Discovery sheds light on how a low-calorie diet extends lifespan

Mice, rats, worms, flies, and yeast all live longer on a low-calorie diet, which also seems to protect mammals against cancer and other aging-related diseases.

A gene called SIR2 is thought to control this process. Now, researchers at Harvard Medical School and UC Davis have discovered four cousins of the SIR2 gene that also extend lifespan, suggesting that the whole family of SIR2 genes is involved in controlling lifespan. The research indicates potential targets for developing drugs to lengthen life and prevent or treat aging-related diseases. The findings are reported July 28 in the advance online edition of Science. This discovery comes on the heels of the Harvard group's discovery of a molecule in red wine that extends the lifespan of every organism so far tested.

"We think these new Sir2 genes are as important as any longevity genes discovered so far," said molecular biologist David Sinclair, director of the Paul F. Glenn Laboratories for Aging Research at Harvard Medical School and co-author of the new study. "There is a growing realization from the aging field that we might finally understand how to control certain aspects of the aging process and one day have drugs that can fight some of the disabilities the process causes."

Sinclair's research group previously reported in the journal Nature the first genetic link between environmental stresses and longer life. Triggered by low salt, heat, or extreme calorie restriction, a yeast "master longevity regulator" called PNC1 stimulated Sir2 activity. This new work, led by Harvard graduate student Dudley Lamming, demonstrates that PNC1 regulates the whole SIR2 family of genes, suggesting that a human PNC1 gene might protect against diseases of aging such as cancer, heart disease and diabetes.