Biologists have found a class of chemicals that they hope will make people live longer by activating an ancient survival reflex. One of the chemicals, a natural substance known as resveratrol, is found in red wines, particularly those made in cooler climates like that of New York... Pinot Noir tends to have high levels of the chemical, while Cabernet Sauvignon has lower levels. "Wines produced in cooler regions or areas with greater disease pressure, such as Burgundy and New York, often have more resveratrol," the book says, whereas wines from drier climates like California or Australia have less.

The finding could help explain the so-called French paradox, the fact that the French live as long as anyone else despite consuming fatty foods deemed threatening to the heart.

...

A calorically restricted diet includes all necessary nutrients but has some 30 percent fewer calories than usual. The diet extends the life span of rodents by 30 to 50 percent, and even if it is started later has a benefit proportionate to the remaining life span. Scientists hope, but do not yet know, that the same will be true in people.

A similar mechanism exists in simpler forms of life, making biologists believe that they are looking at an ancient strategy, formed early in evolution and built into all animals. The strategy allows an organism, when food is scarce, to live longer, postpone reproduction and start breeding when conditions improve.

...

The possible benefits could be significant. The chemicals are designed to mimic the effect of a very low-calorie diet, which is known to lengthen the life span of rodents. Scientists involved in the research say that human life spans could be extended by 30 percent if humans respond to the chemicals in the same way as rats and mice do to low calories. Even someone who started at age 50 to take one of the new chemicals could expect to gain an extra 10 years of life, said Dr. Leonard Guarente of the Massachusetts Institute of Technology, one of the pioneers of the new research.

...

Besides resveratrol, another class of chemical found to mimic caloric restriction is that of the flavones, found abundantly in olive oil, Dr. Howitz said.

...

Dr. Guarente next found that when yeast live longer because of starvation, sir2 is the gene that mediates the response. His research then started to fuse with longstanding work on caloric restriction as he and others showed that starvation is sensed by sir2, which triggers the cellular changes that lead to increased life span.

...

What Dr. Sinclair and Dr. Howitz did was to take the human version of sirtuin, the enzyme produced by the sir2 gene, and devise a test to tell when the enzyme was activated. They then screened a large batch of likely chemicals to see if any made the enzyme more active.

Their screen produced two active chemicals, both of a similar chemical structure and known as polyphenols. That led them to expand the search to more polyphenols. The most active compound in the second screen was resveratrol.

Dr. Sinclair said he was amazed "that in an unbiased screen we pulled out something already associated with health benefits."

Much attention has been paid to resveratrol in the last few years because it is a candidate for explaining the apparent innocuousness of the French diet despite its artery-weakening ingredients. Epidemiological studies point to red wine as containing some beneficial antidote, but it is not yet certain whether alcohol, or resveratrol, or both, are the active ingredients.

Why should chemicals like resveratrol play a role both in the French paradox and in caloric restriction? Dr. Sinclair believes the chemicals are produced by plants in response to stresses like starvation and that browsing animals may have evolved to make use of the chemicals as a signal of hard times ahead. Other scientists said this idea was possible but not particularly plausible.

-- MattWalsh - 24 Aug 2003