The science of ageing, with Dr Andrew Steele
发布时间 2021-12-27 00:00:00 来源
From BBC Science Focus magazine, this is Instant Genius, a bike-sized masterclass in podcast form.
来自BBC科学焦点杂志，这是《Instant Genius》节目，一节大小像自行车的大师课程的播客形式。
I'm Sarah Riegby, online staff writer. This week I'm joined by Dr Andrew Steele, author of Ageless, the new science, getting older without getting old. He studied for a PhD in Physics of University of Oxford before switching fields to computational biology.
我是在线编辑Sarah Riegby。这一周，我有幸邀请到Andrew Steele博士与我进行访谈，他是《Ageless》一书的作者，书中介绍了新的科学方法，让我们变老但不会老。他在牛津大学获得物理学博士学位，然后转向计算生物学领域进行研究。
He tells me everything I need to know about the science of aging, including the species that don't seem to age at all.
他告诉我关于衰老的科学知识，包括那些似乎永不衰老的物种，让我了解所有必要的信息。
So first of all, could you please just tell us a bit about your book?
首先，您可以请告诉我们一下您的书的情况吗？
My book is called Ageless, the new science of getting older without getting old, and it's asking us to reimagine the aging process. I think it's something that a lot of us think is just a natural, inevitable part of being alive, but in the book I characterise it as our greatest humanitarian challenge.
我的书叫做《永驻青春：不老的新科学》，它要求我们重新想象老化过程。我认为很多人认为老化只是生命中自然而然的、不可避免的部分，但在这本书中我把它描述为我们最大的人道主义挑战。
Now that might sound like a slightly strange thing to say, but actually if you look at the sort of biology of this, aging is behind all of the biggest killers in the modern world. Things like cancer, heart disease, stroke, dementia, these are all diseases that are essentially caused by the aging process, if you look at the biology.
现在这可能听起来有点奇怪，但实际上，如果你了解这方面的生物学，老化是现代世界所有最严重疾病的根源。像癌症、心脏病、中风、失智症等这些疾病，本质上都是老化过程引起的，如果你从生物学角度来看的话。
And that means that by tackling by understanding the aging process, we can potentially create medicines that could prevent or even defer these diseases all at the same time. And that's something I just find really, really exciting. And I guess I wrote a book about it.
这意味着，如果我们能够理解衰老过程并解决它，我们有可能同时创造出能够预防甚至推迟这些疾病的药物。我觉得这非常令人兴奋，所以我写了一本书。
And there are lots of different theories about what happens in the body when we age on there.
有很多不同的理论关于当我们变老时，身体里会发生什么。
What's the main theory of what biologically causes aging?
生物老化的主要理论是什么？
I actually think I'm going to disagree slightly with the question there. So there have been dozens and dozens of theories. There is even a joke, which might even have been accurate back when the joke was made that there are more aging theories and they were researchers to study them. And that's partly because aging is just such a small field.
我其实觉得对于这个问题，我会稍微有不同的意见。关于衰老有很多理论，甚至有一个笑话，它可能在它被说出来时是准确的，那就是衰老理论更多而且有研究员来研究。这也部分是因为衰老只是一个非常小的领域。
There have been a comparatively tiny number of researchers working on this historically, but also because there is this vast burgeoning number of different theories about why we age. Is it caused by reactive molecules inside our bodies? Is it caused by damage to our DNA? Is it caused by our mitochondria? Is it little powerhouses inside our cells that generate all of our energy?
有史以来从事这项研究的研究人员相对较少，另外这也是因为对于造成人类衰老的各种理论的数量日益增长。是我们体内的反应分子造成的吗？还是我们 DNA 的受损？还是我们的线粒体？是我们细胞内的小能量块，产生我们所有的能量？
And actually, although quite a lot of them have either been disproven or just fallen by the wayside, I think what we've got now isn't one overarching theory as to why we age, but an understanding that it's a contribution from lots of different processes all acting together.
其实，尽管很多理论已经被证伪或被抛弃，但我认为我们现在所拥有的不是一个关于衰老原因的全部理论，而是对于衰老是由很多不同的过程共同作用的一个理解。
So in the book, I break it down to 10, what I call the hallmarks of the aging process. And these are the fundamental cellular, molecular, biological underpinnings of everything from the way that our cells age, to the way that those cells grouped together into organs, those organs age, to the way that our whole body age is whole systems in our bodies, and things like the immune system deteriorating with time.
在这本书中，我将老化过程分解为10个核心特征，也就是我所称的老化过程的特征。这些是细胞、分子、生物学的根本基础，涵盖了我们的细胞老化的方式，组合成器官的那些细胞老化的方式，以及我们整个身体老化的方式，包括身体中的各个系统，例如免疫系统随着时间逐渐退化等等。
And it's the combination of these 10 hallmarks ultimately causes to grow old. And these things are very interrelated, so in a sense something like the damage to the DNA is perhaps one of the most fundamental hallmarks. This is the instruction manual in the centre of every one of our cells, but that can then go on to cause things like the cells themselves to age.
这10个标志的组合最终导致我们变老。这些事物非常相互关联，所以可以说，像对DNA的损伤之类的事情可能是最基本的标志之一。这是我们每个细胞中心的指南手册，但也可能导致细胞本身老化。
And then the aging of those cells can be partly what's behind the aging of the immune system. So all of these things are very interconnected.
那些细胞的老化可能是免疫系统老化的一部分原因。因此，所有这些事情都是非常相互关联的。
And what's most exciting about this is firstly, although 10 might sound like quite a big number, actually it's a tiny, tiny number when you compare it to the sheer volume of age related diseases. There are hundreds of kinds of cancer. There are dozens and dozens of different ways your heart could go wrong, your brain can go wrong in dementia. And yet we think that this comparatively small number of underlying processes is what gives rise to everything from cancer to basically wrinkles and gray hair.
对于这件事最令人兴奋的是，首先虽然10听起来像个很大的数字，但当你将其与涉及年龄的疾病的数量相比较时，它实际上是微小极了。有数百种癌症，数十种不同的心脏问题，数十种不同的痴呆症。然而我们认为这个相对较小的潜在过程从癌症到基本上皱纹和白发的产生都是一致的。
All of these things are caused by the same underlying biology. So as we understand it, hopefully we can do something about it.
