Can We Slow Aging?

So some scientists began to look for ways to trigger the sirtuin system into action without restricting calories. In 2003, a handful of sirtuin-activating compounds (STACs) were discovered. Resveratrol--a molecule produced in plants (such as red-wine grapes)--was the most potent. Since then, resveratrol and other STACs have enhanced the vitality and extended the life span of every species they have been fed to: yeast, fruit flies, worms and fish. The maximum life span of the fish increased 59 percent, the equivalent of a human's living to 194 years. Remarkable results, no doubt, but does resveratrol work in warmblooded furry animals?

In early November, a research team (co-led by Sinclair) reported in the journal Nature the first study of resveratrol's effects on the life span of a mammal. The study compared three groups of middle-aged mice on three different diets: (1) a standard diet; (2) a high-calorie, high-fat diet, and (3) a high-calorie, high-fat diet spiked with resveratrol. As expected, compared with the mice on a standard diet, the mice on the high-calorie, high-fat diet gained weight and developed fatty livers, inflammation in their heart muscle and a diabetes-like condition. And they died at a younger age. However, the mice on the high-calorie, high-fat diet that were also given resveratrol developed none of these complications: their physiology was that of a lean mouse. They were also more physically active, outperforming the untreated and overfed mice on tests of physical performance. Most striking, resveratrol reduced the risk of death by 30 percent.

Then, in mid-November, another research team reported in the journal Cell that mice treated with resveratrol were leaner and developed a greatly enhanced aerobic capacity; their muscles were like Lance Armstrong's, consuming oxygen more efficiently and containing greater numbers of healthy mitochondria (and thus greater capacity to generate energy). Incredibly, the mice could run twice as far without getting tired, despite never having run on a treadmill before. At least for mice, resveratrol is an outstanding performance-enhancing drug.

Tantalizing evidence indicates that resveratrol may also protect against aging-related diseases. In labs around the world, resveratrol has protected mice against heart disease, cancer, diabetes and Alzheimer's--the very diseases that reduce most people's life span.

The obvious question: what does all this mean for humans? Like the mice in these recent studies, many of us are also middle-aged mammals on a high-calorie, high-fat diet. Things that are true in mice are often, but not always, true in humans. In 2007 there will be much more aging research conducted in animals, and in humans. Some of the first human studies of resveratrol will see whether it can help people with either type 2 diabetes or a rare condition called MELAS syndrome that causes brain and muscle destruction in children. More important, research is underway to find sirtuin activators that have the same effects as resveratrol but are more potent. Several have already been identified, and their health effects in animals are being studied.

Because resveratrol is found in red wine, some people ask whether they should drink more red wine, or drink red wine to the exclusion of other alcoholic beverages. There is not enough resveratrol in red wine to make that a good idea: it would take 1,000 glasses to equal the daily dose given to the mice. Resveratrol tablets and capsules are now sold over the counter, but they are of no proven value in humans, and their manufacture is not controlled by the Food and Drug Administration. It is hard to predict whether or when resveratrol, or one of the other STACs, would be approved for use as a pharmaceutical, but it seems unlikely in the next seven to 10 years.