Sex specific differences in the response to short term muscle disuse in middle aged adults

Research on short term muscle disuse has demonstrated the numerous adverse effects it causes on skeletal muscle, primarily, reductions in function and mass, as well as in insulin sensitivity, mitochondrial function and muscle protein synthesis. However, the sex specific differences in how males and females respond to short term disuse requires further investigation. We hypothesized that males would have greater reductions in MPS, mitochondrial function and leg strength compared to females. Sixteen healthy, middle-aged adults (7 males; 59.0±1.7 yr; BMI 29.7±1.3 kg·m -2 ; 9 females; 55.1±1.6 yr; BMI 28.9±1.0 kg·m -2 ) underwent 7 days of unilateral leg immobilization via unilateral lower limb suspension (ULLS). Muscle biopsies from the vastus lateralis were collected prior to and following immobilization (in both control [CON] and immobilized [IMM] legs). We applied the stable isotope tracer deuterium oxide to measure muscle protein synthesis (MPS), high resolution respirometry to assess mitochondrial function, and assessed leg strength changes via unilateral leg extension 1 repetition maximum (1RM). MPS was 33.0±10.2 % and 16.5±15.6 % lower in the IMM leg compared to the CON leg in females (p<0.05) and males (P=0.32) respectively during immobilization. Female MPS approached a trend to decline to a greater extent than male MPS during immobilization (P=0.14). Leg extension 1RM declined to the same extent in females 17.1±2.1 % and males 24.2±2.4 % after 7 days of IMM (both p<0.01) with no change in the CON leg (P>0.05). Mitochondrial function was unaltered by IMM in both males and females (P>0.05). We conclude that males and females experience similar reductions in leg strength following short-term disuse, however, females tended to have a greater reduction in MPS than males. NIH R01AG064386; NIH P30AG044271 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.