25 June 2003 0:00 GMT

by Bea Perks

Philadelphia - Good news for reluctant dieters. Restricting your diet today has the same longevity-increasing effect as if you'd embarked on the same diet years ago, according to unpublished findings in Drosophila. Now, geneticists are on their way to identifying the genes responsible.

The link between diet restriction and increased longevity is clearly a well-conserved mechanism, says Scott Pletcher of Baylor College of Medicine in Houston, Texas. Restricting an animal's diet to 65% of normal consumption levels has previously been shown to improve longevity in Drosophila, mice, Daphnia, and probably primates.

Pletcher has been trying to identify the genetic modifications responsible for this effect - a tall order, he says, given the paucity of data on longevity in general.

One way of measuring how longevity is affected in flies treated in different ways might be to measure the fraction of individuals alive as a function of age. "But just looking at survivorship really doesn't satisfy the needs that we have today," said Pletcher.

Instead, he uses a measure of the instantaneous risk of dying. "In other words, the probability of that individual ... to die in the next short period of time." In this framework, he says, young individuals are healthy and have a low probability of dying, but this increases as age sets in. Studies in Pletcher's lab of long-lived versus control flies show that lifespan extension is brought about by a slowing of the rate at which this deterioration occurs.

Pletcher has restricted the dietary intake of amino acids and sugars of his Drosophila, and found, as expected, that dietary restriction increases survival and reduces age-specific mortality. But looking at the genetic consequences of this is complicated.

Dietary restriction has a "gigantic effect" on gene expression - about a third of the entire genome exhibits altered expression levels. The problem is to determine which of those are responsible for the observed effect, and which are simply downstream effects.

To narrow his search, he has been looking to see which genes are expressed differently following a sudden, acute reduction in dietary intake. He treated two groups of flies in different ways - the first group had their diets restricted when they were relatively young, the second group when they were relatively old.

One obvious hypothesis, says Pletcher, is that dietary restriction prolongs lifespan by slowing down the accumulation of damaging effects, such as oxidation. If this were the case, animals would benefit most from a longer period of dietary restriction. But Petchey's findings suggest otherwise.

Within just 48 hours of the switch to a restricted diet, the second group of flies reverted to mortality rates seen in the first group of flies who had been on restricted diets from an early age. And it works in reverse, he says. If flies are switched from a restricted to a high nutrient diet, there is a similarly rapid increase, rather than decrease, in mortality rate. "History is irrelevant," said Pletcher.

The surprising findings are good news for future research. "The diet restriction response provides a temporal focus for identifying regulatory genes," he said. Rather than looking at gene expression throughout an entire lifespan, he says, geneticists can home in on the 48-hour "switch period." Petchey has begun to do just that, and narrowed the hunt for candidate genes down from about 3000 genes to just 20 or 30.

The data intrigue John Kopchick, professor of molecular biology at Ohio University, who chaired today's session on longevity. "It'll be interesting to see what we have for lunch today," he said, "nothing?"

For other stories from ENDO 2003, click through to BioMedNet Conference Reporter.