Lifespan genes discovered

by Daniel McCabe

At first glance, they look pretty much like any other worm. They wouldn't seem out of place in a garden or on the hook of a fishing rod. But the worms in biology professor Siegfried Hekimi's lab are very special worms indeed.

So special that they're generating a huge buzz among researchers across the world and finding themselves covered in publications such as The New York Times, Science and The Los Angeles Times.

What Hekimi, graduate student Bernard Lakowski and their research team have managed to do with the worms is nothing short of amazing--by manipulating the creatures' genes, they have created mutant worms that live five times longer than normal. Worms which ordinarily survive for nine days have lived as long as two months. No creature has ever had its life span increased to that extent before.

Commenting on Hekimi and Lakowski's accomplishment in the current issue of Science, Judith Campisi, a molecular biologist at the Lawrence Berkeley National Laboratory in California, called their results "phenomenal."

What makes Hekimi and Lakowski's work truly significant is that it points to a new way of understanding how organisms age. The McGill biologists have identified new genes--called clk-1, clk-2 and clk-3--which, when mutated in the worms, made the creatures live their existences in a kind of "slow motion." The mutant worms took longer to develop into adulthood, they ate more slowly, swam more slowly and took far more time than usual to age and perish.

These genes each seem to have specific functions. Mutations in clk-1, for instance, prompted individual cells to divide more slowly. The McGill team achieved its most dramatic results when they manipulated the clk-1, clk-2 and clk-3 genes together in their mutant worms. These worms lived the longest.

Hekimi thinks the research points to the fact that all organisms have internal "biological clocks" that govern the aging process and ensure that everything from cellular processes to behavioural patterns evolves in a synchronic manner.

Hekimi calls the genes he and Lakowski uncovered "Clock genes." He posits that these genes likely play a vital role in all organisms--ensuring that activities that have some temporal component are consistent with one another. "If somebody ate quickly all the time, but always digested his meals slowly, he would be in trouble. There is generally an overall logic in how these things relate to one another," says Hekimi.

He notes that some animals live their short lives at frantic speeds, such as hummingbirds, while others, like the albatross, live a slow-paced, long life. "Either aging is a developmental phenomenon--like puberty or menopause--or it's a secondary consequence of the general evolutionary choices of a species," says Hekimi. "Sparrows evolved in such a way that they might only live for two summers, but they are able to reproduce two weeks after they're born. Humans, on the other hand, have a very protracted development. The length of life depends on the speed of life."

Hekimi says we die--to a large extent--from the accumulated damage we receive from just living normally. "For instance, the metabolic processes surrounding the intake of oxygen are toxic for our own cells. If you lived life more slowly, you would accumulate this sort of damage more slowly and you should probably live longer as a result."

One aspect of the McGill team's research that stands out is the fact that, even when worms were given a mutated form of the clk-1 gene from their father, if the clk-1 gene they received from their mother was normal, the worms would have a typical life-span. This could be evidence that maternal clk-1 genes play the decisive role in determining the life-span of offspring.

Everyone seems to agree that Hekimi and Lakowski's findings are pivotal, but some researchers aren't so sure that the Clock genes alone determine how aging proceeds. Huber Warner, from the National Institute on Aging in Bethesda, Maryland, told Science, "There's both genetic and environmental factors."

Still, there is little doubt that other scientists are anxious to study the Clock genes further. Will the lessons learned from Hekimi and Lakowski's mutant worms enable humans to live longer lives? Hekimi says it's far too soon to say, but adds, "Clearly the aging process is very similar in most organisms."