Microgravity affects the nervous system and aging in <i>C. elegans</i> through reduced tactile stimulation

ABSTRACT Space travel is becoming accessible, yet our understanding of how space environment and microgravity (µG) affect biology, physiology, and health remains incomplete. We investigated µG effects on neuromuscular development and aging in Caenorhabditis elegans . Nematodes in µG 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 µG 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 µG-induced body length reduction and changes in extracellular matrix gene expression. µG conditions suppressed mechanoreceptor genes, suggesting multiple mechanosensory systems are affected. Physical stimulation through culture medium with small beads in space mitigated many µG-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. SIGNIFICACE We found that microgravity (µG) conditions suppress the expression of multiple mechanoreceptor genes in Caenorhabditis elegans , indicating that several mechanosensory systems are affected during spaceflight. Importantly, reintroducing physical stimulation by adding small beads to the culture medium in space partially reversed many of these µG-induced gene expression changes. This intervention also mitigated neuromuscular defects and aging-related phenotypes observed under µG conditions. Collectively, these findings underscore the essential role of mechanical stimuli in preserving neuromuscular integrity during space missions and suggest that restoring tactile input may be a promising strategy to counteract the health risks associated with reduced tactile stimulation during prolonged spaceflights.