Muscle disuse alters skeletal muscle contractile function at the molecular and cellular levels in older adult humans in a sex‐specific manner

Key points Muscle disuse that accompanies ageing and chronic disease may hasten physical disability by impairing skeletal muscle contractility. We compared skeletal muscle contractile function at the various anatomic levels between two groups of older men and women matched for sex, health status and body size, of which one group was habitually active and the other inactive. Muscle disuse reduced force generation, power output and contractile velocity in single muscle fibres, with differential adaptations in some parameters in men and women. Sex‐specific cellular phenotypes were explained by differential adaptations in molecular muscle function. Moreover, aspects of the molecular functional phenotype apparent in inactive women could be recapitulated in vitro by chemical modification of protein thiols. Our results identify molecular and cellular contractile dysfunction in skeletal muscle that may contribute to reduced physical function with muscle disuse, with sex‐specific differences that may explain a greater disposition towards disability in women. Physical inactivity that accompanies ageing and disease may hasten disability by reducing skeletal muscle contractility. To characterize skeletal muscle functional adaptations to muscle disuse, we compared contractile performance at the molecular, cellular and whole‐muscle levels in healthy active older men and women (n = 15) and inactive older men and women with advanced‐stage, symptomatic knee osteoarthritis (OA) (n = 16). OA patients showed reduced (P