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Aging Factor: Gene mutations may be key to long life

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12:28pm, March 5, 2008
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Juicing up with growth hormones may build muscles, but probably won't help you live to see 100 candles on your birthday cake, a new study suggests.

A study of 384 aged Ashkenazi Jews shows that a decrease in insulinlike growth factor 1 (IGF-1) activity is associated with long life, Nir Barzilai and his colleagues report in the March 4 Proceedings of the National Academy of Sciences.

For a decade, Barzilai has studied centenarians, a rare group of people who live to be 100 or older, looking for genes that contribute to longevity. But he never expected IGF-1, or growth hormone, would be involved, says Barzilai, director of the Institute for Aging at the Albert Einstein College of Medicine in New York City.

Practitioners of antiaging medicine tout IGF-1 as a youth-restoring treatment because it helps firm skin and build muscles. The substance is good for the heart, brain, and bones, stimulating stem cells to replace damaged cells, says Jan Vijg of the Buck Institute for Age Research in Novato, Calif. Reducing IGF-1 activity in people was thought to lead to diabetes, heart disease, and other illnesses.

Reducing growth factor activity dramatically lengthens the life of nematodes, fruit flies, and other animals, but many scientists thought the pathway played no role, or had the opposite effect, in human aging.

But when Barzilai and his colleagues tested blood levels of IGF-1 in children of centenarians, the researchers found that daughters of centenarians had altered levels of the growth factor compared to the control group. These daughters were also, on average, 2 centimeters shorter than those in the control group.

Neither the centenarians nor their younger counterparts (the control group) had mutations in the gene encoding IGF-1. The mutation was instead in the IGF-1 receptor, which the hormone binds to in order to trigger a signal that, ultimately, tells cells to grow. Nine centenarians—both women and men—and one person in the control group carried this mutation, which reduced the growth hormone's activity.

Mutations in the receptor may extend life by helping people avoid cancer, Vijg says. "Osteoporosis and heart disease you may be able to live with, but cancer, I don't think so. You just die."

It may take more than a single mutation to achieve a very long life, says Cynthia Kenyon, a molecular biologist at the University of California, San Francisco. Several different factors may determine life span in humans, she says. "We don't know how complicated it is."

Taking growth hormone likely won't lengthen life, Vijg says. "You may do great at the gym lifting weights, but you may not live any longer."

No one knows whether lowering growth factor activity late in life will increase longevity either.

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