Eating less may lengthen your life. Researchers have increased life-spans in yeast and mice by having them consume fewer calories per day, and ongoing studies suggest that a strict low-calorie diet may slow aging in primates, too. But the mechanism behind the gains has puzzled scientists for years. Now a study published in the 22 September issue of Science uncovers the first genetic clue to how eating less may increase longevity.

Cutting yeast cells' glucose intake by as much as 75% increases their life-span by 25%, says molecular biologist Leonard Guarente from the Massachusetts Institute of Technology. To hunt down genes involved in the change, Guarente and his team first knocked out a gene called SIR2, known to be important in yeast's life-span. A restricted diet didn't help these altered cells live longer, confirming that SIR2 plays a key role in this type of life-span extension. But because SIR2 requires a molecule called NAD for activation, Guarente then deleted another gene, called NPT1, which is involved in making NAD. Cells lacking NPT1 did not benefit from caloric restriction either, reinforcing the idea that SIR2 has an important role in extending life.

But how? Guarente says that in cells on a strict diet, more NAD is available to SIR2, increasing its activity. SIR2, in turn, "silences" certain other genes, reducing harmful chromosomal changes by encoding a protein that prevents a gene from being copied. SIR2 also suppresses the formation of short, circular DNA fragments, which accumulate with age and are known to shorten yeast's life-span. Together, the changes appear to help increase life-span.

The discovery may have relevance for people: Although mammals don't accumulate DNA circles with age, a SIR2-like gene, regulated by NAD, silences our chromosomes too. If that gene proves important in aging, Guarente says, it may provide "one of the most promising avenues toward getting a drug that would affect the aging process."

Aging researcher Judith Campisi of the Lawrence Berkeley National Laboratory agrees that SIR2 "provides a molecular clue" to aging, but warns the discovery is a far cry from the fountain of youth some people dream about. Still, she says, "I'm encouraged that we will learn quite a lot about human aging from this study."

--CAROLINE SEYDEL

Related sites
Guarente's page at MIT
Aging research in yeast, from the Sinclair lab at Harvard
Ray Walford, a proponent of caloric restriction in humans