Posted: Mar 11, 2013 8:46 PM by Michelle Castillo - CBS News
After some debate, Harvard Medical School researchers are saying they have confirmed that compound resveratrol that's found in red wine does provide anti-aging benefits.
The study, which was published on March 8 in Science, shows that resveratrol stimulates production of SIRT1, a serum that blocks diseases by speeding up the cell's energy production centers known as mitrochondria.
Researchers have also figured out which gene allows resveratrol to produce SIRT1, and believe that some drugs currently in clinical trials may be able to provide the same anti-aging benefits as well.
"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," senior author David Sinclair, Harvard Medical School professor of genetics, said in a press release. "Almost all drugs either slow or block them."
Resveratrol is a naturally-occuring polyphenols antioxidant that is found in some plant products like grapes and cocoa. It is categorized as a phytoalexin, an antimicrobial compound that is produced by plants to protect them from rough environments like excessive ultraviolet light, infections and climate changes.
Resveratrol has been linked to protection against obesity and diabetes, a reduced risk for blood clotting and a way to lower "bad" LDL cholesterol, due to the compound's ability to dilate blood vessels, increase nitric oxide and block the stickiness of platelets. However, some research came into question when Dr. Dipak K. Das, director of the cardiovascular research center at the University of Connecticut who led several reseveratrol studies, was accused of making up results in January 2013.
There was also a controversy behind whether SIRT1's production was actually influenced by resveratrol. Earlier studies have used a man-made chemical group which glowed brighter the more SIRT1 activity went up. Without this chemical, the experiments didn't work. Some scientists believed that because of this, it meant that SIRT1's activity was only a laboratory construct and didn't exist in nature.
"We had six years of work telling us that this was most definitely not an artifact," Sinclair, who initially published a study in 2006 linking resveratrol to SIRT1 and longevity in mice using that man-made chemical, said. "Still, we needed to figure out precisely how resveratrol works. The answer was extremely elegant."
To prove that there was a link between resveratrol and SIRT1, scientists discovered that the man-made chemical was actually close to three amino acids that were naturally found in cells, one of which is tryptophan, the chemical thought to make people drowsy after eating turkey. Instead of using the florescent chemical, researchers used a tryptophan residue in a test tube to see if it would create more SIRT1, which it did.
Then, Sinclair and his team looked at 2,000 mutants of the gene responsible for SIRT1 to find out how resveratrol worked, and found one mutation that stopped resveratrol's effects by swapping out one of the 747 amino acid residues.
After they found where this mutation was found on SIRT1-creating gene and how to control it, researchers replaced the normal SIRT1 gene in manufactured muscle and skin cells with the one that stopped resveratrol's effect. They then introduced resveratrol and some other medications in clinical trials. Resveratrol and some of the medications were able to speed up mitrochondria by activating more SIRT1 in normal cells, but the mutated cells were unaffected by the substances.
"This was the killer experiment," said Sinclair. "There is no rational alternative explanation other than resveratrol directly activates SIRT1 in cells. 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."
It is important to note that Sinclair is a co-founder and scientific advisor of Sirtris, a GlaxoSmithKline company. Sirtris currently has a number of sirtuin (SIRT1)-activating compounds in clinical trials.
Sinclair told the Telegraph in a separate interview that he wants to continue the studies to see if reveratrol can help people who are already really healthy.
"Things there are also looking promising. We're finding that ageing isn't the irreversible affliction that we thought it was," he commented. "Some of us could live to 150, but we won't get there without more research."
Many agree that the information is promising.
"This is not weak evidence at this point," Leonard Guarente, a biologist at the Massachusetts Institute of Technology and a Sirtris scientific advisory board member, added to the Los Angeles Times."You would really bet the ranch on this one."
"It might bring together the different views so we can move forward," Brian Kennedy, president and chief executive of the Buck Institute for Research on Aging in Novato, Calif., added in a press release. Kennedy previously questioned the results of studies using resveratrol and yeast. "This is how science works."