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TEDTalks, Aubrey de Grey – Why we age and how we can avoid it (2005)

Aubrey de Grey – Why we age and how we can avoid it (2005)

18 minutes is an absolutely brutal time limit, so I'm going to dive straight in, right at the point where I get this thing to work. Here we go. I'm going to talk about five different things. I'm going to talk about why defeating aging is desirable. I'm going to talk about why we have to get our shit together, and actually talk about this a bit more than we do. I'm going to talk about feasibility as well, of course. I'm going to talk about why we are so fatalistic about doing anything about aging. And then I'm going spend perhaps the second half of the talk talking about, you know, how we might actually be able to prove that fatalism is wrong, namely, by actually doing something about it.

I'm going to do that in two steps. The first one I'm going to talk about is how to get from a relatively modest amount of life extension -- which I'm going to define as 30 years, applied to people who are already in middle-age when you start -- to a point which can genuinely be called defeating aging. Namely, essentially an elimination of the relationship between how old you are, and how likely you are to die in the next year -- or indeed, to get sick in the first place. And of course, the last thing I'm going to talk about is how to reach that intermediate step, that point of maybe 30 years life extension.

So I'm going to start with why we should. Now, I want to ask a question. Hands up: Anyone in the audience who is in favor of malaria? That was easy. OK. OK. Hands up, anyone in the audience who's not sure whether malaria is a good thing or a bad thing? OK. So we all think malaria is a bad thing. That's very good news, because I thought that was what the answer would be. Now the thing is, I would like to put it to you that the main reason why we think that malaria is a bad thing is because of a characteristic of malaria that it shares with aging. And here is that characteristic. The only real difference is that aging kills considerably more people than malaria does.

Now, I like in an audience, in Britain especially, to talk about the comparison with fox-hunting, which is something that was banned after a long struggle, by the government not very many months ago. I mean, I know I'm with a sympathetic audience here, but, as we know, a lot of people are not entirely persuaded by this logic. And this is actually a rather good comparison, it seems to me. You know, a lot of people said, "Well, you know, city boys have no business telling us rural types what to do with our time. It's a traditional part of the way of life, and we should be allowed to carry on doing it. It's ecologically sound; it stops the population explosion of foxes." But ultimately, the government prevailed in the end, because the majority of the British public, and certainly the majority of members of Parliament, came to the conclusion that it was really something that should not be tolerated in a civilized society.

And I think that human aging shares all of these characteristics in spades. What part of this do people not understand? It's not just about life, of course -- (Laughter) it's about healthy life, you know -- getting frail and miserable and dependent is no fun, whether or not dying may be fun. So really, this is how I would like to describe it. It's a global trance. These are the sorts of unbelievable excuses that people give for aging. And, I mean, OK, I'm not actually saying that these excuses are completely valueless. There are some good points to be made here. Things that we ought to be thinking about, forward planning so that nothing goes to hell, so that we minimize the turbulence when we actually figure out how to fix aging.

But these are completely crazy, when you actually remember your sense of proportion. You know, these are arguments, these are things that would be legitimate to be concerned about. But the question is, are they so dangerous -- these risks of doing something about aging -- that they outweigh the downside of doing the opposite, namely, leaving aging as it is? Are these so bad that they outweigh condemning 100,000 people a day to an unnecessarily early death. You know, if you haven't got an argument that's that strong, then just don't waste my time is what I say. (Laughter)

Now, there is one argument that some people do think really is that strong, and here it is. People worry about overpopulation; they say, "Well, if we fix aging, no one's going to die to speak of, or at least the death toll is going to be much lower, only from crossing St. Giles carelessly. And therefore, we're not going to be able to have many kids, and kids are really important to most people." And that's true. And you know, a lot of people try to fudge this question, and give answers like this. I don't agree with those answers. I think they basically don't work. I think it's true, that we will face a dilemma in this respect. We will have to decide whether to have a low birth rate, or a high death rate. A high death rate will, of course, arise from simply rejecting these therapies, in favor of carrying on having a lot of kids.

And, I say that that's fine -- the future of humanity is entitled to make that choice. What's not fine is for us to make that choice on behalf of the future. If we vacillate, hesitate, and do not actually develop these therapies, then we are condemning a whole cohort of people -- who would have been young enough and healthy enough to benefit from those therapies but will not be, because we haven't developed them as quickly as we could -- we'll be denying those people an indefinite life span, and I consider that that is immoral. That's my answer to the overpopulation question.

Right. So the next thing is, now why should we get a little bit more active on this? And the fundamental answer is that the pro-aging trance is not as dumb as it looks. It's actually a sensible way of coping with the inevitability of aging. Aging is ghastly, but it's inevitable, so, you know, we've got to find some way to put it out of our minds, and it's rational to do anything that we might want to do, to do that. Like, for example, making up these ridiculous reasons why aging is actually a good thing after all. But of course, that only works when we have both of these components. And as soon as the inevitability bit becomes a little bit unclear, and we might be in range of doing something about aging, this becomes part of the problem. This pro-aging trance is what stops us from agitating about these things. And that's why we have to really talk about this a lot -- evangelize, I will go so far as to say -- in order to get people's attention, and make people realize that they are in a trance in this regard. So that's all I'm going to say about that.

I'm now going to talk about feasibility. And the fundamental reason, I think, why we feel that aging is inevitable is summed up in a definition of aging that I'm giving here. A very simple definition. Aging is a side effect of being alive in the first place, which is to say, metabolism. This is not a completely tautological statement; it's a reasonable statement. Aging is basically a process that happens to inanimate objects like cars, and it also happens to us, despite the fact that we have a lot of clever self-repair mechanisms, because those self-repair mechanisms are not perfect.

So basically, metabolism, which is defined as basically everything that keeps us alive from one day to the next, has side effects. Those side effects accumulate and eventually cause pathology. That's a fine definition. So we can put it this way: we can say that, you know, we have this chain of events. And there are really two games in town, according to most people, with regard to postponing aging. They're what I'm calling here the gerontology approach and the geriatrics approach. The geriatrician will intervene late in the day, when pathology is becoming evident, and the geriatrician will try and hold back the sands of time, and stop the accumulation of side effects from causing the pathology quite so soon. Of course, it's a very short-termist strategy, it's a losing battle, because the things that are causing the pathology are becoming more abundant as time goes on.

The gerontology approach looks much more promising on the surface, because, you know, prevention is better than cure. But unfortunately the thing is that we don't understand metabolism very well. In fact, we have a pitifully poor understanding of how organisms work -- even cells we're not really too good on yet. We've discovered things like, for example, RNA interference only a few years ago, and this is a really fundamental component of how cells work. Basically, gerontology is a fine approach in the end, but it is not an approach whose time has come when we're talking about intervention. So then, what do we do about that? I mean, that's a fine logic, that sounds pretty convincing, pretty iron-clad, doesn't it?

But it isn't. Before I tell you why it isn't, I'm going to go a little bit into what I'm calling step two. Just suppose, as I said, that we do acquire -- let's say we do it today for sake of argument -- the ability to confer 30 extra years of healthy life on people who are already in middle age, let's say 55. I'm going to call that robust human rejuvenation. OK. What would that actually mean for how long people of various ages today -- or equivalently, of various ages at the time that these therapies arrive -- would actually live? In order to answer that question -- you might think it's simple, but it's not simple. We can't just say, "Well, if they're young enough to benefit from these therapies, then they'll live 30 years longer." That's the wrong answer. And the reason it's the wrong answer is because of progress.

