外表如何。
David Sinclair: 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.
大卫·辛克莱：没有人死于白发，但总的来说，你可以从皮肤支撑自身的能力、皮肤的厚度、皱纹的数量来了解。
Andrew Huberman: Very interesting.
安德鲁·休伯曼：非常有趣。
So, 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.
所以，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，就是发育不会在 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。
Andrew Huberman: 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.
安德鲁·休伯曼：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。
And I know we normally look at babies, and children, and kids in puberty and we think, "Oh, they're so vital.
我知道我们通常会看着婴儿、儿童和青春期的孩子，我们会想，“哦，他们是如此重要。
They're so young."
他们太年轻了。”
Andrew Huberman: 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?
安德鲁·休伯曼：然而，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，充满活力的时期是否与我们衰老得更快的时期相同？
David Sinclair: Yes.
大卫·辛克莱：是的。
Really good question.
真是个好问题。
So, those chemicals we can measure.
所以，我们可以测量这些化学物质。
It's also known as the Horvath clock.
它也被称为霍瓦斯时钟。
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。
There are some people that are 10, 20 years younger than other people biologically.
有些人的生理年龄比其他人年轻10、20岁。
And 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，如果你从出生开始测量这个时钟，甚至在出生之前，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: So, you're right.
大卫·辛克莱：所以，你是对的。
So, 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.
所以，这是非常重要的一点，在生命的最初几年里，你会加速衰老，然后它会在你的余生中呈线性增长。
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。
David Sinclair: So, what's causing the scratches?
大卫·辛克莱：那么，是什么造成了划痕呢？
Well, we know of a couple of things in my lab we figured out.
嗯，我们知道我们在实验室中发现了一些事情。
One is broken chromosomes, DNA damage, particularly cuts to the DNA breaks.
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 and you'll get your broken chromosomes, that accelerates the unwinding of those beautiful DNA loops that I mentioned.
所以，如果你有 X 射线，或者宇宙射线，或者即使你出去晒太阳，你也会得到断裂的染色体，这会加速我提到的那些美丽的 DNA 环的解开。
David Sinclair: We can actually do this to a mouse.
David Sinclair：我们实际上可以对老鼠做到这一点。
We can accelerate that process, and we get an old mouse, 50% older, and it has this bent spine, kyphosis.
我们可以加速这个过程，我们得到了一只老老鼠，老了 50%，它的脊柱弯曲，驼背。
It has gray hair.
它有灰色的头发。
It's organs are old.
它的器官已经老了。
So, we now can control aging in the forwards direction.
因此，我们现在可以向前控制衰老。
The other thing that accelerates aging is massive cell damage or stress.
另一件加速衰老的因素是大量的细胞损伤或压力。
So, we pinched nerves, and we saw that their aging process was accelerated as well.
所以，我们捏紧神经，我们发现他们的衰老过程也加速了。
Andrew Huberman: Incredible.
安德鲁·休伯曼：难以置信。
Yeah, this is more of an anecdotal phenomenon.
是的，这更多的是一个轶事现象。
It is an anecdotal phenomenon.
这是一个轶事现象。
But I had this experience of in junior high school, you know, going home for a summer and you come back and then some of the kids, they grew beards over the summer, or they completely matured quickly over the summer.
但我在初中时有过这样的经历，你知道，回家过一个夏天，然后你回来，然后有些孩子，他们在夏天留了胡子，或者他们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？
David Sinclair: Well, yeah, I don't want to scare anybody.
大卫·辛克莱：嗯，是的，我不想吓到任何人。
Andrew Huberman: Sure.
安德鲁·休伯曼：当然。
David Sinclair: There are studies that show that the slower you take to develop it also is predictive of having a longer, healthier life.
大卫·辛克莱（David Sinclair）：有研究表明，你的发展速度越慢，也预示着你的寿命会更长、更健康。
And it may have something to do with growth hormone.
而且可能和生长激素有关系。
We know that growth hormone is pro-aging, because anyone who's taking growth hormone for a short amount of time, you'll build up muscle, you feel great, but it's like burning your candle at both ends.
我们知道生长激素具有延缓衰老的作用，因为任何人只要短时间服用生长激素，就会增加肌肉，感觉很棒，但这就像蜡烛两头都烧了一样。
David Sinclair: Ultimately, if you want to live longer, you want less of that.
