The Longevity Gene Theory

Over recent years scientists have sought to understand how resveratrol seems to offer so many different health benefits. Research has uncovered a number of mechanisms that resveratrol uses to influence or help regulate a wide variety of biological processes. Even more fundamental then these, however, is how resveratrol may interact with our DNA.

Sirtuin Genes

Many researchers, over years of studies, have come to believe that the answer to what makes resveratrol so potent lies in understanding its interaction with the sirtuin gene family. Of the seven sirtuin genes known in humans, the SIRT1 gene is perhaps the best known and studied for producing enzymes that appear to increase DNA stability and protect against cellular degenerative processes throughout the body, but scientists continue to gain a more thorough understanding about the role of other sirtuins in human health every year.²⁶

Typically sirtuin genes are activated when the cell or body is under some sort of biological stress, like that of calorie-restriction.²⁶ But a more accurate view of sirtuin genes is that they are intricately connected to metabolic cellular activity—regulating the production of enzymes, hormones, and other proteins in response to physiological conditions.⁵⁹

Effects of SIRT1 and Resveratrol

Studies have shown that calorie-restricted rats have increased life-spans with fewer health problems, and rats given resveratrol with diets of 60% fat experienced similar effects on lifespan and health. Although not all the mechanisms are known yet, scientists believe that one way resveratrol and SIRT1 may do this is by regulating the protein and enzyme-altering effects of oxidizing agents.²⁶

One example of evidence that supports this theory comes from a study in 2008 involving two such oxidizing agents—hydrogen peroxide and UV radiation. Both are known to cause or promote skin cell damage and death by changing the structure of a cell protein. Results of this study suggest that the SIRT1 enzyme inhibits this modification and prevents cell damage, and agents that hamper the activation of SIRT1 subsequently increase cell death. Conversely, resveratrol is thought to activate SIRT1 genes and thus lowers the rate of cell damage and death.⁶⁰

Contradicting the Longevity Gene Theory?

Recent evidence in 2009 refutes the resveratrol-sirtuin activation mechanism as the explanation for resveratrol’s beneficial effects—at least in terms of some of the sirtuin genes. Researchers at Amgen, Inc.’s Department of Neuroscience conducted studies that confirm results published in an earlier paper by scientists at the University of Wisconsin-Madison’s Department of Biomolecular Chemistry that found that resveratrol did not activate SIRT2 at all, and only activated SIRT1 if bound to a compound called fluorophore. This compound is the chemical probe that was only intended as an experimental tool to determine if resveratrol activated the SIRT1 genes, but these two studies suggest that the fluorophore activated the SIRT1 genes, and not resveratrol. However, resveratrol’s biological interactions with our cells are complex, and in fact the Amgen study recognizes the validity of studies showing resveratrol’s positive health effects—with or without SIRT1.^61-62