Abstract Head‐down tilt bedrest (HDBR) models the effects of mechanical unloading on neuromuscular function. The efficacy of exercise in preserving motor unit (MU) function in older adults during HDBR remains unclear. This study investigated the effects of 14‐day HDBR on MU properties in older adults and the protective role of exercise. Fifteen participants aged 55–65 years were randomized to Control group ( n = 7, passive mobilization only) or Exercise group ( n = 8, daily mixed resistance and aerobic training) during 14 days of strict HDBR. Knee extensor strength and leg lean mass were measured, and intramuscular EMG was used to record MU firing rate (MUFR), MU potential (MUP) area and complexity, and neuromuscular junction (NMJ) transmission instability during contractions normalized to 25% of pre‐bedrest strength. Plasma C‐terminal agrin fragment (CAF) was also measured. Following HDBR, knee extensor strength decreased more in the Control group (−33.4 N m; P < 0.001; ∼18% decrease) than in the Exercise group (−14.5 N m; P = 0.027; ∼8% decrease; interaction P = 0.045). Leg lean mass decreased similarly in both groups (−0.418 kg; P = 0.013). Exercise prevented the decrease in MUP area observed in Controls (−65 mV·ms, P = 0.240 vs. −253 mV·ms, P < 0.001) and led to a reduction in MUFR (−1.05 pulses/s, P < 0.001) not seen in Controls. NMJ transmission stability and CAF levels were unchanged in both groups. HDBR reduced leg lean mass and strength. Exercise attenuated declines in strength and MUP area, likely by preserving muscle fibre size despite reduced MUFR, without evidence of NMJ disruption. Exercise effectively attenuates neuromuscular decrements following HDBR in older adults, with implications for clinical care and spaceflight.
St‐Martin et al. (Fri,) studied this question.