• Article by: Geoffrey Mohan Los Angeles Times
• March 8, 2013 - 8:12 PM

Scientists hoping to mimic the life-extending qualities produced by a chemical found in red wine and dark chocolate say they have solved one of the mysteries about how this compound works to combat the effects of obesity, diabetes, certain cancers and a host of other maladies.

The findings, published in Friday’s edition of the journal Science, could lay the foundation for a variety of drugs that act like concentrated amounts of resveratrol, the compound that has inspired a $30-million-a-year supplement business. Pharmaceutical giants have invested millions of dollars in the quest to improve on the compound that helps rev up the body’s cellular defenses against disease and aging.

Harvard geneticist David Sinclair and his colleagues have been working for more than a decade to uncover a chemical link between resveratrol and a group of enzymes known as sirtuins, which can trigger proteins that rejuvenate cells. The new results will help achieve a “more rational design” of resveratrol-related drugs, Sinclair said. “We were working in the dark before.”

Sinclair’s resveratrol-related research has vaulted him to rock-star status by the standards of biochemists. He has sipped wine on “Nightline” and “60 Minutes” and presented his work at industry conferences. In 2008, GlaxoSmithKline paid $720 million for Sirtris, the biotech firm he cofounded to commercialize his discoveries.

But his results touched off an academic imbroglio, some of it fueled by rival companies.

Scientists on both sides reacted with enthusiasm to the latest findings, saying they would lay to rest a key disagreement, even if they won’t dispel skepticism about the possibility for a pharmaceutical fountain of youth.

“We’ve known that it’s true in the test tube,” said Matt Kaeberlein, a University of Washington biogerontologist who has questioned some of Sinclair’s studies. “What this does is suggest the same thing is true in cells.”

The latest advance isn’t likely to have the mass appeal of earlier studies that showed resveratrol could improve heart function in people and make obese mice as nimble as thin ones. Those results fueled the rise of high-dose resveratrol supplements, which have not been vetted the way drugs are. Interest in the compound has also boosted sales of red wine, though scientists have cautioned that oenophiles would have to drink about 100 bottles of wine each day to get anywhere near a workable dose of resveratrol.

The new work in effect put to rest contentions that earlier results were unlikely to occur in nature. Detractors had claimed Sinclair’s data were influenced by a fluorescent chemical that he used to measure the activation of sirtuin proteins by resveratrol-like compounds. For the new study, Sinclair and his colleagues repeated the experiment with naturally occurring amino acids instead. The reaction worked.

A branch of anti-aging research centers on the effects of calorie restriction, which can send cells into a crisis mode that prompts them to repair damage and stave off hazardous cellular changes. But how resveratrol and similar compounds worked remained something of a mystery. Scientists believe it stimulates a sirtuin known as SIRT1 that breaks up certain proteins, helping them change cell behavior in beneficial ways. Sinclair said: “SIRT1 is like a Pac-Man that removes these proteins and tells other proteins to go out and repair the cell.”