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Think You Know How Resveratrol Works? Think Again

Scientists discover new mechanism for the anti-aging benefits of red wine’s most controversial polyphenol

Esther Mobley
Posted: January 14, 2015

The red-wine polyphenol resveratrol has become a contentious subject in scientific circles. It's been both heralded for its potential as a fountain of youth and dismissed for its ineffectiveness at normal doses in humans. But now scientists at the Scripps Research Institute have found that resveratrol may activate a powerful stress response in cells. And their results suggest a fundamentally different mechanism than has been found in resveratrol previously. The findings may shed new light on the health benefits of wine consumption.

The vast majority of resveratrol research in the past has focused on the polyphenol’s relationship to the SIRT1 gene, which gets activated in times of extreme calorie restriction. Once activated, SIRT1 produces anti-inflammatory and antioxidant proteins, and has been shown to be associated with a longer lifespan. Resveratrol, some studies have found, can activate the SIRT1 gene just as calorie restriction would. But the research has been inconclusive, and the successful results were obtained using very high doses of resveratrol, much higher than could be consumed drinking wine.

The Scripps researchers are looking at a mechanism that takes place at much lower concentrations of resveratrol, however—as much as 1,000 times lower than what’s been seen in previous studies, according to a statement by the scientists. “Based on these results, it is conceivable that moderate consumption of a couple of glasses of red wine (rich in resveratrol) would give a person enough resveratrol to evoke a protective effect via this pathway,” said lead study author Dr. Mathew Sajish.

Published in the journal Nature, the study involved injecting mice with resveratrol. It found that resveratrol mimics an amino acid called tyrosine. Under stressful conditions, tyrosine binds with the enzyme TyrRS, a tRNA synthetase that helps our genes create proteins. When the amino acid binds to TyrRS, it halts its protein translation activity and moves it into the cell nucleus.

Once TyrRS and tyrosine—or its imposter resveratrol—are in the cell nucleus, they activate the gene PARP1, which in turn activates a number of other genes. This is where the scientists begin to see anti-aging potential: PARP1 is a stress-response gene, known to repair DNA and promote longevity; other genes that it activates include p53, a tumor suppressor, and FOXO3A and SIRT6, both known to increase lifespan.

“We believe that TyrRS has evolved to act as a top-level switch or activator of a fundamental cell-protecting mechanism that works in virtually all forms of life,” said Sajish, noting that resveratrol probably exists in plants such as grapevines in the first place because it performs the same protective function in those organisms.

Sajish and his colleagues will continue to investigate other possible amino-acid mimics. Their research has not directly examined the effects of wine consumption, but their findings here may mark a promising new chapter in our quest to understand resveratrol.

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