大卫·辛克莱（David Sinclair）：最终，如果你想活得更长，你想要的就更少。
And 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，以及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。
Andrew Huberman: Can we say that there's a direct relationship between body size and longevity or duration of life?
安德鲁·休伯曼：我们可以说身体尺寸和寿命或寿命之间有直接关系吗？
David Sinclair: Well, there is, but that doesn't mean that you're a slave to your early epigenome, nor to your genome.
David Sinclair：嗯，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.
好消息是表观基因组是可以改变的。
Those loops and structures can be modified by how you live your life.
这些循环和结构可以根据您的生活方式进行修改。
No matter what size you are, you can have a bigger impact on your life than anything your genes give you.
无论你的体型有多大，你对生活的影响都比你的基因给你的影响更大。
80% is epigenetic, not genetic.
80%是表观遗传的，而不是遗传的。
Andrew Huberman: 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.
Andrew Huberman：那么，让我们来谈谈人们可以做的一些事情，我已经将这些事情分成了几类，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.
所以，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.
我经常听到这样的说法：禁食对我们有好处。
But rarely do I hear why it's good for us.
但我很少听到为什么这对我们有好处。
Andrew Huberman: 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 to fast, I think should be dictated by some understanding of the mechanism.
安德鲁·休伯曼：我认为理解这一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，或者禁食多久，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, and/or why is it that having periods of time each day, or perhaps longer, can extend our lifespan?
那么，为什么血糖、葡萄糖和胰岛素升高会使我们更快衰老，和/或为什么每天花一段时间或更长的时间可以延长我们的寿命呢？
David Sinclair: Well, let's start with what I think was a big mistake, was the idea that people should never be hungry.
大卫·辛克莱：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。
Some people never experience hunger in their whole lives.
有些人一生从未经历过饥饿。
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，这是基于 20 世纪的观点，即您不想给胰腺带来压力，并且您会尽力保持胰岛素水平相当稳定，而不会有这种波动。
David Sinclair: 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.
David Sinclair：我和我的同事们在长寿领域的实际发现是，首先观察动物，无论是狗、老鼠还是猴子，寿命最长的动物，到目前为止，寿命延长了 30%，并且保持健康，是那些不一直吃东西的动物。
Actually, it was first discovered back in the early 20th century, but people ignored it, and then it was rediscovered in the 1930s.
其实早在20世纪初就被发现了，但人们忽视了它，直到20世纪30年代才被重新发现。
Clive McKay did caloric restriction.
克莱夫·麦凯进行了热量限制。
David Sinclair: 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.
David Sinclair：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 年代发生了几件事后，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.
我研究的这组基因被称为 Sirtuins。
There's seven of them.
他们有七个。
David Sinclair: And 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.
David Sinclair：我们在 2005 年的一篇科学论文中表明，如果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。
One of them that's really important is called SIRT1.
其中非常重要的一个称为 SIRT1。
But by having high levels of insulin all day, being fed, means your longevity genes are not switched on.
但是，如果整天摄入高水平的胰岛素，并且进食，则意味着您的长寿基因没有开启。
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，你的维持细胞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, okay?
你的时钟因为总是吃饱而走得更快，好吗？
David Sinclair: 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 re-establish the epigenome, and so it also is accelerating in that direction.
David Sinclair：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，因此它也在朝这个方向加速。
David Sinclair: 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.
大卫·辛克莱：还有很多其他原因，但并不那么深刻，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，这非常好。
You don't want to have glucose flowing around too much.
您不希望葡萄糖流动过多。
And that will ward off Type 2 diabetes.
这将预防 2 型糖尿病。
Andrew Huberman: What is the protocol that people can extrapolate from that?
Andrew Huberman：人们可以从中推断出什么协议？
David Sinclair: Well, if there's one thing I could say, I would say definitely try to skip a meal a day.
大卫·辛克莱：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: Does it matter which meal, or are they essentially equivalent?
Andrew Huberman：哪顿饭很重要，或者它们本质上是等价的吗？
David Sinclair: Well, as long as it's at the end or the beginning of the day, because then you add that to the sleep period where you're hopefully not eating.
