精华：延缓与逆转衰老的生物学 | 大卫·辛克莱博士

欢迎来到《Huberman实验室精华》，我们重温往期节目，为您带来最有效且实用的科学工具，助力心理健康、身体健康与表现提升。我是Andrew Huberman，斯坦福医学院神经生物学与眼科学教授。现在开始我与David Sinclair博士的对话。感谢您的到来。

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. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. And now my conversation with Doctor. David Sinclair. Thanks for being here.

关于衰老、长寿、寿命以及延长寿命的可操作方案等问题，我有大量问题想请教您。首先想从一个简单问题开始：长寿、抗衰老与将衰老视为疾病这三者之间有何区别？因为我将您与'衰老是一种疾病'这一观点联系在一起，对吧？

I have a ton of questions for you about aging longevity, lifespan, actionable protocols to increase how long we live, etcetera. 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? Because I associate you with the statement, aging is a disease. Right.

长寿是我们研究领域更学术化的表述。抗衰老本质相同，但这个术语因被许多外行滥用而声名狼藉，所以我非常不喜欢'抗衰老'这个说法。但将衰老视为疾病和长寿都是讨论这个主题的合理方式。让我们以'衰老是疾病'的角度来探讨。当我在哈佛医学院开始研究时，疾病的定义是：如果某种异常发生在不足50%的人群中，那它就被认定为疾病。

Well, so longevity is the more academic way we describe what we research. 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. 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. So let's talk about aging as a disease. 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 fifty percent of the population, that's definitely a disease.

人们终其一生试图治愈这种病症。于是我查阅了衰老的定义：它是健康状况的恶化，会导致疾病甚至死亡——通常确实如此。这听起来完全符合疾病特征，但争议点在于：如果超过半数人群出现衰老症状，它就被归入不同类别。这种划分简直荒谬，因为这完全是个武断的界限标准。

And then people work their whole lives to try and cure that condition. And so I looked up, what's the definition of aging? And 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, but the caveat is that if more than half the population gets this condition aging, it's put in a different bucket, which is, first of all, that's outrageous because it's just a totally arbitrary cutoff.

但请思考：我们正在忽视所有这些疾病的根本诱因。衰老导致80%-90%的心脏病和阿尔茨海默症。如果我们不会衰老，身体保持年轻状态，就不会罹患这些疾病。我们实验室的研究证明：当组织时钟回拨时，这些疾病就会消失。所以说衰老才是症结所在。

But think about this, that we're ignoring the major cause of all these diseases. Aging is eighty to ninety percent the cause of heart disease, Alzheimer's. If we didn't get old and our bodies stayed youthful, we would not get those diseases. And actually what we're showing in my libels, if you turn the clock back in tissues, those diseases go away. So aging is the problem.

然而过去两百年来，我们主要在衰老引发的疾病出现后贴创可贴式治疗，那时已为时过晚。解决方案有两个：一是延缓衰老进程以预防疾病；二是当疾病发生时，不要仅作表面治疗，而是逆转身体年龄，这样疾病自会消退。这个观点让很多问题变得清晰——

And instead, through most of the last two hundred years, we've been sticking band aids on diseases that have already occurred because of aging, and then it's too late. So there are a couple of things. One is you want to slow aging down so we don't get those diseases. And when they do occur, don't just stick a bandaid on, reverse the age of the body, and then the diseases will go away. That clarifies a

我明白了许多，谢谢。我们能否指出导致衰老的某个具体普遍生理机制？

lot for me. Thank you. Can we point to one specific general phenomenon in the body that underlies aging?

幸运的是，在2000年代，我们确定了八到九种主要的衰老原因。这八到九种原因至少首次让我们能够聚在一起讨论。我们把它们放在一张披萨上，这样每个人都能分到均等的份额。但我认为其中有一块披萨比其他大得多，我们可以重点讨论这个——那就是细胞中被称为表观基因组的信息。

Fortunately, during the 2000s, we settled on eight or nine major causes of aging. These eight or nine causes, at least for the first time, allowed us to come around and talk together. 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, and we can get to that, but that's the information in the cell that we call the epigenome.

那么，请再详细介绍一下表观基因组，为我们做个概述。然后我们再探讨如何以积极的方式调整表观基因组。

Well, tell us a little bit more about the epigenome and frame it for us, if you will, And then we'll get into ways that one can adjust the epigenome in positive ways.

是的，在科学领域，我作为还原论者喜欢将其简化。我最终将衰老归结为一个方程式：由于熵导致的信息丢失。要克服热力学第二定律很难，这很公平。但这个方程式真正体现的是——我认为衰老就像信息丢失，就像你把文件复印一千次会丢失信息，或者复制磁带时，甚至通过互联网传输信息时都会有所丢失。这就是我认为的衰老本质。

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. It's a hard thing to overcome second law of thermodynamics, that's fair. 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. That's what I think is aging.

人体内存在两类信息。一类是数字化的遗传信息——ATCG这些DNA化学字母。但另一类信息同样重要，事实上是至关重要的，那就是控制基因开关的系统：在什么细胞、什么时间、根据我们吃什么等条件来激活或关闭哪些基因。事实证明，我们未来80%的寿命和健康都受控于第二部分——表观遗传信息，即这些控制系统。我把DNA比作DVD或CD上的音乐（为还记得这些设备的年轻人打个比方）。

And there are two types of information in the body. 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, etcetera. And it turns out that 80% of our future longevity and health is controlled by the second part, the epigenetic information, the control systems. I liken the DNA to the music that's on a DVD or a compact disc for the younger people who used to use these I recall.

没错。而表观基因组就像是读取器，它决定在这个细胞里播放哪组歌曲，在另一个细胞里播放不同的歌曲。但随着时间的推移，衰老就像划伤CD和DVD，导致无法播放正确的歌曲——当细胞听不到正确的指令时，它们就会出错并功能失常。这就是我认为衰老的主要驱动力。

Yeah. 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. And that is what I'm saying is the main driver of aging.

