Dr. Peter Attia: Supplements for Longevity & Their Efficacy

Peter Attia 博士：长寿补充剂及其功效

2024-07-29 | 官方页面 YouTube 官方音频

Andrew Huberman:

安德鲁·休伯曼：

Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life.

欢迎来到休伯曼实验室播客，我们在这里讨论科学和基于科学的日常生活工具。

I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine.

我是安德鲁·胡伯曼，斯坦福大学医学院神经生物学和眼科教授。

My guest today is Dr. Peter Attia.

Dr. Peter Attia is a medical doctor who did his training at Stanford University School of Medicine and Johns Hopkins School of Medicine.

Peter Attia 博士是一名医学博士，曾在斯坦福大学医学院和约翰霍普金斯大学医学院接受培训。

Dr. Attia is one of the world's most trusted voices on the topics of healthspan and lifespan, and with good reason.

阿蒂亚博士是世界上在健康和寿命话题上最值得信赖的代言人之一，这是有充分理由的。

He is known to systematically review the research literature, the clinical trials, and he maintains an avid clinical practice.

众所周知，他以系统地回顾研究文献和临床试验而闻名，并且一直热衷于临床实践。

So when it comes to the topic of whether or not a particular molecule or supplement or prescription drug is indeed something that we should be thinking about and perhaps even taking in order to improve our healthspan and lifespan, Dr. Attia is the person that I choose to sit down with and discuss it.

So today, we are going to discuss the so-called NAD pathway.

所以今天我们要讨论的是所谓的NAD途径。

This is a pathway that's received a lot of attention in recent years as a potential target for improving lifespan.

近年来，这一途径作为延长寿命的潜在目标而受到广泛关注。

That is, for living longer.

Today, we discuss the various molecules in this pathway and the various approaches to increasing NAD, which is the end target goal of anyone that's trying to augment the NAD pathway, so to speak.

So for instance, we talk about taking NR versus NMN versus direct infusions or even orally taking NAD, and we compare them in terms of both what's known and what is not known about their ability to get into cells and any efficacy they may have for either longevity or healthspan.

Dr. Attia and I compare and contrast the literature on this, again, both research and clinical literature, and we discuss whether or not he or I take NAD, NMN, or NR.

And if so or if not, the reasons for that.

We also each go through our own supplement regimen, which of course reflects what we do believe can potentially have an effect on healthspan and/or lifespan.

So by the end of today's episode, you'll learn a lot about NAD, you'll learn a lot about the biological pathway, you'll learn a lot about the delivery routes, the various supplements, and why people think they may be useful, why others, perhaps even Dr. Attia and myself, think they may not be useful for longevity.

You'll have to listen to find out what the answer is there.

你必须倾听才能找出答案。

I should also mention that we give somewhat of an overview or a framework for thinking about approaches to longevity.

我还应该提到，我们为思考长寿方法提供了一些概述或框架。

So if you're interested in things like rapamycin, metformin, and whether or not fasting can improve longevity, we get into that as well.

因此，如果您对雷帕霉素、二甲双胍以及禁食是否可以延长寿命感兴趣，我们也会对此进行探讨。

Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford.

在开始之前，我想强调一下，这个播客与我在斯坦福大学的教学和研究角色是分开的。

It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public.

然而，我的愿望和努力的一部分是向公众提供有关科学和科学相关工具的零成本消费者信息。

In keeping with that theme, I'd like to thank the sponsors of today's podcast.

为了与这个主题保持一致，我要感谢今天播客的赞助商。

Our first sponsor is LMNT.

我们的第一个赞助商是LMNT。

LMNT is an electrolyte drink that has everything you need and nothing you don't.

LMNT 是一种电解质饮料，拥有您需要的一切，没有您不需要的东西。

That means the electrolytes, sodium, magnesium, and potassium in the correct ratios, but no sugar.

这意味着电解质、钠、镁和钾的比例正确，但没有糖。

Now, proper hydration is critical for the optimal functioning of all the cells in your body, and that's especially true for the neurons, the nerve cells.

现在，适当的水合作用对于体内所有细胞的最佳功能至关重要，对于神经元、神经细胞来说尤其如此。

In fact, we know that even a slight degree of dehydration can diminish both cognitive and physical performance.

事实上，我们知道，即使是轻微程度的脱水也会降低认知和身体表现。

So to make sure that I'm getting proper hydration and electrolytes, I personally dissolve one packet of LMNT in about 16 to 32 ounces of water when I first wake up in the morning and I drink that or sip that across the first half hour of the day or so.

And then I also make it a point to drink another packet of LMNT dissolved in an equal amount of water, so 16 to 32 ounces, at some other point during the day, and maybe even a third if I'm exercising and/or sweating a lot.

然后，我还会在白天的其他时间喝另一包溶解在等量水中的 LMNT，即 16 至 32 盎司，如果我锻炼和/或出汗很多，甚至可能喝三分之一。

I should mention that LMNT tastes absolutely delicious.

值得一提的是，LMNT 的味道绝对美味。

My favorite flavor is watermelon, although I also confess I like the raspberry flavor, the citrus flavor.

我最喜欢的口味是西瓜，虽然我也承认我喜欢覆盆子味、柑橘味。

Basically, I like all the flavors.

基本上所有的口味我都喜欢。

If you'd like to try LMNT, you can go to drinklmnt.com/huberman to claim a free LMNT sample pack with the purchase of any LMNT drink mix.

如果您想尝试 LMNT，可以访问 Drinklmnt.com/huberman，购买任何 LMNT 混合饮料即可领取免费 LMNT 样品包。

Again, that's drinklmnt.com/huberman to claim a free sample pack.

再次强调，请访问 Drinklmnt.com/huberman 索取免费样品包。

Today's episode is also brought to us by Levels.

今天的节目也是Levels给我们带来的。

Levels is a program that lets you see how different foods impact your health by giving you real-time feedback on your diet using a continuous glucose monitor.

One of the most important factors in both short and long-term health is your body's ability to manage blood glucose.

短期和长期健康最重要的因素之一是您的身体管理血糖的能力。

To maintain optimal energy and focus throughout the day, you want to keep your blood glucose levels steady without big spikes or crashes.

为了全天保持最佳的精力和注意力，您希望保持血糖水平稳定，不要出现大幅峰值或崩溃。

I first started using Levels about three years ago as a way to try and understand how different foods impacted my blood glucose levels, and it's proven incredibly useful for determining what food choices I should make, when best to eat certain foods, especially around things like workouts, and when and what to eat relative to when I go to sleep in order to allow for the best possible night's sleep and stable blood sugar throughout the night and when I wake up in the morning.

So if you're interested in learning more about Levels and trying a CGM yourself, go to levels.link/huberman.

因此，如果您有兴趣了解有关 Levels 的更多信息并亲自尝试 CGM，请访问levels.link/huberman。

Levels recently launched a new CGM sensor that's even smaller and has even better tracking than their previous version.

Levels 最近推出了一款新的 CGM 传感器，与之前的版本相比，它更小，跟踪能力更好。

Right now, they're also offering an additional two free months of membership.

现在，他们还提供额外两个月的免费会员资格。

Again, that's levels.link, spelled L-I-N-K, /huberman to try the new sensor and two free months of membership.

同样，这是levels.link，拼写为L-I-N-K，/huberman，用于尝试新传感器和两个月的免费会员资格。

Today's episode is also brought to us by Eight Sleep.

今天的节目也是八觉给我们带来的。

Eight Sleep makes smart mattress covers with cooling, heating, and sleep tracking capacity.

August Sleep 生产具有冷却、加热和睡眠跟踪功能的智能床垫套。

Now, I've spoken many times before on this podcast about the critical need for us to get adequate amounts of quality sleep each night.

现在，我之前已经在这个播客中多次谈到我们每晚获得充足的优质睡眠的迫切需要。

One of the best ways to ensure a great night's sleep is to control the temperature of your sleeping environment.

确保一夜好眠的最佳方法之一是控制睡眠环境的温度。

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.

这是因为为了入睡并保持深度睡眠，您的体温实际上必须下降约一到三度。

And in order to wake up feeling refreshed and energized, your body temperature actually has to increase by about one to three degrees.

为了醒来时感觉神清气爽、精力充沛，您的体温实际上必须升高约一到三度。

Eight Sleep makes it incredibly easy to control the temperature of your sleeping environment by allowing you to program the temperature of your mattress cover at the beginning, middle, and end of the night.

八睡眠让您可以非常轻松地控制睡眠环境的温度，您可以在晚上的开始、中间和结束时对床垫套的温度进行编程。

I've been sleeping on an Eight Sleep mattress cover for well over three years now, and it has completely transformed my sleep for the better.

我已经睡在八睡眠床垫罩上三年多了，它彻底改变了我的睡眠质量。

Eight Sleep recently launched their newest generation pod cover, the Pod 4 Ultra.

八睡眠最近推出了他们最新一代的 Pod 4 Ultra。

The Pod 4 Ultra has improved cooling and heating capacity, higher fidelity sleep tracking technology, and it also has snoring detection that remarkably will automatically lift your head a few degrees to improve your airflow and stop your snoring.

Pod 4 Ultra 具有改进的冷却和加热能力、更高保真度的睡眠跟踪技术，并且还具有打鼾检测功能，可以自动将您的头部抬起几度，以改善气流并停止打鼾。

If you'd like to try an Eight Sleep mattress cover, you can go to eightsleep.com/huberman to save $350 off their Pod 4 Ultra.

如果您想尝试八睡眠床垫套，您可以访问八睡眠.com/huberman，在 Pod 4 Ultra 上可节省 350 美元。

Eight Sleep currently ships to the USA, Canada, UK, select countries in the EU, and Australia.

八睡眠目前运往美国、加拿大、英国、欧盟部分国家和澳大利亚。

Again, that's eightsleep.com/huberman.

再说一遍，这是八睡眠.com/huberman。

And now for my discussion about NAD and longevity with Dr. Peter Attia.

现在我将与 Peter Attia 博士讨论 NAD 和长寿。

Peter Attia, welcome.

彼得·阿蒂亚，欢迎。

Dr. Peter Attia:

彼得·阿蒂亚博士：

How are you?

你好吗？

Andrew Huberman:

安德鲁·休伯曼：

Great to see you again.

很高兴再次见到你。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Great to be here again.

很高兴再次来到这里。

Andrew Huberman:

安德鲁·休伯曼：

Should we parse this NAD thing?

Dr. Peter Attia:

彼得·阿蒂亚博士：

I think we should.

我认为我们应该。

Andrew Huberman:

安德鲁·休伯曼：

Do you mind if I set up a little bit of a framework?

你介意我建立一些框架吗？

Great.

伟大的。

So for people that want to live as long as possible, I figure there are at least four categories of approaches, broadly speaking.

因此，对于那些想要尽可能长寿的人来说，我认为总的来说，至少有四类方法。

The first, I'll just call the do's and don'ts.

You've talked a lot about these.

Your book, "Outlive," beautifully covered these, and I tend to regurgitate some of what you say on this podcast.

你的书《Outlive》完美地涵盖了这些内容，我倾向于重复你在这个播客上所说的一些内容。

Namely, you want to move appropriately and often enough, so get enough zone two cardio, do your resistance training, keep nerve to muscle connections strong, avoid the sorts of things that would lead to falling and being immobile.

Eat right.

吃得对。

There's a whole category of things there we're not going to talk about today, although we might touch on a bit.

尽管我们可能会触及一些，但今天我们不会讨论一整类事情。

And know your genetics and make some good decisions on the basis of your genetics.

了解你的基因，并根据你的基因做出一些好的决定。

So the do's and don'ts.

所以该做什么和不该做什么。

The second category I would put under the umbrella of calories, glucose, insulin, et cetera, that all kind of funnel in, at least in my mind, to mTOR, mammalian target of rapamycin.

A molecule that's robustly expressed during development in essentially all cells of the body, and then across the lifespan tapers off.

一种在发育过程中在身体几乎所有细胞中强烈表达的分子，然后在整个生命周期中逐渐减弱。

During puberty especially, well, let's say infancy through puberty, cells are expressing so much mTOR, and they're growing like crazy, and we often associate that early stage of life as youth, not aging, because we think of it as a kind of a timestamp as opposed to the verb.

特别是在青春期，好吧，比如说从婴儿期到青春期，细胞表达大量的 mTOR，它们疯狂地生长，我们经常将生命的早期阶段与青春期联系起来，而不是衰老，因为我们认为它是一种时间戳，而不是动词。

But I would argue, as a developmental neurobiologist by training, that it's one of the most rapid phases of aging of our entire lifespan.

但作为一名训练有素的发育神经生物学家，我认为这是我们整个生命周期中衰老最快的阶段之一。

Look at a picture of you when you were five.

Look at a picture of you when you were eight versus 15.

看看你 8 岁和 15 岁时的照片。

You look very different, and your size is robustly different.

你看起来很不一样，而且你的身材也有很大不同。

Dr. Peter Attia:

彼得·阿蒂亚博士：

By the way, I just did this exercise because my daughter, her 16th birthday is around the corner, and we take a picture of her every single year at the minute of her birth.

顺便说一句，我之所以做这个练习是因为我的女儿，她的 16 岁生日即将到来，我们每年都会在她出生的那一刻给她拍一张照片。

So we have a picture of her every single year holding a clock that says 3:56 at 3:56 PM, because that's when she was born.

所以我们每年都会有一张她在下午 3:56 拿着一个写着 3:56 的时钟的照片，因为那是她出生的时间。

And I just went through and pulled each of the last 16 of them from the day she was born all the way up.

我刚刚把最后 16 个从她出生那天起一直到最后的都列出来了。

And you're right, the biggest changes are actually in about the first 10 years.

你是对的，最大的变化实际上是在前 10 年左右。

The difference between being 13 and 14, 14 and 15, 15 and 16 becomes incrementally less and less and less.

13和14、14和15、15和16之间的差异逐渐变得越来越小。

Whereas going from two to three and three to four and four to five are ridiculous changes.

而从二到三、三到四、四到五则是荒谬的变化。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

The same brain has to learn an entirely new body every year-

同一个大脑每年都必须学习一个全新的身体——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah

是啊

Andrew Huberman:

安德鲁·休伯曼：

...

in terms of how to move it, limb length, et cetera.

就如何移动它、肢体长度等等而言。

So a lot of the so-called anti-aging or longevity approaches that fall under this umbrella relate to things like caloric restriction or taking drugs such as rapamycin.

And of course, mammalian target of rapamycin is the target of rapamycin, duh, in an effort to essentially remove excess insulin, blood glucose, and thereby reduce mTOR activity, so essentially slow cellular growth.

And all that fits nicely into the logic that mTOR is associated not just with development, but with aging because development is aging.

所有这些都非常符合 mTOR 不仅与发育相关，而且与衰老相关的逻辑，因为发育就是衰老。

And then I would say there's a third category, and it's the one we are going to talk about today, which is targeting specific cellular pathways that some people have deemed potentially interesting for longevity.

And the pathway that we're going to spend some time on is the so-called NAD pathway.

我们将花一些时间研究的途径是所谓的 NAD 途径。

NR, NMN, NAD being the major players, and we'll talk about some of the biochemical and enzymatic steps in between.

NR、NMN、NAD 是主要参与者，我们将讨论其间的一些生化和酶促步骤。

And then I suppose there's a fourth category, which we could say is the do everything, even the most esoteric of things category.

然后我想还有第四类，我们可以说它是无所不能，甚至是最深奥的事物类别。

This is a rarer category.

There are folks like Bryan Johnson who spend a lot of time in this category specifically, taking very high doses of polyphenols, limiting their caloric intake to just early part of the day.

像布莱恩·约翰逊这样的人在这一类别上花费了大量时间，服用非常高剂量的多酚，将热量摄入限制在一天的早些时候。

I think he eats dinner at 11:00 a.m.

I don't know if it still qualifies as dinner at 11:00 a.m., but his final bite of calories is, I believe, at 11:00 a.m.

我不知道上午 11:00 是否仍然可以作为晚餐，但我相信他最后一口卡路里是在上午 11:00 时。

Doing everything from red light to PRP, platelet-rich plasma, excuse me, and essentially the kitchen sink approach to longevity and aging.

对不起，从红光到 PRP、富含血小板的血浆，基本上都是通过厨房水槽来实现长寿和衰老的方法。

Did I miss any categories?

Dr. Peter Attia:

彼得·阿蒂亚博士：

So I would frame it slightly differently because I like categories to be more MECE, mutually exclusive, collectively exhaustive.

所以我的框架会略有不同，因为我喜欢类别更加 MECE、相互排斥、集体详尽。

So I don't know that I would formulate it that way, right?

所以我不知道我会这样表述，对吗？

I might say, look, category one are sort of the essential behavioral things that you have no choice but to engage in, whether you want to or not, right?

我可能会说，看，第一类是你别无选择只能参与的基本行为，无论你愿意与否，对吗？

So you have to eat.

所以你必须吃饭。

You have to sleep.

你必须睡觉。

You have to move.

你必须移动。

You just have a choice in do you want to do those things correctly or not correctly, or do you want to do those things in a manner that promotes health or erodes health, right?

So again, there's nobody listening to us who doesn't eat, but again, you can choose how much you eat and what you eat and when you eat.

再说一遍，没有人不吃东西，但你可以选择吃多少、吃什么以及何时吃。

There's nobody who's alive who isn't moving because locomotion is life, and the absence of life is the absence of locomotion, but you can certainly choose to move very little.

活着的人都在移动，因为运动就是生命，没有生命就是没有运动，但你当然可以选择很少移动。

You can choose to move a lot, and you can choose to decide on how you move.

您可以选择经常搬家，也可以选择决定如何搬家。

You alluded to it already, right?

You can move in a certain way that puts your aerobic system in a zone that maximizes fat oxidation.

您可以以某种方式移动，使您的有氧系统处于最大化脂肪氧化的区域。

We call that zone two.

我们称之为第二区。

You can move at a level where you consume incredible amounts of oxygen at your maximum aerobic level.

您可以在最大有氧水平下消耗大量氧气的水平上运动。

You can choose to move in a manner that uses resistance and gravity against you and all those sorts of things.

你可以选择以一种利用阻力和重力来对抗你和所有这些东西的方式移动。

Similarly, we all have to sleep, right?

Matt Walker would probably tell us the number of days you could go without sleep before you would literally perish.

马特·沃克可能会告诉我们，在你真正死去之前，你可以不睡觉多少天。

But again, you have a lot of choices in how you do it.

但同样，您在如何做方面有很多选择。

So anyway, I agree, that's kind of category one, but that's kind of the way I would frame it.

所以无论如何，我同意，这是第一类，但这就是我构建它的方式。

And then I would put in category two, sort of what are the molecules that you would exogenously take to try to impact any of those systems?

然后我会放入第二类，即您会外源地尝试影响任何这些系统的分子是什么？

And again, I'm not saying my framework is correct and yours isn't.

再说一遍，我并不是说我的框架是正确的，而你的框架则不正确。

I'm just saying this is the way I think about it.

我只是说这就是我的想法。

I would then say, what are the molecules that I could take that specifically target disease processes?

然后我会说，我可以采取哪些专门针对疾病过程的分子？

So I kind of think of like, if we want to live longer, and I describe this, I think, in chapter four of "Outlive," that turns out to be mathematically equivalent in the modern society to delaying the onset of chronic disease.

所以我想，如果我们想活得更久，我想，我在《活下去》第四章中描述了这一点，结果在现代社会中，这在数学上相当于延迟慢性病的发作。

Now, that wasn't true 100 years ago.

100 years ago, if you wanted to live longer, a few things had to be true.

100 年前，如果你想活得更久，有几件事必须是正确的。

You couldn't die during childbirth, because that was a huge hit on mortality.

你不可能在分娩时死亡，因为这对死亡率造成了巨大的影响。

And then you had to not get an infection or succumb to trauma.

然后你必须不被感染或死于创伤。

And then maybe 150 years ago, that was the case.

But today, most of those things are taken care of by antibiotics, sanitation, and the modern miracle of childbirth in this era.

但今天，这些事情大部分都由抗生素、卫生设施和这个时代的现代分娩奇迹来解决。

So now, for you and I to live longer, we basically have to delay the onset of cardiovascular disease, cerebrovascular disease, cancer, neurodegenerative disease, dementing diseases, and metabolic diseases.

所以现在你我要想活得更久，基本上就得延缓心血管疾病、脑血管疾病、癌症、神经退行性疾病、痴呆疾病、代谢疾病的发病。

We have to delay the onset of those things.

The longer we delay the onset, the longer we will live, full stop.

我们推迟发病的时间越长，我们的寿命就越长，句号。

So you can use everything that you talked about in the first category plays into that, but you also have this other category of where you can take molecules that specifically target those things.

因此，您可以使用您在第一类中讨论的所有内容，但您还可以使用其他类别，您可以在其中使用专门针对这些事物的分子。

You can take metformin or an SGLT2 inhibitor or a GLP-1 agonist, and you will directly impact those things.

您可以服用二甲双胍或 SGLT2 抑制剂或 GLP-1 激动剂，您将直接影响这些事情。

You could take a PCSK9 inhibitor or a statin or bempedoic acid.

您可以服用 PCSK9 抑制剂或他汀类药物或 bempedoic 酸。

You will directly impact those disease processes.

您将直接影响这些疾病的进程。

You will delay the onset of those diseases, and you will reduce the mortality associated with them.

您将推迟这些疾病的发作，并降低与之相关的死亡率。

Then I would go to a third category that says, are there exogenous molecules that you can take that don't target a disease per se specifically, but we're going to put them in a category called geroprotective, which is they target hallmarks and pathways of aging that you've described.

然后我会谈到第三类，即是否有可以服用的外源分子本身并不专门针对疾病，但我们将把它们归入称为老年保护的类别，即它们针对您所描述的衰老标志和途径。

So we talk about all of these things that occur in an aging phenotype where we see more inflammation, we see a greater abundance of senescent cells.

因此，我们谈论在衰老表型中发生的所有这些事情，我们看到更多的炎症，我们看到更多的衰老细胞。

We see reduced nutrient sensing capacity of mTOR, which you describe as probably the most important nutrient sensing system in our body.

我们发现 mTOR 的营养感应能力降低，您将其描述为可能是我们体内最重要的营养感应系统。

So we have somewhere between nine and 14, the number just keeps changing arbitrarily, but it doesn't really matter.

所以我们有 9 到 14 之间的某个地方，这个数字只是不断地任意变化，但这并不重要。

We have these central things that everybody would agree define what an aging phenotype is, and can we use exogenous molecules to target those specifically?

我们有这些每个人都同意定义衰老表型的核心内容，我们可以使用外源分子来专门针对这些内容吗？

You gave one example, which I would argue is the single best example, which is rapamycin.

你举了一个例子，我认为这是最好的例子，那就是雷帕霉素。

So rapamycin targets a very specific hallmark of aging, and we can talk about what the experimental evidence is to suggest that that makes you live longer.

因此，雷帕霉素针对的是一种非常具体的衰老标志，我们可以讨论哪些实验证据表明雷帕霉素可以让你活得更久。

So I would sort of say those are the big three categories.

所以我想说这就是三大类。

And then basically the fourth category you could just say is like how do you put them all together and how aggressive do you want to be in culminating those?

然后基本上你可以说的第四个类别就像你如何将它们放在一起以及你想以多大的积极性来完成这些？

Of course, none of this touches on another area that I want to talk about that we won't talk about today, which is like how does all that factor into kind of emotional health and happiness and well-being, where none of this other stuff matters if you're kind of unhappy.

当然，这些都没有涉及我想谈论但我们今天不会谈论的另一个领域，这就像所有这些因素如何影响情绪健康、幸福和幸福，如果你不开心，其他这些都不重要。

And you've done so many podcasts on that topic, right?

你已经制作了很多关于这个主题的播客，对吧？

You've had Paul Conti on, where you kind of go through the understanding of ourselves and our minds and why that's also a very important part of it.

保罗·孔蒂（Paul Conti）让你了解了我们自己和我们的思想，以及为什么这也是其中非常重要的一部分。

Because it actually does impact how long you live.

因为它确实会影响您的寿命。

Because if that piece isn't working, it's very difficult to regulate the first bucket, because the first bucket takes so much work.

因为如果那块不起作用，那么调节第一个桶就非常困难，因为第一个桶需要做很多工作。

So if you can't regulate yourself, it's very difficult to regulate the dos and don'ts.

因此，如果你不能规范自己，就很难规范该做什么和不该做什么。

But even absent just length of life stuff, it impacts quality of life, which is this idea of health span as well.

但即使没有生命长度的因素，它也会影响生活质量，这也是健康寿命的概念。

So I guess that's just my slightly different way to frame it, but it's a little bit more MECE, in that we talk about the behaviors, the exogenous molecules that target diseases, the exogenous molecules that target aging.

所以我想这只是我的框架方式略有不同，但它更像是 MECE，因为我们谈论行为、针对疾病的外源分子、针对衰老的外源分子。

Andrew Huberman:

安德鲁·休伯曼：

Aside from food, what exogenous molecules do you take?

除了食物之外，您还服用哪些外源分子？

Dr. Peter Attia:

彼得·阿蒂亚博士：

I take a few, right?

我拿几个吧？

So I take some that are disease specific, right?

So I take a PCSK9 inhibitor.

I take bempedoic acid.

我服用贝贝多酸。

I take an SGLT2 inhibitor.

And then I take at least one that is purely just based on the belief of its capacity in geroprotection, which is rapamycin.

然后我至少选择一种纯粹基于其老年保护能力的信念，那就是雷帕霉素。

And also the SGLT2 inhibitor, I think, is probably just broadly geroprotective, and we can even talk about that a little bit in terms of the success of one of those molecules called canagliflozin in the Interventions Testing Program, the ITP, which I am sure we'll talk about in the context of NAD as well.

我认为，SGLT2 抑制剂可能只是广泛的老年保护作用，我们甚至可以稍微讨论一下干预测试计划 ITP 中一种名为卡格列净的分子的成功，我相信我们也会在 NAD 的背景下讨论这一点。

Andrew Huberman:

安德鲁·休伯曼：

What dosage of rapamycin do you take?

Dr. Peter Attia:

彼得·阿蒂亚博士：

I take eight milligrams once a week for as long as I can tolerate it, but I usually have to take breaks.

只要我能忍受，我每周服用一次八毫克，但我通常必须休息一下。

Andrew Huberman:

安德鲁·休伯曼：

Why is that?

这是为什么呢？

Dr. Peter Attia:

彼得·阿蒂亚博士：

I get these vicious aphthous ulcers, little mouth sores.

我得了恶性口疮，小口腔溃疡。

Andrew Huberman:

安德鲁·休伯曼：

Canker sores.

溃疡疮。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yes.

是的。

Andrew Huberman:

安德鲁·休伯曼：

Ugh.

呃。

Dr. Peter Attia:

彼得·阿蒂亚博士：

About 10% of people get them.

Andrew Huberman:

安德鲁·休伯曼：

Hmm.

嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

It's paradoxically the only biomarker we probably have.

矛盾的是，它是我们可能拥有的唯一生物标志物。

So I secretly rejoice in knowing that at least I'm getting a good batch of rapamycin.

所以我暗暗庆幸，至少我得到了一批好雷帕霉素。

Andrew Huberman:

安德鲁·休伯曼：

By virtue of the side effect.

Dr. Peter Attia:

彼得·阿蒂亚博士：

By virtue of these miserable side effects.

Andrew Huberman:

安德鲁·休伯曼：

Interesting.

有趣。

Dr. Peter Attia:

彼得·阿蒂亚博士：

But so in reality, what it works out to is I'm probably on it for two months and then off it for a month, on it for two months, off it for a month, or thereabouts.

但实际上，结果是我可能会使用两个月，然后关闭一个月，使用两个月，关闭一个月，等等。

Andrew Huberman:

安德鲁·休伯曼：

And the idea there is that you're limiting mTOR.

You're Causing your cells to grow less, mature slower, and in that sense, slowing down aging.

你正在导致你的细胞生长减少，成熟缓慢，从这个意义上说，减缓衰老。

Is that the idea?

是这个想法吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

And this will be an important theme today, right?

这将是今天的一个重要主题，对吧？

It's like we can talk all day long about mechanisms and theoretical arguments for why it would work.

就好像我们可以整天谈论它为何有效的机制和理论论证。

And I think my conviction around taking rapamycin is less about looking at the molecular explanation for why rapa works, although I find that to be quite convincing, and why does the inhibition of mTOR stimulate autophagy?

我认为我对服用雷帕霉素的信念并不是关注雷帕霉素为何起作用的分子解释，尽管我发现这很有说服力，以及为什么抑制 mTOR 会刺激自噬？

Why would that suppress senescent cells?

But truthfully, my conviction around mTOR is far more based on the experimental data, something that is actually sorely lacking in the NAD story, which we'll discuss.

但说实话，我对 mTOR 的信念更多地基于实验数据，而这在我们将讨论的 NAD 故事中实际上非常缺乏。

So the experimental data are far more convincing, right?

那么实验数据更有说服力吧？

Which is when you look at the administration of rapamycin or its analogs, for example, everolimus, when you look at the administration of these molecules to organisms that are as close as possible to the species of interest.

当您考虑雷帕霉素或其类似物（例如依维莫司）的给药时，当您考虑将这些分子给药于尽可能接近目标物种的生物体时。

We're the species of interest.

我们是感兴趣的物种。

So looking at mammals such as mice and small primates, looking at fruit flies, looking at worms, and even looking at yeast, although that's so far from us that you would argue that's the least important.

因此，观察小鼠和小型灵长类动物等哺乳动物，观察果蝇，观察蠕虫，甚至观察酵母，尽管它们离我们太远，以至于你会认为这是最不重要的。

You see something that you don't see for a single other molecule, which is uniform life extension.

你会看到一些其他分子看不到的东西，那就是均匀的寿命延长。

No other molecule has done this.

没有其他分子做到过这一点。

It's very important to understand there are only two interventions, full stop, that have ever extended life across those four categories of eukaryotes.

非常重要的是要了解，只有两种干预措施可以延长这四类真核生物的寿命。

Andrew Huberman:

安德鲁·休伯曼：

Caloric restriction.

热量限制。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And rapamycin.

还有雷帕霉素。

Very important point, right?

非常重要的一点，对吧？

Andrew Huberman:

安德鲁·休伯曼：

How do you feel when you're on rapamycin, aside from the canker sores?

当您服用雷帕霉素时，除了口腔溃疡之外，您还有什么感觉？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, which fortunately aren't that frequent.

是的，幸运的是这种情况并不那么频繁。

I don't feel anything, and the very few of my patients who take it, because maybe 10% of my patients also take it.

我没有任何感觉，而且我的病人很少有人服用它，因为也许我的病人中有 10% 也服用它。

Actually, that's not true.

事实上，事实并非如此。

I've probably heard two people say they feel better on it, but I don't know what to make of that.

我可能听过两个人说他们感觉好多了，但我不知道该怎么解释。

Maybe they do.

也许他们会。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And maybe that's just a placebo effect.

也许这只是安慰剂效应。

Andrew Huberman:

安德鲁·休伯曼：

Does it synergize with caloric restriction or collide with caloric excess?

