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NIH Research Matters

April 25, 2011

Gene Could Hold Key to Muscle Repair

Researchers have identified a gene that is critical for maintaining and regenerating muscle. The finding may lead to therapies for muscle-wasting diseases and age-related muscle decline.

Photo of an older man flexing large biceps.

Young people may lose muscle after a period of inactivity, but usually rebuild it as activity resumes. However, in the elderly, muscles are less resilient. Elderly people who lose muscle strength following bed rest can find it difficult or impossible to regain strength. Similarly, patients with Duchenne muscular dystrophy (DMD), the most common form of muscular dystrophy, develop muscle properly, but can’t maintain and regenerate it. DMD causes progressive weakness and degeneration of the skeletal muscles, usually beginning before the age of 6. Patients with DMD typically succumb to the fatal disease by early adulthood.

Muscle is maintained by a specialized population of cells called satellite cells. These cells are critical for the development of skeletal muscle in the embryo and fetus. Satellite cells continue to actively increase muscle mass through infancy. After that, they decrease in number and become inactive until injury or degeneration causes them to proliferate and become active again. If scientists could understand how to boost the activity of these cells, they might be able counteract the muscle decline of DMD and aging.

A research team led by Dr. Vittorio Sartorelli of NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) suspected that a genetic switch might turn off satellite cell proliferation. The scientists looked to a gene called Ezh2, which is known to keep the activity of other genes in check through histone methylation—a modification to DNA that affects gene expression without altering the genetic sequence.

As reported on April 15, 2011, in the journal Genes and Development, when the researchers genetically inactivated Ezh2 in satellite cells of laboratory mice, the mice had reduced muscle mass and failed to repair muscle damage. Upon closer examination, the scientists found that the satellite cells didn’t proliferate normally. Furthermore, genes that are expressed in nonmuscle cells were more active than they normally are in muscle cells.

Ezh2 expression is known to decline during aging. This new finding in mice suggests that therapies to activate Ezh2 and promote satellite cell proliferation might eventually help in treating degenerative muscle diseases.

"We will not be able to cure the muscular dystrophies with this approach because the mutation in the gene that causes the diseases would remain. But certainly, if we can extend the period in which the satellite cells proliferate and compensate for the underlying defect, we might increase the lifespan of people with muscular dystrophy," says Sartorelli. “We could certainly increase their quality of life.”

Likewise, tweaking the gene in satellite cells of elderly people could increase their quality of life by helping to prevent falls and enabling better movement and walking as they go about their daily activities. But Sartorelli cautions that while identifying the role of Ezh2 is a crucial step, any therapies are still many years away.

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Editor: Harrison Wein, Ph.D.
Assistant Editors: Vicki Contie, Carol Torgan, Ph.D.

NIH Research Matters is a weekly update of NIH research highlights from the Office of Communications and Public Liaison, Office of the Director, National Institutes of Health.

This page last reviewed on December 3, 2012

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