How to live forever
如何长生不老 Jan 3rd 2008 From The Economist print edition
It looks unlikely that medical science will abolish the process of ageing. But it no longer looks impossible
医学似乎不大可能阻止衰老的进程。但是，防止衰老也不是不可能的事情。
Stephen Jeffrey
“IN THE long run,” as John Maynard Keynes observed, “we are all dead.” True. But can the short run be elongated in a way that makes the long run longer? And if so, how, and at what cost? People have dreamt of immortality since time immemorial. They have sought it since the first alchemist put an elixir of life on the same shopping list as a way to turn lead into gold. They have written about it in fiction, from Rider Haggard's “She” to Frank Herbert's “Dune”. And now, with the growth of biological knowledge that has marked the past few decades, a few researchers believe it might be within reach.
约翰.梅纳德.凯恩斯说：“从长远来看，我们都得死 ”。确实如此。但我们能不能让死亡离我们更远一些呢？如果那样的话，又怎么做到，要花费多大的代价呢？自远古时候起，人们就梦想长生不老。自从第一位炼金术士把长生不老药写入处方作为点石为金的法术，人们把这写进了小说，从瑞德尔.哈格德作品中的“她”到富兰克作品中的“多恩”都体现了这点。如今，随着过去几十年的生物科技的发展，一些研究者认为长生不老是可以实现的。
To think about the question, it is important to understand why organisms—people included—age in the first place. People are like machines: they wear out. That much is obvious. However a machine can always be repaired. A good mechanic with a stock of spare parts can keep it going indefinitely. Eventually, no part of the original may remain, but it still carries on, like Lincoln's famous axe that had had three new handles and two new blade。
要弄清这个问题，首先我们得知道为什么包括人在内的所有生物体都会衰老。人也象机器一样，会磨损。这一点是众所周知的。然而机器总是可以维修的。好的机械工用一批备用零件可以大致让它不停的运转。最终，机器的原来的零件一个都不剩了，但它仍继续运转，就像林肯的那把有名的斧头，换过三个柄和两个刀锋。
The question, of course, is whether the machine is worth repairing. It is here that people and nature disagree. Or, to put it slightly differently, two bits of nature disagree with each other. From the individual's point of view, survival is an imperative. You cannot reproduce unless you are alive. A fear of death is a sensible evolved response and, since ageing is a sure way of dying, it is no surprise that people want to stop it in its tracks. Moreover, even the appearance of ageing can be harmful. It reduces the range of potential sexual partners who find you attractive—since it is a sign that you are not going to be around all that long to help bring up baby—and thus, again, curbs your reproduction.
当然，问题在于这个机器值不值得修。这正是人和自然不一样的地方。或者换句话来说，自然中两个部分彼此不一样。从个人的观点来看，生存是必不可少的条件。只有活着人才会繁衍后代。对死亡的恐惧是一种合理演化的反应，因为衰老是死亡的必经之路，所以毫不奇怪，人们想阻止它的发生。而且，即使出现衰老也会对人不利。这也减少了你所能吸引的性伴侣的范畴，因为衰老表明你无法一直承担抚养孩子的重任，因而，这也妨碍了你繁衍后代的能力。
The paradox is that the individual's evolved desire not to age is opposed by another evolutionary force: the disposable soma. The soma (the ancient Greek word for body) is all of a body's cells apart from the sex cells. The soma's role is to get those sex cells, and thus the organism's genes, into the next generation. If the soma is a chicken, then it really is just an egg's way of making another egg. And if evolutionary logic requires the soma to age and die in order for this to happen, so be it. Which is a pity, for evolutionary logic does, indeed, seem to require that.
矛盾之处在于人们想要不变老的想法是与另一种进化力量想悖：抛弃肌体。Soma在希腊语中是“肌体”之意，它意为人体的细胞与生殖细胞分离。躯体的作用就是获得生殖细胞，并把机体的基因传给下一代。如果这个躯体是鸡，那么它会以鸡生蛋的方式制造出另一个鸡蛋。如果根据进化法则，人的肌体要衰老，而且因为这而逝去，那么就让它进行下去吧。遗憾的是，进化法则确实是这样的。
The argument is this. All organisms are going to die of something eventually. That something may be an accident, a fight, a disease or an encounter with a hungry predator. There is thus a premium on reproducing early rather than conserving resources for a future that may never come. The reason why repairs are not perfect is that they are costly and resources invested in them might be used for reproduction instead. Often, therefore, the body's mechanics prefer lash-ups to complete rebuilds—or simply do not bother with the job at all. And if that is so, the place to start looking for longer life is in the repair shop.
