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Wine Health with Bex Bishop, Winemaker at BX of Napa

SIRT1

“Conclusive Evidence” for Red Wine's Health and Longevity Benefits


Researchers have demonstrated what they consider conclusive evidence that the red wine compound resveratrol directly activates a protein that promotes health and longevity in animal models. Furthermore, the Harvard Medical School team uncovered the molecular mechanism for this interaction, and they show that a class of more potent drugs currently in clinical trials acts in a similar fashion. 

Pharmaceutical compounds similar to resveratrol may potentially treat and prevent diseases related to aging in people, the researchers contend. Studies over the last decade have demonstrated that resveratrol, a compound found in the skin of grapes as well as in peanuts and berries, increases the activity of a specific sirtuin, SIRT1, that protects the body from diseases by revving up the mitochondria. Mice on resveratrol have twice the endurance and are relatively immune from effects of obesity and aging. In experiments with yeast, nematodes, bees, flies, and mice, lifespan has been extended.

"In the history of pharmaceuticals, there has never been a drug that binds to a protein to make it run faster in the way that resveratrol activates SIRT1," says David Sinclair, Harvard Medical School professor of genetics and senior author on the paper. "Almost all drugs either slow or block them."
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The authors thus propose a model for how resveratrol works: When the molecule binds, a hinge flips, and SIRT1 becomes hyperactive. Although these experiments occurred in a test tube, once the researchers identified the precise location of the accelerator pedal on SIRT1—and how to break it—they could test their ideas in a cell. They replaced the normal SIRT1 gene in muscle and skin cells with the accelerator-dead mutant. Now they could test precisely whether resveratrol and the drugs in development work by tweaking SIRT1 (in which case they would not work) or one of the thousands of other proteins in a cell (in which they would work). While resveratrol and the drugs tested revved up mitochondria in normal cells (an effect caused activating by SIRT1), the mutant cells were completely immune.

"There is no rational alternative explanation other than resveratrol directly activates SIRT1 in cells,” says Sinclair. “Now that we know the exact location on SIRT1 where and how resveratrol works, we can engineer even better molecules that more precisely and effectively trigger the effects of resveratrol."


Red Wine Compound Activates Gene Needed for Healthy Cells

More on the debate on the effectiveness and amount of resveratrol in humans...
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Harvard scientists said they have settled a debate over whether a compound found in red wine activates a gene that keeps cells healthy.

Researchers repeated a 10-year old study using a new method to validate earlier findings that resveratrol turns on a gene that recharges mitochondria, tiny structures that produce fuel for cells. By revving up mitochondria, the agent may protect against aging-related diseases, said David Sinclair, a Harvard Medical School genetics professor and the study’s senior author.

Sinclair’s earlier research was disputed in studies in 2009 and 2010 saying that resveratrol only activated the gene, a sirtuin called SIRT1, in experiments that used a synthetic fluorescent chemical to track activity. Since these chemicals aren’t found in cells or nature, other studies said the effect would only work in lab tests and not in humans. The new study, published today in the journal Science, got rid of the chemical.

“Controversy is a difficult thing to deal with, and I hope this paper gives some clarity to the field,” Sinclair said in a telephone interview.

The Harvard group set out to see if the effect was an artifact of the synthetic chemicals or was something that occurred naturally as well. They swapped out the fluorescent chemicals for a group of naturally occurring amino acids, including tryptophan, and found resveratrol did activate SIRT1.

Resveratrol Drugs
Sinclair’s earlier work led to the formation of Sirtris Pharmaceuticals which focuses on developing drugs from resveratrol. GlaxoSmithKline Plc (GSK) acquired the company in 2008 for $720 million. A little more than two years later, Glaxo shelved development of the lead compound from that acquisition, SRT501, when the medicine didn’t appear to work well enough in cancer patients and worsened kidney damage.

Resveratrol is currently being tested in at least two dozen clinical trials to gauge its effects on human health. It’s also packaged as a natural supplement, with $34 million in U.S. sales last year, according to the Nutrition Business Journal.

Further doubt was cast on resveratrol’s abilities after a prominent researcher and promoter of the compound, Dipak Das, who was the director of the University of Connecticut Health Center’s cardiovascular research center, was found to have fabricated and falsified data in numerous studies...

To contact the reporter on this story: Ryan Flinn in San Francisco at rflinn@bloomberg.net



Resveratrol is back on again - saving you from aging! Well, almost...

Resveratrol certainly is good for you. But how good, how much is needed, and under what circumstances seems be the big question. Well, hallelujah, a new research says... well, in short, go ahead and feel good about drinking your glass of red wine again.
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Red wine molecule could be healthy
Grab a glass of red - it seems to be a rejuvenating drink again. Red wine goes in and out of health fashion. But now it's back as a possible preventer or fighter of aging diseases. 

That good news for wine lovers comes thanks to the efforts of 30 researchers from around the globe. They've produced a paper saying that under certain conditions SIRT1, the human sirtuin protein known to combat many age-related diseases, can be activated by resveratrol and other sirtuin-activating compounds (STACs)...