Biology subjects

Porcelli, S.

Publications and source records attributed to Porcelli, S..

4 recordsLinked to original sources

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↗

bioRxiv2025

Sex differences in durability following heavy intensity cycling exercise in trained athletes

The ability to withstand impairments in key physiological variables during prolonged exercise, known as durability, is emerging as an important factor in cycling performance. While females possess physiological characteristics that could confer enhanced durability relative to males, little is known about potential sex differences. 32 trained cyclists (16 males and 16 females) performed an incremental exercise test to exhaustion in visit 1. In visit 2 they performed 90 minutes of heavy intensity cycling (HVY) at 110% of gas exchange threshold (GET), followed by another incremental test. During HVY, pulmonary gas exchange ([V]O2 and [V]CO2) ventilation ([V]E), heart rate (HR), rating of perceived exertion (RPE), near-infrared spectroscopy and electromyography were recorded, and blood lactate (BLa) was collected. Before and after HVY, maximal voluntary contraction (MVIC), voluntary activation (VA) and potentiated twitches (100Hz, 10Hz, Qtw{middle dot}pot) of the knee extensors were assessed. Power at GET (-16{+/-}15% vs -2{+/-}13%) and respiratory compensation point (-13{+/-}10% vs -6{+/-}9%) decreased more in males than females (P[≤]0.049). All aspects of neuromuscular function decreased from pre to post (all P<0.001), without sex differences (P[≥]0.096). During HVY, HR, [V]O2 (%peak), relative energy expenditure increased more in males (P[≤]0.008), whereas respiratory exchange ratio decreased more in females (P=0.001). BLa was higher in males than females (P=0.030). Muscle oxygen extraction was lower (P=0.004) and tissue saturation index higher for females (P<0.001). The smaller reductions exhibited by females in submaximal thresholds, associated with lesser derangements to oxidative efficiency, highlight the need to consider sex-specific training prescription and pacing strategies for long duration events. Key PointsO_LIDurability, as measured by the reduction in incremental exercise test outcomes, is relatively unexplored in females compared to males, despite physiological sex differences that might confer a female advantage. C_LIO_LIAfter 90 minutes of heavy intensity cycling, males demonstrated greater reductions in the power outputs associated with gas exchange threshold and respiratory compensation point. C_LIO_LIThe maximal rate of oxygen consumption and incremental test peak power output decreased similarly in both sexes. C_LIO_LIThese changes are associated with greater carbohydrate metabolism and losses of efficiency in males, whereas no sex differences were observed in neuromuscular fatigue. C_LI

physiology↗

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↗

bioRxiv2023

Boosting bactericidal immunity of a recombinant Mycobacterium smegmatis strain via zinc-dependent ribosomal proteins

Tuberculosis (TB) continues to be a major global health burden and kills over a million people annually. New immunization strategies are required for the development of an efficacious TB vaccine that can potentially induce sterilizing immunity. In this study, we first confirmed that various strains of the IKEPLUS vaccine confer a higher survival benefit than BCG in a murine model of intravenous Mycobacterium tuberculosis (Mtb) infection. We have shown that there was a significant increase in the expression of the Rv0282 when IKEPLUS was grown in low zinc and iron containing Sauton medium. We confirmed on biofilm assays that zinc plays a vital role in the growth and formation of Mycobacterium smegmatis (M. smegmatis) biofilms. IKEPLUS grown in low zinc media led to better protection of mice after intravenous challenge with very high dosage of Mtb. We also showed that various variants of IKEPLUS induced apoptotic cell-death of infected macrophages at a higher rate than wild type M. smegmatis. We next attempted to determine if zinc containing ribosomal proteins such as rpmb2 could contribute to protective efficacy against Mtb infection. Since BCG has an established role in anti-mycobacterial efficacy, we boosted BCG vaccinated mice with rmpb2 but this did not lead to an increment in the protection mediated by BCG.

microbiology↗