大卫·辛克莱：嗯，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睡眠时间中，在该时间里你希望不吃东西。
Beware that the first two to three weeks when you try that, you will feel hungry, and you'll also have a habit of wanting to chew on something.
请注意，在尝试这样做的前两到三周，您会感到饥饿，并且还会养成想咀嚼某些东西的习惯。
There's a lot of physical parts to it.
它有很多物理部分。
But try to make it through the first three weeks and do without breakfast or do without dinner, and you'll get through it.
但试着熬过前三周，不吃早餐或不吃晚餐，你就会度过难关。
Andrew Huberman: Do you ever do longer fasts, like 48 hours or 72 hours or week-long fasts?
Andrew Huberman：您是否曾经进行过较长时间的禁食，例如 48 小时或 72 小时或为期一周的禁食？
David Sinclair: Not very often.
大卫·辛克莱：不经常。
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.
但当我这样做时，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。
So, 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.
因此，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。
Macroautophagy it's name is.
它的名字是巨自噬。
David Sinclair: 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.
大卫·辛克莱：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，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。
And 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: When you are fasting, regardless of how long, I know you're ingesting fluids like water, and presumably some caffeine.
安德鲁·休伯曼：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 espresso today.
我听说你今天喝了几杯或更多浓缩咖啡。
Are you also ingesting electrolytes?
你也摄入电解质吗？
I know some people get light-headed.
我知道有些人会感到头晕。
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.
当他们禁食时，他们开始感到摇摇欲坠，而在水中添加钠或钾、镁现在变得更流行了。
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这样做？
David Sinclair: Well, it makes sense, but I haven't had a need to do it, so I don't.
David Sinclair：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.
我白天喝茶，醒来时喝咖啡。
Andrew Huberman: Mm-hmm.
安德鲁·休伯曼：嗯嗯。
David Sinclair: And I don't get the shakes, so I don't fix what's not broken.
David Sinclair：我不会感到震惊，所以我不会修复没有损坏的东西。
Andrew Huberman: Okay.
安德鲁·休伯曼：好的。
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 pro-longevity anti-aging mechanisms, 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.
您告诉我们，有充分的证据表明，每 24 小时保持一段时间的低血糖有助于触发一些延年益寿的抗衰老机制，而将这些机制延长两到三天可以触发吞噬死亡细胞和类似物质的其他机制。
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 cellular 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呢？
David Sinclair: Yeah, there's a really good question.
大卫·辛克莱：是的，这是一个非常好的问题。
That proves you're a scientist, or a world-leading one.
这证明你是一名科学家，或者是世界领先的科学家。
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.
我们常常说，“哦，我的长寿基因比你的更重要。”这太荒谬了。
Because they're all talking to each other.
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。
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。
David Sinclair: So, the sirtuins will mainly respond to sugar and insulin, 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.
David Sinclair：所以，sirtuins 主要对糖和胰岛素做出反应，然后还有另一个称为 mTOR 的系统，它可以感知进入您体内的蛋白质或氨基酸的数量，并且它们会相互通信。
We can pull one and affect the other, and vice versa.
我们可以拉动一个并影响另一个，反之亦然。
David Sinclair: But together, when you're fasting, you'll get the sirtuin activation, which is good for you, and you'll also, through lack of amino acids, particularly three of them, leucine, isoleucine, valine, the body will downregulate mTOR, and it's that up sirtuin, down mTOR that is hugely beneficial and turns on all of the body's defenses.
David Sinclair：但同时，当你禁食时，你会激活sirtuin，这对你有好处，而且，由于缺乏氨基酸，特别是其中的三种氨基酸，亮氨酸、异亮氨酸、缬氨酸，身体会下调mTOR，而sirtuin的上升、mTOR的下降是非常有益的，可以开启身体的所有防御能力。
David Sinclair: The chewing up the old proteins, improving insulin sensitivity, giving us more energy, repairing cells, all of that, and so these two pathways, I think, are the most important for longevity.
大卫·辛克莱：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，所以我认为这两条途径对于长寿来说是最重要的。
Andrew Huberman: You mentioned leucine.
Andrew Huberman：你提到了亮氨酸。
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.
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，肌肉生长，但也只是健康。
Andrew Huberman: But what I interpret your last statement to mean is that leucine, because it triggers cellar growth, is actually pro-aging in some sense.