所有这些问题都源于同一种基础生物学原因。因此，我们希望能够理解它，做些什么来解决它。
Right. What is it exactly that does give rise to the outer trappings of age that we see like gray hair and wrinkles?
对了。到底是什么引起了我们所看到的外部年龄迹象，比如白发和皱纹呢？
Well, it's a variety of different things, as I said, it's all of these different hallmarks acting together.
嗯，这是许多不同的因素，就像我说的，所有这些不同的特点一起起作用。
I think perhaps the two most significant in terms of wrinkles. Firstly, there's DNA damage. So our skin is a place where we get an awful, awful lot of damage to that instruction manual in the centre of our cells. And that's because unlike most of our body, which of course is encased in our skin, our skin is subject to the vagaries of the external environment in particular.
我认为在皱纹方面最重要的可能是两件事情。首先，有DNA损伤。因此，我们的皮肤是我们的细胞中心指令手册上获得了许多损害的地方。这是因为不同于我们身体的大多数部分被皮肤覆盖着，我们的皮肤特别容易受到外部环境的影响。
If you don't wear enough sunscreen, if you spend a lot of time on the beach, or even if you've just been alive for 70 years, so you've spent quite a lot of time outdoors, the ultraviolet rays from the sun can damage that DNA inside our skin cells. And obviously the worst consequence of this, a lot of people have heard of his cancer, because that's caused by mutations, by damage to our DNA, essentially getting to a point where the cells start dividing uncontrollably.
如果你不涂足够的防晒霜，如果你在海滩上呆了很长时间，甚至只是因为你已经活了70年，所以你在户外花费了相当多的时间，太阳的紫外线会损坏我们皮肤细胞内部的DNA。显然，这种情况的最严重后果，很多人听说过的就是癌症，因为这是由突变引起的，由于我们的DNA受到损伤，基本上会导致细胞开始无限制地分裂。
But we actually understand that now that even if your cells don't get to the point of becoming a full cancer, they can still start to behave in ways that are detrimental to the skin overall. Another hallmark that's really, really crucial to the aging of our skin is the degradation of the proteins inside our skin.
但实际上我们现在已经了解到，即使您的细胞未达到成为完整的癌症的程度，它们仍然可能开始以对整个皮肤有害的方式行为。另一个对我们皮肤老化非常非常重要的标志是皮肤内蛋白质的降解。
The reason that skin, when you're young, is youthful, it's flexible, it's soft and supple, and not wrinkly, is because of proteins like collagen and elastin, which are these structural proteins. So these are molecules that hold together the skin, they maintain its structure, they make sure it's not too stiff, not too soft, but just right for maintaining a barrier.
皮肤在年轻时之所以年轻，是因为像胶原蛋白和弹性蛋白这样的蛋白质，它们是这些结构性蛋白质。所以这些分子可以维持皮肤的结构，使皮肤柔软有弹性，不会有皱纹，同时保持合适的刚柔度，以维护皮肤的屏障。
But unfortunately, as we get older, and one of the driving factors is, again, the UV, but there are also a number of other factors involved there. These proteins start to get lower in number, they get less effective at their job, they get damaged themselves. And so it's a combination of all these different things that cause you to get wrinkly.
不幸的是，随着我们年龄的增长，其中一个主要原因是紫外线对皮肤的伤害，但同时还有很多其他因素。这些蛋白质开始减少，变得不那么有效，甚至自己也受损了。因此，造成皮肤皱纹的是多种原因的综合作用。
But actually what's really interesting, as I said, is that these external signs, there's good reason to believe that they are caused by these same biological processes, and that there are two ways to think about this. The first of which is actually, how old you look is a really good indicator of how old you are biologically.
但其实真的很有趣的是，就像我说的，这些外在的迹象，有很好的理由认为它们是由同样的生物过程引起的，而且有两种思考方式。首先，你看起来有多老其实是你生物年龄的一个很好的指标。
So there was a fascinating study that was done a few years ago, where they asked people to rate how old photographs of people looked, and what they found was that people who looked old for their age actually were old for their age biologically. They went on to get more diseases, they went on to die sooner than people who looked younger. So that really shows us that there is something a bit more fundamental about wrinkles and gray hair than you might think, they're not just cosmetic signs.
前几年进行了一项非常有趣的研究，他们要求人们评估一些人的照片看起来有多老，结果发现那些看起来比他们的实际年龄老的人，其实在生物上也比同龄人老。他们更容易得病，比那些看起来年轻的人更早去世了。这实际上表明了皱纹和白发并不仅仅是外观上的标志，而是更深层次的东西。
And the second thing is that because these hallmarks affect both the same hallmarks effectively, affect both our skin and the other parts of our body, I talked about the damage to the collagen in your skin being one of the things that drives the wrinkles as you get older. Damaged ecology is actually a fundamental driver of damage to your arteries and veins, the little vessels inside your body that carry your blood around.
第二件事是，因为这些特征对我们的皮肤和身体的其他部位都有影响，所以我谈到了您皮肤中胶原蛋白受损是导致皱纹随着年龄增长的原因之一。受损的生态环境实际上是损害您身体内的动脉和静脉，那些运输您鲜血的小血管的基本驱动力。
And so it's the stiffening of those. It's one of the driving factors behind heart disease and other cardiovascular problems that we get as we get older. And so although I wouldn't necessarily go after these cosmetic things first, I actually wonder if some of them are going to be fixed almost as a side effect of other treatments, because one of the researchers I was speaking to said she was obviously far more excited about having supple youthful arteries and wrinkly skin than the other way around. But it might be that when she develops some of these therapies that can improve the quality of the collagen and our aging arteries, maybe some of those drugs will make it into our skin and improve the aged collagen there too. So you can potentially fix multiple things at the same time. And that's what we're so excited about with these anti-aging treatments.