它与热量限制有协同作用还是与热量过量相冲突？

Meaning, if you're taking rapamycin, but you're slightly over your caloric needs, maybe you're trying to add a little bit of body weight-

意思是，如果您正在服用雷帕霉素，但您的热量需求略高于您的热量需求，也许您正在尝试增加一点体重 -

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm-hmm

嗯嗯

Andrew Huberman:

安德鲁·休伯曼：

...

or happen to overeat a little bit just because, is it going to collide with rapamycin's potential positive impact on slowing aging?

或者只是因为吃得过多，会与雷帕霉素延缓衰老的潜在积极影响发生冲突吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, it's a good question, Andrew.

是的，这是个好问题，安德鲁。

I don't know.

我不知道。

I don't think we know.

我想我们不知道。

We do know that there's one other really important readout we're waiting for, which is Matt Kaeberlein's dog aging study, which is going to be an exciting readout in 2026.

我们确实知道，我们正在等待另一个非常重要的结果，那就是 Matt Kaeberlein 的狗衰老研究，这将是 2026 年令人兴奋的结果。

We're also waiting for another readout out of the University of San Antonio, looking at another trial in mammals, and again, I think those two will be really interesting, right?

我们还在等待圣安东尼奥大学的另一份读数，研究另一项哺乳动物试验，我认为这两项试验真的很有趣，对吧？

Because we have just an overabundance of mouse data that are so reproducible, and reproducible in really good mouse models.

因为我们拥有大量的小鼠数据，这些数据非常可重复，而且在非常好的小鼠模型中也可重复。

As you know, I'm sure from your work, the model you choose matters, right?

如您所知，我从您的工作中确信您选择的模型很重要，对吗？

In an ideal world, you want to use a mouse model that is not inbred, that is more closely related to what we care about, which is ourselves.

在理想的情况下，您希望使用非近交的小鼠模型，它与我们关心的事物（即我们自己）更密切相关。

And so when you see many labs getting the same result over and over again, regardless of how they do it, you really start to believe there's a signal there.

因此，当你看到许多实验室一遍又一遍地得到相同的结果时，无论他们如何做，你真的开始相信那里有一个信号。

So now to be able to see this in a higher order mammal-

所以现在能够在高等哺乳动物身上看到这一点——

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm

嗯嗯

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

and ultimately in companion dogs, which is where Matt Kaeberlein is looking, I think that's going to be really exciting.

最终，马特·凯伯莱因（Matt Kaeberlein）正在研究伴侣犬，我认为这将非常令人兴奋。

And I've often said to my patients, "Look, in 2026, I'm either going to feel a lot more conviction about taking rapamycin and prescribing it to some of my patients," though, again, not most, "or I'm going to have a second look at this and say, maybe we just shouldn't be taking this," right?

我经常对我的患者说，“看，到 2026 年，我要么会对服用雷帕霉素并向我的一些患者开出更有信心的处方，”不过，不是大多数患者，“或者我会重新审视这个问题并说，也许我们不应该服用这个，”对吧？

Because I do think that the dog study is going to be more telling.

因为我确实认为狗的研究会更有说服力。

But again, we'll have to wait and see what that shows.

但同样，我们必须等待，看看会显示什么。

Andrew Huberman:

安德鲁·休伯曼：

Without going off track too much, my understanding is that the dog study was halted because of a lack of federal funding.

在没有偏离太多轨道的情况下，我的理解是，由于缺乏联邦资金，狗研究被停止。

Is it continuing?

还在继续吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

It is going to go on.

它将会继续下去。

So initially, there was insufficient funding to do the study in an adequate way.

因此，最初没有足够的资金来以适当的方式进行这项研究。

And then it turned out there was a shortfall of about two and a half million dollars to do the study that Matt really wanted to do.

结果发现，马特真正想做的研究还缺少大约二百五十万美元。

And then actually, a group of us raised that money for Matt and did that.

然后实际上，我们一群人为马特筹集了这笔钱并做到了这一点。

Andrew Huberman:

安德鲁·休伯曼：

Great.

太棒了。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Me and a few of my patients and a couple of other folks came together and put the money in to close the gap.

我和我的一些病人以及其他一些人聚集在一起，投入资金来缩小差距。

But yes, what did get pulled back by the NIH, inexplicably and in my view, totally incorrectly, was the ongoing surveillance program, the funding for the ongoing surveillance program that would allow this type of work to continue and to allow greater follow-up on this.

但是，是的，国家卫生研究院确实莫名其妙地、在我看来完全错误地撤回了正在进行的监测计划，为正在进行的监测计划提供资金，该计划将使此类工作能够继续进行，并允许对此进行更多的后续行动。

So yes, unfortunately, until we can get more funding, we're not going to be able to maybe do as much as we'd like to do and understand this, which again, when you look at some of the things that are funded, it's hard to believe that there's not a more interesting question right now in biology than this drug that seems so promising.

所以，是的，不幸的是，在我们获得更多资金之前，我们可能无法做我们想做的事情并理解这一点，同样，当你看到一些资助的事情时，很难相信目前生物学中没有比这种看起来如此有前途的药物更有趣的问题了。

Why we wouldn't want to know if this is something we should all be taking is kind of a mystery to me.

为什么我们不想知道这是否是我们都应该服用的东西，这对我来说有点神秘。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Well, I was on NIH study sections for many years reviewing grants.

嗯，我在美国国立卫生研究院的研究部门工作了很多年，审查拨款。

I rotated off as a regular member a little over a year ago, and I can tell you that the whole process is designed to be as targeted to the best and most exciting work possible, but there's a number of features now that make it such that it's largely the work that's already mostly completed that gets funded.

一年多前，我作为正式会员轮换了，我可以告诉你，整个过程的设计目标是尽可能最好、最令人兴奋的工作，但现在有很多功能，使得它主要是已经大部分完成的工作获得资助。

You're going to go, "How does that work?" But anyway, we could have a whole other journal club discussion about funding, but I had to ask.

你会问，“那是如何运作的？”但无论如何，我们可以就资金问题进行另一个期刊俱乐部的讨论，但我不得不问。

I was curious.

我很好奇。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

So hopefully that study will get completed, and thanks for raising those funds.

希望这项研究能够完成，并感谢您筹集这些资金。

Let's talk about NAD.

我们来谈谈NAD。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yes.

是的。

Andrew Huberman:

安德鲁·休伯曼：

It's in essentially every cell of the body except red blood cells, correct?

除了红细胞之外，它基本上存在于身体的每个细胞中，对吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

I don't even know if it's in red blood cells.

我什至不知道它是否存在于红细胞中。

My intuition is.

我的直觉是。

I've never looked, to be honest with you, but given that red blood cells have a different metabolic pathway, where they're purely glycolytic, they wouldn't have the need for it in the way that others would.

老实说，我从来没有看过，但考虑到红细胞有不同的代谢途径，它们纯粹是糖酵解，它们不会像其他细胞那样需要它。

But they might.

但他们可能会。

Because they still undergo redox potential.

因为它们仍然具有氧化还原电位。

So it's possible NAD is in every single cell.

所以 NAD 可能存在于每个细胞中。

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

And it's generally thought to be associated with energy production and mitochondrial pathways in every single cell.

人们普遍认为它与每个细胞的能量产生和线粒体途径有关。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Right.

对。

So NAD is, again, one of the most ubiquitous molecules in the body, and most of what it does, and I mean most meaning like somewhere between five and six hundred pathways of it, utilize NAD as a cofactor, meaning that it's not consumed in a chemical reaction, but rather it serves as an electron shuttle.

因此，NAD 又是体内最普遍的分子之一，它的大部分作用，我的意思是，它的五到六百条通路都利用 NAD 作为辅助因子，这意味着它不会在化学反应中被消耗，而是充当电子穿梭机。

So NAD and NADH basically play catch with electrons, and that's 99% of what NAD is doing in the body.

因此，NAD 和 NADH 基本上与电子发挥作用，这就是 NAD 在体内所做的 99% 的作用。

And for that reason, NAD is so tightly regulated in the body.

正因为如此，NAD 在体内受到严格的监管。

The levels of NAD in the cell are really tightly regulated, and that shouldn't be surprising.

细胞中 NAD 的水平确实受到严格调节，这不足为奇。

Just as glucose, really tightly regulated.

就像葡萄糖一样，确实受到严格监管。

pH or hydrogen ion concentration, really tightly regulated.

pH 值或氢离子浓度，确实受到严格控制。

We, as a species, cannot survive outside of a very narrow band of pH.

作为一个物种，我们无法在非常狭窄的 pH 范围之外生存。

Right?

正确的？

If it's below seven or above 7.8 on a 0 to 14 scale, we die, full stop.

如果它在 0 到 14 的范围内低于 7 或高于 7.8，我们就死了，句号。

So similarly, NAD is managed across all ages and across all physiologic conditions in a super tight band.

同样，NAD 在所有年龄段和所有生理条件下都在一个超紧密的范围内进行管理。

There's another place where NAD shows up, and that shows up as a substrate.

NAD 还出现在另一个地方，它作为底物出现。

Right?

正确的？

So cofactor means used, coenzyme, used but not consumed, recycled.

所以辅因子的意思是使用过的，辅酶，使用过但没有消耗掉，回收的。

That's 99% of it.

这就是 99%。

A small fraction of it is used, and it's used by these things called sirtuins that consume NAD as an actual substrate in the process of DNA repair.

其中一小部分被使用，被称为 Sirtuins 的东西所使用，这些东西在 DNA 修复过程中消耗 NAD 作为实际底物。

And maybe we can go into this, but this is really where the story picks up.

也许我们可以深入探讨这一点，但这确实是故事的重点。

Andrew Huberman:

安德鲁·休伯曼：

It's also, as I recall, where the story began.

我记得，这也是故事开始的地方。

Dr. Peter Attia:

彼得·阿蒂亚博士：

That's exactly right.

完全正确。

Andrew Huberman:

安德鲁·休伯曼：

It was some experiments where the sirtuins were mutated in one direction or the other, meaning gain of function or loss of function.

在一些实验中，去乙酰化酶在一个方向或另一个方向发生突变，这意味着功能的获得或功能的丧失。

These days, people hear gain of function and they immediately think to pandemic-related themes.

如今，人们一听到功能增强，就会立即想到与流行病相关的主题。

But gain of function is a way of changing genes, typically, to augment a function, increase its robustness, or in some cases, to rescue a phenotype where you have a knockout mouse that lacks a gene, so that's loss of function, or a strain of yeast that lacks a gene, and then you do the gain of function rescue experiment.

但功能获得是改变基因的一种方式，通常是为了增强功能，增加其稳健性，或者在某些情况下，为了拯救表型，如果你有一只缺乏基因的敲除小鼠，那么这就是功能丧失，或者是缺乏基因的酵母菌株，然后你进行功能获得拯救实验。

You reintroduce the gene of interest.

您重新引入感兴趣的基因。

It's an important-- I wouldn't even call it a control.

这是一个重要的——我什至不会称其为控件。

It's an important experiment in any case, because loss of function will tell you a lot.

无论如何，这都是一个重要的实验，因为功能丧失会告诉你很多信息。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep.

是的。

Andrew Huberman:

安德鲁·休伯曼：

But gain of function and loss of function, assuming that the results jibe, tells you much, much more.

但是，假设结果一致，功能的获得和功能的丧失会告诉你更多很多。

This is one of the major areas, I think this is very important to highlight, where human genetics really struggles, because you can get humans with a mutation in a particular pathway, like, I don't know, the sonic hedgehog pathway.

这是主要领域之一，我认为这一点非常重要，因为人类遗传学确实在其中挣扎，因为你可以让人类在特定途径中发生突变，比如，我不知道，音速刺猬途径。

Somebody is hypomorphic for sonic hedgehog, and they might actually lack a major tooth up the middle because the role of sonic hedgehog at the midline, and you could say, "Okay, well, loss of function here.

有些人对于音速刺猬来说是低等位的，他们可能实际上在中间缺少一颗大牙，因为音速刺猬在中线的作用，你可以说，“好吧，好吧，这里功能丧失了。

Here's the role of sonic hedgehog." But the ideal experiment is to put the gene back in and then rescue that phenotype, because as any logical mind can tell, there could be many things downstream of sonic hedgehog that could create the phenotype that you observe.

这就是音速刺猬的角色。”但理想的实验是将基因放回原处，然后拯救该表型，因为任何逻辑思维都可以看出，音速刺猬的下游可能有很多东西可以创造出你观察到的表型。

But if you put sonic hedgehog back in, yes, that's still true, but you get more reassurance that that's the gene of interest.

但如果你把音速刺猬放回去，是的，这仍然是事实，但你会更加确信那是感兴趣的基因。

So with respect to sirtuins, as I recall, they deleted the sirtuins in the yeast.

因此，就去乙酰化酶而言，我记得他们删除了酵母中的去乙酰化酶。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

So let's use another example of what the gold standard is here, or what a great example is.

因此，让我们用另一个例子来说明什么是黄金标准，或者什么是一个很好的例子。

So, I recently did a podcast with Dena Dubal from UCSF on Klotho.

所以，我最近和加州大学旧金山分校的 Dena Dubal 在 Klotho 上做了一个播客。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Which is an amazing scientific story.

这是一个令人惊奇的科学故事。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And it's a great story because it shows how accidents can lead to great discoveries, right?

这是一个很棒的故事，因为它展示了意外如何带来伟大的发现，对吗？

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So there was a researcher in Japan who was really interested in understanding hypertension, high blood pressure, and they had created a mouse model where they were trying to knock out certain sodium channels to see if they could perturb blood pressure.

日本有一位研究人员对了解高血压非常感兴趣，他们创建了一个小鼠模型，试图敲除某些钠通道，看看它们是否会扰乱血压。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And then there was this one strain of mouse with this one knockout that died really, really quickly, and it developed devastating neurodegenerative disease and died very quickly.

然后，有一种基因敲除小鼠，它死得非常非常快，而且它发展出了毁灭性的神经退行性疾病，而且死得非常快。

And like a good scientist, he didn't say, "Well, that sucks.

就像一个优秀的科学家一样，他没有说：“好吧，这很糟糕。

I'm going to discard that one because it didn't give me what I wanted," which was the blood pressure change.

我要放弃那个，因为它没有给我我想要的东西，”这就是血压变化。

And he went and figured out what was going on, and he figured out that there was a certain gene that he had hit that wasn't a sodium transporter and instead was this other gene.

他去弄清楚发生了什么事，他发现他击中的某个基因不是钠转运蛋白，而是另一个基因。

He named it Klotho.

他把它命名为克洛托。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So you had this one piece of evidence right now, which was if you knock out that gene, you kill an animal very quickly.

所以你现在有一个证据，那就是如果你敲除那个基因，你会很快杀死一只动物。

Now, that doesn't mean it's a longevity gene.

但这并不意味着它是长寿基因。

You have to do the other experiment, to your point.

你必须做另一个实验才能达到你的观点。

You have to overexpress that gene and ask the question, do you live longer?

你必须过度表达该基因并提出问题，你活得更长吗？

And sure enough, when they overexpressed that same gene that they had just knocked out and killed the mouse, the thing was living 15% to 20% longer.

果然，当他们过度表达刚刚敲除并杀死老鼠的同一个基因时，老鼠的寿命延长了 15% 到 20%。

Andrew Huberman:

安德鲁·休伯曼：

So it's both necessary and sufficient-

所以这既是必要的也是充分的——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah

是啊

Andrew Huberman:

安德鲁·休伯曼：

...

for extended life.

为了延长寿命。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So that's how you can say, "Well, that's a longevity gene."

所以你可以这样说：“嗯，这是一个长寿基因。”

Andrew Huberman:

安德鲁·休伯曼：

As many of you know, I've been taking AG1 for more than 10 years now, so I'm delighted that they're sponsoring this podcast.

你们很多人都知道，我服用 AG1 已有 10 多年了，所以我很高兴他们赞助这个播客。

To be clear, I don't take AG1 because they're a sponsor.

需要明确的是，我选择 AG1 并不是因为他们是赞助商。

Rather, they are a sponsor because I take AG1.

相反，他们是赞助商，因为我选择了 AG1。

In fact, I take AG1 once and often twice every single day, and I've done that since starting way back in 2012.

事实上，我每天服用一次 AG1，经常服用两次，早在 2012 年我就开始这样做了。

There is so much conflicting information out there nowadays about what proper nutrition is, but here's what there seems to be a general consensus on.

关于什么是适当的营养，现在有很多相互矛盾的信息，但以下是似乎达成的普遍共识。

Whether you're an omnivore, a carnivore, a vegetarian, or a vegan, I think it's generally agreed that you should get most of your food from unprocessed or minimally processed sources, which allows you to eat enough but not overeat Get plenty of vitamins and minerals, probiotics, and micronutrients that we all need for physical and mental health.

无论你是杂食动物、肉食动物、素食主义者还是纯素食主义者，我认为人们普遍认为你应该从未经加工或最低限度加工的来源获取大部分食物，这可以让你吃得足够，但不会吃得过饱，获得充足的维生素和矿物质、益生菌和微量营养素，这些都是我们身心健康所需要的。

Now, I personally am an omnivore, and I strive to get most of my food from unprocessed or minimally processed sources.

现在，我个人是杂食动物，我努力从未加工或最低限度加工的来源获取大部分食物。

But the reason I still take AG1 once and often twice every day is that it ensures I get all of those vitamins, minerals, probiotics, et cetera, but it also has adaptogens to help me cope with stress.

但我仍然每天服用一次 AG1（通常是两次）的原因是它可以确保我获得所有维生素、矿物质、益生菌等，而且它还含有适应原来帮助我应对压力。

It's basically a nutritional insurance policy meant to augment, not replace, quality food.

它基本上是一项营养保险政策，旨在增强而不是取代优质食品。

So by drinking a serving of AG1 in the morning and again in the afternoon or evening, I cover all of my foundational nutritional needs.

因此，通过早上喝一份 AG1，然后在下午或晚上再喝一次，我就可以满足我所有的基本营养需求。

And I, like so many other people that take AG1, report feeling much better in a number of important ways, such as energy levels, digestion, sleep, and more.

和许多其他服用 AG1 的人一样，我报告在许多重要方面感觉好多了，例如能量水平、消化、睡眠等。

So while many supplements out there are really directed towards obtaining one specific outcome, AG1 is foundational nutrition designed to support all aspects of well-being related to mental health and physical health.

因此，虽然许多补充剂实际上是为了获得一种特定的结果，但 AG1 是基础营养，旨在支持与心理健康和身体健康相关的各个方面的福祉。

If you'd like to try AG1, you can go to drinkag1.com/huberman to claim a special offer.

如果您想尝试 AG1，可以访问 Drinkag1.com/huberman 申请特别优惠。

They'll give you five free travel packs with your order, plus a year's supply of vitamin D3K2.

您订购后，他们将赠送 5 个免费旅行套装，以及一年的维生素 D3K2。

Again, that's drinkag1.com/huberman.

再说一遍，这是 Drinkag1.com/huberman。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So let's go to the sirtuin story.

那么让我们来看看 Sirtuin 的故事。

So it goes back to the late '90s.

事情可以追溯到 90 年代末。

Matt Kaeberlein again.

马特·凯伯莱因又来了。

This is amazing, right?

这太棒了，对吧？

So you have this guy who's the leading authority, or one of the leading authorities on the work going on today with rapamycin, along with one of his colleagues, David Sabatini, and a few others.

因此，这个人是当今雷帕霉素研究的主要权威或主要权威之一，以及他的一位同事大卫·萨巴蒂尼（David Sabatini）和其他一些人。

But when Matt was a postdoc, he did an experiment in a strain of mice-- pardon me, a strain of yeast.

但当马特还是一名博士后时，他在一种小鼠身上做了一个实验——请原谅我，是一种酵母菌。

I think it was the W303 strain of yeast.

我认为是 W303 酵母菌株。

And he overexpressed SIR2.

而且他过度表达了SIR2。

And lo and behold, the yeast lived longer.

你瞧，酵母的寿命更长了。

Now, a year later, someone else in the same lab took a different strain of yeast and calorically restricted them, and they also lived longer.

现在，一年后，同一实验室的其他人采用了不同的酵母菌株并限制了它们的热量，它们的寿命也更长了。

I forget what that strain was.

我忘记那是什么压力了。

It was something 316.

这是 316 的事情。

But it was a different strain of yeast.

但它是一种不同的酵母菌株。

At that moment, again, this is about 25 years ago, a hypothesis emerged, which was we have two different strains of yeast, and in one of them, when you overexpress SIR2, this gene, they live longer, and in this other strain, if you calorically restrict them, they live longer.

在那一刻，大约 25 年前，出现了一个假设，那就是我们有两种不同的酵母菌株，在其中一种菌株中，当你过度表达 SIR2（这个基因）时，它们会活得更长，而在另一种菌株中，如果你限制它们的热量，它们会活得更长。

The understandable hypothesis was caloric restriction, which we had known was life-extending, is working through sirtuins.

可以理解的假设是热量限制，我们知道热量限制可以延长寿命，这是通过 Sirtuins 发挥作用的。

That hypothesis sort of fell apart about four years later when Matt Kaeberlein, again, this time with Brian Kennedy, did another experiment in yet a third strain of yeast that allowed them to test hypothesis.

大约四年后，当马特·凯伯莱因（Matt Kaeberlein）再次与布莱恩·肯尼迪（Brian Kennedy）一起在第三种酵母菌株中进行了另一项实验，使他们能够检验假设时，这个假设有点分崩离析。

Because there was a problem with the story I just told.

因为我刚才讲的故事有问题。

When you took the 303 strain, this is the strain that when overexpressing SIR2 lived longer, if you took that strain and you calorically restricted them, no change.

当您服用 303 菌株时，这种菌株在过度表达 SIR2 时寿命更长，如果您服用该菌株并限制它们的热量，则不会发生任何变化。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

That's odd.

这很奇怪。

Even more odd is when you took the 316 strain, and this is the strain that lived longer with CR, if you overexpress SIR2, no change.

更奇怪的是，当你服用 316 菌株时，这种菌株在 CR 下寿命更长，如果你过度表达 SIR2，则没有变化。

So right off the bat, the story didn't make sense.

所以，这个故事立刻就没有意义了。

But it was further solidified that that story didn't make sense when Brian and Matt published in 2004 in yet a different strain, God, I'm blanking on the name, it's like BY4742.

但当 Brian 和 Matt 于 2004 年以另一种风格出版时，这个故事就变得毫无意义了，天哪，我对这个名字一片空白，就像 BY4742 一样。

These don't matter.

这些都不重要。

If you calorically restricted them, they lived longer.

如果你限制它们的热量，它们就会活得更久。

If you overexpress SIR2, they lived longer.

如果过度表达 SIR2，它们的寿命就会更长。

If you did both, they lived even longer.

如果你两者都做到了，他们的寿命会更长。

It was additive.

它是附加的。

Again, further suggesting that overexpression of SIR2 and caloric restriction independently and separately extended lifespan.

再次进一步表明，SIR2 的过度表达和热量限制独立且分别延长了寿命。

Andrew Huberman:

安德鲁·休伯曼：

These are parallel pathways.

这些是平行的路径。

Dr. Peter Attia:

彼得·阿蒂亚博士：

They're parallel pathways.

它们是平行的路径。

For reasons that honestly escape me, Andrew, there are still people who maintain that the benefit of sirtuin overexpression is through the caloric restriction pathway, and vice versa.

老实说，出于我无法理解的原因，安德鲁，仍然有人坚持认为沉默调节蛋白过度表达的好处是通过热量限制途径实现的，反之亦然。

Andrew Huberman:

安德鲁·休伯曼：

And that's wrong.

那是错误的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

My reading of the literature, in addition to every person I have talked to on this who works in the space, including Matt Kaeberlein, who has done the most research on this, is that there is no evidence that caloric restriction and sirtuins operate through the same pathway.

我对文献的阅读，以及与我交谈过的每个在该领域工作的人，包括对此进行最多研究的 Matt Kaeberlein，都表明没有证据表明热量限制和去乙酰化酶通过相同的途径发挥作用。

And in that sense, I think there's relatively uniform agreement that caloric restriction extends life across the model systems we discussed, right?

从这个意义上说，我认为我们讨论的所有模型系统都一致认为热量限制可以延长寿命，对吗？

Andrew Huberman:

安德鲁·休伯曼：

What about in humans?

那么在人类呢？

Dr. Peter Attia:

彼得·阿蒂亚博士：

What about it specifically?

具体来说呢？

Andrew Huberman:

安德鲁·休伯曼：

Does it extend life?

它能延长寿命吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Caloric restriction or sirtuin?

热量限制或去乙酰化酶？

Well, that experiment's never been done and never will be done.

嗯，那个实验从来没有做过，也永远不会做。

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

The joke I was trying to set up for is the one I'll make now, which is no one wants to be in the control experiment.

我本来想开的玩笑就是我现在要开的玩笑，没有人愿意参加对照实验。

That said, nobody wants-

也就是说，没有人愿意——

Dr. Peter Attia:

彼得·阿蒂亚博士：

I would argue no one wants to be in the treatment experiment either.

我认为也没有人愿意参与治疗实验。

Andrew Huberman:

安德鲁·休伯曼：

Oh, you got me.

哦，你抓住了我。

You beat me to the punch.

你先于我。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yes.

是的。

Andrew Huberman:

安德鲁·休伯曼：

No one wants to be in the treatment group either because it requires eating so little.

也没有人愿意加入治疗组，因为它只需要吃得很少。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

The mere appearance of people-

光是人的外表——

Dr. Peter Attia:

彼得·阿蒂亚博士：

The joke is you probably will live longer, and it will feel even worse.

笑话是你可能会活得更久，但感觉会更糟。

Caloric restriction, which by the way, there are real debates about whether it will extend life in humans because it will clearly-- I shouldn't say clearly.

顺便说一句，热量限制是否会延长人类的寿命存在真正的争论，因为它显然会——我不应该说清楚。

I think it would be a very safe bet that severe caloric restriction will absolutely reduce the risk of most chronic diseases.

我认为严格的热量限制绝对会降低大多数慢性病的风险，这是一个非常安全的赌注。

Meaning, I think there's very good reason to believe that if an individual constitutively consumed 25% fewer calories than they were meant to eat, their risk of cardiovascular disease, cancer, Alzheimer's disease would go down.

意思是，我认为有充分的理由相信，如果一个人摄入的热量比应摄入量少 25%，那么他们患心血管疾病、癌症、阿尔茨海默病的风险就会降低。

The problem is what things go up.

问题是事情会怎样发展。

What does that do to your immune system?

这对你的免疫系统有什么作用？

What does that do with respect to sarcopenia?

这对肌肉减少症有什么作用？

What does that do to your risk of falling?

这对您跌倒的风险有何影响？

Like this-

像这样——

Andrew Huberman:

安德鲁·休伯曼：

Yeah, frailty.

是的，脆弱。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, exactly.

是的，完全正确。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So you trade one set of diseases for another.

所以你用一种疾病换取另一种疾病。

It's not at all clear that lifespan goes up.

寿命是否会延长还不清楚。

And by the way, when you even look at some of the animal literature where they're using different strains of mice that are not inbred, and they don't put them in hermetically sealed situations, they don't live longer.

顺便说一句，当你看一些动物文献时，他们使用的是非近亲繁殖的不同品系的小鼠，并且没有将它们置于密封的环境中，它们的寿命并不会更长。

So it's not always the case that caloric restriction extends life.

因此，热量限制并不总是能延长寿命。

And therefore, while it's safe to say caloric restriction probably reduces the onset of chronic disease, that might not translate to an all-cause mortality benefit based on those downsides.

因此，虽然可以肯定地说热量限制可能会减少慢性病的发病，但这可能不会转化为基于这些缺点的全因死亡率益处。

But all of that said, I think the whole sirtuin story got off to an incorrect start, where it basically lopped on to the CR story, which was, "Hey, we've got this thing, CR, that we've known since-"

但综上所述，我认为整个 Sirtuin 故事的开头是错误的，它基本上跳到了 CR 故事，即“嘿，我们有了这个东西，CR，我们从那时起就知道了——”

Andrew Huberman:

安德鲁·休伯曼：

Caloric restriction.

热量限制。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Right.

对。

Caloric restriction.

热量限制。

We've got this thing, which for 50 years, we've known has a signal that really says it's life-extending, and we've got this yeast where it works and this other yeast where sirtuin activation works.

我们已经找到了这个东西，50 年来我们就知道它有一个信号，确实表明它可以延长寿命，我们已经找到了它起作用的酵母和另一种可以激活沉默调节蛋白的酵母。

Oh, it's got to be-- But again, if you go through the story in detail, as I just did, there's no evidence whatsoever that sirtuins have anything to do with caloric restriction and vice versa.

哦，一定是——但是，如果你像我刚才那样详细地了解这个故事，没有任何证据表明去乙酰化酶与热量限制有任何关系，反之亦然。

Andrew Huberman:

安德鲁·休伯曼：

It's incredibly interesting because I think when you look at cell biology and you see these parallel pathways, when you see these effects of experiments where changing sirtuins or changing caloric restriction independently increase lifespan, combine the two, you get what appears to be a synergistic effect, but it's, as you pointed out, an additive effect.

这非常有趣，因为我认为当你研究细胞生物学时，你会看到这些平行的途径，当你看到改变去乙酰化酶或改变热量限制独立延长寿命的实验效果时，将两者结合起来，你会得到看似协同效应，但正如你所指出的，它是一种累加效应。

It seems like a pretty straightforward experiment to do.

这似乎是一个非常简单的实验。

You could just do an occlusion, right?

你可以做一个遮挡，对吧？

You could-

你可以-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Of course

当然

Andrew Huberman:

安德鲁·休伯曼：

...

then put back in the sirtuin or adjust calories and see whether or not you get effectively whether the math is corrected.

然后放回sirtuin或调整卡路里，看看数学是否正确，是否有效。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

So-

所以——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Now, none of this gets to the question you raised yet.

现在，这些都还没有解决您提出的问题。

That's all prologue, right?

这就是序幕，对吗？

That's like where did this story come up?

好像这个故事是从哪里来的？

But then the question becomes, well, if you believe that sirtuins are truly a factor that drives longevity, how can you activate them, right?

但问题就变成了，如果你相信去乙酰化酶确实是延长寿命的一个因素，你该如何激活它们，对吗？

How do you activate a sirtuin?

如何激活 Sirtuin？

So we have to now simultaneously start to hold things true in parallel that may or may not be true.

因此，我们现在必须同时开始同时承认可能是真的也可能不是真的事情。

So we want to then ask the question, do we believe that what we saw in yeast, which I think is the only reproducible finding I can draw, meaning this is a reproducible finding.

所以我们想问一个问题，我们是否相信我们在酵母中看到的东西，我认为这是我可以得出的唯一可重复的发现，这意味着这是一个可重复的发现。

In many but not all strains of yeast, if you overexpress sirtuins, the yeast will live longer.

在许多（但不是所有）酵母菌株中，如果过度表达去乙酰化酶，酵母的寿命会更长。

So let's park that in the parking lot as a very likely statement.

因此，让我们把它停在停车场作为一个很可能的声明。

You would then say, well, if it does it in yeast, does it do it in flies?

