It's not easy being short—at 5'2", I know—and a string of studies over the last few years has made it seem even harder. According to the research, tall people make more money, have higher self-esteem and may even be smarter than their more diminutive counterparts. But a new study this week looks as though it's on my side. In the latest issue of the Proceedings of the National Academy of Sciences, researchers report that a variant of a gene linked to very long life and small stature in animals may be linked to both in humans as well. Children of centenarians are more likely to have the genetic variant; they're also more likely to be lacking in the height department. In other words, short people may live longer. Still, I'm not smugly e-mailing this study to all my tall friends just yet. The evidence is intriguing, but as full-on proof that I'm going to make it to 110, it comes up, well, short.
The study began with a group of Ashkenazi Jews, all of them over 95. Researchers asked them why they thought they had lived for so long. "We would get two answers. One was, 'My mother was 102 and my grandmother was 108'—a strong family history," says one of the scientists, Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine in New York City. "Then we would say, 'Come on, tell us the real reason. Maybe you ate yogurt all your life.' But hundreds of cases later, we didn't have any yogurt-eaters. We didn't have any athletes. Twenty percent of our subjects had smoked for decades. We had one woman who was 105 and had smoked for 90 years. As a population, this group was doing exactly what we tell our patients not to do." Clearly, then, for the centenarians, the secret to long life wasn't lifestyle—it was being born with the right genes. But which ones?
Barzilai was especially interested in the so-called "Methuselah" gene, which has been linked to small size and long life in the lab. By tinkering with the gene, scientists can make roundworms live 30 to 50 percent longer than they normally would. The worms also end up being smaller, because their bodies process less of a hormone called IGF-1, which encourages growth. A similar link has shown up mammals. By disrupting IGF-1's effects, researchers can delay the onset of age-related diseases in mice and increase their lifespan by as much as 40 percent. (Females seem to more susceptible to the effect than males.) IGF-1 is also what accounts for size differences in dogs—a German shepherd's body processes much more of the stuff than a chihuahua's does. The bottom line: more IGF-1 means a bigger body and a smaller lifespan. 
Barzilai thought his centenarians might have a Methuselah mutation that was tamping down their bodies' responsiveness to IGF-1. Sure enough, he found that in a few of them a variant of the Methuselah gene seemed to doing just that. The subjects had plenty of the hormone, but they weren't reacting to it. They were, of course, long-lived. They were also short—and had always been, even in their prime, before age began to shrink their bones. The reason for both traits, he reasoned, might be their inefficiency in using IGF-1.
So then Barzilai and his colleagues turned to the centenarians' children. This group too had an unusual variety of mutations that affected the IGF-1 pathway—they had high levels of the hormone but didn't seem to be processing it normally. The cellular receptors that take instructions from the hormone were basically hard of hearing; the subjects' bodies had turned up the volume by producing more of the hormone, but to no effect. Like the female mice, the women in the group seemed to be feeling more of the gene's effects; their levels of IGF-1 were much higher than a control group's, probably because their bodies were trying to compensate for the faulty receptors that weren't using it properly. There was only one more thing to measure: their height. Indeed, they were smaller than average, about an inch shorter than a control group with relatively normal IGF-1 function.
So should they start planning on a long and healthy retirement, capped by a birthday party with more than 100 candles on the cake? Not necessarily. For one thing, the Methuselah variant is very rare, even in people who live a long time; only 2 percent of the centenarians had it, which suggests that something else was at work in the other 98 percent. There are dozens of other genes that affect the IGF-1 pathway, height or longevity; any one of those could either amp up or cancel out the Methuselah gene's effects. And plenty of previous nongenetic studies have tackled the question of height and age, with mixed results; some show that short people live longer, some show the opposite. Personally, I'm going to hope that Barzilai keeps working on this question until he figures out a way we all can live longer, tall people included.