其他衰老特征大多是这一过程的表现形式。你说的划痕具体指什么？DNA展开有六英尺长。如果把所有染色体连起来，每个细胞就有六英尺长，足够在你体内往返月球八次。

And these other hallmarks are largely manifestations of that process. What are the scratches that you're referring to? So DNA is six foot long. So if you join your chromosomes together, get a six foot per cell. So there's enough to go to the moon and back eight times in your body.

这些DNA必须经过折叠才能存在于我们体内。但折叠并非杂乱无章，不是随便一团线。它是经过精密包装的，这种包装方式决定了哪些基因会被开启或关闭。当我们在胚胎中发育时，细胞会用化学物质标记DNA，标明'这个基因是用于神经细胞的'。

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. It's wrapped up very carefully in ways that dictates which genes are switched on and off. 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.

你的细胞如果幸运的话，未来一百年都会保持为神经细胞。千万别变成皮肤细胞，那会很糟糕。那些化学物质有很多种类，其中一种叫甲基化。这些小小的甲基会标记你余生中哪些基因会被表达。还有其他标记每天都在变化。

You cell will stay a nerve cell for the next hundred years if you're lucky. Don't turn into a skin cell, 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. And there are other marks that change daily.

但总的来说，我们想说的是身体通过标记DNA的能力来控制基因组——压缩某些部分，沉默那些基因不让它们表达，同时保持其他应该开放的基因开放。这种基因沉默与开放的模式决定了细胞类型和功能。而所谓的'划痕'就是这种模式的破坏。比如本该在皮肤中表达的基因开始在大脑中激活，这本来不该发生，但我们确实观察到了这种现象。

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. And that pattern of genes that are silent and open, silent, open is what dictates the cells type, the cells function. 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.

反之亦然，随着年龄增长，某些基因可能会逐渐关闭。细胞会逐渐失去这些结构，丧失其特性。它们忘记了自己该做什么，于是我们就生病了。我们称之为衰老。而这个过程是可以测量的。

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. We call that aging. And we can measure that.

事实上，我们的测量方法已经能根据这些化学物质的变化来预测一个人的死亡时间。这些变化是否与那些...

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. Are these changes the same sorts of changes that underlie the

我们常见的外表衰老特征有关？比如头发变白、皮肤起皱、面部下垂？还是说我们讨论的是那些看起来会更老，但实际寿命更长的人群？

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, or are we talking about people that potentially are going to look older, but simply live longer?

其实广义来说，你看上去多老就是多老。以百岁老人家族为例，这些家族成员通常能活过100岁。他们70岁时看起来还像50岁或更年轻。所以外貌确实是很好的指标。

Well, it's actually, you are as old as you look, if you want to generalize. So let's start with centenarian families. These are families that tend to live over 100. When they're 70, they still look 50 or less. So it is a good indicator.

虽然不完全准确——比如我在澳大利亚长大加速了皮肤老化——但总体上，从皮肤紧致度、薄厚程度、皱纹数量等外观特征，就能对衰老程度有个基本判断。毕竟没人会因为头发变白而死，但这些外在特征确实能说明问题。

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. No one's ever dyed 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.

非常有趣。我想稍作休息，感谢我们的赞助商之一大卫。大卫生产了一种与众不同的蛋白棒。每根含有28克蛋白质，仅150卡路里且零糖分。没错，28克蛋白质且75%的热量来自蛋白质。

Very interesting. I'd like to take a quick break and acknowledge one of our sponsors, David. David makes a protein bar unlike any other. It has 28 grams of protein, only 150 calories and zero grams of sugar. That's right, 28 grams of protein and 75% of its calories come from protein.

这比其他蛋白棒的蛋白质含量高出50%。DAVID的这款蛋白棒口感也非常棒。目前我最喜欢新出的肉桂卷口味，但我也喜欢巧克力曲奇面团口味和咸味花生酱口味。还有个好消息，大卫蛋白棒现已重新上架。由于太受欢迎，它们曾断货数月，但现在已恢复供应。

That's 50% higher than the next closest protein bar. These bars from DAVID also taste amazing. Right now, my favorite flavor is the new cinnamon roll flavor, but I also like the chocolate chip cookie dough flavor, and I also like the salted peanut butter flavor. Also big news, David Bars are now back in stock. They were sold out for several months because they are that popular, but they are now back in stock.

通过食用大卫蛋白棒，我能在零食的热量摄入中获得28克蛋白质，这让我很容易实现每天每磅体重摄入1克蛋白质的目标，且不会摄入过多热量。我通常在下午吃一根大卫蛋白棒，出门或旅行时也总会随身携带，因为它们能非常方便地补充蛋白质。正如我提到的，它们非常美味，且28克蛋白质仅150卡路里，饱腹感很强。因此也很适合作为加餐。如果你想尝试大卫蛋白棒，可以访问davidprotein.com/huberman。

By eating a David Bar, I'm able to get 28 grams of protein in the calories of a snack, which makes it very easy for me to meet my protein goals of one gram of protein per pound of body weight per day, and to do so without eating excess calories. I generally eat a David bar most afternoons, and I always keep them with me when I'm away from home or traveling because they're incredibly convenient to get enough protein. As I mentioned, they're incredibly delicious and given that 28 grams of protein, they're pretty filling for just 150 calories. So they're great between meals as well. If you'd like to try David, you can go to davidprotein.com/huberman.

再次强调，网址是davidprotein.com/huberman。我最初从事发育神经生物学研究。早期学到的、至今仍深信不疑的一点是：发育不会在12岁、15岁甚至25岁停止，人的整个生命就是一条漫长的发育弧线，对吧？在思考这条弧线的不同阶段时，婴儿期尤其是青春期，似乎是衰老速度特别快的阶段。虽然我们看着婴儿、儿童和青春期的孩子总觉得他们充满活力、非常年轻。

Again, that's davidprotein.com/huberman. 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, right? 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. And I know we normally look at babies and children and kids in puberty, we think, oh, they're so vital, they're so young.