There are two sorts of technological progress really, for this purpose. There are fundamental, major breakthroughs, and there are incremental refinements of those breakthroughs. Now, they differ a great deal in terms of the predictability of time frames. Fundamental breakthroughs: very hard to predict how long it's going to take to make a fundamental breakthrough. It was a very long time ago that we decided that flying would be fun, and it took us until 1903 to actually work out how to do it. But after that, things were pretty steady and pretty uniform. I think this is a reasonable sequence of events that happened in the progression of the technology of powered flight. We can think, really, that each one is sort of beyond the imagination of the inventor of the previous one, if you like. The incremental advances have owed up to something which is not incremental anymore.

This is the sort of thing you see after a fundamental breakthrough. And you see it in all sorts of technologies. Computers, you can look at a more or less parallel time line, happening of course a bit later. You can look at medical care. I mean, hygiene, vaccines, antibiotics -- you know, the same sort of time frame. So I think that actually step two, that I called a step a moment ago, isn't a step at all. That in fact, the people who are young enough to benefit from these first therapies that give this moderate amount of life extension, even though those people are already middle-aged when the therapies arrive, will be at some sort of cusp. They will mostly survive long enough to receive improved treatments that will give them a further 30 or maybe 50 years. In other words, they will be staying ahead of the game. The therapies will be improving faster than the remaining imperfections in the therapies are catching up with us.

This is a very important point for me to get across. Because, you know, most people, when they hear that I predict that a lot of people alive today are going to live to 1,000 or more, they think that I'm saying that we're going to invent therapies in the next few decades that are so thoroughly eliminating aging that those therapies will let us live to 1,000 or more. I'm not saying that at all. I'm saying that the rate of improvement of those therapies will be enough. They'll never be perfect, but we'll be able to fix the things that 200-year-olds die of, before we have any 200-year-olds. And the same for three- and 400 and so on. I decided to give this a little name, which is "longevity escape velocity." (Laughter) Well, it seems to get the point across.

So, these trajectories here are basically how we would expect people to live, in terms of remaining life expectancy, as measured by their health, for given ages that they were at the time that these therapies arrive. If you're already 100, or even if you're 80 -- and an average 80-year-old, we probably can't do a lot for you with these therapies, because you're too close to death's door for the really initial, experimental therapies to be good enough for you. You won't be able to withstand them. But if you're only 50, then there's a chance that you might be able to pull out of the dive and, you know -- (Laughter) eventually get through this. And start becoming biologically younger in a meaningful sense, in terms of your youthfulness, both physical and mental, and in terms of your risk of death from age-related causes. And of course, if you're a bit younger than that, then you're never really even going to get near to being fragile enough to die of age-related causes.

So this is a genuine conclusion that I come to, that the first 150-year old -- we don't know how old that person is today, because we don't know how long it's going to take to get these first-generation therapies. But irrespective of that age, I'm claiming that the first person to live to 1,000 -- subject of course, to, you know, global catastrophes -- is actually, probably, only about 10 years younger than the first 150-year old. And that's quite a thought.

All right, so finally I'm going to spend the rest of the talk, my last seven and a half minutes, on step one; namely, how do we actually get to this moderate amount of life extension that will allow us to get to escape velocity? And in order to do that, I need to talk about mice a little bit. I have a corresponding milestone to robust human rejuvenation. I'm calling it robust mouse rejuvenation, not very imaginatively. And this is what it is. I say we're going to take a long-lived strain of mouse, which basically means mice that live about three years on average. We do exactly nothing to them until they're already two years old. And then we do a whole bunch of stuff to them, and with those therapies, we get them to live, on average, to their fifth birthday. So, in other words, we add two years -- we treble their remaining lifespan, starting from the point that we started the therapies.

The question then is, what would that actually mean for the time frame until we get to the milestone I talked about earlier for humans? Which we can now, as I've explained, equivalently call either robust human rejuvenation, or longevity escape velocity. Secondly, what does it mean for the public's perception of how long it's going to take for us to get to those things, starting from the time we get the mice? And thirdly, the question is, what will it do to actually how much people want it? And it seems to me that the first question is entirely a biology question, and it's extremely hard to answer. One has to be very speculative, and many of my colleagues would say that we should not do this speculation, that we should simply keep our counsel until we know more.

I say that's nonsense. I say we absolutely are irresponsible if we stay silent on this. We need to give our best guess as to the time frame, in order to give people a sense of proportion so that they can assess their priorities. So, I say that we have a 50/50 chance of reaching this RHR milestone, robust human rejuvenation, within 15 years from the point that we get to robust mouse rejuvenation. 15 years from the robust mouse. The public's perception will probably be somewhat better than that. The public tend to underestimate how difficult scientific things are. So they'll probably think it's five years away. They'll be wrong, but that actually won't matter too much. And finally, of course, I think it's fair to say that a large part of the reason why the public is so ambivalent about aging now is the global trance I spoke about earlier, the coping strategy. That will be history at this point, because it will no longer be possible to believe that aging is inevitable in humans, since it's been postponed so very effectively in mice. So we're likely to end up with a very strong change in people's attitudes, and of course that has enormous implications.

So in order to tell you now how we're going to get these mice, I'm going to add a little bit to my description of aging. I'm going to use this word "damage" to denote these intermediate things that are caused by metabolism, and that eventually cause pathology. Because the critical thing about this is that even though the damage only eventually causes pathology, the damage itself is caused ongoingly throughout life, starting before we're born. But it is not part of metabolism itself. And this turns out to be useful. Because we can re-draw our original diagram this way. We can say that, fundamentally, the difference between gerontology and geriatrics is that gerontology tries to inhibit the rate at which metabolism lays down this damage. And I'm going to explain exactly what damage is in concrete biological terms in a moment. And geriatricians try to hold back the sands of time by stopping the damage converting into pathology. And the reason it's a losing battle is because the damage is continuing to accumulate.

So there's a third approach, if we look at it this way. We can call it the engineering approach, and I claim that the engineering approach is within range. The engineering approach does not intervene in any processes. It does not intervene in this process, or this one. And that's good because it means that it's not a losing battle, and it's something that we are within range of being able to do, because it doesn't involve improving on evolution. The engineering approach simply says, "Let's go and periodically repair all of these various types of damage -- not necessarily repair them completely, but repair them quite a lot, so that we keep the level of damage down below the threshold that must exist, that causes it to be pathogenic." We know that this threshold exists, because we don't get age-related diseases until we're in middle age, even though the damage has been accumulating since before we were born.

Why do I say that we're in range? Well, this is basically it. The point about this slide is actually the bottom. If we try to say which bits of metabolism are important for aging, we will be here all night, because basically all of metabolism is important for aging in one way or another. This list is just for illustration, it is incomplete. The list on the right is also incomplete. It's a list of types of pathology that are age-related, and it's just an incomplete list. But I would like to claim to you that this list in the middle is actually complete, this is the list of types of thing that qualify as damage, side effects of metabolism that cause pathology in the end, or that might cause pathology. And there are only seven of them. They're categories of thing, of course, but there's only seven of them. Cell loss, mutations in chromosomes, mutations in the mitochondria and so on.

First of all, I'd like to give you an argument for why that list is complete. Of course one can make a biological argument. One can say, OK, what are we made of? We're made of cells and stuff between cells. What can damage accumulate in? The answer is, long-lived molecules, because if a short-lived molecule undergoes damage, but then the molecule is destroyed -- like by a protein being destroyed by proteolysis -- then the damage is gone, too. It's got to be long-lived molecules. So, these seven things were all under discussion in gerontology a long time ago and that is pretty good news, because it means that, you know, we've come a long way in biology in these 20 years, so the fact that we haven't extended this list is a pretty good indication that there's no extension to be done. However, it's better than that; we actually know how to fix them all in mice, in principle -- and what I mean by in principle is, we probably can actually implement these fixes within a decade. Some of them are partially implemented already, the ones at the top.

