Age-related differences in skeletal muscle protein synthesis: relation to markers of immune activation

Abstract

Aging is associated with decreased skeletal muscle mass and function. These changes are thought to derive, in part, from a reduction in skeletal muscle protein synthesis. Although some studies have shown reduced postabsorptive muscle protein synthesis with age in humans, recent studies have failed to find an age effect. In addition to this disparity, few studies have attempted to characterize the hormonal factors that may contribute to changes in protein synthesis. Thus we examined the effect of age on skeletal muscle protein metabolism, with a specific emphasis on myosin heavy chain (MHC) protein, and the relationship of protein synthesis rates to plasma hormone levels. We measured body composition, muscle function, muscle protein synthesis, MHC and actin protein content, MHC isoform distribution, and plasma concentrations of cytokines and insulin-like growth factor-I (IGF-I) in 7 young [29 +/- 2 (SE) yr] and 15 old (72 +/- 1 yr; P < 0.01) volunteers. Mixed-muscle (-19%; P = 0.11), MHC (-22%; P = 0.08), and nonmyofibrillar (-17%; P = 0.10) protein synthesis all tended to be lower in old volunteers. Old volunteers were characterized by increased circulating tumor necrosis factor-alpha receptor II (P < 0.05) and reduced IGF-I (P < 0.01). In addition, plasma C-reactive protein, interleukin-6, and tumor necrosis factor-alpha receptor II concentrations were negatively related to mixed-muscle and MHC protein synthesis rates (range of r values: -0.422 to -0.606; P < 0.05 to <0.01). No differences in MHC or actin protein content were found. Old volunteers showed reduced (P < 0.05) MHC IIx content compared with young volunteers but no differences in MHC I or IIa. Our data show strong trends toward reduced postabsorptive muscle protein synthesis with age. Moreover, reduced muscle protein synthesis rates were related to increased circulating concentrations of several markers of immune activation.