Sex Differences in Neuromuscular Aging: The Role of Sex Hormones.

Males and females experience different trajectories of neuromuscular function across the lifespan, with females demonstrating accelerated deconditioning in later life. We hypothesize that the menopause is a critical period in the female lifespan, during which the dramatic reduction in sex hormone concentrations negatively impacts synaptic input to the motoneuron pool, as well as motor unit discharge properties.

The reproducibility of dendritic cell and T cell counts to a 30-min high-intensity cycling protocol as a tool to highlight overtraining.

Heavy training has been reported to be immunosuppressive in athletes and lead to blunted cortisol responses to exercise. Cortisol elevates the number of dendritic cells (DCs), key antigen-presenting cells that interact with T cells to initiate an immune response. Reproducible cortisol responses to a 30-min cycle test have been identified but were based on percentage of work rate maximum. To ensure physiological consistency, submaximal anchors, that is, ventilatory threshold (VT1 ) should prescribe intensity. This study aims to assess the reproducibility of the DC and T cell responses to an adapted stress test to assess its usefulness in assessing DC dysfunction with intensified training. Twelve males cycled for 1 min at 20% below VT1 and 4 min at 50% between VT1 and V ̇ O 2 max ${\dot{V}}_{{{\mathrm{O}}}_{\mathrm{2}}\max }$ , for 30 min (20/50), with blood samples pre-, post- and 30 min post-exercise. This was repeated twice, 2-7 days apart. Flow cytometry assessed total DCs, plasmacytoid DCs, myeloid DCs, total T cells, T helper cells and T cytotoxic cells. No significant trial or interaction effects were found for any variable. A significant main effect of time for all variables was found; immune cells increased from pre- to post-exercise and decreased to baseline 30 min post-exercise, apart from plasmacytoid DCs, which remained elevated 30 min post-exercise. Intraclass correlation coefficients showed overall good-to-excellent reliability for all immune cells, with smallest real difference and Bland-Altman analysis verifying high reproducibility between trials. These results suggest that the 20/50 exercise test induces reproducible DC and T cell count changes, which, implemented before and after a period of intensified training, may highlight the negative states of overtraining.

Menstrual Cycle Associated Alteration of Vastus Lateralis Motor Unit Function.

BACKGROUND: Estrogen and progesterone are the primary female sex hormones and have net excitatory and inhibitory effects, respectively, on neuronal function. Fluctuating concentrations across the menstrual cycle has led to several lines of research in relation to neuromuscular function and performance; however evidence from animal and cell culture models has yet to be demonstrated in human motor units coupled with quantification of circulating hormones. Intramuscular electromyography was used to record motor unit potentials and corresponding motor unit potential trains from the vastus lateralis of nine eumenorrheic females during the early follicular, ovulation and mid luteal phases of the menstrual cycle, alongside assessments of neuromuscular performance. Multi-level regression models were applied to explore effects of time and of contraction level. Statistical significance was accepted as p < 0.05. RESULTS: Knee extensor maximum voluntary contraction, jump power, force steadiness, and balance did not differ across the menstrual phases (all p > 0.4). Firing rate of low threshold motor units (10% maximum voluntary contraction) was lower during the ovulation and mid luteal phases (ß = - 0.82 Hz, p < 0.001), with no difference in motor unit potentials analysed from 25% maximum voluntary contraction contractions. Motor unit potentials were more complex during ovulation and mid luteal phase (p < 0.03), with no change in neuromuscular junction transmission instability (p > 0.3). CONCLUSIONS: Assessments of neuromuscular performance did not differ across the menstrual cycle. The suppression of low threshold motor unit firing rate during periods of increased progesterone may suggest a potential inhibitory effect and an alteration of recruitment strategy; however this had no discernible effect on performance. These findings highlight contraction level-dependent modulation of vastus lateralis motor unit function over the eumenorrheic cycle, occurring independently of measures of performance.

Lymphocyte and dendritic cell response to a period of intensified training in young healthy humans and rodents: A systematic review and meta-analysis.

