Valter Longo, associate professor in gerontology and biological sciences, has made headlines for extending life span in baker’s yeast through a combination of dietary and genetic changes.

In 2005, a counterintuitive experiment that deleted copies of the gene SIR2 led to a dramatic life span increase that at the time was the longest extension on record.

More recently, Longo put baker’s yeast on a calorie-restricted diet, removed the genes RAS2 and SCH9, which promote aging in yeast and cancer in humans, and found a 10-fold life extension, doubling the results of his previous experiment.

Longo’s latest findings, which appear in the July issue of the journal Cell Metabolism, showed that deletion of SIRT 1 in mammals, which is the equivalent of SIR 2 in yeast, offered some protections against oxidative stress in the brain but ultimately did not enable animals to live longer.

“We found that deleting SIRT 1, combined with starvation and some gene manipulation, protected neurons in mice but ultimately SIRT 1 is too important to the mammalian body to live without,” Longo said. “Mice can’t live without SIRT 1; when the gene was removed, they died early.”

The findings demonstrate that each organ in the body may react differently to a SIRT 1 regulation.

Researchers at the Massachusetts Institute of Technology and other universities have shown increased levels of SIRT 1 in mice can prevent problems of the heart and liver even when they are fed high-fat diets.

Such results explain the high hope for resveratrol, the chemical component of red wine that is said to increase SIRT 1 production and in turn mimic the effects of the caloric restriction diet, which has shown to be successful in increasing the life span of mice.

Building upon their success, scientists are hopeful a pill will become available using resveratrol or something similar that can provide the benefits of the caloric restriction diet without forcing people to change their eating habits.

Longo also found increased levels of SIRT 1 may have negative effects on the brain.

Neurons grown in Longo’s laboratory were sensitive to oxidative damage when they made normal amounts of SIRT 1, but reducing the amount of the gene helped the cells better resist oxidative stress.

His findings add fuel to the increasing debate of whether increased levels of SIRT 1 or lower levels of the gene, as in yeast, are better for the life extension of mammals.

“There's no simple answer,” Longo said. “Activating SIRT 1 is probably a good thing in some mammalian cells under some conditions and is probably a bad thing in other cells under other conditions.”

As for resveratrol, although the chemical compound has shown no toxic side effects either in animal or human studies, Longo warned that the amount needed to mimic the beneficial effects on the heart can add up to many bottles of wine per day.

Although the chemical compound is also available in pill form, Longo advised that more research is needed to determine its long-term effects on the body.