Targeting ERRs to counteract age-related muscle atrophy associated with physical inactivity: a pilot study.
This pilot study investigated whether targeting estrogen-related receptors (ERRs) could help counteract muscle atrophy associated with physical inactivity in older women. Twenty women undergoing hip replacement surgery were divided into active (n=10) and inactive (n=10) groups based on self-reported activity levels. Muscle biopsies were collected during surgery and analyzed for key proteins involved in mitochondrial function and oxidative stress. Active women showed greater muscle fiber diameter, better handgrip strength, and lower pain scores. Inactive women's muscle tissue showed higher NOX4 (an oxidative stress marker) and lower levels of SIRT1, PGC-1α, ERRα, and FNDC5 compared to active women. In a separate cell-culture experiment, myoblasts isolated from inactive women's muscle tissue were treated with the ERR agonist SLU-PP-332. Treatment was associated with reduced NOX4, increased SIRT1, PGC-1α, ERRα, FNDC5, Akt, and Bcl-2 expression, decreased cytotoxicity, oxidative stress, and cellular senescence, increased glutathione levels, and enhanced myotube formation. The authors suggest ERR activation as a potential therapeutic strategy for muscle atrophy, while acknowledging that the small sample size, self-reported activity classification, and in vitro nature of the intervention data limit conclusions.