Do Short Women Live Longer?

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.

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