Background: Intensified training coupled with sufficient recovery is required to improve athletic performance. A stress-recovery imbalance can lead to negative states of overtraining. Hormonal alterations associated with intensified training, such as blunted cortisol, may impair the immune response. Cortisol promotes the maturation and migration of dendritic cells which subsequently stimulate the T cell response. However, there are currently no clear reliable biomarkers to highlight the overtraining syndrome. This systematic review and meta-analysis examined the effect of intensified training on immune cells. Outcomes from this could provide insight into whether these markers may be used as an indicator of negative states of overtraining. Methods: SPORTDiscus, PUBMED, Academic Search Complete, Scopus and Web of Science were searched until June 2022. Included articles reported on immune biomarkers relating to lymphocytes, dendritic cells, and cytokines before and after a period of intensified training, in humans and rodents, at rest and in response to exercise. Results: 164 full texts were screened for eligibility. Across 57 eligible studies, 16 immune biomarkers were assessed. 7 were assessed at rest and in response to a bout of exercise, and 9 assessed at rest only. Included lymphocyte markers were CD3+, CD4+ and CD8+ T cell count, NK cell count, NK Cytolytic activity, lymphocyte proliferation and CD4/CD8 ratio. Dendritic cell markers examined were CD80, CD86, and MHC II expression. Cytokines included IL-1ß, IL-2, IL-10, TNF-α and IFN-γ. A period of intensified training significantly decreased resting total lymphocyte (d= -0.57, 95% CI -0.30) and CD8+ T cell counts (d= -0.37, 95% CI -0.04), and unstimulated plasma IL-1ß levels (d= -0.63, 95% CI -0.17). Resting dendritic cell CD86 expression significantly increased (d = 2.18, 95% CI 4.07). All other biomarkers remained unchanged. Conclusion: Although some biomarkers alter after a period of intensified training, definitive immune biomarkers are limited. Specifically, due to low study numbers, further investigation into the dendritic cell response in human models is required.

How Lifestyle Changes during the COVID-19 Global Pandemic Affected the Pattern and Symptoms of the Menstrual Cycle.

This research investigated the implications that the COVID-19 pandemic had on the menstrual cycle and any contributing factors to these changes. A questionnaire was completed by 559 eumenorrheic participants, capturing detail on menstrual cycle symptoms and characteristics prior to and during the COVID-19 pandemic lockdown period. Over half of all participants reported to have experienced lack of motivation (61.5%), focus (54.7%) and concentration (57.8%). 52.8% of participants reported an increase in cycle length. Specifically, there was an increase in the median cycle length reported of 5 days (minimum 2 days, maximum 32 days), with a median decrease of 3 days (minimum 2 days and maximum 17 days). A lack of focus was significantly associated with a change in menstrual cycle length (p = 0.038) reported to have increased by 61% of participants. Changes to eating patterns of white meat (increase p = 0.035, decrease p = 0.003) and processed meat (increase p = 0.002 and decrease p = 0.001) were significantly associated with a change in menstrual cycle length. It is important that females and practitioners become aware of implications of environmental stressors and the possible long-term effects on fertility. Future research should continue to investigate any long-lasting changes in symptoms, as well as providing education and support for females undergoing any life stressors that may implicate their menstrual cycle and/or symptoms.

Teachers' Perceptions and Experiences of Menstrual Cycle Education and Support in UK Schools.

The purpose of this study was 2-fold, to (1) explore current education provision in UK schools including barriers to menstrual cycle education and (2) assess the perceived support teachers received to deliver menstrual cycle education. Seven hundred eighty-nine teachers (91% female) from all stages of school education in England (48%), Scotland (24%), Wales (22%) and Northern Ireland (6%) completed an online survey. The survey captured information on menstrual education in schools, teacher's knowledge and confidence of the menstrual cycle, support provided to teachers, provision of menstrual products in school and perceived impact of the menstrual cycle on young people in school. Four hundred ninety-eight teachers reported lessons were provided on the menstrual cycle (63%), predominantly delivered within personal, social, health and economic or science subjects, with over half of the lessons focusing on the biology (56%) or provision of menstrual products (40%) rather than lived experiences (14%). Teachers perceived the menstrual cycle affected participation in PE (88%), pupil confidence (88%), school attendance (82%) and attitude and behavior (82%). Overall, 80% of teachers felt receiving training would be beneficial to improve menstrual education. The results highlight education is scientifically focused, with less education on management of symptoms or lived experiences. Teachers also perceive the menstrual cycle to influence multiple aspects of school attendance and personal performance. There is a need to address menstrual education provided in schools across the UK to help empower girls to manage their menstrual cycle, preventing a negative impact on health and school performance.

Neuromuscular recruitment strategies of the vastus lateralis according to sex.

