Rodents, worms, flies, and yeast cells live longer when fed a low-calorie diet, which protects mammals against age-related diseases, including cancer. In May, researchers reported the first known genetic link between environmental stress and a longer life span in yeast.*
Triggered by salt, heat, or caloric restriction, a yeast “longevity gene” was found to stimulate the activity of Sir2, an enzyme that belongs to the sirtuin family of enzymes known to extend the life span of yeast and worms.
Now, a group from Pennsylva-nia’s Biomol Research Laboratories has found a way to duplicate the benefits of caloric restriction in yeast cells by polyphenols, antioxidants that are found in vegetables, olive oil, fruit, and wine, and whose levels in plants increase in response to stress. The findings, reported in August in the journal Nature’s advanced online edition, show that polyphenols prompt yeast cells and human cells to prepare for harsh conditions by switching to a life-extending survival program that mimics caloric restriction. This occurs by a mechanism other than their antioxidant action—activation of the sirtuin family, the SIRT2 protein in yeast and SIRT1 protein in humans.
The most potent activator of sirtuins is resveratrol, found in grapes, wine, and peanuts. In yeast, resveratrol mimics caloric restriction by stimulating the SIRT2 enzyme, increasing the stability of DNA, and extending the life span of the yeast cells by 70%.
In experiments with human cells, resveratrol activated a similar pathway that enabled 30% of the cells to survive exposure to radiation, compared to 10% of untreated cells. Little is known about the human SIRT2, except that it switches off p53, a growth-regulating protein that plays a role in programmed cell death. Increasing survival through the activation of SIRT1 and SIRT2 by polyphenols may allow cells time to repair damage, thereby extending their life span.
—Carmia Borek, PhD