恢复青春活力：逆转大脑与身体的衰老 | 托尼·怀斯-科雷博士

我们其实并不知道。

We don't really know.

在衰老研究领域，这被称为拮抗性多效性。

And in the aging field, is called antagonistic pleiotrophy.

所以，某些在年轻时有益的东西，到了年老时反而有害，对吧？

So something that is good when you're young can be bad when you're old, right?

这与这个概念有关。

It relates to this concept.

而人类当然可以说在某种程度上脱离了进化的影响，对吧？

And humans are of course, you know, they're sort of exempt from evolution, if you will, right?

因此，我们自然的寿命可能在30到40岁左右。

So our natural lifespan is probably around 30 to 40.

如果回溯历史，人们当时的寿命就是这样的。

If you look back in history, that's how long people lived.

我的意思是，当然总有少数人寿命特别长，但大多数人早早就去世了。

I mean, were always individuals who had, exceptional lifespan, but most people would die much earlier.

什么？

Of what?

感染，而且很可能主要是传染病。

Infections, and it was probably mostly infectious diseases.

但从进化角度来看，一旦你达到性成熟，繁衍后代，这就已经保证了你的后代，而这个时间点大约在三十到四十岁。

But you know, you could argue from an evolutionary perspective, once you're sexually mature, you reproduce and you guaranteed your offspring, which is around thirty to forty years.

自然不再关心你了。

Nature doesn't care about you anymore.

所以，这么说可能很残酷，但——只要

And so there's no longer, it's very brutal to hear, but- As long

你的孩子足够多，能够养活他们，我的意思是，婴儿自己无法抚养，没错。

as your kids are sufficient enough to raise it, mean, infant can't raise That's right.

七岁的孩子也许可以，如果他们非常勤快的话，但孩子至少需要我们到他们……他们确实需要我们，是的。

A seven year old maybe could, if they were very industrious, you know, but kids need us at least until they They need need us us, yeah.

晚期

Late

对吧？

Right?

那么，你可能会有一些进化压力，促使那些拥有知识和智慧的个体存活下来，以帮助群体生存。

Then, you you may have some evolutionary pressure to maintain individuals who have knowledge and wisdom to help the, you know, the group to survive.

但这种进化力量维持你活着，可能要弱得多，对吧？

But that's probably a much weaker force of evolution to keep you alive, right?

因此，现在越来越多的人认为存在一些转折点，比如更年期，还有男性在30到40岁左右，血液成分也会发生显著变化。

And so that's why people increasingly see now that there are these inflection points that you know, menopause, but also in men around age 30 to 40, dramatic changes in the composition again of the blood.

我们刚刚研究过这一点，我之前提到过，如果你观察从20岁到90岁人类一生中血液成分的变化，我们称之为衰老的波动。

We just looked at this, I mentioned earlier, if you look at the composition of the blood across human lifespan from 20 to 90, We call these waves of aging.

第一波波动出现在35岁左右。

The first wave is around 35 years of age.

许多因子的浓度发生剧烈变化。

Dramatic changes in concentrations of lots of factors.

而且这不仅发生在女性身上，男性也是如此。

And not just in women, in men as well.

35岁。

35.

到35到40岁。

To 35 to four.

有改善吗？

Decoriation, any improvements?

有些上升，有些下降，这虽然只是推测，但是否与自然需要我们多久、之后就不再关心有关？

Some go up, some go down and it's speculative but does that have something to do with this is how long nature needs us and then it doesn't care.

而我们现在平均能活到80岁甚至更长，对吧？

And the fact that we live now 80 or even longer on average, right?

这真的要归功于卫生条件和某些药物，比如控制血压和心脏病的药物，还有抗生素。

Is really thanks to hygiene and certain medications that, blood pressure and heart disease that you Right, have antibiotics.

上周末有个朋友给我打电话，他有一些

Have a friend called me over the weekend, he's got some

抗生素，抱歉，

Antibiotics, I'm sorry,

一场严重的感染几乎让他一只眼睛失明，静脉注射抗生素后，瞬间就好了。

brutal infection that could almost took out his vision in one eye, antibiotics infused, boom, done.

我知道有些听众不喜欢抗生素，他们担心我会说，如果你得了严重的、具有攻击性的感染，而且靠近大脑或眼睛，及时使用正确的抗生素治疗，那你真是幸运至极。

I know some listeners don't like antibiotics, and they're concerned about I'll tell you, if you have a brutal infection that's aggressive, and it's near your brain or your eye, and you get on systemic antibiotics, and they're the right one, you are one lucky individual.

如果你没有及时治疗，可能会面临摘除一只或两只眼睛的风险。

And if you don't, you could be looking at excavating one or both eyes.

这太残酷了。

It's brutal.

是的。

Yeah.

对。

Yeah.

没错。

Yeah.

太棒了，对于许多不同类型的感染，抗生素都是救命的良药。

Wonderful And for many different infections, antibiotics are a lifesaver.

当然。

Absolutely.

对。

Yeah.

这是一个非常好的观点。

So it's a really good point.

实际上，我的朋友汤姆·兰德尔之前提到过，他总是强调，许多研究在动物模型中以寿命作为结果指标，但并没有真正关注这种延长的寿命是怎样的——这些生物只是勉强维持着，还是依然强壮且充满活力，对吧？

And actually my friend Tom Randle mentioned earlier, he always makes that point that, a lot of the study look at lifespan as an outcome in animal models, but they don't really look at how active or, you know, what is sort of the level of that extended lifespan is, are they just hanging in there, these organisms, or are they still strong and vital, right?

活力还在吗？

Is the vitality still there?

我认为我们还没有找到一种能让人长期保持整体健康的神奇方法，尤其是在人类身上。

And I think we don't, we haven't found a magic that would keep everything together for a longer period of time and certainly not in humans.

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If you're a regular listener of the Huberman Lab Podcast, you've no doubt heard me talk about the vitamin mineral probiotic drink AG1.

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And if you've been on the fence about it, now's an awesome time to give it a try.

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For the next few weeks, AG1 is giving away a full supplement package with your first subscription to AG1.

他们将免费赠送一瓶维生素 D3K2、一瓶 Omega-3 鱼油胶囊，以及新推出的睡眠配方 AGZ 的试用装——顺便说一句，这现在是我唯一服用的睡眠补充剂。

They're giving away a free bottle of vitamin D3K2, a bottle of omega-three fish oil capsules, and a sample pack of the new sleep formula AGZ, which by the way is now the only sleep supplement I take.

这太棒了。

It's fantastic.

我服用 AGZ 后的睡眠质量好得不可思议。

My sleep on AGZ is out of this world good.

AGZ 是一种饮品，因此无需服用大量药片。

AGZ is a drink, so it eliminates the need to take a lot of pills.

味道非常好。

It tastes great.

正如我所说，它让我睡得非常好，醒来时比以往任何时候都更精神焕发。

And like I said, it has me sleeping incredibly well, waking up more refreshed than ever.

我非常喜欢它。

I absolutely love it.

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Again, this is a limited time offer, so make sure to go to drinkag1.com/huberman to get started today.

今天的节目还由 Roka 赞助。

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

我很高兴与大家分享，我最近与 Roka 合作推出了一款红色镜片眼镜。

I'm excited to share that Roka and I recently teamed up to create a new pair of red lens glasses.

这款红色镜片眼镜建议在日落后晚间佩戴。

These red lens glasses are meant to be worn in the evening after the sun goes down.

它们可以过滤掉来自屏幕和 LED 灯的短波长光，而这些正是如今最常见的室内光源。

They filter out short wavelength light that comes from screens and from LED lights, which are the most common indoor lighting nowadays.

我要强调，Roka 的红色镜片眼镜并非传统意义上的蓝光过滤镜。

I want to emphasize Roka red lens glasses are not traditional blue blockers.

它们确实会过滤蓝光，但过滤的范围远不止蓝光。

They do filter out blue light, but they filter out a lot more than just blue light.

事实上，它们过滤了整个抑制褪黑激素分泌的短波长光谱范围。

In fact, they filter out the full range of short wavelength light that suppresses the hormone melatonin.

顺便说一下，你希望在晚上和夜间保持较高的褪黑激素水平，这有助于你更容易入睡并保持睡眠。

By the way, you want melatonin high in the evening and at night, makes it easy to fall and stay asleep.

这些短波长光线会促使皮质醇水平上升。

And those short wavelengths trigger increases in cortisol.

