Microgravity accelerates skeletal muscle degeneration: Functional and transcriptomic insights from an ISS muscle lab-on-chip model

Microgravity accelerates skeletal muscle degeneration, mimicking aspects of aging, yet its effects on muscle cell function remain underexplored. Using a muscle lab-on-chip model onboard the International Space Station (ISS), we examined 3D-bioengineered myobundles derived from young and older adult donors under microgravity. Electrical stimulation applied intermittently to the myobundles revealed reduced contraction magnitude in microgravity and decreased protein levels of myosin heavy chain 7, a main isoform in slow-twitch muscle fibers. Transcriptomic profiling revealed active myogenesis across ground and spaceflight samples, but younger electrically stimulated myobundles displayed enhanced mitochondrial-related gene expression in microgravity, while older and non-electrically stimulated myobundles were less responsive. Comparative analysis between young and older derived myobundles identified 86 muscle-specific age-associated genes altered in microgravity, linked to inflammation, mitochondrial dysfunction, and cellular stress. These findings highlight a unique age-related molecular response in microgravity and underscores electrical stimulation as a potential countermeasure. These insights advance our understanding of muscle aging and degeneration in microgravity, guiding future therapeutic strategies.