Motor unit behaviour adaptations across the lifespan: sex differences in young, middle-aged and old adults

Ageing is associated with neuromuscular decline, and emerging evidence suggests that sex may influence the time course of motor unit adaptations. This study examined age- and sex-related differences in motor unit firing behaviour across young (YG), middle-aged (MA), and older adults (OLD), by integrating high-density EMG motor unit analysis with muscle morphology and daily physical activity measurements. The analysis of single motor unit activity during submaximal isometric contractions of the vastus lateralis revealed that older adults had lower firing rates and a reduced capacity to modulate discharge frequency during force-increasing contractions. In the YG and MA groups, females showed higher motor unit firing rates and variability than males, while in OLD these sex differences were no longer present. Females also demonstrated a steeper decline in firing rate modulation between MA and OLD. Reductions in muscle cross-sectional area and thickness were similar between sexes. Physical activity levels declined with age in both sexes. These findings reveal distinct, sex-specific trajectories of neuromuscular ageing, with females showing greater motor neuron function decline between MA and OLD, in the absence of sex-related differences in the rate of morphological deterioration. The attenuation of sex differences in older age suggests a convergence of neuromuscular profiles with ageing. While physical activity may contribute to the observed sex-specific patterns, other mechanisms related to hormonal shifts warrant further investigation. These insights underscore the importance of considering age and sex in the study of motor control and in the development of targeted interventions to preserve muscle function across the lifespan.