Resveratrol, Quercitin, Calorie Restriction, Longevity

Scientific American's new issue contains an article about "longevity genes" and the search to unlock them. Many articles have been written about the Sir and Sirt genes known to influence longevity in yeast and lower animals. The recent SciAm article brings us fairly up to date on the research of the authors and their associates (David Sinclair and Lenny Guarente).

Calorie restriction (CR) was cited as one of the few maneuvers known to increase lifespan of laboratory animals. Not surprisingly, CR works through the Sirt genes. What was surprising was that resveratrol, found in red grapes and wine, also affects the Sirt genes in much the same way as CR.

First of all, the researchers had to dispense with an old theory that turned out to be false:
The phenomenon (life extension through CR) was long attributed to a simple slowing down of metabolism--cells' production of energy from fuel molecules--and therefore reduction of its toxic by-products in response to less food.

But this view now appears to be incorrect. Calorie restriction does not slow metabolism in mammals, and in yeast and worms, metabolism is both sped up and altered by the diet. We believe, therefore, that calorie restriction is a biological stressor like natural food scarcity that induces a defensive response to boost the organism's chances of survival. In mammals, its effects include changes in cellular defenses, repair, energy production and activation of programmed cell death known as apoptosis.

....Yet if humans are ever to reap the health benefits of calorie restriction, radical dieting is not a reasonable option. Drugs that can modulate the activity of Sir2 and its siblings (collectively referred to as Sirtuins) in a similar manner will be needed. Just such a Sirtuin-activating compound, or STAC, called resveratrol has proven particularly interesting. Resveratrol is a small molecule present in red wine and manufactured by a variety of plants when they are stressed. At least 18 other compounds produced by plants in response to stress have also been found to modulate Sirtuins, suggest?-ing that the plants may use such mole?-cules to control their own Sir2 enzymes.

....Feeding resveratrol to yeast, worms or flies or placing them on a calorie-restricted diet extends their life spans about 30 percent, but only if they possess the SIR2 gene. Moreover, a fly that overproduces Sir2 has an increased life span that cannot be further extended by resveratrol or calorie restriction. The simplest interpretation is that calorie restriction and resveratrol each prolong the lives of fruit flies by activating Sir2.

Resveratrol-fed flies not only live longer, despite eating as much as they want, but they do not suffer from the reduced fertility often caused by calorie restriction. This is welcome news for those of us hoping to treat human diseases with molecules that target Sir2 enzymes. But first we want a better understanding of the role of Sir2 in mammals.

....Increased Sirt1 (the mammalian version of Sir2) in mice and rats, for example, allows some of the animals' cells to survive in the face of stress that would normally trigger their programmed suicide. Sirt1 does this by regulating the activity of several other key cellular proteins, such as p53, FoxO and Ku70, that are involved either in setting a threshold for apoptosis or in prompting cell repair. Sirt1 thus enhances cellular repair mechanisms while buying time for them to work.

....Both our labs are running carefully controlled mouse experiments that should soon tell us whether the SIRT1 gene controls health and life span in a mammal. We will not know definitively how Sirtuin genes affect human longevity for decades. Those who are hoping to pop a pill and live to 130 may have therefore been born a bit too early. Nevertheless, those of us already alive could live to see medications that modulate the activity of Sirtuin enzymes employed to treat specific conditions such as Alzheimer's, cancer, diabetes and heart disease. In fact, several such drugs have begun clinical trials for treatment of diabetes, herpes and neurodegenerative diseases.

The authors were careful not to hype resveratrol, since the research is still ongoing. Other people working with CR are a bit more enthusiastic about resveratrol. Both resveratrol and quercetin have been known for a number of years now to influence Sirt genes. Vitamin and supplement makers are growing quite sophisticated in keeping up with research, and waste no time making natural phytochemicals available to the public, where legal.

It is unlikely that these phytochemicals represent a hazard to the public. Certainly I have been imbibing resveratrol in liquid form for several years now, with no untoward effects noted. Nevertheless, it is hazardous to the purse to buy every supplement that some vitamin salesman promotes. Follow the research and make up your own mind.

I recommend reading the Scientific American article in its entirety.