Eat less, live longer? Perhaps but you don't need a calorie restriction regiment

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IN GREEK mythology, the tale of the Trojan prince Tithonus is a tragic one. His lover, the goddess Eos, asks Zeus to grant him eternal life, but forgets to specify eternal youth. Time passes, and while the goddess of dawn stays young and beautiful, Tithonus degenerates into bedridden senility. Eventually Eos shuts him in a chamber of her celestial palace, where his feeble voice can be heard begging for death.

Dreams of eternal youth feature in many cultures throughout history, but it was only in the 20th century that research into longevity really began. Much about ageing is still mysterious - we don't even know the underlying reasons why we journey into old age. There are many lines of enquiry into how to live longer, though, with one of the most intriguing being calorie restriction: in effect, going on a lifelong diet.

Calorie restriction dramatically extends not only the lifespan of laboratory animals, but also their "healthspan" - how long they live free of disease. On the assumption that it has the same effect in people, some individuals have already adopted a restricted diet. The latest evidence suggests that while calorie restriction is indeed beneficial for humans, when it comes to lifespan extension, it may not be the whole story.

The good news is that we might be able to delay ageing without cutting our food intake. "There's a definite possibility that if you balance the diet correctly, a longer lifespan can be achieved without full food restriction," says Matthew Piper, a researcher into ageing at University College London.

There is a definite possibility that if you balance the diet correctly, a longer lifespan can be achieved without full-on food restriction

Interest in calorie restriction began in 1935, when scientists made the surprising discovery that rats on a reduced-calorie diet lived longer, provided they were supplemented with sufficient vitamins and minerals. The idea sounds counter-intuitive; after all, a state of starvation is not usually conducive to health. But there seems to be a window of benefit. While lifespan is reduced if calories are cut too drastically, it can be extended by cutting them moderately (see graph).

Calorie restriction has since been shown to extend the lives of other organisms including yeast, nematode worms, fruit flies and mice. Mice, for example, live up to 50 per cent longer if their calorie intake is cut by 30 to 50 per cent. What's more, mammals are protected from a number of age-associated maladies such as cancer, heart disease, type 2 diabetes and Alzheimer's disease.

It is unclear why eating less should make animals live longer. While a restricted diet triggers numerous changes at the molecular and genetic levels, only some of these are common across all the species tested. However, there does seem to be a general principle that a dearth of nutrients causes organisms to divert resources away from growth and reproduction and towards basic survival functions. From an evolutionary perspective, these adaptations could help an organism survive famine.

Longevity pioneers

The million-dollar question is whether calorie restriction has a similar effect in people. Humans are longer-lived and clearly harder to study than flies or mice, but recently two sources of evidence have hinted that it does.

The first comes from a 20-year study of rhesus macaques, a species obviously closer to humans than worms and mice. When the macaques were about 10 years old, equivalent to young adulthood in humans, half the group were placed on a diet in which they received 30 per cent fewer calories than the others. While none has yet beaten the record for the longest-lived macaque in captivity (about 40 years), the latest results, reported last year, look promising. About 80 per cent of the calorie-restricted monkeys were still alive when the study was published, beating the control group's survival rate of 50 per cent. And the dieting animals were one-third less likely to have died from an age-related disease (Science, vol 325, p 201).

The second strand of evidence comes from studying people who are practising calorie restriction. The first enthusiasts banded together through an email forum in the early 1990s. The group has since evolved into the Calorie Restriction Society International, which now has over 3000 members who refer to themselves as "CRONies", short for Calorie Restriction with Optimal Nutrition.

Needless to say, this lifestyle is not for everyone. Some people report struggling with hunger pangs, and the society warns on its website that side effects can include feeling cold, poor wound-healing and temporary infertility. But many CRONies insist that hunger is not a big problem and that they actually feel happier and healthier on their frugal diet (see "A day in the life of a CRONie").

CRONies typically cut calories by 10 to 30 per cent of the recommended intake, and most hover around the lower limit of "normal" body mass index, at 18.5 kilograms per height-in-metres squared. To ensure they get all the nutrients they need without busting their calorie quota, their diet is mainly vegetable-based and must be carefully planned, often with the help of a computer program. "People think calorie restriction involves tiny portions, but these people are eating huge amounts of low-calorie, nutrient-dense food," says Luigi Fontana, a professor of medicine at Washington University in St Louis and head of the Division of Nutrition and Aging at the Italian National Institute of Health, who has studied CRONies for the past eight years.

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