Life in the Slow Lane

Slow living leads to longer life, at least in a group of common soil worms called nematodes. That's the conclusion of a new study published in today's issue of Science,* which shows that worms with a metabolism-slowing genetic defect live 50% longer lives than their bustling counterparts. The results support the notion that the cumulative buildup of damage to cells is a key--although not the lone--determinant of life-span.

The idea that metabolism plays a key role in aging isn't new. Researchers have long observed that smaller animals have faster metabolic rates and shorter lives than larger ones. The role of genes in aging isn't entirely novel, either. Past work in this area has shown that nematodes with mutations in a gene called clk-1--dubbed the clock gene--live longer lives than their normal counterparts. The new study, however, is the first to make the link between genes, metabolism, and long life.

In making this connection, Canadian biologist Siegfried Hekimi and his colleagues at McGill University in Montréal, Québec, looked at clk-1-mutant nematodes and found that they develop, eat, defecate, and even move at a more relaxed pace than their normal counterparts. When the researchers then inserted a copy of the normal gene back into clk-1 mutants, these worms lived a normal life-span.

The clk-1 gene, report the researchers, appears to act at the level of single-celled eggs and subsequently affects all tissues of the worm throughout life. The same gene, they showed, is also present in yeast, where it has been shown to play a vital role in the ability of these organisms to metabolize sugars. Taken together, this suggests that clk-1 mutations increase the life-span of worms by slowing cellular aging, say the researchers. One possibility for how that happens, says Hekimi, is that slow cellular metabolism delays the normal buildup of metabolic byproducts, such as reactive compounds known as free radicals, that are toxic to cells.

Leonard Guarente, a biologist who studies aging at the Massachusetts Institute of Technology in Cambridge, Massachusetts, agrees. But Guarente says that although metabolism may be a key player in aging, it isn't the whole story. As an example, he points out that bats and mice have the same body weight and metabolic rate, but bats far outlive mice. Furthermore, genes have been shown to control the production of chemicals that counteract the toxic byproducts of metabolism, thereby slowing aging. "There must be some counteracting force that fights against the tide of metabolism," he says. Life-span, he concludes, is influenced by both these forces, and perhaps many others.

* For more details, Science Online subscribers can link to the full text of the Report.