安德鲁·胡伯曼：但我对你最后一句话的解释是，亮氨酸，因为它能引发细胞生长，在某种意义上实际上是促衰老的。
Is that right?
是这样吗？
David Sinclair: That's what the evidence suggests.
大卫·辛克莱：证据就是如此。
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酮？
All of these activities will give you immediate benefits.
所有这些活动都会给您带来立竿见影的好处。
You'll bulk up more, you'll feel better immediately.
你会变得更胖，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，就是我不烧两支蜡烛。
I have one end of the candle lit.
我点燃了蜡烛的一端。
David Sinclair: I'm very careful, I don't blow on it, but I also do enough exercise that I'm building up my muscle, but I'm not huge.
大卫·辛克莱：我很小心，我不会吹气，但我也做了足够的运动来增强我的肌肉，但我并不大。
Anyone who's seen me knows that I'm not a professional bodybuilder, but I try to actually...
任何见过我的人都知道我不是专业的健美运动员，但我实际上尝试......
Here's the key, and I haven't said this publicly that I can remember.
关键是，我记得我还没有公开说过这一点。
David Sinclair: 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 muscle sometimes, because you can't just expect to take something constantly and do something constantly for it to work, and that's why it's taken me about 15 years to develop my protocol, and there's a lot of subtlety to it.
大卫·辛克莱（David Sinclair）：我会进行脉动，这样我就会禁食一段时间，然后我吃东西，然后我服用补充剂，然后我禁食，然后我锻炼，我在正确的时间服用补充剂和饮食，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，这就是为什么我花了大约 15 年的时间来制定我的方案，其中有很多微妙之处。
Andrew Huberman: Mm-hmm.
安德鲁·休伯曼：嗯嗯。
David Sinclair: What you want to do is to get the cells to be perceiving adversity, okay?
大卫·辛克莱：你想要做的是让细胞感知逆境，好吗？
Because our modern life, we're sitting around, we're eating too much, we're not exercising, our cells respond.
因为我们的现代生活，我们坐着，吃得太多，没有锻炼，我们的细胞会做出反应。
They go, "Hey, everything's cool, no problem," and they become relaxed, and they don't turn on their defenses, and we age rapidly.
他们会说，“嘿，一切都很酷，没问题”，然后他们就变得放松，他们不会开启防御，我们就会迅速衰老。
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。
Andrew Huberman: One of the questions I get asked all the time is, "Does ingesting 'blank' break the fast?
安德鲁·休伯曼：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, you know, if I walk in the room and someone else is eating a cracker, does it break my fast?" People get pretty extreme with this.
吃这个或喝这个咖啡，你知道，如果我走进房间而其他人正在吃饼干，这会破坏我的斋戒吗？”人们对此变得非常极端。
David Sinclair: Mm-hmm.
大卫·辛克莱：嗯嗯。
Andrew Huberman: 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.
安德鲁·休伯曼：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。
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, quote, unquote, "break my fast," but the body doesn't have a breaking-the-fast switch.
因此，举例来说，如果我在午夜吃了一顿大餐，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引用或取消引用“打破我的斋戒”，但身体没有打破斋戒的开关。
The body only speaks in the language of glucose, AMPK, mTOR, et cetera.
身体只用葡萄糖、AMPK、mTOR 等语言说话。
Andrew Huberman: So, do you worry that ingesting these calories is going to, quote, unquote, "break your fast?" And more generally, how do you think about the issue of whether or not you're fasting enough to get these positive effects?
安德鲁·休伯曼：那么，你是否担心摄入这些卡路里会导致“打破你的禁食”？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，或者只喝茶，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，或者只喝茶。
David Sinclair: Well, my first answer is not scientific, it's philosophical, but if you don't enjoy life, what's the point?
大卫·辛克莱：嗯，我的第一个答案不是科学的，而是哲学的，但如果你不享受生活，那还有什么意义呢？
And so, I'd like a cup of coffee in the morning, little bit of milk, spoonful of yogurt's not going to kill me, olive oil doesn't have protein or carbs in it, not many, and so I'm probably not affecting those longevity pathways negatively.