I haven't got time to go through them at all, but my conclusion is that, if we can actually get suitable funding for this, then we can probably develop robust mass rejuvenation in only 10 years, but we do need to get serious about it. We do need to really start trying. So of course, there are some biologists in the audience, and I want to give some answers to some of the questions that you may have. You may have been dissatisfied with this talk, but fundamentally you have to go and read this stuff. I've published a great deal on this; I cite the experimental work on which my optimism is based, and there's quite a lot of detail there. The detail is what makes me confident of my rather aggressive time frames that I'm predicting here. So if you think that I'm wrong, you'd better damn well go and find out why you think I'm wrong.

And of course the main thing is that you shouldn't trust people who call themselves gerontologists because, as with any radical departure from previous thinking within a particular field, you know, you expect people in the mainstream to be a bit resistant and not really to take it seriously. So, you know, you've got to actually do your homework, in order to understand whether this is true.

And we'll just end with a few things. One thing is, you know, you'll be hearing from a guy in the next session who said some time ago that he could sequence the human genome in no time, and everyone said, "Well, it's obviously impossible." And you know what happened. So, you know, this does happen. We have various strategies -- there's the Methuselah Mouse Prize, which is basically an incentive to innovate, and to do what you think is going to work, and you get money for it if you win. There's a proposal to actually put together an institute. This is what's going to take a bit of money. But, I mean, look -- how long does it take to spend that on the war in Iraq? Not very long. OK. (Laughter) It's got to be philanthropic, because profits distract biotech, but it's basically got a 90 percent chance, I think, of succeeding in this. And I think we know how to do it. And I'll stop there. Thank you. (Applause)

Chris Anderson: OK. I don't know if there's going to be any questions but I thought I would give people the chance. Audience: Since you've been talking about aging and trying to defeat it, why is it that you make yourself appear like an old man? (Laughter)

AG: Because I am an old man. I am actually 158. (Laughter) (Applause)

Audience: Species on this planet have evolved with immune systems, to fight off all the diseases so that individuals live long enough to procreate. However, as far as I know, all the species have evolved to actually die, so when cells divide, the telomerase get shorter, and eventually species die. So, why does -- evolution has -- seems to have selected against immortality, when it is so advantageous, or is evolution just incomplete?

AG: Brilliant. Thank you for asking a question that I can answer with an uncontroversial answer. I'm going to tell you the genuine mainstream answer to your question, which I happen to agree with. Which is that, no, aging is not a product of selection; evolution is simply a product of evolutionary neglect. In other words, we have aging because it's hard work not to have aging; you need more genetic pathway, more sophistication in your genes in order to age more slowly, and that carries on being true the longer you push it out. So, to the extent that evolution doesn't matter, doesn't care whether genes are passed on by individuals, living a long time or by procreation, there's a certain amount of modulation of that, which is why different species have different lifespans, but that's why there are no immortal species.

CA: The genes don't care but we do?

AG: That's right.

Audience: Hello. I read somewhere that in the last 20 years, the average lifespan of basically anyone on the planet has grown by 10 years. If I project that, that would make me think that I would live until 120 if I don't crash on my motorbike. That means that I'm one of your subjects to become a 1000 year old?

AG: If you lose a bit of weight. (Laughter) Your numbers are a bit out. The standard numbers are that lifespans have been growing at between one and two years per decade. So, it's not quite as good as you might think -- you might hope. But I intend to move it up to one year per year as soon as possible.

Audience: I was told that many of the brain cells we have as adults are actually in the human embryo, and that the brain cells last 80 years or so. If that is indeed true, biologically are there implications in the world of rejuvenation? If there are cells in my body that live all 80 years, as opposed to a typical, you know, couple of months?

AG: There are technical implications certainly. Basically what we need to do is replace cells in those few areas of the brain that lose cells at a respectable rate, especially neurons, but we don't want to replace them any faster than that -- or not much faster anyway, because replacing them too fast would degrade cognitive function. What I said about there being no non-aging species earlier on was a little bit of an oversimplification. There are species that have no aging -- Hydra for example -- but they do it by not having a nervous system -- and not having any tissues in fact that rely for their function on very long-lived cells.

http://www.ted.com/talks/aubrey_de_grey_says_we_can_avoid_aging.html


Aubrey de Grey – Why we age and how we can avoid it (2005) Aubrey de Grey - Warum wir altern und wie wir es vermeiden können (2005) Aubrey de Grey - Por qué envejecemos y cómo podemos evitarlo (2005) オーブリー・デ・グレイ - 人はなぜ老いるのか、どうすれば老いを避けられるのか (2005) Обри де Грей - Почему мы стареем и как этого избежать (2005) Aubrey de Grey - Neden yaşlanırız ve bundan nasıl kaçınabiliriz (2005) Aubrey de Gray – 我們為什麼會變老以及我們如何避免它 (2005)

18 minutes is an absolutely brutal time limit, so I’m going to dive straight in, right at the point where I get this thing to work. 18 Minuten sind ein absolut brutales Zeitlimit, also fange ich direkt an dem Punkt an, an dem ich das Ding zum Laufen bringe. 18 minutes est une limite de temps absolument brutale, donc je vais plonger directement, juste au point où je fais fonctionner cette chose. 18 minutos é um limite de tempo absolutamente brutal, por isso vou mergulhar diretamente no ponto em que consigo pôr esta coisa a funcionar. 18 минут — это абсолютно жесткое ограничение по времени, поэтому я собираюсь погрузиться прямо в тот момент, когда я заставлю эту штуку работать. Here we go. Cá vamos nós. I’m going to talk about five different things. Vou falar de cinco coisas diferentes. I’m going to talk about why defeating aging is desirable. Ich werde darüber sprechen, warum es wünschenswert ist, die Alterung zu besiegen. Je vais vous expliquer pourquoi il est souhaitable de vaincre le vieillissement. Vou falar sobre a razão pela qual é desejável derrotar o envelhecimento. Я збираюся поговорити про те, чому перемогти старіння бажано. I’m going to talk about why we have to get our shit together, and actually talk about this a bit more than we do. Ich werde darüber sprechen, warum wir uns zusammenreißen müssen, und tatsächlich ein bisschen mehr darüber sprechen, als wir es tun. Je vais vous expliquer pourquoi nous devons rassembler nos conneries et en parler un peu plus que nous. Vou falar sobre a razão pela qual temos de nos organizar e, na verdade, falar sobre isto um pouco mais do que o fazemos. I’m going to talk about feasibility as well, of course. Je vais aussi parler de faisabilité, bien sûr. Também vou falar de viabilidade, como é óbvio. Я також збираюся говорити про здійсненність, звичайно. I’m going to talk about why we are so fatalistic about doing anything about aging. Je vais vous expliquer pourquoi nous sommes si fatalistes de faire quoi que ce soit contre le vieillissement. Vou falar sobre a razão pela qual somos tão fatalistas em relação ao envelhecimento. Я збираюся поговорити про те, чому ми такі фаталістичні щодо того, щоб щось робити проти старіння. And then I’m going spend perhaps the second half of the talk talking about, you know, how we might actually be able to prove that fatalism is wrong, namely, by actually doing something about it. Et puis je vais peut-être passer la deuxième moitié de la discussion à parler, vous savez, de la façon dont nous pourrions réellement prouver que le fatalisme est mauvais, à savoir en faisant quelque chose à ce sujet. E depois vou passar talvez a segunda metade da palestra a falar sobre como podemos provar que o fatalismo está errado, nomeadamente, fazendo algo a esse respeito. И затем я собираюсь провести, возможно, вторую половину выступления, говоря о том, как мы могли бы на самом деле доказать, что фатализм ошибочен, а именно, на самом деле что-то делать с этим.