然后你会说，好吧，如果它在酵母中起作用，那么它在苍蝇中也起作用吗？

Does it do it in worms?

它在蠕虫中起作用吗？

Does it do it in mammals?

它在哺乳动物身上也有这种作用吗？

You want to be able to check those three boxes because, again, that's a billion years of evolution.

您希望能够选中这三个框，因为这又是十亿年的进化过程。

So if something works across a billion years, we'd be much more confident it works in us.

因此，如果某种东西在十亿年里都有效，我们就会更有信心它对我们有效。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Making a fly mutant, Drosophila mutant that overexpresses sirtuins, a worm, C.

制造一种果蝇突变体，过度表达sirtuins，一种蠕虫，C.

elegans mutant that overexpresses sirtuins, that's a pretty quick experiment to do-

过度表达去乙酰化酶的线虫突变体，这是一个非常快速的实验-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah

是啊

Andrew Huberman:

安德鲁·休伯曼：

...

because of the short generation time of those species.

因为这些物种的世代时间很短。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Right.

对。

Andrew Huberman:

安德鲁·休伯曼：

Now, a mouse, it's a longer experiment, but I'm guessing all of those experiments have been done.

现在，用老鼠，这是一个更长的实验，但我猜所有这些实验都已经完成了。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, and the only one that I can find that has demonstrated a survival advantage is one particular transgenic mouse experiment that overexpressed SIRT6, and it did indeed, for the male mice, increase lifespan by 10 to 15%.

是的，我能找到的唯一一个显示出生存优势的实验是一项过度表达 SIRT6 的转基因小鼠实验，它确实使雄性小鼠的寿命延长了 10% 到 15%。

So this is one transgenic mouse model that overexpressed SIRT6, and those mice, the male mice, lived 10 to 15% longer.

这是一种过度表达 SIRT6 的转基因小鼠模型，这些小鼠（雄性小鼠）的寿命延长了 10% 至 15%。

The female mice did not.

雌性小鼠则没有。

Andrew Huberman:

安德鲁·休伯曼：

We should probably clarify what a transgenic mouse is.

我们或许应该澄清什么是转基因小鼠。

I talked about knockout mice.

我谈到了基因敲除小鼠。

That's when a gene, or genes in some cases, is deleted from the genome.

此时，一个基因（或某些情况下的基因）会从基因组中删除。

So it's null.

所以它是空的。

It does not express that gene.

它不表达该基因。

The gain of function would be to put back that gene in.

功能的获得将是将该基因放回原位。

That would be a knock-in mouse.

那将是一只敲入鼠标。

So in that case, you still get some normal expression of the gene from the endogenous genome, but now you have a transgene that's inserted there.

因此，在这种情况下，您仍然可以从内源基因组中获得该基因的一些正常表达，但现在您已经插入了一个转基因。

And there are all sorts of important intricacies that relate to this.

还有与此相关的各种重要的复杂问题。

For instance, where the transgene is inserted.

例如，转基因插入的位置。

If it's downstream of an enhancer that's muscle specific, then you can get a mouse that overexpresses sirtuins just in muscle.

如果它位于肌肉特异性增强子的下游，那么您可以获得只在肌肉中过度表达去乙酰化酶的小鼠。

You can get it ubiquitously expressed.

你可以得到它无处不在的表达。

There are a number of different ways that this can happen.

有多种不同的方式可以实现这一点。

I'm assuming this was ubiquitous expression of, you said SIRT6?

我假设这是无处不在的表达，你说的是 SIRT6？

Dr. Peter Attia:

彼得·阿蒂亚博士：

SIRT6, yeah.

SIRT6，是的。

Andrew Huberman:

安德鲁·休伯曼：

So every cell in the body that normally would express SIRT6 would express more SIRT6.

因此，体内通常表达 SIRT6 的每个细胞都会表达更多的 SIRT6。

Dr. Peter Attia:

彼得·阿蒂亚博士：

I don't remember, Andrew, to be honest with you.

老实说，我不记得了，安德鲁。

I'd have to go back and look at the paper.

我得回去看看报纸。

Andrew Huberman:

安德鲁·休伯曼：

Okay.

好的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

I don't know if it was muscle specific or whole body specific.

不知道是肌肉特有的还是全身特有的。

Andrew Huberman:

安德鲁·休伯曼：

I'm guessing unless they made it clear that it was tissue specific, that it's whole body.

我猜除非他们明确表示这是组织特异性的，而是整个身体的。

So we're talking about when Peter says transgenic mouse, he's talking about a mouse that has this transgene that causes it to express more SIRT6 than it ordinarily would.

因此，当 Peter 说转基因小鼠时，我们谈论的是具有这种转基因的小鼠，该转基因使其比平常表达更多的 SIRT6。

And let's assume, although we don't know this for sure, that the other genes in this mouse are functioning as they would normally.

尽管我们不确定，但我们假设这只小鼠的其他基因正常发挥作用。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Right.

对。

So again, just to summarize that, that's 2012.

再次总结一下，那是 2012 年。

We have this one transgenic mouse.

我们有一只转基因小鼠。

You overexpress SIRT6, and all of a sudden, the males were living 10% longer.

如果过度表达 SIRT6，雄性的寿命会突然延长 10%。

Again, to be clear, the females didn't experience a difference.

再次强调，雌性没有感受到差异。

And that's not uncommon or unheard of in longevity research.

这在长寿研究中并不罕见或闻所未闻。

There generally are sex-specific differences, and you always have to read the fine print.

通常存在性别差异，您必须阅读细则。

The first thing I always look at in a study when I see a difference in sexes or frankly, any difference in longevity, but it's always great when they parse them out by sexes, is how long did the controls live?

当我在研究中看到性别差异时，或者坦率地说，寿命上的任何差异时，我总是首先关注的是对照组的寿命有多长？

But I went back and actually looked at the Kaplan-Meier curves on that exact study, and yes, indeed, I think that's a real effect.

但我回去实际上查看了该研究的卡普兰-迈耶曲线，是的，确实，我认为这是一个真正的效果。

So let's take stock of now two pieces of information that I think we could say is probably true.

现在让我们来盘点一下我认为我们可以说可能是真实的两条信息。

It is probably true that in a handful of strains of yeast, if you overexpress SIRT, you are going to live longer.

确实，在少数酵母菌株中，如果过度表达 SIRT，您的寿命就会更长。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

That tends to be completely independent of caloric restriction.

这往往完全独立于热量限制。

That's the single thing I can say with the greatest confidence.

这是我可以充满信心地说的唯一一件事。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And there is at least one transgenic strain of mice that if you get it to overexpress a different SIRT, SIRT6, but again, these are homologues throughout the species, so I don't think we need to get wrapped up in SIRT2 versus SIRT6.

至少有一种转基因小鼠品系，如果你让它过度表达不同的 SIRT，即 SIRT6，但同样，它们在整个物种中都是同源物，所以我认为我们不需要陷入 SIRT2 与 SIRT6 的争论中。

You will at least make the male mice live longer, but not the females.

你至少会让雄性老鼠活得更长，但不会让雌性老鼠活得更长。

Andrew Huberman:

安德鲁·休伯曼：

What sorts of things are downstream of sirtuins?

Sirtuins 的下游有哪些类型的东西？

And that question translated to normal English is what is changing as a consequence-

这个问题翻译成普通英语就是随之而来的变化——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Why is this happening?

为什么会发生这种情况？

Andrew Huberman:

安德鲁·休伯曼：

...

of increasing-

的增加-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah

是啊

Andrew Huberman:

安德鲁·休伯曼：

...

the sirtuin?

瑟土因？

Could it be, for instance, well, unlikely based on what we already know about caloric restriction and the fact that they are independent parallel pathways, but is it something related to glucose metabolism?

例如，根据我们对热量限制的了解以及它们是独立的平行途径这一事实，这是否不太可能，但这是否与葡萄糖代谢有关？

Is it something related to clearance of senescent cells?

是否与衰老细胞的清除有关？

I'm just throwing out possibilities here.

我只是在这里排除可能性。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Actually, you've hit two of the big three right off the top.

事实上，你已经击中了三巨头中的两个。

So we believe that when sirtuins are activated, they're improving mitochondrial biogenesis.

因此我们相信，当沉默调节蛋白被激活时，它们会改善线粒体的生物发生。

They are increasing DNA repair.

他们正在增加 DNA 修复。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So that's probably the biggest one.

这可能是最大的一个。

And by the way, that's sort of what brings us to the NAD story.

顺便说一句，这就是 NAD 故事的原因。

And also reducing SASPs, so the soluble products of senescent cells.

并且还可以减少SASP，从而减少衰老细胞的可溶性产物。

So in other words, those are all three good things.

换句话说，这都是三件好事。

So you tamp down on senescent cells, you increase mitochondrial biogenesis, and you increase DNA repair.

因此，你可以抑制衰老细胞，增加线粒体生物发生，并增加 DNA 修复。

Those would be all great things to do, and we think that sirtuins are probably doing all of them.

这些都是很棒的事情，我们认为 Sirtuins 可能正在做所有这些事情。

Andrew Huberman:

安德鲁·休伯曼：

This business of DNA repair and reducing fragmentation or mutations to DNA that are naturally occurring has been a hot idea in the field of aging for a long time.

DNA 修复和减少自然发生的 DNA 片段或突变的业务长期以来一直是衰老领域的热门想法。

Is that because when X-rays became popular or post-nuclear fallout that people showed accelerated signs of aging?

这是因为当 X 射线流行或核辐射后人们表现出加速衰老的迹象吗？

How did we get from DNA mutation to accelerated aging?

我们是如何从 DNA 突变变成加速衰老的？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Well, I think we know that as we age, it's just a stochastic process.

嗯，我想我们知道，随着年龄的增长，这只是一个随机过程。

Given the ubiquity of DNA replication and the fidelity of the system, which is high, very high, but not perfect, there's going to be mistakes.

鉴于 DNA 复制的普遍性和系统的保真度（很高、非常高，但并不完美），就会出现错误。

Actually, this is an interesting question.

其实，这是一个有趣的问题。

So in 2016, I went to Easter Island with David Sabatini and Nav Chandel and Tim Ferriss.

所以在 2016 年，我和 David Sabatini、Nav Chandel 和 Tim Ferriss 一起去了复活节岛。

So the four of us just took a trip to Easter Island to see the birthplace of rapamycin.

于是我们四个人就去复活节岛一趟，看看雷帕霉素的诞生地。

So it was kind of like vacation/science journey.

所以这有点像假期/科学之旅。

Andrew Huberman:

安德鲁·休伯曼：

That's a nerdy vacation.

这真是一个书呆子的假期。

Dr. Peter Attia:

彼得·阿蒂亚博士：

It was awesome.

太棒了。

So just picture hiking around this incredible island, just talking about science all day.

所以，想象一下在这个令人难以置信的岛屿上徒步旅行，整天谈论科学。

But this was an interesting question that I posed to Nav and to David, which was, why do we see such a clear and present association with cancer as we age, and why is it so nonlinear?

但这是我向纳夫和大卫提出的一个有趣的问题，即为什么随着年龄的增长，我们会看到与癌症如此清晰且现实的关联，以及为什么它如此非线性？

So it's not just that cancer goes up with age, it goes up like that.

因此，癌症的发病率不仅会随着年龄的增长而增加，而且会以这种方式增加。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And I said I'll offer two hypotheses which is more compelling.

我说我将提供两个更有说服力的假设。

Is it simply that as we're aging, DNA replication-- Again, taking a step back for the listener, cancer is a genetic disease, meaning by definition the canonical problem with cancer is a genetic mutation that leads to two properties of a cell, the inability of the cell to control replication, so it interrupts cell signaling, so cells replicate but then don't know when to stop, and then the introduction of the capacity to spread, this property called metastasis.

仅仅是因为随着我们年龄的增长，DNA复制吗？再次，让听众退后一步，癌症是一种遗传性疾病，这意味着根据定义，癌症的典型问题是一种基因突变，它导致细胞的两个特性，即细胞无法控制复制，因此它中断了细胞信号传导，因此细胞复制，但随后不知道何时停止，然后引入扩散能力，这种特性称为转移。

Those are the two hallmarks of cancer.

这是癌症的两个特征。

So we know that that only happens in the context of genetic mutations, but why does this happen later in life and not at the beginning of life, with very few exceptions?

所以我们知道这种情况只发生在基因突变的情况下，但为什么这种情况会发生在生命后期而不是生命之初，除了极少数例外？

And so the question is, is it because over time mutations compound?

所以问题是，是因为随着时间的推移，突变复合了吗？

Is it because there are more mutations as we age, or is there a third issue, which is all of those things are happening normally, and they're no more abundant when you're 80 than when you're 20, but your immune system can't detect them as well?

是因为随着年龄的增长，突变会增多，还是还有第三个问题，即所有这些事情都是正常发生的，当你 80 岁时，它们并不比 20 岁时更丰富，但你的免疫系统也无法检测到它们？

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And the truth of it is, we didn't come up with an answer, but it's probably all of the above.

事实是，我们没有找到答案，但可能就是以上所有。

So it's probably that as we are aging, we are undergoing more DNA damage, or at a minimum, the DNA damage we're undergoing is less amenable to repair.

因此，随着年龄的增长，我们可能会遭受更多的 DNA 损伤，或者至少，我们正在经历的 DNA 损伤不太容易修复。

And that's part of the thesis here.

这是本文的一部分。

Part of the thesis here is as we're aging, we are less and less able to repair DNA.

这里的部分论点是，随着我们年龄的增长，我们修复 DNA 的能力越来越差。

And one of the arguments that put forth, although we're not quite ready for this part of the story yet, but I'll just say it now and we'll come back to it, is we don't have enough of the substrate that the sirtuin needs to repair DNA, and that substrate is NAD.

尽管我们还没有为这部分故事做好准备，但我提出的论点之一是，我们没有足够的 Sirtuin 修复 DNA 所需的底物，而该底物就是 NAD。

So again, remember at the outset, I said, look, there's two big categories to think about NAD.

再说一遍，记住一开始我说过，看，NAD 有两大类需要考虑。

Most of what NAD is doing is operating as a cofactor for electron shuttling.

NAD 所做的大部分工作是作为电子穿梭的辅助因子。

That's the NAD, NADH, electron transport, electron accept, ba ba ba ba ba.

这就是 NAD、NADH、电子传递、电子接受、ba ba ba ba ba。

Okay.

好的。

Not consuming NAD, just using it to pass electrons back and forth.

不消耗NAD，只是用它来来回传递电子。

But then over here, we have this other category where we use NAD as a substrate.

但在这里，我们还有另一个类别，我们使用 NAD 作为底物。

It gets broken down, and that's what the sirtuins are doing to repair DNA.

它被分解，这就是去乙酰化酶修复 DNA 的作用。

Okay, so if that's true, and if NAD levels are declining with age, it's a logical conclusion that should we give more NAD, right?

好吧，如果这是真的，并且 NAD 水平随着年龄的增长而下降，那么我们应该给予更多的 NAD 就是一个合乎逻辑的结论，对吗？

If you're running out of substrate to repair DNA and DNA repair is an important way to thwart aging, it all makes sense.

如果您的 DNA 修复底物已经耗尽，而 DNA 修复是阻止衰老的重要方法，那么这一切都是有道理的。

So we'll keep that over there.

所以我们会把它留在那里。

But before we do, I want to come back to one other story, which is the story of sirtuin activators.

但在我们开始之前，我想回到另一个故事，那就是 Sirtuin 激活剂的故事。

So what's the most famous sirtuin activator of all time?

那么有史以来最著名的 Sirtuin 激活剂是什么？

What is the heavyweight champion of sirtuin activators that has taken up 99% of the bandwidth in this space?

占据该领域 99% 带宽的 Sirtuin 激活器的重量级冠军是什么？

It's a lovely little chemical called resveratrol.

这是一种可爱的小化学物质，叫做白藜芦醇。

Okay, so resveratrol, which gained a lot of fame and notoriety because it happens to be found in trace elements in the skin of grapes and therefore shows up in wine, gained a lot of notoriety about 20 years ago when one lab doing one experiment somehow was able to convince some people, including a very large pharma company, that resveratrol increased lifespan So the thesis was resveratrol activates sirtuins.

好吧，白藜芦醇名声大噪，因为它恰好存在于葡萄皮中的微量元素中，因此也出现在葡萄酒中。大约 20 年前，一个实验室做了一项实验，以某种方式说服了一些人，包括一家非常大的制药公司，白藜芦醇可以延长寿命。所以论文是白藜芦醇激活去乙酰化酶。

Sirtuin activation is important because of all the things we just said.

由于我们刚才所说的所有事情，Sirtuin 激活非常重要。

It improves mitochondrial biogenesis, it suppresses senescent cells, and it enhances DNA repair.

它改善线粒体生物合成，抑制衰老细胞，并增强 DNA 修复。

So if you have something that is such a potent activator of sirtuins and you give it to a mouse, that mouse should live longer.

因此，如果你有一种有效的去乙酰化酶激活剂，然后将其喂给小鼠，那只小鼠应该会活得更久。

Now, lots of experiments were done that couldn't find that.

现在，我们做了很多实验，但都没有找到这一点。

But one experiment was done, but it was an interesting experiment.

但是做了一个实验，却是一个有趣的实验。

I've discussed this at least on two podcasts, including one with Rich Miller, who runs the ITP, the Interventions Testing Program, which later tested resveratrol and found that it did categorically nothing.

我至少在两个播客中讨论过这个问题，其中一个是与里奇·米勒（Rich Miller）一起讨论的，他负责管理 ITP（干预测试计划），该计划后来测试了白藜芦醇，发现它毫无作用。

In this one experiment that worked, the investigators took a bizarre mouse model where they force-fed it an enormously high-fat diet.

在这项有效的实验中，研究人员采用了一种奇怪的小鼠模型，并强制给它喂食极高脂肪的饮食。

And in doing so, they created such an abundance of fatty liver that the livers of these mice encroached the chest, the thoracic cavity of the mice.

在这样做的过程中，他们产生了大量的脂肪肝，以至于这些小鼠的肝脏侵入了小鼠的胸腔。

So the mouse died prematurely because they couldn't breathe.

所以老鼠因无法呼吸而过早死亡。

And in that particular mouse model, resveratrol rescued the mice.

在那个特定的小鼠模型中，白藜芦醇拯救了小鼠。

So again, let's just assume that all of that is correct, and it's possible that there were even errors there, but let's just assume that's correct.

再说一遍，我们假设所有这些都是正确的，甚至可能存在错误，但我们只是假设这是正确的。

Let's assume-

让我们假设-

Andrew Huberman:

安德鲁·休伯曼：

So this is resveratrol delivered orally?

那么这是口服白藜芦醇吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yes.

是的。

Andrew Huberman:

安德鲁·休伯曼：

In the food?

在食物里？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yes.

是的。

Andrew Huberman:

安德鲁·休伯曼：

Very high doses.

剂量非常高。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mega doses.

大剂量。

Andrew Huberman:

安德鲁·休伯曼：

The equivalent of barrels of grape skin.

相当于一桶葡萄皮。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Exactly.

正是如此。

Doses so high you could-- If you recall, we're both of an age that's old enough to remember this.

剂量如此之高，你可以——如果你还记得的话，我们都已经到了足以记住这一点的年龄。

There was this period of time when people thought this was the explanation to the French paradox.

曾经有一段时间，人们认为这就是法国悖论的解释。

Why, on average, do the French live longer when they consume so much wine?

为什么法国人喝这么多酒后平均寿命更长？

And the answer was it's got to be the resveratrol.

答案是它一定是白藜芦醇。

Turns out that's not true at all because you would need to be drinking your body weight in wine a day to get the doses of resveratrol that were needed to produce this effect.

事实证明，这根本不是真的，因为你需要每天喝与体重相同的葡萄酒才能获得产生这种效果所需的白藜芦醇剂量。

But for whatever reason, there was an effect, which is if the thing that was going to kill you was your liver being so full of fat that it shot up into your chest so you couldn't breathe, which I've never seen a human, no matter how bad their fatty liver has been, where that's been the case.

但无论出于什么原因，都会有一种影响，那就是，如果要杀死你的东西是你的肝脏充满了脂肪，以至于它射入你的胸部，让你无法呼吸，我从来没有见过一个人，不管他们的脂肪肝有多严重，情况就是这样。

But if that's the problem you're going to face, it's possible, at least based on this one mouse experiment, that you are going to live longer.

但如果这就是你要面临的问题，那么至少根据这一老鼠实验，你有可能活得更长。

But again, it turned out that there was no other replication of this in mouse models that matter.

但事实证明，在小鼠模型中没有其他重要的复制方法。

And that always comes back to the ITP, the Interventions Testing Program, which is the most robust tool we have scientifically to measure these exogenous molecules.

这总是要回到 ITP（干预测试计划），它是我们科学地测量这些外源分子的最强大的工具。

So the ITP is an NIA-funded program that runs out of three independent labs.

因此，ITP 是一个由 NIA 资助的项目，由三个独立实验室组成。

And by independent, I mean they're each doing the experiments independently, but they're in sync with doing the experiment, but they're doing it in triplicate.

我所说的独立，是指他们每个人都独立地进行实验，但他们与实验同步进行，但他们一式三份地进行。

So you have three great labs doing the experiments in triplicate, and when they did the resveratrol experiment, and they did it in combination with the people who found the result of that study.

因此，三个伟大的实验室一式三份地进行实验，当他们进行白藜芦醇实验时，他们与发现该研究结果的人一起进行了实验。

So they consulted these people and said, "What dose should we give?" And they said, "Do this." And they did it, and nothing.

于是他们咨询了这些人，问道：“我们应该给什么剂量？”他们说：“就这样做吧。”他们做到了，但什么也没做。

There was no effect of resveratrol.

白藜芦醇没有作用。

And that result has been consistent across the board.

这个结果在各个方面都是一致的。

So that's also a very important part of the story, which was if resveratrol was a sirtuin activator, and I don't know if it really is, it clearly has no effect on lifespan with the one little asterisk that says, "Unless your body weight is 50% fatty liver," then maybe it does.

所以这也是故事的一个非常重要的部分，如果白藜芦醇是一种去乙酰化酶激活剂，我不知道它是否真的如此，它显然对寿命没有影响，上面有一个小星号，“除非你的体重有 50% 的脂肪肝”，那么也许它会影响寿命。

Andrew Huberman:

安德鲁·休伯曼：

I'd like to take a quick break to let you know that the Huberman Lab team has launched a new podcast with host Dr. Andy Galpin.

我想稍微休息一下，让您知道 Huberman 实验室团队已经推出了由主持人 Andy Galpin 博士主持的新播客。

Andy is an expert in exercise science and human performance and has long been a fan favorite on the Huberman Lab podcast.

安迪是运动科学和人类表现方面的专家，长期以来一直是休伯曼实验室播客上的粉丝最爱。

This new podcast is called Perform with Dr. Andy Galpin, and it dives into topics such as how to build muscle and strength, how to improve your cardiovascular health, and how to optimize recovery and sleep for performance and much more.

这个新的播客名为“与安迪·加尔平博士一起表演”，它深入探讨了如何增强肌肉和力量、如何改善心血管健康以及如何优化恢复和睡眠以提高表现等主题。

Andy is an absolutely fantastic educator and true expert on all things human performance.

安迪是一位绝对出色的教育家，也是人类表现方面真正的专家。

I know you'll thoroughly enjoy his new podcast and learn a ton of useful knowledge from it.

我知道您会非常喜欢他的新播客，并从中学到大量有用的知识。

So please check it out and give it a subscribe wherever you're watching or listening to podcasts now.

因此，无论您现在正在观看或收听播客，请查看并订阅它。

Again, the podcast is called Perform with Dr. Andy Galpin.

同样，该播客的名称为“与安迪·加尔平博士一起表演”。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So let's see.

那么让我们看看。

Let's just take stock of where we are in this story.

让我们来回顾一下我们在这个故事中所处的位置。

We've got the whole yeast sirtuin situation, which is at least in some yeast, sirtuin overexpression lives longer.

我们已经掌握了整个酵母sirtuin的情况，至少在某些酵母中，sirtuin过度表达的寿命更长。

No evidence that that works through caloric restriction.

没有证据表明这可以通过热量限制发挥作用。

Truly no evidence.

确实没有证据。

That's been known for 20 years now.

这已为人所知 20 年了。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

That paper was published in 2004, and that was a follow-up to papers that had been published in 2002, 1999, et cetera.

该论文发表于 2004 年，是 2002 年、1999 年等发表论文的后续论文。

Later on, you'd have the 2012 transgenic mouse study.

稍后，您将进行 2012 年转基因小鼠研究。

So now the question is, okay-

所以现在的问题是，好吧-

Andrew Huberman:

安德鲁·休伯曼：

How do you activate sirtuins?

如何激活 Sirtuins？

Dr. Peter Attia:

彼得·阿蒂亚博士：

How do you activate sirtuins?

如何激活 Sirtuins？

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Or more to the point, why don't we just give people NAD?

或者更重要的是，我们为什么不直接给人们 NAD 呢？

Okay.

好的。

So again, the NAD story is NAD levels are declining with age in most tissues.

再说一次，NAD 的故事是，大多数组织中的 NAD 水平随着年龄的增长而下降。

It appears most prevalent in the skin of all places.

它在所有部位的皮肤中最为普遍。

And I think we should come back to this because there's one interesting finding associated with augmenting NAD levels in the skin, and my thought is, I wonder if it has to do with the fact that skin experiences the greatest decline in NAD.

我认为我们应该回到这个话题，因为有一个有趣的发现与增加皮肤中的 NAD 水平有关，我的想法是，我想知道这是否与皮肤中 NAD 下降幅度最大这一事实有关。

Andrew Huberman:

安德鲁·休伯曼：

It's also interesting because keratinocytes in skin turn over every 28 days or so.

这也很有趣，因为皮肤中的角质细胞每 28 天左右就会更新一次。

So you could imagine, because it's a novel population of cells, that they would have steady expression of sirtuins and NAD, then they simply die for whatever reason, or that it starts off very high on day one of generation, then tapers off quickly.

所以你可以想象，因为这是一个新的细胞群，它们会稳定表达sirtuins和NAD，然后它们就会因为某种原因而死亡，或者它在一代的第一天开始非常高，然后迅速减少。

But That's not the case, it sounds like.

但事实并非如此，听起来像是。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

You know?

你知道吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

On average, skin over the course of your lifetime will see about a 60% reduction in NAD, whereas other tissues, and this is now based on animal studies, the brain might see a reduction by 15% to 20%, and the same would be found even in humans looking at the blood.

平均而言，在您的一生中，皮肤中的 NAD 会减少约 60%，而其他组织（这是基于动物研究的结果）则大脑中的 NAD 可能会减少 15% 至 20%，甚至在人类血液中也会发现同样的情况。

So if you just sample whole blood in people at the age of 20, 30, 40, 50, 60, 70, 80, you're going to see about a 20% reduction in NAD.

因此，如果您仅对 20、30、40、50、60、70、80 岁人群的全血进行采样，您会发现 NAD 减少了约 20%。

Andrew Huberman:

安德鲁·休伯曼：

What about neurons?

那么神经元呢？

You've got the same set of central nervous system neurons your entire life, and of course, some peripheral neurons as well.

你一生中都会拥有相同的中枢神经系统神经元，当然还有一些周围神经元。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, that's about it.

是的，就是这样。

Andrew Huberman:

安德鲁·休伯曼：

But there's some regeneration in the periphery-

但外围有一些再生——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah

是啊

Andrew Huberman:

安德鲁·休伯曼：

...

so let's just talk about brain.

所以我们只谈谈大脑。

So unless you're talking about the olfactory bulb where you have constant turnover throughout the lifespan, you have the same hippocampal neurons, except a small population, same hippocampal neurons, cortical neurons, retinal neurons that you were born with.

因此，除非你谈论的是在整个生命周期中不断更新的嗅球，否则你拥有相同的海马神经元，除了一小部分，相同的海马神经元、皮质神经元、视网膜神经元与你出生时一样。

Are we observing NAD levels tapering off as we age?

我们是否观察到 NAD 水平随着年龄的增长而逐渐下降？

Dr. Peter Attia:

彼得·阿蒂亚博士：

In animals, yes.

在动物中，是的。

Obviously, in humans, we're not doing that experiment, but yeah.

显然，我们不会在人类身上做这样的实验，但是是的。

Now, here's an interesting point.

现在，这是一个有趣的点。

In 2015, a study was published in PNAS that looked at NAD levels in whole blood over time, and it found indeed NAD levels were going down about 10% to 20% over four decades or so.

2015 年，《PNAS》发表了一项研究，该研究观察了全血中 NAD 水平随时间的变化，结果发现 NAD 水平在四十年左右的时间里确实下降了约 10% 至 20%。

But that same study said NADH levels were going up by the same amount.

但同一项研究表明 NADH 水平也上升了同样的幅度。

Andrew Huberman:

安德鲁·休伯曼：

Explain the role of NADH for people.

解释 NADH 对人们的作用。

Dr. Peter Attia:

彼得·阿蒂亚博士：

NADH is the electron acceptor.

NADH是电子受体。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So let's maybe take a step back of why are you and I sitting here talking and not dead?

那么，让我们退一步思考一下，为什么你和我坐在这里说话而不是死掉？

Andrew Huberman:

安德鲁·休伯曼：

Because we have enough NAD.

因为我们有足够的NAD。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Right.

对。

What's going on, right?

这是怎么回事，对吧？

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

Dr. Peter Attia:

彼得·阿蒂亚博士：

You and I ate something at some point in the foreseeable past that contained chemical energy.

你和我在可预见的过去的某个时刻吃了一些含有化学能的东西。

So we ate something that was organic.

所以我们吃了一些有机的东西。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So primarily fats and carbohydrates contain carbon–carbon bonds and carbon–hydrogen bonds.

因此，脂肪和碳水化合物主要含有碳-碳键和碳-氢键。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And those bonds contain a ton of energy, but how do we liberate the energy?

这些键含有大量的能量，但我们如何释放能量呢？

So we break it all down into these constitutive molecules, namely glucose on the carbohydrate front and free fatty acids on the fat front.

因此，我们将其全部分解为这些组成分子，即碳水化合物前面的葡萄糖和脂肪前面的游离脂肪酸。

And then our bodies break those things down further into smaller molecules that get shuttled into the mitochondria, where the lion's share of our energy liberation comes from.

然后我们的身体将这些物质进一步分解成更小的分子，这些分子被运送到线粒体中，我们释放的大部分能量都来自线粒体。

And what we do is we take that chemical energy that is stored in a carbon to carbon bond or a carbon to hydrogen bond, and we turn it into electrical energy.

我们所做的就是将储存在碳碳键或碳氢键中的化学能转化为电能。

And people have heard this term, it's called the electron transport chain.

人们听说过这个术语，它叫做电子传输链。

So there are these four complexes in the mitochondria, and there's an inner membrane and an outer membrane across which these large mitochondrial complexes reside.

线粒体中有这四个复合体，这些大的线粒体复合体横跨内膜和外膜。

And what they're doing is they're building up a huge electron gradient by breaking them apart and taking the electrons and transferring them between NAD and NADH, so that at the end, they can do another trick, which is transfer those electrons to AMP, ADP, and ultimately make ATP.