问题是，所有的生物体最终都会因为某种原因而逝去。那种原因可能是一次事故，一场争斗，一场病或者遇到饥饿的猎食者。因而，早点养育后代比为了一个可能永远不会有的未来而养精蓄锐要好得多。对人体这个机器的维修为什么不那么理想呢，原因就在于首先维修成本昂贵，其次，对维修的投入可以用来养育后代。因此，通常身体的结构更易接受修补而不是完全的重建，或者对修补不厌其烦。如果那样的话，那么寻求长寿就要从修理店开始。
Seven deadly things
七大关键的问题
One man who has done just that is Aubrey de Grey. Dr de Grey, who is an independent researcher working in Cambridge, England, is a man who provokes strong opinions. He is undoubtedly a visionary, but many biologists think that his visions are not so much insights as mischievous mirages, for he believes that anti-ageing technology could come about in a future that many now alive might live to see.
奥布里. 德. 格雷，英国剑桥大学的一位独立研究者，就做过这样的维修。他坚定的认为人的寿命是可以延长的。毫无疑问他是个幻想家，但许多生物学家认为他的想法与其说是深刻的见解不如说是一种搞笑的幻想/不是深刻的见解而是搞笑的妄想，因为他认为许多现在的人可以活到看到抗衰老科技的出现的那一天。
Vision or mirage, Dr de Grey has defined the problem precisely. Unlike most workers in the field, he has an engineering background, and is thus ideally placed to look into the biological repair shop. As he sees things, ageing has seven components; deal with all seven, and you stop the process in its tracks. He refers to this approach as strategies for engineered negligible senescence (SENS).
不管是幻想还是妄想，德.格雷博士已经清楚地阐明了这个问题。与这个研究领域的大多数人不同，他学过工程学，因而是研究人体生物修复所的理想人选。他认为衰老由七个部分构成；如果解决好了这七个问题，那么你就能够阻止衰老的进程。他把这个措施称作细微老化工程策略。
The seven sisters that Dr de Grey wishes to slaughter with SENS are cell loss, apoptosis-resistance (the tendency of cells to refuse to die when they are supposed to), gene mutations in the cell nucleus, gene mutations in the mitochondria (the cell's power-packs), the accumulation of junk inside cells, the accumulation of junk outside cells and the accumulation of inappropriate chemical links in the material that supports cells.
德.格雷博士想要用他的细微老化工程来解决的这七大问题就是：不可替代细胞的丧失；不良细胞的积聚（细胞在应该调亡时继续存在）；细胞核基因变异；被视为细胞能量中心的线粒体DNA突变；有害废物在细胞空隙之间积累；细胞间废物堆积/不可消化分子阻碍流通；使动脉弹性组织老化的蛋白质的繁殖/糖分子与蛋白质分子结合，随着时间的推移，引起组织变硬。
It is quite a shopping list. But it does, at least, break the problem into manageable parts. It also suggests that multiple approaches to the question may be needed. Broadly, these are of two sorts: to manage the process of wear and tear to slow it down and mask its consequences, or to accept its inevitability and bring the body in for servicing at regular intervals to replace the worn-out parts.
问题够多的。但是，这确实至少是把问题分成了几个可以操作的部分。同时也表明解决衰老的问题是需要多种途径的。从大的方面来看，这些途径可以分为两类：一是减缓磨损的进程，减小它的影响；二是接受细胞磨损的必然性，让肌体接受定期的维修来替代磨损的细胞。
Eat up your greens
吃绿色食品
Managing wear and tear may not be as complicated as it looks, for the last five items on Dr de Grey's list seem to be linked by a single word: oxidation. Regular visitors to the “health and beauty” sections of high-street pharmacies will, no doubt, have come across creams, pills and potions bearing the word antioxidant on their labels and hinting—though never, of course, explicitly saying—that they might possibly have rejuvenating effects. These products are the bastard children of a respectable idea about one of the chief causes of ageing: that one big source of bodily wear and tear, at least at the chemical level, is the activity of the mitochondria.
