Editors' ChoiceSarcopenia

Muscle movement and loss

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Science Translational Medicine  16 Dec 2015:
Vol. 7, Issue 318, pp. 318ec215
DOI: 10.1126/scitranslmed.aad9006

In the young, a cast on a fractured limb can be a badge of courage—a tapestry for artwork and well wishes from friends. But beneath the surface, draconian events occur that melt away valuable skeletal muscle. One’s strength and muscle mass can recover quickly, but repeated periods of disuse over a lifetime, such as prolonged bed rest and limb immobilization, are thought to have cumulative effects that contribute to the progressive loss of muscle mass (sarcopenia) and function observed with aging. Now, a study by Wall and colleagues provides new insights into the effects of short-term immobilization on processes that influence protein balance in human skeletal muscle.

Twelve young, healthy men agreed to have one leg immobilized for 5 days with a full leg cast. Immobilization was associated with an ~4% decrease in the quadriceps-muscle cross-sectional area. To assess rates of muscle protein synthesis, the investigators administered isotopically labeled amino acids to the study participants and measured the incorporation of the labeled reagents into the muscle-protein pool. Measurements of muscle protein synthesis in both legs under fasting and fed states allowed the investigators to determine how short-term immobilization affects muscle protein metabolism and the anabolic response—stimulation of protein synthesis in muscle in response to protein ingestion. Immobilization decreased fasting and post-meal protein synthesis quite rapidly, as well as the anabolic response, which was measured after ingestion of protein. Some mechanistic insights were provided by measuring responsiveness of the mTOR signaling pathway to feeding, which was significantly altered in the immobilized limb. Also, muscle expression of genes involved in protein breakdown and inflammation was elevated in the immobilized but not the control leg, and was not altered by protein ingestion.

A singular aspect of this study was that the investigators circumvented the numerous technical challenges of measuring postprandial protein synthesis to demonstrate that immobilization significantly reduced the anabolic response to feeding. The findings of this study will have an impact on the quest to identify therapeutic strategies to prevent or attenuate the loss of muscle mass that occurs during bed rest or immobilization due to injury.

B. T. Wall et al., Short-term muscle disuse lowers myofibrillar protein synthesis rates and induces anabolic resistance to protein ingestion. Am. J. Physiol. Endocrinol. Metab. 10.1152/ajpendo.00227.2015 (2015). [Full text]

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