他们所做的就是通过将它们分开并获取电子并在 NAD 和 NADH 之间转移来建立一个巨大的电子梯度，这样最后他们就可以做另一个技巧，即将这些电子转移到 AMP、ADP，并最终生成 ATP。

The finished product is water and carbon dioxide.

最终产物是水和二氧化碳。

So we eat, and we take that chemical energy in food, we utilize oxygen in the mitochondria to make ATP, carbon dioxide, which we breathe out, and water, which we breathe and pee out.

所以我们吃东西，我们吸收食物中的化学能，我们利用线粒体中的氧气来制造 ATP、二氧化碳（我们呼出）和水（我们呼出和撒尿）。

So what NAD and NADH are doing is playing an absolutely essential to life role in facilitating the transfer of chemical energy to electrical energy back to chemical energy.

因此，NAD 和 NADH 在促进化学能向电能再转化为化学能方面发挥着对生命绝对重要的作用。

ATP is just taking it from one chemical form in food to the electrical form as the intermediary in the mitochondria, back to an electrical form of ATP.

ATP 只是将其从食物中的一种化学形式转变为电形式（作为线粒体中的中介），再回到 ATP 的电形式。

So you and I are walking around flush with ATP, which as we sit here right now, we're constantly firing off phosphates, again, now turning the chemical energy back into electrical energy, and away we go.

所以你和我都带着 ATP 四处走动，当我们现在坐在这里时，我们不断地释放磷酸盐，现在再次将化学能重新转化为电能，然后我们就出发了。

So yeah, this whole NAD, NADH thing it's as central to our existence as any form of respiration.

所以，是的，NAD、NADH 与任何形式的呼吸一样对我们的存在至关重要。

So my point-- let's go back to the story.

所以我的观点是——让我们回到这个故事。

The story was NAD levels are going down as we age, but NADH levels are going up, suggesting that the total amount of NAD and NADH is the same, and what's declining as we age should less be thought of as a reduction in NAD and should more be thought of as a reduction in what's called redox potential, the ability to do what I just said.

这个故事是，随着我们年龄的增长，NAD 水平会下降，但 NADH 水平会上升，这表明 NAD 和 NADH 的总量是相同的，随着我们年龄的增长，NAD 水平的下降不应该被认为是 NAD 的减少，而应该更多地被认为是所谓的氧化还原电位的减少，即完成我刚才所说的能力的减少。

So when people say NAD levels decline with aging, the answer is, yeah, but what's really declining as we age, and this kind of comes back to what you said at the very, very outset, like what's happening at the cellular level, I think what's happening is our mitochondria are not as good as we age, and we have less redox potential.

因此，当人们说 NAD 水平随着衰老而下降时，答案是，是的，但是随着年龄的增长，真正下降的是什么，这又回到了你一开始所说的，就像在细胞水平上发生的事情一样，我认为发生的事情是我们的线粒体不如我们年龄那么好，我们的氧化还原潜力也更少。

Andrew Huberman:

安德鲁·休伯曼：

And I would say a fair number of so-called anti-aging approaches are targeting the so-called reactive oxygen species, ROS-

我想说，相当多所谓的抗衰老方法都是针对所谓的活性氧，ROS-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah

是啊

Andrew Huberman:

安德鲁·休伯曼：

...

which impede mitochondrial function, essentially.

从本质上讲，这会阻碍线粒体功能。

This is an opportunity for me to call out the work that I think is at least intriguing, which is the work of a colleague by the name of Glenn Jeffrey at the University College London.

对我来说，这是一个机会来介绍我认为至少有趣的工作，这是伦敦大学学院一位名叫格伦·杰弗里（Glenn Jeffrey）的同事的工作。

He's been in the field of visual neuroscience for a very long time, and a few years back, he started doing some experiments on animals, and now also two studies published on humans showing that exposing the aged eye, so 40 and older, to red light and near-infrared light for a couple of minutes a few times a week can spare certain processes involved in vision.

他在视觉神经科学领域工作了很长时间，几年前，他开始在动物身上做一些实验，现在还发表了两项针对人类的研究，表明将老年眼睛（40 岁及以上）每周几次暴露在红光和近红外光下几分钟可以避免涉及视觉的某些过程。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm.

嗯。

Andrew Huberman:

安德鲁·休伯曼：

Photoreceptors.

光感受器。

How does this work?

这是如何运作的？

Well, this isn't proven yet.

嗯，这还没有得到证实。

The idea is that it's reducing reactive oxygen species and thereby improving mitochondrial function in what is perhaps the most metabolically active cell type in the entire body, not just the eye, which are the photoreceptors.

这个想法是，它可以减少活性氧，从而改善线粒体功能，线粒体功能可能是整个身体中代谢最活跃的细胞类型，而不仅仅是眼睛（即光感受器）。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm.

嗯。

Andrew Huberman:

安德鲁·休伯曼：

So it's an intriguing set of studies.

所以这是一组有趣的研究。

Again, we don't have all the mechanisms worked out, but- It brings us around again to this idea that mitochondria are vitally important for the functioning of cells.

再说一遍，我们还没有弄清楚所有的机制，但是——它让我们再次认识到线粒体对于细胞功能至关重要。

Things that impede the function of mitochondria can either reduce the output of and/or kill cells.

阻碍线粒体功能的物质会减少细胞的输出和/或杀死细胞。

And so anything that can improve redox can potentially keep a cell around longer, functioning better.

因此，任何可以改善氧化还原的东西都可以使细胞保持更长时间，更好地发挥作用。

So when I hear about the role of NAD in this pathway, I think like most people, I think, "Okay, well then I should just take more NAD and maybe I will age more slowly, or I will replace some NAD that's missing as I age in whatever cell type." Turns out that might not be so straightforward, right?

因此，当我听说 NAD 在这条通路中的作用时，我像大多数人一样想，“好吧，那么我应该服用更多的 NAD，也许我会衰老得更慢，或者我会补充一些随着年龄增长而在任何细胞类型中缺失的 NAD。”事实证明这可能没那么简单，对吧？

I don't want to jump to supplementation just yet.

我还不想立即开始补充。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep.

是的。

Andrew Huberman:

安德鲁·休伯曼：

But if we are to back up from NAD a little bit and look at the pathway leading to NAD, it's NR, NMN, and NAD.

但如果我们从 NAD 退一步看一下通向 NAD 的途径，那就是 NR、NMN 和 NAD。

We'll spell these out in a moment.

我们稍后会详细说明这些内容。

And the sort of competition that's out there in the market is around either infusing or, in some cases, ingesting NAD directly, taking NMN, which is the precursor to NAD, orally, I haven't heard of anybody infusing it, or taking oral form NR, which is the precursor to NMN.

市场上的竞争要么是输注，要么是在某些情况下直接摄入 NAD，口服 NMN（NAD 的前体），我没有听说有人输注它，或者口服 NR（NMN 的前体）。

My understanding is that NMN is simply NR minus a phosphate group.

我的理解是NMN就是NR减去磷酸基团。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

And I'll take a step back from this first to say the following.

我先退后一步说以下内容。

Again, because this topic is so confusing, I think it's just worth reminding everybody of everything we've said and where it brings us, right?

再说一次，因为这个话题太令人困惑了，我认为值得提醒大家我们所说的一切以及它给我们带来的结果，对吗？

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So I'm not going to repeat the whole sirtuin thing.

所以我不会重复整个 Sirtuin 的事情。

Let's just leave that alone.

我们就别管它了。

But we-

但我们——

Andrew Huberman:

安德鲁·休伯曼：

Because everything we're on right now is upstream of sirtuins.

因为我们现在所做的一切都是 Sirtuins 的上游。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

It's basically like once you establish that we think sirtuins matter, even though they don't work through caloric restriction, and that's about the single most obvious thing I can say, they might still matter.

基本上就像一旦你确定我们认为去乙酰化酶很重要，即使它们不能通过热量限制发挥作用，这是我能说的最明显的一件事，它们可能仍然很重要。

Even though we don't have things that we've figured out can activate sirtuins, like resveratrol, we don't seem to have things that we can give you that activate sirtuins.

尽管我们没有发现可以激活去乙酰化酶的物质，例如白藜芦醇，但我们似乎没有可以为您提供的东西来激活去乙酰化酶。

We're now onto the next part of the story, which is, okay, sirtuins matter, they don't seem to matter.

我们现在进入故事的下一部分，好吧，sirtuins 很重要，但它们似乎并不重要。

We think sirtuins matter because of a few of these overexpression experiments.

我们认为去乙酰化酶很重要，因为其中一些过度表达实验。

And we're making a big leap that because they mattered in yeast, they're going to matter in us.

我们正在迈出一大步，因为它们在酵母中很重要，所以它们对我们也很重要。

That's a huge leap for which there's zero evidence.

这是一个巨大的飞跃，但证据为零。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

And I'm only leaping further to this discussion about how to increase NAD because-

我只是进一步讨论如何增加 NAD，因为-

Dr. Peter Attia:

彼得·阿蒂亚博士：

That's right

没错

Andrew Huberman:

安德鲁·休伯曼：

...

I know that's in the back of people's minds.

我知道这是人们内心深处的想法。

Dr. Peter Attia:

彼得·阿蒂亚博士：

That's right.

没错。

Andrew Huberman:

安德鲁·休伯曼：

We're not going to double-click here just yet.

我们暂时不打算双击此处。

I just want to frame that up.

我只是想把它框起来。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Right, so why are we doing this?

对了，那么我们为什么要这样做呢？

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

Because ultimately that's where we are headed in terms of people making decisions as to whether or not they should take NR or take NMN-

因为最终这就是人们决定是否应该服用 NR 还是服用 NMN 的方向 -

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, and the reason I'm-

是的，我的原因是——

Andrew Huberman:

安德鲁·休伯曼：

...

or infuse NAD or none of the above.

或注入 NAD 或以上均不注入。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And the reason I'm being such a hardass about this, Andrew, is I spend so much time fielding questions on this that I realize we just have to talk about this in the most detailed fashion possible-

安德鲁，我之所以在这件事上如此强硬，是因为我花了太多时间回答这方面的问题，以至于我意识到我们必须以尽可能最详细的方式讨论这个问题——

Andrew Huberman:

安德鲁·休伯曼：

I agree

我同意

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

so that people understand why.

以便人们了解原因。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Because it is just too easy, right?

因为这太容易了，对吧？

There's this great quote by JFK that I'm going to paraphrase, that is basically, people enjoy the comfort of opinion without the discomfort of thought.

我要转述肯尼迪的一句名言，基本上，人们享受观点的安慰，而不享受思想的不适。

Right?

正确的？

So we need to-- this is a podcast to get people to think and understand the entire history of this field so that they can actually make an informed decision about a supplement that I'm going to argue has very little scientific basis for its justification.

所以我们需要——这是一个播客，让人们思考和理解这个领域的整个历史，这样他们就能真正对一种补充剂做出明智的决定，我认为这种补充剂的合理性几乎没有科学依据。

Andrew Huberman:

安德鲁·休伯曼：

I would say scientific justification for longevity.

我想说的是长寿的科学依据。

I'll go on record now saying that I take NMN.

我现在要公开表示我服用 NMN。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm-hmm.

嗯嗯。

Andrew Huberman:

安德鲁·休伯曼：

And in some cases, I will take NR and NMN, and I observe, this is just N of one self-observational data, I observe a very clear positive effect, but I don't think it has anything to do with extending lifespan.

在某些情况下，我会服用NR和NMN，我观察到，这只是N个自我观察数据，我观察到非常明显的积极效果，但我不认为它与延长寿命有任何关系。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And we should talk about both health span and lifespan benefits when we get to that part.

当我们谈到这一部分时，我们应该讨论健康寿命和寿命益处。

But so to bring us up to where we are now, where you are with should people be supplementing NAD, we're basically at the point where we're taking a lot of leaps of faith and saying because NAD levels are going down and redox potential is going down, we believe supplementing NAD in one form or another makes sense.

但是，为了让我们达到现在的水平，如果人们补充 NAD，我们基本上已经到了这样一个阶段：我们的信念发生了很大的飞跃，因为 NAD 水平正在下降，氧化还原电位正在下降，我们相信以一种或另一种形式补充 NAD 是有意义的。

But before we do that, we should acknowledge something.

但在此之前，我们应该承认一些事情。

Yes, NAD levels are going down, but we have no reason to believe that raising NAD levels will correct a problem.

是的，NAD 水平正在下降，但我们没有理由相信提高 NAD 水平就能解决问题。

In other words, if the body operates between this level and this level of NAD, and if you go below this level, you die, and you go above this level, you die, and levels as you age go like this.

换句话说，如果身体在这个水平和这个 NAD 水平之间运行，如果你低于这个水平，你就会死亡，如果你高于这个水平，你就会死亡，随着年龄的增长，水平会像这样。

Do we believe that raising them to this does anything?

我们相信将他们培养到这个程度有什么作用吗？

There's no evidence that says it does.

没有证据表明确实如此。

So that's a leap of faith.

所以这是信仰的飞跃。

It's okay to take leaps of faith.

信仰的飞跃是可以的。

You just have to know you're taking a leap of faith.

你只需要知道你正在实现信念的飞跃。

Okay, so leap of faith number one is the sirtuin thing.

好吧，信仰之跃第一个就是 Sirtuin。

Leap of faith number two is the caloric restriction thing.

第二个信念的飞跃是热量限制。

Leap of faith number three is this matters in our species, the species of interest.

第三个信念的飞跃是这对我们这个物种、我们感兴趣的物种来说很重要。

Leap of faith four is the whole sirtuin activator thing.

信仰之跃四就是整个 Sirtuin 激活剂的事情。

And now this leap of faith is if we just increase NAD levels in us, it will produce a positive benefit.

现在这种信念的飞跃是，如果我们只是增加体内的 NAD 水平，就会产生积极的好处。

Okay, so now how do we do that?

好的，现在我们该怎么做呢？

Now you get into the tactic.

现在你进入策略了。

Okay, there are three ways to do it, as you said.

好吧，正如你所说，有三种方法可以做到这一点。

One is you can intravenously take NAD.

一种是可以静脉注射 NAD。

By the way, you could probably also orally take NAD.

顺便说一下，您也可以口服 NAD。

It would just break down in the gut into its constitutive products-

它只会在肠道中分解成其组成产物——

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm

嗯嗯

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

and then probably reform.

然后可能会进行改革。

But for the purpose of how people actually do this, they intravenously get NAD because it's not orally bioavailable, or, as you said, they orally take two precursors, NR and NMN.

但就人们实际如何做到这一点而言，他们通过静脉注射获取 NAD，因为它不能口服生物利用，或者正如你所说，他们口服两种前体：NR 和 NMN。

My personal view on this is there's not really much of a difference in what you do.

我个人对此的看法是，您所做的事情并没有太大区别。

In other words, at the end of the day, all of these things are generally going to increase NAD levels in the blood.

换句话说，归根结底，所有这些事情通常都会增加血液中的 NAD 水平。

Andrew Huberman:

安德鲁·休伯曼：

So a couple of kind of practical notes.

所以有一些实用的笔记。

I've taken NR in capsule form, I've taken NMN, typically in powdered form where I put it sublingually-

我服用了胶囊形式的 NR，我服用了 NMN，通常是粉末形式，我把它放在舌下 -

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm-hmm

嗯嗯

Andrew Huberman:

安德鲁·休伯曼：

...

under the tongue.

舌下。

My understanding is that-

我的理解是——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Have you done intravenous NAD?

你做过NAD静脉注射吗？

Andrew Huberman:

安德鲁·休伯曼：

I sure have, and what I-

我确实有，而且我-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Did you experience a niacin flush?

您经历过烟酸潮红吗？

Andrew Huberman:

安德鲁·休伯曼：

No. I took NAD as an infusion.

不，我服用 NAD 作为输液。

I've probably done it five or six times, and for the first 10 minutes of the infusion, you feel like somebody's stepping on your chest with a boot.

我可能已经做过五六次了，在输液的前10分钟，你会感觉有人用靴子踩在你的胸口。

Your legs cramp up.

你的腿抽筋了。

You feel nauseous.

你感到恶心。

I did not take the anti-nausea med that was offered.

我没有服用提供的抗恶心药物。

I don't like taking things if I can avoid it.

我不喜欢拿走能避免的东西。

I just figured I'll just experience this.

我只是想我会经历这个。

It was very uncomfortable.

非常不舒服。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm-hmm.

嗯嗯。

Andrew Huberman:

安德鲁·休伯曼：

To the point where you couldn't read a paper or a book.

以至于你无法阅读论文或书籍。

You just want to be left alone.

你只想一个人呆着。

You actually get a little bit irritable.

你实际上有点烦躁。

You're like, "This is awful." Every noise in the room is a bit too loud during that first 10 minutes.

你会说，“这太糟糕了。”在最初的 10 分钟里，房间里的所有噪音都有点太大了。

And then-

然后——

Dr. Peter Attia:

彼得·阿蒂亚博士：

By the way, do you know how many people have said to me that because of that experience, they know it must be doing something good?

顺便问一下，你知道有多少人对我说，因为那次经历，他们知道这一定是在做好事吗？

Andrew Huberman:

安德鲁·休伯曼：

Oh my goodness.

天哪。

Dr. Peter Attia:

彼得·阿蒂亚博士：

To which I'm like, "Why don't you spread your legs?

我的反应是：“你为什么不张开双腿呢？

Let me kick you right in the nuts.

让我狠狠地踢你一脚吧。

That's going to feel even worse.

那感觉会更糟。

Is that doing something good?" Like, the fact that something feels so awful shouldn't be used as an explanation for why it's doing good physiologically.

这是在做好事吗？”就像，某些东西感觉如此糟糕这一事实不应该被用来解释为什么它在生理上表现良好。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

I don't know what it was doing physiologically except making me feel miserable during the infusion.

我不知道它在生理上做了什么，除了让我在输液过程中感到痛苦之外。

There are ways to adjust this, even without the anti-nausea meds.

即使没有抗恶心药物，也有一些方法可以调整这一点。

For instance, you can slow the infusion.

例如，您可以减慢输注速度。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm-hmm.

嗯嗯。

Andrew Huberman:

安德鲁·休伯曼：

That's the typical way.

这是典型的方式。

People will put it in over the course of several hours, anywhere from three hours to as brief as 30 minutes is kind of the record that I've heard about for 500 milligrams of NAD.

人们会在几个小时内将其放入，从三个小时到短至 30 分钟不等，这是我听说的 500 毫克 NAD 的记录。

If you put 1,000 milligrams in there, obviously it's more painful and you have to...

如果你把1000毫克放进去，显然会更痛苦，你必须……

Anyway, there are a bunch of practical considerations.

无论如何，有很多实际的考虑。

You feel, now maybe it's placebo, but one feels quite good afterward.

你觉得，现在也许它是安慰剂，但之后感觉很好。

So as soon as the drip is done, you feel better than you did prior to the drip.

因此，滴注完成后，您会感觉比滴注前更好。

Dr. Peter Attia:

彼得·阿蒂亚博士：

How do you feel if you just receive an IV infusion of the same volume?

如果您刚刚接受相同容量的静脉输液，您感觉如何？

Andrew Huberman:

安德鲁·休伯曼：

I've done that because I've received saline drips.

我这样做是因为我接受了生理盐水滴注。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm-hmm.

嗯嗯。

Andrew Huberman:

安德鲁·休伯曼：

You also feel pretty good.

你也感觉很好。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

It's hard to-

很难——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah

是啊

Andrew Huberman:

安德鲁·休伯曼：

...

disentangle these things.

解开这些事情。

And typically they'll put other things in the bag, glutathione, some vitamin C.

通常他们会在袋子里放其他东西，谷胱甘肽，一些维生素 C。

They tend to sell these as kits.

他们倾向于将这些作为套件出售。

I decided to try it.

我决定尝试一下。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

It seemed fine.

看起来不错。

I did it when traveling.

我旅行的时候就这么做了。

I don't know, maybe I'm due for another one soon.

我不知道，也许我很快就会再去一次。

But for me, the more typical way to try and increase NAD or whatever, because I don't know what it's doing exactly, but I like the effects of taking sublingual NMN.

但对我来说，更典型的方法是尝试增加 NAD 或其他什么，因为我不知道它到底在做什么，但我喜欢舌下含服 NMN 的效果。

The single most, let's say, salient to me, anecdotal data on taking sublingual NMN is that it makes my hair grow really fast, it makes my nails grow really fast, and I do feel an increase in energy, and I take it first thing in the morning.

对我来说，最重要的一点是，舌下含服 NMN 的轶事数据是，它使我的头发长得非常快，它使我的指甲长得非常快，而且我确实感到精力增加，我早上第一件事就是服用它。

Dr. Peter Attia:

彼得·阿蒂亚博士：

At what dose?

什么剂量？

Andrew Huberman:

安德鲁·休伯曼：

One and a half grams.

一克半。

1,500 milligrams.

1,500 毫克。

So-

所以——

Dr. Peter Attia:

彼得·阿蒂亚博士：

By the way, if you translate the doses that they give mice in the studies where they're testing the efficacy, are typically on the order of 500 to 1,000 milligrams per kilogram.

顺便说一句，如果你换算一下他们在测试功效的研究中给予小鼠的剂量，通常约为每公斤 500 至 1,000 毫克。

Andrew Huberman:

安德鲁·休伯曼：

Whoa.

哇哦。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

I'm 100 kilograms.

我有100公斤。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep.

是的。

Andrew Huberman:

安德鲁·休伯曼：

Whoa.

哇哦。

Okay.

好的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So picture that the next time you're giving yourself some NAD or NR.

想象一下，下次您给自己一些 NAD 或 NR 时。

Andrew Huberman:

安德鲁·休伯曼：

I'm not even approaching that-

我什至还没有接近那个-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah

是啊

Andrew Huberman:

安德鲁·休伯曼：

...

at all.

根本不。

Well, it's clear to me, based on my read of the data, that NR can cross the cell membrane directly.

嗯，根据我读到的数据，我很清楚 NR 可以直接穿过细胞膜。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Directly, very easily.

直接，非常容易。

There's no obstacle to NR getting into cells.

NR进入细胞没有任何障碍。

Andrew Huberman:

安德鲁·休伯曼：

Okay.

好的。

And NMN cannot because of that extra phosphate group, so that if you take it sublingually or you ingest it orally, it goes into the gut, the phosphate group is cleaved, and because of that, the argument is that if one were to compare the benefits of taking NR versus NMN, there are more data to support NR as a precursor to NAD, a more effective precursor to NAD than orally ingested NMN.

NMN 不能，因为有额外的磷酸基团，所以如果你舌下含服或口服，它会进入肠道，磷酸基团被裂解，正因为如此，争论是，如果要比较服用 NR 和 NMN 的好处，有更多数据支持 NR 作为 NAD 前体，比口服 NMN 更有效的 NAD 前体。

But some people will say, "Well, I'll just take more NMN than I would NR," and then this gets into the realm of cost effectiveness.

但有些人会说，“好吧，我会服用比 NR 更多的 NMN”，然后这就进入了成本效益的领域。

Dr. Peter Attia:

彼得·阿蒂亚博士：

It's just a commercial issue.

这只是一个商业问题。

Andrew Huberman:

安德鲁·休伯曼：

It starts becoming a battle between commercial sources and-

它开始成为商业来源和——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

This is-

这是——

Andrew Huberman:

安德鲁·休伯曼：

And I don't dispute that NR makes more sense as a precursor, especially at dosages of 300 to 600 milligrams versus 1,500 milligrams, but I've opted to take sublingual NMN mostly based on cost.

我并不否认 NR 作为前体更有意义，尤其是在 300 至 600 毫克的剂量与 1,500 毫克的剂量下，但我选择舌下含服 NMN 主要是基于成本。

NR at the dosages people recommend is quite expensive.

人们推荐的 NR 剂量相当昂贵。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Imagine you had to take it at the mouse doses.

想象一下你必须按照小鼠的剂量服用它。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

Dr. Peter Attia:

彼得·阿蒂亚博士：

You'd be spending about 300 bucks a day.

一天大概要花300块钱。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

It's not feasible.

这是不可行的。

It's just not feasible.

这是不可行的。

So, I don't have a deep desire for my hair to grow faster or my nails to grow faster.

所以，我并没有强烈的愿望让我的头发长得更快或者我的指甲长得更快。

It's more the increase in energy effect.

更多的是能量效果的增加。

Now, I will say that sublingual NMN is also a bit of a laxative.

现在，我要说的是舌下含服 NMN 也有一点泻药的作用。

So there are all these-- and I say that somewhat chuckling, but some people say it makes them feel better.

所以就有了所有这些——我说这话的时候有点轻笑，但有些人说这让他们感觉好多了。

Well, is that because you're evacuating your bowels a few minutes or hours later and then you feel less bloated and you have more energy?

嗯，这是因为几分钟或几小时后你排便，然后你感觉腹胀减轻了，精力更充沛了？

It's very unclear.

非常不清楚。

I think what has not been done, as far as I know, is to compare orally ingested NR at, say, 600 milligrams, a relatively high dose, versus a gram of sublingual NMN and then actually measure blood levels of NAD.

据我所知，我认为尚未完成的是将口服摄入的 NR（相对较高剂量）（例如 600 毫克）与 1 克舌下含服 NMN 进行比较，然后实际测量血液中的 NAD 水平。

If that experiment has been done and I'm not aware of it, I'm not aware of it, then forgive me.

如果那个实验已经完成而我没有意识到，我没有意识到，那么请原谅我。

Maybe someone will put it in the show note captions.

也许有人会把它放在节目注释标题中。

But I guess this gets down to the question of how many people are taking oral NR or NMN, or are taking NAD infusions, which by the way, are quite expensive.

但我想这归根结底是有多少人正在服用口服 NR 或 NMN，或者正在服用 NAD 输注的问题，顺便说一句，这相当昂贵。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm-hmm.

嗯嗯。

Andrew Huberman:

安德鲁·休伯曼：

Anywhere from $300 to $1,000 a drip.

每次滴注费用从 300 美元到 1,000 美元不等。

That's pretty expensive.

那是相当昂贵的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Think about that.

想想看。

Andrew Huberman:

安德鲁·休伯曼：

What benefits are they getting?

他们得到什么好处？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Just think about that, right?

想想看，对吗？

Andrew Huberman:

安德鲁·休伯曼：

What are they getting out of this?

他们从中得到什么？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

What are they getting?

他们得到什么？

Is it an acute increase in NAD that what?

难道NAD急剧升高是怎么回事？

That causes them to live, what?

这让他们活下去，什么？

A week longer?

还要多一周吗？

We have no idea.

我们不知道。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Well, so let's try to use data to answer the question, right?

好吧，那么让我们尝试用数据来回答这个问题吧？

So this is exactly the thing that the ITP, the Interventions Testing Program, was designed to test.

这正是 ITP（干预测试计划）旨在测试的内容。

And again, if people are interested in this, they should go back and listen to my two discussions with Rich Miller, where we go through gory detail of every molecule that has gone through the ITP.

再说一次，如果人们对此感兴趣，他们应该回去听听我与 Rich Miller 的两次讨论，其中我们详细介绍了通过 ITP 的每个分子的血腥细节。

The ITP is hands down the most rigorous tool we have for testing molecules in anything other than the species of interest, because we can't do these experiments in human.

ITP 无疑是我们在除感兴趣物种以外的任何物种中测试分子的最严格的工具，因为我们无法在人体中进行这些实验。

We cannot test lifespan interventions in humans for the obvious reasons.

出于显而易见的原因，我们无法测试人类的寿命干预措施。

So what is the next best thing?

那么下一个最好的事情是什么？

Well, it turns out it's doing it in a non-inbred mouse, in triplicate, in three institutions.

事实证明，它是在三个机构的非近交小鼠身上进行的，一式三份。

You can't get more rigorous than this.

没有比这更严格的了。

The ITP has tested probably north of 50 molecules, meaning it has done the same experiment for 50 different molecules, and very few have extended lifespan.

ITP 已经测试了大约 50 种以上的分子，这意味着它已经对 50 种不同的分子进行了相同的实验，但很少有分子具有延长的寿命。

And a notable failure is NR.

一个值得注意的失败是 NR。

Andrew Huberman:

安德鲁·休伯曼：

Hmm.

嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

NR was tested, and I believe it was tested at a very robust dose, either 500 or 1,000 milligrams per kilogram, and there was no extension of life.

NR经过了测试，我相信它是在非常强的剂量（每公斤500或1,000毫克）下进行测试的，并且没有延长寿命。

There was no improvement in health span.

健康寿命没有改善。

There was no change.

没有任何变化。

Megadose NR, placebo, same result.

大剂量 NR，安慰剂，结果相同。

Conversely, let's consider some of the successes of the ITP.

相反，让我们考虑一下 ITP 的一些成功案例。

Rapamycin.

雷帕霉素。

When you give rapamycin, the first time they did it, because they had a hard time formulating the rapamycin, they weren't able to start it until the mice were 21 months old, which is very old for a mouse.

当你第一次给予雷帕霉素时，他们第一次这样做，因为他们在配制雷帕霉素时遇到了困难，直到小鼠21个月大时才开始使用，这对于小鼠来说已经很大了。

That's like a 60-year-old mouse.

这就像一只60岁的老鼠。

And at that point, they almost aborted the experiment because they were like, "Well, what's the point?

那时，他们几乎放弃了实验，因为他们想，“好吧，有什么意义呢？

Nothing is going to work when you start this late," including caloric restriction, by the way, although it has worked in one experiment.

顺便说一下，当你这么晚开始的时候，什么都不会起作用，包括热量限制，尽管它在一项实验中已经奏效了。

But nevertheless, it worked.

但尽管如此，它还是奏效了。

And when you gave rapa that late in life, it still worked.

当你在晚年给予rapa时，它仍然有效。

Then they redid the experiment, and they gave it earlier.

然后他们重新做了实验，并且提前进行了实验。

It worked.

它起作用了。

Canagliflozin, as I mentioned, which is an SGLT2 inhibitor, it worked.

正如我提到的，卡格列净是一种 SGLT2 抑制剂，它有效。

Acarbose, a drug that inhibits glucose absorption, worked, and interestingly, didn't require weight loss.

阿卡波糖是一种抑制葡萄糖吸收的药物，它确实有效，而且有趣的是，不需要减肥。

So the thesis behind giving acarbose to the mice was, it's a caloric restriction mimetic, a CR mimetic, and it worked, but the treatment mice weren't any lighter than the non-treatment mice, which actually goes back to something you said at the very outset, which suggested that tight glycemic control, independent of weight, is a longevity benefit.

因此，给小鼠服用阿卡波糖背后的论点是，它是一种热量限制模拟物，一种 CR 模拟物，而且它有效，但治疗小鼠并不比未治疗小鼠轻，这实际上可以追溯到您一开始所说的，这表明严格的血糖控制（与体重无关）有利于长寿。

The same was true with the SGLT2 inhibitor, canagliflozin.

SGLT2 抑制剂卡格列净也是如此。

SGLT2 inhibitors cause you to pee out more glucose.

SGLT2 抑制剂会导致您排出更多葡萄糖。

Acarbose prevents you from absorbing it in your gut.

