Epilepsy Drugs Slow Aging in Worms

Credit: Science More life: An epilepsy drug extended the lifespan of roundworms 47%, but researchers aren't yet recommending it for humans

Two epilepsy drugs have been found to slow aging in roundworms, but researchers say it's too soon to start prescribing them to fight aging in humans.

American researchers at Washington University School of Medicine in St. Louis say that a class of anti-seizure medications slows the rate of aging in roundworms, causing them to live longer and retain youthful functions longer.

Because the drugs affect nerve signals, the researchers think they have discovered a way in which the nervous system may influence aging.

Random screening

The researchers made the discovery by randomly screening 19 drugs approved for treating diseases in humans.

"We didn't start with a hypothesis about what causes aging," says Kerry Kornfeld, the study's senior author. "We wanted to look in an unbiased way at available compounds to see if any of them happened to have antiaging activity."

The researchers grew the roundworm C. elegans—commonly used in aging research—in the presence of the 19 drugs.

They found that the anticonvulsant ethosuximide extended their life from an average of 17 days to an average of 20.

Further testing revealed that the anticonvulsant trimethadione had an even bigger effect, extending lifespan by 47%.

Youthful movement

Kornfeld and colleagues then sought to determine why the drugs made worms live longer.

They found it wasn't by mimicking the effects of caloric restriction—known to extend the lifespan of roundworms and every other creature in which it has been tested—and didn't exert its effects by protecting the worms from pathogenic bacteria in their environment—a factor that wouldn't have much applicability to human aging.

What ethosuximide and trimethadione did, however, was significantly delay age-related declines in neuromuscular activity. Treated worms maintained youthful traits of fast body movement and fast pumping of mouthparts near the end of their extended lives.

Further tests showed that the anticonvulsants stimulated transmission of signals in nerves that control body movement.

Using worms with a mutation affecting nervous system and lifespan, the researchers gained further insight into how the anticonvulsants increased longevity, discovering that they didn't extend the lifespan of the mutant worms as much as normal worms. Their findings suggest that the anticonvulsants affect aging by influencing the neural system involved in the insulin signaling pathway, as well as through an independent mechanism. Much research has already linked the insulin signaling pathway with aging and longevity.

"Our experiments show there is an important connection between neural function and longevity," says Kornfeld. "We're continuing this line of research to identify the precise functions of the nervous system that cause the worms to live longer."

Worth the wait

While the findings might tempt some longevity-seekers to get an off-label prescription, it's probably worth waiting for more definitive research.

Biogerontologist Aubrey de Grey, scientific advisor to the Methuselah Mouse Prize to spur antiaging research, says that the new study may in fact have no application to humans at all.

"This means basically nothing for mammals, let alone humans, because there are so many things now known that extend worm lifespan that it's clear that the problem is that 'control' worms are living misleadingly short lives," he says. "We can still get some information from studies like this, but only (in my view) if the environmental aspects of the experiment are optimized."

The research is reported in the journal Science.