AIM: Despite males typically exhibiting greater muscle strength and fatigability than females, it remains unclear if there are sex-based differences in neuromuscular recruitment strategies e.g. recruitment and modulation of motor unit firing rate (MU FR) at normalized forces and during progressive increases in force. METHODS: The study includes 29 healthy male and 31 healthy female participants (18-35 years). Intramuscular electromyography (iEMG) was used to record individual motor unit potentials (MUPs) and near-fibre MUPs from the vastus lateralis (VL) during 10% and 25% maximum isometric voluntary contractions (MVC), and spike-triggered averaging was used to obtain motor unit number estimates (MUNE) of the VL. RESULTS: Males exhibited greater muscle strength (P < .001) and size (P < .001) than females, with no difference in force steadiness at 10% or 25% MVC. Females had 8.4% and 6.5% higher FR at 10% and 25% MVC, respectively (both P < .03), while the MUP area was 33% smaller in females at 10% MVC (P < .02) and 26% smaller at 25% MVC (P = .062). However, both sexes showed similar increases in MU size and FR when moving from low- to mid-level contractions. There were no sex differences in any near-fibre MUP parameters or in MUNE. CONCLUSION: In the vastus lateralis, females produce muscle force via different neuromuscular recruitment strategies to males which is characterized by smaller MUs discharging at higher rates. However, similar strategies are employed to increase force production from low- to mid-level contractions. These findings of similar proportional increases between sexes support the use of mixed sex cohorts in studies of this nature.

Circulating testosterone and dehydroepiandrosterone are associated with individual motor unit features in untrained and highly active older men.

Long-term exercise training has been considered as an effective strategy to counteract age-related hormonal declines and minimise muscle atrophy. However, human data relating circulating hormone levels with motor nerve function are scant. The aims of the study were to explore associations between circulating sex hormone levels and motor unit (MU) characteristics in older men, including masters athletes competing in endurance and power events. Forty-three older men (mean ± SD age: 69.9 ± 4.6 years) were studied based on competitive status. The serum concentrations of dehydroepiandrosterone (DHEA), total testosterone (T) and estradiol were quantified using liquid chromatography mass spectrometry. Intramuscular electromyographic signals were recorded from vastus lateralis (VL) during 25% of maximum voluntary isometric contractions and processed to extract MU firing rate (FR), and motor unit potential (MUP) features. After adjusting for athletic status, MU FR was positively associated with DHEA levels (p = 0.019). Higher testosterone and estradiol were associated with lower MUP complexity; these relationships remained significant after adjusting for athletic status (p = 0.006 and p = 0.019, respectively). Circulating DHEA was positively associated with MU firing rate in these older men. Higher testosterone levels were associated with reduced MUP complexity, indicating reduced electrophysiological temporal dispersion, which is related to decreased differences in conduction times along axonal branches and/or MU fibres. Although evident in males only, this work highlights the potential of hormone administration as a therapeutic interventional strategy specifically targeting human motor units in older age.

Effect of menstrual cycle phase, menstrual irregularities and hormonal contraceptive use on anterior knee laxity and non-contact anterior cruciate ligament injury occurrence in women: a protocol for a systematic review and meta-analysis.

Exercising women report three to six times more ACL tears than men, which happen, in the majority of cases, with a non-contact mechanism. This sex disparity has, in part, been attributed to the differences in reproductive hormone profiles between men and women. Many studies have shown that anterior knee (AK) laxity and the rate of non-contact ACL injuries vary across the menstrual cycle, but these data are inconsistent. Similarly, several studies have investigated the potential protective effect of hormonal contraceptives on non-contact ACL injuries, but their conclusions are also variable. The purpose of this systematic review and meta-analysis is to, identify, evaluate and summarise the effects of endogenous and exogenous ovarian hormones on AK laxity (primary outcome) and the occurrence of non-contact ACL injuries (secondary outcome) in women. We will perform a systematic search for all observational studies conducted on this topic. Studies will be retrieved by searching electronic databases, clinical trial registers, author's personal files and cross-referencing selected studies. Risk of bias will be assessed using the Newcastle Ottawa Quality Assessment Scale for Cohort and Case-Control Studies. Certainty in the cumulative evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. The meta-analyses will use a Bayesian approach to address specific research questions in a more intuitive and probabilistic manner. This review is registered on the international database of prospectively registered systematic reviews (PROSPERO; CRD42021252365).