因此，这些是变得僵硬的。这是我们随着年龄增长而出现的心脏病和其他心血管问题的主要原因之一。因此，尽管我不一定会优先考虑这些美容问题，但我实际上想知道，某些问题是否会作为其他治疗的附带效应而得到解决，因为我所说话的其中一名研究人员明显更为热衷于拥有柔软年轻的动脉和起皱的皮肤。但是，当她开发出能够改善胶原蛋白和我们衰老的动脉质量的一些疗法时，也许有些药物将进入我们的皮肤并改善那里的老化胶原蛋白。因此，您可以同时修复多个问题。这就是我们对这些抗衰老治疗如此兴奋的原因。
And so you mentioned earlier that there are some lots of other theories of aging that have since been disproven. Could you take us through maybe some of the more well-known ones? Because I'm sure lots of people have heard some of these. I think one of the most famous, actually one that sort of persists a staggers on to this day even though the biology has very much disproven it, is something called the mitochondrial reactive oxygen species theory.
那么，你之前提到了有很多其他的衰老理论已经被证明是错误的。你能不能给我们介绍一下其中一些更为知名的理论呢？因为我相信很多人都听过它们。我认为最著名的一个，实际上是一个有些缠绵不舍的理论，即使生物学已经彻底证明了它是错误的，它仍然存在，被称为线粒体反应性氧自由基理论。
And people might not have heard of it in quite that ridiculous biological terms. But we often hear about free radicals being something that causes aging. This is a term that a lot of people I think have heard that might not necessarily know the chemistry of what's going on here. The idea is that when your body is working, obviously you need to eat food, you need to breathe those two of the most fundamental things. And oxygen and things like sugars in the food that we are some of the most reactive chemicals that we come into contact with.
人们可能没有听说过这种荒谬的生物学术语。但是我们经常听到自由基是导致衰老的一种物质。我认为很多人可能听说过这个术语，但不一定知道这里面的化学反应。这个想法是，当你的身体在工作时，显然你需要吃食物，你需要呼吸，这两个是最基本的东西。氧和食物中的糖之类的物质是我们接触到的最反应性强的化学物质之一。
And they have to be reactive. They have to have a lot of energy inside them because that's how we make the energy that allows our bodies to function. But unfortunately, it means that we have got these highly reactive chemicals inside us a lot of the time. And particularly oxygen is a voraciously reactive chemical.
他们必须具有反应性。他们内在必须有很多能量，因为这是我们体内产生能量的方式。但不幸的是，这意味着我们在很多时候身体内含有高度反应性的化学物质。特别是氧气是一种贪婪的反应性化学物质。
And that means that if your body, if you're mitochondria that are generating the energy inside your cells, if they fumble one of these oxygens, they can create something called a free radical. And this is essentially a berserca chemical that goes around your cell, damaging anything it comes into contact with. And for a long time, it was thought that maybe the accumulated damage of fumbled oxygens throughout our whole lifespan are one of the things that caused the aging process.
这意味着，如果你的身体，或者如果你的线粒体在细胞内产生能量，假如它们误操作了其中一个氧气分子，就可能会形成一个叫做自由基的化学物质。这个自由基实际上是一种狂暴的化学物质，会在你的细胞中四处活动，破坏它所接触到的任何东西。长期以来，人们曾经认为，我们整个生命过程中累积的氧气误操作损伤或是导致衰老的原因之一。
Now, unfortunately, we've since discovered that really isn't the case. It's obviously a lot more complicated than that. And actually, with hindsight, that makes a lot of sense because life has been dealing with the consequences of free radicals for more billions of years. This is an afflicted even the first oxygen using cells. And so accordingly, we've got lots of different ways that we use those free radicals for important processes inside the body.
现在，不幸的是，我们后来发现真实情况并非如此简单。显然，这比那更加复杂。实际上，如果回过头来看，这也很有道理，因为生命已经处理自由基的后果达数十亿年之久。这甚至对最早使用氧气细胞造成了影响。因此，我们有许多不同的方法在身体内利用这些自由基进行重要的过程。
Actually, one of my favorite is that when your immune system comes across a bacterial invader, they might bombard that bacterium with free radicals in order to kill it. So there are loads of those functions. They're used for signaling. They're used for cells talking to each other, all kinds of different things.
其实，我最喜欢的是当你的免疫系统遭遇细菌入侵时，它们可能会向那些细菌投放自由基来杀死它们。所以这些功能有很多。它们用于信号传递。它们用于细胞之间的交流，以及各种不同的事情。
And on a less fundamental level, we've got really, really good evidence. We've got huge trials that have involved thousands and thousands of people taking things like vitamin C. So these are supplements that are designed to be antioxidants. They soak up these free radicals without taking damage themselves. But unfortunately, if you take these supplements, what we find, people who take vitamin supplements, unless you've got a specific vitamin deficiency in your doctor has told you to go out and take a particular supplement to correct that deficiency.
"在一个不那么基本的层面上，我们有非常非常好的证据。我们有涉及成千上万人服用维生素C等补品的大型试验。这些是设计成抗氧化剂的补充剂。它们吸收这些自由基而不受损害。但不幸的是，如果你服用这些补品，我们发现，服用维生素补品的人，除非你有特定的维生素缺乏症并且医生告诉你去服用特定的补品来纠正这种缺乏症。"
These people don't live any longer. In fact, some of them even have an increased chance of death versus people not taking the supplements. It's not a massive risk. It's not like you're just killing yourself instantly. But basically, if you take too much of an antioxidant supplement, your body's going to start compensating, producing more of these free radicals to carry on those essential processes, to compensate for what you're doing, and it ends up not extending your life at all.
这些人并没有因为补充剂而活得更长。事实上，他们中的一些人甚至比不服用补充剂的人死亡的机会更高。这不是一个巨大的风险。就像你不会立刻让自己死亡一样。但基本上，如果你过量服用抗氧化剂补充剂，你的身体会开始进行补偿，产生更多的这些自由基来继续进行必要的过程，以弥补你所做的，最终并没有延长你的寿命。
So that's definitely one of the theories that was very, very popular, but has fallen by the way side. Wow. And there's another one that you mentioned in your book about number of heartbeats. And I actually saw this in a museum a few years ago about how the idea that all species have a fixed number of heartbeats. Fascinating idea, isn't it?
所以这绝对是其中一个非常非常受欢迎的理论，但已经被淘汰了。哇。你在你的书中提到了另一个理论，关于心跳次数。几年前我在博物馆看到了这个关于所有物种都有固定心跳次数的想法，非常有趣，不是吗？
That's one of my favorite old theories. And actually, it's sort of in contrast to the free radical theory. It seems to be really quite broadly true. It's fascinating. So the way it's to often status is that animals get a billion heartbeats and then they expire. And this works remarkably well. It's not exactly a billion. But if you look at something like a mouse, it's heartbeats 500 times a minute, and yet mice live an average of two or three years.