皮质醇在一天的早期阶段升高是有益的，但在晚上和夜间你不希望皮质醇水平上升。

Increases in cortisol are great in the early part of the day, but you do not want increases in cortisol in the evening and at night.

这些Roka红色镜片眼镜能确保褪黑激素正常健康地升高，同时让你的皮质醇水平保持在低位——这正是你在晚上和夜间所需要的。

These ROKA red lens glasses ensure normal healthy increases in melatonin and that your cortisol levels stay low, which is again, what you want in the evening and at night.

通过这种方式，这些Roka红色镜片眼镜能帮助你平静下来，改善入睡的过渡过程。

In doing so, these Roka red lens glasses really help you calm down and improve your transition to sleep.

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If you'd like to try Roka, go to roka.com, that's roka.com and enter the code Huberman to save 20% off your first order.

再次提醒，是roka.com，在结账时输入代码Huberman。

Again, that's roca.com and enter the code Huberman at checkout.

最近，我对一些关于日光照射与寿命关系的数据感到有些惊讶，尽管并不完全意外。

Lately, I've been somewhat surprised, although not entirely by some of the data on sunlight exposure and lifespan.

有一项来自瑞典的大规模研究发现，人们接受的日光照射越多，寿命就越长。

There's this really interesting large scale study out of Sweden where the more sunlight exposure people got, the longer they live.

即使是吸烟者，只要接受更多日光，平均来看——请注意这是平均值，分布是有重叠的——他们的寿命也比那些日光摄入不足的非吸烟者更长。

Even smokers who get more sunlight appear to on average, these are averages folks, seem to overlapping distributions, but live longer than non smokers who don't get sufficient sunlight.

不过，大量接受日光也与户外活动、新鲜空气等多种因素相关。

Now getting a lot of sunlight is also correlated with outdoor activity, fresh air, a number of things.

这项研究远非完美。

It's far from perfect study.

但是的，活力与长寿之间的相互作用非常有趣，我认为日光是促进活力的，而我们如今在药物——也可能是补充剂，但主要是药物和生活方式——之间寻求的平衡，就是如何通过干预来延长生命，同时更好地享受生命。

But yeah, the interplay between vitality, I think of sunlight as pro vitality, and longevity is such an interesting one because the dance that we seem to be playing now with medications and it could be supplements, but really medication and lifestyle is what can we do and take to get more life, but also to enjoy that life more.

有一些物质，比如生长激素，能让人感觉年轻许多，改善皮肤、头发，甚至认知能力，还有维持或增加肌肉、减少脂肪等等。

And there are certain things like growth hormone, will make people feel much more youthful, much more youthful, skin, hair, even cognition, etcetera, ability to maintain or put on muscle, lose fat, and on and on.

但总体而言，较高的IGF-1和生长激素水平意味着寿命会缩短。

But higher IGF-one and growth hormone, broadly speaking, means a shorter life.

是的，这可能需要付出代价，没错。

Yeah, maybe comes at a price, yeah.

是的。

Yeah.

所以我想，这取决于个人是否愿意做出这种权衡。

So I guess, I mean, can be determined individually whether or not somebody wants to make that trade off.

但我真正感兴趣的是那些来自年轻人类（可能是我们，但更年轻的个体）的血液输注中的物质，你提到是混合的，它们以不同方式影响细胞功能，恢复活力和长寿。

But what I'm excited about are the things that are possibly in these blood transfusions that come from younger humans, maybe us, but younger humans, you said pooled, that are getting to cellular function in a different way, that are restoring vitality and longevity.

也许你可以和我们讨论一些可能的候选物质，以及它们影响哪些通路。

And maybe there are a few candidates that you could discuss with us and what pathways they impinge on.

我可能不熟悉具体的分子，但它们是否影响DNA或表观基因组？

I probably won't be familiar with the specific molecules, but are they impacting DNA, the epigenome?

它们是否影响线粒体功能？

Are they impacting mitochondrial function?

如果你能的话，能否挑选出你最感兴趣的两到三个候选物质？当然，有些仍在研究中。

If you would maybe pick your two or three favorite candidates, if you can, know some of these are still under study.

这些因子通常是生长因子。

The factors often are growth factors.

GDF11是其中之一，它是一种生长与分化因子。实际上，IGF-1也被发现存在于年轻血液中，且浓度更高。

GDF11 is one of them that has been described, growth and differentiation factor There is, IGF-one actually also has been described to be in young blood is higher.

有一些因子是通过类似于移植年轻与年老血液的方法被识别出来的。

There are factors that have been identified through an approach that is similar to transferring young versus old.

我一名学生在读研期间，在我的实验室里做了这些异体共生实验，这些研究都密切相关。

So what one of my trainees did, it's all related when he was grad student in my lab, he did these parabiosis experiments.

随后，他的实验室和我的实验室分别进行了一个实验：我们让年轻小鼠运动，采集它们的血液，然后注射到没有运动的小鼠体内。

And then his lab and my lab independently did an experiment where we exercised mice, young mice, we took their blood and we injected it in non exercise mice.

我们发现，运动对大脑的有益影响可以通过血液传递。

And we could show that the beneficial effects of exercise on the brain were transmitted again by blood.

你们是把年轻血液输给年轻个体吗？

Were you going young to young?

我们是将年轻血液输给年轻个体，索尔则是将年轻血液输给年老个体，并证明他对大脑的影响比单纯输入年轻血液更强。

We went young to young, Saul went young to old, and could show that he can, has a stronger effect on these brains than just young blood.

如果是经过运动的年轻血液，效果会更好。

If it's exercised young blood, it's even better.

这让我很惊讶，因为我一直认为运动是一种有目的的应激，会诱导炎症分子产生，进而引发适应性反应。但事实上，运动过程中确实会释放一些因子，比如脑源性神经营养因子等，这些都是促进健康和活力的物质，它们并非为了引发适应反应而生，而是我们在运动时细胞释放出的有益物质。

So surprising to me because I think of exercise as a purposeful stress that induces inflammatory molecules that then induce Are an there factors that are liberated during exercise, brain derived nootrophic factor, etcetera, are pro health and vitality that are not designed to get up an adaptation, that are just good stuff coming out of the cells when we exercise.

实际上，他的实验室和我的实验室都发现，运动似乎能以某种方式触发肝脏释放某些因子，这些因子随后进入大脑，使大脑功能变得更好。

Both actually he and my lab found is that somehow this exercise seemed to trigger the release of factors from the liver that then go to the brain and make the brain function better.

在我们的研究中，我们描述了一种名为Clostrin的蛋白质。

In our case we describe the protein that's called Clostrin.

它具有多种不同的功能，能够与脂质结合，也被称为载脂蛋白J。

It has many different roles, it can bind to lipids, it's also called Apolipoprotein J.

它涉及凝血和补体通路，非常复杂。

It's involved in coagulation and complement pathway, very complicated.

我们还没完全弄清楚它是如何产生这些效果的，但我们可以证明，如果我们制造重组合成的凝聚蛋白并注射到小鼠体内，就能模拟出部分效果。

We couldn't quite figure out how does it have these effects, but we could show that if we make recombinant synthetic clustering and inject it into mice, we could mimic some of the effect.

这是凝聚蛋白吗？

This is clustering?

是的。

Yeah.

它在补体通路中。

It's in the complement pathway.

是的。

Yeah.

补体系统最初被发现是免疫系统的一部分，作为免疫系统中‘吃掉我’信号的一部分包裹细胞，但它还有很多其他功能，对吧？

Complement, initially identified as part of the immune system, coats cells as a part of the eat me signal in the immune system, or the eat me system, but does many other things too, right?

参与突触的形成和重塑，我们从贝丝·史蒂文斯和其他人的研究中了解到这一点。

Involved in synapse formation and remodeling, and we know from Beth Stevens' work and others.

太惊人了。

Wild.

太惊人了。

Wild.

是的。

Yeah.

太惊人了。

Wild.

然后索尔发现了另一个叫做GPLDH的因子，他能明确证明它有作用，但具体机制尚不明确。

And then Saul found another factor that's called GPLDH that again he can clearly show has an effect, but how exactly does that is is not clear.

最近，他做了一个非常有创意的实验：他对小鼠进行了热量限制，这本身是一种被广泛接受的、可能促进长寿的有益效应。他提取这些小鼠的血浆，注入其他小鼠体内，再次分离出能模拟这种效应的因子。

Most recently he did another really creative experiment where he did caloric restriction of mice, and again that's sort of an accepted beneficial effect and longevity promoting potentially, and takes the plasma from mice, puts it into other mice, and again can isolate factors that mimic this effect.