但你描述的表观基因组变化，以及将衰老视为疾病的观点让我不禁想问：那些生命力最旺盛的阶段，是否正是我们衰老最快的时期？是的，这是个非常好的问题。

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? Yes, a really good question.

这些可测量的化学物质被称为霍瓦特时钟，也就是生物钟。它不同于你的实际年龄。有些人在生物学上比其他人年轻十到二十岁。研究发现，如果从出生甚至出生前就开始测量这个时钟（观察动物也是如此），生命早期会显示出基于该时钟的年龄急剧增长。

So those chemicals we can measure, it's also known as the Horvath clock. It's the biological clock. It's separate from your chronological age. There are some people that are ten, twenty years younger than other people biologically. 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.

你说得对。生命最初几年存在加速衰老现象，之后趋于平稳，这个观点非常重要。但你提到的另一点也很有趣：我们发现那些出现故障、产生磨损并导致衰老的基因，正是那些早期发育基因。它们在生命后期激活并扰乱系统，而且似乎特别容易受到这些损伤的影响。

So you're right. 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. But there's another interesting thing you brought up, 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. They come on late in life and just mess up the system. And they seem to be particularly susceptible to those scratches.

那么是什么导致了这些损伤呢？我们在实验室里发现了几种原因。一是染色体断裂，DNA损伤，特别是DNA断裂处的切口。无论是X射线、宇宙射线，还是晒太阳，都会导致染色体断裂，这会加速我提到的那些美丽DNA环的解旋。我们甚至能在小鼠身上实现这个过程。

So what's causing the scratches? Well, we know of a couple of things in my lab we figured out. One is broken chromosomes, DNA damage, particularly cuts to the DNA breaks. 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. We can actually do this to a mouse.

我们可以加速这个过程，让小鼠提前衰老50%，出现脊柱弯曲（驼背）、毛发灰白、器官老化等症状。现在我们能正向控制衰老进程。另一个加速衰老的因素是大量细胞损伤或压力。我们通过夹捏神经发现，它们的衰老过程也会加速。

We can accelerate that process and we get an old mouse, 50% older, and it has this bent spine, kyphosis, it has gray hair, its organs are old. So we now can control aging in the forwards direction. 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.

太不可思议了。这更像是个轶事现象。确实是个轶事现象，就像初中时暑假回家，返校后发现有些男生暑假里突然长了胡子，或是迅速成熟。你认为青春期开始和进程的速度能预测整体衰老速度吗？

Incredible. Yeah, this is more of an anecdotal phenomenon. It is an anecdotal phenomenon, but this experience of in junior high school, going home for a summer, and you come back, and then some of the kids, like they grew beards over the summer, or they completely matured quickly over the summer. Do you think there's any reason to believe that rates of entry into and through puberty can predict overall rates of aging?

确实如此，但我不想吓唬任何人。有研究表明，发育越慢的人，往往寿命更长更健康。这可能与生长激素有关——我们知道生长激素会促进衰老。

Well, yeah, I don't want to scare anybody. Sure. There are studies that show that the slower you take to develop, it also is predictive of having a longer, healthier life. And it may have something to do with growth hormone. We know that growth hormone is pro aging.

短期使用生长激素的人会增肌并感觉良好，但这就像同时点燃蜡烛两头。想要长寿就该减少使用。那些基因改造的生长激素低下动物（有些是侏儒）寿命反而最长。我们能否...

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. Ultimately, if you want to live longer, you want less of that. And the animals that have been generated and mutants that have low growth hormone, sometimes these are dwarfs, they live the longest by far. Can we

说体型大小与寿命长短存在直接关系？

say that there's a direct relationship between body size and longevity or duration of life?

确实存在关联，但这不意味着你会被早期表观基因组或基因组所奴役。好消息是表观基因组可以改变——那些DNA环和结构能通过生活方式改变。无论体型如何，你对生命的影响都远大于基因的馈赠。80%取决于表观遗传，而非基因遗传。

Well, there is, but that doesn't mean that you're a slave to your early epigenome, nor to your genome. The good news is that the epigenome can change. Those loops and structures can be modified by how you live your life. No matter what size you are, you can have a bigger impact on your life than anything your genes give you. 80% is epigenetic, not genetic.

那么我们来谈谈一些

So let's talk about some

人们可以做的事情，我大致将这些分门别类，而不是直接讨论可操作方案。首先与食物、血糖、胰岛素相关。我经常听说禁食对我们有益，但很少听到具体原因。我认为理解其机制能让人们做出更明智的选择，而不仅仅是决定是否禁食或禁食时长，这些应该基于对机制的理解。那么为什么血糖、葡萄糖和胰岛素水平升高会加速衰老？又为什么每天或更长时间内保持空腹状态能延长寿命？

of the things that people can do, and I've kind of batched these into categories rather than just diving right into actionable protocols. So the first one relates to food, blood sugar, insulin. 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. 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. 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?

好，让我们从

Well, let's start

我认为的一个重大误区开始——人们永远不该感到饥饿。有些人一生从未体验过饥饿，这对他们非常不利。这源于20世纪的观点，认为不应让胰腺承受压力，要保持胰岛素水平稳定避免波动。但我和同事们在长寿领域研究发现，观察动物——无论是狗、老鼠还是猴子——那些寿命延长30%且保持健康的个体，都是不持续进食的。

with what I think was a big mistake, was the idea that people should never be hungry. Some people never experience hunger in their whole lives. It's really, really bad for them. It was based, I believe, on the twentieth 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. 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.

实际上这一现象早在20世纪初就被发现，但被忽视了。1930年代克莱德·麦凯重新发现热量限制效应，他在大鼠食物中添加纤维素使其无法获取足够热量，这些大鼠寿命延长了30%，但该发现再次沉寂。直到2000年代出现重大转机：我的实验室和其他团队证实人体存在长寿基因，这些基因激活后可抵御衰老和疾病。

Actually it was first discovered back in the early twentieth century, but people ignored it. And then it was rediscovered in the 1930s, Clyde McKay did caloric restriction. 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, but then it went away. And then it came back in the 2000s in a big way when a couple of things happened. 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.

