Gene May Trigger Age-linked Muscle Decline

By Linda Carroll, Nature

 October 23, 2002

A tiny worm may offer clues to understanding why human muscles deteriorate with aging, researchers report.

Just like humans, the muscles of the worm, C. elegans, begin to sag around middle age, according to the report in the journal Nature. Researchers use C. elegans to study processes like aging and cell death because the worms often offer a simplified model of what happens in humans.

"It's an absolutely fantastic little model system," study co-author Monica Driscoll, an associate professor of molecular biology and biochemistry at Rutgers University in Piscataway, New Jersey, said in an interview with Reuters Health. "We know more about this animal's development, genome and anatomy than any other animal on earth. And basically things work the same in (worms) as they do in humans. It's just simpler in C. elegans."

And following the aging process with C. elegans is like viewing time-lapse photography. Within 3-1/2 days, the worm goes from embryo to laying eggs of its own. Most worms have gotten old and died within 18 days.

Driscoll and her colleagues originally wanted to study changes in the nervous system with aging. And because the worms become less mobile and sensitive as they age, the researchers thought they were on the right track.

They pored over the worms' nerves, comparing cells from young worms to old ones. "We looked and looked and looked," Driscoll said. "And we didn't see any evidence of neuron death. But when we looked at the muscles, we saw quite dramatic changes."

Driscoll and her colleagues started looking for genes that might be involved in muscle deterioration in both worms and humans. "We've identified at least one gene involved in the process, PI (3) kinase," she said. "And, what's kind of cool is that we know when this gene is mutated, the onset of muscle degeneration is delayed."

The mutation Driscoll is talking about slows down the production of the enzyme produced by PI (3) kinase.

"So, basically, our goal is to find a pharmacologic intervention that will lower the signaling through this pathway and might help maintain muscle integrity," she explained.

Driscoll and her colleagues had one more interesting finding. They noted that, even though the worms were all genetically the same and were raised in identical environments, they didn't age--or deteriorate--in exactly the same fashion.

"They were all the same at the start," she said. "But if you looked at them at 18 days, you could see four classes of animals. Some were moving like young animals, some were uncoordinated, some were paralyzed and some were dead."

That means that certain components of aging may simply be due to chance errors at the cellular level during a worm's--or a human's--life, Driscoll said.