因为间歇性禁食。

Because of intermittent fasting.

是的。

Yeah.

这告诉我们，这是一种生理现象，我们称之为生理学。

What this tells us is that, this is physiology, We call this physiology.

我们体内的器官会相互交流。

Organs in our body communicate with each other.

存在一种协同作用，导致某些因子被释放到血液中，然后作用于不同器官，在这种情况下产生有益效果。

And there's an orchestration of effects that leads to factors that are released into the blood and then they go to different organs and have, in this case, beneficial effects.

因此，运动的效果并不仅仅是因为你觉得自己在运动，而是确实有某些因子被释放出来，似乎对你的大脑有益。

So the exercise effect is not just because you think you're exercising, but they're actually factors released that seem to benefit your brain.

太有趣了。

So interesting.

有一个观点，至少对我来说，是最早在一本叫《Spark》的书里提出的。

There's this idea that was, at least to me, first put forth in a book called Spark.

你了解约翰·拉迪的这本书吗？

Do you know John Rady's book?

它是在几年前出版的，你知道的。

It's some, it's, you know, came came out some years ago.

他是一位医生，我认为是在哈佛医学院受训的。

He's a physician, I believe trained at Harvard Med.

他谈到了运动对大脑可塑性所必需的基本条件。

And he talked about the essential requirements for movement in brain plasticity.

那是神经可塑性研究的早期阶段，但他提到了脑源性神经营养因子以及其他由运动释放的物质。

This was early days of understanding neuroplasticity, but he talked about brain derived nootrophic factor, other things that are liberated by exercise.

但他书中描述了一些有趣的实验，比如有一种生活在海洋中的生物，会游动，拥有相对复杂的神经系统——至少对它来说是这样。

But he described some interesting experiments in there of, for instance, there's a sea dwelling creature that swims around, and has a fairly elaborate nervous system, at least for it.

但在它生命中的某个时刻，它会附着在岩石上，并且基本上吃掉自己的神经系统。

But then at some point in its life, settles down on a rock, and eats its own nervous system, basically.

有一些有趣的实验研究了当让这种生物（我认为就是这种生物，但也可能是其他生物）持续运动时会发生什么。

There've been some interesting experiments looking at what happens when you get that organism or other organisms, I believe, I think it was that organism, but other organisms to continue moving.

似乎运动过程中肌肉的活动会产生反馈，这种反馈可能是神经肌肉起源的，也可能是激素起源的，我认为我们还不清楚它是否来自肌肉。

It seems like there's feedback from the process of moving the musculature, and then it could be neuromuscular in origin, it could be hormonal in origin, I don't think we know that it comes from muscle.

但运动的需求似乎向大脑传递了一个信号：大脑需要继续存在，不仅仅是控制运动的部分，而是控制运动活动的脑区，身体可能通过化学或其他类型的反馈告诉大脑：如果它在运动并持续运动，大脑就需要保持强健。

But there's something about the requirement for movement that signals to the brain that it needs to continue to exist, and not just the motor portions of the brain, and that it or the portions of the brain controlling motor activity, but that the body may supply chemical or other types of feedback to the brain that if it's moving and continues to move, that the brain needs to continue to be robust.

这让我觉得非常有趣，因为除了激素因素外，很少有其他因素能解释身体运动如何向大脑传递活力信号。

Which I find very interesting, because few things to me explain how movement of the body would signal vitality of the brain, aside from hormone borne factors.

但这在某种程度上是合理的，持续运动身体对于维持大脑的健康至关重要。

But it kind of makes sense, Continuing to move the body is essential for keeping the Yeah, brain

是的。

yeah.

而且，运动干预方面有成千上万的研究表明，运动对心血管健康有益，也对其他类型的运动有益。

And I mean, exercise interventions, there's thousands of studies that show that exercise is beneficial, cardiovascular, but also other exercise.

是的，现在每个人都对力量训练充满热情。

Yeah, now it seems everyone's excited about resistance training.

我的意思是，显然两者都是正确的答案。

I mean, I think both is clearly the answer.

我的意思是，你看起来很棒。

I mean, you look good.

我的意思是，你还没到八十岁，但我可能已经到了。

What's, I mean, you're not in your eighties, but do I might be.

你锻炼吗？

Do you exercise?

对，那确实很了不起。

Right, yeah, that would be impressive.

你的锻炼计划是什么？

What is your exercise regimen?

人们都想了解。

People wanna know.

是的，我喜欢跑步，尤其喜欢在户外跑步，享受阳光。

Yeah, run, I like running outdoors, I like the sun.

我尽量每周跑两次，每次五到十公里？

I try to get two runs, five to 10 ks Per week?

是的。

Yeah.

这主要是我做的锻炼。

That's the main exercise I do.

我每天早上做一些普拉提。

I do some Pilates in the morning.

我注意到，尤其是60岁后受伤，身体恢复得特别快地退化。

I'm struck by how quickly the body degrades after an injury, especially if that injury occurs after age 60.

小时候受伤，我们很快就能康复。

When we are injured as kids, we heal up.

这很神奇，对吧？

It's amazing, right?

意思是，孩子摔伤了，割了个口子，他们就只是说：‘怎么了？’

Mean, kids getting cuts, and they're just like, what happened?

他们很快就愈合了。

It's just they heal right up.

我们知道为什么孩子比成年人愈合得更快吗？

Do we know why we heal more quickly as kids than as adults?

我们知道免疫系统会像其他身体机能一样老化，它会从特异性反应转向非特异性反应，而这通常与炎症有关。

We do know that the immune system ages like everything, and it has this bias that it goes from a more specific response to a non specific response, and that is often associated with inflammation.

所以，有可能部分原因是，当你受伤时，炎症反应过强，而愈合反应却不足。

So it's possible that part of it is that if you have a wound, there's too much of an inflammatory response and less of a healing response.

但我们还知道，从衰老的生物体来看，如果你割伤了，细胞外基质中的蛋白质，比如胶原蛋白等，往往会过度产生，这可能会干扰快速愈合。

But we also know from aging organisms that if you have a cut, there is more of, there's proteins in the extracellular matrix like collagens and things like that, that are often overproduced, and they may interfere with a quick healing response.

所以我认为所有系统都有一点失调，这可能是原因，但我并不清楚具体的细节。

So I think everything is a little bit out of tune, and that might be the reason, but it's not really something I would know the details.

我一直对这样一个事实着迷：如果我们身体表面割伤，它可能愈合后留下疤痕，也可能不留下；但如果我们口腔内部割伤——那里细菌多、温暖潮湿，全天都与外界接触——却往往几乎不留下疤痕，或者疤痕非常轻微。

I've always been fascinated by the fact that if we get a cut on the surface of our body, that it may or may not heal with a scar, but if we get a cut on the inside of our mouth, which is loaded with bacteria, and warm and moist, and in contact with the outside world all day long, it tends to heal with either zero or much less of a scar.

有

Has

很有趣。

to Fascinating.

某种东西在

Be something in the

这是促进愈合的。

That's pro healing.

我相信有人正在研究这个，但必须有人弄清楚这一点。

And I believe people are studying this, but someone's gotta figure this out.

是的，确实如此，可能是唾液。

Yeah, it's true, It could be saliva.

很神奇，对吧？

Wild, right?

我的意思是，愈合速度，我知道那里血供丰富，但鼻子和手部血供也很丰富，而这些地方也会留下疤痕。

I mean, the rate of healing, I know there's a lot of blood supply, but there's also a lot of blood supply to the nose and to the hands, there's scars form on the hands and on the nose.

是的，婴儿身上也会有疤痕，对吧？

Yeah, it's also scarring in babies, right?

婴儿的伤口可能不会留下任何痕迹，但老年人同样的伤口却可能终身留下疤痕，是的。

May not leave, or a cut in a baby may not leave any trace, but the same type of wound in an older person may leave a scar for the rest of their life, yeah.

那么，我们如何超越相关性，真正理解因果关系呢？

So how do we move past correlation and to really understand causative stuff.

我们稍后再谈生活方式因素，但根据你提到的动物研究和人类研究，很明显，年轻血液中存在某种促进大脑和其他组织再生的物质。

So, we'll get back to lifestyle factors, but I mean, it's so very clear from the animal studies and from the human studies that you described that there's something in young blood or things in young blood that are pro rejuvenation for the brain and other tissues.