这个是我最喜欢的一条古老理论之一。实际上，它和自由基理论有所对比，但似乎真的非常普遍适用。非常迷人。所以通常认为，动物有十亿次心跳，然后就死了。这个理论非常管用。当然，不是准确的十亿。不过如果你看一下像老鼠这样的动物，它每分钟心跳500次，但老鼠的平均寿命是两到三年。
That's obviously a very fast heartbeat. They race through their billion beats in no time at all. One of the longer lived animals, something like a Galapagos tourtoise, they can live to 150, maybe even 200 years old. And they've got a heart that beats just six times a minute. So if you work through do the maths, well, actually both of those come out at about half a billion beats.
这显然是一个非常快的心跳。它们只需短短时间便可以完成十亿次跳动。像加拉帕戈斯龟那样相对长寿的动物，可以活到150岁，甚至200岁。它们的心脏每分钟只跳6次。所以，如果你做一下简单的数学计算，实际上这两种动物的心跳次数都是约五亿次。
And humans, if you work through, we get about 60 beats per minute, if you're relatively healthy. And that can then, you know, obviously we can live in 80, 90 years or something like that. We get a substantially increased number of beats compared to some other animals. We get about three billion beats during our lifetime. Nonetheless, you know, a factor of, you know, three or six, isn't that huge a deal in biology?
人类的心率约为每分钟60次，如果相对健康的话，可以活到80、90岁左右。与其它动物相比，我们的心率明显增加了。我们的一生中心脏跳动的次数约为30亿次。然而，在生物学中，三倍或六倍的差异并不是很大的问题。
Those are surprisingly tightly constrained numbers. And I don't think we really understand exactly what the underlying process is here. It's probably down to something that we often call in science a scaling law. So it's very well known that animals that are larger tend to live longer lives. And that's for a variety of different reasons, one of which is that they're just, you know, they're bigger so they get eaten less often.
那些数字受到了很严格的限制，这真的非常令人惊讶，而且我不认为我们真正理解它们的底层过程是什么。这可能与科学中常称为“缩放定律”的某种东西有关。众所周知，体型更大的动物往往会寿命更长，这是因为有很多不同的原因，其中一个原因是它们更大，因此被捕食的次数更少。
And so therefore they can afford to evolve anti-aging defenses in a way that are smaller, more threatened animal can't. And it might be that bigger animals, obviously have bigger hearts and those hearts come more slowly. And so it might just be a sort of side effect of the physics and the engineering of our bodies, but we haven't fully understood why this bizarre observation, you know, seems to persistance really quite, it's a guyling, isn't it?
所以，它们就能够负担起进化出抗衰老防御机制的费用，这是小型、更受威胁的动物无法做到的。可能大型动物拥有更大的心脏，这些心脏跳动比较缓慢。所以，这可能只是我们身体的物理和工程的一种副作用，但我们尚未完全理解为什么这种奇怪的观察结果似乎持续存在，处于一种令人不安的状态。
We do seem to have this fixed number of heartbeats.. Species do tend to age at different rates, but are there any species that don't age at all? Yeah, there are surprising number of species that don't age at all. And actually the Galapagos tortoise, the reason that's on the cover of my book is it's one of these ageless species.
我们似乎有固定的心跳数。不同的物种确实会以不同的速率老化，但有没有不会老化的物种呢？是的，有许多令人惊讶的物种根本不会老化。实际上，加拉帕戈斯象龟是我这本书封面上出现的物种之一，它就是这种永葆青春的物种之一。
What do we mean by ageless? Well, so if you're a human, I guess most people listening to this podcast probably are, then what that means is that you've got a risk of death that doubles about every eight years. So to sort of put that in more concrete terms, I'm 36. That means my risk of not making my 37th birthday starting on my 36th birthday was about one in a thousand. And I like those odds, right?
我们所说的“不老”是什么意思呢？如果你是人类，我想听这个播客的大多数人应该是，那么这意味着你的死亡风险每八年翻一倍。更具体地说，我今年36岁。这意味着从我36岁生日开始，我不能过完37岁生日的风险大约是千分之一。我觉得这个几率不错，对吧？
That means that on average, I'd live into my thousand and 30s on average, if I've got a one in a thousand chance of dying every year. But unfortunately, of course, that isn't what happens. My risk of death doubles about every eight years. And so if I'm lucky enough to make it into my 90s, and of course there's no advance in medicine in the intervening time, my odds of death in one of the years of my 90s is going to be about one in six, so that's sort of life and death at the role of a dice.
这意味着如果我每年有一千分之一的机会死亡，那么平均而言，我要活到1030岁左右。但不幸的是，情况并非如此。我的死亡风险每八年翻一倍。所以，如果我能够幸运地活到九十岁，并且在此期间没有医学进展，那么我在九十岁其中一年死亡的几率约为六分之一，这就像掷骰子一样涉及生命和死亡。
And this is a very sort of visceral statistical way of encapsulating the aging process. We can say that, you know, how fast do humans age? Well, our risk of death doubles every eight years. But if you look at something like a Galapagos tortoise, well, it's risk of death doesn't double. In fact, it stays completely flat once it's reached adulthood. It's constant with time. And so in a very real biological sense, these animals don't age.
这其实是一种非常生动有力的统计方式来表述衰老过程。我们可以说，人类衰老有多快？ 嗯，我们的死亡风险每八年翻一倍。但如果看看像加拉帕戈斯巨龟这样的动物，它的死亡风险却不会变化。实际上，一旦成年后，它的死亡风险完全保持不变。随时间持续。所以在真实的生物学意义上，这些动物不会老化。
And obviously, you know, we're not just interested in these abstract statistical quantities. It's also interesting to look at how healthy these animals stay. And Galapagos tortoises do remain healthy throughout their lives. What you find is that, you know, they don't get frail. They don't get any less reproductively active. They don't get any less cognitively active. They're just effectively as sprightly at 150 as they were at 50 years old.