I’m going to do that in two steps. Vou fazer isso em duas etapas. The first one I’m going to talk about is how to get from a relatively modest amount of life extension -- which I’m going to define as 30 years, applied to people who are already in middle-age when you start -- to a point which can genuinely be called defeating aging. La première dont je vais vous parler est de savoir comment obtenir une prolongation de vie relativement modeste - que je vais définir comme 30 ans, appliquée aux personnes qui sont déjà d'âge moyen lorsque vous commencez - à un point qui peut vraiment être appelé vaincre le vieillissement. A primeira de que vou falar é sobre como passar de um prolongamento relativamente modesto da vida - que vou definir como 30 anos, aplicado a pessoas que já estão na meia-idade quando se começa - para um ponto que se pode genuinamente chamar derrotar o envelhecimento. Первое, о чем я собираюсь рассказать, это как получить от относительно скромного количества продления жизни — которое я собираюсь определить как 30 лет, применительно к людям, которые уже находятся в среднем возрасте, когда вы начинаете — до точки, которую можно смело назвать победой над старением. Перше, про що я збираюся поговорити, це те, як отримати від відносно скромної кількості продовження життя - яке я визначу як 30 років, застосовуючи до людей, які вже перебувають у середньому віці, коли ви починаєте - до точки, яку справді можна назвати перемогою над старінням. Namely, essentially an elimination of the relationship between how old you are, and how likely you are to die in the next year -- or indeed, to get sick in the first place. À savoir, essentiellement une élimination de la relation entre votre âge et votre probabilité de mourir au cours de la prochaine année - ou même de tomber malade en premier lieu. Ou seja, essencialmente uma eliminação da relação entre a idade e a probabilidade de morrer no próximo ano - ou mesmo de ficar doente. А именно, по сути, устранение зависимости между тем, сколько вам лет, и вероятностью вашей смерти в следующем году — или, более того, вероятностью заболеть в первую очередь. And of course, the last thing I’m going to talk about is how to reach that intermediate step, that point of maybe 30 years life extension. E, claro, a última coisa de que vou falar é sobre como alcançar esse passo intermédio, esse ponto de talvez 30 anos de prolongamento da vida. И, конечно же, последнее, о чем я собираюсь рассказать, это как достичь этого промежуточного шага, этой точки возможного продления жизни на 30 лет.

So I’m going to start with why we should. Por isso, vou começar por dizer por que razão o devemos fazer. Итак, я собираюсь начать с того, почему мы должны. Now, I want to ask a question. Agora, quero fazer uma pergunta. Hands up: Anyone in the audience who is in favor of malaria? Hände hoch! Ist jemand im Publikum, der Malaria befürwortet? Levantem as mãos: Alguém na plateia que seja a favor da malária? Поднимите руки: кто-нибудь из зрителей поддерживает малярию? That was easy. Isso foi fácil. OK. OK. Hands up, anyone in the audience who’s not sure whether malaria is a good thing or a bad thing? Mãos ao alto, alguém na audiência que não tenha a certeza se a malária é uma coisa boa ou má? OK. So we all think malaria is a bad thing. Por isso, todos pensamos que a malária é uma coisa má. That’s very good news, because I thought that was what the answer would be. São muito boas notícias, porque pensei que a resposta seria essa. Now the thing is, I would like to put it to you that the main reason why we think that malaria is a bad thing is because of a characteristic of malaria that it shares with aging. Ich möchte Ihnen sagen, dass der Hauptgrund, warum wir Malaria für etwas Schlimmes halten, eine Eigenschaft der Malaria ist, die sie mit dem Altern teilt. Maintenant, le fait est que je voudrais vous dire que la principale raison pour laquelle nous pensons que le paludisme est une mauvaise chose est à cause d'une caractéristique du paludisme qu'il partage avec le vieillissement. O que se passa é que eu gostaria de vos dizer que a principal razão pela qual pensamos que a malária é uma coisa má é devido a uma caraterística da malária que partilha com o envelhecimento. Теперь дело в том, что я хотел бы сказать вам, что основная причина, по которой мы думаем, что малярия — это плохо, заключается в характеристике малярии, которая свойственна старению. Справа в тому, що я хотів би повідомити вам, що головна причина, чому ми вважаємо малярію поганою річчю, полягає в тій характерній рисі малярії, що вона поділяється зі старінням. And here is that characteristic. The only real difference is that aging kills considerably more people than malaria does. A única diferença real é que o envelhecimento mata consideravelmente mais pessoas do que a malária.

Now, I like in an audience, in Britain especially, to talk about the comparison with fox-hunting, which is something that was banned after a long struggle, by the government not very many months ago. Maintenant, j'aime dans un auditoire, en Grande-Bretagne en particulier, parler de la comparaison avec la chasse au renard, qui a été interdite après une longue lutte, par le gouvernement il n'y a pas très longtemps. Agora, gosto de, numa audiência, especialmente na Grã-Bretanha, falar sobre a comparação com a caça à raposa, que é algo que foi proibido após uma longa luta, pelo governo, não há muitos meses. Теперь мне нравится в аудитории, особенно в Британии, говорить о сравнении с охотой на лис, которая была запрещена правительством после долгой борьбы несколько месяцев назад. I mean, I know I’m with a sympathetic audience here, but, as we know, a lot of people are not entirely persuaded by this logic. Я имею в виду, я знаю, что здесь сочувствующая мне аудитория, но, как мы знаем, многие люди не совсем убеждены в этой логике. And this is actually a rather good comparison, it seems to me. E esta é, de facto, uma comparação bastante boa, parece-me. You know, a lot of people said, "Well, you know, city boys have no business telling us rural types what to do with our time. Viele Leute sagten: "Die Jungs aus der Stadt haben uns Landbewohnern nicht zu sagen, was wir mit unserer Zeit anfangen sollen. Vous savez, beaucoup de gens ont dit: "Eh bien, vous savez, les garçons des villes n’ont rien à faire de nous dire aux ruraux ce qu’il faut faire de notre temps. Знаешь, многие говорили: «Ну, знаете, горожанам незачем указывать нам, деревенским, что делать со временем. It’s a traditional part of the way of life, and we should be allowed to carry on doing it. C'est une partie traditionnelle du mode de vie, et nous devrions être autorisés à continuer de le faire. Это традиционная часть образа жизни, и нам должно быть позволено продолжать это делать. It’s ecologically sound; it stops the population explosion of foxes." C'est écologiquement sain; il arrête l'explosion démographique des renards. " Это экологически безопасно; он останавливает взрыв популяции лис». Це екологічно безпечно; це зупиняє вибух популяції лисиць». But ultimately, the government prevailed in the end, because the majority of the British public, and certainly the majority of members of Parliament, came to the conclusion that it was really something that should not be tolerated in a civilized society. Но в конечном итоге правительство победило, потому что большинство британской общественности и, конечно же, большинство членов парламента пришли к выводу, что это действительно нечто такое, чего нельзя терпеть в цивилизованном обществе. Але врешті-решт уряд переміг, тому що більшість британської громадськості, і, звичайно, більшість членів парламенту, дійшли висновку, що це справді те, чого не можна терпіти в цивілізованому суспільстві.

