Cell protein may explain diet link to longevity

In a finding that may explain why lower-calorie diets help people live longer, researchers report that a protein present in every organism from yeast to humans may be the genetic link between calorie intake and aging.

"For the past ten years, we've sought genes that confer longevity," Leonard Guarente, a professor of biology at Massachusetts Institute of Technology in Cambridge, told Reuters Health.

A gene that codes for the protein Sir2 appears to be one of them. In experiments with yeast, researchers have previously found that removing Sir2 from cells shortens their life spans, but adding an extra copy of the gene produces "superlong" cell lives, Guarente said.

Now he and his MIT colleagues have found in studies with yeast and mice that Sir2's activity seems to depend upon metabolism. They report their findings in the current issue of the journal Nature.

Sir2, explained Guarente, performs the necessary function of "silencing" genes, that is, it selectively turns off gene expression. All body cells contain the same DNA, yet these cells serve diverse purposes. A cell's identity -- for example, whether it's a blood cell or a skin cell -- depends on gene expression, Guarente noted. Some genes, he said, "need to be silenced, and some need to be active."

To their surprise, though, Guarente and his colleagues discovered that to do its job, Sir2 depends on a molecule known as nicotinamide adenine dinucleotide, or NAD. Present in all cells, NAD assists in breaking down food and aids metabolism.

This first coupling of metabolism and Sir2 is "incredibly exciting," Guarente said, because it could open up new avenues for slowing down the aging process.

"One of the few universals we know about aging is that calorie restriction can extend life," he noted.

This research offers an explanation: Cutting calories slows metabolism, which, Guarente said, may free up more NAD. In turn, the greater availability of NAD would keep Sir2 working properly. Moreover, keeping Sir2 in good shape should help keep the balance of silent and active genes in check, promoting the health of all body cells.

If further animal studies support this, the findings could do more than bolster the virtues of a lower-calorie diet, according to Guarente. Sir2 could become a drug target for preventing some of the degenerative diseases that come with aging, he said. A drug that, for example, binds with Sir2 and keeps it active may help protect bone and muscle mass from wearing down.

If such a drug is realized, however, it won't tack years onto anyone's life. Guarente said a Sir2-targeting drug would make little difference in longevity, but instead could help people "maintain their vitality longer."