显而易见，我们不仅仅对这些抽象的统计数值感兴趣。看保持这些动物的健康状态也很有意思。而加拉帕戈斯龟一生中都非常健康。你会发现，它们不会变得体弱多病，也不会变得生产力减少，记忆力也不会下降。它们在150岁时和50岁时一样活泼。
We should say, obviously, they're not running around kicking a football. They are tortoises. But nonetheless, this lack of a decline, like, you know, lack of increase of risk of death, lack of increase of risk of frailty, lack of increase of risk of diseases. This is very much something we as humans could aspire to. And the fact that there are, in fact, quite a few animals out there that seem to display this property, which is called negligible senescence, is really encouraging to suggest, you know, this isn't a biological impossibility. This is something that we as humans could strive for.
我们应该明确地说，它们不是在跑来跑去踢足球，它们是乌龟。但是，尽管如此，它们没有衰退，就像我们知道的那样，没有死亡风险的增加，没有虚弱风险的增加，没有疾病风险的增加。这是我们作为人类可以追求的。实际上，事实上有很多动物似乎展示了这种叫做微不足道的衰老的特性，这是非常鼓舞人心的，表明这并不是生物学不可能的事情。这是我们作为人类可以努力追求的东西。
So is there something sort of from the biological angle that we can learn from Galapagos tortoises and apply it to humans, or is it just that it's innate to these sort of immortal species? I think the first thing to say is that it's going to be very, very tough, because, you know, so we were to try and directly port whatever, you know, longevity hacks that Galapagos tortoise has into humans.
那么，从生物角度来看，我们能从加拉帕戈斯龟身上学到什么并运用到人类身上吗？还是说这种长命不老的特性只是固有于这种物种呢？我想首先要说的是这非常非常困难，因为我们如果试图直接将加拉帕戈斯龟的长寿秘诀植入人类身上，那么...
The way we do that is, you know, we might observe their genes are a bit different to ours and maybe, you know, in some future we've got gene therapy, we could start applying some of those genetic changes to ourselves. Ultimately, though, we're going to end up, you know, closer and closer and closer until eventually we become tortoises. You know, they've obviously got a set of adaptations that work very well as a tortoise, but might not necessarily work so well in the context of a human, you know, we're one-blooded, we're a very different kind of animal.
我们做这件事的方式是，你知道的，我们可能会观察到他们的基因和我们的有些不同。也许在未来，我们有了基因治疗，我们可以开始将一些遗传变化应用于我们自己。但最终，我们会越来越接近，直到最终成为乌龟。你知道，他们显然有一组适应乌龟的适应性，但可能不一定在人类的情境下起作用，我们是有单一血液的，是一种非常不同的动物。
However, I think what's really cool about these things, firstly, they are a proof of principle. And secondly, there are some things that we can learn from them, and particularly, I think, from the longer lived, and in fact, some negligibly senescent mammal species. So there's an animal called a naked mole rat. And these are very strange looking little creatures that they're relatively closely related to rats and mice. They're rodents just like they are, but they live in burrows underground, at these enormous colonies, so they're quite a strange species.
然而，我认为这些东西真正酷的地方在于，首先它们是一个原理的证明。 其次，我们可以从它们中学到一些东西，尤其是我认为，从那些具有较长寿命甚至可以说是一些可以忽略衰老的哺乳动物物种中。所以有一种动物叫做裸鼹鼠。这些看起来非常奇怪的小生物与老鼠和小鼠相对密切地相关。它们像老鼠那样是啮齿动物，但它们住在地下的洞穴里，形成了巨大的殖民地，所以它们是相当奇怪的物种。
And they look like, I think they look a little bit like a penis with teeth to be perfectly honest. They're not those beautiful creatures, but these wrinkly little sausages, they've got this incredible property that they can live to about 30 years old.
它们看起来有点像带着牙齿的阴茎，老实说它们并不是那种美丽的生物，而是这些有皱纹的小香肠，它们有一个特殊的能力，可以活到30岁左右。
So, you know, as I said, a mouse lives about two or three years of rats, sort of the same amount of time.. But this very closely related species lives substantially longer. And again, they seem to be negligibly senescent, they don't get any more frail, like Harry on being reproductively active, they scurry around these little burrows just as quickly, right up until their very final years. And so perhaps, you know, these animals that are a bit closer to us, we can start to understand.
嗯，你知道，就像我说的，老鼠和大鼠寿命大约为两到三年，差不多一样长。但是这个非常相关的物种寿命要长得多。而且，它们似乎是不显著衰老的，它们不会因为生殖活动而变得更加脆弱，它们在这些小洞穴中来回蹦跶就像以前一样快，一直到它们的最后几年。所以也许，你知道，我们可以开始了解这些离我们更近的动物。
I think the other thing is that by looking at these creatures that do age more slowly, we can learn more general things about the biology of aging. So it's the case, you know, these ten hallmarks I talked about, they sort of clock at these hallmarks, provide effectively ticks more slowly in animals that are negligibly senescent. And that gives us some confidence that these hallmarks are genuine, sort of universal aspects of the aging process, and not just weird quirks of biology we've happened across.
我认为另一件事是，通过观察那些衰老速度更慢的生物，我们可以学到更普遍的关于衰老的生物学知识。所以实际上，这十个标记我提到的，它们在那些没怎么衰老的动物身上，打上的时钟会慢一些。这让我们有些信心，这些标记是真正的，是衰老过程的普遍方面，而不仅仅是我们偶然发现的奇怪生物学特性。
And what about the other end of the spectrum, species like the Mayfly that live for a very short amount of time? I think that's, yeah, we can certainly try and avoid whatever biological problems they have. I think some of them, some of these species that live for a very short period of time, they often do it for very strange reasons that, you know, aren't necessarily that applicable to human biology.
另一方面，像日蝉这样只活得很短时间的物种又怎么样呢？我认为我们肯定可以尽量避免它们所遇到的生物问题。有些物种只活得很短时间，通常是因为一些很奇怪的原因，这些原因可能并不适用于人类生物学。
For example, there are some insects that live in incredibly short time and literally don't have a mouth, which means they're unable to feed themselves so they can just end up dying of starvation. And I think what this tells us more broadly actually is about the evolutionary history of aging. So, you know, people often think this is strange because evolution is survival of the fittest.
