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More evidence for longevity pathway
Date:5/1/2012

New research reinforces the claim that resveratrola compound found in plants and food groups, notably red wineprolongs lifespan and health-span by boosting the activity of mitochondria, the cell's energy supplier.

"The results were surprisingly clear," said David Sinclair, a professor of genetics at Harvard Medical School and the study's senior author. "Without the mitochondria-boosting gene SIRT1, resveratrol does not work."

The findings are to be published May 1 in the journal Cell Metabolism.

Over the last decade, Sinclair and colleagues including Leonard Guarente at Massachusetts Institute of Technology have published a body of research describing how resveratrol improves energy production and overall health in cells by activating a class of genes called sirtuins that are integral to mitochondrial function. The cell's power supplier, mitochondria are essential not just for longevity but for overall health.

Sinclair and colleagues had studied sirtuins in a variety of model organisms: yeast, worms, flies and mice. For the first three organisms they were able to thoroughly knock out SIRT1 and show that cells lacking the gene don't respond to resveratrol. But no one had been able to demonstrate the effect in mice, which die at birth without the SIRT1 gene.

In order to solve this obstacle, Nathan Price and Ana Gomes, graduate students in the Sinclair lab, spent three years engineering a new mouse model. These mice, seemingly normal in every way, were designed so that SIRT1 would systemically switch off when the mice were given the drug Tamoxifen.

"This is a drug inducible, whole body deletion of a gene," said Sinclair. "This is something that's rarely been done so efficiently. Moving forward, this mouse model will be valuable to many different labs for other areas of research."

The results were plain: when mice were given low doses of resveratrol after SIRT1 was disabled, the researchers
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Contact: Valerie Wencis
valerie_wencis@hms.harvard.edu
617-432-8024
Harvard Medical School
Source:Eurekalert

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