TECH007：长寿路线图与Seb Bunney（科技播客）

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大家好，欢迎来到本周三的《无限科技》节目。就在本月，《麻省理工科技评论》刊登了一篇文章，提到雷·库兹韦尔认为我们将在2032年达到长寿逃逸速度——即医学进步为人类延寿的速度开始超过衰老速度的时刻。这是个大胆的断言，也引发了一个重大问题。

Hey, everyone. Welcome to this Wednesday's release of Infinite Tech. Just this month, MIT Technology Review ran a story saying Ray Kurzweil believes we'll reach longevity escape velocity by 2032. The moment when medical progress starts adding years to our lives faster than we're aging. It's a bold claim and it raises a huge question.

我们真的离这个时间点如此接近吗？为了深入探讨，我和塞布·邦尼将解析大卫·辛克莱的著作《寿命》。这本书是长寿科学领域的里程碑，它提出衰老并非不可避免，而是可以逆转的信息丢失现象。我们将探讨山中因子、去乙酰化酶、NAD+、激效效应科学，并解析这一切对当下生活的意义。

Are we actually that closed out running time? To dig into this, Seb Bunny and I are unpacking David Sinclair's book Lifespan. This is a book that's a landmark in longevity science that argues aging isn't inevitable. It's information loss that can be reversed. We'll cover the Yamanaka factors, sirtuins, NAD plus, the science of hormesis, and explore what all of this means for living right now.

这期节目绝对不容错过。闲话少说，让我们直接进入这本书的内容。

This is surely an episode you will not wanna miss. So without further ado, let's jump right into the book.

您正在通过普雷斯顿·皮什主持的投资者播客网络收听《无限科技》。我们以富足思维和健全货币为视角，探索比特币、人工智能、机器人技术、长寿及其他指数级增长技术。加入我们，共同解析塑造未来十年的突破性进展，助您即刻掌握未来。现在有请主持人普雷斯顿·皮什。

You're listening to Infinite Tech via the Investors Podcast Network hosted by Preston Pysh. We explore Bitcoin, AI, robotics, longevity, and other exponential technologies through a lens of abundance and sound money. Join us as we connect the breakthrough shaping the next decade and beyond, empowering you to harness the future today. And now here's your host, Preston Pisch.

大家好，欢迎来到《无限科技》。今天我和塞布·邦尼一起，又为大家带来一本书。能讨论这个话题让我特别兴奋——我一直想在节目中探讨这个主题，但始终没有合适的机会。

Hey, everyone. Welcome to Infinite Tech. I'm here with Seb Bunny, and we've got another book for you guys. I'm super excited to cover this topic. I've always wanted to cover this topic on the show, but never had the opportunity to cover this topic on the show.

我们将探讨长寿、健康科技的发展方向。我们共读的这本书是大卫·辛克莱所著的《寿命》。虽然这本书已出版数年，但对我而言，它精彩描绘了延长人类寿命的科技发展图景，读来令人振奋。如果你正享受着美好生活，自然会渴望更长的寿命。我已经迫不及待要开始讨论了。

We're talking about longevity, health, health technology, like where this is all going. The book that we both read is called Lifespan by, David Sinclair. And this book has been out for a few years, but it for me was just this really inspirational read on where the technology is moving when it comes to people being able to live longer. And if you're living a good life and you're pretty happy, you wanna live longer. So I'm really excited to get into this.

塞布·邦尼，欢迎回来。你对这本书的初步看法是什么？

Seb Bunny, welcome back. What's your initial thoughts on this book?

你知道吗？我想说，首先，我非常兴奋能讨论这个话题并了解你对这本书的看法。其次，我必须完全坦诚地说明，这不是我的专业领域。我做了大量研究才能真正深入我们将要讨论的主题，以及所有这些围绕遗传学和酶等内容的对话如何相互关联。

You know what? I would say that one, I'm super excited to talk about this and just see your perspective on the book. Two, I should be absolutely transparent and upfront. This is not my area of expertise. Do a ton of research to be able to really dig into the topic which we're going to discuss and how all of this conversation one:thirty around genetics and enzymes and such, how it all pieces together.

这确实花了我相当

It took me definitely quite

多时间研究才能理清头绪，但我非常期待讨论它。

a bit of studying to pieces together, but I'm super excited to discuss it.

阿门。如果你是医生、医疗行业从业者或生物学家，我提前道歉。对于我们可能搞错或误解的所有术语，我深表歉意。但我们会尽力而为。那么让我们开始吧。

Amen. And if you're a doctor or you're in the medical industry or you're a biologist, I apologize upfront. I deeply apologize for all the terminology that we are gonna botch or just get wrong. But we're gonna try our best here. So let's start off here.

今天早上我确实在刷X时看到一条帖子，雷·库兹韦尔——大家都知道这位技术专家，谷歌几十年的首席技术官——引述说，他预计到2032年将达到长寿逃逸速度。意思是到2032年，科学将使人们能够超越我们的死亡率。虽然表述不太准确，但我们实际上将拥有这种技术，使你的寿命延长超过平均死亡率。你觉得呢，塞布？

I was literally scrolling through X this morning and I see a post and Ray Kurzweil, everybody knows the technologist Ray Kurzweil, CTO at Google for decades. And the quote was, he expects to have longevity escape velocity by 2032. Meaning by 2032, the science is going to enable people to outpace what our death rate is. And that's not framed correctly, but we're actually gonna have this technology in place to keep extending your life longer than what the average death rate is. So what do you think, Seb?

这是无稽之谈吗？我们将深入书中内容，书中提出的正是如何实现其中一些可能性。但对于我们听到的这些宣言，你第一直觉是什么？

Is this nonsense? Are we And we're going get into the book and what the book is proposing is like how some of this is possible. But what's your just off the cuff gut feeling about some of these proclamations that we're hearing from people?

我完全坦诚的直觉是——虽然我可以在最后深入探讨更多——我认为先把这本书的内容过一遍是好的，但我的直觉告诉我们往往会被事物的炒作所迷惑。就像我们在货币体系讨论中提到的，我们倾向于归因于‘这就是通胀的原因’或‘这就是银行危机的根源’。实际上，我们面对的是一个复杂适应系统，几乎不可能像非黑即白的故事那样 pinpoint 确切原因。我认为寿命、健康寿命和长寿问题同样如此。

My gut feeling being absolutely transparent is that, and I can dive into a little bit more at the very end, I think it's good to kind of get the book out of the way, but my gut feeling is that I think we get caught up in the hype of things. And just as we've discussed in the monetary system, we tend to point to, well, this is the cause of inflation. This is the cause of the banking crisis. In reality, we are dealing with a complex adaptive system that is almost impossible to be able to pinpoint like these black and white stories about what causes something. And I think the same thing is true for lifespan, health span, longevity.

我觉得有时候我们试图过度简化一个极其复杂的话题。几十年来人们一直在讨论延长寿命，但同时也存在一些矛盾的数据——我最后会深入探讨这部分有趣的内容——这些数据甚至质疑过去两千年人类寿命是否真的有所增长。不过这个我们稍后再谈。我很兴奋能探讨其他相关话题。

I think sometimes we try to simplify a really complex topic. And people have been talking about longevity and increasing lifespan for decades. And there's also some contradictory data, which I'll dive into at the end that I find really interesting, that tends to argue that have we actually seen an increase in lifespan even over the last two thousand years? But we'll leave that for a little bit. I'm excited and it's fun to dive into these other topics.

这个世界确实存在相关技术，也必然存在促进健康的认知进步。

There's definitely technology in this world. There's definitely advancements in understanding that are supporting health for sure.

普雷斯顿：是的。哈佛大学的戴维·辛克莱（本书作者）的核心论点是：衰老本身就是一种疾病。从定义层面看，他试图将其纳入疾病范畴，从而改变医疗健康领域现有的应对方式。因为目前人们的态度就像是‘他们只是老了然后死了’，而他认为这种认知远远不够。

Preston Yeah. So David Sinclair out of Harvard, the author of the book, and his core thesis is that aging itself is a disease. And I think from a definition standpoint, he's trying to get this included as a disease so that the treatment and the way that it's handled from a health medical perspective is treated differently than it's currently approached. Because I think today it's like, well, they just got old and they died. And he's like, that's not good enough.

我们必须改变定义，将其归类为与其他疾病同等的疾病。这样就能吸引更多研究资金投入，彻底打开深入研究这些领域的资金闸门。塞巴斯蒂安，关于他为何如此分类你还有什么要补充的吗？但书中反复强调的这个重新定义——将衰老本身视为疾病——确实是非常关键的部分。

We have to change the definition so that it's bucketed in as a disease like any other disease. And then you're going to get a lot more research dollars into it. You're just going to unlock a whole lot more funding to really dig way deeper into some of these things. Anything you want to add there, Seb, on why you think he's classifying it as that, but this was a really important part that kept coming up in the book is this redefinition of it being a disease itself, aging as a disease itself.

杰里米：完全同意。他在书中多次强调，衰老存在这些标志性特征——基因组不稳定性、端粒损耗、表观遗传改变等等，这些都是导致衰老的原因。但他认为我们关注的是症状，真正导致这些现象的是‘信息丢失’（这个我们稍后肯定会讨论）。他认为存在一个未被讨论的上游问题，如果能识别并修复这个上游问题，就可能延长寿命。

Jeremy Absolutely. I think that he highlights it quite a few times throughout the book that essentially there are these hallmarks to aging and he's like genomic instability, telomere attrition, epigenetic alterations, all of these things that basically lead to aging. But he believes that we're focused on the symptom and actually what leads to those things is this information loss, which I'm sure we'll get into. But he thinks there's this upstream thing that we're not talking about. If we can recognise and fix that upstream issue, then we may be able to increase longevity.

普雷斯顿：没错。他的重大理论突破就是这个‘衰老信息论’。我们节目多次讨论过克劳德·香农的信息论，也邀请过本书作者来讲解香农的理论——本质上就是关于如何通过电线或射频信号在空气中传输信息。

Preston Yeah. So his big theory, his big breakthrough is this idea of the information theory of aging. And we've covered Claude Shannon's information theory on the show numerous times. Had the author of the book come on about Claude Shannon. And just this idea of how do you transmit information across you know, a wire or through the air via signal, RF energy.

大卫·辛克莱将信息传递、信息丢失及噪声因素的概念引入生物学，提出人类衰老的本质是信息丢失——具体而言，是表观遗传信息的丢失。当人们听到这些术语时往往会说：'普雷斯顿，你刚才说的表观遗传信息丢失我完全没听懂'。所以接下来我会用最通俗的语言从头解释——塞巴斯蒂安，如果发现我讲得太过天马行空，随时可以打断我。

And David Sinclair takes this idea of transmitting information or information loss and noise factors to biology and suggests that the reason we age is because it's a loss of information. Specifically, it's a loss of information for your epigenetics. And so when people hear some of this terminology, they're saying, well, Preston, I have no idea what you just said when you said a loss of information of your epigenetics. So what I'm gonna try to do here is explain this from the ground up in Preston verbiage. And Seb, feel free to step in if you feel like I'm stepping out way over my ski tips here.

好的，让我们从这里开始。你们都有...我想大家都熟悉DNA对吧？请允许我用个有趣的比喻来解释。

But okay, let's start here. You got yourself. And I think everybody's familiar with DNA. Okay? Let me just let me explain it like this because I think this is fun to frame it this way.

普通人DNA中约有33亿个碱基对，可以想象成遗传密码——就像运行着33亿行代码的软件系统。有趣的是番茄也是如此，它的DNA也有约30亿个碱基对。

So the typical human has about 3,300,000,000 base pairs in their DNA. So just think of it like genetic code. You got all this software, all this code that's run and it's 3,300,000,000 lines. Think of it like that. Interestingly, a tomato also If you look at the DNA of a tomato, it's about 3,000,000,000 base pairs of DNA as well.

当人们听说番茄的DNA长度（或者说代码行数）和人类相同时，第一反应都是：'等等，这怎么可能？人类这么复杂，我们有大脑...'

So when a person hears that and they say, well, hold on a second. What do you mean DNA of a tomato is the same length or lines of code as a human? And it just doesn't seem to make any sense. Like how is that possible when you think complexity of a human? They got a brain.

我们有心脏、有眼睛、能完成各种行为、能进行社交——而现在你告诉我细胞里的代码长度居然和番茄一样？这完全不合常理。

They got a heart. They got eyes. They can do all these things. They can communicate socially, and you're telling me that the code inside of the cell is of the same length as a tomato. Like, it just doesn't make any sense.

