Hopes of developing anti-ageing drugs have been given a boost by new research involving an ingredient in red wine.
Previous studies have shown that the plant compound resveratrol improves the health of mice fed a high-fat diet and increases their lifespan.
Scientists have now confirmed how this occurs. Resveratrol enhances the activity of energy-generating powerplants in cells via a gene called SIRT1, which is also linked to longevity.
Researchers are already looking at molecules that mimic the effect of resveratrol by targeting SIRT1. Such compounds could form the basis of future drugs that extend disease-free lifespan.
The effect of resveratrol on SIRT1 had been demonstrated in yeast, worms and flies before but never on higher animals.
The experiments involved a new strain of laboratory mouse whose SIRT1 gene can be switched off.
When adult mice were given low doses of resveratrol with SIRT1 disabled, no effect was seen on the cellular powerplants, called "mitochondria".
But mice with normal SIRT1 showed dramatic increases in energy after exposure to resveratrol.
"The results were surprisingly clear," said lead researcher Professor David Sinclair of Harvard Medical School in the US. "Without the mitochondria-boosting gene SIRT1, resveratrol does not work."
The findings are published today in the journal Cell Metabolism.
Resveratrol is a "dirty" molecule that can influence a number of different genes and proteins.
Other research has indicated that its metabolic benefits are derived from an effect on a different gene called AMPK.
This has raised doubts among some experts over whether SIRT1 is the right target for anti-ageing drugs.
The new studies show that even though resveratrol activates AMPK at high doses, this has no impact on mitochondria.
At low doses, resveratrol affects SIRT1 but not AMPK.
George Vlasuk, chief executive of the US biotech company Sirtris, which is trying to develop anti-ageing drugs, said: "The work.. strongly supports the basic rationale being pursued at Sirtris, which focuses on the development of small-molecule compounds that directly activate the enzymatic activity of SIRT1 as a new therapeutic approach to many diseases of ageing."
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