译文:
矮个子的女性更长寿？
做一个“小矮人”可不容易——身高一米五，我知道——而且经过了这几年来的一系列研究，让这变得更加艰难。根据调查，高个子通常赚更多的钱，他们有较强的自尊心而且也许会比那些矮小的同龄人更聪明。但是本周的一项新的研究却好像站在了我的这一边。国家科学院学报里最新的一篇文章中调查者说，动物中有一种和长寿有关的变异基因是与身高较矮的动物息息相关的，而这一点也恨肯对人类也同样有效。并且百岁以上老人的子女更加有可能存在这种基因变异；他们也更有可能在身高这方面有所缺陷。换句话说，矮小的人可能会活的更长。当然，我还并没有洋洋得意的把这份报告电邮给我高大的朋友们，虽然这些证据都非常的有吸引力但是即使我能够得到充分的保证说可以活到一百十岁，但是不得不提的是，我还是很矮。
这项调查是从一组德裔犹太人开始的，他们所有的人都超过了95岁。调查者询问他们如此长寿的原因，其中一位科学家，纽约阿尔伯特爱因斯坦医学院老龄化调查机构的主任尼奥·巴茨莱说“我们得到的基本就是两个答案，一个就是‘我的妈妈活到了102岁，我的外婆活到了108岁’——一个强大的家族史。那么我们会说‘那请告诉我们真实的原因吧。也许你一辈子都坚持喝酸奶之类的。’但是当我们调查了几百个案例以后，我们一个喝酸奶的理由都没有找到。我们也没有运动员，并且百分之二十的受调查者都常年吸烟，我们由一个105岁的老太太烟龄长达就是念。这组人做的都是一些我们告诫病人们不要做的事情。”很明显的，对于这些百岁老人，长寿的秘诀并不在于生活方式——他们只是生来就带着长寿的基因。那么到底是什么呢？
巴茨莱尤其对所谓的“玛士撒拉”（Methuselah）基因感兴趣，因为在实验室里，这个基因是将体型娇小和长寿联系在一起的。科学家可以通过修补基因来使得蛔虫比常规多活30%到50%的寿命。但是蛔虫最终还是会体型小小的死去，因为他们的身体缺少一种名为IGF-1的荷尔蒙，而这种荷尔蒙可以刺激身体生长。在哺乳动物中也出现了一个类似的关联。调查者通过阻碍IGF-1对身体的作用，就可以拖延老鼠身上一些与年龄有关的疾病发作，还可以增加40%的寿命。（这些反应在母鼠身上比公鼠要体现的更加明显。）IGF-1同样也对狗的体型有一定的作用——德国牧羊犬比吉娃娃体内含有更多的此类荷尔蒙。因此，大概的结论就是：大量的IGF-1意味着更大的体型，更短的寿命。
巴茨莱认为那些百岁老人可能就是在他们体内对IGF-1的反应中有一种玛士撒拉基因突变发生。并且他果真发现他们中的一些人好像就是有这些反应。他们有大量的荷尔蒙但是却并不对之有所反应。当然，他们就长寿了。同样的，他们也都很矮——并且一直都很矮，即使是在青春期的时候，他们的身体就开始缩水了。而他说这些特质出现的原因就是他们身体中的IGF-1是无效的。
所以巴茨莱和他的同事们转向了百岁老人的子女们。这一组也有一些不同寻常的基因变异会影响IGF-1的作用——他们有大量的荷尔蒙但是却并不如常人一样有效。那些受荷尔蒙的指令的细胞受体都不太听话，于是身体就会产生更多的荷尔蒙来增大体积，但是却都没有用。正如母鼠一样，该组中的女性也收受到了更多基因的影响；他们体内IGF-1的含量比起对比组来说要高的多，也可能是因为他们的身体要弥补一些他们对其不当利用的过错吧。而这就只有一种解决的办法：她们的身高。确实，他们比同龄人要矮小，大约要比那些IGF-1功能正常的对比组矮一英寸左右。
那么他们是不是应该计划一个更长更健康的退休期，被冠以百岁老人的名号呢？不一定。因为有一点，玛士撒拉变异是非常罕见的，即使是在那些长寿的人当中依旧如此；只有2%的百岁老人有这类变异，也就是说在另外98%中是其他的东西在起作用。能够影响IGF-1，身高或者寿命的基因还有很多种，任何一种都有可能扩大或者消除玛士撒拉的基因影响。而原先大量的非基因调查也已经涉及到这个问题，并且也得出了身高和年龄的交叉关系；一些调查显示矮个子寿命更长，而其他的一些则截然相反。个人来讲，我希望巴茨莱能够就这个问题继续研究，直到他找到一种可以让我们延长寿命，并且能够让高个子也同样享受的办法。