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DateLine Sunday, 15 July 2007

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Gene breakthrough could prolong life

The seemingly far-fetched (unlikely) day when we could live up to 30 years more, simply by taking a pill, has moved a step closer, with the discovery of a "longevity (long life) gene" in the humble worm.

Scientists have long known that a 60 per cent reduction in calorie intake, while maintaining a healthy diet of vitamins, minerals and other nutrients, consistently prolongs (lengthens) life by up to 40 per cent.

That also reduces the risk of cancer, diabetes and cardiovascular (heart) disease, while cutting off age-related degeneration (worsening) of the brain and nervous system. However, the reduction in calories required is so drastic (severe) that many scientists joke that it only feels like you are living longer.

But researchers at the Salk Institute for Biological Studies in La Jolla, California, have identified a gene in


A nematode worm

 nematode worms that specifically (clearly) links eating fewer calories to living longer.

The researchers think the gene provides a vital clue as to why persistent (continuous) hunger promotes long life.

Identifying this "longevity pathway" opens the door to the development of drugs that would mimic (copy) the effects of calorie restriction without having to stick to an austere (harsh) health regime.

In a paper published in Nature, Professor Andrew Dillin and colleagues show that one of the worm's genes, pha-4, has a function associated with living longer.

The gene works by regulating the "sweet spot" of food consumption between the extremes of harm caused by starvation and overeating.

"After 72 years of not knowing how calorie restriction works, we finally have genetic evidence to unravel (explain) the underlying programme required for increased longevity," said Prof. Dillin. "This is the first gene that is absolutely essential and specific for the increased longevity response to dietary restriction."

Longevity was enhanced when researchers made more pha-4 genes within the worms, suggesting that this could offer a target for life extension drugs.

The gene can boost levels of proteins called SODs (Super Oxide Dismutase) which mop up free radicals, harmful chemicals linked with ageing.

Researchers think that this may be a defence mechanism that helps the creatures tolerate starvation.

Humans possess three genes that are "highly similar" to the worm pha-4, all belonging to the Foxa family.

All three play an important role in our early development and then later on in life with the regulation of glucagon, a hormone made by the pancreas that increases the concentration of blood sugar and maintains the body's energy balance, especially during fasting.

When food is in short supply, these genes may alter glucagon levels or cause other changes in hormones that are ultimately able to regulate the ageing process.

The team is now going to study these human genes to see if they react the same way as those in nematodes do when the worms are denied their favourite treat, bacteria. Prof. Dillin said that they would also test a range of drugs to see if they can find some that boost the activity of the human equivalent of the worm gene and in theory, increase longevity.

So far, only one other gene, called sir-2, has been implicated (involved) in the life and health prolonging response of the body to calorie restriction. Increased use of the gene extends longevity of yeast, worms and flies.

However, the link is not so clean cut (clear) because the loss of sir-2 disrupts the calorie restriction response only in some strains of yeast and has no effect on other organisms, such as worms.

The Daily Telegraph

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