Sex disparities of human neuromuscular decline in older humans.

Females typically live longer than males but, paradoxically, spend a greater number of later years in poorer health. The neuromuscular system is a critical component of the progression to frailty, and motor unit (MU) characteristics differ by sex in healthy young individuals and may adapt to ageing in a sex-specific manner due to divergent hormonal profiles. The purpose of this study was to investigate sex differences in vastus lateralis (VL) MU structure and function in early to late elderly humans. Intramuscular electromyography signals from 50 healthy older adults (M/F: 26/24) were collected from VL during standardized submaximal contractions and decomposed to quantify MU characteristics. Muscle size and neuromuscular performance were also measured. Females had higher MU firing rate (FR) than males (P = 0.025), with no difference in MU structure or neuromuscular junction transmission (NMJ) instability. All MU characteristics increased from low- to mid-level contractions (P < 0.05) without sex × level interactions. Females had smaller cross-sectional area of VL, lower strength and poorer force steadiness (P < 0.05). From early to late elderly, both sexes showed decreased neuromuscular function (P < 0.05) without sex-specific patterns. Higher VL MUFRs at normalized contraction levels previously observed in young are also apparent in old individuals, with no sex-based difference of estimates of MU structure or NMJ transmission instability. From early to late elderly, the deterioration of neuromuscular function and MU characteristics did not differ between sexes, yet function was consistently greater in males. These parallel trajectories underscore the lower initial level for older females and may offer insights into identifying critical intervention periods. KEY POINTS: Females generally exhibit an extended lifespan when compared to males, yet this is accompanied by a poorer healthspan and higher rates of frailty. In healthy young people, motor unit firing rate (MUFR) at normalized contraction intensities is widely reported to be higher in females than in age-matched males. Here we show in 50 people that older females have higher MUFR than older males with little difference in other MU parameters. The trajectory of decline from early to late elderly does not differ between sexes, yet function is consistently lower in females. These findings highlight distinguishable sex disparities in some MU characteristics and neuromuscular function, and suggest early interventions are needed for females to prevent functional deterioration to reduce the ageing health-sex paradox.

Skeletal muscle dysfunction with advancing age.

As a result of advances in medical treatments and associated policy over the last century, life expectancy has risen substantially and continues to increase globally. However, the disconnect between lifespan and 'health span' (the length of time spent in a healthy, disease-free state) has also increased, with skeletal muscle being a substantial contributor to this. Biological ageing is accompanied by declines in both skeletal muscle mass and function, termed sarcopenia. The mechanisms underpinning sarcopenia are multifactorial and are known to include marked alterations in muscle protein turnover and adaptations to the neural input to muscle. However, to date, the relative contribution of each factor remains largely unexplored. Specifically, muscle protein synthetic responses to key anabolic stimuli are blunted with advancing age, whilst alterations to neural components, spanning from the motor cortex and motoneuron excitability to the neuromuscular junction, may explain the greater magnitude of function losses when compared with mass. The consequences of these losses can be devastating for individuals, their support networks, and healthcare services; with clear detrimental impacts on both clinical (e.g., mortality, frailty, and post-treatment complications) and societal (e.g., independence maintenance) outcomes. Whether declines in muscle quantity and quality are an inevitable component of ageing remains to be completely understood. Nevertheless, strategies to mitigate these declines are of vital importance to improve the health span of older adults. This review aims to provide an overview of the declines in skeletal muscle mass and function with advancing age, describes the wide-ranging implications of these declines, and finally suggests strategies to mitigate them, including the merits of emerging pharmaceutical agents.

DYNamic Assessment of Multi-Organ level dysfunction in patients recovering from COVID-19: DYNAMO COVID-19.

