Sirtuins, Famine, and the Fountain of Youth

There’s been a lot of buzz lately about a “red wine” drug that could be a fountain of youth—combating the effects of aging and age-related disease. The drug, along with other promising breakthroughs, is being developed by Sirtris Pharmaceuticals—a company recently purchased by drug giant GlaxoSmithKline. The drug is based on resveratrol, a chemical found in red wine that activates important sirtuin genes and has extended healthy life in animal studies.

The Sirtuin Family

Sirtuins are genes found in most organisms—from bacteria to humans. These genes produce proteins that regulate important biological pathways and maintain the function of cells. Scientists believe that sirtuins help control aging so, not surprisingly they have become a prime target for research.

Sirtuins got their name from genes found in yeast called Silent Information Regulators. The genes were found to impact the longevity of yeast and one gene—Sir2—proved to play a particularly important role. Sir2 became the subject of much research and the family of genes came to be known as “sirtuins.” Seven similar genes have since been identified in humans—SIRT1 through SIRT7.

The Connection to Caloric Restriction

Researchers have found a potential link between sirtuins and caloric restriction—the only method proven to increase the lifespan of mice. By feeding the mice a diet that’s healthy, but with 30% fewer calories, they live longer and with fewer diseases.

While it seems like fewer calories might actually harm the body, it turns out the low-cal diet triggers an evolutionary strategy to fight famine that ends up being beneficial. When faced with a calorie shortage, the body switches its focus from reproducing to maintaining tissue. The body’s cells become better equipped to repair themselves and the low-cal mice live longer because they’re better protected from the diseases that usually kill them.

Since starving ourselves seems like a lousy way to live longer, scientists have been studying the science behind the process in order to find drugs that can trigger the same response as the low-cal diet. What they’ve found is that the “famine reflex” may be regulated by the sirtuin genes.

Red Wine & Resveratrol

Certain chemicals are believed to activate sirtuins and so far the most potent activator scientists have found is resveratrol—a natural chemical found in a number of plants, including grapes. While not all scientists believe resveratrol can do all that it’s claimed to do, previous research in mice has shown that it reduces the negative impacts of a high-fat diet, increases stamina, and extends lifespan.

The skin of grapes has the highest concentration of resveratrol, so it can also be found in wines where the skins are left in for a large part of the fermentation process, like red wine. But don’t go prescribing yourself a nightly glass! It turns out the chemical is so scarce, in even the red wines, that you’d have to drink around a thousand bottles a day for it to have an effect.

Potential New Drugs

Scientists are hopeful that they’ll be able to create a drug that magnifies chemicals like resveratrol, or that activates sirtuins in a different way. One of the most promising drugs in the Sirtris pipeline is SRT501, a chemical that is much more potent than naturally occurring resveratrol.

Because the Food and Drug Administration, which must approve all drugs as being safe and effective, does not recognize increased lifespan as a category for approval, Sirtris is testing SRT501 for aging-related diseases. It has shown promise in a number of disease areas including Type 2 diabetes. In human studies, SRT501 has lowered glucose levels and improved insulin sensitivity in Type 2 patients.

Sirtris is also exploring other drugs that target sirtuins. “The excitement here is that we’re not talking about red wine anymore. We’re talking about real drugs. We will make a drug to treat one disease but it will, as an added bonus, protect you against most of the other diseases of the Western world,” said Sirtris co-founder Dr. David Sinclair in an article from The Daily Mail.

Other companies are exploring sirtuins and while it will take years of tests to fully learn their power, we may be in reach of the fountain of youth—or at least a way to stay healthier longer. In a recent interview with SAGE Crossroads, Dr. Leonard Guarente—founder of the field of sirtuin biology—noted that when it comes to the possibilities of resveratrol and other sirtuin activators, although he doesn’t believe we’ll defeat age-related diseases, he thinks “…we have a chance to hold them at bay longer and increase the period when we are healthy and disease free.”