我们如何找到真正的抗衰老药物？

How do we get to a real pro longevity molecule medication

治疗？

treatment?

或者更准确地说，是促进健康？

Or pro health maybe more, right?

我认为这个领域里的大多数人并不真的关心延长寿命，也就是长寿，而是关注健康寿命。

I think most people in the field are not really interested in extending lifespan, which would be longevity, but health span.

我们之前也讨论过这一点，对吧？

So, and we talked about this before, right?

你要努力维持器官的功能，直到去世，这样你的大脑仍然能正常运作，认知能力保持完整。

That you try to maintain the function of your organs until you die so that your brain would still be functioning, you're cognitively intact.

你的所有器官都能相对良好地运作。

All your organs would still be functioned relatively well.

然后，你知道，你睡着了，这就是你生命的终结。

Then, you know, you fall asleep and that's the end of your life.

而且，正如你所说，延长寿命并不一定意味着什么，可能只是多活十年，但过得非常痛苦。

And not necessarily extending lifespan, as you said, it could be that we extend lifespan and you just have ten more miserable years.

这当然没有人想要，对吧？

That certainly nobody would want that, right?

但我觉得要找到因果关系，我们首先需要在动物模型中进行这类生理实验，隔离出各个因素，然后用非常严谨的方法逐一测试，比如确认某个因素是否具有维持小鼠大脑功能的能力。

But I think to get to causation, we need these types of experiments, physiological experiments in animal models first to isolate individual factors and then test them on an individual basis with very rigorous methods which we can do and say, this factor has the capacity to maintain, for example, brain function in the mouse.

然后我们必须在人类身上进行测试，通过精心设计的临床对照试验，让受试者不知道自己是否接受了治疗。

And then we have to test it in humans and do it in a careful clinically controlled trial where people are blinded whether they got the treatment or not.

并且开展足够大规模的研究，以便我们能说：好吧，这确实有效。

And do a big enough study that we can say, okay, this truly works.

然后我们就有了药物。

And then we have a drug.

我们离临床试验还有多近？

How close are we to the clinical trial?

有不同的分子。

There are different molecules.

Closso 其实是另一个。

Closso is actually another one.

这是一种被描述为对多个不同器官有益的蛋白质。

It's this protein that has been described to have beneficial effects on multiple different organs.

其生物学机制再次不太明确，但是

The biology, again, not exactly clear, but

A L O T H O，Clotho。

A L O T H O, Clotho.

没错，是的，对。

That's right, yeah, yeah.

而且你知道，已经有公司在尝试将其推进到人体试验阶段。

And you know, there's companies trying to move this into humans, into human trials.

其他一些因子，我认为他们的公司正在尝试抑制有害因子。

Some of these other factors, think their companies are trying or inhibiting detrimental factors.

通过各自的临床试验，未来五到十年内我们或许就能取得成果，找到可能有效的疗法。

And with individual clinical trials you could get there in the next five, ten years, and maybe something that has an effect.

我认为我们不会拥有一个单一因子，一个能对所有方面都产生奇迹般效果的个体因子。

I think we will not have a factor, an individual factor that just has, you know, this miracle effect on everything.

这一点从年轻血液的研究中已经非常明确了。

This is very clear from the studies of young blood.

它涉及许多不同的因素，它们针对不同组织中的不同通路和不同细胞类型。

It's many different factors and they target different pathways, different cell types in different tissues.

所以你确实需要——可能需要决定，比如这个器官需要这种治疗，那个器官需要那种治疗，以优化其功能并保持其——你知道——以最佳状态运行直到你100岁。

So you really need to, you may have to decide, you know, for this organ we need this treatment, for this organ we need that treatment to optimize its function and keep it, you know, running at full capacity until you're a 100 years old.

我并不是建议任何人这么做，但我确实时不时听说有人已经在使用Clotho了。

I'm not suggesting anyone do this, but I do seem to hear now and again, that people are taking Clotho already.

这并不奇怪。

Not surprising.

人们总会，你知道的，抢先一步。

People will, you know, get ahead of the curve, so to speak.

是的。

Yeah.

我也读到过有人在使用GDF十一。

I've also read people taking this GDF eleven.

我不知道他们从哪里弄到的。

I don't know where they get it.

我猜大概是在墨西哥以及中美洲和南美洲。

I'm guessing it's just Mexico and Central And South America.

有很多诊所都在做这类事情。

There are a lot of clinics that do this sort of thing.

我要讲一个真实的故事作为警示，每当人们说‘我有个朋友’时，这位朋友是位医生，他患有背痛，给他带来了很多困扰。

I will put out a true story cautionary note, a friend who, whenever people say I have a friend, is a medical doctor who had a back pain that was giving him a lot of issues.

于是他去了墨西哥的一家干细胞诊所，接受了椎间盘干细胞注射，我的神经外科医生朋友们告诉我这是个糟糕的主意。

And he went to a stem cell clinic in Mexico, got an injection of stem cells into a spinal disc, which my neurosurgeon friends tell me is a terrible idea.

事实证明，椎间盘无法接受细胞注射。

It turns out the disc cannot accept cellular injections.

一位神经外科主任告诉我的。

A chair of neurosurgery told me that.

所以，如果各位想指责我，尽管来吧，但他是某知名医学院的神经外科主任。

So you can come at me if you want folks, but he's the chair of neurosurgery at a prominent medical school.

因此，椎间盘无法直接接受外来细胞的注射。

So that the disc cannot accept direct injections of foreign cells.

总之，这个人找了另一位不同的医生，去接受了这种注射，结果感染了一个鸡蛋大小的脓肿，导致他瘫痪了。

Anyway, this guy went a different guy, different MD, went and got this injection, and ended up with an egg sized infection that left him paralyzed.

他足够幸运，被空运到美国某家诊所，却被告知：就这样了，你没救了，我们只能切断你的脊髓。

He was fortunate enough to be airlifted to a certain clinic in The United States and told he was, that's it, you're done, we're going to have to just sever your spinal cord.

他被送往另一家诊所，幸运的是，那里的医生成功切除了感染，如今他能够正常活动。

He was taken to another clinic where fortunately they were able to excise this infection and he's mobile today.

他会告诉你，我也会告诉你，任何地方接受细胞注射都必须非常、非常谨慎，因为国外的监管通常没有那么严格。

He will tell you, and I'll tell you that you have to be very, very careful getting injections of cells in anywhere, but the regulations out of country often are not as stringent.

我讲这个故事是因为很多人对干细胞充满热情。

And I tell that story because a number of people are excited about stem cells.

他们对这些技术感到兴奋，但这些技术实际上可能非常危险。

They're excited about these technologies, but it really can be quite dangerous.

再说一遍，正如我们之前讨论的，我们在医学领域积累的经验表明，你必须在人群中以非常受控的方式测试某种疗法，仔细控制剂量，最好采用盲法试验，这样才能确认它确实有效且安全。

And again, this, you know, is what we discussed earlier, this, experience that we have in the medical field that you really need to test something in people in a very controlled fashion, carefully with the dose and then test it in a blinded fashion ideally so that you know it really works and it's safe.

你之前提到的干细胞，目前还没有任何经过严格验证的治疗方法。

And what you mentioned earlier with stem cells, there are no such treatments that have been tested rigorously.

而对于许多其他因素，它们在某些动物模型中有效。

And for many of these other factors, they work in some animal models.

有一些小鼠研究显示它们可能有效，但你不能直接将这些结果推广到人类身上。

There's some mouse studies that showed they might have an effect, but you cannot translate that to humans.

这是一条漫长的路。

It's just a long road.

我会非常谨慎，不会接受任何未经你信任的临床医生开具的治疗。

And I would be extremely cautious to take anything that is not really prescribed to you from a clinician that you trust.

谢谢。

Thank

不客气。

you.

相比之下，富血小板血浆（PRP）已获得美国食品药品监督管理局（FDA）批准。

By way of contrast, platelet rich plasma, PRP, is approved by the FDA.

接受生育治疗的人会将它注射到卵巢中。

People who are undergoing fertility treatments will get injected into their ovary.

人们正在将PRP注射到肩膀、膝盖或其他部位。

People are getting PRP injected into their shoulders, their knees, their whatever.

