Sex disparities of human neuromuscular decline in older humans.

Females typically live longer than males but, paradoxically, spend a greater number of later years in poorer health. The neuromuscular system is a critical component of the progression to frailty, and motor unit (MU) characteristics differ by sex in healthy young individuals and may adapt to ageing in a sex-specific manner due to divergent hormonal profiles. The purpose of this study was to investigate sex differences in vastus lateralis (VL) MU structure and function in early to late elderly humans. Intramuscular electromyography signals from 50 healthy older adults (M/F: 26/24) were collected from VL during standardized submaximal contractions and decomposed to quantify MU characteristics. Muscle size and neuromuscular performance were also measured. Females had higher MU firing rate (FR) than males (P = 0.025), with no difference in MU structure or neuromuscular junction transmission (NMJ) instability. All MU characteristics increased from low- to mid-level contractions (P < 0.05) without sex × level interactions. Females had smaller cross-sectional area of VL, lower strength and poorer force steadiness (P < 0.05). From early to late elderly, both sexes showed decreased neuromuscular function (P < 0.05) without sex-specific patterns. Higher VL MUFRs at normalized contraction levels previously observed in young are also apparent in old individuals, with no sex-based difference of estimates of MU structure or NMJ transmission instability. From early to late elderly, the deterioration of neuromuscular function and MU characteristics did not differ between sexes, yet function was consistently greater in males. These parallel trajectories underscore the lower initial level for older females and may offer insights into identifying critical intervention periods. KEY POINTS: Females generally exhibit an extended lifespan when compared to males, yet this is accompanied by a poorer healthspan and higher rates of frailty. In healthy young people, motor unit firing rate (MUFR) at normalized contraction intensities is widely reported to be higher in females than in age-matched males. Here we show in 50 people that older females have higher MUFR than older males with little difference in other MU parameters. The trajectory of decline from early to late elderly does not differ between sexes, yet function is consistently lower in females. These findings highlight distinguishable sex disparities in some MU characteristics and neuromuscular function, and suggest early interventions are needed for females to prevent functional deterioration to reduce the ageing health-sex paradox.