Scientists Develop Life-Extending Compounds

The scientists who discovered resveratrol, a substance in red wine that extends the lives of mice, say they've developed three drugs that work the same way, but much more powerfully. The most potent of the three controls blood sugar; it is also believed to fight other diseases of aging.
Sales of red wine took a big jump last year after researchers at Harvard published a study on resveratrol. The study showed that large doses of resveratrol helped obese mice live as long as regular mice. The substance also let the mice run longer on a treadmill. And it seemed to prevent a range of diseases associated with aging.

According to David Sinclair, the lead researcher, there was one snag for those looking to uncork a bottle of Pinot Noir to stay young.
"You would need to drink about 1,000 bottles of red wine to get the amount of resveratrol in your body to even have a chance of seeing those benefits," he said.

So Sinclair and a team of researchers have been searching for something like resveratrol, but more powerful.

They came up with three contenders and published a study of the compounds' effects in this week's issue of the journal Nature. All three were tested in rodents. Sinclair said they triggered the same set of chemical reactions in cells – the same chemical pathway – as resveratrol did.
"The best one in this paper is 1,000 times better at activating this anti-aging pathway than resveratrol is, which is great news," he said. "It means that we can potentially have a small pill that would treat many of the diseases of the Western world."

The list could include maladies such as type 2 diabetes, cancer, Alzheimer's and heart disease.

The new compounds are the property of Sirtris, a company that Sinclair helped start. Unlike with resveratrol, which occurs naturally and is sold as a dietary supplement, Sirtris will need FDA approval to market the compounds.

"We're moving away from this molecule in red wine toward real drug discovery, pharmaceutical and rational drug design that most of the drugs we take these days come from," Sinclair said.
And drugs have to be approved to treat a specific disease. So the new study took the most potent new compound and studied its effect on mice and rats with diabetes.

The researchers found that it controlled blood sugar as well as a widely used diabetes drug.

Sinclair believes the compound also will work against other diseases of aging, including cancer.
Less sure is Dr. Randall Holcombe, the chief of hematology and oncology at the University of California-Irvine. He did an experiment comparing pure resveratrol to a powder made from grapes. The goal was to reduce the risk of colon cancer.

"We actually found that the grape powder was more effective than pure resveratrol," Holcombe said, "and that suggested that resveratrol is more active in combination with other compounds such as grapes than it is all by itself."

Holcombe says that raises the possibility that Sinclair's super-resveratrol compounds, by themselves, won't do much to prevent cancer.
Despite the lingering questions, Steven Helfand of Brown University says the research based on resveratrol does seem awfully promising.
"The surprising thing really is how well this molecule has worked so far," Helfand said. He added that he has mixed feelings about the research moving away from dietary supplements and toward more traditional drug development.

On the plus side, he said, the need for FDA approval ensures that any new products will get rigorous testing.
"I think the public should be pleased in that sense. The correct experiments will be done and the correct scrutiny will be given to these compounds," Helfand said. "They will now be scrutinized much more so than they were before."

The downside, Helfand said, is that any product to emerge from this research probably won't be cheap.

David Sinclair said that so far, his company has had no trouble raising money, despite the risk that no drug may ever emerge from the tests.
"The payoff is huge," Sinclair said. "Even diabetes in itself is roughly a $10 billion worldwide market. Some say even higher. And that's just one disease."

Sinclair said the first major studies of resveratrol used on people won't be published until next year. Human studies of the newer, more powerful compounds are even further off."