And I think that human aging shares all of these characteristics in spades. Und ich denke, dass das menschliche Altern alle diese Merkmale in hohem Maße aufweist. Et je pense que le vieillissement humain partage toutes ces caractéristiques à la pelle. И я думаю, что человеческое старение в полной мере разделяет все эти характеристики. What part of this do people not understand? Какую часть этого люди не понимают? It’s not just about life, of course -- (Laughter) it’s about healthy life, you know -- getting frail and miserable and dependent is no fun, whether or not dying may be fun. Il ne s'agit pas seulement de la vie, bien sûr - (Rires), il s'agit d'une vie saine, vous savez - devenir fragile et misérable et dépendant n'est pas amusant, que mourir soit amusant ou non. Конечно, это касается не только жизни — (Смех) речь идет о здоровой жизни, понимаете — становиться слабым, несчастным и зависимым — это не весело, независимо от того, весело ли умирать. Звісно, мова йде не лише про життя -- (Сміх) це про здорове життя, ви знаєте -- стати слабким, нещасним і залежним не весело, незалежно від того, чи весела смерть чи ні. So really, this is how I would like to describe it. It’s a global trance. Es ist eine globale Trance. Это глобальный транс. Це всесвітній транс. These are the sorts of unbelievable excuses that people give for aging. Ce sont les sortes d'excuses incroyables que les gens donnent pour vieillir. Это своего рода невероятные оправдания, которые люди приводят для старения. Ось такі неймовірні виправдання, які люди наводять для старіння. And, I mean, OK, I’m not actually saying that these excuses are completely valueless. И я имею в виду, хорошо, я на самом деле не говорю, что эти оправдания совершенно бесполезны. There are some good points to be made here. Здесь есть несколько хороших моментов. Things that we ought to be thinking about, forward planning so that nothing goes to hell, so that we minimize the turbulence when we actually figure out how to fix aging. Des choses auxquelles nous devons penser, planifier à l'avance pour que rien ne vienne en enfer, afin de minimiser les turbulences lorsque nous découvrons comment réparer le vieillissement. Вещи, о которых мы должны думать, планировать заранее, чтобы ничего не пошло к черту, чтобы мы минимизировали турбулентность, когда на самом деле выясняем, как исправить старение.

But these are completely crazy, when you actually remember your sense of proportion. Но это совершенно безумие, когда вы на самом деле помните свое чувство меры. Але це повне божевілля, якщо згадати своє почуття міри. You know, these are arguments, these are things that would be legitimate to be concerned about. Вы знаете, это аргументы, это вещи, о которых было бы законно беспокоиться. But the question is, are they so dangerous -- these risks of doing something about aging -- that they outweigh the downside of doing the opposite, namely, leaving aging as it is? Mais la question est, sont-ils si dangereux - ces risques de faire quelque chose contre le vieillissement - qu'ils l'emportent sur les inconvénients de faire le contraire, à savoir, laisser le vieillissement tel qu'il est? Но вопрос в том, настолько ли они опасны — эти риски, связанные со старением, — что они перевешивают обратную сторону действий, а именно, оставления старения как есть? Але питання полягає в тому, чи вони настільки небезпечні — ці ризики, пов’язані зі старінням — що вони переважують негативну сторону протилежних дій, а саме — залишити старіння таким, яким воно є? Are these so bad that they outweigh condemning 100,000 people a day to an unnecessarily early death. Sont-ils si graves qu'ils l'emportent sur la condamnation de 100 000 personnes par jour à une mort prématurée inutilement. Неужели они настолько плохи, что перевешивают обречение 100 000 человек в день на излишне раннюю смерть? Невже вони настільки погані, що переважають прирікання 100 000 людей на день на невиправдано ранню смерть? You know, if you haven’t got an argument that’s that strong, then just don’t waste my time is what I say. Знаешь, если у тебя нет такого сильного аргумента, тогда просто не трать мое время, вот что я скажу. (Laughter)

Now, there is one argument that some people do think really is that strong, and here it is. Итак, есть один аргумент, который некоторые люди считают действительно сильным, и вот он. People worry about overpopulation; they say, "Well, if we fix aging, no one’s going to die to speak of, or at least the death toll is going to be much lower, only from crossing St. Люди беспокоятся о перенаселении; они говорят: «Ну, если мы исправим старение, никто не умрет, чтобы говорить о нем, или, по крайней мере, число погибших будет намного меньше, только от пересечения улицы Сент-Луис». Людей хвилює перенаселення; вони кажуть: «Якщо ми вирішимо проблему старіння, ніхто не помре, або, принаймні, кількість смертей буде набагато нижчою, лише від перетину вул. Giles carelessly. Джайлз небрежно. And therefore, we’re not going to be able to have many kids, and kids are really important to most people." И поэтому мы не сможем иметь много детей, а дети действительно важны для большинства людей». And that’s true. And you know, a lot of people try to fudge this question, and give answers like this. Et vous savez, beaucoup de gens essaient de truquer cette question et donnent des réponses comme celle-ci. И вы знаете, многие люди пытаются сфальсифицировать этот вопрос и давать такие ответы. І знаєте, багато людей намагаються обдурити це питання і дають такі відповіді. I don’t agree with those answers. I think they basically don’t work. I think it’s true, that we will face a dilemma in this respect. Я думаю, это правда, что мы столкнемся с дилеммой в этом отношении. We will have to decide whether to have a low birth rate, or a high death rate. Нам придется решить, иметь ли низкую рождаемость или высокую смертность. A high death rate will, of course, arise from simply rejecting these therapies, in favor of carrying on having a lot of kids. Un taux de mortalité élevé résultera, bien sûr, du simple rejet de ces thérapies, en faveur de la poursuite de nombreux enfants. Высокий уровень смертности, конечно же, возникнет из-за простого отказа от этих методов лечения в пользу того, чтобы иметь много детей.

And, I say that that’s fine -- the future of humanity is entitled to make that choice. И я говорю, что это нормально — будущее человечества вправе сделать этот выбор. What’s not fine is for us to make that choice on behalf of the future. Что не хорошо, так это то, что мы делаем этот выбор от имени будущего. If we vacillate, hesitate, and do not actually develop these therapies, then we are condemning a whole cohort of people -- who would have been young enough and healthy enough to benefit from those therapies but will not be, because we haven’t developed them as quickly as we could -- we’ll be denying those people an indefinite life span, and I consider that that is immoral. Если мы колеблемся, колеблемся и на самом деле не разрабатываем эти методы лечения, то мы осуждаем целую группу людей, которые были бы достаточно молоды и здоровы, чтобы получить пользу от этих методов лечения, но не будут, потому что мы не разработали их. их так быстро, как только сможем — мы будем лишать этих людей неопределенной продолжительности жизни, и я считаю, что это аморально. Якщо ми коливаємося, вагаємось і фактично не розробляємо ці методи лікування, тоді ми засуджуємо цілу когорту людей, які були б достатньо молодими та здоровими, щоб отримати користь від цих методів лікування, але не отримають цього, тому що ми не розробили їх якомога швидше -- ми позбавимо цих людей невизначеної тривалості життя, і я вважаю, що це аморально. That’s my answer to the overpopulation question.