解决细胞磨损的问题可能不想它看起来那么复杂，因为德.格雷提到的后五个问题涉及一个共同的词：氧化。经常去街上医疗机构的“健康与美容”部门的人毫无疑问碰到过护肤霜、药丸及药剂，上面的标签上写有抗氧化剂字样，暗示着它们有返老还童之功效，当然这从来是没有明白的说出来的。这些产品都是一个可敬的想法的产物，即肌体磨损的一个最主要的原因至少从化学层面上来讲是由于线粒体的活动，这个是造成衰老的主要原因之一。
Mitochondria are the places where sugar is broken down and reacted with oxygen to release the energy needed to power a cell. In a warm-blooded creature such as man, a lot of oxygen is involved in this process, and some of it goes absent without leave. Instead of reacting with carbon from the sugar to form carbon dioxide, it forms highly reactive molecules called free radicals. These go around oxidising—and thus damaging—other molecules, such as DNA and proteins, which causes all sorts of trouble. Clear up free radicals and their kin, and you will slow down the process of ageing. And the chemicals you use to do that are antioxidants.
线粒体是糖分分解的地方，并且在此与氧分发生作用以释放细胞所需要的能量。在象人类这样的温血生物体内，有很多的氧分参与这个过程，其中有些氧分自行游离。它们没有与碳分子发生作用来形成二氧化碳，它们形成了高度活跃的分子：自由激进分子。这些分子四处氧化其他分子，比如DNA和蛋白质，并损害这些分子，从而造成了各种各样的问题。如果清除这些自由激进分子及其同类，你就可以减缓衰老的进程。而用于这一过程的化学物质就是抗氧化剂。
This idea goes back to one of the founders of scientific gerontology, Bruce Ames of the University of California, Berkeley. Dr Ames began his career studying cancer. He found that damage to certain genes was a cause of cancer. These genes evolved to keep tumours at bay by stopping cells dividing too readily, and the damage was often done by oxidation. Gradually, his focus shifted to the more general damage that oxidation can do—and what might, in turn, be done about it.
这个想法来自于老人医学学科的创立者之一加利福尼亚大学伯克利分校的布鲁斯.阿姆斯。布鲁斯博士的话职业是以研究癌症为开端的。他发现某些基因的损伤是造成癌症的原因之一。这些基因通过阻止细胞快速地分裂来抑制肿瘤。慢慢地，他的注意力转到了氧化所造成的更大的损伤方面，以及对此所能采取的措施。
Some vitamins, such as vitamin C, are antioxidants in their own right. This is the basis of the high-street propaganda, though there is no evidence that consuming such antioxidants in large quantities brings any benefit. A few years ago, however, Dr Ames found he could pep up the activity of the mitochondria of elderly rats—with positive effects on the animals' memories and general vigour—by feeding them two other molecules: acetyl carnitine and lipoic acid. These help a mitochondrial enzyme called carnitine acetyl transferase to do its job. Boosting their levels seems to compensate for oxidative damage to this enzyme. He also reviewed the work of other people and found about 50 genetic diseases caused by the failure of one enzyme or another to link up with an appropriate helper molecule. Such helpers are often B vitamins, and the diseases were often treatable with large doses of the appropriate vitamin.
有些维生素，比如维生素C，本身就是抗氧化剂。大街上的宣传广告正是以这个为噱头，虽然没有证据表明大量使用抗氧化剂可以带来任何好处。然而几年前，阿姆斯博士发现通过喂食其他两种分子：乙酰肉碱和硫辛酸，他能刺激年老老鼠的线粒体的活动，这对两种物质对提高动物的记忆力和生存能力都有积极作用。这能有助于一种叫做肉碱乙酰转移酶的线粒体酶的活动。提高酶的活动能力似乎可以弥补氧化作用对酶所造成的损伤。他也审视了其他人的研究工作，发现大约50种基因疾病是，由于这种或那种形式的酶没有能够用合适的辅助分子连结起来，造成了大约50多种基因有关的疾病。这种辅助分子常常是维生素B，服用大量的维生素通常可以治疗这些疾病。
The enzyme damage in these diseases is similar to that induced by oxidation, so Dr Ames suspects that its effects, too, can be ameliorated by high doses of vitamins. He has gathered evidence from mice to support this idea, but whether it is the case in people has yet to be tested. Nor is it easy to believe it ever will be. The necessary clinical trials would be long-winded. They would also be expensive—and there is no reason for vitamin companies to pay for them since sales are already buoyant and the products could not be patented. Nor is Dr Ames claiming vitamins will make you live longer than a natural human lifespan, even if he thinks they might prolong many individual lives. For that, other technologies will need to be invoked.
