Alterations in Muscle Force Control With Aging: Is There a Modulatory Effect of Lifelong Physical Activity?

Recent technological developments have enabled significant advances in our understanding of the ability to voluntarily control muscle force output. The fluctuations inherent to muscle force output can be quantified according to both their magnitude and temporal structure (or “complexity”), with such quantification facilitating comparison of force control between distinct populations. In comparison to young adults, older adults exhibit an increase in the magnitude (i.e., decreased steadiness) and a decrease in the complexity (i.e., decreased adaptability) of force fluctuations, both of which are indicative of a loss of force control. There remain, however, key gaps in knowledge that limit our interpretation of this age-related loss of force control. One such gap relates to the effect of lifelong physical activity on force control. To date, research on aging and force control has largely been conducted on inactive or moderately active older adults. However, high levels of lifelong physical activity, such as that exhibited by Masters athletes, have been shown to have protective effects on the function and morphology of the neuromuscular system. Some of these effects (e.g., on impaired inhibitory transmission in the motor cortex and on motor unit discharge rates) have the potential to attenuate the age-related loss of force control, while others (e.g., greater motor unit remodeling capacity) have the potential to worsen it. We therefore propose that, in order to progress our knowledge of the effects of aging on force control, future studies must consider the potential modulatory effect of lifelong physical activity

NIHR Nottingham Biomedical Research Centre (BRC) Musculoskeletal theme: virtual conference proceedings 24 th & 25 th February 2022

This paper gives summaries of the keynote lectures given and the research abstracts presented at the NIHR Nottingham Biomedical Research Centre Musculoskeletal theme virtual conference held on 24th and 25th February 2022. The purpose of the conference was to stimulate collaboration within the broad field of musculoskeletal research, by having presentations showing different techniques and topics, given by our experts and our PhD students. Collaboration was encouraged by inviting colleagues to contact each other by email to start a conversation - an invitation that we extend through this paper, and extend to interested colleagues anywhere in the world. This conference was funded by the NIHR Nottingham Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care

Caenorhabditis elegans as a Model System for Duchenne Muscular Dystrophy

The nematode worm Caenorhabditis elegans has been used extensively to enhance our understanding of the human neuromuscular disorder Duchenne Muscular Dystrophy (DMD). With new arising clinically relevant models, technologies and treatments, there is a need to reconcile the literature and collate the key findings associated with this model

Near-Fiber Electromyography

ObjectiveDescribe and evaluate the concepts of near fiber electromyography (NFEMG), the features used, including near fiber motor unit potential (NFMUP) duration and dispersion, which relate to motor unit distal axonal branch and muscle fiber conduction time dispersion, and NFMUP segment jitter, a new measure of the temporal variability of neuromuscular junction transmission (NMJ), and axonal branch and muscle fibre conduction for the near fibres (i.e. NF jitter), and the methods for obtaining their values.MethodsTrains of high-pass filtered motor unit potentials (MUPs) (i.e. NFMUP trains) were extracted from needle-detected EMG signals to assess changes in motor unit (MU) morphology and electrophysiology caused by neuromuscular disorders or ageing. Evaluations using simulated needle-detected EMG data were completed and example human data are presented.ResultsNFEMG feature values can be used to detect axonal sprouting, conduction slowing and NMJ transmission delay as well as changes in MU fiber diameter variability, and NF jitter. These changes can be detected prior to alterations of MU size or numbers.ConclusionsThe evaluations clearly demonstrate and the example data support that NFMUP duration and dispersion reflect MU distal axonal branching, conduction slowing and NMJ transmission delay and/or MU fiber diameter variability and that NFMUP jiggle and segment jitter reflect NF jitter

Molecular and Neural Adaptations to Neuromuscular Electrical Stimulation; Implications for Ageing Muscle

One of the most notable effects of ageing is an accelerated decline of skeletal muscle mass and function, resulting in various undesirable outcomes such as falls, frailty, and all-cause mortality. The loss of muscle mass directly leads to functional deficits and can be explained by the combined effects of individual fibre atrophy and fibre loss. The gradual degradation of fibre atrophy is attributed to impaired muscle protein homeostasis, while muscle fibre loss is a result of denervation and motor unit (MU) remodelling. Neuromuscular electrical stimulation (NMES), a substitute for voluntary contractions, has been applied to reduce muscle mass and functional declines. However, the measurement of the effectiveness of NMES in terms of its mechanism of action on the peripheral motor nervous system and neuromuscular junction, and multiple molecular adaptations at the single fibre level is not well described. NMES mediates neuroplasticity and upregulates a number of neurotropic factors, manifested by increased axonal sprouting and newly formed neuromuscular junctions. Repeated involuntary contractions increases the activity levels of oxidative enzymes, increases fibre capillarisation and can influence fibre type conversion. Additionally, following NMES muscle protein synthesis is increased as well as functional capacity. This review will detail the neural, molecular, metabolic and functional adaptations to NMES in human and animal studies