我研究的基因家族称为sirtuins，共七种。我们在2005年的科学论文中证明，当胰岛素和类胰岛素生长因子水平较低时，会激活长寿基因。其中关键的SERT1基因若因全天高胰岛素水平（持续进食状态）而无法激活，你的表观基因组——维持细胞功能的信息载体——就会加速退化。

The group of genes that I work on are called sirtuins, there's seven of them. 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. One of them that's really important is called SERT1. But by having high levels of insulin all day, being fed means your longevity genes are not switched on. So you're falling apart, your epigenome, your information that keeps your cells functioning over time just degrades quicker.

持续进食状态就像让生命时钟走得更快。另一个可能机制是：持续进食剥夺了细胞修复表观基因组的休息期，从而加速衰老。还有其他虽不显著但重要的因素，比如体内低葡萄糖水平会增强主要肌肉和大脑对胰岛素的敏感性，促进血糖吸收——这是非常有益的，你绝不想让葡萄糖在血液中过度游离。

Your clock is ticking faster by always being fed, okay? 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. 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 and your brain to become more sensitive to insulin and suck the glucose out of your bloodstream, which is very good. You don't want to have glucose flowing around too much.

这能预防2型糖尿病。人们能从中总结出什么方案呢？如果让我说一点，我一定会建议每天少吃一顿饭。这是最有效的方法。具体哪一餐重要吗？还是本质上都一样？

And that will ward off type two diabetes. What is the protocol that people can extrapolate from that? Well, if there's one thing I could say, I would say definitely try to skip a meal a day. That's the best thing. Does it matter which meal or the essentially equivalent?

只要是在一天开始或结束时进行就行，因为这样你可以把禁食时间与睡眠时段叠加——希望你在睡觉时也不会进食。但要注意，刚开始尝试的两三周会感到饥饿，而且会有想嚼东西的习惯。这涉及很多生理因素，但请尽量

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, be aware 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

坚持过前三周，不吃早餐或晚餐，你就能适应。你试过更长时间的禁食吗？比如48小时、72小时或一周？

make it through the first three weeks, and do without breakfast or do without dinner, and you'll get through it. Do you ever do longer fasts, like forty eight hours or seventy two hours or week long fasts?

不常尝试。我发现超过24小时就很困难。但当我这么做时（大概每月一次），会坚持两天。实际上如果坚持三天不进食，会启动更强的延寿效益。人体有个自噬系统，能分解体内老旧和错误折叠的蛋白质。

Not very often. I find it quite difficult to go more than twenty four hours. But when I do it, maybe it's once a month, I'll go for two days. After two, and actually even better if you go for three days without eating, it kicks in even greater longevity benefits. So there's a system called the autophagy system, which digests old and misfolded proteins in the body.

饥饿时会启动一种自然的清洁机制——巨自噬。但我的好友阿尔伯特·爱因斯坦医学院的安娜·玛丽亚·奎尔沃发现了更深层的清洁机制：分子伴侣介导的自噬，在禁食第二、三天启动，能清除深层蛋白质。最让我兴奋的是她刚发表重要论文称：在老年小鼠中激活这一过程可延长35%寿命。

And there's a natural cleansing that happens when you're hungry, macroautophagy its name is. But a good friend of mine, Anna 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. And what what excites me is she just put out a a big paper that said, if you trigger this process in an in an old mouse, it lives 35% longer.

我们早就知道改善睡眠的方法，包括服用苏糖酸镁、茶氨酸、洋甘菊提取物和甘氨酸等成分，以及藏红花和缬草根等较冷门的物质。这些都是经临床验证的成分，能帮助入睡、保持睡眠并醒来更神清气爽。很高兴宣布我们的长期赞助商AG1推出了新产品AGZ——一款助眠饮品，含有精确配比的顶级助眠复合物，只需轻松冲泡即可饮用。

We've known for a long time that there are things that we can do to improve our sleep, And that includes things that we can take things like magnesium threonate, theanine, chamomile extract, and glycine, along with lesser known things like saffron and valerian root. These are all clinically supported ingredients that can help you fall asleep, stay asleep, and wake up feeling more refreshed. I'm excited to share that our longtime sponsor AG1 just created a new product called AGZ, a nightly drink designed to help you get better sleep and have you wake up feeling super refreshed. Over the past few years, I've worked with the team at AG1 to help create this new AGZ formula. It has the best sleep supporting compounds in exactly the right ratios in one easy to drink mix.

这省去了在琳琅满目的助眠补充剂中筛选合适剂量和配方的麻烦。据我所知，AGZ是市面上最全面的睡眠补充剂。我在睡前30-60分钟服用，顺便说一句味道很棒。它显著提升了我的睡眠质量和深度。

This removes all the complexity of trying to forge the vast landscape of supplements focused on sleep and figuring out the right dosages and which ones to take for you. AGZ is to my knowledge, the most comprehensive sleep supplement on the market. I take it thirty to sixty minutes before sleep. It's delicious by the way. And it dramatically increases both the quality and the depth of my sleep.

我之所以知道这一点，既源于我对睡眠的主观体验，也因为我会追踪睡眠数据。我很期待大家尝试这款新的AGZ配方，享受优质睡眠带来的益处。AGZ现有巧克力、薄荷巧克力以及混合莓果三种口味。正如我之前提到的，它们都极其美味。三者中我的最爱应该是薄荷巧克力，不过其实我都喜欢。

I know that both from my subjective experience of my sleep and because I track my sleep. I'm excited for everyone to try this new AGZ formulation and to enjoy the benefits of better sleep. AGZ is available in chocolate, chocolate mint, and mixed berry flavors. And as I mentioned before, they're all extremely delicious. My favorite of the three has to be, I think chocolate mint, but I really like them all.