比如，有些昆虫生命非常短暂，甚至没有嘴巴，这意味着它们无法自给自足，只能最终死于饥饿。我认为，更广泛的意义上，这告诉我们的是衰老的进化历史。所以，你知道的，人们经常认为这很奇怪，因为进化就是适者生存。
What evolution tries to do as it builds an organism is build organisms that are the best, the fastest, the strongest, the fittest for their environment. So what on earth could be fittest about a process of progressive generation of time or on earth could be fittest about, you know, living for a couple of hours or a couple of days and having this sort of big bang of reproduction and then dying as in the case of an animal like a Mayfly.
进化在构建一个生物时，试图构建最好、最快、最强、最适合其环境的生物。那么关于时间的渐进生殖过程或者像一些动物（比如蜉蝣）一样只活上几个小时或几天，然后繁殖后就死亡，有什么道理呢？
And I think what's really important is to look at the evolutionary context in which these arose. So I've already mentioned this in terms of the size of animals. Animals that are bigger tend to live for longer. And one of the reasons for that is because they're less predated upon, they're less eaten.
我认为真正重要的是要看看这些生物是在什么进化背景下出现的。就像我已经提到的，大小也是一个因素。较大的动物往往可以活得更久。其中一个原因是因为它们被捕食的机会较少，被吃掉的几率也就降低了。
And actually, let's think about the mice versus another animal that's another very long lived but closely released animal to bat. A mouse, it can live two or three years I already mentioned it in the lab. And actually they probably live more like six months to a year in the wild. And that's because mice, you know, there are lots of cats out to eat them with, you know, sharp claws. There are lots of diseases that can kill them.
其实，我们来想一想老鼠和另一种又长寿，却和蝙蝠十分相似的动物的区别。老鼠在实验室里可以活两三年，但在野外生活则只能活六个月到一年左右。这是因为老鼠容易被许多有锋利爪子的猫捕食，也容易被很多疾病杀死。
They're also just tiny little animals so they can die of exposure. They can just get so cold that they just end up dying effectively of that. And so that means there are loads of natural ways that a mouse can come to an end that's sort of external to its body. So imagine your evolution trying to put together the perfect mouse. You're not going to bother investing in incredible, perfect anti-cancer defenses that would allow the mouse to live to 30 with not a trace of cancer because the mouse is going to be dead at six months anyway because it's going to have been eaten.
它们也只是小小的动物，所以可以因为暴露而死亡。它们可以变得非常冷，以至于最终死于寒冷。因此，有很多自然的方式，使得老鼠在身体之外结束生命。想象一下你的进化试图组成完美的老鼠。你不会费心去投资于令老鼠能够活到30岁的完美抗癌防御，因为老鼠最终会在六个月内死亡，因为它会被吃掉。
And so what evolution does in the case of something like a mouse is it prioritises really rapid reproduction. You want to grow up fast. You want to pop out as many kids as you can in that first six months to a year in order that your genes get passed on. And as if you're imagining an animal like a bat.
所以，在像老鼠这样的动物身上，进化的作用就是优先追求快速繁殖。你想快速成长，想在第一年里生出尽可能多的孩子，以便你的基因得以传承。就好像你在想象一只蝙蝠一样。
Now the obvious difference between bats and mice is that bats can fly. There isn't the sort of pure joy of aerial living that means bats can then live to 30 of what years old. It's the fact that because they're up in the air, they're at much less risk of predators. And that means they've had time to evolve those evolutionary defenses. It's worth evolution putting Smith into building their bodies carefully in such a way to avoid heart disease or cancer or whatever it is that goes on to kill them.
现在，蝙蝠和老鼠之间的明显不同在于蝙蝠可以飞行。蝙蝠拥有飞行的纯粹喜悦，这意味着它们可以活到30岁左右。它们之所以可以这样，是因为它们在空中飞行，所以遭受的捕食者风险要小得多。这意味着它们有时间进化出进化防御机制。进化可以让斯密斯小心地构建它们的身体，以避免心脏病、癌症或其他导致死亡的疾病。
And that means that because they're killed less by external sources, they can afford to invest in those anti-aging defenses.
这意味着，因为它们受到的外来威胁更少，它们可以投资于那些抗衰老的防护措施。
I think understanding that aging isn't some evolutionary adaptation. This is not something that evolution has chosen for us. It's just sort of a screw up because animals that are killed more easily by other means lose those adaptations that allow them to live longer. I think that again gives us some optimism. This isn't something we're going to have to be cleverer than evolution in order to solve. We just need to fix some of the mistakes that evolution is introduced because we can get killed by other things.
我认为理解衰老不是进化适应是很重要的。这不是进化为我们选择的东西。它只是一种差错，因为那些更容易被其他方式杀死的动物失去了使它们能够活得更久的适应能力。我认为这再次给了我们一些乐观主义。我们不需要比进化更聪明才能解决它。我们只需要修正一些进化引入的错误，因为我们可能会被其他事物杀死。
And so back to humans now. As you mentioned earlier, different people age at different rates. And how much of that is genetic and how much of it is environmental? It's a great question and it's a very hard question. There's a little bit of controversy about answering this.
现在回到人类身上。就如你之前提到的，不同人的衰老速率不同。那么这是多少遗传因素，多少环境因素呢？这是一个很好的问题，也是一个非常困难的问题。关于回答这个问题有一些争议。
But I think what might be surprising to a lot of people is how little of the contribution is genetic. The controversy is basically how small is that genetic contribution. And depending on exactly how you do the maths, you can say this contribution is anywhere between maybe five and 25%. This is a very small amount of what's called the variance in human longevity is driven by the age of your parents.
我认为令很多人惊讶的是，人类寿命的遗传贡献是如此之少。争议的焦点在于这种遗传性贡献的规模有多小。根据你的计算方法不同，你可以说这种贡献仅占人类寿命变异性的百分之五到百分之二十五。这只是父母年龄对于人类寿命变异性所起的一个非常小的作用。
Now there's an optimistic note on this from most of us, which is that how long your parents lived, you know, you need to see that as a ceiling on your own lifespan. If your parents lived to 70 or 80, there's a huge amount of that is within your own control because even on the largest genetic contribution I just mentioned, 75% of how long you live is down to lifestyle and obviously unfortunately luck, which none of us can do anything about.
