Myostatin Inhibition Enhances the Effects of Exercise on Performance and Metabolic Outcomes in Aged Mice

The objective of this study was to examine the effects of short-term exercise training, myostatin inhibition (PF-354), and exercise + PF-354, all relative to a vehicle control, on performance and metabolic measures in 24-month-old mice. At study termination, PF-354 – treated mice exhibited signifi cantly greater muscle weights. Performance measures revealed that exercise + PF-354 increased treadmill running time and distance to exhaustion (more than twofold) and increased habitual activity. Measures of strength were not different; however, all treatment groups demonstrated more than 30% reductions in muscle fatigue. Metabolic measures showed that basal metabolic rates were higher in PF-354 – and exercise + PF-354 – treated mice, and exercise and exercise + PF-354 groups exhibited signifi cantly greater insulin sensitivity. PF-354 was associated with decreased Smad3 phosphorylation and increased peroxisome proliferator-activated receptor gamma coactivator-1 a expression and, similar to exercise, decreased MuRF-1. The data suggest that the combination of exercise training and myostatin blockade may signifi cantly improve physical function and whole-body metabolism in older individuals.