这就涉及到DNA的表观遗传机制了。想象DNA是超长代码串，但真正需要的是读取这些代码来制造心肌细胞、神经元或眼球细胞——这些构成人体各器官的差异化细胞是如何从33亿碱基对中产生的呢？关键就在于书中提到的DNA表观遗传设置。

This is where you step into the epigenetics of the DNA. So what is that? So think of the DNA as this big long line of code, but what's actually needed inside of the code to read it and create, call it a heart cell or a neuron or the cell in your eye. These differentiations that are happening in your organs and just all the different pieces that make up a human, how do you get those different pieces and parts out of those 3,300,000,000 base pairs in the DNA? And the way you do it is through what is referred to in the book as the epigenetic settings of the DNA.

假设所有这些代码都印在纸上——我们有无数的纸张记录着基因序列。要制造心肌细胞时，你需要翻到第50页读取那里的遗传密码。

So just imagine all of that line, all those lines of code are on a piece of paper. Let's say we had thousands and millions and millions of pieces of paper with all this genetic sequence. Okay? Let's say you flip to page 50. And in order to create a heart cell, you need the genetic code on page 50.

你需要第1,000,000页的内容，也需要任意页的内容。其中某些特定页面包含了制造心脏细胞的代码，而另一些则完全不同。必须阅读这些代码的许多页面才能创建一个iCELL。

You need it on page 1,000,000. You need it on page whatever. And there's just very specific pages that that's the code for making a heart cell. And then it's a whole different set of code. There are pages of that code that need to be read in order to create an iCELL.

对于每个器官、人体内的每种细胞类型，这样的清单都无穷无尽。在33亿个碱基对中，只有特定页面需要被读取。当我们谈论表观遗传学时，实际上是在讨论33亿行代码中哪些页面需要被激活以供读取。回到番茄和人类拥有相同数量基因代码的例子，被转录蛋白打开的页面根据构建的有机体或人体内部构造而高度特异且截然不同。

And the list goes on and on for each organ, each cell type in the body. There's only specific pages of the 3,300,000,000 base pairs that exist. You only need certain pages to read in order to do that. So when we say the epigenetics, what we're really saying is which pages of the 3,300,000,000 lines of code actually need to be turned on in order to be read. And so when you think about going back to this example between a tomato and a person having the same amount of genetic code for all intents and purposes, the pages that are being read or the pages that are being flipped open in the book to be read by the transcription proteins are very specific and very different depending on what organism or person or thing is being built and constructed inside of the body.

因此大卫·辛克莱的书希望能帮助理解表观遗传设置——即那些被打开供阅读的页面。关于衰老的信息理论认为：当细胞通过有丝分裂复制时，随着你从20岁到40岁再到60岁的人生历程...

And so David Sinclair's book. So hopefully that provides a little bit of a background on what epigenetic settings are. It's the pages that are open to be read. And this idea of the information theory of aging is as the cells replicate, they go through mitosis. As these cells are as you're living a life, you're in year twenty versus year forty versus year sixty of your life.

当这些细胞不断复制时，那些需要持续构建和转录以产生细胞内蛋白质的页面会轻微变化。原本打开的第50页旁，本不该被阅读的第49页也被打开了。当转录蛋白读取这些本不该读取的代码时，就会在细胞内产生多余物质，这种非预期的干扰正是导致生物体衰老的原因。

As these cells have replicated, the pages that are flipped open for these different things that need to continually be built and transcribed in order to create the proteins inside of the cells, that information of those epigenetic settings, which pages are flipped open, are changing very slightly. And instead of it being page 50 that was open, now it's page 50 and page 49, which was never intended to be read, is also open. And as those transcription proteins go in there and they read that genetic code that it wasn't supposed to be reading, it's now producing and creating extra material inside of the cell. And this this is creating noise that is not intended. And this is what's causing aging inside of anybody or any living thing.

对我而言，读到这些时简直震撼——如此精妙又引人入胜的理论。当你退一步思考：一个心脏细胞本有特定设置，现在却读取并产生了本不该存在的蛋白质，这会引发什么后果？

And so this is a really For me, when I was reading this, I was just like, my mind was blown. I was like, this is so fascinating and so interesting. It's pretty elegant. Right? It's pretty simple when you really pull back and you think about, well, what would be the ramifications of this, of a heart cell that had certain settings, but now it has additional settings that are not supposed to be being read and being produced and being turned into proteins that were never intended to be turned into proteins inside of that cell.

如何关闭这些错误设置使其恢复初始表观遗传状态？Seth，我这样的描述是否偏离重点？能否帮缺乏生物学背景的听众更好地理解这个概念？

And how do you turn those off so that you can get it reset back to the initial epigenetic settings? Seth, am I out to lunch in the way that I'm describing this or do you have anything else that can maybe help the listener piece this together, especially the ones that have no background in biology?

不，Preston，你讲得精彩绝伦。这让我想起书里3:50提到的CD播放器类比——虽然我当时对这个比喻有些困惑...

No, Preston, I think you absolutely crushed it. I think for me it had an analogy in the book three:fifty around this kind of CD player and I struggled a little bit with the analogy and so

稍微想了想

was thinking a little

是啊，我不太喜欢这个。

Yeah, I didn't like it.

对我来说，这不太说得通。所以我多思考了一下，试图用一个类比来理解。我的理解方式是——如果我说错了请纠正——在我看来，衰老更多是软件问题而非硬件问题。想象你的身体是一台电脑，DNA就是硬件，是物理机器，正如你所说，它由四种化学碱基构成：A、T、C、G，我想它们是腺嘌呤、胸腺嘧啶、胞嘧啶和鸟嘌呤。

To me, it didn't make a ton of sense. And so I was thinking a little bit more and I was was really trying to understand this in terms of an analogy. The way that I interpret things and again, correct me if I'm misinterpreting this, but the way I see it is that getting older isn't so much a hardware problem, it's a software problem. And so imagine if your body is a computer and your DNA is effectively the hardware, it's the physical machinery, and it's built upon, as you're talking about, these four chemical bases, A, T, C and G, which I think what are they? Adenine, thymine, cytosine and guanine.

我把这些名字念得乱七八糟。比我强

I butchered those names. Better than I

比我强多了。比我强多了。

would have done. Better than I would have done.

杰瑞米 我们所有的遗传信息都由这四种碱基构成。一切都由这四种碱基组成。这些信息极其稳定——就像1990年代的iMac至今仍是那台iMac。硬件是极其稳定的。

Jeremy So all of our genetic information is made up of these four bases. Everything is made up of these four bases. And that information is remarkably stable. If you have a 1990s iMac, it's still the same 1990s iMac. Hardware is remarkably stable.

它们一生中几乎不会改变。但在此基础上还有表观基因组，也就是你说的表观遗传学。这是软件或操作系统，它指挥电脑该做什么。它决定运行哪些程序、如何使用风扇、如何让这台机器运转。从DNA角度来说，当它决定运行哪个程序时，就像你说的，它在指定：这个该是皮肤细胞，这个该是肝细胞，这个该是脑细胞。

They barely change over a lifetime. But then on top of that, you have the epigenome, which is kind of what you're talking about, the epigenetics. This is the software or the operating system that tells the computer what to do. And so it decides which programs to run, how to use the fan, how to basically enable this machinery to run. And so when it's saying which program is to run from a DNA perspective, to your point, it's saying, well, this needs to be a skin cell, this needs to be a liver cell, this needs to be a brain cell.

问题在于，随着时间的推移，软件开始出现故障并在硬件上引入错误。你会遇到环境压力、DNA损伤和代谢磨损。因此硬件本身仍然完好，但计算机开始冻结、失灵，开始出现关于如何运行的记忆问题。这就是大卫·辛克莱所谈及的衰老现象。这未必是生物信息的丢失，计算机本身仍然完全正常。

The problem is that over time software starts to glitch and introduces error on the hardware. You get environmental stress, you get DNA damage, metabolic wear. And so the hardware itself is still fine, but the computer starts freezing, it starts misfiring, it starts having memory issues as to how it's meant to run. And that is what this guy, David Sinclair, kind of talks about is aging. It's not necessarily the loss of biological information, the computer itself is still totally fine.

更像是它忘记了如何高效运行和操作。他的整个理论是，如果我们能将软件恢复到原始未损坏状态，就可能重启系统并让硬件恢复全部功能。在我看来，遗传学是硬件，表观遗传学则是告诉硬件如何运行的软件。这正是对衰老理解的来源。

It's more it's forgetting how to run and operate efficiently. And his whole thesis is that if we can restore that software to its original uncorrupted state, then we may be able to reboot the system and bring hardware back to its full use. And that's kind of in my mind I see genetics as the hardware and epigenetics as a software telling the hardware how to run. And that is where this understanding of aging comes about.

是的。以你提供的例子来说，计算机上的软件正是告诉它如何使硬件本身恢复活力的。假设硬盘老化衰败，计算机上加载的软件提供信息使其能够自我强化和自我修复硬件。如果软件损坏，它将永远无法执行这些任务或实现硬件的恢复。这真是非常引人入胜的见解。

Yeah. And to that example that you're providing, the software on the computer is what's telling it how to rejuvenate the hardware itself. So let's say that the hard drive was getting old and decrepit, the software that's loaded onto that computer is providing the information to be able to self reinforce and self fix the hardware itself. So if the software gets corrupted, it's never gonna be able to perform those tasks or the rejuvenation of the hardware. So really kind of like fascinating insight.

他在解释所有这些内容方面做得非常好，使其非常易于理解，这正是我喜欢这本书的地方。在我们进一步深入探讨之前，关于衰老的信息理论还有什么你想补充的吗？

He does a really good job kind of explaining all of this stuff that makes it really accessible, which I loved about the book. Anything else that you wanted to cover on the information theory of aging before we go on to putting it into a little bit more context?

是的。我觉得非常引人入胜的是，一旦他分解了衰老的信息理论，接着就会探讨他是如何得出这一理论的。他开始谈论酵母。一开始你可能会想，酵母与人类有什么关系？但你会发现酵母在一周内就会衰老。

Yeah. So what I found was really fascinating is that once he breaks down the information theory of aging, he then goes into, well, how did he get to this theory? And he starts talking about yeast. So at first you're just like, what does yeast got to do with humans? And what you realize is that yeast ages in one week.

人类显然需要几十年。因此你可以有效地快速测试酵母上的长寿理念，而这在人类身上显然是不可能的。如果我们无法创造出某种延长酵母寿命的长寿机制，我们又怎么可能在人类身上实现呢？我认为他们认识到了这一点，而且这不仅仅是大卫·辛克莱的观点。酵母有一整个背景故事，这正是我觉得非常非常引人入胜的地方。

Humans obviously take decades. And so you are able to effectively rapidly test longevity ideas on yeast, which is obviously not possible in humans. And if we can't obviously create some form of longevity mechanism or way to extend a yeast life, how are we ever going to be able to do that in a human? And so I think they recognize this and this wasn't even necessarily even just David Sinclair. There's a whole backstory to yeast and that's what I found was really, really fascinating.

关于酵母，他开始谈论的是在20世纪40年代和50年代，酵母成为一种模式生物。所有这些研究人员开始深入研究酵母是如何衰老的，他们发现罗伯特·莫蒂默和约翰·约翰斯顿意识到母酵母细胞在死亡前只能分裂有限的次数。这是第一个可测量的细胞衰老模型。然后在80年代和90年代，他们发现实际上有与衰老相关的基因，这些基因被称为SIR，即沉默信息调节基因。你可以想象——普雷斯顿，如果我讲错了请随时打断——这些沉默信息调节基因让我觉得非常着迷，我们可以更深入地探讨这一点。

So when it comes to yeast, what he starts talking about is in the 1940s and 50s, yeast becomes like a model organism. All of these researchers start diving into how yeast is aging and what they realize is this guy Robert Mortimer and John Johnston, what they realize is the mother yeast cells can only divide a finite number of times before they're dying. So this is like the first measurable model of cellular ageing. And then from there in the 80s and 90s, they find out that actually there are genes related to ageing and these are called the SIR, the silent information regulator genes. And you can think of and again, feel free to step in Preston if I'm butchering this the silent information regulator genes I found so fascinating and we can dive into more depth on this.