如果你想尝试AGZ，请访问drinkagz.com/huberman获取专属优惠。再次强调，网址是drinkagz.com/huberman。当你禁食时，无论时长多久，我知道你会摄入水等液体，可能还有些咖啡因。听说你今天喝了好几杯浓缩咖啡？你同时也在补充电解质吗？

If you'd like to try AGZ, go to drinkagz.com/huberman to get a special offer. Again, that's drinkagz.com/huberman. When you are fasting, regardless of how long, I know you're ingesting fluids like water and presumably some caffeine. I heard you had several or more espresso today. Are you also ingesting electrolytes?

比如有些人禁食时会头晕手抖，现在往水里添加钠、钾、镁等电解质的做法正逐渐流行起来。这是你日常会做的吗？或者你认为人们有必要这样做吗？

Like, 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. Is that something that you do, or that you see a need for people to do?

嗯，这确实有道理，但我自己没这个需求所以不补充。我白天喝茶，晨起喝咖啡，从不会手抖。既然没出问题就不必调整。

Well, it makes sense, but I haven't had a need to do it, so I don't. I drink tea during the day and coffee when I'm first awake, and I don't get the shakes. So I don't fix what's not broken.

好的。你曾提到大量证据表明，每天保持一段时间低血糖状态能激活促长寿、抗衰老机制，而延长至两三天还能进一步触发清除死亡细胞等额外机制。血糖究竟如何触发这些机制？我们总说降低葡萄糖水平会改善状况，能否详细讲讲背后的细胞与遗传机制？比如sirtuins这类物质，葡萄糖与sirtuins在机制层面究竟如何关联？

Okay. You've told us that there's ample evidence that keeping your blood sugar low for a period of time each twenty four 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. How is it that blood glucose triggers these mechanisms? Because we've said, okay, remove glucose and things get better. 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?

对，这是个

Yeah, that's a

非常好的问题。这证明你是个科学家——还是世界顶尖的那种。我们现在知道这些长寿通路——我们称之为长寿基因——会相互通信。以前我们总争论哪个长寿基因更重要，这其实很荒谬。

really good question. That proves you're a scientist or world leading one. So what we've now know is that these longevity pathways, we call them, these longevity genes talk to each other. And we used to say, oh, my longevity gene's more important than yours. It was ridiculous.

因为它们都在互相交流。你拉动一个杠杆，另一个就会移动。可以这样理解：体内设有检测你饮食的系统。Sirtuins主要对糖分和胰岛素作出反应。还有另一个叫做mTOR的系统，负责感知进入体内的蛋白质或氨基酸含量。

Cause they're all talking to each other. You pull one lever and the other one moves. And the way to think of it is that there are systems set up to detect what you're eating. 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.

它们之间会相互沟通。我们可以通过调节一个来影响另一个，反之亦然。但当你禁食时，会同时激活sirtuin（这对你有益），同时由于缺乏氨基酸（特别是亮氨酸、异亮氨酸和缬氨酸这三种），身体会下调mTOR的活性。正是这种sirtuin上调而mTOR下调的状态带来了巨大益处——它能激活身体所有防御机制：分解老旧蛋白质、提高胰岛素敏感性、增加能量供给、修复细胞等等。

And they talk to each other. We can pull one and affect the other and vice versa. 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 down regulate mTOR. And it's that up sirtuin, down mTOR that is hugely beneficial and turns on all of the body's defenses, chewing up the old proteins, improving insulin sensitivity, giving us more energy, repairing cells, all of that.

所以我认为这两条通路是

And so these two pathways I think are

对长寿最重要的。你提到亮氨酸。显然由于亮氨酸对mTOR通路的影响，现在很多人（不仅限于特定健身群体）都在定期主动增加亮氨酸摄入，以最大化健康水平和运动表现，有些是为了增肌，有些则纯粹为了健康。但我理解你最后那句话的意思是：亮氨酸由于会触发细胞生长，在某种意义上其实是促衰老的？是这样吗？

the most important for longevity. You mentioned leucine. 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. But what I interpret your last statement to mean is that leucine, because it triggers cellular growth, is actually pro aging in some sense. Is that right?

现有证据确实指向这个结论。而且这又

That's what the evidence suggests. And again, it

回到了那个经典争论：是否应该补充生长激素或睾酮？这些行为都能带来立竿见影的好处——肌肉更快增长，即刻感觉更好。但研究表明，这是以牺牲长期健康为代价的。

goes back to the debate, should you supplement with growth hormone or testosterone? All of these activities will give you immediate benefits. You'll bulk up more. You'll feel better immediately. But based on the research, it's at the expense of long term health.

因此我对长寿的实践方式是：不两头烧蜡烛。我只点燃蜡烛的一端——非常小心不让它熄灭，同时保持适量运动来维持肌肉量，但绝不追求夸张体型。见过我的人都知道我不是职业健美运动员，但关键是我试图做到...

So my view of longevity, the way I treat my body is I don't burn both candles. I have one end of the candle lit. 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. Anyone who's seen me knows that I'm not a professional bodybuilder, but I tried to actually, here's the key.

我记得我从未公开说过这件事。我采用间歇性方式：先禁食，然后进食，接着服用补充剂，再次禁食，随后锻炼。通过精准把握补充剂摄入和进食时机，有时能促进肌肉增长。因为持续摄入和持续行动并不会自动见效，这就是为什么我花了约十五年才完善这套方案。

And I haven't said this publicly that I can remember. 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 fifteen years to develop my protocol.

这其中有很多精妙之处。关键在于让细胞感知适度逆境。现代生活中我们久坐不动、饮食过量、缺乏运动，细胞会误以为一切安好。

And there's a lot of subtlety to it. What you want to do is to get the cells to be perceiving adversity, okay? Because our modern life, we're sitting around, we're eating too much, we're not exercising. Our cells respond. They go, Hey, everything's cool, no problem.

