Scientists Have Found the Gene That Decides How Long We Live

By Steve Connor, The Independent. Posted May 5, 2007.

Scientists have come a step closer to understanding the secret of a long, healthy life with the discovery of a gene that plays a central role in the ageing process.

The gene appears to be critical in extending the lifespan of animals that are subjected to a calorie-restricted diet -- when they are slightly starved of high-calorie food but are given all the other nutrients they need.

It is well established that calorie-restricted diets lead to longer maximum lifespans in practically every animal in which they have been studied, although the evidence it not as strong for humans.

The latest study focused on a gene common to nematode worms, mice and humans. When the gene was blocked in the worms, the benefits of a calorie-restricted diet were lost and the worms lived shorter lives. Similarly, when the scientists were able to stimulate the gene they found that they could enhance the longevity of the worms so that their extended lifespans came close to matching those worms on a calorie-restricted diet.

Scientists believe that the findings could unlock a genetic treasure-chest of potential pharmacological targets for developing drugs that can extend the human lifespan without having to follow a rigorous and difficult diet.

"After 72 years of not knowing how calorie restriction works, we finally have genetic evidence to unravel the underlying molecular programme required for increased longevity in response to calorie restriction," said Andrew Dillin, of the Salk Institute in San Diego, California. "It's likely to play a role in the human condition, although we still don't know whether calorie restriction really works in humans. Studies in primates suggest it does."

The first experiments in calorie-restricted diets go back to the 1930s. Laboratory rats and mice fed a severely calorie-restricted diet, but with normal levels of vitamins and minerals, lived almost twice as long as rodents with unrestricted access to food. Experiments with other creatures found that the phenomenon appeared to be ubiquitous in the animal kingdom. Some scientists suggested it was an evolutionary adaptation to surviving hard times until enough food became available.

The longevity-associated gene identified by Dr Dillin and his colleagues is known as PHA-4 -- the name of the protein for which the gene is responsible. The same gene also exists in mice and humans and is known as the Foxa family of genes. Both PHA-4 and Foxa are involved in the complex process of glucose metabolism. In mammals, the gene is linked with a hormone called glucagon which increases levels of glucose in the bloodstream to maintain the body's energy balance especially during fasting.

Scientists from Louisiana State University are monitoring a group of 48 overweight men and women aged between 25 and 50. The study found that those who were able to cut down on their calorie intake improved in terms of metabolic markers that are linked to longer living.

The accepted view among scientists is that there is probably an absolute upper limit to human lifespan of no more than about 125 years -- the oldest person with an authenticated birth record was a Frenchwoman called Jeanne Calment, who died aged 122 years, five months and 14 days. People in the West are living longer, but the extra years are not necessarily healthy ones -- an ageing population is leading to a dramatic rise in senile dementia.

There has been a dramatic increase in longevity over the past couple of centuries due to improvements in housing and sanitation, nutrition and health.

Some 60 per cent of boys and 70 per cent of girls born in 1981 are expected to survive to celebrate their 75th birthday in 2056. In 1881, only a third of girls and just one in five boys reached the same age.

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