阿卡波糖会阻止您在肠道中吸收它。

So two different ways to regulate glucose.

所以有两种不同的方式来调节血糖。

Neither of those experiments resulted in a lower body weight for the mice, and yet they both lived longer.

这两个实验都没有导致小鼠体重减轻，但它们的寿命都更长。

Again, there's something very important about regulating blood glucose.

再说一遍，调节血糖非常重要。

The other thing that worked is 17 alpha-estradiol, and it only worked in male mice.

另一种有效的物质是 17 α-雌二醇，它只对雄性小鼠有效。

So again, suggesting that-- Well, we can come back to that.

再次建议——好吧，我们可以回到这一点。

It's more than we want to get into at the moment.

这超出了我们目前想要了解的范围。

But the point here is, there are very few molecules that have withstood the scrutiny of the ITP.

但这里的要点是，很少有分子能够经受住 ITP 的审查。

Metformin failed, by the way.

顺便说一下，二甲双胍失败了。

Andrew Huberman:

安德鲁·休伯曼：

And the ITP is specifically for offsetting aging.

ITP是专门用来抵消衰老的。

Is that right?

是这样吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

It is lifespan, but it also looks at some measures of healthspan.

它是寿命，但它也着眼于健康寿命的一些衡量标准。

But it is the gold standard for lifespan, yeah.

但这是寿命的黄金标准，是的。

Andrew Huberman:

安德鲁·休伯曼：

Because my understanding is that there are some studies that have explored the role of supplemented NR, maybe NMN as well-

因为我的理解是，有一些研究探索了补充NR的作用，也许还有NMN——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep

是的

Andrew Huberman:

安德鲁·休伯曼：

...

but certainly supplemented NR, for sake of lowering inflammation to offset some of the negative effects of time zone shift, alcohol.

但肯定要补充NR，以降低炎症，以抵消时区转换和酒精的一些负面影响。

I have a few others listed here.

我在这里列出了其他一些。

Overnutrition.

营养过剩。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

So let's talk about that.

那么我们来谈谈这个吧。

So, in 20-- I don't remember what year it was.

所以，20年——我不记得那是哪一年了。

It was somewhat recent.

这是最近的事。

A study was published looking at NR with something called pterostilbene.

发表了一项研究，研究含有紫檀芪的 NR。

So pterostilbene is believed to be a sirtuin activator like resveratrol.

因此，紫檀芪被认为是像白藜芦醇一样的沉默调节蛋白激活剂。

So a commercially available product called Basis, and it was tested.

于是推出了一款名为Basis的市售产品，并对其进行了测试。

It was a three-arm study in humans.

这是一项针对人类的三臂研究。

Roughly 30 people per arm, so decent size study, right?

每只手臂大约有 30 个人，这样的研究规模相当不错，对吧？

This is a big study.

这是一项大研究。

So you take 100 people, more or less, with fatty liver disease.

因此，你选取了 100 名或多或少患有脂肪肝疾病的人。

Now, this was documented with an MRI of the liver.

现在，这已通过肝脏核磁共振成像记录下来。

So they're looking at hepatic fat in the liver by MR. And using this type of MRI, if your hepatic fat index is over 5%, that's a high enough degree of what's called steatosis that you have fatty liver disease.

所以他们正在通过 MR 来观察肝脏中的肝脂肪。使用这种类型的 MRI，如果您的肝脏脂肪指数超过 5%，则表明您患有脂肪肝疾病，即所谓的脂肪变性程度足够高。

Now, of course, this is not a digital thing.

当然，现在这不是数字化的事情。

It's an analog, right?

这是一个模拟，对吧？

There's a spectrum to this.

这是有一个范围的。

So, you start with just fat accumulating in the liver, but as more and more fat accumulates, you start to get inflammation that results in scarring and fibrosis, and ultimately, you would get to cirrhosis.

因此，一开始只有脂肪在肝脏中积累，但随着越来越多的脂肪积累，您开始出现炎症，导致疤痕和纤维化，最终，您会发展为肝硬化。

So just keep in the back of your mind, the threshold at which we would say you're in the danger zone is once you hit 5%.

因此，请记住，一旦达到 5%，我们就会说您处于危险区域。

So this study randomized people to either a placebo or a regular dose of this product or a double dose of the product.

因此，这项研究将人们随机分配到安慰剂或常规剂量的该产品或双倍剂量的该产品。

And I can't remember exactly how much is in the product.

我记不清产品里到底有多少了。

I think it's either 250 or 500.

我认为要么是250，要么是500。

So then that would be what the regular group got of NR, and then the other group was getting 2x that.

那么这就是常规组得到的 NR，然后另一组得到的是 2 倍。

So it's either 250 and 500 or 500 and 1,000.

所以要么是 250 和 500，要么是 500 和 1,000。

I don't recall.

我不记得了。

They looked at many things, right?

他们看了很多东西，对吗？

So they looked at all sorts of biomarkers.

因此他们研究了各种生物标志物。

And the primary outcome for this study was did you see a reduction of this hepatic fat via the MRI?

So what happened?

那么发生了什么？

So they did the study, and lo and behold, there was no difference.

于是他们进行了研究，结果发现并没有什么区别。

There was no difference in anything.

没有任何区别。

Okay, so at high dose, at low dose, there was no difference in how much hepatic fat you had at the end of the study.

好的，所以在高剂量和低剂量下，研究结束时你的肝脂肪量没有差异。

There was no difference in body weight, there was no difference in inflammatory markers, there was no difference in glycemic markers, glucose levels, liver function tests, any of those things.

体重没有差异，炎症标志物没有差异，血糖标志物、血糖水平、肝功能测试等等都没有差异。

So in that sense, it was a null study.

所以从这个意义上说，这是一项无效的研究。

But they did one sub-analysis, which again, you have to be very careful of, because a sub-analysis is not a primary outcome, but it's a way to go and parse the data.

但他们做了一个子分析，同样，你必须非常小心，因为子分析不是主要结果，但它是解析数据的一种方法。

And they did find one statistically significant finding, which was, if you limited the analysis to people who had a hepatic fat score below 27%.

他们确实发现了一项具有统计学意义的发现，那就是，如果将分析限制在肝脂肪评分低于 27% 的人身上。

Remember I said, once you're above 5%, you have fatty liver disease.

Well, they had people anywhere from 10% to 40%.

嗯，他们的人数从 10% 到 40% 不等。

Andrew Huberman:

安德鲁·休伯曼：

Wow.

哇。

Dr. Peter Attia:

彼得·阿蒂亚博士：

But if they looked at people who were below 27%, in the low-dose group, there was a statistically significant reduction in liver fat.

但如果他们观察低于 27% 的人，在低剂量组中，肝脏脂肪有统计学上显着的减少。

If it sounds like I'm machinating, I am.

如果这听起来像是我在搞阴谋，那我确实是在搞阴谋。

Let me say it again.

我再说一遍。

If you limited the analysis to people who had below 27% on this hepatic fat index, the people who got the full dose had no difference.

如果您将分析限制在肝脂肪指数低于 27% 的人群中，则服用全剂量的人群没有差异。

They averaged 20% at the beginning of the trial and 19% at the end, no statistically significant difference.

他们在试验开始时的平均率为 20%，试验结束时的平均率为 19%，没有统计学上的显着差异。

The placebo group averaged 20% at the beginning, 20% at the end.

安慰剂组开始时平均为 20%，结束时为 20%。

But the single dose of the drug went from 20% to 15%, which was statistically significant.

但该药物的单剂量从20%上升到15%，具有统计学意义。

It's not clear that that's clinically significant, which is a pretty consistent theme in this type of research.

目前尚不清楚这是否具有临床意义，但这是此类研究中非常一致的主题。

Never confuse statistical significance with clinical significance.

切勿将统计显着性与临床显着性混淆。

If your blood pressure is 160 over 100, and I give you a drug that lowers it to 157 over 97, that could be statistically significant if the variance is small enough between people in the study.

如果你的血压是 100 分之 160，我给你一种药物可以将血压降低到 97 分之 157，如果研究中的人之间的差异足够小，那么这可能具有统计显着性。

It has no clinical significance.

它没有临床意义。

I haven't changed the course of your life.

我没有改变你的人生轨迹。

So again, that to me is one of the two big findings that people point to, to say, "Aha, there was some benefit in fatty liver disease with this." But again, when you read the fine print, which I just vomited out to you, I don't think anybody is looking at that going, "Oh, we've just found the solution to NAFLD." The second study that people point to a lot was 2021 or 2022.

再说一次，对我来说，这是人们指出的两大发现之一，“啊哈，这对脂肪肝疾病有一些好处。”但同样，当你读到我刚刚吐给你的细则时，我认为没有人会看到这样的内容：“哦，我们刚刚找到了 NAFLD 的解决方案。”人们经常提到的第二个研究是 2021 年或 2022 年。

This came out of a group at Wash U, I believe, and they looked at NMN, and they looked at glucose disposal.

我相信这是来自华盛顿大学的一个小组，他们研究了 NMN，他们研究了葡萄糖处理。

So in this study, they asked the question, we're going to take two groups of people.

因此，在这项研究中，他们提出了这样的问题：我们将选取两组人。

You're going to get a placebo for a period of time, or you're going to get NMN for a period of time.

你会在一段时间内服用安慰剂，或者在一段时间内服用 NMN。

And we're going to then do what's called a type of glucose challenge-

然后我们要做一种所谓的葡萄糖挑战——

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm

嗯嗯

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

where we look at how well you dispose of glucose with and without insulin infusion.

我们会观察您在注射胰岛素和不注射胰岛素的情况下处理葡萄糖的情况。

And in the placebo group, you would look at pre- and post-placebo treatment, was there a difference in glucose disposal with no insulin?

在安慰剂组中，您会观察安慰剂治疗前和治疗后，与不使用胰岛素的情况下，葡萄糖处理是否存在差异？

No. What about with insulin, where you would expect to see much more glucose disposal?

No difference.

没有区别。

But when you did that with the NMN group, there was a statistically significant increase in glucose disposal with insulin infusion, but it was quite small.

但是，当您对 NMN 组进行此操作时，胰岛素输注后的葡萄糖消耗量在统计学上显着增加，但幅度很小。

In other words, it was clinically very insignificant.

And just to sort of figure out how insignificant it was, I went back and actually looked at some of the red light data.

为了弄清楚它有多么微不足道，我回去实际上查看了一些红灯数据。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Because there's an interesting study that shines red light on a person's back and then does an oral glucose tolerance test.

因为有一项有趣的研究，用红光照射人的背部，然后进行口服葡萄糖耐量测试。

Andrew Huberman:

安德鲁·休伯曼：

Oh, yeah.

哦，是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, and you can actually reduce postprandial glucose by 8%.

是的，您实际上可以将餐后血糖降低 8%。

Andrew Huberman:

安德鲁·休伯曼：

Is that meaningful?

这有意义吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Not really.

不是真的。

Not in this patient population, because these people were all pre-diabetic, and they had very high glucose.

不是在这个患者群体中，因为这些人都是糖尿病前期，而且他们的血糖非常高。

So it was another example of something that was statistically significant but not clinically significant.

所以这是另一个具有统计学意义但不具有临床意义的例子。

And the same thing was true in this study, right?

这项研究也是如此，对吧？

But again, people would probably point to these two studies because they're in humans, and you had this one, if you squint and look really hard and take a sub-sub-subset of the analysis on this one measurement, we saw a responsive hepatic fat going from 20 to 15%, which is still 3X above the threshold to have fatty liver disease.

但同样，人们可能会指出这两项研究，因为它们是在人类身上进行的，而你做了这项研究，如果你眯着眼睛仔细观察，并对这一项测量进行子子集分析，我们会看到反应性肝脂肪从 20% 上升到 15%，这仍然比患有脂肪肝疾病的阈值高出 3 倍。

And in this other study, you had this very modest increase in glucose disposal.

在另一项研究中，葡萄糖的消耗量略有增加。

But there's a saying in my mind, Andrew, which is, if you have to resort to really interesting statistical machinations to see something, there probably isn't something very interesting there.

但安德鲁，我心里有一句话，那就是，如果你必须借助非常有趣的统计机制才能看到某些东西，那么那里可能没有什么非常有趣的东西。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

I totally agree.

我完全同意。

And I think, at this point, I'm questioning whether or not I'm wasting my money taking NMN or NR.

我想，在这一点上，我正在质疑我是否在浪费钱购买 NMN 或 NR。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Well, let me tell you one positive thing about this.

好吧，让我告诉你一件积极的事情。

Andrew Huberman:

安德鲁·休伯曼：

The reason I take NR is really for these anti-inflammation reported purported effects.

我服用 NR 的原因实际上是因为这些报道中声称的抗炎作用。

I just want to pay a little bit of attention to the whole commercial battle around this, because I think it's relevant.

我只是想稍微关注一下围绕此展开的整个商业斗争，因为我认为这是相关的。

I think right now, as far as I know, the FDA has essentially said that NMN should not be sold as a supplement, but it is still being sold as a supplement.

我认为目前，据我所知，FDA 基本上已经表示 NMN 不应该作为补充剂出售，但它仍然作为补充剂出售。

So there's a little bit of ignoring of the FDA's request.

因此，FDA 的要求有点被忽视了。

NR, as far as I know, is authorized for sale as a supplement.

据我所知，NR 被授权作为补充剂销售。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

So it's generally regarded as safe.

所以一般认为它是安全的。

It has an FDA designation of GRAS, which means it is not regulated.

它具有 FDA 指定的 GRAS，这意味着它不受监管。

Andrew Huberman:

安德鲁·休伯曼：

Generally recognized as safe.

一般认为是安全的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Right.

对。

And so that means anybody can sell it.

这意味着任何人都可以出售它。

The FDA will have no oversight.

FDA 不会进行任何监督。

They're not going to put a stamp on it that says what they're selling is what it is.

And you can't make a claim about it that isn't validated by some sort of study.

So honestly, Andrew, I think the whole NMN, NR debate is irrelevant.

老实说，Andrew，我认为整个 NMN、NR 争论是无关紧要的。

Andrew Huberman:

安德鲁·休伯曼：

Hmm.

嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

I think it's just a commercial debate.

我认为这只是一场商业辩论。

I think it's literally just posturing about how can I carve out a different market.

我认为这实际上只是在摆出姿态，告诉我如何开拓一个不同的市场。

I don't think there's a scientific reason to favor one over the other.

我认为没有科学理由可以偏袒其中一种。

Andrew Huberman:

安德鲁·休伯曼：

Well, you just answered the question I was going to ask, but I suppose the question therefore becomes, is there any benefit to taking either of them-

好吧，你刚刚回答了我要问的问题，但我想问题就变成了，采取其中任何一个有什么好处吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Okay.

好的。

So-

所以——

Andrew Huberman:

安德鲁·休伯曼：

...

for sake of lifespan and/or healthspan?

为了寿命和/或健康？

Dr. Peter Attia:

彼得·阿蒂亚博士：

There's one benefit I could find.

我能找到一个好处。

There's one benefit I could find that I think is genuine.

我发现有一个我认为是真实的好处。

There are a few other really insignificant ones that fall into the category of goofy studies that cherry-pick by data mining.

还有一些其他真正无关紧要的研究属于通过数据挖掘挑选出来的愚蠢研究的范畴。

Okay, so there's studies that gave people NMN and looked at a shotgun approach of many different things, like did it change LDL cholesterol, HDL cholesterol, triglycerides?

好的，有一些研究给人们提供了 NMN，并观察了许多不同事物的鸟枪法，比如它是否改变了 LDL 胆固醇、HDL 胆固醇、甘油三酯？

And the answer is, oh, look, there's a small decrease, but it was totally insignificant clinically, even if statistically significant.

答案是，哦，看，有小幅下降，但在临床上完全不显着，即使在统计上显着。

And oh, it increased your six-minute walking test or whatever, and it's like a six-minute walk test or whatever in people who are in their 20s is irrelevant.

哦，它增加了你的六分钟步行测试或其他什么，这就像六分钟步行测试或其他对 20 多岁的人来说是无关紧要的。

It had no change in VO2 max.

最大摄氧量没有变化。

It had no change in any meaningful metric of performance.

One test, one study I could find that actually had what looked like a signal to me, and it was a study that looked at skin cancer rates with-- and I can't remember if it was NR or NMN, but honestly, I don't think it matters because I think they're basically equivalent.

我发现一项测试、一项研究实际上对我来说似乎是一个信号，这是一项研究皮肤癌发病率的研究——我不记得它是 NR 还是 NMN，但说实话，我认为这并不重要，因为我认为它们基本上是相同的。

Andrew Huberman:

安德鲁·休伯曼：

It's just got a phosphate group on there.

它只是上面有一个磷酸基团。

You might need to take a little bit more of the NMN versus NR, or maybe a lot more, who knows, in order to get the same increase in NAD, is my understanding.

与 NR 相比，你可能需要多服用一点 NMN，或者可能更多，谁知道呢，为了获得同样的 NAD 增加，这是我的理解。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So this one study found somewhere between a 60 and 80% reduction in basal cell and squamous cell carcinomas.

Now, it found no difference in melanomas.

现在，它发现黑色素瘤没有差异。

So again, you know this because you just did a podcast on this.

再说一次，你知道这一点是因为你刚刚就此做了一个播客。

Melanoma is the skin cancer that kills you, but that's not to say that squamous cell and basal cell carcinomas aren't problematic.

黑色素瘤是一种致命的皮肤癌，但这并不是说鳞状细胞癌和基底细胞癌没有问题。

They can be very deforming.

它们可能会变形。

They can require pretty aggressive surgeries to address them.

And so if indeed there is something that can reduce the risk of basal and squamous cell carcinomas, that may be a rationale for taking it.

因此，如果确实有某种东西可以降低基底细胞癌和鳞状细胞癌的风险，那么这可能是服用它的理由。

Andrew Huberman:

安德鲁·休伯曼：

And I should say that basal and squamous cell carcinomas are very, very common.

我应该说基底细胞癌和鳞状细胞癌非常非常常见。

Dr. Peter Attia:

彼得·阿蒂亚博士：

They are very common, and they are very clearly associated with sun exposure in a way that even melanoma is more complicated and has a genetic component, and there are other things going on.

它们非常常见，而且与阳光照射密切相关，甚至黑色素瘤也更复杂，具有遗传成分，而且还有其他因素在发生。

But squamous and basal cell carcinoma are very clearly related to sun exposure.

但鳞状细胞癌和基底细胞癌与阳光照射密切相关。

As you said, they're quite common.

正如你所说，它们很常见。

And so personally, that's an experiment I would like to see repeated, because if indeed NR and/or NMN reduce the risk that significantly of squamous cell and basal cell carcinomas, I think you could make a case that if you're an individual who's at risk for those things, clearly I'm not, right?

就我个人而言，这是一个我希望看到重复的实验，因为如果 NR 和/或 NMN 确实能显着降低鳞状细胞癌和基底细胞癌的风险，我认为你可以证明，如果你是一个有这些风险的人，显然我不是，对吧？

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

I've never had a sunburn in my life.

我一生中从未被晒伤过。

I don't work outside, so it wouldn't matter to me, but there are a lot of people for whom either their skin color makes them more susceptible or their pastimes or frankly, their line of work makes them more susceptible.

我不在外面工作，所以这对我来说并不重要，但对很多人来说，要么他们的肤色让他们更容易受到影响，要么他们的消遣或者坦率地说，他们的工作让他们更容易受到影响。

Maybe there is a case to be made for it there.

也许这是有道理的。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

If you could literally take 60 to 80% of your risk away on squamous or basal cell carcinoma, that could matter.

And by the way, I don't know if this is true, but you may recall at the outset, I said that when you look at all the tissues in the body where we see a reduction in NAD, do you remember what had the biggest reduction?

顺便说一句，我不知道这是否属实，但你可能还记得一开始，我说过，当你观察体内 NAD 减少的所有组织时，你还记得什么组织减少幅度最大吗？

It was skin.

那是皮肤。

So there's a part of me that wonders, is the reason that the only place we see a really good signal potentially for NR and NMN supplementation is in a skin cancer?

所以我心里有一部分想知道，我们唯一看到 NR 和 NMN 补充剂潜在良好信号的地方是皮肤癌吗？

Andrew Huberman:

安德鲁·休伯曼：

Mm.

嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Although it's not melanoma, which is the one we'd really want to see.

If this reduced the risk of melanoma, I would take it, right?

如果这可以降低患黑色素瘤的风险，我会服用它，对吧？

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Because even though I'm dark-skinned, I'm still susceptible to melanoma.

因为即使我皮肤黝黑，我仍然容易患黑色素瘤。

So I just wonder, that could be true, true, and unrelated, but that's the first thought that crossed my mind when I came across that literature was, hmm, I wonder if the enormous reduction in tissue NAD in this particular tissue explains why maybe there is a benefit to it.

所以我只是想知道，这可能是真的，真的，而且无关，但当我看到那些文献时，我脑海中闪过的第一个想法是，嗯，我想知道这种特定组织中组织 NAD 的大幅减少是否解释了为什么它可能有好处。

Andrew Huberman:

安德鲁·休伯曼：

Assuming somebody is averse to feeling like they have an elephant stepping on their chest and they're going to pay $750 for it, AKA an NAD infusion once a week.

假设有人不喜欢大象踩在胸口的感觉，他们愿意为此支付 750 美元，也就是每周一次的 NAD 注射。

And look, people may opt to do that.

看，人们可能会选择这样做。

People with a disposable income could do that, drip it in slower, not feel nauseous, increase NAD with the hope, hope, hope that maybe it's going to extend your life.

有可支配收入的人可以做到这一点，慢慢地滴进去，不会感到恶心，带着希望、希望、希望也许它会延长你的生命，增加NAD。

Most people considering supplementation to augment the NAD pathway are going to default to either taking NR or taking NMN.

Dr. Peter Attia:

彼得·阿蒂亚博士：

By the way, just going back to the group that have decided that $1,000 for an NAD infusion and dripping it in over two hours is a good use of their time, what do you think would be the improvement in their lifespan if they spent that two hours exercising?

顺便说一句，回到那些决定花 1,000 美元注射 NAD 并在两个多小时内滴注的小组，他们的时间得到了很好的利用，你认为如果他们花这两个小时锻炼的话，他们的寿命会得到怎样的改善？

Andrew Huberman:

安德鲁·休伯曼：

Significantly greater.

Dr. Peter Attia:

彼得·阿蒂亚博士：

Interesting.

有趣。

All right.

好的。

Just noted.

And less expensive, but yeah.

而且更便宜，但是是的。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

You could also weight train for the first hour and then enjoy some food afterwards.

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

Layne Norton taught me that there are data showing that exercise, in particular, resistance training, improves the rewarding properties of food, makes food taste better, which we've all kind of intuitively experienced.

莱恩·诺顿告诉我，有数据表明，运动，特别是阻力训练，可以提高食物的有益性，使食物味道更好，我们都直观地体验到了这一点。

So you spend the first hour working out-

所以你第一个小时就用来锻炼——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah

是啊

Andrew Huberman:

安德鲁·休伯曼：

...

second hour eating.

第二个小时吃饭。

Dr. Peter Attia:

彼得·阿蒂亚博士：

If you had an extra two hours a week-

如果你每周多出两个小时——

Andrew Huberman:

安德鲁·休伯曼：

Right

右

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

to choose between paying 1,000 bucks or 700 bucks for an NAD infusion or lift weights for an hour, go for a half an hour walk, and listen to your favorite podcast, like the Huberman Lab, and then eat a meal for a half an hour.

选择支付 1,000 美元还是 700 美元进行 NAD 输液或举重一小时，步行半小时，听你最喜欢的播客，例如 Huberman Lab，然后花半小时吃一顿饭。

I can just think of so many better ways to spend time and money.

我能想到很多更好的方式来花费时间和金钱。

But anyway, let's move on.

但无论如何，让我们继续前进。

Not digress.

不是离题。

Andrew Huberman:

安德鲁·休伯曼：

Okay.

好的。

Well, I'm going to pull a little bit from marketing text here, but I trust these.

Showing-

显示-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Really?

真的吗？

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Okay.

好的。

Andrew Huberman:

安德鲁·休伯曼：

Yeah, I do, because they have citations to support them, and we can include the citations.

Dr. Peter Attia:

彼得·阿蒂亚博士：

Okay.

好的。

Andrew Huberman:

安德鲁·休伯曼：

I'm not going to say these are not linchpin arguments for doing one thing or the other, but we already established that NR and NMN are quite similar, except for the presence of a phosphate group on NR that gets cleaved off.

我不会说这些不是做某件事或另一件事的关键论据，但我们已经确定 NR 和 NMN 非常相似，除了 NR 上存在被裂解的磷酸基团之外。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So again, you might have a slight dose issue, but at the end of the day, you're giving NR.

NR is freely taken up into cells.

NR 可以自由地被细胞吸收。

It turns into NAD.

它变成NAD。

So this is all a big sort of shell game of how do you get NAD up.

And again, I think we've established, and we can agree that there is an increase in NAD, at least in the blood and probably in the liver, when you take exogenous NAD or a precursor.

再说一遍，我认为我们已经确定并且我们可以同意，当您服用外源性 NAD 或前体时，NAD 会增加，至少在血液中，可能在肝脏中。

Let's pause at that.

让我们暂停一下。

Andrew Huberman:

安德鲁·休伯曼：

Or NR.

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

That's what I mean-

Andrew Huberman:

安德鲁·休伯曼：

Yeah

是啊

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

a precursor.

一个先驱。

Andrew Huberman:

安德鲁·休伯曼：

Yeah, okay.

是啊，好吧。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So.

所以。

Andrew Huberman:

安德鲁·休伯曼：

Great.

太棒了。

Well, then you took the words right out of the-

好吧，那么你就直接从——

Dr. Peter Attia:

彼得·阿蒂亚博士：

That's right

没错

Andrew Huberman:

安德鲁·休伯曼：

...

data I was going to refer to.

我要参考的数据。

Dr. Peter Attia:

彼得·阿蒂亚博士：

That's right.

没错。

Andrew Huberman:

安德鲁·休伯曼：

Because I asked a few folks that helped develop some of the NR supplements, what are the data-

因为我问了一些帮助开发一些 NR 补充剂的人，他们的数据是什么——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep

是的

Andrew Huberman:

安德鲁·休伯曼：

...

that support the use of NR for increasing NAD?

支持使用 NR 来增加 NAD？

Dr. Peter Attia:

彼得·阿蒂亚博士：

And I-

而我——

Andrew Huberman:

安德鲁·休伯曼：

And they say, "NR can cross the cell membrane directly-

他们说，“NR 可以直接穿过细胞膜——

Dr. Peter Attia:

彼得·阿蒂亚博士：

That's right

没错

Andrew Huberman:

安德鲁·休伯曼：

...

NMN cannot." Okay, but-

NMN 不能。” Okay, but-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep.

是的。

Doesn't matter

没关系

Andrew Huberman:

安德鲁·休伯曼：

...

you can just cleave the phosphate group.

你可以只裂解磷酸基团。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Because NMN-

Andrew Huberman:

安德鲁·休伯曼：

Yeah, right.

是的，对。

Exactly.

确切地。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

NR, this is not my claim, but they claim that NR is "25% more effective than NMN in raising whole blood NAD levels." But I'm guessing that's-

NR，这不是我的主张，但他们声称 NR“在提高全血 NAD 水平方面比 NMN 有效 25%”。 But I'm guessing that's-

Dr. Peter Attia:

彼得·阿蒂亚博士：

That's probably dose to dose

这可能是剂量对剂量

Andrew Huberman:

安德鲁·休伯曼：

...

milligram to milligram.

Dr. Peter Attia:

彼得·阿蒂亚博士：

Exactly.

正是如此。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

Okay.

好的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

So then you just adjust the milligram dosage a little bit, and so on.

What's entirely unclear is what raising blood NAD translates to in terms of getting more NAD into cells.

完全不清楚的是，提高血液中的 NAD 会导致更多的 NAD 进入细胞。

I don't know that that's really-

我不知道那真的是——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Specifically cells like skeletal muscles, right?

特别是像骨骼肌这样的细胞，对吗？

I think based on Josh Rabinowitz's work, and I also had Josh Rabinowitz on the podcast to talk about this, and I trust Josh on this much more than I would trust any marketing material-

我认为基于乔什·拉宾诺维茨 (Josh Rabinowitz) 的工作，我还在播客上邀请了乔什·拉宾诺维茨 (Josh Rabinowitz) 来谈论这一点，我在这方面对乔什 (Josh Rabinowitz) 的信任远胜于对任何营销材料的信任——

Andrew Huberman:

安德鲁·休伯曼：

Sure

当然可以

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

because he doesn't have a dog in this fight, right?

He just does the work.

And, what Josh's research showed, which is basically NAD flux research, has demonstrated that, look, the liver is probably the place of greatest uptake-

而且，乔什的研究表明，基本上是 NAD 通量研究，已经证明，看，肝脏可能是吸收最多的地方 -

Andrew Huberman:

安德鲁·休伯曼：

毫米

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

in addition to blood, and that's about all we know.

除了血液之外，这就是我们所知道的一切。

It's not clear how much of this is getting into other cells.

目前尚不清楚其中有多少进入了其他细胞。

So, the rest of it is just I think rearranging deckchairs on a Titanic as far as how much does it really matter.

所以，剩下的只是我认为重新安排泰坦尼克号上的躺椅到底有多重要。

And again, I don't even think it's worth arguing about whether NMN or NR is more bioavailable because, to your point, you can sort of adjust the dose, and I trust that whatever you're taking, NR or NMN, you are getting some NR into the cells, and that's being converted to NAD.

再说一次，我什至不认为值得争论 NMN 还是 NR 是否更具生物利用度，因为就你的观点而言，你可以调整剂量，而且我相信无论你服用 NR 还是 NMN，你都会将一些 NR 进入细胞，然后转化为 NAD。

But we still keep coming back to the jugular question: does that matter?

Does increasing intracellular NAD matter when the system is so tightly regulated?

当系统受到如此严格的监管时，增加细胞内 NAD 是否重要？

So I think what you see is a lot of marketing material that tries to make the case that you can do it.

Great.

伟大的。

I'll grant you that you can do it.

我保证你能做到。

Does it matter?

有关系吗？

Does it matter in lifespan?

对寿命有影响吗？

The answer appears to be unambiguously no at this point.

Does it matter in health span?

这对健康寿命重要吗？

I think that's what we're discussing.

我想这就是我们正在讨论的内容。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

There's something so sticky about the longevity field, just so sticky about this idea that one could take something and extend lifespan, and people don't want to be in the control group, so they're willing to invest significant amounts of money to do it.

长寿领域有一些非常粘性的东西，这种想法非常粘性，人们可以服用某些东西来延长寿命，而人们不想成为对照组，因此他们愿意投入大量资金来做到这一点。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Well, I think the bigger issue is you can't do the longevity experiment in humans, and I'm sure that these companies that sell this, and honestly, I don't follow this space.

好吧，我认为更大的问题是你不能在人类身上进行长寿实验，而且我确信这些出售此产品的公司，老实说，我不关注这个领域。

I don't know how many of these companies there are out there.