但基本上它们的工作原理是这些基因具有双重作用。本质上，这些沉默信息调节基因会附着在DNA上，阻止该DNA信息被读取，从而避免大脑中的细胞转化为肝细胞，或肝脏中的细胞转化为肾细胞。当这种机制失效时，就会出现突变、转移等各种问题。但同时它们还有另一项功能：当DNA发生断裂或出现遗传问题时，它们会离开原位，移动到受损区域进行修复。

But basically the way that they essentially work is these genes have kind of two roles. Essentially what they'll do is these silent information regulator genes will sit on the DNA and they will prevent that DNA, that information, from being read and turning a cell into, say, a liver cell when it's in the brain. Or if you're in the liver, turning that cell into a kidney cell. And that's when you start to get mutations, metastases and all these other issues. But at the same time, they also do something else, which is in the event you have a DNA break, you have some form of genetic issue, they will leave where they're located, they will move to that area and they'll start to repair that break.

修复完成后，它们会返回DNA上的原位，重新抑制这些信息转化为肝细胞或脑细胞。它们会再次关闭这些基因表达。无论如何，它们都会回到最初的位置，重新沉默那些基因，阻止DNA朝特定方向表达。这是80到90年代的研究成果，也就是所谓的沉默信息调节基因。

And then once they're done, they'll go back to the DNA place where they were shutting down this information from turning into a liver cell, a brain cell. They will turn that information back off again. And so anyway, it will return back to its original spot and it will silence those genes again, preventing that gene from that DNA from expressing in a certain direction. And so this was in the 80s or 90s. And so this is the silent information regulated genes.

现在我们要深入探讨这个话题，因为这些SIR基因正是大卫·辛克莱谈论衰老理论的基础。时间推进到80至90年代，这时大卫·辛克莱开始登场。他研究如何使生物体提前衰老，发现某些酵母突变体存在这种变异，并能被诱导提前衰老，这暗示着存在某种普遍的衰老机制。在97到99年间，他意识到如果能过度表达这些SIR基因，就可以减少DNA损伤并将酵母寿命延长达30%。这一发现意义深远，他在书中约三分之一到四分之一处提到：确实存在延长酵母寿命的方法。

Now we're going to talk about this more because these SIR genes were essentially the backbone for this whole idea of aging that David talks about. So that was going up to the 80s and into the 90s, this is where David Sinclair kind of enters the frame. So he starts looking at how to age things prematurely and he figures out that there s these yeast mutants that basically have this mutation and he s able to age them prematurely, hinting at there s some universal aging mechanism. And then in '97 through '99 he recognises that you know what, if they're able to go in and overexpress these SIR genes it's able to reduce and extend sorry, reduce DNA damage and extend the lifespan by up to 30% in this yeast. And so this was profound and he kind of gets to this in about probably one third, one quarter of the way into the book, is that there are ways to be able to extend the lifespan of yeast.

对我来说，从这里开始书变得真正有趣，因为它开始深入探讨技术细节：这究竟是如何实现的？普雷斯顿，我很想听听你的看法。

To me, that's when the book starts to get really interesting because it starts diving into the technicalities of like, well, how is it actually doing this? I'm curious to hear if you have any thoughts on that Preston.

让我们稍事休息，听听今天赞助商的消息。你是否曾对比特币挖矿感兴趣？作为矿工，过去几个月我一直在使用Simple Mining，体验简直无缝衔接。我自选矿池挖矿，比特币直接打入我的钱包。这家总部位于爱荷华州锡达福尔斯的公司提供白手套高端服务，适合从个人爱好者到大型矿场的所有用户。

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他们运营已有三年半，目前管理着超过1万台比特币矿机。得益于爱荷华州丰富的风能资源，其电力65%以上来自可再生能源。他们不仅通过顶级托管和现场维修服务简化挖矿流程，还帮助您以企业形式运营业务，从而获得重大税收优惠，提升投资回报率。您是否曾为矿机维护的复杂性担忧？

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加入我和众多满意的矿工，他们简化了比特币挖矿之旅。立即访问simplemining.i0/preston开始使用。就是simplemining.i0/preston，今天就开始吧。Simple Mining让一切变得简单。

Join me and many satisfied miners who have simplified their Bitcoin mining journey. Visit simplemining.i0/preston to get started today. That's simplemining.i0/preston to get started today. With Simple Mining, they make it simple.

作为小企业主，你没有提前下班的奢侈。你的生意24/7都在你脑海中。所以当你招聘时，你需要一个和你一样努力的合作伙伴。这个招聘伙伴就是LinkedIn Jobs。当你下班时，LinkedIn开始工作。

As a small business owner, you do not have the luxury of clocking out early. Your business is on your mind twenty four seven. So when you're hiring, you need a partner that works just as hard as you do. That hiring partner is LinkedIn jobs. When you clock out, LinkedIn clocks in.

LinkedIn让你轻松免费发布职位，分享到人脉网络，并在一个地方管理所有合格候选人。LinkedIn甚至能帮你撰写职位描述，并通过深度候选人洞察快速将职位展示给合适人选。你可以免费发布职位或推广以获得三倍多的合格申请者。72%使用LinkedIn的中小企业表示它帮助他们找到高质量候选人，让你对获得最佳申请者充满信心。了解为何我们企业和超过250万家其他小企业今天使用LinkedIn进行招聘。

LinkedIn makes it easy to post your job for free, share it with your network, and get qualified candidates that you can manage all in one place. LinkedIn can even help you write job descriptions and quickly get your job in front of the right people with deep candidate insights. You can post your job for free or promote it to get three times more qualified applicants. And with LinkedIn, you can feel confident that you're getting the best applicants as 72 of small and medium sized businesses using LinkedIn say it helps them find high quality candidates. Find out why our business and more than 2,500,000 other small businesses use LinkedIn for hiring today.

免费在linkedin.com/studybill发布职位。就是linkedin.com/studybill，免费发布你的职位。条款与条件适用。有一种更好的面对面方式——卓越的Paper Pro Move。它既是纸质平板，也是数字笔记本，将纸张的熟悉触感与平板的数字功能相结合。

Post your job for free at linkedin.com/studybill. That's linkedin.com/studybill to post your job for free. Terms and conditions apply. There's a better way to meet face to face, remarkable paper pro move. It's a paper tablet, a digital notebook that combines the familiar feel of paper with the digital powers of a tablet.

首先使用数十种内置模板中的任意一种做笔记，然后将手写内容转换为打印文本并通过电子邮件或Slack分享。想想看，我们随时随地记录想法的方式都有其缺点。纸张难以整理且容易丢失。笔记本电脑过于笨重且不舒适。而在手机上，我们的注意力很容易被分散。

Start by taking notes with any of the dozens of built in templates, then turn your handwriting into typed text and share it by email or Slack. Think about it, the ways we capture thoughts on the go, all have their drawbacks. Paper's hard to organize and easy to lose. Laptops are too bulky and uncomfortable. And on our phones, our attention can quickly get hijacked.

卓越Paper Pro Move与你其他设备完全不同。它的显示屏看起来、感觉起来甚至听起来都像纸张。它能容纳你所有的笔记和文档，单次充电可持续两周，但能轻松放入你的外套口袋。最重要的是，卓越的使命是帮助你更好地思考。这意味着没有应用、社交媒体或其他干扰，只有你和你的想法。

Remarkable Paper Pro Move is nothing like your other devices. It has a display that looks, feels and even sounds like paper. It can fit all of your notes and documents and lasts up to two weeks on a single charge, but it slips easily into your jacket pocket. And most importantly, Remarkable's mission is about helping you think better. That means no apps, social media, or any other distractions, just you and your thoughts.

你可以免费试用卓越Paper Pro Move五十天。如果不符合你的需求，可全额退款。访问remarkable.com了解更多信息并立即获取你的纸质平板。就是remarkable.com。

You can try the Remarkable Paper Pro Move for fifty days for free. And if it's not what you're looking for, you get your money back. Visit remarkable.com to learn more and get your paper tablet today. That's remarkable.com.

普雷斯顿：好的，回到节目。普雷斯顿：他一开始就让我印象深刻的是，这个人是个第一性原理思考者。他们采用的解决方法也完全基于第一性原理。就像是要回归生命本质的源头——那片原始沼泽的淤泥。

Preston All right. Back to the show. Preston The thing that I took away when he started there was like, this guy's a first principled thinker. And the approach that they're taking to try to solve this is very first principle. Was like, let's go back to the essence or the start of life itself, which was the swamp sludge.

让我们看看这一切是如何开始的，看看自我保存机制中生长与收缩的动态如何相互作用，是哪些触发因素或信号导致生命体想要扩张、收缩或仅仅维持自身。通过从这个起点出发——他在书中对此的阐述非常出色，比我和塞布平时零散讨论书中各种观点时要系统得多。这本书布局精妙，以极具深度的方式引导读者理解他如何得出这些理论。我认为书中另一个精彩之处是他如何逐步验证这个衰老信息理论，其中他谈到了表观遗传时钟的概念。

Let's see how it all started and how the mechanics of growth or contraction of self preservation interacts and what are those triggers or what are those cueings that are causing life to want to expand or contract or just preserve itself. And so by starting there, was just like, and he does a really good job of framing this in the book way better than probably Seb and I had done as we're just sporadically talking about all the different ideas in the book. But it's laid out really well in the book and organized in a really thoughtful way to walk you through how he's arrived at a lot of these theories. One of the things that I also thought was really well done in the book was how he was walking through his proof of this information theory of aging. And one of the things that he talks about is this idea of an epigenetic clock.

他的观点是：如果衰老本质上是信息丢失（对吧？），回到这本书的核心思想——想象你有一部记录所有遗传密码（DNA）的巨著。要制造一个心脏细胞，需要读取第50页、第500页和第5000页等特定页码的内容。他认为如果确实发生了信息丢失，同时其他页码被意外打开读取，那么我们理应能通过观察细胞的表观遗传特征（即DNA甲基化程度）来准确判断生物体的年龄。

And so what he's saying is if aging is truly information loss, okay? And going back to this idea of the book, right? You got this big giant book of all the code, the genetic code, the DNA. And if to make a heart cell, is page 50 and page 500 and page 5,000 and just name out those very specific pages in the code that have to be read to create that heart cell. His opinion is if it's truly an information loss that's occurring and other pages are accidentally getting opened and getting read, we should be able to peer into a cell and look at the epigenetics and determine how old something is just based off of and this is called methylation, the methylation of the DNA.

实验发现，当他们全面审核DNA时，通过对比特定细胞类型应有的DNA开放区域与实际开放区域，能精准测定实验鼠的生理年龄。这种检测同样适用于人类，其精确度已成为衡量实际健康状况的最佳指标之一。例如某人实际年龄40岁，但表观遗传时钟检测可能显示其生理年龄仅30岁，因为其DNA保持良好状态未受破坏——就像文件未被损坏一样。

And what he found is that when they did this and they go in and they do an audit of the entire DNA and they see how much of the DNA is supposed to be opened for a specific cell type versus what is actually opened, they were able to pinpoint the age of the rat that they were doing a lot of this testing on. They were able to pinpoint that with a lot of accuracy. And you can even do an epigenetic clock test on a human. What they're finding is that the accuracy of the test is one of the best markers of a person's actual health. Because somebody might be 40 years old, but when they go in there and they do this epigenetic clock test, the person might have the age of a 30 year old because their DNA is so in good working order and hasn't been The files haven't been corrupted.

所以如果你去长寿诊所，现在很多机构开始提供这种表观遗传时钟检测，用来评估你当前状态，并测算他们能通过修复表观遗传损伤帮你逆转衰老的程度。

So if you ever go into a longevity clinic, I think a of them are starting to roll out these epigenetic clock tests to see where you're at versus where they think they can get you as far as dialing back a lot of the corruption that's happened in your epigenetics.

不，我认为你完全正确。他论述中一个有趣的观点是：要证明这个衰老信息理论，其实可以采用逆向验证——如果我们认同是这种'噪声'导致衰老，那该如何测试？他们最终采用了所谓的DNA划痕测试（实际运用了CRISPR技术，虽然我可能解释不清CRISPR原理，欢迎专业人士在推特上补充说明）。

No, I think you're absolutely spot on. And I think that one of the interesting points that he talks about is obviously he needed to prove his information theory of aging. And so you could almost prove it in reverse, which is if we believe that it's this noise which is creating aging, well, how do we test that? So they ended up using I think they call it the DNA scratch test. They ended up using CRISPR and I'm going to butcher if I try to explain CRISPR, but basically for anyone who can explain it better, we would love that.