Right. So the next thing is, now why should we get a little bit more active on this? And the fundamental answer is that the pro-aging trance is not as dumb as it looks. И фундаментальный ответ заключается в том, что транс, способствующий старению, не так глуп, как кажется. It’s actually a sensible way of coping with the inevitability of aging. C'est en fait une façon sensée de faire face à l'inévitabilité du vieillissement. На самом деле это разумный способ справиться с неизбежностью старения. Насправді це розумний спосіб впоратися з неминучістю старіння. Aging is ghastly, but it’s inevitable, so, you know, we’ve got to find some way to put it out of our minds, and it’s rational to do anything that we might want to do, to do that. Le vieillissement est horrible, mais c'est inévitable, alors, vous savez, nous devons trouver un moyen de le faire sortir de nos esprits, et il est rationnel de faire tout ce que nous pourrions vouloir faire, de le faire. Старение ужасно, но оно неизбежно, так что, вы знаете, мы должны найти какой-то способ выкинуть это из головы, и разумно делать все, что мы можем захотеть сделать, сделать это. Старіння – це жахливо, але воно неминуче, тому, знаєте, ми повинні знайти спосіб викинути це з голови, і було б раціонально робити все, що ми можемо захотіти, робити це. Like, for example, making up these ridiculous reasons why aging is actually a good thing after all. Comme, par exemple, inventer ces raisons ridicules pour lesquelles le vieillissement est en fait une bonne chose après tout. Как, например, выдумывание этих нелепых причин, по которым старение — это, в конце концов, хорошо. But of course, that only works when we have both of these components. And as soon as the inevitability bit becomes a little bit unclear, and we might be in range of doing something about aging, this becomes part of the problem. Und sobald die Unvermeidbarkeit ein wenig unklar wird und wir in der Lage sind, etwas gegen das Altern zu tun, wird dies Teil des Problems. Et dès que l'inévitabilité devient un peu floue, et que nous pourrions être à portée de faire quelque chose contre le vieillissement, cela devient une partie du problème. This pro-aging trance is what stops us from agitating about these things. Cette transe pro-vieillissement est ce qui nous empêche d'agiter sur ces choses. And that’s why we have to really talk about this a lot -- evangelize, I will go so far as to say -- in order to get people’s attention, and make people realize that they are in a trance in this regard. І ось чому ми дійсно маємо багато говорити про це — проповідувати, я зайду так далеко, що скажу — щоб привернути увагу людей і змусити людей усвідомити, що вони перебувають у трансі з цього приводу. So that’s all I’m going to say about that.

I’m now going to talk about feasibility. Зараз я поговорю про здійсненність. And the fundamental reason, I think, why we feel that aging is inevitable is summed up in a definition of aging that I’m giving here. Und ich denke, der Hauptgrund, warum wir das Altern für unvermeidlich halten, lässt sich in der Definition des Alterns zusammenfassen, die ich hier gebe. A very simple definition. Aging is a side effect of being alive in the first place, which is to say, metabolism. This is not a completely tautological statement; it’s a reasonable statement. Aging is basically a process that happens to inanimate objects like cars, and it also happens to us, despite the fact that we have a lot of clever self-repair mechanisms, because those self-repair mechanisms are not perfect. Старіння — це, по суті, процес, який відбувається з неживими об’єктами, такими як автомобілі, і це також відбувається з нами, незважаючи на те, що у нас є багато розумних механізмів самовідновлення, тому що ці механізми самовідновлення не ідеальні.

So basically, metabolism, which is defined as basically everything that keeps us alive from one day to the next, has side effects. Those side effects accumulate and eventually cause pathology. That’s a fine definition. So we can put it this way: we can say that, you know, we have this chain of events. And there are really two games in town, according to most people, with regard to postponing aging. They’re what I’m calling here the gerontology approach and the geriatrics approach. Це те, що я тут називаю підходом геронтології та підходом геріатрії. The geriatrician will intervene late in the day, when pathology is becoming evident, and the geriatrician will try and hold back the sands of time, and stop the accumulation of side effects from causing the pathology quite so soon. Лікар-геріатр втрутиться пізно ввечері, коли патологія стане очевидною, і геріатр спробує стримати піски часу та зупинити накопичення побічних ефектів, які викликають патологію досить швидко. Of course, it’s a very short-termist strategy, it’s a losing battle, because the things that are causing the pathology are becoming more abundant as time goes on. Звичайно, це дуже короткострокова стратегія, це програшна битва, тому що речей, які викликають патологію, з плином часу стає все більше.

The gerontology approach looks much more promising on the surface, because, you know, prevention is better than cure. But unfortunately the thing is that we don’t understand metabolism very well. In fact, we have a pitifully poor understanding of how organisms work -- even cells we’re not really too good on yet. Насправді ми дуже погано розуміємо, як функціонують організми - навіть клітини, з якими ми ще не надто добре розбираємося. We’ve discovered things like, for example, RNA interference only a few years ago, and this is a really fundamental component of how cells work. Basically, gerontology is a fine approach in the end, but it is not an approach whose time has come when we’re talking about intervention. So then, what do we do about that? I mean, that’s a fine logic, that sounds pretty convincing, pretty iron-clad, doesn’t it? Я маю на увазі, що це гарна логіка, це звучить досить переконливо, досить залізно, чи не так?

But it isn’t. Before I tell you why it isn’t, I’m going to go a little bit into what I’m calling step two. Just suppose, as I said, that we do acquire -- let’s say we do it today for sake of argument -- the ability to confer 30 extra years of healthy life on people who are already in middle age, let’s say 55. Просто припустімо, як я вже сказав, що ми справді отримуємо – скажімо, ми робимо це сьогодні заради аргументу – здатність надати 30 додаткових років здорового життя людям, які вже перебувають у середньому віці, скажімо, 55. I’m going to call that robust human rejuvenation. Я називатиму це потужним людським омолодженням. OK. What would that actually mean for how long people of various ages today -- or equivalently, of various ages at the time that these therapies arrive -- would actually live? In order to answer that question -- you might think it’s simple, but it’s not simple. We can’t just say, "Well, if they’re young enough to benefit from these therapies, then they’ll live 30 years longer." That’s the wrong answer. And the reason it’s the wrong answer is because of progress.

There are two sorts of technological progress really, for this purpose. There are fundamental, major breakthroughs, and there are incremental refinements of those breakthroughs. Є фундаментальні, серйозні прориви, і є поступове вдосконалення цих проривів. Now, they differ a great deal in terms of the predictability of time frames. Fundamental breakthroughs: very hard to predict how long it’s going to take to make a fundamental breakthrough. It was a very long time ago that we decided that flying would be fun, and it took us until 1903 to actually work out how to do it. But after that, things were pretty steady and pretty uniform. Aber danach waren die Dinge ziemlich stabil und ziemlich gleichmäßig. Але після цього все стало досить стабільним і досить рівномірним. I think this is a reasonable sequence of events that happened in the progression of the technology of powered flight. Я вважаю, що це розумна послідовність подій, які відбулися в процесі розвитку технології польоту з двигуном. We can think, really, that each one is sort of beyond the imagination of the inventor of the previous one, if you like. Насправді ми можемо думати, що кожен із них начебто перевершує уяву винахідника попереднього, якщо хочете. The incremental advances have owed up to something which is not incremental anymore. Поступові аванси завдячують чомусь, що більше не є поступовим.

This is the sort of thing you see after a fundamental breakthrough. And you see it in all sorts of technologies. Computers, you can look at a more or less parallel time line, happening of course a bit later. You can look at medical care. I mean, hygiene, vaccines, antibiotics -- you know, the same sort of time frame. So I think that actually step two, that I called a step a moment ago, isn’t a step at all. That in fact, the people who are young enough to benefit from these first therapies that give this moderate amount of life extension, even though those people are already middle-aged when the therapies arrive, will be at some sort of cusp. Насправді, люди, які є достатньо молодими, щоб отримати користь від цих перших методів лікування, які дають таку помірну кількість продовження життя, навіть якщо ці люди вже були середнього віку, коли лікування з’явилося, будуть на якомусь порозі. They will mostly survive long enough to receive improved treatments that will give them a further 30 or maybe 50 years. In other words, they will be staying ahead of the game. The therapies will be improving faster than the remaining imperfections in the therapies are catching up with us.