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

Contrast‐enhanced ultrasound repeatability for the measurement of skeletal muscle microvascular blood flow

Contrast-enhanced ultrasound (CEUS) can be used to directly assess skeletal muscle perfusion. However, its repeatability over time has not yet been validated and therefore its use in longitudinal measures (i.e., exploring the impact of a chronic intervention or disease progression) is limited. This study aimed to determine the repeatability of CEUS for the measurement of skeletal muscle microvascular blood flow (MBF) at baseline and in response to exercise, across independent assessment sessions. Ten healthy volunteers (five female; 30 ± 6 years) had CEUS of the right vastus lateralis recorded in two separate sessions, 14 days apart. Measurements were taken at baseline, during an isometric leg extension and during recovery. Acoustic intensity data from a region of interest were plotted as a replenishment curve to obtain blood volume (A) and flow velocity (β) values from a one-phase association non-linear regression of mean tissue echogenicity. Linear regression and Bland–Altman analyses of A and β values were performed, with significance assumed as P < 0.05. Strong positive correlations were observed across sessions for all A and β values (both P < 0.0001). Bland–Altman analysis showed a bias (SD) of −0.013 ± 1.24 for A and −0.014 ± 0.31 for β. A bias of 0.201 ± 0.770 at baseline, 0.527 ± 1.29 during contraction and −0.203 ± 1.29 at recovery was observed for A, and −0.0328 ± 0.0853 (baseline), −0.0446 ± 0.206 (contraction) and 0.0382 ± 0.233 (recovery) for β. A strong agreement between CEUS MBF measures across independent sessions suggests it to be a repeatable method for assessing skeletal muscle perfusion over time, and therefore facilitates wider use in longitudinal studies

Ageing and exercise-induced motor unit remodelling

A motor unit (MU) comprises the neuron cell body, its corresponding axon and each of the muscle fibres it innervates. Many studies highlight age-related reductions in the number of MUs, yet the ability of a MU to undergo remodelling and to expand to rescue denervated muscle fibres is also a defining feature of MU plasticity. Remodelling of MUs involves two coordinated processes: (i) axonal sprouting and new branching growth from adjacent surviving neurons, and (ii) the formation of key structures around the neuromuscular junction to resume muscle–nerve communication. These processes rely on neurotrophins and coordinated signalling in muscle–nerve interactions. To date, several neurotrophins have attracted focus in animal models, including brain-derived neurotrophic factor and insulin-like growth factors I and II. Exercise in older age has demonstrated benefits in multiple physiological systems including skeletal muscle, yet evidence suggests this may also extend to peripheral MU remodelling. There is, however, a lack of research in humans due to methodological limitations which are easily surmountable in animal models. To improve mechanistic insight of the effects of exercise on MU remodelling with advancing age, future research should focus on combining methodological approaches to explore the in vivo physiological function of the MU alongside alterations of the localised molecular environment

Relationship of anabolic hormones with motor unit characteristics in quadriceps muscle in healthy and frail ageing men

ContextAnabolic hormones are important factors in maintaining muscle mass for ageing men, but their role in overall motor unit structure and function is unclear.ObjectiveTo determine associations of anabolic and reproductive hormone levels with motor unit characteristics in quadriceps muscle in older healthy and frail men.DesignObservational cohort study of community dwelling men.ParticipantsHealthy and frail men > 65 years old.InterventionNone.Outcome measureQuantitative assessments of electromyography-derived motor unit potential size (MUP) and compound muscle action potential size (CMAP) of vastus lateralis muscle.ResultsWe studied 98 men (mean±SD: age 73±6 years; BMI 25.7±4.0 kg/m2; diabetes 11%) of whom 45% were prefrail and 18% frail. After adjusting for age, BMI and prevalent diabetes, higher total and free testosterone levels were significantly related to larger CMAP (total testosterone: β (95% CI): 0.3 (0.08, 0.53); free testosterone: 0.34 (0.13, 0.56)). Exploratory analysis showed the relationship between free testosterone and CMAP was stronger in frail rather than robust men. In univariate analyses, estradiol was associated with CMAP size (0.37 (0.16, 0.57)); and vitamin D was associated with MUP size (0.22 (0.01, 0.43)) but these relationships were no longer significant after adjusting for potential confounders.ConclusionOur data highlight the associations between androgen levels and the electrophysiological characteristics of older men, particularly in the frail. Clinical trials involving administration of androgens will help to elucidate the potential benefits of intervention on neuromuscular function and/or frailty status