双语时事系列207:复活节岛上的长寿秘密

复活节岛上的长寿秘密

Secret to a longer life lies on Easter Island

Probably the world's most remote and least-visited inhabited island, Easter Island is globally famous for its haunting monumental stone statues of human faces.

A drug originating on Easter Island, the mysterious South Pacific home of a lost statue-building people, may become the first substance to slow down human ageing, new research indicates.

Rapamycin, a pharmacological product used to prevent rejection in organ transplants, has been found to extend the lifespan of mice by up to 38 per cent, raising the possibility that it may delay ageing in people.

Hitherto a matter for science fiction, the idea of an anti-ageing drug which would allow people to prolong their natural lifespan and also to avoid age-related diseases is now being seriously considered for the first time as a result of the findings by American researchers.

Rapamycin is a bacterial product originally found in a soil sample from Easter Island. Originally developed as an anti-fungal agent, rapamycin was soon found to have powerful immuno-suppressant properties and thus be valuable for preventing rejection of transplanted organs. It was also found to delay the ageing process when used experimentally with three sets of lower organisms: yeast, nematode worms and fruit flies.

Now, however, it has been shown to affect the ageing of mice – the first time that this has ever been shown with a mammal.

A team of 14 researchers from three institutions, led by David Harrison from the Jackson Laboratory at Bar Harbor in Maine, fed rapamycin to mice late in their life – at 600 days of age – and showed that both the median and maximal lifespan of treated animals were considerably extended. Currently, the only way to extend the life of a rodent is by severely restricting its diet, so this marks the first report of a pharmacological intervention that lengthens the life of mammals – with clear implications for humans.

The results, published recently in an online paper on the website of the journal Nature, are attracting considerable excitement, and an accompanying article in Nature by two of the world's leading experts on the ageing process, Matt Kaeberlein and Brian K Kennedy from the University of Washington, Seattle, headed "A Midlife Longevity Drug?" openly asks the question: "Is this the first step towards an anti-ageing drug for people?"

Their answer is that it may well be. Dr Kaeberlein and Dr Kennedy first issued a warning to people not to start taking rapamycin at once in the hope of prolonging their lives – "the potential immuno-suppressive effects of this compound alone are sufficient to caution against this," they advised.

But they added: "On the basis of animal models, however, it is interesting to consider that rapamycin ... might prove useful in combating many age-associated disorders. Also ... it may be possible to develop pharmacological strategies that provide the health and longevity benefits without unwanted side-effects.”

"So, although extending human lifespan with a pill remains the purview of science fiction writers for now, the results of Harrison et al provide a reason for optimism that even during middle age, there's still time to change the road you're on."

Rapamycin was known to have an influence on ageing in the lower organisms by disrupting the influence of an enzyme known as TOR, which regulates cell growth. Dr Harrison and colleagues found that this was also the case with mice, and found that rapamycin feeding could extend mouse lifespan even when started late in life.

The maximum lifespan went up from 1,094 days to 1,245 days for female mice, and from 1,078 to 1,179 for male mice – a striking increase of life expectancy of 38 per cent for females and 28 per cent for males.

Dr Harrison and his colleagues conclude: "An effective anti-ageing intervention that could be initiated later than the midpoint of the lifespan could prove to be especially relevant to clinical situations, in which the efficacy of anti-ageing interventions would be particularly difficult to test in younger volunteers. Our data justify special attention to the role of the TOR pathway in control of ageing in mammals and in the pathogenesis of late-life illnesses."

Also known as sirolimus, rapamycin was first discovered as a product of the bacterium Streptomyces hygroscopicus, which was found in an Easter Island soil sample.

复活节岛上的长寿秘密

世界上最偏远的，少有人居的岛屿——复活节岛，很可能是因为令人难以忘怀的不朽石雕人像而举世闻名。

最新研究表明，一种来源于位于南太平洋已经消失的那个雕刻石像民族的神秘家园——复活节岛上的药物，可能成为第一种延缓人类衰老的物质。

一种用于器官移植的抗排斥药物雷帕霉素已被发现可以延长小鼠的寿命，最多可达38%。这也增加了推迟人类衰老的可能性。

虽然迄今为止抗衰老药物还只是科幻小说里的事情，但作为上述发现的结果，美国的研究者们正首次认真地考虑这种既能延长人们自然寿命，同时也能避免患上与年龄相关疾病的抗衰老药物的想法。

雷帕霉素是一种最初发现于来自复活节岛土壤样本中细菌的制品。雷帕霉素，原本是作为抗真菌药剂而开发出来的，但很快被发现其具有强大的免疫抑制属性，因此在防止器官移植排斥方面非常有价值。人们还发现在对三种低等有机物，即酵母菌、线虫和果蝇进行试验使用时它还可以延缓其衰老的过程。

然而现在，研究已经表明雷帕霉素能够影响小鼠的衰老——这是首次发现它能有效延长哺乳动物的寿命。

来自于缅因州巴哈伯杰克逊实验室的大卫.哈里森领导的3个研究院的14人研究小组给处于老年时期即600天左右的小鼠喂食雷帕霉素，结果表明参与实验动物的寿命的中间值和最大值都有显著的延长。当前，延长啮齿类动物寿命的惟一方法就是严格限制它的饮食。因此，该实验结果标志着通过药物干预来延长哺乳类动物寿命的第一份报告的诞生。这一点也很有可能适用于人类。

近期在《自然》杂志网站电子版上发表的这一实验结果正激起大家的极度兴奋。在刊发于《自然》杂志上的由两位从事衰老进程研究的世界顶尖级专家——来自于西雅图华盛顿大学的马特.卡伯雷和布莱恩.K.肯尼迪撰写的另外一篇标题为“中年长寿药物？”的配套文章里，他们公开发问“这是人类抗衰老药物研究走出的第一步吗？”

他们的答案是很有可能。卡伯雷和肯尼迪博士率先向人们提出警告不要立即开始服用雷帕霉素以期延长寿命。他们建议：“这种复合制剂的潜在抑制免疫系统的效果足够警示你不用它。”

但是他们又补充道：“然而，在动物样本的基础上，考虑雷帕霉素在对抗与许多与年龄相关的失调问题上可能证明有效，这一点也很有趣。研发出没有不想要的副作用而只带来提供健康和长寿益处的药物策略也是可能的。”

“因此，尽管目前通过一粒药丸来延长人类寿命还只属于科幻作家的范畴，但是哈里森等人的研究结果给人们提供了一个令人乐观的原因：即使人到中年，仍然有时间改变你的人生旅程。

我们知道雷帕霉素通过破坏一种叫做TOR——用来调控细胞生长的酶的作用来影响低等有机物的衰老。哈里森博士和他的同事发现这一点在小鼠身上也是如此。他们发现即使在小鼠老年时才开始喂食雷帕霉素，也能够延长小鼠的寿命。

雌鼠的寿命最长可达到1094天至1245天，而雄鼠的寿命可达到1078天至1179天——也就是说，预期寿命的显著增长对雌鼠来说达到了38%，而对雄鼠来说达到了28%。

哈里森博士和他的同事们得出结论：“在中年以后开始进行有效的抗衰老干预证明与随后的临床状况特别相关，即在比较年轻的志愿者身上测试抗衰老干预的功效将会特别困难。实验数据证明，我们应该特别关注TOR在控制哺乳动物衰老以及老年疾病致病机理方面的作用。

雷帕霉素也被称作西罗莫司，最初是作为吸水链霉菌制品被发现的。该细菌来自于复活节岛的土壤样本中。

（原著：Michael McCarthy）

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