Age-related changes in isolated mouse skeletal muscle function are dependent on sex, muscle, and contractility mode

Abstract

The present study aimed to simultaneously examine the age-related, muscle-specific, sex-specific, and contractile mode-specific changes in isolated mouse skeletal muscle function and morphology across multiple ages. Measurements of mammalian muscle morphology, isometric force and stress (force/cross-sectional area), absolute and normalized (power/muscle mass) work-loop power across a range of contractile velocities, fatigue resistance, and myosin heavy chain (MHC) isoform concentration were measured in 232 isolated mouse (CD-1) soleus, extensor digitorum longus (EDL), and diaphragm from male and female animals aged 3, 10, 30, 52, and 78 wk. Aging resulted in increased body mass and increased soleus and EDL muscle mass, with atrophy only present for female EDL by 78 wk despite no change in MHC isoform concentration. Absolute force and power output increased up to 52 wk and to a higher level for males. A 23–36% loss of isometric stress exceeded the 14–27% loss of power normalized to muscle mass between 10 wk and 52 wk, although the loss of normalized power between 52 and 78 wk continued without further changes in stress ( P > 0.23). Males had lower power normalized to muscle mass than females by 78 wk, with the greatest decline observed for male soleus. Aging did not cause a shift toward slower contractile characteristics, with reduced fatigue resistance observed in male EDL and female diaphragm. Our findings show that the loss of muscle quality precedes the loss of absolute performance as CD-1 mice age, with the greatest effect seen in male soleus, and in most instances without muscle atrophy or an alteration in MHC isoforms.