据我理解，研究人员会用CRISPR对年轻小鼠的DNA进行精准编辑，通过制造人为的DNA损伤喷雾来模拟数十年积累的损伤（但不引入实际突变）。结果这些小鼠迅速出现白发、器官衰竭等衰老特征——尽管DNA序列（硬件）未变，仅仅是添加了这些'噪声'干扰。然后——

Go and explain it on Twitter. CRISPR, my understanding, they would go into the DNA and they would make precise edits and they would create these sprays in the DNA of these young mice, mimicking decades of accumulated DNA damage, but without actually introducing any mutations. And the result is that the mice ended up aging rapidly and they showed grey hair, fragility, organ decline, even though the DNA sequence, the hardware was unchanged. They just added in all this noise. Then-

我想说，是的，基本上这是我的看法，我也可能是错的，塞斯，

I would say, yeah, basically my take, and I might be wrong too, Seth,

但普雷斯顿他们用CRISPR技术进入细胞，在DNA这本书中打开额外的页面，引入更多噪音因素，就像理论预测的那样会让物种显得衰老。当他们用老鼠做实验时，老鼠开始长出灰毛，变得衰弱，基本上就像濒死的老鼠一样——通过这种DNA表观遗传甲基化操作。

but Preston they use CRISPR to go there and open up additional pages in the cell, in the DNA book, to have more noise factors, just like what the theory suggests should make the species look old. When they did this with a rat, it started getting gray hairs and it was decrepit and basically was just acting like a rat that was on its deathbed by going in and performing this epigenetic methylation of the DNA.

我们稍微岔开一下话题，再回到老鼠这里。最令人着迷的是这本书开始探讨这些叫做山中因子的东西。这位山中伸弥博士在2006年基本上发现了这四种基因：OCT4基因、SOX2基因、KLF4基因和CMYC基因。这部分内容让我震惊，因为我一直认为一旦干细胞分化成某种特定细胞——无论是肝细胞还是脑细胞——就绝不可能逆转衰老使其变回未分化的干细胞。

We're going to take a little bit of a tangent and come back to the mouse here for a second. But what is fascinating is the book starts going into these things called Yamanaka genes. And this doctor, Shinya Yamanaka, in 2006 he basically discovered these four genes. And these four genes were kind of the OCT4 gene, the SOX2 gene, the KLF4 gene and the CMYC gene. And this is where it just kind of blew my mind because I always believed once a stem cell had grown into some form of specialized cell, a liver cell, a brain cell, there's no way to reverse that aging back into a stem cell, an unspecialized cell.

这位博士发现，实际上通过调控这些基因，你可以将细胞重置回胚胎状态、未分化状态。这个发现最终获得了2012年诺贝尔奖。但最神奇的是辛克莱深入研究这些山中因子后，想在老鼠身上测试。于是他们用山中因子重启了那隻快速衰老老鼠的表观遗传程序，成功逆转了衰老迹象。对我来说，这简直不可思议。

And this doctor basically found out, well, actually through these genes, tinkering with these genes, you can reset them back to their embryonic state, their unspecialized state. And it actually ended up winning the Nobel prize in 2012. But what is fascinating is that Sinclair had dug into these Yamanaka genes and wanted to test this on these mice. And so this mouse that they had aged rapidly, well, they went back and rebooted the epigenetic software using these Yamanaka genes and they were able to reverse the signs of aging. And she was just like, to me, that was mind blowing.

太震撼了。人们经常听说干细胞，我想大多数听众大概知道是什么。但如果不清楚，我简单解释下：把干细胞想象成DNA序列，它能开放成为任何类型的特定细胞。

Mind blowing. People hear stem cells all the time. And I would imagine most listeners kinda know what that is. But if not, I'm just gonna quickly explain it. Think of a stem cell as the DNA sequence, and it's open to become any type of specialized cell.

所以它可以变成肝细胞，可以变成神经元，可以变成任何细胞。因为它没有任何表观遗传设定，不是说只能读第50页或1000页，而是可以读任何页面，变成任何你想要的细胞类型。

So it could become a liver cell. It could become an, you know, a neuron. It could become whatever. And so because it doesn't have any epigenetics set, it's not saying read page 50, read page 1,000. It's saying you can read any page and become any type of cell you want.

这就是干细胞。这个过程叫做细胞分化。当它开始分化为皮肤细胞或体内任何细胞时，原本作为干细胞时完全打开的这本书，随着分化过程，所有页面开始闭合，只有特定页面保持开放可供读取和转录。所以就像塞布提到的山中因子，这三段基因序列就像重置按钮，能把这本书...

That's what a stem cell is. And so this is called differentiation of a cell. Once it starts to differentiate itself as a skin cell or you name it inside the body, that's when the pages the book is wide open as a stem cell, but as it starts to differentiate, all those pages start to get closed and only a select number of pages are open to be read and transcribed. So to Seb's point here about the Yamanaka factors, these three genes inside thirty:fifty the sequence are almost like a reset button to push the book so

它完全开放，可以再次变成任何东西，甚至重新成为干细胞。

that it's wide open to become anything again and become a stem cell again.

大卫·辛克莱给出的类比是，想象一颗弹珠位于山脉中。所有弹珠最初都位于未分化的山顶，但随着它们滚下山谷，就会变得特化。问题在于，在山中因子基因被发现之前，我们一直认为这是一条单向轨迹。一旦弹珠落入谷底，如何让它们重新爬上山峰并跨越到另一个山谷？我们曾认为这是不可能的。

Analogy I think David Sinclair gives is like, imagine a marble sitting in a mountain range. All marbles start out at the top of the mountain range unspecialised, but as they roll down the mountain down into a valley, they become specialised. And the problem is up until this point of these Yamanaka genes being discovered, we just assumed that it was kind of a one way trajectory. Once the marbles are down in the valley, how are you getting them back up the hill and then crossing over into another valley? We thought that was impossible.

所以对我来说，我完全不知道这竟然可能。这真的让我大开眼界。书中展示了大量案例，列举了许多他们进行的研究。大部分是在小鼠身上，但也提到了一些人类实验，不过主要还是小鼠研究。

And so this to me, I had no idea this was possible. And it really opened my eyes. Shows a whole bunch throughout the book. Gives a whole bunch of studies in which they've done. Of them on mice, but some of them they've mentioned even with some humans, but most of them have been on mice.

他们做了眼睛再生研究。甚至还有针对因化疗导致不孕的老年雌鼠的实验，通过类似方法成功恢复了它们的卵子。这让我震惊不已，我根本没想到这居然可以实现。

They did an eye regeneration study. They even had ones where they had old female mice that were infertile and they were able to restore eggs after chemotherapy and everything through a similar approach. To me, I'm just like this, I had no idea this was possible.

普雷斯顿：山中因子不仅在宏观层面上对细胞重置回干细胞状态至关重要——这使得细胞能够按需分化——还存在一种叫去乙酰化酶（sirtuin）的蛋白质或酶。这些去乙酰化酶的功能是进入并更新或修复现有设置。如果DNA受损，它们能解除特定组蛋白尾部的甲基化，使表观遗传以正确方式重置。我把它们分为两类：去乙酰化酶负责修复现有结构。

Preston Not only are the almanaca factors really important in the grand scheme of things as far as being able to reset the cell back to this stem cell state, which would enable it to differentiate in any way that it wants, There's also a thing called sirtuin proteins or enzymes. And what the sirtuin proteins and enzymes do is they're able to go in and update or fix the existing settings. So if there was damage to the DNA, if there was damage to it can go in and unmethylate certain histone tails so that the epigenetics reset in the right way. But these sirtuin, I put it into two different camps here. You got the sirtuin proteins, which are going and fixing what's already there.

然后是山中因子，这是四种能让DNA完全重置回干细胞状态的特定基因。他详细讨论了这些内容，并介绍了大量相关研究——因为去乙酰化酶有七种不同类型，技术性很强。但我会将这两类因素视为他书中讨论的主要研究来源。

And then you have the Yamanaka factors. These are four specific genes that enable the DNA to go reset completely back to the stem cell. So he talks about a lot of these and he talks about a lot of the research that's happening because the sirtuin proteins, there's seven different types and goes on and on. Gets very technical. But I would just put those two camps or those two factors as where a lot of his research or at least the research that he talks about in the book comes from.

杰里米：我认为你指出了一个关键点——将这两者划分为不同领域。显然山中因子是四种基因，而那些通路...我甚至想补充两点：他提到的去乙酰化酶（命名源自酵母中的SIRs，即沉默信息调节因子）是驻留在DNA上的酶，既能抑制基因表达又能修复DNA。可以说去乙酰化酶就是身体的'长寿管理团队'——目前已发现人类有七种这类酶，其核心职能就是稳定DNA、修复损伤，并确保特定基因的正确开关。

Jeremy And I think you made a really good point and that is being able to break those two things into two different areas. And I think that you've got, obviously these Yamanaka factors are four genes, and then you've got these pathways. I would even add two more to that because he talks about the sirtuins and the sirtuins are named after, as I mentioned, when it came to yeast, there were these SIRs, silent information regulator, these enzymes which sit on the DNA and preventing it from expressing or it goes and repairs DNA. And so you've got sirtuins, which are basically these enzymes and it's the body's longevity managers or maintenance crew. So basically there's these seven various enzymes which are being found in humans and their job is essentially just to stabilise the DNA, repair the DNA, and then make sure certain genes are properly switched on and off.

它们的工作原理让我豁然开朗——原来都依赖于一种叫NAD（烟酰胺腺嘌呤二核苷酸）的分子。这些化学名词我连发音都困难，简直束手无策。

And how they work and this is where, again, it just opened my mind they rely on a molecule called NAD, nicotinamide adenine, and I'm not even gonna pro it, dinucleotide. I cannot pronounce any of these of these chemistry. Useless at it.

这期节目也带点喜剧色彩，我们就是想让大家都开心。萨姆，你接着说吧。

This episode is part comedy too. We're just trying to make sure you all are entertained. Go ahead, Sam.

本质上它们依赖NAD。NAD是激活sirtuin蛋白的燃料。当体内NAD水平较高时——比如年轻时或禁食运动期间——sirtuin就会活跃起来修复受损DNA并关闭基因。但随着年龄增长NAD水平骤降（中年时约减少一半），这些蛋白就跟不上了。缺乏NAD会导致基因失调、DNA修复迟缓，细胞甚至会逐渐丧失自身特性。

And so you've basically they rely on NAD. NAD is what fuels these sirtuins. And when levels of NAD in the body are high as they are in youth or during fasting and exercise, sirtuins basically become active and they repair damaged DNA and they silence genes. But when they falter, as we age, and as we age we also see our NAD levels decline sharply by about half by midlife, these sirtuins just can't keep up. Without this NAD, genes start to lose coordination, DNA repair slows and cells begin to basically just forget their identity.

除了sirtuin还有两个关键角色：一个是mTOR（雷帕霉素机制靶点）。说真的读这些书最难的倒不是原理复杂，而是这些专业术语——我经常读到一半就懵了，得反复回看才能理解。

And so you've basically got these sirtuins and then you've got two more which he talks about. One of them is called mTOR, M T O R, which is basically the mechanistic target of rapamycin. Side tangent, I've found that the hardest part about reading these books is once you actually understand how they work, it's not actually that complex, but the words themselves- because just never come across these words. My mind is just lost half the time. I'm like, Oh wait, what are they talking about again?

mTOR相当于人体的生长开关，调控细胞分裂增殖。营养充足时（比如暴饮暴食），mTOR活跃会促使身体储能造蛋白。但过度激活会导致持续生长状态——

So I've got to go back and actually figure out like just trying to understand how they work. So mTOR is basically the body's growth switch. And so mTOR tells cells when to grow and when to divide. And so when nutrients are plentiful, so if you're eating a lot, mTOR is active and it signals the body to store energy, make proteins, go and build tissue. However, when it's overactive, you can get constant activation from this as overeating, frequent meals.

这恰是全球现状：食物过剩使细胞长期处于生长模式，反而加速衰老诱发癌症。通过禁食、低蛋白饮食或雷帕霉素可以关闭mTOR，此时它才转向维护修复功能。最后要说的AMPK——

I think this is what's happening globally. We've just got an abundance of food and then it keeps cells in this growth mode, which then can accelerate aging, lead to cancer and all of those other things. And we're able to turn mTOR off through things like fasting, low protein intake or the drug rapamycin. And so when we're turning it off, that's when it's able to help with maintenance or repair. And so the final one, and I'll summarize these after just so kind of bring it back full circle, is we have this other one called AMPK.

