We cannot make people younger, like Benjamin Button. But can we stop them from growing older?

Almost two years ago, a brief piece appeared in the New York Times that described a magical pill, a molecule called resveratrol, that had the following properties:

Imagine a pill, derived from a compound found in something as benign as red wine, that treated the most feared and debilitating diseases of aging: illnesses like diabetes, neurodegenerative conditions like Alzheimer’s and Parkinson’s, and many forms of cancer. Imagine, furthermore, that this pill had no injurious side effects. Imagine, finally, that the pill’s only side effect conferred what human beings have always wanted: an increase in life span. (NYT, July 8 2007).

Resveratrol is the discovery of David Sinclair, Professor Pathology at Harvard Medical School. Sinclair partnered with Christoph Westphal, M.D. and Ph.D. and a venture capitalist, in 2004, to found  Sitris Pharmaceuticals. This startup was built to commercialize Sinclair’s amazing discovery, made in 2003 when Sinclair was only 37, that resveratrol, found in red wine and other plant products, extends the life span of mice by as much as 24 percent and the life span of other animals, such as flies and fish, by as much as 59 percent. It also helps those with diabetes.  

How does resveratrol work? Apparently it turns on the SIRT1 gene, found in all living cells, that is normally inactive but has the ability to delay aging. Resveratrol is found in red wine and comes from the skin of red grapes. In grapes, it evolved to battle insects and pests. There have been numerous reports that drinking red wine slows aging. Alas, according to Dr. Westphal, interviewed on the CBS program 60 Minutes, you would have to drink 1,000 bottles of red wine daily to get enough resveratrol to matter

“Not recommended,”  Dr. Westphal says drily. 

But concentrated, in a pill, that’s a different matter. Resveratrol has had startling results in mice, and is now undergoing additional clinical trials in humans. It may be on the market within five years. 

How does the SIRT1 gene get turned on, to slow aging and prevent disease? Dr. Sinclair’s mentor at MIT, who discovered the gene family of which SIRT-1 is one, believes that SIRT-1 is normally activated by caloric restriction.   That is, somehow, if the body is hungry, it activates the gene. A long series of studies shows that a 30 per cent reduction in calories extends life substantially among both people and mice and reduces morbidity. Apparently hunger turns on SIRT1. Most of us, however, are not able to slash our caloric intake by that much for extended periods — even though there is a society known as CRS, Caloric Restriction Society, whose members do precisely that, and show great vigor and good health. (They are now the subjects of a large clinical study). But popping a reservatrol pill daily? Well —  that’s easy. And reservatrol  does turn on that powerful SIRT1 gene.  

For those who understand genetic biology, some of the results from Sinclair’s lab were published in a leading academic journal, Cell, in November 2008. And it is already possible to buy resveratrol (unofficially) on the Web.

By the way, Sitris was acquired by Glaxo Smith Wellcome. The price: $750 m. Apparently Glaxo sees big profit in a drug that may make aging obsolete.