I can name two because five years ago, which was the last time I really dug into this, I knew who the two dominant players were.

For all I know, there could be 20 companies today that are selling NR and NMN.

I don't know any of them.

我一个都不认识。

Andrew Huberman:

安德鲁·休伯曼：

There were probably about 30 to 50 prior to this FDA ruling-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Okay

好的

Andrew Huberman:

安德鲁·休伯曼：

...

which is kind of an interesting situation in its own right.

这本身就是一个有趣的情况。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

What happened there was the supplement NMN, suddenly the FDA decided that it should not be sold over the counter anymore because there was a clinical trial initiated on NMN, which essentially makes NMN a drug for clinical testing and thereby can't be classified as a supplement any longer.

发生的事情是补充剂NMN，突然FDA决定不再在柜台销售，因为NMN已经启动了临床试验，这本质上使NMN成为临床试验药物，从而不再被归类为补充剂。

That was the rationale as I understood it.

这就是我所理解的理由。

But as with things like N-acetylcysteine-

但就像 N-乙酰半胱氨酸这样的东西一样——

Dr. Peter Attia:

彼得·阿蒂亚博士：

That was more of a lobbying effort, though-

不过，这更多的是一种游说努力——

Andrew Huberman:

安德鲁·休伯曼：

Right

右

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

I think.

我想。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

Dr. Peter Attia:

彼得·阿蒂亚博士：

I don't think actually that was a scientific decision.

I think that was more of a lobbying decision-

我认为这更多的是一个游说决定——

Andrew Huberman:

安德鲁·休伯曼：

Right

右

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

from an IP protection standpoint.

从IP保护的角度来看。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

And this had happened prior for N-acetylcysteine-

N-乙酰半胱氨酸之前就发生过这种情况-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep

是的

Andrew Huberman:

安德鲁·休伯曼：

...

NAC, which some people take.

NAC，有些人服用。

It's a mucolytic.

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep.

是的。

Andrew Huberman:

安德鲁·休伯曼：

It's actually a great decongestant-

它实际上是一种很好的减充血剂——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep

是的

Andrew Huberman:

安德鲁·休伯曼：

...

if you're congested, and it increases glutathione.

That's my understanding.

这是我的理解。

And I believe, somebody check me on this-

我相信，有人会检查我的情况-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Does it decrease or increase glutathione?

它会减少还是增加谷胱甘肽？

Andrew Huberman:

安德鲁·休伯曼：

Increases glutathione-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah

是啊

Andrew Huberman:

安德鲁·休伯曼：

...

is my understanding.

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

If I have that wrong, someone will tell me quickly in the comments.

My understanding is that in Europe, NAC might even be available by prescription.

In the US, you can still buy it over the counter, but a few years back, the FDA said, "Nope, can't sell NAC any longer," and there was a pushback lobby-

在美国，你仍然可以在柜台购买它，但几年前，FDA 表示，“不，不能再销售 NAC”，并且存在一个阻力游说团体 -

Dr. Peter Attia:

彼得·阿蒂亚博士：

毫米

Andrew Huberman:

安德鲁·休伯曼：

...

to keep it on the market, and you can still buy it on Amazon.

使其留在市场上，并且您仍然可以在亚马逊上购买。

The same thing has more or less happened with NMN, and certainly with NR, although NR was never in question in terms of whether or not it should be sold as a supplement or not, because as far as I know, there's no clinical trial on NR, at least not currently.

同样的事情或多或少地发生在 NMN 上，当然还有 NR 上，尽管 NR 从来没有被质疑是否应该作为补充剂出售，因为据我所知，还没有针对 NR 的临床试验，至少目前还没有。

So there's a clinical trial on NMN, which classifies it as an experimental drug, and therefore the FDA said, "Nope, you can't sell it as a supplement." A few companies, major companies, pulled NMN from the market in the US.

因此，有一项针对 NMN 的临床试验，将其归类为实验药物，因此 FDA 说：“不，你不能将其作为补充剂出售。”一些公司，大公司，将 NMN 从美国市场撤下。

Many smaller companies Just kind of watched and waited and continued to sell it, and I checked prior to the beginning of this episode, and you can still buy it online.

许多小公司只是观看、等待并继续出售它，我在本集开始之前检查过，你仍然可以在网上购买。

But of course, a lot of what we're saying today is kind of a why would you?

We're not really coming up with strong arguments for taking NMN, at least not in today's discussion.

我们并没有真正提出服用 NMN 的有力论据，至少在今天的讨论中是这样。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Again, I think the strongest argument I could make based on the data would be potentially on the basal cell and squamous cell carcinoma risk reduction, if indeed those results are reproducible.

再次，我认为根据数据我可以提出的最有力的论点可能是基底细胞癌和鳞状细胞癌风险的降低，如果这些结果确实是可重复的。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Again, that would be justification, again, for the right individual.

Wouldn't be a justification for me, might be a justification for somebody.

这不会成为我的理由，可能会成为某人的理由。

But really the rest of it is, why do you need to do experiments on this if you're selling a supplement when you don't need to make claims to sell a supplement?

但实际上剩下的问题是，如果您销售补充剂而无需声称出售补充剂，为什么还需要对此进行实验呢？

If it's a drug, you have to have an indication.

如果是药物，就必须有适应症。

You can't sell a drug without rigorous trials that demonstrate both safety and efficacy.

如果没有经过严格的试验来证明安全性和有效性，就无法销售药物。

I do think NR and NMN are probably safe.

我确实认为 NR 和 NMN 可能是安全的。

There has been some-

已经有一些——

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm

嗯嗯

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

voice around the idea that NR could increase the risk of cancer.

人们普遍认为 NR 可能会增加患癌症的风险。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

And the experts in this area, like Charles Brenner, have pushed back hard on that.

而查尔斯·布伦纳 (Charles Brenner) 等该领域的专家则强烈反对这一观点。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm-hmm.

嗯嗯。

Andrew Huberman:

安德鲁·休伯曼：

Arguing that the studies were not done well, as I recall.

我记得，我认为这些研究做得不好。

Dr. Peter Attia:

彼得·阿蒂亚博士：

I think that's probably fair.

我认为这可能是公平的。

I don't think there's been a well-done study in this entire field is part of the problem, right?

我不认为整个领域的出色研究是问题的一部分，对吧？

And that's probably too harsh a statement, but this is not a field that's necessarily lending itself to the rigor that you would in pharmacotherapy.

这可能是一个过于严厉的说法，但这并不是一个必然需要像药物治疗那样严格的领域。

And you mentioned Charles Brenner, I think Charles does good work.

你提到了查尔斯·布伦纳，我认为查尔斯做得很好。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Right?

对吗？

Andrew Huberman:

安德鲁·休伯曼：

And he works on many things, not just this.

他从事很多事情，而不仅仅是这个。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

And by the way, I don't hear Charles out there saying that NR increases lifespan.

顺便说一句，我没有听到 Charles 说 NR 可以延长寿命。

Andrew Huberman:

安德鲁·休伯曼：

No. In fact, I don't want to quote him at all, but I think he would argue that sirtuins, NR, NMN should not logically or practically be linked to efforts to extend lifespan, but that there are some interesting positive effects of augmenting NR as a means to increase NAD for sake of anti-inflammation and some of these other effects that we've been discussing.

不。事实上，我根本不想引用他的话，但我认为他会争辩说，sirtuins、NR、NMN 在逻辑上或实际上不应该与延长寿命的努力联系在一起，但为了抗炎和我们一直在讨论的一些其他影响，增强 NR 作为增加 NAD 的一种手段会产生一些有趣的积极作用。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, that's my understanding of his position as well, is that I think he firmly agrees with what I laid down at the outset of this, which is there is no meaningful, logical connection between the relationship of sirtuins, caloric restriction, and NR.

是的，这也是我对他立场的理解，我认为他坚决同意我一开始就设定的观点，即去乙酰化酶、热量限制和 NR 之间没有有意义的逻辑联系。

That's a shell game that is empty.

那是一场空洞的骗局。

And you're right.

你是对的。

Part of the reason why I think there's much better research going on with rapamycin is that there's really no commercial interest in rapamycin.

我认为雷帕霉素正在进行更好的研究，部分原因是雷帕霉素确实没有商业利益。

Nobody's going to make money selling rapamycin.

没有人会靠销售雷帕霉素赚钱。

Andrew Huberman:

安德鲁·休伯曼：

Because it's so cheap?

因为这么便宜？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Well, yeah, and it's actually not cheap, but it's a drug that is off patent.

嗯，是的，它实际上并不便宜，但它是一种专利到期的药物。

Andrew Huberman:

安德鲁·休伯曼：

Oh, okay.

哦，好吧。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So this is a drug that was approved by the FDA 25 years ago.

所以这是25年前FDA批准的药物。

Andrew Huberman:

安德鲁·休伯曼：

So generic forms are inexpensive enough that no big-

因此，通用形式足够便宜，无需大

Dr. Peter Attia:

彼得·阿蒂亚博士：

Believe it or not, they're not.

不管你信不信，他们不是。

This is the irony of it.

这就是它的讽刺之处。

So Rapamune is the brand drug that was initially approved in 1999, and today, if you go and buy rapamycin, you're going to not buy Rapamune, you're going to probably buy generic sirolimus or rapamycin, and yet it's surprisingly quite expensive.

所以雷帕鸣是 1999 年最初批准的品牌药物，今天，如果你去购买雷帕霉素，你不会购买雷帕鸣，你可能会购买仿制药西罗莫司或雷帕霉素，但它的价格却出人意料地相当昂贵。

Now, it's not enormously expensive because you're not taking much of it, but it's about five bucks a milligram.

现在，它并不是非常昂贵，因为你服用的量并不多，但每毫克大约五美元。

That's pretty expensive.

那是相当昂贵的。

So if you're taking eight milligrams a week, that's 40 bucks a week-

所以如果你每周服用 8 毫克，那就是每周 40 美元 -

Andrew Huberman:

安德鲁·休伯曼：

Yeah

是啊

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

is probably what I spend on rapamycin.

可能是我花在雷帕霉素上的钱。

That ain't cheap.

那可不便宜。

Andrew Huberman:

安德鲁·休伯曼：

No.

不。

Dr. Peter Attia:

彼得·阿蒂亚博士：

I mean, it's cheaper than some things I take, but it's not cheap.

我的意思是，它比我拿的一些东西便宜，但也不便宜。

But the point is nobody has a commercial interest in rapamycin, right?

但关键是没有人对雷帕霉素有商业利益，对吧？

It's sort of an irrelevant drug.

这是一种无关紧要的药物。

But the interest is scientific, right?

但兴趣是科学的，对吗？

And the commercial interest is in what we call rapalogs, which are analogs of rapamycin that are being investigated by a number of companies to look at new indications.

商业利益在于我们所说的雷帕霉素类似物，它们是雷帕霉素的类似物，许多公司正在研究它们以寻找新的适应症。

For example, immunity, immune function, right?

比如免疫力，免疫功能吧？

So rapamycin historically is thought of as an immune suppressant because that's the context in which it was approved for patients undergoing organ transplantation.

因此，雷帕霉素历史上被认为是一种免疫抑制剂，因为这是它被批准用于接受器官移植的患者的背景。

But I think Joan Mannick and Lloyd Clickstein, when they published that paper in 2014 using everolimus, where they took a group of 65-year-olds and randomized them to either a placebo or different doses and dosing schedules of everolimus, found an enhanced immunity in response to an influenza vaccine.

但我认为，当 Joan Mannick 和 Lloyd Clickstein 在 2014 年使用依维莫司发表那篇论文时，他们将一组 65 岁的人随机分配到安慰剂组或不同剂量和给药方案的依维莫司组，发现流感疫苗的免疫力增强。

Which again, for me, that was the turning point, right?

对我来说，这又是一个转折点，对吧？

That's when rapamycin went from something that was interesting based on the first ITP in 2009 to maybe we should be taking this in 2014.

就在那时，雷帕霉素从 2009 年第一个 ITP 中令人感兴趣的东西变成了也许我们应该在 2014 年使用它。

So between 2009 and 2014, I was kind of looking at the curiosity of rapamycin and saying, "Well, cool that it worked in mice.

所以在 2009 年到 2014 年间，我对雷帕霉素感到好奇，然后说：“嗯，它对小鼠有效，这很酷。

I don't think humans should ever consider this."

我认为人类不应该考虑这一点。”

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

To that study, which was like, "Wait a minute, something's different." If you take rapamycin as a human, at least, every day, it seems to suppress your immune system.

对于这项研究来说，“等一下，有些东西不一样了。”如果您作为人类至少每天服用雷帕霉素，它似乎会抑制您的免疫系统。

But if you just pulse it once a week, as they did in that study, it seems to improve immune function.

但如果你每周脉冲一次，就像他们在该研究中所做的那样，似乎可以改善免疫功能。

Which, again, means it's an immune modulator.

这再次意味着它是一种免疫调节剂。

It can go up or down on the immune system.

它对免疫系统的影响可能会上升或下降。

That was really the hypothesis that emerged from that experiment.

这确实是从那个实验中得出的假设。

And so now the question is, could you design drugs that are more specific to mTOR complex 1, which rapamycin is not, but you can get around that by dosing it intermittently.

所以现在的问题是，你能否设计出对 mTOR 复合物 1 更特异的药物（雷帕霉素不是），但你可以通过间歇性给药来解决这个问题。

And then, of course, is it a drug that has efficacy in terms of other things that can be tested in humans that are not longevity?

当然，它是否是一种药物，在可以在人类身上测试的其他非长寿方面具有功效？

Because you can't test lifespan in humans, obviously.

显然，因为你无法测试人类的寿命。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

You're 50, right?

你50岁了，对吧？

50 years old?

50岁？

Dr. Peter Attia:

彼得·阿蒂亚博士：

51.

Andrew Huberman:

安德鲁·休伯曼：

You seem to be vigorous.

看来你精力充沛。

You take great care of yourself.

你照顾好自己。

How much do you think taking rapamycin, for how many years have you been taking it?

您认为雷帕霉素的服用量是多少？您服用雷帕霉素已有多少年了？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Six.

六。

Andrew Huberman:

安德鲁·休伯曼：

Has contributed to your current state or vigor?

对你现在的状态或者活力有贡献吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Zero idea.

零想法。

Andrew Huberman:

安德鲁·休伯曼：

This is my opportunity to ask about your belief or lack of belief in biological aging tests.

这是我询问您对生物衰老测试的信念或不信念的机会。

Because if somebody's going to experiment with any or all of these things, they may want to evaluate whether or not their biological age is changing.

因为如果有人要尝试任何或所有这些东西，他们可能想评估他们的生物年龄是否正在改变。

And there are a number of these tests available.

并且有许多此类测试可供使用。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm-hmm.

嗯嗯。

Andrew Huberman:

安德鲁·休伯曼：

And people love this stuff.

人们喜欢这个东西。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Love them.

爱他们。

Andrew Huberman:

安德鲁·休伯曼：

They love them.

他们爱他们。

Who wouldn't want to see that they are 51 years old, but their biological age is 37?

谁不想看到自己已经51岁了，而生理年龄却是37岁呢？

Dr. Peter Attia:

彼得·阿蒂亚博士：

I just did a movement test the other day.

我前几天刚做了运动测试。

So it's a very fancy camera system where it's got a million cameras on you, and you go through this whole exercise.

所以这是一个非常奇特的摄像系统，有一百万个摄像头对着你，你可以完成整个练习。

How high can you jump?

你能跳多高？

How far can you throw?

你能扔多远？

It was awesome.

太棒了。

And then it gives you a movement age.

然后它会给你一个运动年龄。

Andrew Huberman:

安德鲁·休伯曼：

Hmm.

嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Andrew, I was 22.

安德鲁，我 22 岁。

Andrew Huberman:

安德鲁·休伯曼：

I believe it.

我相信。

Dr. Peter Attia:

彼得·阿蒂亚博士：

I should feel amazing.

我应该感觉很奇妙。

Do you actually think I move like a 22-year-old?

你真的认为我的动作像22岁的人吗？

Are you freaking kidding me?

你他妈是在开玩笑吗？

Andrew Huberman:

安德鲁·休伯曼：

No, you look-

不，你看——

Dr. Peter Attia:

彼得·阿蒂亚博士：

I bet you if I went and did that again tomorrow, I'd come back at 31 or something.

我敢打赌，如果我明天再去这样做，我会在 31 点左右回来。

There is so much nonsense in this type of testing.

这种类型的测试有很多废话。

Look, there's probably something to be said if I do that and I come out at 22 as I did versus 92.

听着，如果我这么做了，并且我的成绩是 22 分，而我的成绩是 92 分，那么可能会有一些话要说。

Andrew Huberman:

安德鲁·休伯曼：

Sure.

当然。

Dr. Peter Attia:

彼得·阿蒂亚博士：

I would grant you that if you took 150 year olds and you put them through a movement test, the ones that really, really are struggling will come out older, and the ones that really, really are doing great are going to come out younger.

我同意，如果你对 150 岁的人进行运动测试，那些真正处于挣扎状态的人会变得更老，而那些真正表现出色的人会变得更年轻。

So great.

太棒了。

I guess I move reasonably well for a 51-year-old.

我想对于一个 51 岁的人来说我的动作还算不错。

But it's simply impossible to believe that I can do today what I could do when I was 22 with respect to movement and strength and power, which is what that was assessing.

但根本无法相信，在运动、力量和爆发力方面，我今天能做到 22 岁时能做到的事情，这正是评估的内容。

You're doing a lot of jumping, single leg jump here, do all this kind of stuff, balance testing, all sorts of things.

你在这里做了很多跳跃，单腿跳跃，做所有这些事情，平衡测试，各种各样的事情。

And I guess I would say the gold standard for any of these biologic aging tests has to be the following.

我想我会说任何这些生物老化测试的黄金标准必须如下。

What is a better predictor of remaining years of life, chronologic age or biologic age?

剩余寿命、实际年龄或生物学年龄哪个更好的预测指标？

That's, to me, the most important standard.

对我来说，这是最重要的标准。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So how old are you chronologically?

那么按时间顺序你多大了？

Andrew Huberman:

安德鲁·休伯曼：

I turn 49 in six weeks.

六周后我就 49 岁了。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Okay.

好的。

So I'm sure your listeners will not like to hear this because they would probably hope and believe that you are immortal, but-

所以我确信你的听众不会喜欢听到这个，因为他们可能希望并相信你是不朽的，但是-

Andrew Huberman:

安德鲁·休伯曼：

Some might want to hear that I'm going to be taken out soon.

有些人可能想知道我很快就会被淘汰。

Dr. Peter Attia:

彼得·阿蒂亚博士：

But let's just grant your mortality as a given.

但我们还是把你的死亡率视为既定事实吧。

Based just on your chronologic age, an actuary would come up with a pretty decent prediction of how long you're going to live.

仅根据您的实际年龄，精算师就会对您的寿命做出相当不错的预测。

Now, I would argue that that's a crude assumption because it doesn't take into account the fact that you're metabolically healthy, that you do all of the things that you do.

现在，我认为这是一个粗略的假设，因为它没有考虑到您的新陈代谢健康以及您所做的所有事情这一事实。

But just based on the fact that you are a man who is 49 years old and who doesn't smoke, those three things would give me, if I were an actuary, a very good prediction of your life expectancy.

但仅基于您是一位 49 岁且不吸烟的男性这一事实，如果我是一名精算师，这三件事就能让我对您的预期寿命做出很好的预测。

And because I'm not an actuary, I don't know the exact number, but my guess is it would be predicted at this point at another 37 years.

因为我不是精算师，所以我不知道确切的数字，但我的猜测是，此时预计再过 37 年。

Andrew Huberman:

安德鲁·休伯曼：

Okay.

好的。

Well, I bought that chart, my life in weeks.

嗯，我买了那张图表，我的生命几周。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yes.

是的。

Andrew Huberman:

安德鲁·休伯曼：

In fact, I bought two of them, for reasons that are uninteresting.

事实上，我出于一些无趣的原因买了其中的两个。

But I've watched that chart fill, not quite what you predicted, but I put my estimated lifespan to be 95.

但我已经看到该图表的填充情况，与您预测的不太一样，但我将我的估计寿命定为 95 岁。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Great.

太棒了。

That's fine.

没关系。

Andrew Huberman:

安德鲁·休伯曼：

And then I have little lines on the side-

然后我的侧面有一些小线条-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm-hmm

嗯嗯

Andrew Huberman:

安德鲁·休伯曼：

...

of how much vigor I felt, and just overall wellness, completely subjective, of zero being completely cratered, near death, to 10, as best I've ever felt.

我感受到了多少活力，以及整体健康状况，完全主观，从零到完全崩溃，濒临死亡，到十，这是我所感受到的最好的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

But you make that note every how often?

但你每隔多久就会做一次这样的笔记？

Andrew Huberman:

安德鲁·休伯曼：

Okay, so what I did is from 10 to 15, I felt blank.

好吧，所以我做的就是从10到15，我感觉一片空白。

And then in my 20s, I actually didn't feel so great because I was working 80-hour weeks commonly.

然后在我 20 多岁的时候，我实际上感觉不太好，因为我通常每周工作 80 小时。

You can ask my former lab technicians.

你可以问问我以前的实验室技术人员。

I was just talking to Fong Lynn recently, and I used to work to collapse, not healthy.

我最近刚刚和Fong Lynn聊天，我以前工作到崩溃，不健康。

80 hour a week, maybe 100 hours occasionally, maybe 70, maybe back to 40, but just too much work, not enough sleep, nutrition not great.

每周 80 小时，偶尔可能 100 小时，也许 70 小时，也许回到 40 小时，但工作太多，睡眠不足，营养也不好。

Just not doing the right things, but just gave my 20s to being in lab, basically, and a lot of my 30s as well.

只是没有做正确的事情，只是把我20多岁的时间都花在了实验室里，基本上，还有很多30多岁的时间。

So I would say from 40 to 45, my vigor was higher than in my 30s.

所以我会说从40岁到45岁，我的活力比30多岁时更高。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm-hmm.

嗯嗯。

Andrew Huberman:

安德鲁·休伯曼：

And then now I track, I would say about every two months, I'll start filling in that line, and it's adjusted for by stressors and adjusted for by positive things in life.

然后现在我跟踪，我会说大约每两个月，我将开始填写该行，它会根据压力源进行调整，并根据生活中的积极事物进行调整。

And the goal for me is to figure out what are the behavioral tools and other things I can do or take that are going to keep the vigor as high as possible.

我的目标是找出我可以做或采取的行为工具和其他事情，以尽可能保持活力。

Vigor, wellbeing, internal peace, et cetera, all of that combined, kind of what I'm calling wellness in this very subjective measure, as high as possible as I transition to my 50s, my 60s, 70s, and 80s.

活力、幸福感、内心平静等等，所有这些结合在一起，就是我所说的健康，在这个非常主观的衡量标准中，随着我过渡到 50 多岁、60 多岁、70 多岁和 80 多岁，尽可能高。

And I'm guessing that I'm going to have to do many more things in my 80s and 90s in order to maintain a similar, hopefully, level of vigor and wellbeing than I do now.

我猜我在 80 多岁和 90 多岁的时候必须做更多的事情，才能保持与现在类似的活力和幸福水平。

And the question is-

问题是——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Maybe

也许

Andrew Huberman:

安德鲁·休伯曼：

...

will I be able to?

我能做到吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, maybe.

是的，也许吧。

I might take a slightly different angle on that.

我可能会采取稍微不同的角度。

But let me go back and make one point, and then we'll come back to this point, which is actually-

但让我回过头来说一说，然后我们再回到这一点，这实际上是——

Andrew Huberman:

安德鲁·休伯曼：

Yeah, the chart

是的，图表

Dr. Peter Attia:

彼得·阿蒂亚博士：

...

really interesting.

真的很有趣。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

Because I think the chart is great.

因为我认为图表很棒。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

I think the chart, more than any supplement for longevity, gives one a visual perspective of where they sit in this long arc, and I don't think The brain is very good at anchoring us to the notion that we are mortal.

我认为这张图表比任何长寿补充品都更能让人直观地了解他们在这条长弧线中所处的位置，而且我不认为大脑很擅长将我们固定在我们终有一死的观念上。

Because if we think about that for even a few moments too long, it makes us anxious.

因为如果我们想这个问题的时间太长，即使是几分钟，也会让我们感到焦虑。

And I think we are very good at avoiding that reality.

我认为我们非常善于避免这个现实。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Well, as you said, it's very difficult to contemplate finitude.

嗯，正如你所说，思考有限性是非常困难的。

So I actually want to talk about that because I think it's so interesting.

所以我实际上想谈谈这个，因为我认为它很有趣。

But I just want to make this point about the actuarial point.

但我只想就精算点提出这一点。

So, let's just say actuarially, your expectation is 40 years more at this point because you're 49, you're a male, and you don't smoke, so we believe you have somewhere between 35 and 40 more years of life predicted on the basis of your biologic age.

所以，从精算角度来说，您的预期寿命是 40 年，因为您 49 岁，您是男性，而且您不吸烟，所以我们相信根据您的生物年龄，您的寿命预计还会有 35 到 40 年。

Andrew Huberman:

安德鲁·休伯曼：

That's it?

就这样？

That's all I got?

这就是我得到的全部吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, because you're going to live to, whatever, 88 to 91 or something.

是的，因为你会活到 88 岁到 91 岁之类的。

I'm making that up.

我正在弥补。

But that's okay.

但没关系。

Andrew Huberman:

安德鲁·休伯曼：

I better get cracking on some stuff.

我最好开始研究一些东西。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So now let's pretend you went and did a biologic age test.

现在让我们假设您去做了生物年龄测试。

Okay.

好的。

So let's say you did that, and let's say it came back and said you're 25.

假设你这么做了，然后它回来告诉你你已经 25 岁了。

So if I had a 25-year-old male non-smoker in front of me, what's his life expectancy?

那么，如果我面前有一位 25 岁的男性不吸烟者，他的预期寿命是多少？

Well, it's about 60 to 65 years.

嗯，大约是60到65年。

Does that mean that you, Andrew, have 60 to 65 more years of life based on a fact that your biologic clock says you're 25?

安德鲁，根据你的生物钟显示你已经 25 岁，这是否意味着你还有 60 到 65 年的寿命？

Do you believe that?

你相信吗？

Andrew Huberman:

安德鲁·休伯曼：

No. No way.

不，不可能。

Dr. Peter Attia:

彼得·阿蒂亚博士：

No, of course not.

不，当然不是。

Now, this would be an easy thing to test.

现在，这将是一件很容易测试的事情。

Not in humans, but you could do it in mice.

在人类身上不行，但你可以在老鼠身上做到这一点。

Right?

正确的？

Interesting that to my knowledge, that experiment hasn't been done.

有趣的是，据我所知，该实验尚未完成。

So right out of the gate, when I look at people talking about their biologic age, "Well, I'm actually 60 years old chronologically, but my biologic age is 35," my response is, "Who cares?" truthfully.

所以一开始，当我看到人们谈论他们的生物学年龄时，“嗯，按时间顺序我实际上已经 60 岁了，但我的生物学年龄是 35 岁，”我的回答是，“谁在乎呢？”说实话。

Is that a good thing?

这是一件好事吗？

Yes, probably.

是的，可能是。

But is it tangibly, measurably meaningful to have a biologic age of 35 versus 40 versus 30 if you're 60?

但是，如果你已经 60 岁了，那么生理年龄分别为 35 岁、40 岁和 30 岁，是否具有切实、可衡量的意义呢？

I think we're applying a very false level of precision to something that might only need to be directionally true.

我认为我们正在将非常错误的精度水平应用于可能只需要方向正确的东西。

Secondly, we don't really yet understand the biologic noise in that measurement, right?

其次，我们还没有真正理解该测量中的生物噪音，对吗？

So there are lots of things that we measure that are really noisy.

因此，我们测量的很多东西确实很吵。

So if I measured your, I don't know.

所以如果我测量了你的，我不知道。

Let's think of something that's very biologically noisy.

让我们想想一些生物学上非常嘈杂的东西。

Your triglyceride level.

您的甘油三酯水平。

Your triglycerides are pretty noisy unless I do something very important, which is standardize it by how long it's been since your last meal.

你的甘油三酯非常吵闹，除非我做一些非常重要的事情，即根据你上一顿饭以来的时间对其进行标准化。

If you ask me right now what my trigs are, I have no earthly idea because I probably ate three hours ago, and I don't even remember what I ate, how much fat was in it, how much carbohydrate was in it.

如果你现在问我我的三角肌是什么，我根本不知道，因为我可能在三个小时前吃了东西，我什至不记得我吃了什么，其中有多少脂肪，有多少碳水化合物。

I have no idea.

我不知道。

So the only way you could really get a triglyceride measurement and put any weight to it is if you've been fasting for 8 to 12 hours.

因此，真正获得甘油三酯测量值并对其进行衡量的唯一方法是您是否已经禁食 8 至 12 小时。

Then we can at least say, hey, a triglyceride level of 50 milligrams per deciliter is excellent, whereas a triglyceride level of 120 milligrams per deciliter is lousy.

那么我们至少可以说，嘿，甘油三酯水平为每分升 50 毫克就很好，而甘油三酯水平为每分升 120 毫克就很差。

But if you measured my trigs today, meaning at this moment, and they were 150, that could be totally reasonable, even though at fasting levels, I'm at 50.

但如果你今天测量我的三角肌，即此刻，它们是 150，那可能是完全合理的，即使在禁食水平下，我的三角肌值是 50。

So we know that because we know exactly what goes into the triglyceride measurement.

所以我们知道这一点是因为我们确切地知道甘油三酯测量的内容。

But when you look at a biologic clock that takes into account your glucose level, your vitamin D level, your epigenetic marker here or there, those are very noisy things.

但当你观察一个考虑了你的血糖水平、维生素 D 水平、表观遗传标记的生物钟时，你会发现这些都是非常嘈杂的东西。

So how do I know when I measure it in you now versus when I measure it in you a year from now, I captured you in the exact same space?

那么我怎么知道当我现在在你身上测量它时与一年后我在你身上测量它时，我在完全相同的空间中捕捉到了你？

I don't.

我不知道。

So it's for that reason that I just have a very hard time putting any stock in this.

因此，正是出于这个原因，我很难对此持有任何股票。

Now, does that mean that in the future we won't find some benefit in this?

现在，这是否意味着将来我们不会从中找到任何好处？

I think we probably will.

我想我们可能会的。

I do think of all the things that go into it, probably the epigenetic part of it would be the most interesting.

我确实想到了其中的所有内容，其中表观遗传部分可能是最有趣的。

But again, what most people don't understand as sort of a dirty little secret is how difficult it is to measure and to sequence the epigenome, right?

但同样，大多数人不理解的是，测量和测序表观基因组是多么困难，这是一个肮脏的小秘密，对吗？

So to my knowledge, none of the companies that are doing this, I may be incorrect on this by the way, but the last time I looked, which was about a year ago, not a single company was correctly sequencing the epigenome on these things.

据我所知，没有一家公司在做这件事，顺便说一句，我在这方面可能是不正确的，但我上次查看时，大约一年前，没有一家公司对这些东西的表观基因组进行了正确的测序。

Andrew Huberman:

安德鲁·休伯曼：

Hmm.

嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So they were not able to accurately say.

所以他们也无法准确的说出。

They were giving you an average representation of your methylation, but they weren't going base pair by base pair and actually sequencing this the way we would sequence a genome.

他们为您提供了甲基化的平均表示，但他们并没有逐个碱基对进行碱基对的测序，并像我们对基因组进行测序的方式进行实际测序。

So again, it's so much noise in this system, and I just think it creates a little bit of a distraction for people, truthfully.

再说一次，这个系统中有太多的噪音，说实话，我只是认为它会分散人们的注意力。

Andrew Huberman:

安德鲁·休伯曼：

Do you avoid going through the non-traditional scanner at the airport, the one that might use higher levels of radiation?

您是否避免在机场使用非传统扫描仪（可能使用较高辐射水平的扫描仪）？

No.

不。

Dr. Peter Attia:

彼得·阿蒂亚博士：

No.

不。

Andrew Huberman:

安德鲁·休伯曼：

Do you think about how many flights you take as a-

你有没有想过你乘坐了多少次航班——

Dr. Peter Attia:

彼得·阿蒂亚博士：

否

Andrew Huberman:

安德鲁·休伯曼：

...

source of radiation?

辐射源？

Dr. Peter Attia:

彼得·阿蒂亚博士：

No.

不。

Andrew Huberman:

安德鲁·休伯曼：

Do you-

你有吗——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Let's just keep this all in context.

让我们将这一切放在上下文中。

So the NRC recommends that a human being, or at least an American, should expose themselves to less than 50 millisieverts of radiation a year.

因此，NRC 建议人类，或者至少是美国人，每年暴露在低于 50 毫西弗的辐射下。

Okay, so that number doesn't mean anything to somebody, so let me give people a sense of what that means.

好吧，这个数字对某些人来说没有任何意义，所以让我让人们了解一下这意味着什么。

So how many millisieverts of radiation do you and I receive because we both live at sea level?

那么，因为我们都生活在海平面上，所以你和我会受到多少毫西弗的辐射呢？

So just ambient radiation, living at sea level is one millisievert a year.

因此，生活在海平面的环境辐射每年为一毫西弗。

Okay, so we just chewed up 2% of our annual allocation.

好的，我们只用掉了年度拨款的 2%。

What if you moved to Colorado?

如果你搬到科罗拉多州怎么办？

Now you're a mile up.

现在你已经进步了一英里。

That increases you from one to two millisieverts a year.

这会使您每年从一毫西弗增加到两毫西弗。

Okay.

好的。

What if you had a CT scan of your chest, a CT angiogram?

如果您对胸部进行 CT 扫描、CT 血管造影会怎么样？

Well, it depends on where you got it done.

嗯，这取决于你在哪里完成的。

If you got it done at a really good place with a fast scanner and great software, probably three millisieverts a year.

如果你在一个非常好的地方用快速扫描仪和出色的软件完成它，一年可能会花费三毫西弗。

If you got it done at a place that's sort of average, might be 10 to 15 millisieverts, pardon me, per scan.

如果你在一个平均水平的地方完成它，可能是 10 到 15 毫西弗，请原谅，每次扫描。

Now here's what's really interesting.

现在真正有趣的是。

By the way, I'm totally fascinated by this question, which is how much radiation is too much?

顺便说一句，我对这个问题非常着迷，即多少辐射算过量？

A DEXA scan, by the way, you can't even measure how many millisieverts you're getting.

顺便说一下，DEXA 扫描你甚至无法测量你得到了多少毫西弗。

So a DEXA scan is less radiation than a cross-country flight.

因此，DEXA 扫描的辐射比越野飞行要少。

So it's super low, less than an X-ray or anything like that.

所以它的强度非常低，比 X 射线或类似的东西还要低。

People who work in nuclear plants, I'm told, I haven't looked at the primary data on this, but I've talked to people who incessantly do this, so it's possible I'm a little bit off on this, but I'm told that these people are at 10 times that level of radiation exposure and sometimes higher.

有人告诉我，在核电站工作的人，我没有看过这方面的主要数据，但我和那些不断这样做的人交谈过，所以我可能在这方面有点偏差，但我听说这些人的辐射水平是这个水平的 10 倍，有时甚至更高。

So they're not getting 50.

所以他们没有得到50。

They might be getting like 500 millisieverts a year.

他们每年可能会增加 500 毫西弗。

And yet interestingly, they're not at an increased risk for cancer.

但有趣的是，他们患癌症的风险并没有增加。

Now, I'm not sure what to make of that.

现在，我不知道该怎么做。

But it suggests to me that we probably don't need to worry about things like airport scanners and flights.

但这对我来说意味着我们可能不需要担心机场扫描仪和航班之类的事情。

In fact, even if you look at pilots who do constant flights across the poles, because you're going to get the most radiation going over the pole, to my knowledge, there's no convincing data that suggests those people are at an increased risk of cancer either.

事实上，即使你看看那些经常飞越两极的飞行员，因为据我所知，你会受到最多的辐射穿过两极，但也没有令人信服的数据表明这些人患癌症的风险增加。

And they're obviously at the upper end of what a civilian would experience in terms of radiation.

就辐射而言，它们显然处于平民所经历的上限。

So, I'm not convinced that that's something we should be stressed about.

所以，我不认为这是我们应该强调的事情。

Andrew Huberman:

安德鲁·休伯曼：

Well, I think you just relieved a lot of people of some unnecessary concern.

嗯，我想你刚刚让很多人摆脱了一些不必要的担忧。

Dr. Peter Attia:

彼得·阿蒂亚博士：

I want to go back to what you were saying earlier about what you need to do in your 90s versus what you're doing now.

我想回到您之前所说的关于 90 多岁需要做什么和现在正在做什么的问题。

So you said you think that in your 80s and 90s, you're going to have to work harder to preserve the vitality that you have now.

所以你说你认为在80、90岁的时候，你必须更加努力地工作才能保持现在的活力。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Grip strength, jumping, cognitive function.

握力、跳跃、认知功能。

I've got very good genes in terms of longevity on one side of my family, pretty good on the other, although not as robust.

我的家族一方面拥有非常好的长寿基因，另一方面也相当不错，尽管没有那么强大。

If I just look historically.

如果我只看历史的话。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Who knows, right?

谁知道，对吧？

But my sense is that I'll live to be 95 if, barring, a bullet, bus, or cancer.

但我的感觉是，如果没有子弹、公共汽车或癌症，我会活到 95 岁。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So I would say that, yes, you're going to have to work hard in that last decade of life to preserve those things, but I think it's the work we do now that sets the stage for that.

所以我想说，是的，你必须在生命的最后十年努力工作才能保护这些东西，但我认为我们现在所做的工作为此奠定了基础。

It's the foundational work that we do in this period of our lives.

这是我们一生中这个时期所做的基础工作。

You and I are only a couple of years apart, but I think this is the critical decade.

你和我只相差几年，但我认为这是关键的十年。

It's in your 50s to your 60s and in your 60s to your 70s that I think is the deciding time.

我认为50多岁到60多岁以及60多岁到70多岁是决定性的时期。

Andrew Huberman:

安德鲁·休伯曼：

50s to 70s.

50 年代到 70 年代。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

50s to 70s.

50 年代到 70 年代。

So, what is it about this window that you and I are just entering now, and why is it so important?

那么，你我现在刚刚进入的这个窗口有什么意义，为什么它如此重要？

I think it's important because we're getting to that point where aging does start to show up.

我认为这很重要，因为我们已经到了衰老确实开始出现的阶段。

Andrew Huberman:

安德鲁·休伯曼：

Mm.

嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

I think if you and I are being brutally honest, we're kind of half the men we used to be.

我想如果你和我都非常诚实的话，我们就已经是过去的一半了。

And again, that just means like, look, a night of poor sleep shows up more, right?

再说一次，这只是意味着，看，一晚睡眠不好的情况会更多，对吧？

When you were working in the lab as hard as you were describing it, you could probably walk through walls when you were exhausted.

当你在实验室里像你描述的那样努力工作时，当你筋疲力尽时，你可能会穿墙而过。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

A short nap would reset me near completely.

短暂的小睡会让我几乎完全恢复过来。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

I got more colds and flus in that time because I wasn't taking such good care of, but then again, I was indoors more, so it's an imperfect experiment, but you're right.

那段时间我得了更多的感冒和流感，因为我没有照顾得很好，但话又说回来，我更多地待在室内，所以这是一个不完美的实验，但你是对的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

I think that as I've approached 50, I need to do more.

我觉得我已经快50岁了，我需要做更多的事情。

Dr. Peter Attia:

彼得·阿蒂亚博士：

You need to do more self-care.

您需要进行更多的自我护理。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

You need to be more mindful of what you're eating, how you're sleeping, how you're recovering from those workouts, because we still do hard workouts, but recovery plays a greater role.

你需要更加注意自己的饮食、睡眠方式以及锻炼后的恢复情况，因为我们仍然进行艰苦的锻炼，但恢复起着更重要的作用。

In other words, we're just not quite as resilient as we used to be.

换句话说，我们只是不像以前那么有弹性了。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

I was telling somebody the other day, they asked me about my residency.

前几天我告诉别人，他们问我关于我的居住地的情况。

I don't think I'm being hyperbolic when I say this.

当我这么说时，我不认为我是夸张的。

I couldn't do one month of what I did for five years.

我五年来所做的事情，一个月都做不到。

I really couldn't do it.

我实在做不到。

There's no way I could go back to that level of sleep deprivation for a month, let alone five years.

我不可能再回到那种一个月睡眠不足的状态，更不用说五年了。

So, that's just a fact of aging, I think.

所以，我认为这只是衰老的事实。

But what we have to do during this period of time is build up as much physiologic reserve as possible.

但这段时间我们要做的就是尽可能多地建立生理储备。

And so the important thing is we have to stay in the game because compounding makes such a difference, right?

因此，重要的是我们必须留在游戏中，因为复利会产生如此大的影响，对吗？

So, we're still young enough that we can actually put on muscle mass.

所以，我们还年轻，实际上可以增加肌肉质量。

Now, that's not always going to be the case.

现在，情况并非总是如此。

It's going to be very difficult to add muscle mass when you're in your mid to late 70s.

当你70岁中后期时，增加肌肉质量将非常困难。

It's doable, but it's very difficult.

这是可行的，但是非常困难。

So instead, we want to be putting on as much muscle mass as we can and increasing or at least maintaining strength as much as we can.

因此，我们希望尽可能多地增加肌肉质量，并尽可能地增加或至少保持力量。

Again, probably increasing it is unlikely.

同样，增加它可能不太可能。

Clearly, we're not increasing power as we age, right?

显然，随着年龄的增长，我们的力量并没有增加，对吗？

Andy Galpin has talked a lot about this, the atrophy of the type two muscle fibers.

安迪·加尔平（Andy Galpin）对此谈了很多，即二型肌纤维的萎缩。

The 2A muscle fibers really start to atrophy in your 20s and 30s.

2A肌纤维在20多岁和30多岁时才真正开始萎缩。

So I know I don't have a fraction of the power that I used to have, and I know that because my vertical jump is literally half what it was when I was a teenager.

所以我知道我的力量已经不及以前的一小部分了，我知道这一点是因为我的垂直弹跳力实际上只有我十几岁时的一半。

I mean, I measured this.

我的意思是，我测量了这个。

Andrew Huberman:

安德鲁·休伯曼：

Well, mine was never very good, so I-

嗯，我的从来都不是很好，所以我-

Dr. Peter Attia:

彼得·阿蒂亚博士：

It doesn't matter how good it was.

它有多好并不重要。

My point is like, if you know what your vertical jump was at 18, 19, 20, and then you do it today, it's literally 50%, and that's one of the purest tests of power.

我的观点是，如果你知道你在 18、19、20 岁时的垂直弹跳是多少，然后你今天就做了，它实际上是 50%，这是最纯粹的力量测试之一。

So power's going down, strength is going down, but not as much.

所以力量在下降，强度在下降，但下降幅度不大。

Muscle mass is actually not, because remember, that's the order in which you lose things, right?

肌肉质量实际上不是，因为记住，这就是你失去东西的顺序，对吧？

You're going to lose power, strength, and size of muscle.

你将会失去力量、力量和肌肉的大小。

But again, size still matters.

但同样，尺寸仍然很重要。

It's still a glucose sink, all these other things.

它仍然是一个葡萄糖汇，所有这些其他的东西。

But what we don't want to do is be out of the game, right?

但我们不想做的就是退出游戏，对吗？

What we don't want to do is injure ourselves and get a setback that becomes very difficult to recover from.

我们不想做的就是伤害自己并遭受难以恢复的挫折。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Because when you're our age, if you're inactive for months at a time, it's going to be two to one or three to one ratio of inactivity to activity to get it back.

因为当你到了我们这个年纪，如果你一次不活动几个月，那么要恢复活动，不活动与活动的比例将是二比一或三比一。

Andrew Huberman:

安德鲁·休伯曼：

What about energy?

能源呢？

Sorry to interrupt.

抱歉打扰。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

But since we've been talking about molecules and energetic pathways What about energy?

但既然我们一直在谈论分子和能量途径，那么能量呢？

Just that get up and go, let's just say after a decent night's sleep-

就这样起身走吧，我们只是说在睡了一晚好觉之后-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah

是啊

Andrew Huberman:

安德鲁·休伯曼：

...

seven and a half hours, waking up same time, more or less, 6:30, 7:00 a.m.

七个半小时，或多或少在同一时间起床，早上 6:30、7:00

probably for you or me.

可能适合你或我。

And why is it that as we get older, we have less energy?

为什么随着年龄的增长，我们的精力会越来越少？

Our mutual good friend, the late Ben Barris, used to ask about this.

我们共同的好朋友，已故的本·巴里斯 (Ben Barris) 曾经问过这个问题。

He used to say-- he called me Andy.

他过去常说——他叫我安迪。

He was like, "Andy, why do I have so much less energy?" And I was like, "I don't know.

他说，“安迪，为什么我的精力这么少？”我当时想，“我不知道。

It's a great question." Now, unfortunately, he died of pancreatic cancer.

这是一个很好的问题。”现在，不幸的是，他死于胰腺癌。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

So there may have been other things going on, but that was prior to the cancer, at least as far as I know.

所以可能还发生了其他事情，但那是在癌症之前发生的，至少据我所知。

It's a very interesting question.

这是一个非常有趣的问题。

Why do we have less energy?

为什么我们的能量越来越少？

And I don't think anyone's ever been able to answer that question.

我认为没有人能够回答这个问题。

Dr. Peter Attia:

彼得·阿蒂亚博士：

No, and when you have kids, you're going to be even more starkly confronted with that.

不，当你有了孩子时，你会更加直面这个问题。

Because actually, it's one of the things I am most amazed by when I look at my kids, especially the youngest ones, the boys, who are seven and 10, is what I just described as spontaneous outbursts of energy.

因为实际上，当我看到我的孩子们时，最令我惊讶的事情之一，尤其是最小的孩子，分别是七岁和十岁的男孩，就是我刚才所说的自发的能量爆发。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Like, their inability to sit still, their kinetic desire to just-- I remember once we were walking through a mall, and we're walking through the mall, they are sprinting ahead of us, sprinting back, sprinting ahead of us, sprinting back.

就像，他们无法安静地坐着，他们强烈的渴望——我记得有一次我们穿过一个购物中心，当我们穿过购物中心时，他们在我们前面冲刺，向后冲刺，在我们前面冲刺，向后冲刺。

Like, imagine if you and I were walking through the mall, and I just started running ahead and running back.

就像，想象一下，如果你和我正在穿过购物中心，而我开始向前跑，然后向后跑。

Andrew Huberman:

安德鲁·休伯曼：

You'd be so sore the next day.

第二天你会很痛。

Dr. Peter Attia:

彼得·阿蒂亚博士：

But it just wouldn't occur to me to ever run unless being chased, right?

但除非被追赶，否则我不会想到逃跑，对吗？

Like, we now live a life like I think our ancestors did, which was, if we're not deliberately in the business of moving for a reason, like you're exercising, you're going for a walk for the sake of going for a walk, it wouldn't occur to you go and expend energy for no reason.

就像，我们现在过着像我认为我们的祖先那样的生活，也就是说，如果我们不是出于某种原因而刻意地移动，就像你在锻炼，你为了散步而散步，你就不会无缘无故地去消耗能量。

And yet kids do this.

然而孩子们却这么做了。

It's amazing.

太棒了。

And look, it's going to go down by the time you're a teenager.

瞧，到你十几岁的时候，它就会下降。

Like, just going from being 10 to 18, there's probably a significant reduction in spontaneous outbursts of energy, let alone where we are now.

就像，从 10 岁到 18 岁，自发的能量爆发可能会显着减少，更不用说我们现在的情况了。

And it's a great question.

这是一个很好的问题。

Maybe it's NAD.

也许是NAD。

I mean, I don't know.

我的意思是，我不知道。

Andrew Huberman:

安德鲁·休伯曼：

Maybe.

也许吧。

Although up until now, we've been talking about all these ways to try and increase NAD in the bloodstream and hopefully in cells, and I don't know.

尽管到目前为止，我们一直在讨论所有这些方法来尝试增加血液中以及细胞中的 NAD，但我不知道。

I take my NMN and my NR, and I feel a little bit of a boost in energy, but I can't say that it's so significant that I feel like I can sprint back and forth just spontaneously these days.

我服用了 NMN 和 NR，我感觉精力有点增加，但我不能说这很重要，以至于我觉得这些天我可以自发地来回冲刺。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Again, it's just so hard for me to imagine that any supplement or any drug, including rapamycin, which I think is the most promising geroprotective drug we have.

再说一次，我很难想象任何补充剂或任何药物，包括雷帕霉素，我认为这是我们拥有的最有前途的老年保护药物。

I just can't imagine that those things even compare to what good sleep, good exercise, and good nutrition do for your energy levels and vitality.

我无法想象这些东西与良好的睡眠、良好的锻炼和良好的营养对你的能量水平和活力的作用相比。

And the reality of it is all three of those things are hard to do.

而现实情况是，这三件事都很难做到。

Andrew Huberman:

安德鲁·休伯曼：

Yeah, they do.

是的，他们确实这么做了。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Especially if you're an adult.

尤其是如果你是成年人的话。

Like, especially if you have a real life.

就像，尤其是如果你有现实生活的话。

You've got kids, you've got a job, which is presumably many people listening to us right now.

你有孩子，你有工作，现在想必很多人都在听我们的讲话。

Like, there's very few people listening to us right now whose only purpose in life is to take care of their health.

就像，现在很少有人听我们的，他们人生的唯一目的就是照顾自己的健康。

Everybody's got something else they have to do, which means you have competing interests for how do you take care of yourself.

每个人都有自己必须做的事情，这意味着你们在如何照顾自己方面存在相互竞争的利益。

So to sleep is not easy, right?

所以睡觉并不容易，对吧？

Like, we all are busy as hell.

就像，我们都忙得不可开交。

We don't want to have to stop what we're doing to undergo a nighttime routine, to put ourselves in the right headspace, to be able to sleep, do all the things necessary, give ourselves that eight hours in bed to hopefully get seven, seven and a half hours of sleep.

我们不想必须停止正在做的事情来进行夜间例行公事，让自己处于正确的头脑空间，能够入睡，做所有必要的事情，在床上睡八个小时，希望能睡七、七个半小时。

Even people like me who like exercise, I know you like exercise, it still is a sacrifice in terms of time.

即使像我这样喜欢运动的人，我知道你喜欢运动，但在时间上仍然是一种牺牲。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And for many people, certainly for me, food is the hardest of these all, right?

对于很多人来说，当然对我来说，食物是最难的，对吧？

If left to my own devices, I'd eat freaking Froot Loops all day.

如果由我自己决定，我会整天吃该死的果圈。

Like, I love Froot Loops, right?

就像，我喜欢果圈，对吧？

Andrew Huberman:

安德鲁·休伯曼：

Interesting.

有趣。

By way of contrast, the food part is easy for me.

相比之下，食物部分对我来说很容易。

I like healthy food and-

我喜欢健康食品并且-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Oh, I like healthy food.

哦，我喜欢健康食品。

I just like all food.

我只是喜欢所有的食物。

Andrew Huberman:

安德鲁·休伯曼：

Okay.

好的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

There's nothing I don't like.

没有什么是我不喜欢的。

Andrew Huberman:

安德鲁·休伯曼：

Yeah, I don't like unhealthy food.

是的，我不喜欢不健康的食物。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Oh, I do.

哦，我愿意。

Andrew Huberman:

安德鲁·休伯曼：

I've weaned myself off it.

我已经戒掉它了。

I never really liked it that much.

我从来没有那么喜欢过它。

I like a great tasting slice of pizza or ice cream every once in a while, but I much prefer meat, fish, chicken, eggs, fruits, vegetables, rice, oatmeal.

我喜欢偶尔吃一块美味的披萨或冰淇淋，但我更喜欢肉、鱼、鸡肉、鸡蛋、水果、蔬菜、大米、燕麦片。

I just like that stuff.

我就是喜欢那些东西。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm-hmm.

嗯嗯。

Andrew Huberman:

安德鲁·休伯曼：

I'm a weirdo that way, I suppose.

我想我在这方面是个怪人。

But on the topic of exercise as it relates to vigor and longevity, I'm intrigued by how some forms of exercise give us more energy, especially the same day, and how some forms of exercise or even timing of exercise tends to deplete us.

但在与活力和长寿相关的运动这个话题上，我对某些形式的运动如何给我们带来更多能量（尤其是在同一天）以及某些形式的运动甚至运动时间如何倾向于耗尽我们的能量感兴趣。

Because I think one of your major sort of calls to the public has been to move more-

因为我认为您对公众的主要呼吁之一就是采取更多行动-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah

是啊

Andrew Huberman:

安德鲁·休伯曼：

...

for sake of their health span and lifespan.

为了他们的健康和寿命。

But because of the time investment that it takes to work out in a gym or to go for a run or a ruck, I think some people think, well, that's a lot of time.

但由于在健身房锻炼或跑步或跑步需要投入时间，我想有些人会认为，嗯，这是很多时间。

But if it gives you more energy and more focus to do other things, well, then it's great.

但如果它能让你有更多的精力和更多的注意力去做其他事情，那就太好了。

So it's not just about living longer, it's about-

所以这不仅仅是为了活得更长，而是为了——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Absolutely

绝对

Andrew Huberman:

安德鲁·休伯曼：

...

being able to do more.

能够做更多的事情。

And I've noticed, I don't have any science to back this up, but I'd love someone to run a test on this, that if I complete my workout before 9:00 a.m., even if I have to start it while I'm a little bit fatigued, I have more energy all day long.

我注意到，我没有任何科学依据来支持这一点，但我希望有人对此进行测试，如果我在上午 9:00 之前完成锻炼，即使我必须在有点疲劳的时候开始锻炼，我一整天都会更有精力。

But that if I initiate that workout, say, mid to late morning-

但如果我开始锻炼，比如说，上午中后期——

Dr. Peter Attia:

彼得·阿蒂亚博士：

毫米

Andrew Huberman:

安德鲁·休伯曼：

...

I'm pretty tired in the afternoon.

下午我实在是太累了。

It's like I give everything I have to that workout, and so it becomes a little bit defeating since I'm not a professional athlete or even an amateur athlete.

就好像我为这项训练付出了一切，所以它变得有点失败，因为我不是职业运动员，甚至不是业余运动员。

I'm working out for health span, lifespan, but I want to do exercise that gives me more life during my waking hours.

我锻炼身体是为了健康、延长寿命，但我想做一些运动，让我在醒着的时候更有活力。

I think somebody should study this.

我认为应该有人研究这个。

And I'm convinced that it has something to do with the change in body temperature that occurs across the day and the additional change in body temperature that occurs as a consequence of exercise.

我确信这与一天中发生的体温变化以及运动导致的额外体温变化有关。

That's my hypothesis.

这是我的假设。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Do you notice a seasonal change in that?

您注意到其中的季节变化吗？

Do you experience it more or less in one season or the other?

你在一个季节或另一个季节或多或少地经历过这种情况吗？

Andrew Huberman:

安德鲁·休伯曼：

I haven't thought about it that much, but not so much.

我没有考虑那么多，但也没有那么多。

Not so much.

没那么多。

And I wonder whether folks like our friend Jocko Willink are able to do so much.

我想知道像我们的朋友乔科·威林克这样的人是否能够做这么多。

He has so much vigor-

他有那么大的活力——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm-hmm

嗯嗯

Andrew Huberman:

安德鲁·休伯曼：

...

that guy, in part because he basically exercises at just after the lowest temperature phase of the circadian rhythm, and he uses exercise-

那家伙，部分原因是他基本上在昼夜节律的最低温度阶段之后进行锻炼，并且他使用锻炼-

Dr. Peter Attia:

彼得·阿蒂亚博士：

毫米

Andrew Huberman:

安德鲁·休伯曼：

...

presumably to drive himself out of that and get that temperature increase that's the consequence of waking.

大概是为了让自己摆脱这种状态，让体温升高，这就是醒来的结果。

But in his case, he's waking up so early, 4:30 is when he starts those workouts.

但就他而言，他起得很早，4:30 就是他开始锻炼的时间。

So it's something for people to play with.

所以这是给人们玩的东西。

It's something that I don't think gets discussed enough, which is, yes, you should exercise, do resistance training, do cardiovascular training, but play with the timing of those and see how-

我认为这一点没有得到足够的讨论，那就是，是的，你应该锻炼，做阻力训练，做心血管训练，但要注意这些的时间安排，看看如何-

Dr. Peter Attia:

彼得·阿蒂亚博士：

毫米

Andrew Huberman:

安德鲁·休伯曼：

...

at a given intensity, it impacts your energy levels for the remainder of the day.

在给定的强度下，它会影响您当天剩余时间的能量水平。

I think it's an important metric that, again, I just don't see a lot of attention to.

我认为这是一个重要的指标，但我并没有看到太多的关注。

Because I think if people could experience the increase in energy that is the consequence of working out at the right intensity, in the right way, at the right times for them, they'd be much more apt to do it.

因为我认为，如果人们能够体验到在正确的时间以正确的强度、以正确的方式锻炼所带来的能量增加，他们就会更容易做到这一点。

It wouldn't feel like spending money on something that sure will make you live longer, but then you're depleted and you can't do cognitive work.

花钱买东西肯定不会让你活得更久，但随后你就会精疲力竭，无法进行认知工作。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

There's something pretty impressive about the fact that, as far as I know, the last three, let's just call them, I don't want to call anyone out specifically, major pillars of the high-level administration at Stanford School of Medicine, to my knowledge, were all 5:00 a.m.

令人印象深刻的是，据我所知，最后三位，我不想具体称呼任何人，据我所知，斯坦福大学医学院高层管理的主要支柱都在凌晨 5:00 出席。

runners.

跑步者。

There's something about early morning exercise.

晨练是有一定道理的。

And my good friend Eddie Chang, who's the chair of neurosurgery at UCSF, he's been on this podcast.

我的好朋友艾迪·张（Eddie Chang）是加州大学旧金山分校神经外科的主任，他也参加了这个播客。

I've known him since we were seven years old.

我从七岁起就认识他了。

He's an early morning exerciser, and then he's got tons of energy all day.

他是一个清晨锻炼者，然后他一整天都精力充沛。

Dr. Peter Attia:

彼得·阿蒂亚博士：

What about the reverse causality there?

那么反向因果关系又如何呢？

Andrew Huberman:

安德鲁·休伯曼：

Sure.

当然。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Do you think it's possible that they have a system of high energy that makes Jocko who he is or makes these people who they are?

你认为他们是否有可能拥有一个高能量的系统，使乔科成为他自己或使这些人成为他们自己？

Andrew Huberman:

安德鲁·休伯曼：

I don't doubt it.

我毫不怀疑。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And as a result of that, they're able to work out five o'clock in the morning.

因此，他们能够在早上五点钟锻炼。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

I don't doubt it.

我毫不怀疑。

I just have noticed that in the few times in my life where I've kicked my own butt to get up and start working out really early, I have more energy all day long.

我只是注意到，在我一生中为数不多的几次，我很早就起床并开始锻炼时，我一整天都有更多的精力。

Sometimes I still require-

有时我还是需要——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah

是啊

Andrew Huberman:

安德鲁·休伯曼：

...

a brief nap, but it's a pretty striking effect as compared to the 10:00 a.m.

短暂的小睡，但与上午 10:00 相比，这是一个相当惊人的效果。

workout effect.

锻炼效果。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

So I've started setting a standard of trying to get my workout done before 9:00 a.m.

因此，我开始设定一个标准，争取在上午 9:00 之前完成锻炼。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm-hmm.

嗯嗯。

Andrew Huberman:

安德鲁·休伯曼：

So anyway, it's something for people to play with because the more energy to live in your waking hours, perhaps not longer, but certainly have more energy in terms of output, I think is a significant and undervalued parameter.

所以无论如何，它是人们可以玩的东西，因为在你醒着的时候生活的能量越多，也许不是更长，但在输出方面肯定有更多的能量，我认为这是一个重要且被低估的参数。

So let's quickly return to supplements.

那么让我们快速回到补充剂上来。

We, I think are converging on an answer about NR, NMN, and NAD, which is you don't take them.

我认为我们正在就 NR、NMN 和 NAD 的答案达成一致，那就是你不接受它们。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Correct.

正确。

Andrew Huberman:

安德鲁·休伯曼：

I take NR and NMN with not a lot of religious adherence, I should say.

我应该说，我服用 NR 和 NMN 时并没有太多的宗教信仰。

If I ran out, I might not buy it for a while, and the only observed effect for me is this accelerated hair growth, which is a pain in the butt, frankly, because it just means I have to get my hair cut more often.

如果我用完了，我可能会暂时不会购买它，对我来说唯一观察到的效果是加速头发生长，坦率地说，这是一种痛苦，因为这意味着我必须更频繁地剪头发。

I'm not trying to grow my hair faster.

我并不是想让头发长得更快。

But okay, what are some other supplements, if any, that you take that are peripheral to this pathway or separate from this pathway?

但是好吧，您服用的其他补充剂（如果有的话）还有哪些是该途径的外围或与该途径分开的？

Rapamycin is a prescription drug only, right?

雷帕霉素只是处方药，对吗？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm-hmm.

嗯嗯。

Andrew Huberman:

安德鲁·休伯曼：

So are there any over-the-counter things that you take that you would place into the lifespan category?

那么，是否有任何非处方药可以归入寿命类别呢？

Maybe they touch into healthspan as well.

也许它们也涉及健康寿命。

I'm happy to list off what I do, but what are your, let's just say top five, at least?

我很高兴列出我所做的事情，但你的工作是什么，至少说前五名吧？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Well, I don't take that many, so top five would be a pretty exhaustive list.

嗯，我不会拿那么多，所以前五名将是一个非常详尽的列表。

I think the other supplements that I take, I do take EPA and DHA.

我认为我服用的其他补充剂中，我确实服用了 EPA 和 DHA。

Andrew Huberman:

安德鲁·休伯曼：

In the form of liquid or capsule fish oil?

液体或胶囊鱼油的形式？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Capsules.