这是身体的能量感应器，在禁食/运动/寒冷时激活。它能开启节能模式：促进脂肪燃烧、增强胰岛素敏感性、改善线粒体健康。简而言之我们刚讨论的就是这两大调控系统。

And this is kind of the body's energy sensor. And so this activates when cellular energy is low, again, during fasting, exercise, cold exposure. Essentially what it does is it switches the body into energy saving mode, which increases fat burning and insulin sensitivity and boosts mitochondrial health. Going back to what we were just discussing, you effectively got these two areas. You've got these genes.

基因本身对调控细胞衰老至关重要，正如普雷斯顿你刚才讨论的，我们能够将细胞重置回未分化状态。但同时，这些功能是通过特定通路实现的——sirtuins蛋白作为长寿管理者和维护团队，mTOR是身体的生长开关，而AMPK则是能量传感器。我认为本书的核心就是深入探讨这些不同领域，包括如何检测这些指标以及如何在人体中激活或抑制特定功能。

The genes themselves are absolutely necessary for governing aging in the cells, and you're able to reset cells back to their unspecialised state, as Preston, you were discussing. But then at the same time, you've got these pathways which then help do this, and that is through the sirtuins, which is their longevity managers and maintenance crew, MTOR, which is the body's growth switch, and then you've also got the AMPK, which is the body's energy sensor. So this is I think the foundation of the book is diving into these kind of different areas and how to test for these things and what to do in humans to be able to activate or deactivate certain areas.

比尔，我们先稍事休息，听听今天赞助商的信息。

Bill Let's take a quick break and hear from today's sponsors.

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好的，回到节目。我要用个例子说明——不是这本书，而是另一本帮我理解'成长模式'与'收缩优化模式'区别的著作。作者布鲁斯·利普顿写过《信念的力量》，还有本叫《细胞的智慧》。

All right, back to the show. I'm gonna use an example that I read from not this book, but a different book that really kind of helped me understand this idea of growth versus the sell kind of hunkering down and optimizing itself. The author of the book was Bruce Lipton. He has a book called Biology of Belief. I think there's another one called The Wisdom of Your Cells.

书中有个通俗易懂的例子（可能记忆有误，因阅读年代久远）：想象个农夫在晴天无风暴时下地劳作，忙着收割庄稼——这时他处于成长模式。而村里有个警报喇叭，当轰炸机来袭时会通知大家躲避。

And in the book, he provided an example that I think everybody can kind of wrap their head around. He was and I might mess up the example because I read this book a long time ago, but it went something like this, where he was saying, imagine a farmer that's there you know, working in his fields because the sun's out, there's no storms, there's nothing to be worried of. He's out there. He's harvesting. He's doing all this work.

听到警报后，农夫躲进地堡紧闭舱门，不知要待多久。在此期间，他做着各种自我优化：规划收割时间表、设计粮食储存方案，在充满恐惧的外部环境中进行着内省式思考。

He's in growth mode. Now imagine that there is a loudspeaker in the town that alerts him when there might be bombers that are coming overhead. So he hears the alert, get inside, hunker down, get safe. And so the farmer goes into a bunker, he closes the hatch, he goes in there, he has no idea how long it's going to take. But while he's in there, he's trying to do things that allow himself to self optimize.

利普顿用这个例子阐释细胞运作原理：你体内每个细胞都如此运作。当你遭遇困境——比如断粮缺水，或刚跑完马拉松时，细胞也会进入这种防御优化状态。（注：保留原文'right?'口语化特征未直译）

He's coming up the plans of when he's going to harvest. He's going to come up with the plans on where he's going to store all of his crops. He's going to do all of these self reflective type things as he's hunkered down because there's fear and there's concern in the environment in the outside world that he is trying to always operate in and trying to grow within. And Lipton used this example as a way for you to understand how the cell operates and how the cell, every cell in your body is functioning. If you are experiencing hardship, let's say you don't have any food, let's say you're lacking water, let's say you've just run a marathon, right?

你提到的压力，正是身体细胞进入高效模式的表现。它们会思考：如何最高效运作？如何修复细胞内损伤？如何在无法扩张或转录DNA以合成新蛋白质和促进生长时，完成这类修复活动？

You name it, stress. The cells in your body are kicking into efficiency mode. How can I operate most efficiently? How can I fix the damage inside of the cell? How can I do these types of activities that it can't do when it's expanding or transcribing the DNA in order to build new proteins and expand its growth?

对吧？他描述的这种细胞自我清理与重置的往复过程，实际上极其有益健康。正如大卫·辛克莱在书中提到的，某些sirtuin蛋白质会协同七种酶前往清理细胞并修复损伤——这种修复机制的触发信号正是来自细胞内部的应激反应，即hormesis（低剂量应激效应）。

Right? And what he says is this back and forth where the cell is basically cleaning up itself and having this time to reset is actually extremely healthy. And, you know, David Sinclair in his book is talking about these sartoon proteins that then go and the enzymes, the seven enzymes that go there and kind of clean up the cell and fix the damage that's been done in the cell. The queuing for this, for these start to proteins comes from stress. It comes from hormesis, the stress inside the cell.

因此可以通过禁食实现。这也是他推崇间歇性禁食的原因：将进食窗口控制在8小时内。尝试冷暴露、热应激（比如桑拿）、运动锻炼等——只要适度进行，这些实际上都非常有益健康。

And so this could be through fasting. This is why he's promoting the idea of fasting. Eat in an eight hour window. Go out there, experience cold exposure, experience heat stress, go into a sauna, go exercise. All of these types of things are actually very healthy if you do it in somewhat moderation.

你打算整整一周不进食吗？那可能不健康。但偶尔禁食24小时呢？这反而可能是非常有益的做法，因为它会迫使全身细胞进入优化状态。还有什么要补充的吗？

Do you wanna go out there and not eat for a week? That's probably not healthy. Do you wanna go out there and and not eat for, you know, maybe a day? That might actually be a really healthy thing to do from time to time because it's forcing your cells, all the cells in your body to go in there and optimize. But yeah, anything to add on that?

不，我觉得你说得非常到位。你总能精准阐述这些复杂概念，这个类比也完美。他主要强调四个关键领域：如你所说要少吃；以植物性饮食为主（这点我们最后可以讨论，我个人持部分异议，尽管有很多支持证据）；

No, I think you nailed it. I think you're so good at being able to articulate these complex ideas and I think that's a perfect analogy. He essentially just talks about kind of these four different areas which make a big difference and that is eat less to your point, it is plant heavy foods. This is something that we can talk about in the end. I tend to disagree with somewhat and I think there's a lot of evidence to support it.

他更倾向素食主义。此外还有限时进食法，以及冷热暴露疗法。这些方法的核心逻辑都是hormesis理论——你需要给身体施加良性压力。压力之所以有益，是因为它能激活细胞修复机制。我必须向听众强调：这本书最让我着迷的正是对sirtuins蛋白的解读。

He is more vegetarian, plant based, and then you've got the fasting time restricted eating and then the cold and heat exposure. And the idea behind a lot of this stuff is essentially that hormesis idea is that you want to stress the body. Stress is good because it puts the cells into kind of cellular repair. Again, I can't stress people that are listening to this. To me, I would say what was so fascinating about this book is just understanding these sirtuins.

我原先完全不知道：除了DNA外，这些sirtuins蛋白会覆盖在DNA上抑制特定基因表达。我之所以重复这点，是因为它是我从书中获得的最重要认知——它们驻守在DNA上阻止细胞错误分化（比如大脑中出现肝细胞会造成严重问题），但当基因损伤发生时，这些蛋白又会离开岗位前去修复。

I had no idea that we essentially have we've got obviously our DNA and these sirtuins sit on top of the DNA preventing it from expressing in certain ways. As I mentioned at this part, and I'm repeating this because I think it's really important to understand because I would say it was the biggest takeaway from the book for me, is just how these situate work, that they'll sit on the DNA preventing it from expressing in certain ways. So you don't want a liver cell in the brain that's going to create massive issues. And so the sirtuins will sit on the DNA preventing that cell from expressing as a liver cell. However, at the same time when there starts to be genetic damage those sirtuins leave their little outpost, they go and repair that genetic damage.

然而，当它们长时间缺失时，细胞就可能开始出现问题。它会开始表达本不该在该身体区域出现的物质，这正是导致健康状况下降和衰老等问题的根源。一旦DNA被修复，它就会回到自己的小据点并沉默那个基因。问题在于随着年龄增长，我们体内会出现越来越多的DNA问题，而我们的去乙酰化酶会离开它们的据点，不再阻止DNA以某些方式表达。于是我们开始出现突变、肿瘤以及其他各种健康问题。

However, while they're gone many times that cell can start to have issues. It can start to express as things that it doesn't want to be in that area of the body, which is what leads to a lot of this decline in health and aging and such. And then the moment it's repaired that DNA, it goes back to its little outpost and then silences that gene. The problem is as we get older and we get more and more DNA issues throughout the body and our sirtuins leave their little outposts, they're no longer preventing the DNA from expressing in certain ways. So we start to get mutations, we start to get tumors, we start to get all of these other health issues.

据我理解，有时去乙酰化酶在回家的路上也会迷路，无法回到最初的位置。因此，他一直在研究的就是如何刺激更多去乙酰化酶或增强其活性？正如我之前提到的，这一切都通过NAD实现。如果我们能获得更多NAD来为去乙酰化酶提供能量，这有助于修复DNA，并防止基因以我们不希望的方式表达。这正是我觉得非常非常神奇的地方。

And sometimes the statuins, from my understanding, can also get lost on their way home and they can't find their way back to where they initially were. And so this is where essentially what he's been doing is how do we stimulate more sirtuins or to increase their activity? And that is all through, as I mentioned previously, NAD. And if we can get more NAD that fuels the sirtuins, which helps with repairing DNA and it helps with preventing genes from expressing in ways that we don't want them to be expressing. And that is just what I found really, really fascinating.

归根结底，回到你刚才提到的普雷斯顿，我认为他非常推荐关注少食、多植物、限时禁食以及冷热暴露等方法，这些都有助于支持身体自然的修复机制。

So ultimately, going back to kind of what you were talking about Preston, I think he very much recommends focusing, eating less, plant heavy, fasting time restricted eating and cold and heat exposure, and that helps support these bodies' natural repair mechanisms.

杰森：是的。我们来谈谈书中让我觉得非常有趣的部分——关于老鼠视神经的实验。他们通过CRISPR技术调整表观遗传学来加速老鼠衰老，以此证明可以人为制造衰老。辛克莱在书中有句话：'如果我能让你变老，那么我也应该能逆转衰老。'对他而言，验证方法就是在这个领域进行小鼠视神经手术实验。

Jason Yes. Let's talk about what I found to be a really interesting part of the book, which was this where they took the optical nerve on the rat. So going back to this idea that they were making the rats older, the mice older by adjusting their epigenetics through CRISPR to prove that they could create age or someone aging faster. And Sinclair had this comment in the book, if I can give you age, if I can increase your age, then I should also be able to take the age away. And for him, the way to prove this, I guess there's a test in this community where they can go and they can perform surgery on a mouse of its optical nerve.

视神经连接着眼睛和大脑，它将信号传回大脑使老鼠能够看见。实验中他们通过手术钳夹视神经造成损伤。视神经是人体无法自我修复的部位之一，这种损伤一旦造成就是永久性的——至少过去一直被认为是不可逆的。

Optical nerve connects the eye to the brain. It sends the signal back to the brain so that the mouse can see. And what they do is they perform a surgery where they go in, they pinch this optical nerve to cause damage. And the optical nerve is one of the parts of the body that cannot rejuvenate itself. So once this damage is done, it's irreversible, or at least it always has been irreversible.

他们通过手术钳压视神经造成损伤后，启用了山中因子（四种基因）。据我理解他们使用了其中三种基因，并以脉冲方式激活基因转录——不是持续激活，因为如果持续开启可能导致癌变，因为该区域的细胞会重置为干细胞状态，失去分化能力而不知该成为什么细胞。所以他们采用了脉冲式激活。

So what they did is they did the surgery, caused the optical nerve to have damage through pinching it, and they crushed it. And then they went to these Yamanaka factors, these four genes. And my understanding is they they used three of the genes and they pulsed the genes so that they were only being transcribed occasionally. It wasn't like it was full on because there's issues with it becoming cancerous if they can just constantly have these turned on because basically the cells in that region basically reset to a stem cell, there's no differentiation and the cell has no idea what to be or what to do. So what they did is they pulsed it.