我并不是想贬低这种疗法，它确实获得了FDA批准。

I'm not trying to be disparaging of this, it is FDA approved.

据我所知，富血小板血浆不包含干细胞。

To my knowledge, platelet rich plasma does not contain stem cells.

没错。

That's correct.

但它似乎足够有效且安全，因此获得了FDA的批准。

But it seems to be beneficial enough and safe enough that the FDA has approved it.

那富血小板血浆到底是怎么回事？

What is the deal with platelet plasma?

它被证明真正对哪些情况有效？

What has it been shown to be actually useful for?

因为某物被批准用于一种用途，并不意味着它在所有其他用途上都有充分的证据支持。

Because just because something is allowed for one indication and is used broadly for a bunch of things, doesn't mean that there's evidence that it works for all those things.

没错。

That's right.

没错。

That's right.

富血小板血浆中含有大量富含生长因子的血小板。

So platelet rich plasma has these platelets in there that are full of growth factors.

这些血小板含有颗粒，有助于伤口愈合，这是其主要功能，而它在运动损伤中的应用似乎也有效，因此常被使用。

They have these granules that help in wound healing, it's a primary function, and somehow that seems to be beneficial in sports injuries, it's often given.

据我所知，它是从你自己的血液中提取并浓缩血小板，然后释放这些生长因子。

And as far as I know, I think it's from your own blood, concentrate these platelets, and then they release these factors.

因此，你可能会获得大量生长因子，帮助你愈合前面提到的各种组织。

So you may have a massive load of growth factors that help you heal these various tissues that you mentioned.

是的。

Yeah.

是的，我本人没试过，但我认识一些尝试过的人，他们报告说有一些积极效果。

Yeah, I haven't tried it, but I know people who have and reported some positive effect.

我也听说过很多关于外泌体的事情，我认为有些诊所已经获得FDA批准将外泌体作为治疗方法。

I've heard also a lot about exosomes and there are some clinics I believe where I think exosomes are FDA approved as a treatment.

外泌体是什么？在研究或临床中，它们被证明对哪些方面有效？

What are exosomes and what have they been shown to be useful for in studies and or clinical?

我不清楚在临床研究中它们是如何使用的，但细胞会释放出一些充满蛋白质的小囊泡，其中还含有RNA分子、脂质和代谢物。有些细胞会持续不断地释放这些物质，比如癌细胞，而一些免疫细胞也会活跃地释放这些被称为囊泡的小结构，里面充满了各种不同的分子。

I don't know in clinical studies how they're used, but, so cells can release sort of little packages of material that is filled with proteins, but there's also RNA molecules in there, lipids, metabolites, and some cells do this all the time, cancer cells for example do it, but also some immune cells have very active release of these little sort of like little packages, vesicles we call them, that are filled with again all these different molecules.

在血液中可以找到大量这些外泌体，它们通常就是从血液中纯化出来的。

In the blood you find large numbers of these exosomes and that's where they usually purified from.

不同细胞的囊泡中含有不同的物质，似乎它们在一定程度上起到在细胞间传递信息的作用。

Different cells have different cargo in these vesicles and it seems that they function to some extent to deliver information from one cell to another.

这仍然是一个非常新的领域，但人们正在探索它们是否可用于治疗目的，也可用于诊断目的。

It's still a very new field, but people explore, you know, whether they can be used for treatment purposes, but also for diagnostic purposes.

它们能否告诉你某个特定器官或正在发展的肿瘤的信息？

Do they tell you something about a specific organ or a tumor that is developing?

所以当我们测量之前提到的血液中的这些蛋白质时，实际上也在测量外泌体内的内容物。

So when we measure these proteins that we talked about earlier in the blood, we actually measure what's in the exosomes also.

这些外泌体基本上像免疫细胞一样漂浮在血液中，我们打开它们，然后测量里面的内容。

So these exosomes, they float basically like immune cells, they float in the blood and we open them up and we measure what's inside.

我们或许应该谈谈一些损害活力和长寿的因素。

We should probably talk about some of the things that damage vitality and longevity.

除了意外和伤害之外，我们知道吸烟，尤其是尼古丁，会损伤DNA，增加炎症，并缩短寿命。

Accident and injury aside, we know that smoking, especially nicotine, damages DNA, increases inflammation, and will shorten your life.

我认为这一点没有任何争议。

I don't think there's any debate about that.

是的。

Yeah.

对吧？

Right?

但其他一些可能造成低水平DNA损伤的因素呢？

But what about some of the other things that might produce low level DNA damage?

特别是现在，我对电磁场非常感兴趣。

In particular, these days, I'm very interested in EMFs.

我并不认为大多数技术中存在的低水平电磁场会像你所想的那样，靠近它们就会立即造成伤害，但确实有一种观点认为，这些影响可能是累积的，对吧？

I don't actually believe that the low levels of EMFs that are present in most technologies are damaging in the acute way that, you know, being near them is gonna harm you, but there is the idea that things can be cumulative, right?

我的意思是，我每隔几年去看牙医时才会做一次X光检查，但医生之所以躲到墙后，是因为他们不希望每天暴露在这种辐射下。

I mean, I get one x-ray every few years when I go to the dentist, but there's a reason the clinician runs behind the wall, he or she doesn't wanna be exposed to that on a daily basis.

那么，我们该如何看待那些在低剂量下不会损伤DNA或突变蛋白质，但长期暴露后可能造成这种影响的事物呢？

So how do we feel about things that at a low dose don't damage DNA, or mutate proteins either, but that if we are exposed to them over a lot of time, could very well do that.

你对这个问题有什么看法？

What are your thoughts on this?

这是一个非常困难的问题。

A very difficult question.

我的意思是，你可以对任何我们发明并添加到食物中、或让我们接触到的化学物质提出同样的问题，对吧？

I mean, you could ask the same question about any chemical that we invent and we put into food, or we get exposed to, right?

比如塑料，你知道，我们用塑料杯喝水，用塑料涂层的杯子喝热饮，而我们体内已经充满了塑料。

The, you know, the plastic, know, we drink out of cups, hot stuff out of a cup that is coated with plastic and, you know, we're full of plastic.

这会如何影响我们的寿命？

How is that gonna change our lifespan?

到目前为止，还没有可测量的影响，对吧？

It hasn't in a measurable way so far, right?

但我们不知道二十年、三十年后会发生什么。

But we don't know what's going to happen in twenty, thirty years.

或者有人合成了一种化合物，它看起来无害，经过测试也被认为是安全的，但实际上是有害的。

Or if people, you know, synthesize a compound that is detrimental, it doesn't look detrimental, that has been tested and is safe.

但正如你所说，如果它在体内累积，或者与其他物质共同作用，可能会产生危害。

But as you said, if it accumulates maybe, or in combination with other stuff, it may be detrimental.

我时不时会思考这个问题，想知道我的环境中有哪些是我能轻易控制的。

I think about this from time to time, and I wonder about what's in my environment that I can easily control.

我尽量不从塑料杯里喝水。

I try not to drink out of plastic.

你知道，如果可能的话，我会选择喝那些不含双酚A等物质的罐装饮料。

You know, I try and drink out of cans that don't have BPAs and things like that if I can.

是的，如果你走这条路，你会发疯的，你可能什么都不能做，甚至什么都不能吃。

Yeah, if you go down that route, you know, it drives you crazy and you could, you know, sort of not do anything anymore or not eat anything.

如今，过一种干净的生活越来越难了。

Well, getting harder nowadays to live a clean life.

我的意思是，你来美国之前在瑞士待了多久？

I mean, how long were you in Switzerland before you came to The States?

我当时26岁。

I was 26.

是的。

Yeah.

我们在一个非常洁净的环境中长大。

Were weaned in a very clean environment.

这不仅仅是瑞士人爱整洁干净的刻板印象——街道确实异常干净。

That's not just a stereotype about the Swiss being that things are, yes, very tidy and clean, the streets are remarkably clean.

你甚至可以直接从苏黎世的湖里喝水，也许吧。

You could drink out of the lake in Zurich, Maybe

不是湖水，但在任何村庄，基本上都能找到地下水喷泉，可以直接饮用，是的。

not the lake, but there's still fountains with groundwater where you can drink in any village, basically, yeah.