现在大多数人持乐观态度，认为你需要把你父母的寿命看作是你自己寿命的上限。如果你的父母活到了70或80岁，你的生命能够延续的很长时间是在你自己的掌控之中的，因为即使是我刚刚提到的最大的基因贡献也只占你寿命长短的75%，其余的取决于你的生活方式，当然还有不幸的运气，这是我们谁都无法控制的。
A place where the ceases to be the case is in people who live an incredibly long time. So if you look at people like Centenarians, that's people who make it to 100, suddenly there does seem to be a much larger genetic contribution. If you've got a grandfather or a grandmother who lived to 100, then you should start getting a little bit excited because that does seem to run in families. And if you've got a parent or a sibling who makes it to 100, you've got about a 10 times greater chance than someone in the rest of the population doing the same. So there clearly is some potential for us to mind the genetics of these incredibly, you know, super old, super fit healthy people in order to try and let the sound will allow them to get to those incredibly advanced ages.
一个不太可能出现的地方就是那些活得非常长寿的人身上。如果我们看像百岁老人那样的人，也就是活到了100岁的人，基因的贡献就会更加显著。如果你有一个活到了100岁的爷爷或奶奶，那么你应该会感到有些振奋，因为这种长寿的特质似乎在家族中是常见的。如果你有一个100岁的父母或兄弟姐妹，你比其他人拥有10倍的机会也能达到同样的年龄。所以，我们有能力从这些逐渐衰老但仍然健康的人的遗传因素中获取一些灵感，让更多的人能够活到那样高龄。
We often talk about people dying of old age. Is there an actual biological thing that is dying of old age? I think this is a bit of a myth that's been perpetuated for many, many years. This was actually a perfectly legitimate thing to write on a death certificate as a doctor. You know, someone got to 80 and they just died in their sleep. They wouldn't bother investigating exactly what had killed them. But I think what we've come to understand is that, you know, although there is a sense in which 90% of people in the rich world die of old age, you know, that's the percentage of deaths that are caused by aging. And that's one of the reasons that I call it our greatest humanitarian challenge. Because it's just, you know, it's the single largest cause of death around the world.
我们经常说人们因年老而死亡，但真的有一种实际的生物正在因年老而死亡吗？我认为这是很多年来一直被传颂的神话。实际上，医生在死亡证明上写这个完全是合法的。例如，有人活到了80岁，就安详地在睡梦中辞世，这时候他们就不会去研究具体是什么导致了他们的死亡。但我认为我们现在明白的是，虽然富裕国家90%的人死于老年，这是由衰老导致的死亡占死亡总数的比例，但是这也是我称其为我们最大的人道主义挑战之一的原因之一，因为这是全球最大的死因。
Actually, you know, what goes on to kill you is that as you get older, you get a higher risk of these diseases because of all these changing hallmarks in your body, you get a higher risk of cancer, higher risk of heart disease, higher risk of dementia, these diseases can take years to develop, but eventually one of them becomes severe enough that it can take your life. And so ultimately, everyone does die of some specific disease. It's just that that disease will probably have been made substantially more likely by the aging process.
其实啊，你知道，年岁越长，身体里的所有这些变化标志物就会让你更容易患上这些疾病，比如更容易得癌症、心脏病和痴呆症等等，这些疾病可能需要数年时间才能发展出来，但最终会有一种疾病严重到足以威胁到你的生命。所以说，最终每个人都是死于某种具体的疾病。只是因为衰老进程的加剧，这种疾病患病的可能性显著增加了。
Is there a biological limit to how old humans can be? I think this is another fascinating and controversial question. I really think it depends what you mean by it. So I think in the sense that current humans, if I could give you the absolutely optimal lifestyle, you know, the perfect, you could be lucky enough to have the perfect genetics and so on, there probably is some kind of limit as to how long you can live because, you know, humans evolved in a certain environment. There'd be absolutely no need for a free historic human to make it to 122, which is the current human lifespan record.
人类寿命是否存在生物学上的极限？我认为这是一个引人入胜且备受争议的问题。我真的认为这取决于你的理解。如果我能为你提供绝对理想的生活方式，也就是完美的，你可能会很幸运地拥有完美的基因等等，那么就当前人类而言，可能存在一定的寿命极限，因为人类是在特定的环境中进化而来的。从历史上来看，真没有必要让人类活到122岁，那是目前人类寿命的最高纪录。
So clearly, there is sort of an evolutionary, you know, time available into all of us that's going to eventually cause our bodies to wear out. However, what I'm really optimistic about is that we can start to sidestep some of these things. We can start to make some tweaks that evolution wasn't able to make because there were no, you know, 100 year old humans to optimize in the evolutionary environment.
很明显，我们每个人都有一种进化的时间，最终会导致我们的身体耗尽。然而，我真正乐观的是，我们可以开始规避这些问题。我们可以开始进行一些调整，这些调整是进化无法实现的，因为进化环境中没有一百岁的人需要优化。
And because they'd already produced long, long ago, they'd pass on their genes long, long ago. So there was no sort of scope for evolution to try and tweak those people. And I think that by, you know, coming up with therapies that can reduce some of these hallmarks and defer these diseases later in the future, I don't know how long we're going to live because it depends how fast some of these therapies are developed. But I don't really think areas are fundamental limit on human lifespan.
因为他们早在很久以前就已经繁殖了，他们早在很久以前就传递了他们的基因。所以进化没有机会去调整这些人。我认为，通过研发能够减轻这些症状并推迟这些疾病发生的治疗方法，我不知道我们会活多久，因为这取决于这些治疗方法的开发速度。但我不认为寿命有什么根本限制。
And you know, you can get that idea by looking at the Galapagos tortoises again, all these negligibly senescent animals, their risk of death doesn't change with time. And so although it's very hard to predict when we could get to that kind of state for humans, it's not something that's biologically impossible. It's just a question of how clever we can be and how quickly and lucky we can get, you know, developing these therapies.
你知道，通过再次观察加拉帕戈斯象龟，就可以得到这个想法，所有这些几乎长寿的动物，它们的死亡风险不会随着时间而改变。虽然很难预测我们何时能够达到这种人类状态，但这并不是生物学上不可能的事情。这只是一个关于我们能有多聪明，多快速地幸运地开发这些疗法的问题。
So is it a case that we age because we evolved to age or we aged because we haven't evolved not to age? I think it's more the latter to be honest because you find with these negligibly senescent species or species that just live a long time, they're in an environment or they're in a situation where it's necessary for them to, where it's, it's okay for them to live a long time.