他们通过让老鼠间歇性饮用含有特殊成分的水（具体成分我记不清了）来激活四种——抱歉是三种山中因子基因，从而重置视神经细胞的表观遗传。实验证明这确实能恢复小鼠视力。这是书中非常重要的一个例证，表明通过调控山中因子，他们实际上能够逆转衰老，使细胞基本实现完全重置。这是否意味着能让人从60岁变回40岁？答案是他们正在朝这个方向努力，但尚未实现。

They did it through forcing the mice to drink some water occasionally with, I forget what they had in the water that caused these four genes or I'm sorry, three of the four Yakamoto genes to basically reset the epigenetics of the cells in the optical nerve. And so when they did this, it was provable that they were actually able to restore the eyesight of the mice. And so this was kind of a really big point in the book where they're proving that depending on how they're able to access these Yamanaka factors, they're actually able to reverse aging and bring something basically a full reset back to the cells. Now, does this mean that they can turn back the clock and let's say you're 60 years old and now all of a sudden that they can make you 40? I think the answer is that's what they're trying to do, but they're not there yet.

但他们正在试验一些近乎科幻小说般的疯狂想法。进展看起来非常迅速。回到节目开始时我们提到的MIT雷·库兹韦尔的评论——到2032年我们将达到长寿逃逸速度。这些研究和讨论的课题中，我认为有些已有五到七年的历史，相关研究已经取得了很多进展。

But they're experimenting with really crazy ideas like this that almost seem like it's out of a fiction novel. It seems to be moving there very quickly. Going back to the original comment that we had at the start of the show when we said about the MIT Ray Kurzweil comment that we're going to be at the longevity escape velocity by 2032. A lot of this research and a lot of the things that we're talking about, I think some of these things are five years old to seven years old, some of these studies that have been done. So there's been a lot of progress.

我很好奇你对AI加速这一进程的看法，因为涉及到专业术语时——塞巴斯蒂安，我完全同意你的观点，观众们也都会认同，尤其是非医学或生物学领域的人。面对如此复杂且术语密集的领域，AI将轻松化解大量混乱与困惑，并带来我们甚至无法预见的洞见。也许这就是雷·库兹韦尔的价值所在，他擅长用系统思维看待各种因素（比如AI）如何共同推动时间线加速。

I'm curious your thoughts on AI just accelerating so much of this because when it comes to the terminology, right? To your point, Seb, I'm with you 100%. I think everybody in the audience is with you 100%, especially if they're not in the medical or biology space. Piecing this all together for something that is so complex and so terminology heavy, AI I think is going to just eat through so much of that chaos and confusion with ease. And it's going to lead the insights that I don't even think that we can possibly And maybe that's why you have Ray Kurzweil, he's really good at seeing a systems of systems kind of culmination of how everything vectors into an accelerated timeline because of these additional factors like AI.

你怎么看？你认为AI会在未来进程中扮演重要角色吗？

What are your thoughts? Do you think that that's going to play a huge part in a lot of this moving forward?

确实如此。因为在我看来，学习曲线上的障碍往往不是事件本身的复杂性，而是整合信息所需的语言门槛。我经常要反复确认：NAD到底是什么？它在细胞中起什么作用？即便你理解原理，这本质上就像学习一门全新语言。

I believe so. Because I think the way I look at it and similar to what you just mentioned is part of the learning curve is not actually the complexity of what's happening, it's the language to be able to actually piece everything together. So half the time I'm going back and being like, Wait, wait, what is NAD again? What is NAD doing in the cell? And so although you understand this stuff, it's essentially like learning a whole new language.

但一旦掌握这门语言，交流起来就和用英语或西班牙语没太大区别，关键是要理解术语。回顾这些研究也让我看到了可能性——之前简单提过他们研究小鼠生育力的实验，如今社会普遍认为女性出生时卵子数量就固定了。

But once you've learned that language, it's not that much different communicating in English as it is to communicating Spanish. Just got to understand the terminology. And I think going back as well to some of these studies, it opened my eyes as to what was possible. I mentioned it very briefly previously, they were also looking at fertility in mice. One of the things there's this kind of common held belief in society today, women are born with a finite amount of eggs.

随着年龄增长，可用卵子逐渐减少直至耗尽——这正是我们在生育力衰退中观察到的现象。实验中，研究人员让雌鼠接受化疗失去全部活性卵子（他们称这种小鼠为'绝育鼠'），然后给它们服用NMN（NAD的前体物质）。我深入研究后发现，NAD通过激活sirtuins蛋白来修复DNA断裂，而直接补充NAD会被肠道破坏吸收率极低。

And as you age, the amount of eggs you have slowly die off, they become unusable, as we see in fertility. What he was able to do is he put female mice through chemotherapy and they'd lost all of their viable eggs and he called this mouse supports. And then they were given something called NMN and NMN is the precursor to NAD. I dug into this a little more because I didn't quite understand it. But NAD which is necessary for these sirtuins, it feeds the sirtuins to be able to remember silenced genes and go and repair DNA breaks.

当这些小鼠服用NMN提升NAD水平后，原本不育的个体竟恢复了生育能力，有些甚至再次产下后代。

Or NMN, if you actually take NMN, it's the precursor to NAD production in the body so that it actually feeds the tuins. If we just go and take NAD, from my understanding, when it enters the gut, most of it just gets destroyed. We can't actually absorb most of the NAD when we go and take it through supplement levels. So they were feeding these mice NMN and were boosting these NAD levels. And then what was happening is these infertile mice were regaining fertility and some even produced offspring again.

你会觉得，这简直太不可思议了。如果我没记错故事里的情节，他的一位朋友或家人——别太当真——最后推荐了NMN给一位可能正处于更年期的女性，结果她居然恢复了月经周期。这真的让人着迷。我认为长寿领域绝对是个有趣的方向。有些观念比如我们卵子数量有限这种，未来会有越来越多研究证明这是可逆的。

You're just like, that is mind blowing. And if I remember correctly in the story, one of his friends or family member, so don't quote me on this, he ended up recommending, I think she was going through menopause or something like that and he recommended NMN to her and she actually went back and started having a period again. And so you're just like, this is fricking fascinating. And so I think the world around longevity is definitely an interesting space. I think there's some beliefs such as the fact that we have a finite amount of eggs that I think we're increasingly going to see studies that allow us to reverse that.

是啊，我们根本想象不到接下来会有多疯狂。我觉得未来十年会变得相当魔幻。

Yeah, I don't think that we have any idea how crazy some of this is about to get. I think in the coming decade, it's going to get pretty wild.

正在收听播客的朋友们，你刚才拿出了一个容器，那是...

So for those that are listening to the podcast, you just showed a container of Was that an

所以我们才笑出声。如果只听音频的话，你会突然听到我们爆笑然后继续聊天。自从读了那本书——其实好多年前读的——我就开始服用NMN，大概两年了吧。

That's why we laughed. If if you were just listening to the audio, you just heard us burst out laughing and we just kept talking. I've been taking since I read this book, you know, I read this book years ago, but since I read the book, I've been actually taking NMN ever since I read it, probably two years ago or whenever.

那你感觉到变化了吗？

And Did you notice a difference?

完全没有。不过书里提到，我的底线是如果出现任何不适比如反胃之类的，就会立即停用。但最让我意外的是居然什么感觉都没有。书里大卫·辛克莱提到他父亲也在服用NMN，至于是否延长寿命...这个增效作用我不确定。

No. I I don't notice a difference at all. But, you know, in the book, my big thing was is if I was feeling any different, like, in a bad way or upset stomach or whatever, like, I was gonna stop immediately. But I think the thing that surprised me most was how I don't feel anything at all. Just for reference in the book, David Sinclair says that he has his father taking NMN and, you know, whether it has a longer lifespan, you know, enhancement, I don't know.

不确定，但我一直在服用。说到Seb的观点，这个确实能激活sirtuin蛋白——理论上它能促进细胞修复。其实通过我们之前说的那些艰难方式也能达到类似效果：少吃、蒸桑拿、冷水浴，这些都能提升NAD+水平，向身体发出修复信号。你可以用这种免费方式稍微给自己些压力，连药都不用吃。

I don't know, but I've been taking it. And this boost, going to Seb's point, this boost your sirtuin protein. Supposedly it's boosting your sirtuin proteins to repair your cell. It's a precursor to You get a very similar effect if you do these hard things that we were talking about earlier, which was eat less, go out there, sit in a sauna, do a cold plunge, you do these types of things and you're creating the same NAD plus levels and signaling to yourselves to repair themselves. You can just do the free version of that by stressing yourself a bit and then you don't even have to take bills.

但是

But

我一直试图...这让我想到很多人对长寿研究的抵触——我们总在寻找某种万能药。人们不愿付出努力，总想跳过过程直接通过吃药获得益处。人们希望不去健身房就能获得健身效果。就像无数研究显示桑拿、冷水浴、限制饮食等带来的惊人益处，但人们就是不愿承受不适。

I've been trying to This brings me to the pushback on a lot of this longevity stuff is that we're always looking for a pill for something. People don't like doing the work. People want to skip the work in order to be able to just take some form of pill that gets the benefits. People want to be able to have the benefits of the gym without going to the gym. And so it's just like, I think there's countless studies which are showing the amazing benefits of sauna, cold plunge, restrictive eating, those kinds of things, but people don't like discomfort.

问题就在于此。

That's the problem.

是啊。阿门。没错。这就是症结所在。

Yeah. Yeah. Amen. Yeah. That is the issue.

你对逆转衰老这件事怎么看？假设人们想激活山中因子，能让自己年轻十岁重置状态，皱纹开始消失等等。辛克莱在书里也讨论过这个，他到处巡回演讲时——

What are your thoughts on let's say you can dial back the clock. Let's say that people wanna tap into these Yamanaka factors and they can knock ten years off their life and reset and they start the wrinkles start going away and whatever. So what are your thoughts? Like, you know, Sinclair talks about this in the book. He goes and he does all these different speaking tours.

他问观众：如果能活到120岁你们怎么看？他是这么设问的：如果能活到120甚至130岁？结果在场所有人基本都反应'天啊不要，我可不想活那么久'。

He asked the audience, you know, what are your thoughts if you could live to a 120? And he frames the question this way. Like, if you could live to a 120, a hundred thirty, and everybody in the audience for all intents and purposes are just like, oh, god. No. I wouldn't wanna do that.

他说这种对长寿的污名化源于人们认为百岁老人肯定坐轮椅或拄拐杖，无法像30岁时那样自由行动。但辛克莱提出：如果百岁时仍能行动自如、思维清晰呢？人们会因此改变主意吗？这个问题常让人陷入认知混乱，甚至不确定自己究竟想要什么。

And he says that a lot of the stigmatism around, like, not wanting to live longer is people equate once I'm 100, I'm literally in a wheelchair or I am, you know, going around with a walker and I'm not living a life that I wanna live where I have full mobility to do and act the way I was when I was 30. And Sinclair is kind of making the argument, well, what if you could? What if you could have full mobility, full cognitive control, and all these types of things at a 100 or a 110? Would you still want to live longer? And it just kind of throws people into this cognitive, like, confused state of, like, not even really fully knowing if that's what they want.

我认为这涉及到一个更宏观的问题，不过我想在此暂停一下，听听塞布你的看法。

And I think this goes to a bigger point, but I'm gonna pause right there and just kinda get your thoughts Seb.

这个问题可以从很多角度来探讨。首先我想说的是，你可以纯粹从利己主义视角来看——只要延长寿命的同时能维持健康寿命（他所说的'健康寿命'与'总寿命'的区别），让健康寿命与总寿命基本匹配，那我就是在享受有质量的人生。我绝不愿意成为卧床不起、丧失行动能力、记忆衰退的植物人状态，这对我毫无吸引力。

So there's so many different ways you can take this. And the first thing I'll say is that I think you can look at it purely from a selfish perspective and it's like, for sure, let's just go extend life as long as I'm expanding my, as he calls it, his health span, the difference between lifespan and health span. And I think as long as my health span is matching somewhat of my lifespan, then I'm actually living a quality life and I'm able to go and do things. I do not want to be a vegetable laying in a bed, unable to do anything, poor memory. That just does not interest me.