所以，我早上想喝一杯咖啡，一点牛奶，一勺酸奶不会杀死我，橄榄油中不含蛋白质或碳水化合物，数量不多，所以我可能不会对这些长寿途径产生负面影响。
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。
David Sinclair: Second, well, the olive oil is not as great as the yogurt, but I'm trying to optimize, and there's no perfect solution to what we're doing, and we're still learning.
大卫·辛克莱：其次，橄榄油不如酸奶好，但我正在努力优化，而且我们正在做的事情没有完美的解决方案，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。
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。
David Sinclair: If you go from regular living to don't eat the whole day, you're going to fail.
大卫·辛克莱：如果你从正常的生活变成一整天不吃东西，你就会失败。
It's like quitting smoking cold turkey.
这就像戒掉火鸡烟一样。
It's easier to chew gum and stick the patch on, because your body has to get used to all sorts of habits, and it's social, it's physical, putting stuff in your mouth, chewing, not just the low blood sugar levels, and your brain will fight it.
咀嚼口香糖并贴上贴片会更容易，因为你的身体必须习惯各种习惯，这是社交的，是身体的，把东西放进嘴里咀嚼，而不仅仅是低血糖水平，你的大脑会与之对抗。
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, but you do it in stages.
但一旦你克服了它，你就会变得更好，但你要分阶段进行。
David Sinclair: Don't go cold turkey, 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.
大卫·辛克莱：不要突然戒掉，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: That captures the essence of fasting rationally and a rational approach to supplementation very well.
Andrew Huberman：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?
沿着补充路线，NMN 怎么样？
How does one incorporate that into a supplementation protocol should they choose to do that?
如果人们选择这样做，如何将其纳入补充方案中？
David Sinclair: All right.
大卫·辛克莱：好的。
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。
David Sinclair: And one of my first postdocs, actually literally my first postdoc, Chaim Cohen, published a great paper and found that turning on the Sirtuin 6 gene, remember there's seven, number six gene is very potent, it extended the lifespan dramatically of mice that he engineered, both males and females, which is great.
David Sinclair：我的第一个博士后之一，实际上是我的第一个博士后，Chaim Cohen，发表了一篇很棒的论文，发现打开 Sirtuin 6 基因，记住有七个，第六个基因非常有效，它极大地延长了他改造的小鼠的寿命，无论是雄性还是雌性，这很棒。
So, what you want to do is naturally boost the activity of these sirtuins.
所以，你要做的自然就是提高这些sirtuins的活性。
They are genes, but they also make proteins, that's what genes typically make or encode, and then those proteins take care of the body in many different ways.
它们是基因，但它们也制造蛋白质，这就是基因通常制造或编码的东西，然后这些蛋白质以许多不同的方式照顾身体。
David Sinclair: NAD levels are really important for keeping those sirtuin defenses at a youthful level.
David Sinclair：NAD 水平对于将 Sirtuin 防御保持在年轻水平非常重要。
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, but if you take it for about two weeks, you'll double, on average double your NAD levels in the blood.
因此，通过对数十个人的测量，我知道，如果你在我服用的时间段内服用 NMN，我已经服用它很多年了，但如果你服用大约两周，你的血液中 NAD 水平就会增加一倍，平均增加一倍。
David Sinclair: So, I just want people to be aware that what I do may not perfectly work at all for others.
大卫·辛克莱：所以，我只是想让人们意识到，我所做的事情可能对其他人来说并不完全有效。
But I have studied, as I said, dozens of people who take NMN at a gram, sometimes two grams, 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.
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，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。
Anecdotally, because I've been taking this for a long time, if I don't take it, I start to feel 50 years old.
有趣的是，因为我已经服用这个药物很长时间了，如果我不服用它，我就会开始感觉自己像50岁了。
It's horrible.
太可怕了。
I can't think straight.
我无法正常思考。
David Sinclair: It may be placebo, but who knows?
大卫·辛克莱：这可能是安慰剂，但谁知道呢？
Andrew Huberman: Mm-hmm.
安德鲁·休伯曼：嗯嗯。
David Sinclair: But what we're doing now are very careful clinical trials.
David Sinclair：但我们现在正在做的是非常仔细的临床试验。
Andrew Huberman: I want to talk about iron and iron load.
Andrew Huberman：我想谈谈铁和铁负荷。
I don't think we can get right down into how much iron somebody needs, because it'll vary person to person, but I was surprised to learn that iron is actually going to accelerate the aging process in various contexts.
