Biology subjects

Critchlow, A.

Publications and source records attributed to Critchlow, A..

3 recordsLinked to original sources

bioRxiv2026

Muscle mass and denervation explain variability in maximal power and rapid force across the adult female lifespan

BackgroundDynamic power declines earlier across the lifespan and shows a more pronounced and complex pattern than isometric strength, particularly in ageing females. However, the functional, skeletal muscle and molecular mechanisms underpinning power loss across the female lifespan remain to be collectively examined. MethodsEighty-six females aged 18-80 years and stratified per decade of age completed a series of maximal voluntary knee extensions to construct torque-velocity and power-velocity relationships of the quadriceps. Data points corresponding to >95% maximal power were selected for the evaluation of rate of torque development (RTD) and quadriceps surface electromyography (EMG). Outcomes were quantified within discrete 50ms time bins from torque onset to +200ms and included absolute RTD, RTD normalised to peak force, and EMG amplitude and rate of rise normalised to the maximal compound action potential. Quadriceps morphology was assessed via computed tomography, and a vastus lateralis muscle biopsy was collected to assess markers of denervation and expression of genes associated with the neuromuscular junction and calcium-handling transcriptome. ResultsAgeing led to linear reductions in maximal power (-1.39 {+/-} 0.01% p/year), torque (-0.98 {+/-} 0.13% p/year) and velocity (-0.38 {+/-} 0.01% p/year) (all p < 0.05). Quadriceps skeletal muscle CSA attenuated power loss by [~]40% (p < 0.001), largely through reduction of the decline in torque ([~]50%), with no effect on the decline in velocity. During early time bins, older females generated higher relative RTD accompanied by higher EMG amplitude, whereas during later time bins, older females generated less absolute and relative RTD accompanied by lower EMG amplitude and rate of rise (all p < 0.05). Ageing increased neural cell adhesion molecule (NCAM) positive fibres and fibrosis (both p < 0.05). The presence of NCAM{square} fibres was associated with attenuation of the age-related decline in maximal power ([~]15%), torque ([~]35%) and velocity ([~]60%), suggesting that NCAM{square} fibre prevalence may partially explain the observed age associations. Within the neuromuscular junction transcriptome, ageing reduced acetylcholinesterase and increased laminin alpha-2 and muscle-specific kinase (all FDR < 0.05), whereas lesser changes were observed within the calcium-handling transcriptome. ConclusionsSkeletal muscle CSA explains [~]40% of the age-related decline in quadriceps dynamic maximal power across the female lifespan, whereas a neurodegenerative profile mainly evidenced by age-related changes in voluntary neural drive, denervation and markers of neuromuscular junction instability further contribute to the decline.

physiology↗

bioRxiv2024

The transcriptomic signature of age and sex is not conserved in human primary myocytes

BackgroundHuman primary muscle cell (HPMC) lines derived from skeletal muscle biopsies are potentially powerful tools to interrogate the molecular pathways underlying fundamental muscle mechanisms. HPMCs retain their genome in culture, but many endogenous circulating factors are not present in the in vitro environment, or at concentrations that do not mirror physiological levels. To address the assumption that HPMCs are valid models of age and sex-specificity in human muscle research, we examined to what extent HPMC lines retain their source phenotype in culture. MethodsBiopsies from the vastus lateralis muscle were collected from ten males aged 18-30, ten females aged 18-30 and ten males aged 60-75 recruited from a general, healthy population. A portion of the muscle was used for the establishment of 30 individual HMPC lines. The remaining sample was immediately snap frozen and stored for further analysis. RNA was extracted from muscle tissue samples and their corresponding, fully differentiated HMPCs and analysed using RNA Sequencing. To compare their transcriptomic signature, principal component analysis (PCA), differential expression analysis, single-cell deconvolution and pathway enrichment analysis were conducted in R. ResultsA comparison of the transcriptomic signature of 30 human muscle biopsies and their corresponding HPMCs indicated a near-complete lack of retention of the genes and pathways differentially regulated in vivo when compared to their in vitro equivalent, with the exception of several genes encoded on the Y-chromosome. ConclusionsThe diversity of resident cell populations in muscle tissue and the lack of sex- and age-dependent circulating factors in the cellular milieu likely contribute to these observations, which call for caution when using HPMCs as an experimental model of human muscle sex or age.

cell biology↗

bioRxiv2024

The effect of age and sex hormones on female neuromuscular function across the adult lifespan

Neuromuscular ageing is characterized by neural and/or skeletal muscle degeneration that decreases maximal force and power. Female neuromuscular ageing occurs earlier in life compared to males, potentially due to sex hormone changes during the menopausal transition. We quantified neuromuscular function in 88 healthy females represented equally over each decade from 18-80 years of age and investigated the potential role of decreased ovarian hormone concentrations following menopause. Neuromuscular assessment included quadriceps maximal voluntary and evoked isometric torque and surface electromyography measurements, plus one-repetition maximum leg press. Voluntary and evoked torques and one-repetition maximum decreased non-linearly with age, with accelerated reductions starting during the fourth decade. An absence of changes in volitional recruitment of existing quadriceps motor units and Ia afferent facilitation of spinal motoneurons suggests that functional decline was largely mediated by impairment in intrinsic muscle function and/or neuromuscular transmission. Maximal muscle compound action potential amplitude decreased with increasing age for rectus femoris only, indicating increased vulnerability to neuromuscular degeneration compared to vastus lateralis and medialis. In postmenopausal females, some variance in data was explained by inter-individual differences in body composition and physical activity level, however, changes in total or free concentrations of oestrogen, progesterone and/or testosterone were correlated with all age-related decreases in neuromuscular variables. In conclusion, we demonstrate an accelerated onset of neuromuscular degeneration of muscular origin around menopause onset, which is associated with changes in sex hormone concentrations. Interventions aimed at mitigating declines in ovarian hormones and their subsequent effects on neuromuscular function postmenopause should be further explored. Key PointsO_LINeuromuscular deterioration with age is associated with poor physical function and quality of life in older adults, but female-specific trajectories and mechanisms remain unclear. C_LIO_LIThis study is the first to map neuromuscular function across each decade of the adult lifespan in 88 healthy females from 18 to 80 years old and to examine the potential role of hormonal changes after menopause C_LIO_LIWe show an accelerated reduction in neuromuscular function, primarily of muscular origin, that occurs between 40 and 50 years of age, coinciding with the onset of menopause. C_LIO_LIIn postmenopausal females, age-related reductions in neuromuscular function can be explained by differences in body composition, physical activity, and sex hormone concentrations. C_LIO_LIThese findings help us better understand the factors that contribute to the loss of neuromuscular function with age in females, enabling the identification of potential therapeutic interventions to prolong the female health span. C_LI

physiology↗