是的，如果你幸运地在自来水干净、食物基本不含色素和防腐剂、饮食以全天然食材为主、自己烹饪的地方长大，那你的生活就会是这样——新鲜的水果和蔬菜，现做的食物，对吧？

Yeah, if you're lucky enough to grow up in a place where the tap water is clean, the food tends to be pretty devoid of dyes and preservatives, and your home is centered around eating mostly whole foods, foods that you cook, Yeah, fresh fruits and vegetables, and freshly prepared, right?

就连甜点也是现做的，对吧？

Even desserts that are prepared, right?

与大量包装食品相比。

As opposed to a lot of packaged foods.

这显然与如今大多数美国人所经历的截然不同。

It seems that that's a far and away different experience than most certainly Americans get nowadays.

没错。

Right.

你会想知道这会带来什么影响。

And you wonder what the effect of that is going to be.

我们 simply 不知道。

We simply don't know.

是的，我们不知道。

Yeah, we don't know.

我知道现在人们对食品色素有很多批评，但目前还没有确凿的数据证明它们有直接危害。

And I know now there's a big, you know, kind of attack on food dyes as the thing, and there's no smoking gun data on any of those.

但我认为，这些因素的累积效应值得考虑，对大多数人来说都是如此。

But I think the cumulative effects of things are worth considering, I think for most people.

我尽量不去想太多，但话说回来，我成长的环境里，我们家有个很大的菜园。

I try not to think too much about it, but I also, I mean, growing up in an environment where, you know, we had a big vegetable garden.

我自己也有个菜园，种了很多果树，尽量从自家园子里摘东西吃。

I have a vegetable garden, you know, I have lots of fruit trees and try to get, you know, stuff out of my own garden.

当然，对很多人来说这是一种奢侈。

That's a luxury, of course, for a lot of people.

但正如你所说，你也可以买新鲜水果。

But as you said, you can also buy fresh fruit.

这需要更多功夫，对吧？

It's more work, right?

这比直接买现成的食物更费事，但你知道自己在煮什么，里面有什么。

It's more work than just buying ready made food, but you know what you're cooking and what's in there.

我最近对有机与非有机水果蔬菜的数据很着迷。

I'm fascinated these days by the data on organic versus non organic fruits and vegetables.

我多花钱买有机的，但越深入研究，越发现差异并没有那么大。

I spend the extra money on organic, but the more I look into it, the more you find that the differences aren't that great.

现在味道可能会有所不同，理想情况下你是从本地农场采购的，但我有个朋友，其实我可以直接说，他不会介意的。

Now taste can be different, and ideally you're sourcing from local farms, but I have a friend, actually I'll just, he will be okay with me saying this.

我们有个朋友，他是一位医生。

We had, he's a physician, Doctor.

特奥·索莱马尼，他是一位皮肤肿瘤科医生，他的儿子为学校的项目做了一个实验，比较了有机和非有机果蔬在污染物、农药等方面的差异，结果发现——虽然这只是个孩子的研究，但在这批果蔬中，几乎没有显著差异。

Teo Soleimani, he's a derm oncologist whose son ran an experiment for his school project, looking at the differences between organic and non organic fruits and vegetables in terms of what contaminants and things are on them, pesticides, etcetera, and found, this is one kid's study, but essentially no significant differences in that particular set of batches of fruits and vegetables.

因此，这在某种程度上令人安心，因为它意味着那些买不起有机食品的人，其健康状况可能和买得起的人差不多。

And so that is, I would say reassuring on the one hand, because it means that people who can't afford organic will probably be doing about as well as people who can.

但我认为，如果你能自己种植或从本地农场获取，那肯定更干净。

But I think if you can grow your own or access from local farms, I mean, surely it's cleaner.

事实上，内分泌干扰物含量最高的地方往往在农村地区。

I mean, the highest rates of endocrine disruptors are found in rural areas.

我一直以为，大城市对肺部和内分泌健康最危险。

I always thought that being in a big city was the most dangerous for your lungs and endocrine health.

我们曾经邀请过肖娜·斯旺做客播客，她是在这个领域认真研究的专家。

And we had Shauna Swan on the podcast, serious researcher in this area.

她说，不，我的意思是，如果你住在喷洒农药的地区，会有癌症风险和内分泌干扰。

She said, no, I mean, if you live in an area where they're spraying crops, cancer risk, endocrine disruption.

这非常严重。

That's very serious.

过去曾有帕金森病的关联研究。

Association of Parkinson's disease in the past.

对。

Right.

我想短暂休息一下，感谢我们的赞助商Function。

I'd like to take a quick break and acknowledge one of our sponsors, Function.

去年，我在寻找最全面的实验室检测方案后，成为了Function的会员。

Last year, I became a Function member after searching for the most comprehensive approach to lab testing.

Function提供超过100项先进实验室检测，能全面反映你的身体状况。

Function provides over 100 advanced lab tests that give you a key snapshot of your entire bodily health.

这些检测结果能帮助你了解心脏健康、激素水平、免疫功能、营养状况等多方面信息。

This snapshot offers you with insights on your heart health, hormone health, immune functioning, nutrient levels, and much more.

他们最近还新增了针对毒素的检测，例如来自有害塑料的BPA暴露，以及PFAS或永久性化学物质的检测。

They've also recently added tests for toxins such as BPA exposure from harmful plastics and tests for PFAS or forever chemicals.

Function不仅提供超过100种对您的身心健康至关重要的生物标志物检测，还会分析这些结果，并提供相关领域顶尖医生的专业见解。

Function not only provides testing of over a 100 biomarkers key to your physical and mental health, but it also analyzes these results and provides insights from top doctors who are expert in the relevant areas.

例如，在我第一次使用Function进行检测时，我发现自己血液中的汞含量偏高。

For example, in one of my first tests with function, I learned that I had elevated levels of mercury in my blood.

Function不仅帮助我发现了这个问题，还提供了降低汞水平的最佳建议，包括减少金枪鱼的摄入。

Function not only helped me detect that, but offered insights into how best to reduce my mercury levels, which included limiting my tuna consumption.

我那时大量食用金枪鱼，同时努力多吃绿叶蔬菜，并补充NAC和乙酰半胱氨酸，这两种物质都能支持谷胱甘肽的生成和解毒功能。

I'd been eating a lot of tuna while also making an effort to eat more leafy greens and supplementing with NAC and acetylcysteine, both of which can support glutathione production and detoxification.

我应该说，通过第二次使用Function检测，我发现这种方法是有效的。

And I should say by taking a second function test, that approach worked.

全面的血液检测至关重要。

Comprehensive blood testing is vitally important.

有许多与您的身心健康相关的问题，只有通过血液检测才能发现。

There's so many things related to your mental and physical health that can only be detected in a blood test.

问题是血液检测一直非常昂贵且复杂。

The problem is blood testing has always been very expensive and complicated.

相比之下，Function的简洁性和成本水平让我印象深刻，它非常实惠。

In contrast, I've been super impressed by Function simplicity and at the level of cost, it is very affordable.

因此，我决定加入他们的科学顾问委员会，并且很高兴他们赞助了这个播客。

As a consequence, I decided to join their scientific advisory board and I'm thrilled that they're sponsoring the podcast.

如果你想尝试Function，可以访问functionhealth.com/huberman。

If you'd like to try Function, you can go to functionhealth.com/huberman.

Function目前有超过25万人的等候名单，但他们为Huberman播客的听众提供了早期访问权限。

Function currently has a wait list of over 250,000 people, but they're offering early access to Huberman podcast listeners.

再次强调，访问functionhealth.com/huberman即可获得Function的早期访问权限。

Again, that's functionhealth.com/huberman to get early access to function.

既然我们谈到了食物，我们也应该讨论一下不进食，也就是禁食。

Well, as long as we're talking about food, we should talk about not eating, we should talk about fasting.

现在有大量研究表明，在蠕虫、小鼠、猴子甚至可能人类中，长期低热量摄入或间歇性禁食（我们可以讨论如何定义）能够延长寿命。

So many studies now showing in worms, in mice, in monkeys, and perhaps even in humans, that subcaloric intake or for long periods of time, or perhaps intermittent fasting, we can talk about how we define that, can extend life.

人们认为这是如何起作用的？

How is that thought to work?

是由于mTOR（哺乳动物雷帕霉素靶点）的减少吗？

Is it the reduction in this mTOR, mammalian targeted rapamycin?

是炎症的减少吗？

Is it reduction inflammation?

是清除衰老细胞吗？

Is it clearing of senescent cells?

请给我们一个总体概述，并具体谈谈间歇性禁食，也许先说明一下你如何定义间歇性禁食。

Give us the overview and any specifics about intermittent fasting and perhaps start by saying how you define intermittent fasting.