Lifelong exercise is associated with more homogeneous motor unit potential features across deep and superficial areas of vastus lateralis.

Motor unit (MU) expansion enables rescue of denervated muscle fibres helping to ameliorate age-related muscle atrophy, with evidence to suggest master athletes are more successful at this remodelling. Electrophysiological data has suggested MUs located superficially are larger than those located deeper within young muscle. However, the effects of ageing and exercise on MU heterogeneity across deep and superficial aspects of vastus lateralis (VL) remain unclear. Intramuscular electromyography was used to record individual MU potentials (MUPs) and near fibre MUPs (NFMs) from deep and superficial regions of the VL during 25% maximum voluntary contractions, in 83 males (15 young (Y), 17 young athletes (YA), 22 old (O) and 29 master athletes (MA)). MUP size and complexity were assessed using area and number of turns, respectively. Multilevel mixed effects linear regression models were performed to investigate the effects of depth in each group. MUP area was greater in deep compared with superficial MUs in Y (p<0.001) and O (p=0.012) but not in YA (p=0.071) or MA (p=0.653). MUP amplitude and NF MUP area were greater, and MUPs were more complex in deep MUPs from Y, YA and O (all p<0.05) but did not differ across depth in MA (all p>0.07). These data suggest MU characteristics differ according to depth within the VL which may be influenced by both ageing and exercise. A more homogenous distribution of MUP size and complexity across muscle depths in older athletes may be a result of a greater degree of age-related MU adaptations.

Influence of sex on the age-related adaptations of neuromuscular function and motor unit properties in elite masters athletes.

KEY POINTS: Masters athletes maintain high levels of activity into older age and allow an examination of the effects of aging dissociated from the effects of increased sedentary behaviour. Evidence suggests masters athletes are more successful at motor unit remodelling, the reinnervation of denervated fibres acting to preserve muscle fibre number, but little data are available in females. Here we used intramuscular electromyography to demonstrate that motor units sampled from the tibialis anterior show indications of remodelling from middle into older age and which does not differ between males and females. The age-related trajectory of motor unit discharge characteristic differs according to sex, with female athletes progressing to a slower firing pattern that was not observed in males. Our findings indicate motor unit remodelling from middle to older age occurs to a similar extent in male and female athletes, with discharge rates progressively slowing in females only. ABSTRACT: Motor unit (MU) remodelling acts to minimise loss of muscle fibres following denervation in older age, which may be more successful in masters athletes. Evidence suggests performance and neuromuscular function decline with age in this population, although the majority of studies have focused on males, with little available data on female athletes. Functional assessments of strength, balance and motor control were performed in 30 masters athletes (16 male) aged 44-83 years. Intramuscular needle electrodes were used to sample individual motor unit potentials (MUPs) and near-fibre MUPs in the tibialis anterior (TA) during isometric contractions at 25% maximum voluntary contraction, and used to determine discharge characteristics (firing rate, variability) and biomarkers of peripheral MU remodelling (MUP size, complexity, stability). Multilevel mixed-effects linear regression models examined effects of age and sex. All aspects of neuromuscular function deteriorated with age (P < 0.05) with no age × sex interactions, although males were stronger (P < 0.001). Indicators of MU remodelling also progressively increased with age to a similar extent in both sexes (P < 0.05), whilst MU firing rate progressively decreased with age in females (p = 0.029), with a non-significant increase in males (p = 0.092). Masters athletes exhibit age-related declines in neuromuscular function that are largely equal across males and females. Notably, they also display features of MU remodelling with advancing age, probably acting to reduce muscle fibre loss. The age trajectory of MU firing rate assessed at a single contraction level differed between sexes, which may reflect a greater tendency for females to develop a slower muscle phenotype.

Targeted genotype analyses of GWAS-derived lean body mass and handgrip strength-associated single-nucleotide polymorphisms in elite master athletes.

