http://www.telegraph.co.uk/news/main.jhtml?xml=/news/2007/05/03/nelixir03.xml
Scientists find elixir of eternal life - in a worm
By Roger Highfield, Science Editor
Last Updated: 2:15am BST 04/05/2007
The seemingly far-fetched day when all of us could extend our life spans by up to 30 years simply by taking a pill has moved a step closer, with the discovery of a “longevity gene” in the humble worm.
Scientists have discovered the key to longevity in the humble worm
Scientists found a gene in a worm that links eating less with longer life
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 life by up to 40 per cent.
That regime also reduces the risk of cancer, diabetes, and cardiovascular disease, while staving off age-related degeneration of the brain and nervous system.
However, the reduction in calories required is so drastic 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 critical gene in nematode worms that specifically links eating fewer calories to living longer.
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The researchers think the gene provides a crucial clue as to why persistent hunger promotes long life.
Identifying this “longevity pathway” opens the door to the development of drugs that would mimic the effects of calorie restriction and might allow people to reap the benefits without adhering to an austere regime that only the toughest ascetics can endure.
In a paper published today in Nature, Professor Andrew Dillin and colleagues show that one of the worms’ 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 the underlying program 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.
Detailed work showed that the gene can boost levels of proteins called SODs (superoxide dismutase) which mop up free radicals, harmful chemicals linked with ageing.
The 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, boost longevity.
So far, only one other gene, called sir-2, has been implicated 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 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.