Microgravity-induced muscle atrophy in rodent and human models

Exposure to microgravity leads to severe skeletal muscle atrophy, particularly in muscles that act to maintain posture against gravity, and results in significant reductions in muscle mass, cross-sectional area, and contractile force. This review examines the physiological and cellular response of microgravity in both rodent and human models, emphasizing shifts in muscle fiber type, altered contractile properties, and molecular adaptations. Specifically, rodents exhibit rapid atrophy, predominantly in slow-twitch fibers, whereas human studies suggest greater intersubject variability, with both slow- and fast-twitch fibers significantly affected. Cellular responses due to microgravity reveal mitochondrial dysfunction, oxidative stress, and impaired synaptogenesis as key contributors to muscle degradation. Further, despite exercise countermeasures, spaceflight induced atrophy remains a significant challenge. Understanding these mechanisms is crucial for developing therapeutics to mitigate musculoskeletal degradation during prolonged spaceflight. The aim of this review is to compare the effects of microgravity-induced skeletal muscle atrophy across rodent, human, and in vitro models, highlight species differences in responses, and evaluate Reactive Oxygen Species (ROS)-mediated mechanisms that underlie muscle loss throughout spaceflight.