New study results demonstrate evidence that the red wine compound resveratrol directly activates a protein that promotes health and longevity in animals.
What’s more, the researchers have uncovered the molecular mechanism for this interaction, and show that a class of more potent drugs currently in clinical trials act in a similar fashion. Pharmaceutical compounds similar to resveratrol may potentially treat and prevent diseases related to aging in people, the authors contend.
These findings are published in the March 8 issue of Science.
For the last decade, the science of aging has increasingly focused on sirtuins, a group of genes that are believed to protect many organisms, including mammals, against diseases of aging. Mounting evidence has demonstrated that resveratrol, a compound found in the skin of grapes as well as in peanuts and berries, increases the activity of a specific sirtuin, SIRT1, that protects the body from diseases.
“In the history of pharmaceuticals, there has never been a drug that binds to a protein to make it run faster in the way that resveratrol activates SIRT1,” said David Sinclair, Harvard Medical School professor of genetics and senior author on the paper. “Almost all drugs either slow or block them.”
Does resveratrol directly activate SIRT1 or is the effect indirect? “We had six years of work telling us that this was most definitely not an artifact,” said Sinclair. “Still, we needed to figure out precisely how resveratrol works. The answer was extremely elegant.”
Sinclair and Basil Hubbard teamed up with a group of researchers from both the National Institutes of Health and Sirtris Pharmaceuticals to address this question. The team addressed the problem of the fluorescent chemical group. In nature, there are three amino acids that resemble the fluorescent chemical group, one of which is tryptophan, a molecule abundant in turkey and notable for inducing drowsiness. When researchers repeated the experiment, swapping the fluorescing chemical group on the substrate with a tryptophan residue, resveratrol and similar molecules were once again able to activate SIRT1.
“We discovered a signature for activation that is in fact found in the cell and doesn’t require these other synthetic groups,” said Hubbard, first author of the study. “This was a critical result, which allowed us to bridge the gap between our biochemical and physiological findings.