我认为我们无法直接确定一个人需要多少铁，因为它会因人而异，但我惊讶地发现铁实际上会在不同情况下加速衰老过程。
David Sinclair: This is a new finding out of Spain, Manuel Serrano's lab has found that excess iron will increase the number of senescent cells in the body.
David Sinclair：这是西班牙的一项新发现，Manuel Serrano 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 these 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，它们呆在那里，主要引起炎症，也可能导致癌症。
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，或者从不积累它们，你就会保持年轻。
David Sinclair: In animals, and there's some really interesting studies out of Mayo Clinic in humans as well.
David Sinclair：在动物方面，梅奥诊所在人类方面也进行了一些非常有趣的研究。
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, we're not anemic, and we're getting along great in life.
例如，我发现，人们非常健康，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，我们不贫血，我们生活得很好。
David Sinclair: But a doctor who just looks at that might say, "Oh, we need to give you more iron." All right, 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.
大卫·辛克莱：但是医生可能会说，“哦，我们需要给你更多的铁。”好吧，我要说的是一个例子，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，不仅仅是针对普通人，而是针对对人类最有利的方式。
Andrew Huberman: I love that answer.
安德鲁·休伯曼：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, 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.
我喜欢数据。
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？
Andrew Huberman: 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?
安德鲁·休伯曼：我的意思是，我们并不是要求你反对任何人的医生，但是如果人们选择获取这些分子，他们应该开始自我教育，了解这些分子在图表上的内容，你会看什么？
David Sinclair: Yeah.
大卫·辛克莱：是的。
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 over time, and if you can have a decade or more of data, it's super informative, 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，如你所知，它的信息量非常大。
But there are some main ones, I would say your blood sugar levels, you want to do your HbA1c, which is your average glucose levels over the month, there's CRP which I mentioned for inflammation.
但有一些主要的，我会说你的血糖水平，你想要做你的 HbA1c，这是你这个月的平均血糖水平，还有我提到的用于炎症的 CRP。
Andrew Huberman: 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, a variety of different things.
Andrew Huberman：是的，让我们再谈谈 C 反应蛋白，因为我认为，它已被证明是黄斑变性、心脏病和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。
David Sinclair: It is the best marker for cardiovascular inflammation, and also, we use it as a predictor of longevity.
David Sinclair：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。
And its levels go up with mortality.
而且它的水平随着死亡率的增加而上升。
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.
所以，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。
David Sinclair: And the levels usually go up with age, and with levels of inflammation.
大卫·辛克莱（David Sinclair）：这种水平通常会随着年龄和炎症水平的增加而升高。
So, the ways to get it down would be to switch the diet, eat less, try to eat more vegetables, you'll find it will come down.
所以，降下来的方法就是改变饮食，少吃点，尽量多吃蔬菜，你会发现它会降下来。
There are also drugs that can do it, anti-inflammatories can do it as well.
还有药物可以，消炎药也可以。
But CRP, it's actually hCRP, there's a high sensitivity for hsCRP.
但是CRP，它实际上是hCRP，hsCRP有很高的敏感性。
Your doctor will know.
你的医生会知道的。
David Sinclair: Get one of those readings, because if you've got normal blood sugar levels, or fasting blood sugar levels, your doctor might say you're fine.
大卫·辛克莱：获取这些读数之一，因为如果您的血糖水平或空腹血糖水平正常，您的医生可能会说您很好。
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.
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: Zooming way out, what are the behavioral tools that one can start to think about in terms of ways to modulate these, you know, basically the way that DNA is being expressed and functioning?
Andrew Huberman：从长远来看，人们可以开始考虑哪些行为工具来调节这些行为，你知道，基本上就是 DNA 表达和功能的方式？
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 realize that there are caveats, we can't go directly from a behavior to sirtuins, but in the general theme, what can people do, what do you do?
我意识到有一些警告，我们不能直接从行为到 Sirtuins，但在总体主题中，人们可以做什么，你会做什么？
David Sinclair: Well, we know that aerobic exercise in mice and rats raises their NAD levels, and their levels of sirt, one of the genes, goes up.
David Sinclair：嗯，我们知道小鼠和大鼠的有氧运动会提高它们的 NAD 水平，并且它们的基因之一的 Sirt 水平也会升高。
Two actually, number one and number three.
