'Marathon mice' elucidate little-known muscle type

Researchers report in the January issue of the journal Cell Metabolism, published by Cell Press, the discovery of a genetic "switch" that drives the formation of a poorly understood type of muscle. Moreover, they found, animals whose muscles were full of the so-called IIX fibers were able to run farther and at higher work loads than normal mice could.

The findings could ultimately lead to novel drugs designed to change the composition of muscle, the researchers said. Such treatments might have the potential to boost physical strength and endurance in patients with a variety of muscle wasting conditions.

The research team, led by Bruce Spiegelman of Harvard Medical School, found that increasing activity of the gene known as PGC-1 in the skeletal muscles of mice caused them to become crowded with IIX muscle fibers, which are normally much less prevalent.

"One reason why less is known about IIX fibers is that no one muscle group is packed with them," Spiegelman said. "For the first time, we have a mouse model very enriched in IIX fibers. These mice show a greatly increased capacity to sustain physical activity."

Skeletal muscle converts chemical energy into motion and force, ranging from rapid and sudden bursts of intense activity to continuous low-intensity work, the researchers said. At one functional extreme, muscles such as the soleus--a broad, flat muscle found in the calf of the leg--perform slow but steady activities such as maintaining posture. At the other extreme, muscles such as the quadriceps typically perform intense and rapid activities.

To fulfill these varied roles, muscles vary in their proportion of "slow-twitch" muscle fibers (types I and IIA), ideal for slow and constant roles, and "fast-twitch" fibers (type IIB), better suited to rapid and sudden activity of shorter duration. The fiber types are defined by which "myosin heavy chains" (MHCs) they contain and by their metabolic capacity, a feature

Contact: Erin Doonan
Cell Press

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