Even so, the discovery promises to open up new leads in the quest to understand longevity and ageing, says Tom Kirkwood, an expert on ageing at the University of Newcastle upon Tyne. "What we are looking at here is a pretty fundamental mechanism."
This is the first time that simply feeding a drug to flies has made them live longer. And in a twist that contradicts theories on ageing, there seems to be no price to pay for this extra time. The flies are as healthy and fecund as their untreated peers.
Kyung-Tai Min and a team of researchers at the National Institutes of Health and the California Institute of Technology made the discovery by accident when they were testing a drug called 4-phenylbutyrate (PBA) on flies with neurodegenerative disease. They found that feeding the drug extended maximum lifespan of healthy flies by over 50 per cent, and their average lifespan by one-third. Intriguingly, higher doses of the drug were either toxic or less effective, hinting that you need to strike a delicate balance to maximise the repair mechanisms in cells.
Previous studies suggest that reduced fertility and semi-starvation can extend fruit flies' lifespan, so the team wondered whether PBA was mimicking these effects. But when they weighed the flies and counted their offspring, they found they were normal.
To test the flies' resistance to stress, they then starved them and fed them a chemical that generates free radicals. But far from having to pay for their longevity with a weaker constitution, the PBA flies survived better than the controls. "We are going to test more, but so far, it seems they are perfect," says Min. Kirkwood, however, is sceptical. "The drug might be incurring a cost that isn't visible yet," he says. For instance, the pampered lab flies may have to eat more than usual to keep them going. "They might not be so competitive in the wild."
PBA works its dramatic effects by blocking the activity of histone deacetylases, enzymes involved in switching genes on and off. Min found that 100 genes were switched on in response to PBA, including the one for superoxide dismutase, a protein well known for its anti-ageing effects. About 50 others were switched off. Min's team are investigating these genes, and how PBA has its effect on the histone deacetylases.
So will we be popping anti-ageing pills any time soon? Kirkwood thinks not. "It's just not that easy to bring about changes which alter lifespan without deleterious effects," he says.
Unlike flies, mammalian cells continue to divide and renew throughout life, so inducing large changes in gene expression may be risky. However, Min points out that PBA has been approved in the US for treating cystic fibrosis and sickle cell anaemia, and seems to have few side effects. He and his team will be testing the drug on mice very soon.
Author: Claire Ainsworth
More at: Proceedings of the National Academy of Sciences (vol 99, p 838)
New Scientist issue: 26th January 2002
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