胶囊。

Not because I have an affection for capsule over liquid.

不是因为我对胶囊的喜爱超过了液体。

It's just going to increase my compliance.

这只会增加我的依从性。

I've done both, and I've noticed when I was taking liquid, because you're storing it in the fridge, it's just one more step removed, and I was just less likely to remember to take it twice a day.

我都做了，而且我注意到当我服用液体时，因为你把它储存在冰箱里，它只是多了一步，而且我不太可能记得每天服用两次。

I take theracumin, and there's some reasonable evidence in MCI patients that theracumin improves cognitive function.

我服用 Theracumin，并且有一些合理的证据表明 MCI 患者中 Theracumin 可以改善认知功能。

So I think there's a relatively low downside to the hypothesis that theracumin may preserve cognitive function.

因此，我认为 Theracumin 可能保留认知功能的假设的负面影响相对较小。

Again, I wouldn't put that in the category of beat the table for it, right?

再说一次，我不会把它归入击败桌子的范畴，对吗？

I think it's just reasonable evidence.

我认为这只是合理的证据。

I do take vitamin D because interestingly, despite the fact that I'm outside every day, without supplemental vitamin D, my levels are surprisingly low.

我确实服用维生素 D，因为有趣的是，尽管我每天都在外面，没有补充维生素 D，但我的维生素 D 水平却出奇地低。

Andrew Huberman:

安德鲁·休伯曼：

How much do you take?

你服用多少？

Dr. Peter Attia:

彼得·阿蒂亚博士：

I take 5,000 IU.

我服用 5,000 IU。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And that takes me from a level of 30-ish to a level of 50-ish.

这让我从 30 左右的水平上升到 50 左右的水平。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And there's a lot of debate about how high vitamin D levels should be.

关于维生素 D 的水平应该保持在多高，存在很多争论。

That's a whole separate podcast.

这是一个完全独立的播客。

We could waste time on that in 10 years.

十年后我们可能会在这上面浪费时间。

Andrew Huberman:

安德鲁·休伯曼：

Great.

太棒了。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

My appetite to talk about that one.

我很想谈论这个。

Let me think, what else do I take?

让我想想，我还拿什么？

Oh, I do take methylfolate and methyl B12.

哦，我确实服用甲基叶酸和甲基 B12。

And again, the rationale there is, I do think there's some evidence that elevated levels of homocysteine are bad in and of themselves.

再说一遍，我确实认为有一些证据表明同型半胱氨酸水平升高本身就是有害的。

So there's no denying the fact that elevated levels of homocysteine are associated with bad things.

因此，不可否认的是，同型半胱氨酸水平升高与坏事有关。

That's unambiguously clear, meaning there's an association between badness and homocysteine.

这是非常明确的，这意味着不良和同型半胱氨酸之间存在关联。

What's not clear is, is it causal?

不清楚的是，这是因果关系吗？

Now, there's definitely one mechanism you can point to, although, again, mechanisms are what they are.

现在，你肯定可以指出一种机制，尽管机制就是它们本身。

We just spent how many hours talking about mechanisms that theoretically make sense that never pan out.

我们只是花了多少时间讨论理论上有意义但从未成功的机制。

But mechanistically, homocysteine will inhibit the clearance of something called symmetric and asymmetric dimethylarginine.

但从机制上讲，同型半胱氨酸会抑制对称和不对称二甲基精氨酸的清除。

Have you heard of these things, SDMA and ADMA?

您听说过 SDMA 和 ADMA 这两个东西吗？

So ADMA and SDMA regulate nitric oxide synthase, and homocysteine impairs their clearance, and therefore, when you have high levels of homocysteine, it results ultimately in impaired nitric oxide synthase, and therefore lower nitric oxide.

因此，ADMA 和 SDMA 调节一氧化氮合酶，而同型半胱氨酸会损害其清除率，因此，当同型半胱氨酸水平较高时，最终会导致一氧化氮合酶受损，从而降低一氧化氮。

So this has been proposed as at least one mechanism by which homocysteine might negatively impact vascular disease.

因此，这被认为是同型半胱氨酸对血管疾病产生负面影响的至少一种机制。

And we also know, by the way, that ADMA and SDMA are cleared by the kidneys, and therefore this is also proposed as one of the mechanisms by which impaired kidney function impacts vascular health.

顺便说一句，我们还知道 ADMA 和 SDMA 是由肾脏清除的，因此这也被认为是肾功能受损影响血管健康的机制之一。

Because that's a known, right?

因为这是已知的，对吧？

If your kidneys don't work well, your risk of heart disease goes way up.

如果您的肾脏功能不佳，患心脏病的风险就会大大增加。

So this is now proposed as a link between what we observe with homocysteine and impaired renal function.

因此，现在有人提出，我们观察到的同型半胱氨酸与肾功能受损之间存在联系。

So, we know that if you take methylfolate and methyl B12, you're going to lower homocysteine.

因此，我们知道，如果您服用甲基叶酸和甲基 B12，您就会降低同型半胱氨酸。

That's abundantly clear.

这非常清楚。

So the thinking is that that might actually lower ADMA, SDMA, and raise nitric oxide synthase.

因此，我们的想法是，这实际上可能会降低 ADMA、SDMA，并提高一氧化氮合酶。

Again, relatively low cost, low risk thing to take at modest doses.

同样，适度剂量的服用成本相对较低、风险较低。

There's probably some evidence that over-supplementing vitamin B is problematic, especially B6.

可能有一些证据表明过度补充维生素 B 是有问题的，尤其是维生素 B6。

So I don't-

所以我不-

Andrew Huberman:

安德鲁·休伯曼：

Because of peripheral nerve damage?

因为末梢神经损伤？

Dr. Peter Attia:

彼得·阿蒂亚博士：

Exactly.

正是如此。

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

So I don't supplement B6, I'm just taking a bit of folate and methyl B12.

所以我不补充B6，只是服用一点叶酸和甲基B12。

Let me think, what else do I take?

让我想想，我还拿什么？

Because I do take a couple other things.

因为我确实还拿了一些其他东西。

Oh, I take magnesium L-threonate and ashwagandha for sleep.

哦，我服用 L-苏糖酸镁和南非醉茄来睡觉。

Andrew Huberman:

安德鲁·休伯曼：

Mm-hmm.

嗯嗯。

Dr. Peter Attia:

彼得·阿蒂亚博士：

I take Slow-Mag, which is just a magnesium chloride slow-releasing version of magnesium, and I take magnesium oxide.

我服用 Slow-Mag，它只是镁的缓释版氯化镁，我服用氧化镁。

So I take magnesium in three forms.

所以我以三种形式服用镁。

So I'm long magnesium.

所以我做多镁。

Andrew Huberman:

安德鲁·休伯曼：

You're carpet bombing with magnesium.

你正在用镁进行地毯式轰炸。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

I'm big on magnesium, right?

我很喜欢镁，对吧？

Andrew Huberman:

安德鲁·休伯曼：

Yeah.

是的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Great for bowel function.

对肠道功能很有帮助。

I don't know the last time I had a cramp in my life.

我不知道我生命中最后一次抽筋是什么时候。

It's been years since I've had a cramp, despite exercising in a really hot place like Austin, Texas, where I'm sweating like there's no tomorrow.

尽管我在得克萨斯州奥斯汀这样非常热的地方锻炼，但我已经有很多年没有抽筋了，在那里我一直出汗，就像没有明天一样。

Whether you call it a supplement or not, I take electrolytes.

无论你是否称其为补充剂，我都会服用电解质。

I take LMNT, which I should disclose I'm an investor in that company.

我选择了 LMNT，我应该透露我是该公司的投资者。

So I drink an LMNT a day.

所以我每天喝一杯LMNT。

I take creatine monohydrate, five grams a day.

我服用一水肌酸，每天五克。

I take AG most mornings.

我大多数早上都服用 AG。

Oh, and I take Pendulum, the probiotic.

哦，我服用 Pendulum，益生菌。

Andrew Huberman:

安德鲁·休伯曼：

Got it.

明白了。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep.

是的。

As far as I know, there's no other probiotic that has any meaningful effect on the body outside of Pendulum, right?

据我所知，除了Pendulum之外，没有其他益生菌对身体有任何有意义的影响，对吗？

Because if you buy the argument that a probiotic for your gut needs to have anaerobic bacteria in it, there's no value in giving you aerobic bacteria.

因为如果你相信肠道益生菌需要含有厌氧菌的论点，那么为你提供需氧菌就没有价值了。

So you have to have something anaerobic.

所以你必须吃一些无氧的东西。

So Akkermansia, which works through the GLP-1 butyrate pathway, is anaerobic, and Pendulum's the only company that can make it.

因此，通过 GLP-1 丁酸途径发挥作用的 Akkermansia 是厌氧的，而 Pendulum 是唯一一家能够制造它的公司。

I have no affiliation with this company.

我与这家公司没有任何关系。

I think you should have the CEO, Colleen Cutcliffe, on your show.

我认为你的节目应该邀请首席执行官科琳·卡特克利夫 (Colleen Cutcliffe)。

She's an actual scientist, and she's fantastic.

她是一位真正的科学家，而且她很棒。

And it's a really interesting story how they developed this and how difficult it is to actually make an anaerobic bacteria.

这是一个非常有趣的故事，他们是如何开发这种细菌的，以及实际制造厌氧细菌是多么困难。

And so this is kind of an odd company because it's a supplement company, but they have to basically adhere to pharma GMP conditions to make it because of the anaerobic vats that you have to use infused with nitrogen to be able to make an anaerobic bacteria.

所以这是一家奇怪的公司，因为它是一家补充剂公司，但他们必须基本上遵守制药 GMP 条件才能制造它，因为你必须使用注入氮气的厌氧罐才能制造厌氧细菌。

So anyway, so I take three of their products.

所以无论如何，我拿了他们的三个产品。

I take something called Glucose Control, I take Polyphenol, and I take Akkermansia.

我服用一种叫做“血糖控制”的药物，服用多酚，还服用阿克曼西亚。

Andrew Huberman:

安德鲁·休伯曼：

Okay.

好的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

And I think that's the list.

我想这就是清单。

Andrew Huberman:

安德鲁·休伯曼：

Okay.

好的。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

Andrew Huberman:

安德鲁·休伯曼：

I'll try and move through my list pretty quickly.

我会尝试快速浏览我的列表。

I may miss one or two things, and I don't know, maybe we'll put the list someplace online and fill in any gaps.

我可能会错过一两件事，我不知道，也许我们会将列表放在网上的某个地方并填补任何空白。

I definitely take AG, AG1.

我肯定选AG，AG1。

That's my typical ad read.

这是我典型的广告阅读方式。

I've been doing it since 2012.

我从2012年就开始这么做了。

That's true.

确实如此。

I take one or two servings a day, three if I'm traveling, and I'll generally do that first thing in the morning or in the evening.

我每天服用一到两份，如果我在旅行，则服用三份，而且我通常会在早上或晚上做第一件事。

For me, it's really about capping off the vitamin minerals that I might be lacking in my diet, and also the whole adaptogen business, I think, and polyphenols.

对我来说，这实际上是为了限制我的饮食中可能缺乏的维生素矿物质，以及我认为的整个适应原业务和多酚。

And I'm very interested in Pendulum because part of the reason I take AG1 is for the gut health aspect.

我对 Pendulum 非常感兴趣，因为我服用 AG1 的部分原因是为了肠道健康。

I think just bowel movements are more where I'd want them.

我认为排便更符合我的意愿。

It sounds kind of weird to talk about, but you just feel better when your gut motility is right.

这听起来有点奇怪，但当你的肠道蠕动正常时，你就会感觉更好。

I feel like it adjusts my gut motility, so it's neither too fast nor too slow.

我觉得它调整了我的肠道蠕动，所以它既不太快也不太慢。

So that's first and foremost.

所以这是首要的。

I take a quality fish oil, either the one that AG makes or Carlson's in liquid form-

我选择优质鱼油，要么是 AG 生产的，要么是 Carlson 的液体形式-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm-hmm

嗯嗯

Andrew Huberman:

安德鲁·休伯曼：

...

that has that lemon flavoring, and I make sure I get above one gram per day of EPA.

有柠檬味，我确保每天摄入超过一克的 EPA。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yep.

是的。

Andrew Huberman:

安德鲁·休伯曼：

So that's usually a tablespoon, sometimes two tablespoons.

所以通常是一汤匙，有时是两汤匙。

I make sure that I get enough D3, typically from the dropper, 5,000 IU per day approximately, sometimes 3,000, sometimes 7,000.

我确保获得足够的 D3（通常通过滴管）每天大约 5,000 IU，有时 3,000，有时 7,000。

I kind of play around that.

我有点在玩这个。

And I test my blood levels.

我测试了我的血液水平。

I also take methyl B12, and I also take tongkat ali, so I take one capsule of that in the early part of the day.

我还服用甲基 B12，还服用东革阿里，所以我在当天早些时候服用一粒胶囊。

That has lowered my sex hormone binding globulin, freeing up a bit more testosterone.

这降低了我的性激素结合球蛋白，释放出更多的睾酮。

That's why I like it.

这就是我喜欢它的原因。

And I take a couple of green tea capsules in the morning.

我早上服用几粒绿茶胶囊。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Oh, yeah.

哦，是的。

Andrew Huberman:

安德鲁·休伯曼：

I drink yerba mate.

我喝马黛茶。

That's more of a stimulatory effect, and I take the NMN in powder form, sometimes NR as well.

这更多的是一种刺激作用，我服用粉末形式的 NMN，有时也服用 NR。

And again, if I run out of that, I tend to go long periods of time without.

再说一次，如果我用完了，我往往会很长一段时间没有。

I use LMNT-

我用LMNT-

Dr. Peter Attia:

彼得·阿蒂亚博士：

Mm-hmm

嗯嗯

Andrew Huberman:

安德鲁·休伯曼：

...

as an electrolyte.

作为电解质。

So people are probably noticing this is all pretty basic.

所以人们可能注意到这都是非常基本的。

I take, in my case, 10 grams of creatine monohydrate per day.

就我而言，我每天服用 10 克一水肌酸。

I sometimes forget to take it.

我有时会忘记拿它。

That's why I take 10 grams.

这就是为什么我服用 10 克。

I'll sometimes miss a day.

有时我会错过一天。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Okay.

好的。

Andrew Huberman:

安德鲁·休伯曼：

And I certainly feel the effects of that in the gym because of the greater water volume in the muscles.

我在健身房里确实感受到了这种影响，因为肌肉中的水量更大。

But there are a lot of data on creatine monohydrate for sake of either maintaining or offsetting some of the cognitive dysfunction associated with sleep deprivation, maybe aging, altitude, and some other things as well.

但有大量关于一水肌酸的数据，目的是为了维持或抵消一些与睡眠不足相关的认知功能障碍，可能是衰老、海拔高度和其他一些因素。

And then for a few months, I was playing around with, let's say, nicotine gums.

然后几个月来，我一直在玩尼古丁口香糖。

I stopped doing that.

我不再这样做了。

First of all, I was dipping it, and I ended up lisping for an entire episode of the Lex Fridman podcast that I only realized later.

首先，我正在沉浸其中，结果我用口齿不清的方式听完了莱克斯·弗里德曼播客的一整集，我后来才意识到这一点。

So I stopped taking it also because it gave me a kind of a tick and cough when I wasn't chewing it.

所以我停止服用它，因为当我不咀嚼它时，它会给我一种蜱虫和咳嗽的感觉。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Hmm.

嗯。

Andrew Huberman:

安德鲁·休伯曼：

And then I felt like I needed to chew it, and it's a little too stimulatory for me.

然后我觉得我需要咀嚼它，这对我来说有点太刺激了。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Hmm.

嗯。

Andrew Huberman:

安德鲁·休伯曼：

Before sleep, I take magnesium threonate.

睡觉前，我服用苏糖酸镁。

I'm really bullish on magnesium as well.

我也非常看好镁。

Apigenin, 50 milligrams, which is essentially chamomile extract, and theanine.

芹菜素，50 毫克，本质上是洋甘菊提取物和茶氨酸。

And occasionally I'll take 900 milligrams of inositol also.

有时我也会服用 900 毫克肌醇。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Hmm.

嗯。

Andrew Huberman:

安德鲁·休伯曼：

Or instead, kind of mix those up and around.

或者相反，将它们混合起来。

And then I use a quality whey protein as a protein replacement, that kind of thing.

然后我使用优质乳清蛋白作为蛋白质替代品，诸如此类。

And I've played around with various things like shilajit, and I'll sometimes get the sense that it's having an effect.

我尝试过各种东西，比如喜来芝，有时我会感觉到它正在发挥作用。

But then I'll stop taking it for long periods of time.

但之后我会长时间停止服用它。

There are very few things that I've stayed with for long periods of time, and I basically just described what those are.

我能长期坚持的东西很少，我基本上只是描述了那些东西。

If ever someone were to design a supplement that would provide more energy all day long that wasn't caffeine, I'd probably look to that.

如果有人要设计一种非咖啡因的补充剂，可以全天提供更多能量，我可能会关注。

But I ingest caffeine in the form of yerba mate and coffee.

但我以马黛茶和咖啡的形式摄入咖啡因。

I've played around with caffeine tablets, taking 50 milligrams of caffeine in tablet form.

我尝试过服用咖啡因片，服用 50 毫克片剂形式的咖啡因。

I mention that only because it has a distinctly different feel than ingesting caffeine through liquid form.

我提到这一点只是因为它与通过液体形式摄入咖啡因的感觉截然不同。

It feels stronger, and I don't know why that is.

感觉更强烈了，我不知道为什么。

In fact, there's a very well-known podcaster who drinks peppermint tea and takes caffeine tablets as a way to, oh, I don't know, drink peppermint tea, which sounds very nice and mellow, but also get the stimulant effect.

事实上，有一个非常知名的播客，他喝薄荷茶，并服用咖啡因片作为一种方式，哦，我不知道，喝薄荷茶，听起来非常好听，醇厚，而且还能获得兴奋的效果。

So anyway, that's pretty much it.

无论如何，差不多就是这样了。

And then I do a lot of things, as I know you do, mainly based on suggestions you've made about getting zone two cardio, rucking, weight vest walks and hikes three times a week, resistance training three times a week, cardiovascular training, one long, one medium, one short.

然后我做了很多事情，正如我知道你所做的那样，主要是基于你提出的建议，比如每周三次二区有氧运动、反屈、举重背心步行和徒步旅行、每周三次阻力训练、心血管训练，一次长、一次中、一次短。

And I try and hit the sauna and the cold once a week.

我每周尝试一次桑拿和冷敷。

And yeah, that's pretty much it.

是的，差不多就是这样。

I think there are a bunch of other supplements that are really interesting and kind of fun to play with if one wants to.

我认为还有很多其他补充剂非常有趣，如果有人愿意的话，玩起来也很有趣。

Like 600 milligrams of alpha-GPC or 900 milligrams of alpha-GPC in a double espresso prior to a workout.

比如锻炼前的双倍浓缩咖啡中含有 600 毫克 α-GPC 或 900 毫克 α-GPC。

You feel different.

你感觉不同了。

It's a stimulant.

这是一种兴奋剂。

But I don't like to do that too often because of the increase in TMAO that occurs, and then you have to take 600 milligrams of garlic to offset that increase, and you start getting-

但我不喜欢经常这样做，因为TMAO会增加，然后你必须服用600毫克大蒜来抵消增加的量，然后你开始——

Dr. Peter Attia:

彼得·阿蒂亚博士：

If we believe TMAO matters.

如果我们相信 TMAO 很重要。

Andrew Huberman:

安德鲁·休伯曼：

Right.

对。

If you believe TMAO matters and-

如果您认为 TMAO 很重要并且-

Dr. Peter Attia:

彼得·阿蒂亚博士：

I don't.

我不知道。

Andrew Huberman:

安德鲁·休伯曼：

Okay, great.

好的，太好了。

Even better.

甚至更好。

I'll maybe skip the garlic.

我也许会不吃大蒜。

So things like that.

诸如此类的事情。

I prefer to just eat garlic anyway.

无论如何，我更喜欢只吃大蒜。

So there are a bunch of things like that-

所以有很多这样的事情——

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah

是啊

Andrew Huberman:

安德鲁·休伯曼：

...

that are kind of fun to play with as pre-workouts.

作为训练前的游戏，这很有趣。

But yeah, that's the core supplement regimen, and it's the one I've stuck with for, gosh, at least 10 years.

但是，是的，这就是核心补充疗法，天哪，我已经坚持了至少 10 年。

Or in the case of AG, more than that.

或者就 AG 而言，还不止这些。

So I should say, because any discussion around supplements, I think is going to have people pricking up their ears to, okay, this is like a sales pitch or something.

所以我应该说，因为任何关于补充剂的讨论，我认为都会让人们竖起耳朵，好吧，这就像推销或其他东西。

I absolutely want to go on record.

我绝对想记录下来。

The things you choose to do and not do are going to have much greater effect on your health span and lifespan, that is the behavioral things, in particular, sleep, exercise, nutrition, sunlight, et cetera, than any one supplement that you're going to take.

您选择做和不做的事情将对您的健康寿命和寿命产生更大的影响，即行为因素，特别是睡眠、锻炼、营养、阳光等，比您要服用的任何一种补充剂影响更大。

So I do view supplements, I think, through the appropriate lens, which is that they are indeed a supplement.

因此，我认为，我确实通过适当的视角来看待补充剂，即它们确实是一种补充剂。

They are not necessary.

它们是没有必要的。

Many of them are simply sufficient to serve as an insurance policy or to augment mental and physical health, maybe longevity, in ways that make it worthwhile given my disposable income that I want to devote to supplements.

其中许多都足以充当保险单或增强身心健康，也许可以延长寿命，考虑到我想用于补充品的可支配收入，这些都是值得的。

But I don't think you need them.

但我认为你不需要它们。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah.

是的。

I'll go even more extreme on that statement.

我会更加极端地对待这一说法。

Everything we have talked about on this podcast today, whether it be NR, NAD, NMN, theracumin, magnesium, this supplement, that supplement, all of that stuff, while potentially mattering, I would put in the category of, was the Titanic serving lobster or steak?

我们今天在这个播客上讨论的所有内容，无论是 NR、NAD、NMN、theracumin、镁、这种补充剂、那种补充剂，所有这些东西，虽然可能很重要，但我会把它归入以下类别：泰坦尼克号供应龙虾还是牛排？

Look, I like steak more than lobster.

瞧，我比龙虾更喜欢牛排。

That's a relative discussion.

这是一个相对的讨论。

Exercise, sleep, nutrition, emotional health is the question of what was the heading of the Titanic?

运动、睡眠、营养、情绪健康是泰坦尼克号的标题是什么？

Okay.

好的。

So I just want people to understand the magnitude of what we're talking about.

所以我只是想让人们了解我们正在谈论的事情的重要性。

How you eat, how you sleep, how you train, and how you take care of your mental health is the equivalent of what direction was the Titanic going with respect to the iceberg.

你如何饮食、如何睡眠、如何训练以及如何照顾自己的心理健康，就相当于泰坦尼克号相对于冰山的走向。

All this supplement bullshit that we just talked about is equivalent to were they serving lobster or were they serving steak, and was the band playing this song or that song?

我们刚才谈到的所有这些补充废话相当于他们提供龙虾还是牛排，乐队演奏的是这首歌还是那首歌？

I'm not saying those things don't matter, but just put them in the context of the direction the Titanic is going.

我并不是说这些事情不重要，只是将它们放在泰坦尼克号前进方向的背景下。

Andrew Huberman:

安德鲁·休伯曼：

Okay.

好的。

So I completely agree with you.

所以我完全同意你的观点。

Exercise, sleep, nutrition, and emotional health, not listed in any particular order.

锻炼、睡眠、营养和情绪健康，未按任何特定顺序列出。

Peter and I both completely agree those are the critical four.

彼得和我都完全同意这四个是关键的。

Before we close, NR, NMN, NAD, and NAD in particular, how do we view this?

在我们结束之前，尤其是 NR、NMN、NAD 和 NAD，我们如何看待这一点？

Is it a pathway that we should be focusing on in terms of supplementation or infusions for sake of extending our life?

为了延长寿命，我们是否应该关注补充或输液的途径？

My answer on that is no

我对此的回答是否定的

Dr. Peter Attia:

彼得·阿蒂亚博士：

Yeah, I would say the same.

是的，我也会这么说。

I don't remember who said this, but someone, maybe it was Nassim Taleb, said, "Don't tell me what you think, show me what's in your portfolio." Meaning people who pontificate about this stock versus that stock, he's like, assuming it was him that said this, he's like, "Okay, I don't care what you're telling me.

我不记得是谁说的，但有人，也许是纳西姆·塔勒布（Nassim Taleb）说，“不要告诉我你的想法，让我看看你的投资组合中有什么。”意思是那些武断地谈论这只股票与那只股票的人，他就像，假设是他说的，他就像，“好吧，我不在乎你告诉我什么。

Tell me what you own.

告诉我你拥有什么。

That's going to show me your conviction." So through that lens, look, I'll show you my conviction on exercise.

这会让我看到你的信念。”因此，通过这个镜头，看，我将向您展示我对锻炼的信念。

I'll show you what I do.

我会告诉你我是做什么的。

I'll show you my conviction on sleep.

我将向您展示我对睡眠的信念。

This is what I do.

这就是我所做的。

I'll show you my conviction on all these other things.

我将向你展示我对所有其他事情的信念。

I don't take these supplements, full stop.

我不服用这些补充剂，完全停止。

I don't take them because I can't afford-- It's not that I can't afford them.

我不买它们是因为我买不起——并不是我买不起。

It's not that they're any inconvenience to me to take them.

并不是说带它们对我来说有什么不便。

I passionately do not believe they do anything for me, and why would I waste time, money, anything on something that I really don't believe makes a difference?

我热切地不相信他们为我做任何事，为什么我要浪费时间、金钱或任何东西在我真的不相信有什么作用的事情上呢？

Now, again, I am always happy to be proven wrong, and I am very happy to say that two years from now, five years from now, we could be doing this exercise again, and in the presence of new information, maybe I'm not taking rapamycin and maybe I am fistfuling NR and NMN.

现在，我总是很高兴被证明是错误的，我很高兴地说，两年后，五年后，我们可以再次进行这项练习，在新信息的存在下，也许我不会服用雷帕霉素，也许我会握着 NR 和 NMN。

Possible.

可能的。

I will reserve the right to change my mind for the rest of my life in the presence of new data.

我将在余生中保留在新数据出现时改变想法的权利。

But as it stands today, I do not take these supplements, and I have no foreseeable plan to do so until information changes.

但就目前情况而言，我不服用这些补充剂，并且在信息发生变化之前我没有可预见的计划这样做。

Andrew Huberman:

安德鲁·休伯曼：

Great.

太棒了。

Thank you for that clear stance and the willingness to change it in light of new data.

感谢您的明确立场以及根据新数据改变立场的意愿。

Peter, so good to sit down with you again and talk science, talk health, and in this case, talk about the supplements that we're not going to take in addition to the ones that we do take.

彼得，很高兴再次与您坐下来谈论科学，谈论健康，在这种情况下，谈论除了我们确实服用的补充剂之外我们不会服用的补充剂。

We will do this again sometime very soon, hopefully.

希望我们很快就会再次这样做。

Dr. Peter Attia:

彼得·阿蒂亚博士：

In Austin.

在奥斯汀。

Andrew Huberman:

安德鲁·休伯曼：

Would love that.

会喜欢的。

Thanks, Peter.

谢谢，彼得。

Dr. Peter Attia:

彼得·阿蒂亚博士：

Thanks, man.

谢谢，伙计。

Andrew Huberman:

安德鲁·休伯曼：

Thank you for joining me today for my discussion with Dr. Peter Attia.

感谢您今天加入我与 Peter Attia 博士的讨论。

If you're learning from and/or enjoying this podcast, please subscribe to our YouTube channel.

如果您正在学习和/或喜欢此播客，请订阅我们的 YouTube 频道。

In addition, please subscribe to the podcast on both Spotify and Apple.

此外，请在 Spotify 和 Apple 上订阅该播客。

That's a terrific zero-cost way to support us.

这是支持我们的绝佳零成本方式。

In addition, you can leave us up to a five-star review on either Spotify or Apple.

此外，您可以在 Spotify 或 Apple 上给我们留下五星级评价。

Please also check out the sponsors mentioned at the beginning and throughout today's episode.

另请查看今天节目开头和整个节目中提到的赞助商。

That's the best way to support this podcast.

这是支持这个播客的最佳方式。

If you have questions for me or comments about the podcast or topics or guests that you'd like me to consider for the Huberman Lab podcast, please put those in the comments section on YouTube.

如果您对我有疑问，或者对播客有任何意见，或者您希望我为 Huberman Lab 播客考虑的主题或嘉宾，请将这些意见放入 YouTube 的评论部分。

I do read all the comments.

我确实阅读了所有评论。

If you're not already following me on social media, I am Huberman Lab on all social media platforms.

如果您还没有在社交媒体上关注我，我是所有社交媒体平台上的 Huberman Lab。

So that's Instagram, X, formerly known as Twitter, Threads, LinkedIn, and Facebook.

这就是 Instagram、X，以前称为 Twitter、Threads、LinkedIn 和 Facebook。

And on all those platforms, I discuss science and science-related tools, some of which overlaps with the content of the Huberman Lab podcast, other of which is distinct from the content on the Huberman Lab podcast.

在所有这些平台上，我讨论科学和与科学相关的工具，其中一些与胡伯曼实验室播客的内容重叠，另一些则与胡伯曼实验室播客的内容不同。

So again, it's Huberman Lab on all social media platforms.

再说一遍，所有社交媒体平台上都是 Huberman Lab。

And if you haven't already subscribed to our Neural Network Newsletter, our Neural Network Newsletter is a zero-cost monthly newsletter that includes what we call protocols in the form of brief one to three-page PDFs on everything from neuroplasticity and learning, to optimizing your sleep, to improving dopamine regulation, to foundational fitness protocol that includes both resistance training and cardiovascular training.

如果您还没有订阅我们的神经网络时事通讯，我们的神经网络时事通讯是一份零成本的月度时事通讯，其中包括我们所说的一到三页 PDF 形式的简短协议，内容涉及从神经可塑性和学习到优化睡眠、改善多巴胺调节，再到包括阻力训练和心血管训练的基础健身协议。

It details sets and reps.

它详细介绍了组数和次数。

All of that and more is completely zero cost.

所有这些以及更多都是完全零成本的。

You simply go to hubermanlab.com, go to the Menu tab, scroll down to Newsletter, and provide your email.

您只需访问 hubermanlab.com，转到“菜单”选项卡，向下滚动到“时事通讯”，然后提供您的电子邮件即可。

And I should point out that we do not share your email with anybody.

我应该指出，我们不会与任何人分享您的电子邮件。

Thank you once again for joining me for today's discussion, all about NAD and longevity with Dr. Peter Attia.

再次感谢您参加今天的讨论，与 Peter Attia 博士讨论 NAD 和长寿问题。

And last but certainly not least, thank you for your interest in science.

最后但并非最不重要的一点是，感谢您对科学的兴趣。