所以从最基础的利己角度来说，这听起来很棒。但有几个问题值得思考：首先，我认为正是生命的有限性赋予了生命价值。正因为人生短暂，我们才更珍惜那些美好时刻。如果我能活到500岁甚至1000岁，基本上可以体验所有职业、探索各种领域，反而会对生活失去大部分兴趣。

And so you could say at the base of it, if you're kind of thinking about it from a purely selfish perspective, it sounds great. However, there's a couple of things that kind of come to mind. First off, I think that it's actually the finality of life that gives value to life. It's because we only have a finite amount of time on this earth that actually allows us to enjoy these amazing moments. Whereas if I live to 500, if I live to a thousand, you can pretty much go experience most careers, you can go dive down most rabbit holes, and I think you'd lose a lot of interest in life.

另一个有趣的现象是：我查阅了一些研究资料，特别是塞缪尔·埃利斯2018年的研究。他追踪了52个物种，发现哺乳动物中具有生殖后生命阶段的极为罕见，基本上只有人类和少数齿鲸。这并非偶然——进化更倾向于让寿命刚好足以保证成功繁殖和后代存活。一旦完成这个使命，继续存活对进化而言收益递减，因为会消耗本可用于下一代的资源。

I think that the other thing that's interesting is I went and dug into a handful of studies. One in particular, there's a guy called Samuel Ellis. And in 2018 he followed 52 different species and found post reproductive stages are rare in mammals and essentially it's only humans and there's a couple of toothed whales that have post reproductive life. And you could argue that this isn't accidental, it's that evolution tends to favor lifespans that are just long enough to ensure successful reproduction and survival of the offspring. But once that job is done, continued existence offers very diminishing evolutionary returns because you're obviously now consuming resources that could be for the next generation and are necessary for that generation to survive.

因此我认为长寿会带来适应性问题：老一辈离世后，更适应环境的新生代才会涌现。物种寿命越长，其生理和行为模式就会越僵化。我们在金融界也看到类似现象：标普500企业的平均寿命从百年前的50年骤降到如今的9年左右，正是因为僵化速度太快了。

And so I think there's an adaptability issue that arises with longevity around as older generations pass on, newer ones emerge that are better suited to the current environment. And the longer species live, the more ossified I think they become, both biologically and behaviorally. And we even see this in the financial world, the S and P 500, the average age of a company in the S and P 500 today, if you look a hundred years ago, it was like fifty years. Today it's like nine years or something like that. It's dropping so rapidly because it's so easy to become ossified.

作为物种而言，如果希望人类繁荣发展，我认为长寿可能并非正途。保持与生俱来的自然寿命反而更有利于环境适应。最后我想指出：当前长寿研究热潮很大程度上源于恐惧。对比东西方医学传统——在现代医学出现前，东方人面对绝症时往往数月内就会离世，因此人们经常目睹长辈迅速逝去。

And I think that as a species, if we want humanity to thrive, I would argue that longevity is probably not going to be the way for humanity to thrive. It's actually probably just maintaining whatever lifespan we're meant to be born with because it allows us to adapt to our environment. And the final point that I'll kind of mention along those lines is that I think that a lot of this longevity space evolved out of fear. Like if we look at the difference between Western medicine and Eastern medicine, well, pre current modern medicine, the Eastern side of things, like if you got ill, you got a terminal illness, you're going to die within a few months. So a lot of people experienced and saw their elders pass on very rapidly.

这使得他们能与长辈充分交流智慧传承，死亡被视为生命自然部分。但如今我们虽能延长寿命却无法保证健康质量，很多人带着阿尔茨海默症或肿瘤痛苦地多活15-20年，毫无生活质量可言。正因如此，西方社会对死亡产生了极大恐惧——因为他们几乎看不见自然死亡的过程。

So they spent a lot of time with their elders, they passed on wisdom. Death was a part of life. But I think that as we've got better at being able to extend life but not necessarily health, we see people that live for another fifteen, twenty years with Alzheimer's and tumours and they're suffering and the quality of life is just not there. And so we've now got this fear of death. People in the Western world are so scared of death because they just don't see it.

最终我们把许多老人送进养老院。这本质上就像把他们关起来。我们看不见他们，也体验不到死亡。所以我认为当今生活中，许多人都对死亡充满恐惧。

And we end up putting a lot of these elderly people in homes. We essentially just kind of locking them up. We don't see them. We don't experience death. So I think that a lot of life today, we are fearful of death.

我们总想不断延长寿命，但我不认为这就是我们应该延长寿命的理由。我很想听听你的看法。

We want to constantly extend life, but I don't necessarily think that's the reason why we should be extending life. I'm curious to hear your thoughts.

普雷斯顿，我认为核心问题是，如果一个人觉得自己无法为社会创造价值，那延长生命的意义何在？因为内心深处，如果人们觉得自己无法以某种方式做出贡献，或提供某种服务或生产力，他们就不会快乐。你会感到无聊、停滞、不满足。你知道，我们经常听到那些赚了大钱的人说，'我赚了5000万美元'之类的话。

Preston I just think at the core, if a person doesn't feel like they're providing value to society, what's the point? What's the point of extending your life? Because deep down inside, I don't think people are going to be happy if they don't feel like they're contributing in some way, some fashion, or feel like they're providing some type of service or productivity to society, you get bored, you get stagnant, you just get unsatisfied. You know, you hear this all the time with people that make a bunch of money, all the time. People say, oh, yeah, I made $50,000,000 or whatever the number is.

然后他们说，'我卖掉了公司，之后真的不知道该做什么'。在很长一段时间里，我都感到极度不满。我认为当一个人真正年老时，这种感受很大程度上源于身体上无法做任何事情。他们成了环境的受害者，因为他们甚至无法自由活动和做事。那么在那个阶段，他们如何为社会创造价值呢？

And then they're like, and I sold my business, and, like, I just didn't really know what to do after that. And I was just deeply dissatisfied for quite a period in my life. And I think that when you think of a person that's really older and of age, a lot of that comes from just not physically being able to do anything. They're just kind of they've become a victim of their own environment because they just can't even really get around and be mobile and do things. So how can they create value to society at that point?

他们的认知能力衰退了，很难参与竞争。虽然有朋友陪伴，但他们某种程度上已经准备好离开了。不是他们想走，但也不是对此感到难过。我认为这很大程度上取决于你是否感到自己在为世界贡献新事物或独特事物的幸福感。

They're cognitively declined. It's really hard to compete. They've got their friends and whatnot, but at the same time, they're just kind of ready to go. It's not that they want to go, but it's not like they're upset about it at the same time. And I think a lot of it comes down to just your happiness of feeling like you're contributing something new to the world or something novel to the world.

几年前我记得查过——别引用我的话——我记得查过英国最高龄的在职工作者。如果没记错，这个人从15岁就开始抽烟。他下班后去酒吧喝一品脱啤酒，吃用植物油煎炸的炸鱼薯条。这家伙大概106岁了还在全职工作。你会觉得，这家伙完全颠覆了我们关于长寿的所有讨论。

A few years back, I remember looking into and don't quote me on this, I remember looking into the oldest working individual in The UK. And if I remember correctly, this guy has basically smoked since he was like 15 years old. He finishes work, he goes down the pub and has a pint and eats fish and chips, which are basically just cooked in seed oils. This guy was like 106 or something of that and he's still working full time. And you're just like, This guy has just defied everything that we've been discussing in the whole idea of longevity.

于是你会问：根源是什么？我认为有时我们试图在细胞层面改变自己，但正如你所说，如果要延长寿命，关键可能不在于细胞层面，而在于找到人生目标。如果你读过维克多·弗兰克尔的《活出生命的意义》——他经历过二战——书中谈到，一个人已实现的成就与想要实现的成就之间的张力，正是让我们得以生存的原因。我记得他在书中举例说，有个在二战集中营里被关押多年的人，支撑他活下去的信念是：如果能出去，他就要去寻找妻子。但后来他得知妻子已被杀害，第二天他就去世了。

And so then you ask, you're like, Well, what is at the root of this? And I think sometimes we are trying to alter ourselves on a cellular level yet what if it's, and to your point, what if it's actually got, if you want to extend life, it's not about the cellular level, it's about finding purpose. If you ever read the book, Man's Search for Meaning by Viktor Frankl, who was kind of in World War II, he talks about how the tension between what a man has achieved and what they want to achieve is what basically allows us to survive. And there's people I think one of the analogies or one of the examples he gives in the book is there was this guy that had been in one of these camps for during World War II, had been in one of these heinous camps for multiple years and what had kept him alive is knowing that if he's able to get out of this camp, he's going to go find his wife. And he ends up finding out that his wife had been killed and he dies the next day.

你会想，那不过是希望让他活下来。是他的精神毅力让他活了下来。所以我认为我们可以在细胞层面随心所欲地改变自己，但最终最重要的因素——这又回到你提到的普雷斯顿的观点——是人生目标。就是真正感觉到我们在为社会创造价值。因为即使我们可能健康，即使我们可能延长寿命等等，如果我们没有人生目标，那又有什么意义呢？

You wonder, you're like, that was just hope keeping him alive. It was his mental perseverance keeping him alive. And so I think that we can change ourselves in a cellular level as much as we want, but in the end the most important factor, and this goes back to your point Preston, is purpose. It's like actually feeling like we're creating value in society. Because even if we may be healthy, even if we may be able to extend longevity and stuff, if we don't have purpose in life, what is the point?

普雷斯顿 是啊。我觉得很多人也不愿意重塑自我，因为那需要付出很多努力。这就像坐在冷水浴或进入桑拿房的困难一样。有些人受不了，有些人却乐在其中。

Preston Yeah. Think a lot of people just don't want to reinvent themselves too, because that's a lot of work. It goes back to the difficulty of sitting in a cold plunge or getting into a sauna. Some people can't stand it. Other people like it.

但我觉得当你考虑创造价值时，这个世界是个超级竞争的地方。很多时候人们想掌控自己创造的东西。而在很多工作中你并没有控制权，只是听命于人。所以如果你一直为别人工作，由于竞争极其激烈，你甚至从未有机会自己创造些什么。

But I think when you think about adding value, the world is a super competitive place. And a lot of the times people wanna be in control of whatever they're creating. And a lot of jobs you're not in control. You're just answering to somebody else that's telling you. And so if you've worked that job for somebody else and you've never really even had the opportunity to create something yourself because it's super hard and super competitive.

随着年龄增长，当你经历这些到了80、90甚至100岁时，我想很多人可能不愿继续为创造价值而战斗了。他们差不多精疲力尽了。不知道，也许这是种悲观看法，但确实有些人会非常享受这种竞争并想继续下去，对吧？

You get older and you've gone through this and you're 80, 90, 100 years old, I think a lot of people may not want to keep battling the competition to add value. They're just kind of done, they're tapped out. I don't know, maybe that's a pessimistic way to look at it, but I think there are going to be some people that enjoy the hell out of that competition and they're going to want to keep going, right?

我发现一件很有趣的事：不久前我读了凯瑟琳·沙纳汉写的《深度营养》这本书——我强烈推荐给任何想深入了解健康和饮食方面的人。她提到一项研究，我不得不翻看她的笔记来查找。她提到他们在1994年做了项名为《古代世界寿命长度对照研究》的项目，基本上研究了罗马在6月到6月间...不，是跨越一千二百年间的数据。

One thing that I found really interesting is a little while back I read a book called Deep Nutrition and this lady, Catherine Shanahan, this book I highly recommend for anyone who's kind of diving into the health side of things, the food side of things. And she mentioned a study and I had to go back through her notes to try and find this study. One of the things she mentioned is they did this study in 1994 called Length in Life in the Ancient World, a Controlled Study. And they basically looked at Rome between the years of June and June. So this is like a thousand year no, twelve hundred year period.

他们只研究了男性，排除了婴儿死亡率、死刑处决和战死人员。结果发现当时罗马人的平均寿命在75到80岁之间。你会觉得这太疯狂了。当我们排除婴儿死亡率、死刑和战争死亡这些因素后，再来对比今天的美国——昨天我查了CDC数据，2023年美国男性平均寿命是75.8岁。

And they looked just at males, they removed infant mortality, they removed people that were assassinated through the death penalty and they removed death in battle. And what they found is that the average person in Rome during that time was living between 75 to 80 years old. And you're just like, wild. So when you remove these other issues, infant mortality, death penalty, death in battle, well now let's compare that to The US today. Well in 2023 and I had a look up yesterday, the CDC, the Center for Disease Control, says that the average male in The US in 2023 lived to 75.8 years old.