实际上是两个，第一和第三。
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。
The two main ones are you want to maintain your hormone levels.
两个主要因素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。
David Sinclair: And by exercising, I will maintain that, and have.
大卫·辛克莱：通过锻炼，我将保持这一点，并且已经做到了。
In fact, I probably haven't had a body like this since I was 20, so that's one of the benefits of having this lifestyle.
事实上，我可能从20岁起就没有拥有过这样的身体了，所以这是拥有这种生活方式的好处之一。
Andrew Huberman: What about estrogen?
安德鲁·休伯曼：雌激素呢？
Because women are different in the sense that the number of eggs that they...
因为女性的不同之处在于她们的卵子数量......
And the ovaries change over time, right?
卵巢会随着时间的推移而变化，对吗？
Do you think that they can maintain estrogen levels 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较长时间内维持雌激素水平吗？
David Sinclair: 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 at a year of age, a mouse gets infertile, a female mouse-
大卫·辛克莱：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，所以大约在一岁的时候，一只老鼠变得不育，一只雌性老鼠——
Andrew Huberman: Due to fasting?
安德鲁·休伯曼：由于禁食？
David Sinclair: No, due to-
大卫·辛克莱：不，因为——
Andrew Huberman: Or due simply to aging?
Andrew Huberman：或者仅仅是因为衰老？
David Sinclair: Due to aging.
大卫·辛克莱：由于衰老。
Andrew Huberman: Yeah.
安德鲁·休伯曼：是的。
David Sinclair: Due to aging.
大卫·辛克莱：由于衰老。
The fasting, it's not an extreme fast, it's just less calories.
禁食，并不是极度禁食，只是减少热量摄入。
Andrew Huberman: Got it.
安德鲁·休伯曼：明白了。
David Sinclair: Then you put them back on a regular food and they become fertile again for many, many months afterwards.
大卫·辛克莱（David Sinclair）：然后你让它们重新吃普通食物，它们会在很多很多个月后再次变得有生育能力。
David Sinclair: So, the effect on slowing down aging is also on the reproductive system.
大卫·辛克莱（David Sinclair）：所以，延缓衰老的效果也适用于生殖系统。
Andrew Huberman: Interesting.
安德鲁·休伯曼：有趣。
David Sinclair: And so, I wouldn't say to any woman, I wouldn't think that they should become super skinny to try and preserve fertility.
大卫·辛克莱：所以，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。
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, one group of mice was 16 months old.
我们给了老老鼠，一组老鼠16个月大。
David Sinclair: Remember, they became infertile at 12.
David Sinclair：记住，他们在 12 岁时就变得不孕。
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。
Andrew Huberman: Mm-hmm.
安德鲁·休伯曼：嗯嗯。
David Sinclair: They became fertile again, which goes against textbook biology, which is that female mammals run out of eggs.
大卫·辛克莱：它们再次变得具有生育能力，这违背了生物学教科书，即雌性哺乳动物的卵子耗尽了。
Andrew Huberman: Mm-hmm.
安德鲁·休伯曼：嗯嗯。
David Sinclair: Turns out, that's not true.
大卫·辛克莱：事实证明，这不是真的。
You can rejuvenate the female reproductive system, and even get them to come out of mouse-pause, as we call it.
你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“老鼠停顿期”。
Andrew Huberman: Mm-hmm.
安德鲁·休伯曼：嗯嗯。
David Sinclair: So, that's a whole new paradigm in biology as well.
大卫·辛克莱：所以，这也是生物学的一个全新范式。
What I think is really interesting is that what we're 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.
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.
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。
And the body can really get rejuvenated in ways that, in the future, we'll wonder, "Why didn't we work on this earlier?"
身体真的可以通过某种方式恢复活力，在未来，我们会想，“为什么我们不早点做这件事呢？”
Andrew Huberman: And thank you for talking to us today.
Andrew Huberman：感谢您今天接受我们的采访。
I realize I took us down deep into the guts of mechanism, and as well talking about global protocols, 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.
我意识到我让我们深入到了机制的内部，并谈论了全球协议，从人们可以做的事情和采取的，如果他们选择对他们来说是正确的，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: Thanks, Andrew.
大卫·辛克莱：谢谢，安德鲁。