Pilotto, A. M. | bioRxiv Science

bioRxiv2025

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.

neuroscience↗

bioRxiv2024

Human skeletal muscle possesses an epigenetic memory of high intensity interval training

INTRODUCTIONHuman skeletal muscle displays an epigenetic memory of resistance exercise induced by hypertrophy. It is unknown, however, whether high-intensity interval training (HIIT) also evokes an epigenetic muscle memory. This study employed repeated training intervention interspersed with a detraining period to assess epigenetic memory of HIIT. METHODSTwenty healthy subjects (25{+/-}5yrs) completed two HIIT interventions (training and retraining) lasting 2 months, separated by 3 months of detraining. Measurements at baseline, after training, detraining and retraining included maximal oxygen consumption ([V]O2max). Vastus lateralis biopsies were taken for genome-wide DNA methylation and targeted gene expression analyses. RESULTS: [V]O2max improved during training and retraining (p<0.001) without differences between interventions (p>0.58). Thousands of differentially methylated positions (DMPs) predominantly demonstrated a hypomethylated state after training, retained even after 3-months exercise cessation and into retraining. Five genes; ADAM19, INPP5a, MTHFD1L, CAPN2, SLC16A3 possessed differentially methylated regions (DMRs) with retained hypomethylated memory profiles and increased gene expression. The retained hypomethylation during detraining was associated with an enhancement in expression of the same genes even after 3 months of detraining. SLC16A3, INPP5a, CAPN2 are involved in lactate transport and calcium signaling. CONCLUSIONSDespite similar physiological adaptations between training and retraining, memory profiles were found at epigenetic and gene expression level, characterized by retained hypomethylation and increased gene expression after training into long-term detraining and retraining. These genes were associated with calcium signaling and lactate transport. Whilst significant memory was not observed in physiological parameters, our novel findings indicate that human skeletal muscle possesses an epigenetic memory of HIIT.

physiology↗