Recent large genome-wide association studies (GWAS) have independently identified a set of genetic loci associated with lean body mass (LBM) and handgrip strength (HGS). Evaluation of these candidate single-nucleotide polymorphisms (SNPs) may be useful to investigate genetic traits of populations at higher or lower risk of muscle dysfunction. As such, we investigated associations between six SNPs linked to LBM or HGS in a population of elite master athletes (MA) and age-matched controls as a representative population of older individuals with variable maintenance of muscle mass and function. Genomic DNA was isolated from buffy coat samples of 96 individuals [consisting of 48 MA (71 ± 6 yr, age-graded performance 83 ± 9%) and 48 older controls (75 ± 6 yr)]. SNP validation and sample genotyping were conducted using the tetra-primer amplification refractory mutation system (ARMS). For the three SNPs analyzed that were previously associated with LBM (FTO, IRS1, and ADAMTSL3), multinomial logistic regression revealed a significant association of the ADAMTSL3 genotype with %LBM (P < 0.01). For the three HGS-linked SNPs, neither GBF1 nor GLIS1 showed any association with HGS, but for TGFA, multinomial logistic regression revealed a significant association of genotype with HGS (P < 0.05). For ADAMTSL3, there was an enrichment of the effect allele in the MA (P < 0.05, Fisher's exact test). Collectively, of the six SNPs analyzed, ADAMTSL3 and TGFA showed significant associations with LBM and HGS, respectively. The functional relevance of the ADAMTSL3 SNP in body composition and of TGFA in strength may highlight a genetic component of the elite MA phenotype.

Greater maintenance of bone mineral content in male than female athletes and in sprinting and jumping than endurance athletes: a longitudinal study of bone strength in elite masters athletes.

We investigated longitudinal changes in tibia bone strength in master power (jumping and sprinting) and endurance (distance) athletes of both sexes. Bone mass but not cross-sectional moment of inertia was better maintained in power than endurance athletes over time, particularly in men and independent of changes in performance. OBJECTIVE: Assessment of effects of sex and athletic discipline (lower limb power events, e.g. sprint running and jumping versus endurance running events) on longitudinal changes in bone strength in masters athletes. METHODS: We examined tibia and fibula bone properties at distal (4% distal-proximal tibia length) and proximal (66% length) sites using peripheral quantitative computed tomography (pQCT) in seventy-one track and field masters athletes (30 male, 41 female, age at baseline 57.0 ± 12.2 years) in a longitudinal cohort study that included at least two testing sessions over a mean period of 4.2 ± 3.1 years. Effects of time, as well as time × sex and time × discipline interactions on bone parameters and calf muscle cross-sectional area (CSA), were examined. RESULTS: Effects of time were sex and discipline-dependent, even following adjustment for enrolment age, sex and changes in muscle CSA and athletic performance. Male sex and participation in power events was associated with better maintenance of tibia bone mineral content (BMC, an indicator of bone compressive strength) at 4% and 66% sites. In contrast, there was no strong evidence of sex or discipline effects on cross-sectional moment of inertia (CSMI, an indicator of bone bending and torsional strength-P > 0.3 for interactions). Similar sex and discipline-specific changes were also observed in the fibula. CONCLUSIONS: Results suggest that male athletes and those participating in lower limb power-based rather than endurance-based disciplines have better maintenance of bone compressive but not bending and torsional strength.

Comparison of Muscle Function, Bone Mineral Density and Body Composition of Early Starting and Later Starting Older Masters Athletes.

Masters endurance runners can epitomize healthy aging; being reflective of the physiological processes of aging without the compounded effects of inactivity. The primary aim of the present study was to determine, using cross-sectional data, whether individuals taking up training after the age of 50 years can achieve the same level of athletic performance and musculoskeletal characteristics in their older age as those who trained all of their adult lives. A total of 150 master endurance runners [age 68 (5) years; 111 male, 39 female] were divided into early starters (training all of their adulthood) and late starters (started training after age 50 years). A comparative non-athletic group of 59 healthy older adults [age 73 (4) years; 30 female, 29 male] were additionally included for analysis. Training intensity, age-graded performance (AGP) and musculoskeletal assessments were performed. Results showed that there was no difference between athlete groups for training intensity or age-graded performance, despite the 30-year difference in training history. Body fat percentage and leg lean mass did not differ between athlete groups, but were 17% lower and 12% greater, respectively, in athlete groups compared with controls. Power normalized to body mass did not differ between any groups. Spine BMD was lower in late starters than controls, while early starters did not differ from late starters or controls. Hip BMD did not differ between any of the groups. These findings show that the Masters athletes we studied that started intense endurance running after the age of 50 years had lower body fat and higher leg lean mass compared to non-athletes. Body composition and athletic performance of the late starters was very similar to those who trained all of their adult lives.