( r environment.Ethosuximide and trimeth...)Research on Worms Yields Clues on Aging

r environment. Ethosuximide and trimethadione did, however, significantly delay age-related declines in neuro-muscular activity. Treated worms continued to display the youthful traits of fast body movement and fast pumping of mouthparts during the latter phase of their extended lives. Further tests showed that the anticonvulsants stimulated transmission of signals in nerves that control body movement. Scientists previously had found genetic mutations in C. elegans that affect both the nervous system and life span. The researchers used these mutant worms to further pin down the mechanism by which the anticonvulsants increased longevity. The worms' mutated genes affect the function of sensory neurons that regulate the release of an insulin-like hormone. "Sensory inputs from the outside regulate the level of insulin signaling inside the body, which then in turn regulates longevity in the worms," Kornfeld says. Testing the anticonvulsants on longer-lived mutant worms, the researchers found the drugs further extended their lives, although not to the same degree they extended the lives of worms with no mutations. That indicates the anticonvulsants may affect aging partly through their influence on the neural system involved in the insulin signaling pathway and partly through an independent mechanism, according to Kornfeld. "Our experiments show there is an important connection between neural function and longevity," Kornfeld says. "We're continuing this line of research to identify the precise functions of the nervous system that cause the worms to live longer." Because the researchers found that anticonvulsants affect the nervous system of C. elegans, they also plan to use the worms as model organisms to investigate how the drugs inhibit seizures in epileptic patients, a mechanism that currently is not well understood. Such research could lead to more effective treatments for epilepsy.
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Source:Washington University in St.Louis


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