Long lived. Epilepsy drugs may increase the lifespan of C. elegans.

Fountain of Youth, for Worms

There's no magic pill that fights aging, but new evidence suggests that the right prescription for longevity may already be hidden behind the pharmacy counter. Researchers have shown that a class of antiseizure drugs markedly extends the life span of the roundworm Caenorhabditis elegans—a finding that may have implications for higher organisms.

Since the early 1990s, researchers have linked mutations in dozens of C. elegans genes to extension of the creature's life. Given all the drugs on the market, geneticist Kerry Kornfeld and his colleagues at Washington University in St. Louis, Missouri, speculated that some of these drugs might retard aging or promote longevity by affecting one of those gene targets.

So about 4 years ago, Kornfeld's graduate student Kimberley Evason began exposing separate groups of 50 worms to various drugs, from diuretics to steroids. Most of the compounds the worms ate off their petri dishes had toxic effects. But when Evason tested the anticonvulsant ethosuximide (Zarontin), the drug extended the worm's median life span 17% to 19.6 days. Evason then discovered that two related anticonvulsants also lengthened worms' lives, one of them by as much as 47%. By contrast, a chemically related compound that does not have antiseizure activity had no similar effect, the team reports in the 14 January issue of Science.

The anticonvulsant drugs are thought to control seizures in people by acting on certain neuronal calcium channels. Exactly how the drugs extend life span in worms is mysterious, although they seem to stimulate the nematode's neuromuscular system (the neurons that control movement and muscles).

"These compounds are approved for human use, so they have [molecular] targets in humans," says Kornfeld, although he cautions that there is no evidence yet that the anticonvulsants he tested slow aging in people.

Because these drugs act on the neuromuscular systems of both humans and worms, the finding also hints at a direct link between the neuromuscular system and the aging process, says geneticist Catherine Wolkow of the National Institute on Aging in Baltimore, Maryland. There may be more to the story, too. "The work opens up the possibility that there may be new targets not yet explored that affect aging and neuromuscular function," says Wolkow. "That's a pretty important finding."

Related sites
Kerry Kornfeld's webpage
National institute on Aging