为什么斯坦李一直客串:长生不老有可能吗？

生物学家在理解衰老这个问题上已经取得了很大进展，但尽管如此，他们并没能够减缓衰老。有个版本说有一类基因能够延长寿命，但是如果人没有这个基因，寿命就不太可能延长。来自明尼苏达州梅约诊所的Darren Baker在这周的Nature上发表的一篇报告中提到，一种能够改善其过程的特别的结论。Baker医生在老鼠体内发现，老化的体细胞不但让老鼠们痛苦，而且其不良反应还会影响到周围健康的细胞。更重要的是，如果这些衰老细胞被选择性的破坏，不良作用就会消除。

The story starts with an observation, made a few years ago, that senescent cells often produce a molecule called P16INK4A. Most body cells have an upper limit on the number of times they can divide—and thus multiply in number. P16INK4A is part of the control mechanism that brings cell division to a halt when this limit is reached.

文章源起几年前的一个观察，当时发现衰老细胞通常会产生一种名为P16INK4A的分子。大多数的体细胞都有分裂倍数上限，因此体细胞的繁殖才会成倍增长。而P16INK4A就是其控制机构的一部分，当分裂倍数到达时，它会停止细胞分裂。

The Hayflick limit, as the upper bound is known (after Leonard Hayflick, the biologist who discovered it), is believed to be an anticancer mechanism. It provides a backstop that prevents a runaway cell line from reproducing indefinitely, and thus becoming a tumour. The limit varies from species to species—in humans, it is about 60 divisions—and its size is correlated with the lifespan of the animal concerned. Hayflick-limited cells thus accumulate as an animal ages, and many biologists believe they are one of the things which control maximum lifespan. Dr Baker’s experiment suggests this is correct.

Hayflick极限，就是大家知道的生命自然极限（在生物学家Leonard Hayflick发现后以其名字命名）被认为是一个抗癌的机制。它会派出一个捕手来防止流失的细胞素繁殖导致形成肿块。生命极限因物种不同而不同，在人类体内有60个分区，区域的大小与生物的寿命息息相关。Hayflick极限细胞因此像动物增岁一样累积，很多生物学家认为这是众多控制最大寿命因素中的一项。Baker医生的实验也证明此观点正确。

Age shall not weary them

衰老不会使其疲倦

Dr Baker genetically engineered a group of mice that were already quite unusual. They had a condition called progeria, meaning that they aged much more rapidly than normal mice. (A few unfortunate humans suffer from a similar condition.) The extra tweak he added to the DNA of these mice was a way of killing cells that produce P16INK4A. He did this by inserting into the animals’ DNA, near the gene for P16INK4A, a second gene that was, because of this proximity, controlled by the same genetic switch. This second gene, activated whenever the gene for P16INK4A was active, produced a protein that was harmless in itself, but which could be made deadly by the presence of a particular drug. Giving a mouse this drug, then, would kill cells which had reached their Hayflick limits while leaving other cells untouched. Dr Baker raised his mice, administered the drug, and watched.

Baker医生起初设计了一组不寻常小鼠的实验。这些小鼠都有早衰迹象，就是说它们要比正常鼠衰老更迅速！（一些不幸的人们也遭受相似的症状。）Baker医生在小鼠们得DNA上加了一个多余的扭用以消灭细胞繁殖P16INK4A。他通过在临近生成P16INK4A基因的动物DNA中写入第二个基因，因为位置靠近，所以可以被相同的遗传切换控制。这第二个基因会在生成P16INK4A的这个基因活动时被激活，然后产生一种本身有害的营养物质，但当一种特定的毒素产生时，它便会被杀死。向小鼠体内注入这种毒素，然后便会杀死那些已经达到Hayflick极限的细胞，保证留下其他的细胞不受感染。Baker医生自己养殖小鼠，注入毒素，然后进行观察。

The results were spectacular. Mice given the drug every three days from birth suffered far less age-related body-wasting than those which were not. They lost less fatty tissue. Their muscles remained plump (and effective, too, according to treadmill tests). And they did not suffer cataracts of the eye. They did, though, continue to experience age-related problems in tissues that do not produce P16INK4A as they get old. In particular, their hearts and blood vessels aged normally (or, rather, what passes for normally in mice with progeria). For that reason, since heart failure is the main cause of death in such mice, their lifespans were not extended.

