Friday, May 4, 2007

Scientists identify gene that boosts longevity and quality of life

PARIS: The elixir of youth may ultimately be hidden in a poorly-understood gene that not only fosters longevity but enhances quality of life, according to a landmark study released yesterday.In a series of experiments on earthworms, a team of scientists at the Salk Institute in San Diego, California, have identified for the first time a gene, known as PHA-4, which plays a critical role in prolonging life without tapping into insulin-regulating neural pathways that also control the ageing process.Other molecular biologists hailed the study as a ‘breakthrough’ that will change research agendas in the new but burgeoning field of longevity genetics.But they also cautioned that duplicating the results in humans is far more complicated.Only within the last decade have scientists understood that single genes can significantly affect ageing, once though to be an uncontrollable process of decay.“There are two major ways to prolong life,” biologist Hugo Aguilaniu, one of the study’s co-authors, explained in an interview.One is to decrease sensitivity at the cellular level to insulin. “This is already well known — genetically modified mice have been created that live twice as long as a result,” he said.But there are unwelcome side-effects, including stunted growth and reproductive malfunction.The other way is dietary restriction. “If you give an animal 70% of its normal intake, it will live 20 to 30% longer,” said Aguilaniu.In a human being, that adds up to an additional 15 to 20 years of life. A restricted diet, however, is not the same as near starvation, and must consist of a balanced mix of nutrients to be effective.The link between eating less and living longer has been known for decades. “But we had no idea what the molecular actor of this process was,” he said.In the study, led by Andrew Dillin and published in the British journal Nature, C. elegans worms were fed a bacteria laced with genetic material that selectively switched off the PHA-4 gene. As suspected, the worms no longer enjoyed a longer lifespan when placed on a slimmed down diet.But while this first experiment showed that the gene was critical for diet-induced longevity, it did not prove that the PHA-4 directly triggered longer life, so another test was devised.“When we over-expressed the gene” — making it more active that it would be naturally — “the animals lived longer, up to 20 or 30%,” even when they ate normally, said Aguilaniu.Adding dietary restrictions boosted longevity even further.The researchers conducted a separate set of experiments to be sure that PHA-4 was acting independently from any insulin signalling pathways.“What is most interesting is that diet-restricted animals are more dynamic. We like to talk not just about life span but ‘health-span expansion’ — being healthier over a longer period of time,” Aguilaniu said.The millimeter-long C. elegans worm is frequently used in the laboratory because it is easy for researchers to disrupt the functions of its nearly 20,000 genes to determine what they do. Many, including PHA-4, have specific counterparts in humans.Scientists familiar with the study described it as significant. “It answers a question we have been asking for a long time,” commented Martin Holzenberger, a researcher at France’s National Institute for Health and Medical Research.“It is certainly a real breakthrough in our understanding of diet restriction,” he said, adding that the study showed PHA-4 to be “a key gene” that regulates others. – AFP

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