Higashitani, A.; Moon, J.-H.; Hwang, J.-I.; Higashitani, N.; Hashizume, T.; Abu, A. A.; Ooizumi, K.; Sazuka, I.; Hashizume, Y.; Umehara, M.; Alcantara, A. V.; Kim, B.-s.; Etheridge, T.; Szewczyk, N. J.; Abe, T.; Lee, J. I.; Higashibata, A.

Space travel is becoming accessible, yet our understanding of how space environment and microgravity (uG) affect biology, physiology, and health remains incomplete. We investigated uG effects on neuromuscular development and aging in Caenorhabditis elegans. Nematodes in uG showed downregulation of genes related to synaptic signaling, dopamine response, locomotion, and cuticle development, with impaired synaptic vesicle dynamics, reduced motility, and shorter body lengths. Aged worms in uG showed decreased collagen gene expression, increased motor neuron defects, synaptic vesicle accumulation and decreased release, and mitochondrial morphology collapse in body wall muscles, indicating accelerated aging. MEC-4 mechanoreceptor was identified as a key mediator of uG-induced body length reduction and changes in extracellular matrix gene expression. uG conditions suppressed mechanoreceptor genes, suggesting multiple mechanosensory systems are affected. Physical stimulation through culture medium with small beads in space mitigated many uG-induced expression changes, including mechanoreceptors, neuromuscular defects, and aging-related phenotypes. These results highlight mechanical stimuli's role in maintaining neuromuscular integrity during spaceflight and suggest restoring tactile input could counter health risks from reduced stimulation in long-term space missions.