这些疾病中酶的损坏害与氧化所造成的相类似，所以阿姆斯博士怀疑酶的损害能也能够靠服用大量的维生素来加以改善。他从老鼠身上搜集了支持这个观点的证据，但是否在人身上也会是如此还有待检验，要相信它会也是件很难的事情。必要的临床试验将会需要很长时间，而且花费不菲，维生素生产商没有理由为此买单，因为维生素的销售看涨，而且这些产品又不能取得专利。即使是阿姆斯博士认为维生素能延长许多人的生命，他也没有说维生素能让人的寿命长于人的正常寿命。鉴于此，我们就要采用其他的科学技术。
Stemming time's tide
阻击时间
One way that might let people outlive the limit imposed by disposable somas is to accept the machine analogy literally. When you take your car to be serviced or repaired, you expect the mechanic to replace any worn or damaged parts with new ones. That, roughly, is what those proposing an idea called partial immortalisation are suggesting. And they will make the new parts with stem cells.
让人的寿命突破我们可抛弃躯体限度的一个方法完全接受机器维修的比拟。当你去保养或是维修车的时候，你会想要机械工把磨损或者损坏的零部件用新的替换掉。大致说来，这就是那些提出部分寿命延长的人所说的概念。他们会用干细胞来制造新的零部件。
The world has heard much of stem cells recently. They come in several varieties, from those found in embryos, which can turn into any sort of body cell, to those whose destiny is constrained to becoming just one or a few sorts of cell. The thing about stem cells of all types, which makes them different from ordinary body cells, is that they have special permission to multiply indefinitely.
最近，干细胞这个词人们已经听得多了。干细胞有很多种，有的能转变为任何人体细胞，有的只能成为某一种或者少数几种细胞。干细胞与普通不同之处在于，干细胞能够无限制的复制。
For a soma to work, most of its component cells have to accept they are the end of the line—which, given that that line in question stretches back unbroken to the first living organisms more than 3 billion years ago, is a hard thing to do. There are, therefore, all sorts of genetic locks on such cells to stop them reproducing once they have arrived at their physiological destination. If these locks are picked (for example by oxidative damage to the genes that control them, as discovered by Dr Ames), the result is unconstrained growth—in other words, cancer. One lock is called the Hayflick limit after its discoverer, Leonard Hayflick. This mechanism counts the number of times a cell divides and when a particular value (which differs from species to species) is reached, it stops any further division. Unless the cell is a stem cell. Every time a stem cell divides, at least one daughter remains a stem cell, even though the other may set off on a Hayflick-limited path of specialisation.
人体要运作，其许多的构成细胞须承认它们位于人体细胞链条的最末断，假如这个链条可以完整地追溯到30亿年前最先出现的生命体，这是件很困难的事情。一旦它们达到了自己的生理目标，就有各种各样的基因锁阻止它们的复制。如果出现这些锁（比如对控制它们的基因造成氧化损害的锁，正如阿姆斯博士所发现的一样），它们就会不加节制的生长，换句话说，就是癌症。有一种锁以它的发现者黑福利科命名。这个机制会计算细胞分裂的次数，当分裂达到了一定的数值（因物种不同而不同），它就会阻止细胞进一步的分裂，除非这个细胞是干细胞。每次干细胞分裂的时候，分裂后的细胞至少有一个仍然是干细胞，即使其他的可能受到黑福利科的限制踏上专门化之旅。
Some partial immortalisers seek to abolish the Hayflick limit altogether in the hope that tissue that has become senescent will start to renew itself once more. (The clock that controls it is understood, so this is possible in principle.) Most, though, fear that this would simply open the door to cancer. Instead, they propose what is known as regenerative medicine—using stem cells to grow replacements for tissues and organs that have worn out. The most visionary of them contemplate the routine renewal of the body's organs in a Lincoln's axish sort of way.