现在，如果你排除美国的婴儿死亡率（大约是每千人或万人中有6例死亡），这个数字会上升到76.2岁。但排除这些因素后，6.2岁的差距并不比罗马人活得更长。这让我开始思考利益驱动问题——制药和医疗行业有动机宣扬我们正在延长寿命，声称在全球各种问题下仍能提高人均寿命。但实际上，有些研究可能会表明这并不完全正确。

Now, you remove infant mortality from that, which in The US is like six deaths per I think it was like a thousand or ten thousand or something. And so if you remove infant mortality from that, it increases it to 76.2. Well, 6.2 is no longer than what the Romans were living once you remove out those factors. And so this is where I think you start to look at the incentives and there is an incentive for pharma and the medical industry to push that we have been aging, that we have been able to increase the average age of the individual in the face of all of these things that are going on in the world. But in reality, I think there are some studies that would say that's not necessarily true.

我认为还可以这样说，当今普通人群的健康状况，比如过去大约五十年间，我们看到糖尿病发病率上升，过敏症和慢性病发病率也在攀升，所有这些现象。不能说普通人是健康的。因此我倾向于认为，如果你查阅期刊数据、科学文献，很多这类资料当你深入探究时都是经过筛选的。大量数据被操纵。我认为换个角度审视这些数据时，我们寿命的延长程度可能并不像我们以为的那么显著。

I think that what you can also say is that the health of the general population today, like from over the last, say, fifty years, we have seen rising rates of diabetes, we have seen rising rates of allergies, chronic illness, all of these things. Would not say that the average person is healthy. So that's where I tend to think that if you're looking at the journal data, the scientific journals, a lot of this stuff, when you start going down these rabbit holes is curated. A lot of it is manipulated. And I would argue that when you start looking at the data from a different perspective, we may not have increased lifespan to the extent that we might believe we have increased lifespan.

不知道你对此有何看法。

I don't know what your thoughts are on that.

是的。我认为迄今为止你说得非常正确。特别是将指标与古罗马时期相比对吧？这很荒谬。不过我倒不觉得意外。

Yeah. I think to date, I think you're exactly right. I don't think that there's anything that's Especially comparing the metric back to Rome, right? That's crazy. It doesn't surprise me though.

确实不意外。我认为观察当前西方饮食模式，这正是问题如此严重的原因之一。但我预感在未来一二十年内，我们将真正看到人类寿命上限被打破，特别是如果人们饮食得当，并且运用那些我认为我们正开始深入理解的技术——

It doesn't surprise me. I think that when you look at a western diet right now, I think that's one of the reasons why it's as bad as it is. But I think I kind of suspect in the coming decade or two that we're going to really start to see the glass ceiling get shattered with respect to the ages that we see people start living, especially if people are eating appropriately and and you lean into some of this technology that I think we're really starting to deeply thirty:fifty):

关于人体实际运作和自我调节机制的技术。

understand of how the body actually functions and how it regulates itself.

我想未来50年会很有趣。普雷斯顿，当你100岁我80岁时，我们可以回听这期节目，看看发生了什么。

I think it'll be interesting over the next say 50. Preston, when you hit a 100 and when I hit 80, we'll have a look back and listen to this episode and see what's happening.

您这话是什么意思，先生？您暗示什么？我脸都红了。好吧，我就说这么多。

What are you implying here, sir? What are you implying? I'm turning red. Okay. That's all I had.

关于这个特定话题，Seb，你还有什么想讨论的吗？

Is there anything else you wanna cover on this particular one, Seb?

我又做了一点研究，因为我总想弄清楚这些信息的准确性。为了公正看待科学，有趣的是实际上有大量研究结果与寿命学说相悖。特别是有位叫Charles Brenner的研究者，他对此做了大量研究。其中一项发现是：在酵母中，sirtuin基因仅能让500万个细胞中的1个活得更久，而对整个500万细胞群体而言，这些基因实际上会缩短寿命。

I did a little bit of research again, because I like to try to understand what is the accuracy of this information? And I think to be able to be fair to the science, what's interesting is there is actually quite a lot of studies that go against what lifespan has also been saying. And so there was a guy specifically, Charles Brenner, and he did a whole bunch of studies on this stuff. And one of the things he found is like in yeast, sirtuin genes help only one in 5,000,000 cells live longer. And across the whole batch of 5,000,000 cells, they actually shorten lifespan.

酵母中的寿命延长效应在统计学上可忽略不计。2011年有另一项研究显示，来自七家机构的研究人员发表结论称sirtuin基因无法延长蠕虫或果蝇的寿命。随后出现的大量结果表明存在严重的媒体偏见——阳性结果登上全球头条，而许多阴性结果未被发表。

Lifespan extension effect in yeast is statistically negligible. There was another study that looked at in 2011. Researchers from seven institutions published that sirtuin genes do not extend lifespan in worms or flies. And then there was basically just a whole other bunch of results that there was a lot of media bias. The positive results made global headlines, a lot of the negative results were not published.

这某种程度上是选择性叙事。总的来说——我很想听听你的想法——我认为这本书非常引人入胜。通过深化我对身体修复机制和衰老过程的理解，它极大地开拓了我的视野。不过我觉得作者似乎过度认同医疗行业和制药工业的观点，比如他引用'纯素食主义最健康'这类主张。

So there's a bit of selective storytelling. And so overall, and I'm curious to hear your thoughts, I thought the book was really fascinating. And I think that from deepening my understanding about how our body thinks about repair, how our body thinks about aging, it opened my eyes massively. However, I would say that the author, it sounds like he's very much like bought into the medical industry, the pharmaceutical industry. And as a result of that, like he's citing things like, well, he wants to be like vegan vegetarian is best.

但现在我们看到大量新文献开始推翻历史文献，因为人们意识到那些历史文献是被某些能从特定叙事中获利的公司和机构收买的。我认为书中确实有许多值得深挖的精彩观点，但其中部分关于食物与健康的论述未必符合当前科学认知。不过总体而言，这确实是本超级有趣的书。

But now we're starting to see a lot of the literature coming out, which is disproving a lot of the historical literature because you realise that historical literature has been bought and paid for by certain corporations and entities that benefit from that narrative. So I think that there's definitely fascinating points that you can dig into throughout the book, but I think there's some interesting points as well, which I think aren't necessarily backed up by current understanding of food and health and such. But overall, I thought it was a really super interesting book.

Preston，是的。我想从对立角度补充几点：首先他在许多相关领域公司都有大量投资。另外我多年前就听说这本书某种程度上是为他实验室筹集研究资金的宣传工具。关于sirtuin酶的观点特别有趣，因为我从未考虑过藻类生命周期的问题——在如此短暂的时间跨度里，统计上能否证明其寿命确实被延长了。

Preston Yeah. I would say on the contrarian point to add some to what you're saying. Number one, he has a lot of investments in a lot of these companies that are working in some of these areas. The other thing that I had heard, this was years ago, was that the book was somewhat of a fundraising tour to raise money for his lab and the research that he was doing to get more money there. The point on the sartuins, the enzymes, was really interesting because I never even thought about that life or the time of the algae and whether statistically being able to prove whether that's actually extending it or not because it's such a short span of time.

这个观点我从未想过，但确实非常独到。有个理论我莫名地非常认同——衰老源于信息丢失。他在书中的阐述让我直觉上就觉得合理，简洁到足以反映可能的真实情况。

I never even thought about that, but that's a really interesting point of view. The one thing that I think is, for whatever reason, I just really buy into it. This idea that it's based the aging is based on information loss, I just totally buy into it. Like, the way he lays it out in the book, it just intuitively makes sense. It seems to be simple enough to actually represent what's probably taking place.

我认为关于表观遗传学信息丢失的观点，他们这个简单的想法确实触及了某些重大发现。但众所周知，人体复杂得令人发指。我想这就是为什么我对他们引入AI辅助深入研究感到兴奋，这可能会引领未来方向。

And I think that the loss of information with respect to the epigenetics, I think they're onto something really, really big with that simple idea. But as we know, the body is so freaking complex. I guess that's why I'm kind of excited for them to stick AI on it and to assist in some of the further research and where it might be all going in the future.

普雷斯顿，我觉得这里会很有意思，因为这些都是多因素问题。我们或许能逆转某些细胞的衰老，但如果一个人失去求生欲望，生命是否仍会终结？所以真正有趣的是要权衡这些不同理念——生活目标、灵性等等，这些都极其迷人。不过话说回来，这绝对是本值得一读的书，我强烈推荐大家看看。他们用老鼠做的一些实验案例简直令人震惊。

Preston This is where I think it'll be interesting to see, this is all very multifactorial. So we may be able to go in and reverse aging in some of these cells, but if a person doesn't have a desire to live, is their life still going to come to an end? And so I think that that's where it's really interesting is weighing up all of these different ideas and purpose and spirituality and all of this stuff I think is really, really fascinating. But again, it's definitely an interesting book to read and I definitely recommend people giving it a read. And some of the stories, some of the examples of what they're doing in mice is mind blowing.

另外我想说的是，参加过这么多比特币会议和聚会后，我发现比特币爱好者们特别热衷讨论长寿话题。他们能随口抛出我们节目中谈到的各种术语，大多数币圈人都会附和'对对对，这个我熟'，然后就开始跑题。不知道塞巴斯蒂安你有没有同感，但我和比特币爱好者交流时发现他们对此简直痴迷。

One other thing that I'll say, having gone to a lot of Bitcoin conferences and meetups and talking to a lot of Bitcoiners, Bitcoiners love talking about longevity. Can throw around a lot of these terms that we were talking about on this show and most people in the Bitcoin space are like, Oh yeah, yeah, yeah, I know all about that. Then they go off on their tangent. I And don't know if that's been your experience, Seb, but that's been my experience talking to Bitcoiners as they're totally into this

确实如此。

stuff. Absolutely.

好吧，就当是个小插曲。今天就到这里，如果术语使用不当或案例不够贴切，我们深表歉意。我们真的尽力了。

Yeah. Anyway, just a side note. That's all we have for you guys. I apologize if our terminology is off or examples we provided weren't helpful. We were trying.

录制过程很愉快，至少我个人玩得很开心。非常感谢大家的收听！如果你们有推荐的长寿类书籍或这个领域的新见解，我们很乐意继续探讨。我就爱研究这类东西。塞巴斯蒂安，你有什么想推广或补充的吗？

We had fun recording it. Personally, I had fun recording this, and we really appreciate you guys tuning in. And if you have any good longevity books or any new insights into this space, we would love to cover it more. I love learning about this kind of stuff. Seb, give people a hand off to anything that you want to promote or talk about.\

酷，谢谢普雷斯顿。同样感谢收听的各位。就像普雷斯顿说的，有些解释可能不够准确，还请见谅。

Cool. Thanks Preston. Yeah. And again, I really appreciate it if I'm just giving this a listen. And just as Preston mentioned, I apologize we butchered some of explanations.

我觉得你们很多人会跟Preston和我一起学习这些内容——确实如此。我强烈推荐大家读读这本书，真正深入思考书中的观点，因为通过在这个播客上共同讨论，我对这些主题的理解有了巨大提升。可能看起来不像，但确实大幅提高了我的理解。所以强烈建议做笔记、深入研究。如果有不太明白的地方，现在可以上YouTube搜索，或者问问AI。

Lot of this stuff I feel like you guys are going to be learning alongside Preston and I- Absolutely. And I highly recommend giving the book a read and really just trying to dig in and think about what it is they're saying, because I've found that actually having to speak about this together on this podcast has hugely improved my understanding of these topics. May not seem like that, but it has hugely improved my understanding of these topics. So highly recommend taking notes, going and digging into this stuff. If you don't quite understand something, type it into YouTube, type it into AI these days.

AI让我惊叹不已。你只需提问'我不太理解这个，能否解释并用类比说明？'它就能给出绝妙的例子。如果想联系我，可以在Twitter上找到我，账号是justsaidbunny（B U N N E Y）。

AI has blown me away. You just ask a question, I don't quite understand this. Can you explain it to me and give me an analogy? And it just lays out phenomenal examples. If anyone wants to find me, you can find me at just said bunny, B U N N E Y on Twitter.

还有我的网站saidbunny.com，上面可以找到我的著作《金钱的竞价成本》等。再次感谢大家的收听，也特别感谢Preston邀请我参加节目。

And then you've got my website said bunny dot com, which you can find my books, A Bidding Cost of Money and such. But again, as always, I appreciate you guys giving it a listen and thanks a lot Preston for having me on.

好的，下周见。感谢收听。

Okay. Until next week. Thanks for listening.

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