We evaluated the impacts of COVID-19 on multi-organ and metabolic function in patients following severe hospitalised infection compared to controls. Patients (n = 21) without previous diabetes, cardiovascular or cerebrovascular disease were recruited 5-7 months post-discharge alongside controls (n = 10) with similar age, sex and body mass. Perceived fatigue was estimated (Fatigue Severity Scale) and the following were conducted: oral glucose tolerance (OGTT) alongside whole-body fuel oxidation, validated magnetic resonance imaging and spectroscopy during resting and supine controlled exercise, dual-energy X-ray absorptiometry, short physical performance battery (SPPB), intra-muscular electromyography, quadriceps strength and fatigability, and daily step-count. There was a greater insulin response (incremental area under the curve, median (inter-quartile range)) during the OGTT in patients [18,289 (12,497-27,448) mIU/min/L] versus controls [8655 (7948-11,040) mIU/min/L], P < 0.001. Blood glucose response and fasting and post-prandial fuel oxidation rates were not different. This greater insulin resistance was not explained by differences in systemic inflammation or whole-body/regional adiposity, but step-count (P = 0.07) and SPPB scores (P = 0.004) were lower in patients. Liver volume was 28% greater in patients than controls, and fat fraction adjusted liver T1, a measure of inflammation, was raised in patients. Patients displayed greater perceived fatigue scores, though leg muscle volume, strength, force-loss, motor unit properties and post-exercise muscle phosphocreatine resynthesis were comparable. Further, cardiac and cerebral architecture and function (at rest and on exercise) were not different. In this cross-sectional study, individuals without known previous morbidity who survived severe COVID-19 exhibited greater insulin resistance, pointing to a need for physical function intervention in recovery.

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 effects of neuromuscular electrical stimulation on hospitalised adults: systematic review and meta-analysis of randomised controlled trials.

INTRODUCTION: Neuromuscular electrical stimulation (NMES) is a treatment to prevent or reverse acquired disability in hospitalised adults. We conducted a systematic review and meta-analysis of its effectiveness. METHOD: We searched MEDLINE, EMBASE, Cumulative Index to Nursing & Allied Health (CINAHL) and the Cochrane library. Inclusion criteria: randomised controlled trials of hospitalised adult patients comparing NMES to control or usual care. The primary outcome was muscle strength. Secondary outcomes were muscle size, function, hospital length of stay, molecular and cellular biomarkers, and adverse effects. We assessed risk of bias using the Cochrane risk-of-bias tool. We used Review Manager (RevMan) software for data extraction, critical appraisal and synthesis. We assessed certainty using the Grading of Recommendations Assessment, Development and Evaluation tool. RESULTS: A total of 42 papers were included involving 1,452 participants. Most studies had unclear or high risk of bias. NMES had a small effect on muscle strength (moderate certainty) (standardised mean difference (SMD) = 0.33; P < 0.00001), a moderate effect on muscle size (moderate certainty) (SMD = 0.66; P < 0.005), a small effect on walking performance (moderate certainty) (SMD = 0.48; P < 0.0001) and a small effect on functional mobility (low certainty) (SMD = 0.31; P < 0.05). There was a small and non-significant effect on health-related quality of life (very low certainty) (SMD = 0.35; P > 0.05). In total, 9% of participants reported undesirable experiences. The effects of NMES on length of hospital stay, and molecular and cellular biomarkers were unclear. CONCLUSIONS: NMES is a promising intervention component that might help to reduce or prevent hospital-acquired disability.

Common synaptic inputs and persistent inward currents of vastus lateralis motor units are reduced in older male adults.

Although muscle atrophy may partially account for age-related strength decline, it is further influenced by alterations of neural input to muscle. Persistent inward currents (PIC) and the level of common synaptic inputs to motoneurons influence neuromuscular function. However, these have not yet been described in the aged human quadriceps. High-density surface electromyography (HDsEMG) signals were collected from the vastus lateralis of 15 young (mean ± SD, 23 ± 5 y) and 15 older (67 ± 9 y) men during submaximal sustained and 20-s ramped contractions. HDsEMG signals were decomposed to identify individual motor unit discharges, from which PIC amplitude and intramuscular coherence were estimated. Older participants produced significantly lower knee extensor torque (p < 0.001) and poorer force tracking ability (p < 0.001) than young. Older participants also had lower PIC amplitude (p = 0.001) and coherence estimates in the alpha frequency band (p < 0.001) during ramp contractions when compared to young. Persistent inward currents and common synaptic inputs are lower in the vastus lateralis of older males when compared to young. These data highlight altered neural input to the clinically and functionally important quadriceps, further underpinning age-related loss of function which may occur independently of the loss of muscle mass.