有些追求部分长寿者试图完全消除黑福利科限制，希望衰老的细胞组织再次更新。（因为知道控制它的生物钟，所以理论上来说是可能的。）虽然大多数人担心这会导致癌症的出产生。然而，他们建议用再生药—就是用干细胞培育出可以替代磨损的组织和器官的产品。其中最具想象力的就是考虑用林肯的那种更换斧头部件的方式来对磨损的器官进行例行更新。
In theory, only the brain could not plausibly be replaced this way (any replacement would have to replicate the pattern of its nerve cells precisely in order to preserve an individual's memory and personality). Even here, though, stem-cell therapists talk openly of treating brain diseases such as Parkinson's with specially grown nerve cells, so some form of partial immortalisation might be on the cards. But it is a long way away—further, certainly, than Dr Ames's vitamin therapy, if that is shown to work.
从理论上讲，只有人脑无法以这种方式被替换（任何替换得精确地复制人脑的神经细胞，以便保留人的记忆和个性）。虽然临床医学家公开地谈论用特殊方式培养的神经细胞来治疗比如像帕金森症这样的病，因此某种形式的部分长寿是有可能的。但那是很遥远的事情—当然，比阿姆斯博士的维生素治疗法还要遥远，如果那样有效的话。
Neither prevention, nor repair, is truly ready to roll out. But there is one other approach, and this is based on the one way of living longer that has been shown, again and again, in animal experiments, to be effective. That is to eat less.
防止和修复衰老的方法还不会立即出现。但还有一种方法，能让人活得更长一些，此方法在动物身上一再得到证明。那就是少吃。
From threadworms to mice, putting an animal on a diet that is near, but not quite at, starvation point prolongs life—sometimes dramatically. No one has done the experiment on people, and no one knows for sure why it works. But it does provide a way of studying the problem with the reasonable hope of finding an answer.
让动物节食，从蛲虫到老鼠，近乎饥饿的状态可以延长生命—有时是延长很多。没人在人类身上做过此类试验，也没有人确切知道这为什么会有用。但这确实提供了一种让人还算可以抱有一些合理希望的研究方法。
Gluttons for punishment
贪吃的惩罚
You would, of course, have to wish a lot for a long life to choose to starve yourself to achieve it. Extrapolating from the mouse data, you would need to keep your calorie intake to three-quarters of the amount recommended by dieticians. That means about 1,800 for sedentary men and 1,500 for sedentary women. But several people are trying to understand the underlying biology, in order to develop short cuts.
当然，你会非常希望挨饿来活得长久。根据从老鼠试验得出的数据，你需要摄入的热量应是营养学家推荐的三分之二。那就是说久坐的男性摄入的热量大约是1800卡路里，而女性则是1500。但为了找到一条捷径，有人想竭力了解其中的生物奥秘。
One such is David Sinclair of Harvard University. Unlike those trying to fight the causes of ageing or to repair the damage done, Dr Sinclair thinks he has found, in caloric restriction as the technique is known, a specifically evolved natural anti-ageing mechanism that is quite compatible with disposable-soma theory.
其中一位就是哈佛大学的大卫.辛克莱。与那些想要逆转衰老的结果或是修补衰老造成的损伤的人不同，辛克莱博士认为在限制卡路里摄入中[这时众所周知的]他已经发现了一个特别演化的自然抗衰老的机制，这与抛弃躯体理论是一致的。
The reason for believing that prolonged life is an evolutionary response to starvation rather than just a weird accident is that when an animal is starving the evolutionary calculus changes. An individual that has starved to death is not one that can reproduce. Even if it does not die, the chance of it giving birth to healthy offspring is low. In this case, prolongation of life should trump reproduction. And that is what happens, even among people. Women who are starving stop ovulating. The billion-dollar trick would be to persuade the body it is starving when it is not. That way people could live longer while eating normally. They might even, if the mechanism can truly be understood, be able to reproduce, as well.