是每天进行，还是每周两三天？

Is it daily or is it two, three days?

我认为

I think

为了回答这个问题，其实并没有一个统一的定义。

just to answer that, there is no definition.

好的。

Okay.

没有定义。

There is no definition.

整个领域也一团混乱。

And the whole field is also a mess.

你知道，比如把小鼠的研究结果直接套用到人类身上。

You know, it's again taking studies in mice for example, and then translating them to humans.

要知道，它们的寿命、整个生物节律以及生存环境都和我们的环境截然不同，对吧？

Know, that their lifespan, whole rhythm, their environment is so different from our environment, right?

因此把这些发现直接套用到人类身上总是牵强的。

That to translate these is always a stretch.

目前还没有临床研究能明确证明禁食对人类有明显益处。

And there's no clinical studies that show a clear benefit of fasting in humans.

一些关于猴子的研究甚至表明，禁食对猴子可能是有害的。

And some studies in monkeys actually suggest that it's detrimental for monkeys to fast for example.

它们的肾功能更差，还有类似的问题。

They had more, think worse kidney function and things like that.

所以总的来说，从动物研究来看，很明显你激活了某些有益的通路。

So overall from animal studies it's very clear that you activate sort of beneficial pathways.

这些通路非常多样。

They're very diverse.

现在，我们可以对生物体中多种不同细胞类型进行无偏倚的评估，分析成千上万个基因的表达情况。

Again we can now use unbiased assessment of many different cell types in an organism at gene expression across thousands of genes.

我们发现不同细胞的反应方式各异，并且会带来功能上的改善。

And we see that different cells respond in different ways and you get functional improvements.

但这些影响非常广泛：部分细胞的炎症减轻，其他细胞在能量代谢、蛋白质周转以及处理细胞内积累的所谓‘废物’方面获得益处。

But they're very broad, they're in part reduced inflammation, other cells you get benefits on their energy metabolism, protein turnover, how they handle sort of what we call the garbage that accumulates in cells.

总体而言，这些动物研究清楚地表明，减少热量摄入具有益处。

Overall from these animal studies clearly benefits from reducing calorie intake.

此外，还减少了我们所说的氧化损伤。

Also less what we call oxidative damage.

所以这就像是你点燃了一堆火，对吧？

So it's like you burn a fire, right?

如果这堆火太猛烈，可能会造成更多损害。

And if that fire is really intense you may cause more damage.

但如何将这一点真正转化为对人类的切实益处，我不确定。

But how you translate this really to tangible benefits in humans, I'm not sure.

你有实践间歇性禁食吗？

Do you practice intermittent fasting?

很少。

Rarely.

你喜欢吃早餐吗？

You like breakfast?

我试过几次朗戈的饮食法，就是减少热量摄入，沃尔特·朗戈。

I tried, you know, Longo's diet a few times where I reduce calorie, Walter Longo.

我熟悉他，这个饮食的具体内容是什么？

I'm familiar with him, what's the contour of the diet?

所以你主要是转为生酮饮食，也就是高脂肪饮食，这样你的新陈代谢基本上就从以葡萄糖为主的饮食转变为燃烧脂肪。

So it's mostly you switch to a ketogenic diet, so a fat rich diet, so your metabolism changes basically from a regular sort of glucose driven diet to burning fat.

当你开始挨饿时，你会感觉到身体似乎发生了一些变化，你变得稍微更清醒了。

And you feel that when you start to starve, that somehow it's almost like your body changes a little bit and you get a bit more alert almost.

从某种角度来说，这很合理，对吧？

And in a way that makes sense, right?

如果你想象自己身处野外，无论是动物还是人类，如果食物不足，你最不希望的就是大脑无法正常工作。

If you think you're out there in the wild, whether you're an animal or a human being, if you don't have enough food, the last thing you want is that your brain doesn't work well.

没错。

Right.

我猜儿茶酚胺、多巴胺、肾上腺素都会增加。

I imagine the catecholamines, dopamine, epinephrine, and epinephrine increase.

是的。

Yeah.

所以你会更清醒。

So you get more alert.

你有点饿怒了。

You're a little hangry.

是的，就是饿怒，没错。

Yeah, hangry, exactly.

但我不确定这种状态能持续多久，长期来看是否真的有益。

But I'm not sure how long that lasts and how beneficial this is in the long run.

不过我确实试过几次，你知道的，会坚持一周，把每日热量摄入降到大约一千卡。

But yeah, I've done it a few times, know, you do one week, you lower your calories I think down to a thousand per day.

这相当残酷。

So it's pretty brutal.

但只持续五天，然后我们就恢复正常了，是的。

But only for five days then we go back to normal, yeah.

我知道有几个人进行过长期禁食，连续三到四天只喝水和电解质，有时补充一些酮体，他们当时超重，体内脂肪很多。

I know of a few people who've done long term fast, so three or four days with just water and electrolytes, maybe some ketones, and they were very overweight, carrying a lot of excess body fat.

当他们恢复进食后，声称自己的食欲发生了永久性改变，尤其是对食物类型的渴望。

And when they returned to eating, claimed that their appetite was forever changed, in particular the types of foods they were hungry for.

这被认为是对肠道微生物群的影响，进而影响大脑。

And that's thought to be an effect on the gut microbiome, which then impacts the brain.

因此，这些较长的禁食方式可能有其作用。

So, there may be a place for those longer fasts.

它们叫什么？

What do they call them?

医学监督下的禁食。

Medically supervised fasts.

是的，没错。

Yeah, exactly.

我通常只喝咖啡因、电解质和水，直到上午十点或十一点左右。

I generally just like caffeine, electrolytes, and water until about ten or 11AM.

然后我喜欢在八小时内吃完饭。

And then I like to eat no later than eight hours.

现在我最晚在晚上七点吃，因为我睡得比较早。

No later than, nowadays at 7PM because I go to bed a little earlier.

那么这是间歇性禁食，还是只是一个想睡得好、坚持锻炼的忙碌人士的做法？

So is that intermittent fasting, or is that just being a busy person who wants to still sleep well and exercise?

是的，这算是一种禁食，对吧？

Yeah, is sort of a fast, right?

我的意思是，在英语里，我们称之为'打破禁食'。

I mean, in English, call it a break fast.

这就像是，你知道，大概十二个小时不吃东西。

And it is like, you know, twelve hours maybe where you have no food.

我认为这可能会触发一些与持续进食不同的代谢活动。

And I think that probably triggers some metabolic activity that is different than if you continue to eat.

我觉得最糟糕的可能就是身体一直在吃东西。

I think the worst is probably for the body to eat all the time.

就像很多人整天都在吃零食。

Like a lot of people snack the whole day.

这不是我们原本的样子，也不是我们进化的方式，对吧？

That's not how we were, how we evolved, right?

我们进化过程中经常经历饥饿。

We evolved being starved on a regular basis.

但这是一件好事还是坏事呢？

But is that a good thing or a bad thing?

我们的身体肯定已经适应了这种状态。

For sure our body is used to it.

这个说法很合理。

That's a fair statement.

身体能够应对这种情况。

It can handle it.

我无法做到一天只吃一顿，因为那一顿会变得特别多，导致我胃部不适，进而影响睡眠。

I can't do the one meal per day thing because that meal ends up being so large that I get a lot of gastric discomfort, and then it disrupts my sleep.

我也想谈谈睡眠的问题。

And that's what I'd like to discuss also is sleep.

如果过去十年公共卫生讨论中至少有一次重大胜利，那我们真的要感谢马特·沃克，他写了《我们为什么要睡觉》。

If there's been at least one, there's probably been three in my mind, but at least one major triumph in the public health discussion over the last, let's say ten years, and we can really truly thank the great Matt Walker for this, who wrote Why We Sleep.

他是第一个明确指出：如果你睡眠不足，就会发生所有这些糟糕的事情，而且每个人需要的睡眠量都不同。

He was the first person to really say, Hey, these are all the terrible things that are gonna happen to you if you don't sleep enough, and everyone needs different amounts.

我六小时就够了，所以我不认为每个人都需要八小时。

I'm fine on six hours, so I don't believe everyone needs eight.

七小时我很好，但六小时我也能应付，尤其是偶尔小睡一下。

Seven, I'm great, but I'm fine on six, especially with a little nap here and there.

