Gene find helps show how eating a lot less could extend life

Scientists have identified a gene which helps to explain how drastically reducing food intake can extend lifespan. The discovery suggests that calorie restriction, which has been shown to work in animals, may also be beneficial to humans. It also opens the door for the development of drugs which could mimic the advantages of eating less without the need for people to alter their diets.

Until now, there has been scant evidence to suggest that calorie restriction diets extend human lives. But this has not stopped more than 1,000 people around the world from joining the Calorie Restriction Society, a California group which promotes the idea that eating less than half the recommended 2,000 calories a day can switch on physiological changes that slow the ageing process.

Experiments in the early 1930s showed that calorie-restricted laboratory animals lived longer and had a lower risk of cancer, diabetes and cardiovascular disease.

To get the life enhancement benefits, diets have to be restricted to 60-70% of the calories of normal food intake. “Dietary restriction is one of the universal forms of increasing longevity and this has been shown in everything ranging from yeast all the way up to dogs,” said Andrew Dillin, of the Salk Institute for Biological Studies in California. By using genetically modified variants of the nematode worm – Caenorhabditis elegans – Professor Dillin’s team found that the pha-4 gene was a key part of the life-enhancing response to restricting diet. Prof Dillin said that the results, published today in Nature, lay down “the cornerstone of defining the molecular pathway that responds to reduced food intake that results in increased longevity”.

Pha-4 is the first gene to be exclusively linked to extending lifespan in response to calorie restriction in animals. Prof Dillin speculated that pha-4, which has an analogue in mice and humans with the Foxa family of genes, probably evolved to protect animals when food was scarce.

He said that it was unclear whether restricting diets would necessarily increase lifespan in humans. But he added: “The primate study that’s going on right now, and is 35 years in, looks like the primates are going to respond very well to reduced food intake and going to live longer.” As part of their experiment, the scientists also stimulated the pha-4 gene in the worms so that it worked harder than normal. They found that the worms could mimic the life-enhancing effects of dietary restriction without needing to restrict calories.

Prof Dillin said that the findings opened up new avenues of research to extend life in more complex animals. “Can people eat their normal diets but really … enjoy the benefits of dietary restriction without having to go through the whole regimen?”

Alok Jha, science correspondent
The Guardian

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