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The discovery that a compound in red wine may provide a healthier and longer life had guaranteed popular appeal, but the suggestion has been attacked from all sides. One such skirmish — a debate about the hypothesized benefits of one particular compound — may now be resolved.
In Science this week, researchers show that the compound, called resveratrol, acts directly on a protein that has been linked to cell metabolism and inflammatory diseases.
“This will be a major step forward for the field,” says David Sinclair, a molecular biologist at Harvard Medical School in Boston, Massachusetts, and lead author of the study. ”The controversy has no doubt scared people off from studying these molecules.”
Unhealthy glow
A decade ago, Sinclair and his co-workers reported that resveratrol activated SIRT1, a member of a family of enzymes that remove acetyl groups from proteins and are thought to be involved in ageing and metabolism. The team's result was based on an assay that used a peptide bearing a tag that would fluoresce when the acetyl group was removed.
Shortly afterwards, Sinclair co-founded Sirtris, a company in Cambridge, Massachusetts, that used the assay to search for SIRT1-activating compounds that might serve as potential therapies for ageing-related diseases. Just four years later, GlaxoSmithKline (GSK), a large pharmaceutical company based in London, snatched up the company for US$720 million. It was a controversial acquisition, in part because GSK’s internal scientists couldn't reproduce the SIRT1 activation with untagged peptides.
They were not the only ones: other groups had reported that resveratrol boosted the activity of SIRT1 only when a bulky, hydrophobic tag was present on the peptide. “People thought it was an artifact,” says Brian Kennedy, chief executive of the Buck Institute for Research on Aging in Novato, California, and one of the researchers who initially reported concerns about the assay.
Direct evidence
But Sinclair and his colleagues now report that some of the naturally occurring targets that are amenable to SIRT1 activation by resveratrol and other such compounds have a common feature: bulky, hydrophobic amino acids at a key position.
The team also identified a SIRT1 mutation that blocked the effects of resveratrol and other SIRT1-activating compounds on mitochondria
The study provides an important clarification, says Matt Kaeberlein, who studies ageing at the University of Washington in Seattle. But resveratrol interacts with numerous proteins, he adds, and it is still unclear to what extent the compound's biological effects are caused by its interaction with SIRT1.
And for now, those biological effects remain controversial, as laboratories quarrel over whether SIRT1 activation really does boost lifespan, notes Kaeberlein.
“The field is overly polarized right now,” agrees Kennedy. “We need to find the correct middle ground.”
This article is reproduced with permission from the magazine Nature. The article was first published on March 7, 2013.
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6 Comments
Add CommentMiddle ground my boots, science isn't a democracy.
Reply | Report Abuse | Link to thisWhat you need to find is explanations and backing evidence. Opinions are a dime a dozen; produce the evidence and you silence controversy - either way.
Since I just put down the last of a batch of ninety bottles I made I am personally thrilled and very soon I hope be thrilled a lot more on a regular basis.
Reply | Report Abuse | Link to thisHow does the conclusion : ' “The field is overly polarized right now,” agrees Kennedy. “We need to find the correct middle ground.” ' matches the tile of the article "Red Wine's Link to Health Gains Support"?
Reply | Report Abuse | Link to thisI'll do my own research and so far I'm feeling pretty good about the lab work.
Reply | Report Abuse | Link to thisAccording to wikipedia, there's actually very little resveratrol in red wine. If the stuff really is worth something, it means taking it as a supplement. Sounds like that's a big If at this juncture.
Reply | Report Abuse | Link to thisI heard it 'on the grapevine'... grapeskins are good for the longevity of grapes- shielding their precious seeds from ultraviolet sun damage - so what's good for them is good for us - it's as easy as that!
Reply | Report Abuse | Link to thisHere in Australia, it's grape harvesting time in March now, wonderful dark-blue shiraz grapes waiting to be enjoyed, fermented or not. Long live resveratrol!