Researchers say they have found a key gene that helps to regulate the process by which extremely low-calorie diets can extend life spans.
The finding is an early step in the quest to understand the genetic mechanisms that lead to aging. Scientists hope that understanding these processes will yield new drugs that delay the onset of age-related diseases, such as Alzheimer's and cancer.
"This gene is absolutely essential for the response to dietary restriction" in prolonging life span, said Andrew Dillin, a researcher at the Salk Institute for Biological Studies in La Jolla, Calif., and senior scientist of the study. However, he noted, "we're still in the identification [of genes] phase and a long way from clinical trials." The research was published online by the journal Nature.
The link between calorie restriction and increased longevity has intrigued scientists for decades. In the 1930s, animal tests showed that cutting normal calorie intake by about a third boosted life spans by 30% to 40%. Lately, there's been evidence to suggest that calorie restriction might slow human aging, too.

Its promise has prompted several biotechnology ventures and scientists to try to design medicines to mimic the anti-aging effects of calorie restriction. Recently, some researchers found that resveratrol, a compound found in red wine, can impede aging in mice. But their notion -- that resveratrol works because it influences the same mechanism that calorie restriction does -- is controversial.

Researchers theorize that an extremely low-calorie diet triggers a "starvation response" in animals -- an old adaptation trick that lets them survive through tough times, such as drought, by slowing the rate of aging. The response blocks growth and reproduction in order to free up energy to retard aging. But scientists want to pinpoint the specific genetic machinery that senses calorie intake and, when it is low, sparks cellular changes that retard aging. That could lead them to drugs that can switch on this machinery and thereby prevent or slow age-related diseases, just as calorie restriction does in animals.

The gene discovered by Dr. Dillin and his colleagues, known as PHA-4, was discovered in worms, where it plays a key role in the embryonic development of the intestine. However, PHA-4 also coordinates other genes that influence how the adult worm's body responds to a restricted diet. Humans possess three genes that are very similar to PHA-4. A future drug that turns those human genes on could yield a health and longevity response, Dr. Dillin said.

Other researchers have studied a different gene, SIR-2, which plays a role in extending longevity of yeast, worms and flies. However, its role isn't as specific in influencing the calorie-restriction response as PHA-4 is, Dr. Dillin said.

A lot more work needs to be done. Scientists still need to identify other genes that either regulate -- or are regulated by -- PHA-4. And no one knows exactly what prompts this genetic machinery to get turned on.