This is a very important point for me to get across. Because, you know, most people, when they hear that I predict that a lot of people alive today are going to live to 1,000 or more, they think that I’m saying that we’re going to invent therapies in the next few decades that are so thoroughly eliminating aging that those therapies will let us live to 1,000 or more. I’m not saying that at all. I’m saying that the rate of improvement of those therapies will be enough. They’ll never be perfect, but we’ll be able to fix the things that 200-year-olds die of, before we have any 200-year-olds. And the same for three- and 400 and so on. I decided to give this a little name, which is "longevity escape velocity." Ich habe beschlossen, dem Ganzen einen kleinen Namen zu geben, nämlich "Langlebigkeit - Fluchtgeschwindigkeit". Я вирішив дати цьому коротке ім’я, а саме «швидкість втечі довголіття». (Laughter) Well, it seems to get the point across. (Gelächter) Nun, es scheint den Punkt zu treffen. (Сміх) Що ж, здається, це зрозуміло суть.

So, these trajectories here are basically how we would expect people to live, in terms of remaining life expectancy, as measured by their health, for given ages that they were at the time that these therapies arrive. If you’re already 100, or even if you’re 80 -- and an average 80-year-old, we probably can’t do a lot for you with these therapies, because you’re too close to death’s door for the really initial, experimental therapies to be good enough for you. You won’t be able to withstand them. But if you’re only 50, then there’s a chance that you might be able to pull out of the dive and, you know -- (Laughter) eventually get through this. And start becoming biologically younger in a meaningful sense, in terms of your youthfulness, both physical and mental, and in terms of your risk of death from age-related causes. And of course, if you’re a bit younger than that, then you’re never really even going to get near to being fragile enough to die of age-related causes.

So this is a genuine conclusion that I come to, that the first 150-year old -- we don’t know how old that person is today, because we don’t know how long it’s going to take to get these first-generation therapies. But irrespective of that age, I’m claiming that the first person to live to 1,000 -- subject of course, to, you know, global catastrophes -- is actually, probably, only about 10 years younger than the first 150-year old. Але незважаючи на цей вік, я стверджую, що перша людина, яка дожила до 1000 років — звісно, за умови, знаєте, глобальних катастроф — насправді, ймовірно, лише приблизно на 10 років молодша за першу 150-річну. . And that’s quite a thought.

All right, so finally I’m going to spend the rest of the talk, my last seven and a half minutes, on step one; namely, how do we actually get to this moderate amount of life extension that will allow us to get to escape velocity? And in order to do that, I need to talk about mice a little bit. І для цього мені потрібно трохи поговорити про мишей. I have a corresponding milestone to robust human rejuvenation. У мене є відповідна віха для надійного омолодження людини. I’m calling it robust mouse rejuvenation, not very imaginatively. Я називаю це надійним омолодженням миші, не надто образно. And this is what it is. I say we’re going to take a long-lived strain of mouse, which basically means mice that live about three years on average. Я кажу, що ми візьмемо довгоживучу лінію мишей, що в основному означає мишей, які живуть у середньому близько трьох років. We do exactly nothing to them until they’re already two years old. And then we do a whole bunch of stuff to them, and with those therapies, we get them to live, on average, to their fifth birthday. So, in other words, we add two years -- we treble their remaining lifespan, starting from the point that we started the therapies. Таким чином, іншими словами, ми додаємо два роки -- ми потроюємо їхню тривалість життя, що залишилася, починаючи з того моменту, коли ми почали терапію.

The question then is, what would that actually mean for the time frame until we get to the milestone I talked about earlier for humans? Which we can now, as I’ve explained, equivalently call either robust human rejuvenation, or longevity escape velocity. Secondly, what does it mean for the public’s perception of how long it’s going to take for us to get to those things, starting from the time we get the mice? And thirdly, the question is, what will it do to actually how much people want it? And it seems to me that the first question is entirely a biology question, and it’s extremely hard to answer. One has to be very speculative, and many of my colleagues would say that we should not do this speculation, that we should simply keep our counsel until we know more. Треба бути дуже спекулятивним, і багато моїх колег сказали б, що ми не повинні займатися цими спекуляціями, що ми повинні просто дотримуватися наших порад, доки не дізнаємося більше.

I say that’s nonsense. I say we absolutely are irresponsible if we stay silent on this. We need to give our best guess as to the time frame, in order to give people a sense of proportion so that they can assess their priorities. Нам потрібно якнайкраще припустити часові рамки, щоб дати людям відчуття міри, щоб вони могли оцінити свої пріоритети. So, I say that we have a 50/50 chance of reaching this RHR milestone, robust human rejuvenation, within 15 years from the point that we get to robust mouse rejuvenation. Отже, я кажу, що у нас є 50/50 шансів досягти цієї віхи RHR, надійного омолодження людини, протягом 15 років з моменту, коли ми досягнемо надійного омолодження миші. 15 years from the robust mouse. 15 років надійній миші. The public’s perception will probably be somewhat better than that. The public tend to underestimate how difficult scientific things are. So they’ll probably think it’s five years away. They’ll be wrong, but that actually won’t matter too much. And finally, of course, I think it’s fair to say that a large part of the reason why the public is so ambivalent about aging now is the global trance I spoke about earlier, the coping strategy. І нарешті, звичайно, я вважаю справедливим сказати, що значна частина причин, чому громадськість зараз так неоднозначно ставиться до старіння, це глобальний транс, про який я говорив раніше, стратегія подолання. That will be history at this point, because it will no longer be possible to believe that aging is inevitable in humans, since it’s been postponed so very effectively in mice. So we’re likely to end up with a very strong change in people’s attitudes, and of course that has enormous implications. Тож ми, швидше за все, призведемо до дуже сильної зміни у ставленні людей, і, звичайно, це має величезні наслідки.

So in order to tell you now how we’re going to get these mice, I’m going to add a little bit to my description of aging. I’m going to use this word "damage" to denote these intermediate things that are caused by metabolism, and that eventually cause pathology. Я збираюся використовувати це слово «пошкодження», щоб позначити ці проміжні речі, які викликані метаболізмом і які врешті-решт викликають патологію. Because the critical thing about this is that even though the damage only eventually causes pathology, the damage itself is caused ongoingly throughout life, starting before we’re born. But it is not part of metabolism itself. And this turns out to be useful. Because we can re-draw our original diagram this way. We can say that, fundamentally, the difference between gerontology and geriatrics is that gerontology tries to inhibit the rate at which metabolism lays down this damage. Можна сказати, що принципова різниця між геронтологією та геріатрією полягає в тому, що геронтологія намагається загальмувати швидкість, з якою метаболізм завдає цієї шкоди. And I’m going to explain exactly what damage is in concrete biological terms in a moment. And geriatricians try to hold back the sands of time by stopping the damage converting into pathology. And the reason it’s a losing battle is because the damage is continuing to accumulate.

So there’s a third approach, if we look at it this way. We can call it the engineering approach, and I claim that the engineering approach is within range. The engineering approach does not intervene in any processes. It does not intervene in this process, or this one. And that’s good because it means that it’s not a losing battle, and it’s something that we are within range of being able to do, because it doesn’t involve improving on evolution. The engineering approach simply says, "Let’s go and periodically repair all of these various types of damage -- not necessarily repair them completely, but repair them quite a lot, so that we keep the level of damage down below the threshold that must exist, that causes it to be pathogenic." We know that this threshold exists, because we don’t get age-related diseases until we’re in middle age, even though the damage has been accumulating since before we were born.

