Wednesday, May 23, 2007

Longevity gene linked to low-calorie diets

Scientists have identified the first gene essential to extending the lives of animals on low-calorie diets, raising the prospects of a longevity pill.
In earlier research, "caloric restriction" extended the life, sometimes 40 percent longer than average, of creatures ranging from mice to worms. Some studies in people and monkeys are exploring whether near-starvation diets, which consist of perhaps 70 percent of the calories consumed in a normal diet, will help them live longer, too.
But "those diets are pretty tough to stick with," says Andrew Dillin of the Salk Institute for Biological Studies in La Jolla, Calif., whose international team's gene research is reported in today's issue of the journal Nature. Discovery of the gene, called PHA-4, raises hopes that uncovering the genetic machinery behind caloric restrictions may enable people to skip starvation and still live longer.
Other genes have been linked to low-calorie diets and life extension in the past, but in the new study, the team found that the presence or absence of PHA-4 in worms was the make-or-break factor in whether a starvation diet extended their lives, regardless of whether they had any of those other genes.
Dillin calls PHA-4 the "primordial" gene underlying a process that likely arose in feast-or-famine conditions in the past, where creatures that evolved metabolisms that worked more efficiently under starvation conditions survived. Versions of the gene, which the team has patented in worms, are found in mammals, too, and the team is conducting experiments on mice to see its effect.
"We are on the threshold of some pretty big discoveries in caloric restriction," says MIT biologist Leonard Guarente, who was not part of the PHA-4 study.
A number of recent discoveries, such as last year's report by Harvard Medical School researchers that resveratrol, which is found in red wine, has life-extending properties in mice, also have boosted hopes for life-extension treatments.
"My suspicion is that (treatment) won't be a substitute for a healthy lifestyle. You'll still need to go to the gym," Guarente says. "But if you are fit, we'll find something to make you fitter and if you aren't, we'll likely find something to help."
In the study, Dillin's team turned their gene on and off by adding gene-silencing compounds to the worm's food. If similar experiments work in mice, a final step would be to try boosting the activity of the mammalian version of the gene, called Foxa1, in people.
Starvation is nothing new in human history, Dillin notes, but in previous centuries people lacked antibiotics, sanitation and hospitals, likely disguising any longevity benefits hidden in famine.

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