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Scientists Find Gene Linking Lifespan to Calorie Restriction


U.S. researchers have discovered a gene that promotes longer life in earthworms that eat much less than normal. Humans have similar genes, and VOA's David McAlary reports that, if they work the same way as in the worms, a drug that mimics them might someday, if not extend life, at least make it healthier.

Studies since the 1930s have shown that animals from fruitflies to monkeys increase their lifespan as much as 40 percent if they subsist on a near starvation diet. They also have less risk of cancer, diabetes, and heart disease and ailments caused by nerve degeneration.

But why is such a regimen beneficial? The answer has been elusive, but researchers at the Salk Institute for Biological Studies in La Jolla, California say they have found a genetic reason. In a paper in the journal Nature, they identify a gene called pha-four that makes hungry worms live longer.

"This is the first gene that is absolutely essential and specific for eliciting the dietary restriction response," says Salk Institute researcher Andrew Dillin, speaking on a Nature magazine podcast.

He says his experiments lengthened or shortened the lifespan of earthworms by altering the impact of the pha-four gene. Those worms with normal levels of the gene lived longer when on a very low calorie regimen. When researchers amplified the gene, the worms lived even longer, even with a normal amount of food. When they inactivated it, the worms had a standard lifespan.

Dillin says humans have three genes similar to pha-four and suggests that they are part of an internal defense mechanism to protect against famine.

"Definitely starvation is going to shorten your lifespan, but also the really high calorie diets are going to shorten our lifespan as well," he said. "But there is an intermediate level that actually increases lifespan in mammals by 30 to 40 percent. So there is this really small window where you are on the borderline of crossing into starvation or crossing into being fat. That is the calorie restriction window that we actually need to be in to increase longevity."

Dillin says that activating the pha-four gene is one of two major ways to lengthen life in laboratory animals. Another is to decrease their sensitivity to insulin, a hormone that regulates blood sugar. But this has unwelcome side effects, such as stunting and reproductive problems.

It is a long evolutionary leap from earthworms to people, but Dillin says it is worth determining if the human versions of the pha-four gene operate the same way. The goal would be to develop a drug that could activate them so people could benefit from their effects without going on a near-starvation diet.

"Whether or not it is going to extend human longevity - I don't think that is actually the goal. The goal is actually to reduce the onset of these age-related diseases," he said.

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