于是它们放松警惕，不启动防御机制，导致我们加速衰老。生物钟数据明确显示：坚持运动且节制饮食者衰老更慢。这是不争的事实。

And they become relaxed and they don't turn on their defenses, and we age rapidly. We can see it in the clock. People who exercise and eat less have a slower ticking clock. It's a fact. One of

最常被问到的问题是：摄入XX会打破禁食状态吗？无论是食物、咖啡，还是看到别人吃饼干——人们对此非常极端。我的理解（如有误请指正）是这取决于前夜状况、是否糖尿病等多重因素。比如午夜大餐后6点起床，黑咖啡或加奶咖啡可能'打破'禁食，但身体根本没有'禁食开关'这种机制。

the questions I get asked all the time is, does ingesting blank break the fast? 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? People get pretty extreme with this. 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. So for instance, if I eat an enormous meal at midnight, go to sleep, wake up at 6AM, 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.

身体只懂葡萄糖、AMPK、mTOR等生化语言。你真正该担心的是这些热量摄入是否会影响禁食效果？更根本的是：如何判断禁食程度足以产生益处？毕竟不是所有人都能（或愿意）仅靠水或茶度过特定时段。

The body only speaks in the language of glucose, AMPK, mTOR, etcetera. 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? 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.

首先从哲学层面回答：若生活毫无乐趣，长寿何益？晨间咖啡加点牛奶，一勺酸奶不会致命。橄榄油几乎不含蛋白质或碳水。

Well, my first answer is not scientific. It's philosophical. If you don't enjoy life, what's the point? 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.

因此这些行为不太会负面干扰长寿通路。但若完全禁止这些，我的生活质量会下降。虽然橄榄油不如酸奶理想，但我们都在尝试优化——本就没有完美方案。现有认知仍有限，连对我个人的最优解都尚未明确，更遑论普适标准。

And so I'm probably not affecting those longevity pathways negatively. But without that, first of I wouldn't enjoy my life as much. 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. We don't know what's optimal for me, let alone everybody else.

但我支持你。我不认为吃几勺东西会伤害你，除非是高果糖玉米糖浆。这么做的关键在于尽力而为。如果你从正常生活突然变成整天不进食，你肯定会失败。就像突然戒烟一样。

But I'm with you. I don't believe that taking a couple of spoonfuls of something, unless it's high fructose corn syrup, is gonna hurt you. The point about doing this is that you try to do your best. If you go from regular living to don't eat the whole day, you're gonna fail. Like quitting smoking cold Turkey.

嚼口香糖和贴戒烟贴更容易，因为你的身体需要适应各种习惯。这既是社交行为也是生理行为——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。你的边缘系统会不断怂恿你去做。你必须与之抗争。但一旦度过这个阶段，你会变得更好，关键是要循序渐进。

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. Your limbic system is gonna go, hey, do it, it, do it. And you're gonna have to fight it. But once you get through it, you'll be better, but you do it in stages.

不要突然完全戒断，因为众所周知，如果你一开始就尝试严格节食...

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

...几乎必定会失败。这很好地诠释了理性禁食和科学补充剂的本质。说到补充剂，NMN（β-烟酰胺单核苷酸）呢？如何将其纳入补充方案？是否建议这样做？

gates, you'll almost always fail. That captures the essence of fasting rationally and a rational approach to supplementation very well. Along the lines of supplementation, what about NMN? How does one incorporate that into a supplementation protocol? Should they choose to do that?

好的。免责声明：我不推荐任何产品，但可以分享我的做法。先科普一下：这些Sirtuin长寿基因是我们最初在麻省理工学院的酵母细胞中发现，2000年代我到哈佛后又在动物身上验证的。我的第一位博士后研究员柴姆·科恩发表了重要论文，发现激活Sirtuin6基因（记住七种Sirtuin中的第六种）效果非常显著，使他改造的实验鼠寿命显著延长——无论雄雌，这很棒。

All right. Well, disclaimer is that I don't recommend anything, but I talk about what I do. So a bit of scientific background, 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. And one of my first postdocs, actually literally my first postdoc, Chaim Cohen, published a great paper and found that turning on the sirtuin six gene, remember the seven, number six gene is very potent. It extended the lifespan dramatically of mice that he engineered, both males and females, which is great.

所以关键是要自然提升这些Sirtuin的活性。它们是基因，但也会制造蛋白质（基因通常就是编码蛋白质的）。这些蛋白质会以多种方式维护身体健康。NAD水平对维持Sirtuin防御系统的年轻态至关重要。

So what you want to do is naturally boost the activity of these sirtuins. 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. NAD levels are really important for keeping those sirtuin defenses at a youthful level.

我服用NAD的前体物质NMN，身体只需一步就能将其转化为NAD分子。通过测量数十人的数据发现：按照我的服用时长（我已持续数年），大约两周后血液NAD水平平均能翻倍。我要说明：我的方法未必适合所有人。但我研究过数十位每天服用1-2克NMN的受试者，无一例外地发现，采用我的方案后NAD水平都提升了约两倍或更多。

I take a precursor to NAD called NMN, and the body uses that to make the NAD molecule in one step. 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. So I just wanna people to be aware that what I do may not perfectly work at all for others. 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.

根据个人经验，因为我长期服用这个。如果不服用，我就感觉自己像50岁。太可怕了，我无法清晰思考。可能是安慰剂效应，但谁知道呢？

Anecdotally, because I've been taking this for a long time. If I don't take it, I start to feel 50 years old. It's horrible. I can't think straight. It may be placebo, but who knows?

但我们现在正在进行非常谨慎的临床试验。

But what we're doing now are very careful clinical trials.

我想稍作休息，感谢我们的赞助商Eight Sleep。Eight Sleep生产具有冷却、加热和睡眠追踪功能的智能床垫罩。确保良好睡眠的最佳方法之一是保持睡眠环境温度适宜。因为要进入并保持深度睡眠，你的体温实际上需要下降约1到3度；而为了醒来时感觉神清气爽，体温又需要回升约1到3度。

I'd like to take a quick break and acknowledge our sponsor, Sleep. Eight Sleep makes smart mattress covers with cooling, heating, and sleep tracking capacity. One of the best ways to ensure a great night's sleep is to make sure that the temperature of your sleeping environment is correct. And that's because in order to fall and stay deeply asleep, your body temperature actually has to drop by about one to three degrees. And in order to wake up feeling refreshed and energized, your body temperature actually has to increase by about one to three degrees.

