Study of roundworms yields potential clues in human aging

SAN ANTONIO (Jan. 8, 2012) — “You can learn a lot from studying a worm,” said Shane Rea, Ph.D., of the Barshop Institute for Longevity and Aging Studies, part of The University of Texas Health Science Center at San Antonio.

Indeed. To uncover mechanisms of the biology of aging, Dr. Rea and his research team study Caenorhabditis elegans — roundworms that reach a length of only 1/25th of an inch. Eighty percent of roundworm proteins are actually closely related to those found in humans. And while several biological processes are worm-specific, the majority appear to cross species lines.

Longevity varies

Roundworms live 3 weeks on average, yet some survive more than half a year. Others last only a few days. At the Barshop Institute, Dr. Rea and Robert Mishur, Ph.D., postdoctoral fellow, are analyzing the biology of very-long- and very-short-lived mutants for clues that might have implications for helping humans live healthier to the end of their years.

“Scientists are like mechanics certified to work on specific cars,” said Dr. Rea, assistant professor of physiology in the School of Medicine at the Health Science Center. “In our lab we study why a particular species of worm, C. elegans, ages.”

Millions of test subjects

In a recent study that consisted of dozens of meticulous experiments, more than 7 million worms were used. The study, published online by Aging Cell in November, measured the metabolites in worms’ cells — comparing the mutants’ output with that of worms with normal life spans.

Inside cells a multitude of chemicals cooperate to run the everyday reactions of life. These chemicals are collectively referred to as metabolites, and their presence or absence provides a fingerprint as to which particular reactions are in use. Some of the most important reactions in cells take place in power plants called mitochondria, and they produce energy in the form of ATP.


“There seems to be a very distinct pattern of metabolite production associated with the long-lived mutant strains and another pattern associated with the short-lived mutant strains, and both patterns are different from the signature seen in normal-lived worms,” Dr. Mishur said.

The long-lived worms inactivated an enzyme called DLD, and the unique metabolites of these animals appeared to be responsible for this inhibition. The team found that by artificially knocking down the gene that makes DLD in regular worms, life span could be extended. These were the chief findings of the Aging Cell article, Dr. Rea said. Further investigation of DLD might result in its being viewed as a target for a drug to combat aging. The researchers are also very intrigued by the fact that changes in the DLD gene have been linked with Alzheimer’s disease.

Whole-worm effects

“We think the metabolites that build up in long-lived worms spread throughout the cell and the body of the worm,” Dr. Mishur said. “As a result several processes are reprogrammed, leading to long life.”

“We’re not saying you do this to humans and you make them long-lived,” Dr. Rea said. “But we think we’ve learned of an avenue to study. This finding in worms will inform us in what we’re looking for in humans.”

This work was supported in part by grants from the Ellison Medical Foundation, the American Federation for Aging Research and the National Institutes of Health, National Institute on Aging (RAG025207A), to Shane L. Rea, Ph.D., principal investigator. Robert J. Mishur, Ph.D., was also supported in part by a National Research Service Award Biology of Aging training grant (5T32AG021890-09, Steven Austad, Ph.D., program director).

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