Sexual dimorphism in skeletal muscle protein turnover

Abstract

Skeletal muscle is the major constituent of lean body mass and essential for the body's locomotor function. Women have less muscle mass (and more body fat) than men and are therefore not able to exert the same absolute maximal force as men. The difference in body composition between the sexes is evident from infancy but becomes most marked after puberty (when boys experience an accelerated growth spurt) and persists into old age. During early adulthood until approximately the fourth decade of life, muscle mass is relatively stable, both in men and women, but then begins to decline, and the rate of loss is slower in women than in men. In this review we discuss the underlying mechanisms responsible for the age-associated sexual dimorphism in muscle mass (as far as they have been elucidated to date) and highlight areas that require more research to advance our understanding of the control of muscle mass throughout life.

Keywords: aging; hypertrophy; muscle protein; protein turnover.

Fig. 1.

Schematic presentation of the regulation of muscle mass and age-associated changes in muscle protein synthesis. Top: in healthy young and middle-aged adults, when muscle mass is constant, the rate of muscle protein synthesis (MPS) over the course of a day matches the rate of muscle protein breakdown (MPB). An imbalance between MPS and MPB results in either a net gain (MPS > MPB) or net loss (MPB > MPS) of muscle mass. During basal, postabsorptive conditions (overnight fast), the rate of MPB exceeds the rate of MPS, resulting in net loss of muscle protein. Meal intake compensates for these losses because protein/amino acids and insulin stimulate MPS and inhibit MPB, resulting in net muscle protein accretion. Exercise (both resistance and endurance) stimulates MPS, and the net protein balance after exercise in the postprandial state exceeds the net balance after meal intake alone. Conversely, muscle disuse suppresses MPS and initially (within the first few days) upregulates but then downregulates markers of proteolysis and blunts the anabolic response to hyperaminoacidemia/protein ingestion. There are no established sex differences in the regulation of muscle protein turnover in young and middle-aged adults. Bottom: aging is associated with an increase in the basal rate of MPS in women (but not in men) and both men and women have a blunted MPS response to amino acids/protein and exercise but the reduction is greater in women than in men. Potential differences in MPB between older men and women have yet to be evaluated.

Fig. 2.

Muscle mass throughout life in men and women. At any given total body weight, girls and women have less muscle mass than boys and men. The difference is evident from infancy but becomes most marked after puberty (when boys experience an accelerated growth spurt) and persists into old age. The aging-associated loss of muscle mass, which starts in midlife, coincides with the onset of menopause in women, is accelerated during the transition into menopause, and then proceeds at a slower rate in women than in men. Advanced age (∼80 yr and older), periods of inactivity, and disease accelerate the catabolic process.