Why do I say that we’re in range? Well, this is basically it. The point about this slide is actually the bottom. Суть цього слайда – це дно. If we try to say which bits of metabolism are important for aging, we will be here all night, because basically all of metabolism is important for aging in one way or another. Якщо ми спробуємо сказати, які фрагменти метаболізму важливі для старіння, ми будемо тут всю ніч, тому що в основному весь метаболізм так чи інакше важливий для старіння. This list is just for illustration, it is incomplete. The list on the right is also incomplete. It’s a list of types of pathology that are age-related, and it’s just an incomplete list. But I would like to claim to you that this list in the middle is actually complete, this is the list of types of thing that qualify as damage, side effects of metabolism that cause pathology in the end, or that might cause pathology. And there are only seven of them. They’re categories of thing, of course, but there’s only seven of them. Cell loss, mutations in chromosomes, mutations in the mitochondria and so on.

First of all, I’d like to give you an argument for why that list is complete. Of course one can make a biological argument. One can say, OK, what are we made of? We’re made of cells and stuff between cells. What can damage accumulate in? The answer is, long-lived molecules, because if a short-lived molecule undergoes damage, but then the molecule is destroyed -- like by a protein being destroyed by proteolysis -- then the damage is gone, too. It’s got to be long-lived molecules. So, these seven things were all under discussion in gerontology a long time ago and that is pretty good news, because it means that, you know, we’ve come a long way in biology in these 20 years, so the fact that we haven’t extended this list is a pretty good indication that there’s no extension to be done. However, it’s better than that; we actually know how to fix them all in mice, in principle -- and what I mean by in principle is, we probably can actually implement these fixes within a decade. Some of them are partially implemented already, the ones at the top.

I haven’t got time to go through them at all, but my conclusion is that, if we can actually get suitable funding for this, then we can probably develop robust mass rejuvenation in only 10 years, but we do need to get serious about it. We do need to really start trying. So of course, there are some biologists in the audience, and I want to give some answers to some of the questions that you may have. You may have been dissatisfied with this talk, but fundamentally you have to go and read this stuff. Можливо, ви були незадоволені цією розмовою, але в принципі ви повинні піти і прочитати ці речі. I’ve published a great deal on this; I cite the experimental work on which my optimism is based, and there’s quite a lot of detail there. Я опублікував багато про це; Я цитую експериментальну роботу, на якій базується мій оптимізм, і там досить багато деталей. The detail is what makes me confident of my rather aggressive time frames that I’m predicting here. So if you think that I’m wrong, you’d better damn well go and find out why you think I’m wrong.

And of course the main thing is that you shouldn’t trust people who call themselves gerontologists because, as with any radical departure from previous thinking within a particular field, you know, you expect people in the mainstream to be a bit resistant and not really to take it seriously. So, you know, you’ve got to actually do your homework, in order to understand whether this is true.

And we’ll just end with a few things. One thing is, you know, you’ll be hearing from a guy in the next session who said some time ago that he could sequence the human genome in no time, and everyone said, "Well, it’s obviously impossible." And you know what happened. So, you know, this does happen. We have various strategies -- there’s the Methuselah Mouse Prize, which is basically an incentive to innovate, and to do what you think is going to work, and you get money for it if you win. У нас є різні стратегії – є премія «Мишка Мафусаїл», яка, по суті, є стимулом до інновацій і робити те, що, на вашу думку, спрацює, і ви отримаєте за це гроші, якщо виграєте. There’s a proposal to actually put together an institute. This is what’s going to take a bit of money. But, I mean, look -- how long does it take to spend that on the war in Iraq? Not very long. OK. (Laughter) It’s got to be philanthropic, because profits distract biotech, but it’s basically got a 90 percent chance, I think, of succeeding in this. (Сміх) Це має бути філантропія, тому що прибутки відволікають увагу від біотехнологій, але я вважаю, що в основному є 90 відсотків шансів досягти успіху в цьому. And I think we know how to do it. And I’ll stop there. Thank you. (Applause)

Chris Anderson: OK. I don’t know if there’s going to be any questions but I thought I would give people the chance. Audience: Since you’ve been talking about aging and trying to defeat it, why is it that you make yourself appear like an old man? (Laughter)

AG: Because I am an old man. I am actually 158. (Laughter) (Applause)

Audience: Species on this planet have evolved with immune systems, to fight off all the diseases so that individuals live long enough to procreate. Аудиторія: Види на цій планеті еволюціонували з імунною системою, щоб боротися з усіма хворобами, щоб особини жили достатньо довго для продовження роду. However, as far as I know, all the species have evolved to actually die, so when cells divide, the telomerase get shorter, and eventually species die. Однак, наскільки мені відомо, усі види еволюціонували так, що фактично гинуть, тому, коли клітини діляться, теломераза стає коротшою, і зрештою види гинуть. So, why does -- evolution has -- seems to have selected against immortality, when it is so advantageous, or is evolution just incomplete? Отже, чому - еволюція - здається, вибрала проти безсмертя, коли це так вигідно, чи еволюція просто неповна?

AG: Brilliant. Thank you for asking a question that I can answer with an uncontroversial answer. Дякую, що задали питання, на яке я можу відповісти беззаперечно. I’m going to tell you the genuine mainstream answer to your question, which I happen to agree with. Я збираюся дати вам справжню основну відповідь на ваше запитання, з якою я випадково згоден. Which is that, no, aging is not a product of selection; evolution is simply a product of evolutionary neglect. Це означає, що ні, старіння не є продуктом відбору; еволюція є просто продуктом еволюційного нехтування. In other words, we have aging because it’s hard work not to have aging; you need more genetic pathway, more sophistication in your genes in order to age more slowly, and that carries on being true the longer you push it out. So, to the extent that evolution doesn’t matter, doesn’t care whether genes are passed on by individuals, living a long time or by procreation, there’s a certain amount of modulation of that, which is why different species have different lifespans, but that’s why there are no immortal species.

CA: The genes don’t care but we do?

AG: That’s right.

Audience: Hello. I read somewhere that in the last 20 years, the average lifespan of basically anyone on the planet has grown by 10 years. If I project that, that would make me think that I would live until 120 if I don’t crash on my motorbike. That means that I’m one of your subjects to become a 1000 year old?

AG: If you lose a bit of weight. (Laughter) Your numbers are a bit out. The standard numbers are that lifespans have been growing at between one and two years per decade. So, it’s not quite as good as you might think -- you might hope. But I intend to move it up to one year per year as soon as possible.

Audience: I was told that many of the brain cells we have as adults are actually in the human embryo, and that the brain cells last 80 years or so. Аудиторія: Мені сказали, що багато клітин мозку, які ми маємо у дорослому віці, насправді знаходяться в людському ембріоні, і що клітини мозку живуть близько 80 років. If that is indeed true, biologically are there implications in the world of rejuvenation? Якщо це справді так, чи є біологічні наслідки у світі омолодження? If there are cells in my body that live all 80 years, as opposed to a typical, you know, couple of months?

AG: There are technical implications certainly. Basically what we need to do is replace cells in those few areas of the brain that lose cells at a respectable rate, especially neurons, but we don’t want to replace them any faster than that -- or not much faster anyway, because replacing them too fast would degrade cognitive function. По суті, нам потрібно замінити клітини в тих кількох ділянках мозку, які втрачають клітини з поважною швидкістю, особливо нейрони, але ми не хочемо замінювати їх швидше за це — чи не набагато швидше, тому що заміна вони занадто швидко погіршать когнітивні функції. What I said about there being no non-aging species earlier on was a little bit of an oversimplification. There are species that have no aging -- Hydra for example -- but they do it by not having a nervous system -- and not having any tissues in fact that rely for their function on very long-lived cells. Існують види, які не старіють — наприклад, гідра, — але вони це роблять, не маючи нервової системи — і фактично не маючи жодних тканин, які покладаються для своєї функції на дуже довгоживучі клітини.

http://www.ted.com/talks/aubrey_de_grey_says_we_can_avoid_aging.html