结果是惊人的。这些从出生开始后每三天被注入毒素的小鼠们比那些没有注射毒素的同伴们更加少遭受与衰老相关的机体消耗。它们损耗极少的脂肪组织，肌肉也保持得很丰满（跑台实验它们同时也很高效），它们也没有受白内障困扰。但是这些小鼠在它们变老时仍旧在承受不产生P16INK4A所带来的与衰老相关的体内组织问题，特别是它们的心脏和血液组织正常衰老（或许这些在早衰老鼠体内依旧维持正常），正是由于这个原因，心脏起搏失败时这些鼠死亡的主因，它们的寿命便没有得以延长。

The drug, Dr Baker found, produced some benefit even if it was administered to a mouse only later in life. Though it could not clear cataracts that had already formed, it partly reversed muscle-wasting and fatty-tissue loss. Such mice were thus healthier than their untreated confrères.

Baker医生发现这个毒素甚至小鼠出生后一段时间内在注入同样会产生某种益处。尽管不太清晰的白内障已经形成，但却会部分改变肌肉耗损和脂肪组织的损失。这些白鼠因此会比那些没注射毒素的同伴更健康。

Analysis of tissue from mice killed during the course of the experiment showed that the drug was having its intended effect. Cells producing P16INK4A were killed and cleared away as they appeared. Dr Baker’s results therefore support the previously untested hypothesis that not only do cells which are at the Hayflick limit stop working well themselves, they also have malign effects (presumably through chemicals they secrete) on their otherwise healthy neighbours.

在为证实毒素有其预期效果的实验中死去的老鼠，有一份组织分析报告。生成P16INK4A的细胞在出现时刻就被杀死和清除。因此Baker医生得出的结论支持了之前未被证实的假设。在Hayflick极限里，不仅仅是细胞停止了工作，它们也同样对周边健康的细胞产生非常恶劣的影响（通过其分泌的化学物）。

Regardless of the biochemical details, the most intriguing thing Dr Baker’s result provides is a new way of thinking about how to slow the process of ageing—and one that works with the grain of nature, rather than against it. Existing lines of inquiry into prolonging lifespan are based either on removing the Hayflick limit, which would have all sorts of untoward consequences, or suppressing production of the oxidative chemicals that are believed to cause much of the cellular damage which is bracketed together and labelled as senescence. But these chemicals are a by-product of the metabolic activity that powers the body. If 4 billion years of natural selection have not dealt with them it suggests that suppressing them may have worse consequences than not suppressing them.

不管生化细节，Baker医生的结论提供了一个很有趣的事，就是一种思考如何缓解衰老进程的途径，这种途径要与自然天性相协作，而不是抵抗其天性。现存的延长寿命的调查都是基于移动寿命极限而进行的，其实这样反而会造成很多不幸的结果或是抑制氧化物生成，后果就是更多地引起与衰老相关的细胞损坏。但是这些化学物质都是启动机体新陈代谢活动的副产品。如果说400万年的自然选择都没能使其消退的话，那便意味着压抑它们会比放任它们后果更加糟糕。

By contrast, actually eliminating senescent cells may be a logical extension of the process of shutting them down (they certainly cannot cause cancer if they are dead), and thus may not have adverse consequences. It is not an elixir of life, for eventually the body will run out of cells, as more and more of them reach their Hayflick limits. But it could be a way of providing a healthier and more robust old age than people currently enjoy.

相比之下，事实上消除衰老细胞可能是关闭细胞过程中的逻辑上的生命延长（这些细胞在死亡之后自然不会引发癌症），因此也就不会产生不利后果。但这不是长生不老的药物，因为到最后，人体还是会在到达生命极限时消耗细胞，直到耗尽所有细胞。但它却可以成为缔造比现今人们享受到的一个更加健康和充满活力的老年人的途径。

Genetically engineering people in the way that Dr Baker engineered his mice is obviously out of the question for the foreseeable future. But if some other means of clearing cells rich in P16INK4A from the body could be found, it might have the desired effect. The wasting and weakening of the tissues that accompanies senescence would be a thing of the past, and old age could then truly become ripe.

在一个可以预测的未来，以Baker医生对待白鼠的方式在人体上实验这种基因工程是毫无问题的。但是如果可以找到那种能迅速从体内清除P16INK4A的方法，预期效果可以变成现实。伴随着衰老出现的体内组织的损耗和衰弱将会成为过去，那么年长则会真正变为成熟而非衰老！