有人认为生命延长是对饥饿演化的一个反应，而仅仅是一个怪异的事件，其原因在于当动物饥饿的时候，其演化结构也会改变。饿死了的人不是能够繁衍后代的人。就算他不死，生下健康的后代的可能性也是很小的。既然这样，延长寿命就要重于繁衍后代。事实就是如此，对人类也是如此。女性饥饿就停止排卵。而花费颇多的事情将会是在人体不饥饿之时说服它它正饥饿着。这样人就能既正常的饮食也能够长寿。如果能真正了解这个机制，那么人也可能会繁衍后代。
In Dr Sinclair's view, the way caloric restriction prolongs life revolves around genes for proteins called sirtuins. Certainly, these genes are involved in life extension in simple species such as threadworms and yeast. Add extra copies of them to these organisms' chromosomes, or force the existing copies to produce more protein than normal, and life is prolonged. This seems to be because sirtuins control the abundance of a regulatory molecule called nicotinamide adenine diphosphate which, in turn, controls the release of energy in the mitochondria.
就辛克莱博士看来，限制热量的摄入来延长寿命的方法是以基因为依托来获取一种叫做sirtuins的蛋白质。当然，这些基因也出现在简单物种的生命延长上，比如蛲虫和酵母。让这些生物体增添更多的这种基因，或者让已有的基因比一般的产生更多的蛋白质，寿命则得以延长。这是因为sirtuins控制着一种叫做烟碱腺嘌呤二磷酸的调节性分子的数量，而这种分子反过来又控制着线粒体中的能力释放。
The most intriguing connection in this story is with the French paradox. This is the fact that the French tend to eat fatty diets rich in red meat but to have the survival characteristics of those whose diets are lean and vegetarian. Some researchers link this with their consumption of red wine—and, in particular, of a molecule called resveratrol that is found in such wine. Resveratrol activates sirtuins, and some similar molecules activate them much more. It is these sirtuin super-stimulators that interest Dr Sinclair.
最有意思的就是法国人令人费解的做法。法国人喜欢吃牛羊肉含高脂肪的食物，但却跟那些吃不含脂肪食物及蔬菜的人有一样的生存特点。有些科学家把这与他们喝红酒联系起来—尤其是红酒中的一种叫做resveratrol的物质。Resveratrol激活sirtuins, 一些类似的分子更多地激活它们。就是这些sirtuin超级刺激物引起了辛克莱博士的兴趣。
Not everyone is convinced, but Dr Sinclair has done experiments on mice that look promising, and has started a company called Sirtris Pharmaceuticals to follow it up. The fact that he is (at least in his own eyes) working with nature rather than against it argues that this is the most promising approach of all.
不是每个人都相信这些，但辛克莱博士在老鼠身上做过试验，看起来大有希望，他接着就开办了一家公司，叫做Sirtris 医药公司。至少在他看来，他的方法是与自然和谐一致，不是背道而驰，因此，这是最有希望的方法。
That said, the logic of the disposable-soma theory is profound. Even working with its grain may do no more than buy a few extra years of healthy living. Dr de Grey's reason for thinking that some people now alive may see their lives extended indefinitely is based on the hope that those few extra years will see further discoveries and improved life-extension technologies based on them—a process he describes as achieving “longevity escape velocity”.
可抛弃躯体理论的内在逻辑是有深刻意义的。就算它意义深刻，也不过是花钱多过几年健康的生活。得格雷博士认为有些人可以看到自己的生命能不定的延长，是因为在他们多活的那几年中，可能会有延长寿命的新的发现和科技的进步，他把这个过程描述为实现“ 寿命逃离速度”。
The chances are that it will not work. But hope springs eternal. To end with another quote, this time from Woody Allen, “I don't want to achieve immortality through my work. I want to achieve immortality through not dying.” If any researcher manages to beat evolutionary history and achieve his goal, he might get to do both.
这也有可能不起作用。但希望孕育永恒。在文章的最后，我们引用乌迪.埃伦的一句话：“我不想通过我工作来拥有不朽人生。我要通过摆脱死亡来获得不朽。”如果有研究者设法战胜进化史来实现生命的延长，那他可能会既摆脱死亡又获得长寿。