我们衰老是因为我们进化了而变老，还是因为我们没有进化来不变老呢？说实话，我认为更可能是后者，因为对于那些可忽略衰老物种或只能活很长时间的物种，它们处于一个情境当中，要求它们长寿是必要的，这是可以接受的。
They're not going to get killed by external factors or it's really, really important that they stay alive at older ages. And I think a really good example actually of this is fish. So there are some species of fish that are negligibly senescent, they've got a risk of death that doesn't change with time.
他们不会被外部因素杀死，或者他们能够在晚年保持健康是非常非常重要的。我认为一个非常好的例子就是鱼。有一些鱼类是可忽略的衰老，他们的死亡风险不会随时间改变。
And it's probably the case that this is because of their reproductive strategy. So in a lot of animals, the way that reproduction is done is, you know, and this is true in humans as well, it's primarily done by the youthful members of the species. But in fish, you get fish, get bigger and bigger and bigger as they get older.
很可能是由于它们的繁殖策略而引起这种情况。 所以在很多动物中，繁殖的方式是，你知道的，在人类中也是如此，它主要由物种年轻成员完成。 但是在鱼类中，鱼随着年龄的增长变得越来越大。
And actually it's the biggest oldest female fish that are most important contributors to the reproductive system in those species. They're actually called Bof, which stands for big old fat fertile female fish. I think I've got that right. There's a lot of Fs in there. And these massive matriarchs, they can put out, you know, dozens of times more eggs than a young female, the eggs are often more successful so that it's more likely that they're going to grow up into healthy, healthy, young fish as well.
实际上，在这些物种中，最重要的繁殖系统贡献者是最大最老的雌鱼。它们实际上被称为Bof，代表着大而老和肥沃的雌鱼。我想我说对了。里面有很多F。而这些巨大的女族长可以产下数十倍于年轻雌鱼的卵子，卵子通常更成功，因此它们更有可能成长为健康的年轻鱼。
And so they've just got a very different population structure to something like, you know, humans or rats or mice or whatever living on land. And that means suddenly evolution has a huge incentive to keep these pinnacles of reproductive fitness alive. They want to keep them alive as long as possible. And that's probably why evolution is invested in the defenses that allow those fish to carry on living in a carry on reproducing at the very, very old age.
所以，它们的人口结构和生活在陆地上的人类、老鼠等都非常不同。这意味着进化突然有了一个巨大的动力，要让这些繁殖能力的巅峰生物尽可能长寿。它们希望它们能活得尽可能长，并且这也是进化投资于保护这些鱼类能够在非常非常高龄仍然继续生存和繁殖的原因。
Whereas a human, you know, by the time you're 30 in prehistoric times, you've probably reproduced, and you're basically on this graph heap as far as evolution is concerned because you passed on your genes. And so it doesn't bother investing in those defenses that, you know, I guess in the modern world, all of us wish it would put a little bit more time into.
一个人在史前时代，到了30岁，很可能就已经繁殖了，基本上在进化的角度来看，你已经成为了基因堆的一部分。所以，它不会费心去投资那些防御措施，我想在现代世界，我们都希望它能多花点时间在这方面。
Finally, what three things do you think we all should know about the science of aging? I think the three most important things are firstly, what I started out by saying that this is our biggest humanitarian challenge.
最后，您认为我们都应该知道关于衰老科学的三件事是什么？我认为最重要的三件事首先是，正如我开头所说的，这是我们最大的人道主义挑战。
Two thirds of deaths around the world are caused by diseases that are caused by aging essentially. And that means it's the single biggest cause of death. I'd also argue the single biggest cause of suffering for our species. And therefore, it is our biggest humanitarian challenge. And it's vital that we do something about it.
全球三分之二的死亡是由基本上受老化影响的疾病引起的，这意味着它是最主要的死亡原因。我还认为它是我们人类最大的苦难来源。因此，它是我们最大的人道主义挑战。现在我们必须采取行动。
The second thing is that we understand or certainly beginning to understand in quite a lot of detail how it is that we age. We've got this idea of the 10 hallmarks. There are a few different theories we're converging upon. And that means that we've got the biological understanding to start to think about doing something about it.
第二件事是我们正在逐渐了解我们如何衰老。我们有关于“十个标志”的概念。我们正在聚焦于几个不同的理论。这意味着我们已经具备了生物学的理解，可以开始考虑对此采取行动。
And thirdly, that these are treatments that are very much on the horizon. We've already got treatments in clinical trials in several cases for particular hallmarks. And the idea is that by reversing these hallmarks by slowing down the rate at which certain things accumulate and so on, we can defer or potentially prevent a whole range of these age-related diseases.
第三，这些治疗方法非常接近实现。我们已经在进行多个特定病征的临床试验治疗。通过减缓某些物质的积累速度并逆转这些病征，我们可以推迟或潜在地预防整个一系列老年病。
So this is a really exciting time. This isn't sci-fi. And I just think this is something we all need to know a lot more about in order that we can spread the word, get investments at the level that it's needed and try and get some of these therapies into humans as quickly as possible..
所以现在这是非常令人激动的时刻。这不是科幻小说。我想这是我们所有人都需要更多了解的事情，以便我们可以传播信息、获得所需的投资，并尽快将一些治疗方法应用到人类身上。
Thank you for listening to this episode of Instant Genius. That was Dr Andrew Steele. If you want to know more about aging, check out his book Ageless. To hear him tell me about the exciting treatments that could stop us from getting old altogether, head over to Instant Genius Extra, available only on Apple Podcasts.
谢谢您收听这一期《迅捷天才》节目。刚刚为您讲解的是安德鲁·斯蒂尔博士。如果您想了解更多关于衰老的知识，他的书《不老青春》是不错的选择。如果您想听他讲述一些令人激动的防止老化的治疗方法，可以前往仅在苹果播客上提供的《迅捷天才Extra》栏目收听。
The new year issue of BBC Science Focus magazine is on sale this week. Pick up a copy and store or visit sciencefocus.com..
这周，BBC科学聚焦杂志的新年刊正式上市。赶紧去购买一份并将其存放起来，或者访问sciencefocus.com。