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Anti-Aging Drug for Humans Hinted at by Worm Study

Stefan Lovgren
for National Geographic News
January 13, 2005
 
Researchers have found that drugs used to treat human seizures can delay aging in worms by as much as 50 percent.

The roundworms used for the study are similar to humans in their molecular makeup, raising the possibility that the drugs could also extend the life span of humans.

The discovery may also shed light on the little-understood aging process. Since the drugs act on the neuromuscular systems of both humans and worms, the findings hint at a link between neural activity and aging.

"By finding a class of drugs that delays aging we have found a relationship between the function of the nervous system and aging that was not well understood," said Kerry Kornfeld, a geneticist at the Washington University School of Medicine in St. Louis, Missouri.

The findings are detailed this week in the journal Science.

Ideal Worms

The discovery came out of the thesis work by one of Kornfeld's graduate students, Kimberley Evason. About four years ago, Evason began exposing groups of the roundworm Caenorhabditis elegans to commercially available drugs to see if the drugs would delay aging or promote longevity.

Unlike vertebrates, the worms are ideal subjects for the study of aging because of their short life spans, which last only a couple of weeks in a laboratory. The worm is well known in genetics, and the worm's genome has been sequenced.

Over eight months the scientists tested 20 drugs, all with negative results. Finally they tested the anticonvulsant drug ethosuzimide. Researchers found that the drug extended the life span of roundworms from 16.7 days to 19.6 days, a 17 percent increase.

Later the scientists discovered that two related anticonvulsant drugs also lengthened the lives of the worms—in the case of one drug, by almost 50 percent.

"This was a big surprise to use," Kornfeld said. "We didn't think anticonvulsant drugs had any particular relationship to aging. That connection was completely unexpected."

Extending Life

The discovery that the drugs extend the life span of roundworms could have important implications for human aging as well.

There are strong similarities on the molecular level between the proteins and genes that constitute the worm and those that make up other animals, including humans.

"Many basic processes are highly related, including neural function, insulin signaling, and probably important aspects of the aging process," Kornfeld said. "There's every reason to think that these animals are a good model for higher animals, such as people."

But Kornfeld said scientists will not know about the applicability of the drugs in humans until a similar study is done on humans.

"What's very encouraging is that these drugs were developed to treat humans, and they are well understood, because they've been used for a long time," he said.

Ethosuzimide, which was developed in the 1950s, is commonly used to treat epilepsy, though it is not known precisely how the drug controls convulsions. There is no anecdotal evidence that it has had an anti-aging effect in people.

The next step, Kornfeld says, is to test if the drugs have an anti-aging effect on animals like flies and mice.

A Big Void

Very little is known about the aging process. From genetic analysis, researchers have found that an insulin-like signaling system regulates aging and longevity. A good diet can delay aging and extend a person's life span.

But scientists know virtually nothing about the effect of drugs on aging. "It's a big void," Kornfeld said.

In addition to delaying age-related degenerative changes, the drugs also increased neuromuscular activity, suggesting a link between the neuromuscular system and the aging process.

"Somehow the neural activity seems to regulate the aging of all of the body … the skin, musculature, and reproductive tract," Kornfeld said. "Somehow the nervous system coordinates the progress of all these tissues, evidently, though the life stages. But we don't know how it does that."

There may also be other targets not yet explored that affect aging and neuromuscular function. Said Kornfeld: "The process of aging remains mysterious."

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