Eight Sleep会根据你的个人需求整夜自动调节床温。我使用Eight Sleep床垫罩已超过四年，它彻底改变并提升了我的睡眠质量。Eight Sleep刚推出了最新款Pod 5，具备多项重要新功能，其中之一是'自动驾驶'——这个AI引擎能学习你的睡眠模式，根据不同睡眠阶段调节环境温度。

Eight Sleep automatically regulates the temperature of your bed throughout the night according to your unique needs. I've been sleeping on an Eight Sleep mattress cover for over four years now, and it has completely transformed and improved the quality of my sleep. Eight Sleep has just launched their latest model, the Pod five, and the Pod five has several new important features. One of these new features is called autopilot. Autopilot is an AI engine that learns your sleep patterns to adjust the temperature of your sleeping environment across different sleep stages.

如果你打鼾，它还会抬高你的头部，并进行其他调整以优化睡眠。Pod 5底座还配有集成扬声器，可同步Eight Sleep应用播放助眠音频。音频库包含多个NSDR（非睡眠深度休息）脚本，这些是我与Eight Sleep合作录制的。NSDR通过引导深度身体放松配合简单呼吸练习，经同行评审研究证实能恢复身心活力。

Also elevates your head if you're snoring and it makes other shifts to optimize your sleep. The base on the Pod five also has an integrated speaker that syncs to the eight Sleep app and can play audio to support relaxation and recovery. The audio catalog includes several NSDR, non sleep deep rest scripts that I worked on with eight Sleep to Record. If you're not familiar, NSDR involves listening to an audio script that walks you through a deep body relaxation combined with some very simple breathing exercises. And that combination has been shown in peer reviewed studies to restore your mental and physical vigor.

这很棒，因为虽然我们都希望按时就寝并获得完美睡眠，但现实常常会晚睡或早起赶时间。NSDR能缓解轻微睡眠不足的负面影响，并帮助你在夜醒后更快重新入睡。这是个立竿见影且持续有效的强大工具。想尝试Eight Sleep，请访问8sleep.com/huberman，新款Pod 5最高可享350美元优惠。

And this is great because while we would all like to get to bed on time and get up after a perfect night's sleep, oftentimes we get to bed a little late or later. Sometimes we have to get up early and charge into the day because we have our obligations. NSDR can help offset some of the negative effects of slight sleep deprivation and NSDR gets you better at falling back asleep should you wake up in the middle of the night. It's an extremely powerful tool that anyone can benefit from the first time and every time. If you'd like to try eight Sleep, go to 8sleep.com/huberman to get up to $350 off the new Pod five.

Eight Sleep配送范围覆盖全球多国，包括墨西哥和阿联酋。再次提醒：8sleep.com/huberman可省350美元。现在我想谈谈铁元素和铁负荷。虽然具体需求量因人而异，但令我惊讶的是铁质在某些情况下竟会加速衰老过程。

Eight Sleep ships to many countries worldwide, including Mexico and The UAE. Again, that's 8sleep.com/huberman to save up to $350. I wanna talk about iron and iron load. 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.

这是来自西班牙的新发现。曼努埃尔·塞拉诺实验室发现，过量铁元素会增加体内衰老细胞数量。衰老细胞是随着年龄增长积累的'僵尸细胞'，它们主要引发炎症，也可能导致癌症。研究发现，若能清除或避免积累这些细胞，就能保持年轻状态。在动物实验中已证实这点，梅奥诊所关于人类的研究也得出有趣结论。以我观察为例，那些非常健康、生活方式与我相似、饮食偏素食但不严格的人，血红蛋白、铁蛋白水平往往略低，但我们却拥有超乎寻常的精力。

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, 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. And it's found that if you get rid of these cells or never accumulate them, you stay younger. In animals, and there's some really interesting studies out of Mayo Clinic in humans as well. 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.

我们并不贫血，生活状态极佳。但只看数据的医生可能会建议补铁。我想强调的是，这正体现了医疗需要个性化——必须长期观察个体，了解什么对他们有效且健康，不应只追求平均值，而应追求最优化状态。

We're not anemic and we're getting along with great in life. 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.

这个回答太棒了。您提到长期追踪数据，这正是您长期专注的领域。我从大学起就每半年做一次血液检测，我热爱数据。有哪些您特别关注、认为值得普通人留意的指标吗？

I love that answer. 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. I've been getting blood work done about every six months, I was in college. Got, I like data. Are there any things that you pay attention to that you think are particularly interesting for people to just take note of?

我们并非要挑战医生的专业意见，但如果人们选择查看自己的检测报告，应该了解哪些分子指标？您会重点关注哪些项目？

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 you look at?

首先必须建立追踪机制，因为单次检测远远不够。这些指标会波动，十年以上的数据才真正具有参考价值，这点您也清楚。关键指标包括：血糖水平、糖化血红蛋白（HbA1c，反映月度平均血糖）。

Yeah. The first is that you should be tracking things, because one measurement isn't enough. These things vary, and over time, and if you can have a decade or more of data, it's super informative, as you know. But there are some main ones. Would say your blood sugar levels, want to do your HbA1c, which is your average glucose levels over the month.

还有我提过的炎症指标C反应蛋白（CRP）。对，我们来详细说说

There's CRP, which I mentioned for inflammation. Yeah, let's talk

CRP（C反应蛋白）值得深入讨论，因为它已被证明是黄斑变性、心脏病等多种疾病的早期标志物。但我觉得这个指标目前关注度远远不够。

about C reactive protein for a second, because I think it's been shown to be an early marker of macular degeneration, of a heart disease, of a variety of different things. CRP is something that we don't hear enough about, I think.

