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Life-Lengthening Hormone Found in Mouse Research

A 2-month-old mouse deficient in the Klotho protein, center, shows signs of aging, compared with a normal mouse, left. A 3-year-old mouse with an overabundance of the protein, right, has lived beyond the normal life span.
A 2-month-old mouse deficient in the Klotho protein, center, shows signs of aging, compared with a normal mouse, left. A 3-year-old mouse with an overabundance of the protein, right, has lived beyond the normal life span. (By Aline Mckenzie -- University Of Texas Southwestern Medical Center At Dallas)

The Klotho hormone appears to have a similar effect, Kuro-o said.

"Our work shows that the Klotho gene is an aging-suppressor gene," he said.

Other researchers said the findings were remarkable because no one had previously found a naturally occurring hormone capable of extending the life span of a mammal.

"You have lots of ways to shorten the life of an animal, but it's hard to get an animal to live longer," said George M. Martin of the University of Washington, who is scientific director of the American Federation for Aging Research. "You can kick a radio to make it not work so well, but it's hard to make it work better. It's quite a wonderful discovery."

Kuro-o and his colleagues plan to inject the substance into normal mice to see whether it extends their life spans and to measure the substance in humans to determine whether levels of the protein are correlated with longevity. Previous research has shown that humans have the protein in their blood, and that people with a certain variation of the gene are prone to age-related diseases such as heart attacks, strokes and osteoporosis.

Scientists will have to determine whether the protein can be produced in sufficient quantities to use it as a drug. It may turn out that other substances that mimic the protein's effects would also work or be safer, Kuro-o said. "That might be more practical," he said.

Kuro-o and others cautioned, however, that agents that appear effective and safe in mice often produce complications in humans. The hormone, for example, appears to decrease the effectiveness of insulin, which could limit its usefulness.

"It appears to play a role in the same pathway in people, but that doesn't necessarily mean it's going to be as straightforward to extend life span in people as it is in mice," said Valter Longo of the University of Southern California. "But this adds a new component to our picture and perhaps a component that could extend life span with few ill effects."

Beyond the possible clinical applications, other researchers said the finding underscores the growing understanding of the basic biology of aging.

"Papers like this are filling in the pieces of the puzzle that will explain the evolutionary biology of aging," said L. Stephen Coles of the UCLA School of Medicine.


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