但马特让人们对睡眠产生了恐惧，接着又开始思考如何改善睡眠，我和其他人也为此投入了大量时间。

But Matt got people scared, then he got people thinking about how to improve their sleep, and I and others have spent time on this.

我认为这是公共卫生传播领域，基于最佳科学取得的伟大成就之一。

I think that's one of the great victories of public health communication around the best science.

另一个成就是运动的重要性，包括有氧运动和抗阻训练。

The other would be the importance of exercise, both cardiovascular and resistance training.

但在睡眠期间，我们知道存在所谓的脑淋巴系统清除机制。

But during sleep, we know that there's this so called glymphatic clearance.

这种机制通过胶质细胞促进全身组织，尤其是大脑中废物的清除，因此被称为脑淋巴系统。

The clearance of junk from all the tissues, but in particular from the brain, that's facilitated by the glia, hence glymphatic.

你们有没有研究过年轻和年老动物之间的淋巴液？

Have you guys looked at lymph between young and old animals?

我非常感兴趣

I'm fascinated I

还没研究过。

by have not.

这会是非常有趣的研究。

That would be very interesting to do.

因为这是来自血液的废物，对吧？

Because it's the debris from the blood, right?

其实是那些没有被血液清除的细胞外空间的废物。

Well, it's the debris from the extracellular space that doesn't get picked up by the blood.

也就是说，主要是那些额外的有害物质，比如氨、细胞碎片和残骸。

Mean, it's essentially the extra bad stuff, all the ammonia and cellular debris and fragments.

我非常希望你们能做一个实验，比较年轻和年老动物的淋巴液。

I would love for you guys to do an experiment looking at lymph from young and old animals.

我的意思是，我们研究过脑脊液，但那当然不一样。

I mean, we looked at the cerebrospinal fluid, but it's of course different.

而这一点，同样随着年龄变化巨大。

And that, again, differs dramatically with age.

它的成分发生了显著变化。

The composition changes dramatically.

我有一位同事，足够勇敢或疯狂地从小鼠身上采集了年轻动物的脑脊液。

And I had a fellow who was heroic enough or crazy enough to collect young CSF from animals, from mice.

你不能多做点吗？

Can't you do

再多做一点？

any more?

是的。

Yeah.

哇。

Wow.

然后通过泵持续一个月将它注入老年动物体内。

And then infuse it via a pump over a month into old animals.

她证明了你可以再生大脑，改善这些小鼠的认知功能，而少突胶质细胞——这些包裹神经元之间连接的细胞——就像它们为电线包裹了绝缘层一样，你懂的。

And she could show that you can regenerate the brain, improve cognitive function in these mice, and oligodendrocytes, these cells that wrap the connections between neurons, it's like they produce the plastic around the wire, right, if you will.

如果我们以无偏见的方式观察，它们是最显著的目标。

They were the strongest target if we looked in an unbiased way.

因此，她现在在自己的实验室里研究这个。

And so she's studying that now in her own lab.

但这以另一种方式表明，年轻与年老的体液发生了变化，而年轻体液中似乎含有对老年大脑有益的因子。

But it shows you in another way how a fluid changes from young to old and the young fluid somehow has beneficial factors that benefit the old brain.

因此，我不惊讶于脑淋巴系统或淋巴系统中可能存在对老年生物有益的因子。

And so I wouldn't be surprised that there could be beneficial factor in the Glymph or the lymphatics that might benefit an old organism.

我们曾考虑过，但我觉得在小鼠身上做起来极其困难。

We thought about it, but it's, I think in mice, it's extremely difficult.

还有间质液本身，人们已经收集过，但他们通常通过注入人工脑脊液来收集，结果几乎把里面的东西都冲走了。

There's also the interstitial fluid itself that people have collected, but they usually collect it by infusing artificial spinal fluid and then you almost wash out what it's in there.

人们已经在神经递质领域使用过这种方法，最近也用来研究β-淀粉样蛋白或大脑中蛋白质沉积的积累。

People have used that in the neurotransmitter field and also more recently to look at, you know, A beta, or accumulation of protein deposits in the brain.

为什么不直接用人类做实验呢？

Why not just go straight to humans?

我的意思是，说实话，长期以来我的实验室一直研究多种物种，包括人类。

I mean, I feel like Yeah, mean, it's always our randomized lab for a long time, I've worked on so many different species, including humans.

但是

But

既然在小鼠和人类身上开展探索性研究的成本大致相当，除非某个问题只能在小鼠身上解决，否则为什么不直接从年轻和年老的人类身上获取脑脊液呢？

it seems like given the relatively equal expense of doing exploratory science in mice and humans, unless there's a question you can only address in mice, why not just take CSF from young and old humans and

哦，对，我们确实这么做过，是的。

Oh yeah, that's what we have done, yeah.

哦，原来如此。

Oh, okay.

脑脊液没问题，是的。

CSF is no problem, yeah.

好的。

Okay.

对。

Yeah.

所以我们测量脑脊液中的蛋白质，同样是数千种蛋白质，我们想知道，有哪些蛋白质与认知功能、抗压能力或衰退相关？

So we measure proteins in the CSF, and again, thousands of proteins, and we ask, are there proteins that correlate with cognitive function, with resilience or decline?

真正有趣的是，我们是以完全无偏见的方式进行这项研究的。

What's really interesting is, so we did this in a completely unbiased way.

你会发现一些蛋白质随着认知能力上升或下降，呈正相关或负相关。

You find proteins that go up and go down together with cognition, that positively or negatively correlate.

几乎所有排名靠前的蛋白质都是突触蛋白。

And almost all the top proteins are synaptic proteins.

然后我们选取变化最显著的两个蛋白质，一个上升最多，一个下降最多，计算它们的比值。

We then use the top two, the one that goes up the most and goes down the most, made a ratio of the two.

这个比值是预测认知抗压能力的强效指标，而令人担忧的是，这种比值从成年早期就开始持续变化。

And that ratio is a very strong predictor for cognitive resilience or And what's scary is that ratio continues to change from early adulthood.

因此，你基本上会看到这个信号的持续退化。

So you get a continuous basically degradation of that signal.

我们在最高和最低四分位数之间得到了非常显著的风险预测。

And we get very prominent risk prediction between the top and the bottom quartile.

这是基于我们拥有脑脊液的3000名个体。

This is based on 3,000 individuals where we had CSF from.

而且它独立于病理标志物。

And it's independent of pathological markers.

因此，我们还包括了处于不同疾病阶段的阿尔茨海默病患者。

So we also had people with Alzheimer's and Alzheimer's disease in there at different stages of disease.

所以，如果你只关注基于记忆测试所预测的认知功能，我们会发现这些突触蛋白是非常强的预测因子。

So if you look for what is only predicted of cognitive function based on a memory test, we find these synaptic proteins are very strong predictors.

因此，这再次表明组成发生了变化，然后你可以问：这是变化的反映，还是实际上在推动变化？

So again suggesting that the composition change and then you can ask, is this a reflection of the change or is it actually driving the change?

而且看起来两者都是。

And it seems to be both again.

要确定因果关系总是很困难，但每当我看到一些研究，从相关性角度分析哪些运动员寿命最长时，

It's always tough to get to causality, but anytime I see a study that looks in a correlative way at, like, which athletes live the longest.

这

It's

都很有趣，对吧？

very interesting, right?

是的。

Yeah.

我的意思是，我完全没有跑马拉松的意愿。

I mean, I have no desire to run a marathon.

对。

Yeah.

但如果我知道跑步能让我多活二十年或十五年，我可能会开始成为马拉松运动员。

But if I knew that it was gonna add twenty years to my life, or fifteen years, I might start becoming a marathoner.

但最近一项研究表明，最长寿的是撑杆跳运动员——我就不深入说了，还有体操运动员，我认为还有跳高运动员和短跑运动员。

But a recent study showed that it's the pole vaulters, not gonna get into that, and the gymnasts, and I think the high jumpers, and the sprinters.

所以那些快肌纤维的人确实能显著延长寿命，大约五到八年，是的。

So the fast twitch muscle folks that they get a substantial longevity effect, you know, five to eight years Yeah.

平均而言。

On average.

是的。

Yeah.

比同龄人还要长。

More than their age match cohorts.

这真的很有意思。

That's really interesting.

甚至与其他高度训练的运动员相比。

Even compared to other highly trained athletes.

是的。

Yeah.

所以我看到这样的结果。

So I see a result like that.