它是心血管炎症的最佳标志物，同时我们也将其作为长寿预测指标，其水平会随死亡率上升。虽然这只是相关性，但有充分数据表明，若你的CRP水平偏高，就需要迅速降低。该水平通常随年龄和炎症程度上升。降低方法包括调整饮食、减少进食量、多吃蔬菜，你会发现指标会下降。也有药物可以做到这一点。

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. And so this is an association, but there's enough data that I would say, you have high levels of CRP, you need to get your levels down quickly. And the levels usually go up with age and with levels of inflammation. 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. There are also drugs that can do it.

抗炎药物同样有效。但CRP实际上是HCRP（高敏C反应蛋白），还有HSCRP（超敏C反应蛋白）。你的医生会清楚该测哪一种。

Anti inflammatories can do it as well. But CRP is, it's actually HCRP. There's a high sensitive or HSCRP. Your doctor will know. Get one

要关注这些指标，因为即使血糖值正常——无论是空腹血糖还是常规血糖——医生可能告诉你一切正常。但许多人血糖正常却CRP偏高，这对长期健康同样有害，并能预测未来心脏病发作。宏观来看，有哪些行为工具能调节这些机制？本质上就是调控DNA表达和功能的方式？换句话说，人们能通过哪些方式改善sirtuin通路？当然这存在前提条件。

of those readings because if you've got normal blood sugar levels, your doctor, 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. 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? In other words, what are the sorts of things that people can do to improve the sirtuin pathway? And I realize that there are caveats.

我们无法直接将特定行为与sirtuins关联，但总体而言，人们能做什么？你本人是怎么做的？

We can't go directly from a behavior to sirtuins, but in the general theme, what can people do? What do you do?

我们知道小鼠的有氧运动能提升其NAD水平，SERT基因（实际有两个基因：1号和3号）表达也会增强。我的运动方案基于科学文献，这些研究证明保持肌肉量至关重要，原因包括：首要两点是维持激素水平。作为年长男性，我的睾酮和肌肉量会随时间流失。通过锻炼我保持了这些指标，事实上可能自20岁后就没再有过这样的体魄。

Well, we know that aerobic exercise in mice and rats raises their NAD levels, and their levels of SERT, one of the genes goes up, two actually, number one and number three. I base my exercise on the scientific literature, which has shown that maintaining muscle mass is very important for a number of reasons. The two main ones are you want to maintain your hormone levels. I'm an older male, losing my testosterone and muscle mass over time. And by exercising, I will maintain that and have, in fact, I probably haven't had a body like this since I was 20.

这就是这种生活方式的好处之一。那么雌激素呢？因为女性情况不同，她们体内的...

So that's one of the benefits of having this lifestyle. What about estrogen? Because women are different in the sense that they do, the number of

卵子数量会随时间变化，卵巢功能也是，对吧？你认为女性能否通过这些相同方案长期维持雌激素水平？

eggs that they, and the ovaries change over time, right? Do you think that they can maintain estrogen levels over longer periods of time using some of these same protocols?

我不想过多讨论轶事，但我要告诉你科学事实：如果你对一只老鼠进行禁食或热量限制，直到它本应失去生育能力的阶段——大约在1岁左右，雌鼠就会不育。

I don't wanna 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, female mouse.

是由于禁食还是单纯因为衰老？

Due to fasting or due simply to aging?

是因为衰老，纯粹是衰老。禁食并不极端，只是减少热量摄入。

Due to aging, due to aging. The fasting, it's not an extreme fast. It's just less calories.

明白了。

Got it.

当你让它们恢复正常饮食后，它们会在之后很多个月里重新恢复生育能力。这说明延缓衰老的效果也作用于生殖系统。有趣的是，我绝不会建议任何女性通过过度消瘦来试图保持生育力——这不是我的观点。

Then you put them back on a regular food and they become fertile again for many, many months afterwards. So the effect on slowing down aging is also on the reproductive system. Interesting. And so I wouldn't say to any woman, I wouldn't think that they should become super skinny to try and preserve fertility. That's not what I'm saying.

但我们研究的这些通路，这些Sirtuins蛋白，已知能延缓雌性动物的不育。举例来说，我是一篇论文的主要作者之一，我们使用NMN（记住这是Sirtuins的燃料）对老年老鼠进行实验——其中一组老鼠已16个月大（它们本应在12个月时失去生育能力），给它们服用NMN。

But these pathways that we work on, these sirtuins, are known to delay infertility in female animals. Case in point, I'm one of the lead authors on a paper where we used NMN. Remember, this is the gas, the fuel, the petrol for the sirtuins. We gave old mice, one group of mice was 16 old. Remember they became infertile at 12, gave them NMN.

仅六周后它们就产下了后代，重新获得了生育能力。这颠覆了生物学教科书的理论——雌性哺乳动物的卵子会耗尽。事实证明这是错误的，你可以使雌性生殖系统恢复活力，甚至让它们重新进入发情期（我们称之为‘老鼠鼓掌’）。这完全是生物学的新范式。

And I think it was only six weeks later they had offspring. They became fertile again, which goes against biology, textbook biology, which is that female mammals run out of eggs. Turns out that's not true. You can rejuvenate the female reproductive system and even get them to come out of mouse applause as we call it. So that's a whole new paradigm in biology as well.

我认为非常有趣的是，从你及同事们的研究成果以及我实验室的工作中，我们了解到人体拥有惊人的自愈和从疾病创伤中恢复的能力。我们曾认为这是条单行道——某些损伤无法修复，某些疾病无法克服，但现在发现系统可以重置，身体能以令人惊叹的方式重获新生，未来人们甚至会疑惑为何我们没有更早研究这些。感谢你今天与我们分享这些见解。我意识到我们深入探讨了机制原理，也谈及了全球性方案——从个人可选择且适合自身的干预措施，到如何思考我们讨论寿命时涉及的整个过程，一如既往地极具启发性。

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. 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 will wonder why didn't we work on this earlier? And thank you for talking to us today. 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, as always, incredibly illuminating.

谢谢，大卫。谢谢，安德鲁。

Thank you, David. Thanks, Andrew.