Mathew Piasecki

Age‐related neuromuscular changes affecting human vastus lateralis

Skeletal muscle size and strength decline in older age. The vastus lateralis, a large thigh muscle, undergoes extensive neuromuscular remodelling in healthy ageing, as characterized by a loss of motor neurons, enlargement of surviving motor units and instability of neuromuscular junction transmission. The loss of motor axons and changes to motor unit potential transmission precede a clinically‐relevant loss of muscle mass and function.

A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia

Declining muscle mass and function is one of the main drivers of loss of independence in the elderly. Sarcopenia is associated with numerous cellular and endocrine perturbations, and it remains challenging to identify those changes that play a causal role and could serve as targets for therapeutic intervention. In this study, we uncovered a remarkable differential susceptibility of certain muscles to age-related decline. Aging rats specifically lose muscle mass and function in the hindlimbs, but not in the forelimbs. By performing a comprehensive comparative analysis of these muscles, we demonstrate that regional susceptibility to sarcopenia is dependent on neuromuscular junction fragmentation, loss of motoneuron innervation, and reduced excitability. Remarkably, muscle loss in elderly humans also differs in vastus lateralis and tibialis anterior muscles in direct relation to neuromuscular dysfunction. By comparing gene expression in susceptible and non-susceptible muscles, we identified a specific transcriptomic signature of neuromuscular impairment. Importantly, differential molecular profiling of the associated peripheral nerves revealed fundamental changes in cholesterol biosynthetic pathways. Altogether our results provide compelling evidence that susceptibility to sarcopenia is tightly linked to neuromuscular decline in rats and humans, and identify dysregulation of sterol metabolism in the peripheral nervous system as an early event in this process.

Sex differences in the effects of 12 weeks sprint interval training on body fat mass and the rates of fatty acid oxidation and VO2max during exercise

Background The purpose of this study was to examine whether very short duration, very high intensity sprint interval training (SIT) leads to loss of body fat mass in association with improvements to VO2max and fatty acid oxidation, and to assess the extent of sex dimorphism in these physiological responses. Methods A total of 24 men and 17 women (mean (SEM) age: 39 (±2) years; body mass index 24.6 (0.6)) completed measurements of the maximal rate of oxygen uptake (VO2max) and fatty acid oxidation (FATmax). Body fat and lean mass were measured by dual emission x-ray absorptiometry, and fasting blood lipid, glucose and insulin profiles were assessed before and after training. SIT consisted of 4×20 s sprints on a cycle ergometer at approximately 175% VO2max, three times per week for 12 weeks. Results Fat mass decreased by 1.0 kg, although men lost statistically significantly more fat than women both when expressed in Kg and as % body fat. VO2max increased by around 9%, but women improved VO2max significantly more than men. FATmax improved by around 13%, but fasting plasma glucose, insulin, total triglyceride, total cholesterol and high-density lipoprotein (HDL) did not change after training, while low-density lipoprotein decreased by 8% (p=0.028) and the HDL:Total Cholesterol ratio improved by 6%. There were no sex differences in these metabolic responses to training. Conclusions These results show lower body fat %, and higher rates of fatty acid oxidation and VO2max after 12 weeks of training for just 4 min per week. Notably, women improved VO2max more than men, while men lost more fat than women.

Motor unit number estimates and neuromuscular transmission in the tibialis anterior of master athletes: evidence that athletic older people are not spared from age-related motor unit remodeling.

Muscle motor unit numbers decrease markedly in old age, while remaining motor units are enlarged and can have reduced neuromuscular junction transmission stability. However, it is possible that regular intense physical activity throughout life can attenuate this remodeling. The aim of this study was to compare the number, size, and neuromuscular junction transmission stability of tibialis anterior (TA) motor units in healthy young and older men with those of exceptionally active master runners. The distribution of motor unit potential (MUP) size was determined from intramuscular electromyographic signals recorded in healthy male Young (mean ± SD, 26 ± 5 years), Old (71 ± 4 years) and Master Athletes (69 ± 3 years). Relative differences between groups in numbers of motor units was assessed using two methods, one comparing MUP size and muscle cross‐sectional area (CSA) determined with MRI, the other comparing surface recorded MUPs with maximal compound muscle action potentials and commonly known as a “motor unit number estimate (MUNE)”. Near fiber (NF) jiggle was measured to assess neuromuscular junction transmission stability. TA CSA did not differ between groups. MUNE values for the Old and Master Athletes were 45% and 40%, respectively, of the Young. Intramuscular MUPs of Old and Master Athletes were 43% and 56% larger than Young. NF jiggle was slightly higher in the Master Athletes, with no difference between Young and Old. These results show substantial and similar motor unit loss and remodeling in Master Athletes and Old individuals compared with Young, which suggests that lifelong training does not attenuate the age‐related loss of motor units.

Failure to expand the motor unit size to compensate for declining motor unit numbers distinguishes sarcopenic from non-sarcopenic older men

The age‐related loss of muscle mass is related to the loss of innervating motor neurons and denervation of muscle fibres. Not all denervated muscle fibres are degraded; some may be reinnervated by an adjacent surviving neuron, which expands the innervating motor unit proportional to the numbers of fibres rescued. Enlarged motor units have larger motor unit potentials when measured using electrophysiological techniques. We recorded much larger motor unit potentials in relatively healthy older men compared to young men, but the older men with the smallest muscles (sarcopenia) had smaller motor unit potentials than healthy older men. These findings suggest that healthy older men reinnervate large numbers of muscle fibres to compensate for declining motor neuron numbers, but a failure to do so contributes to muscle loss in sarcopenic men.

Measurement of muscle health in aging

Abstract Muscle health is a critical component in the struggle against physical frailty and the efforts to maintain metabolic health until the limit of chronological age. Consensus opinion is to evaluate muscle health in terms of muscle mass, strength and functional capability. There has been considerable variability in the components of muscle health which have been investigated in addition to variability in the tools of assessment and protocol for measurement. This is in stark contrast to the validated measurement of bone health across the adult life span. The purpose of this review was to identify indices of muscle mass, strength and functional capability most responsive to change with ageing and where possible to provide an estimate of the rate of change. We suggest lean tissue mass (LTM) or skeletal muscle (SM) is best evaluated from the thigh region due to its greater responsiveness to ageing compared to the whole body. The anterior compartment of the thigh region undergoes a preferential age-related decline in SM and force generating capacity. Therefore, we suggest that knee extensor torque is measured to represent the force generating capacity of the thigh and subsequently, to express muscle quality (strength per unit tissue). Finally, we suggest measures of functional capability which allow participants perform to a greater maximum are most appropriate to track age-related difference in functional capacity across the adult lifespan. This is due to their ability encompass a broad spectrum of abilities. This review suggests indices of muscular health for which reference ranges can be generated across the lifespan.

The Contributions of Fiber Atrophy, Fiber Loss, In Situ Specific Force, and Voluntary Activation to Weakness in Sarcopenia

Abstract The contributions of fiber atrophy, fiber loss, in situ specific force, and voluntary activation to weakness in sarcopenia remain unclear. To investigate, 40 older (20 women; age 72 ± 4 years) and 31 younger adults (15 women, age 22 ± 3 years) completed measurements. The knee extensor maximal voluntary torque (MVC) was measured as well as voluntary activation, patella tendon moment arm length, muscle volume, and fascicle architecture to estimate in situ specific force. Fiber cross-sectional area (FCSA), fiber numbers, and connective tissue contents were also estimated from vastus lateralis biopsies. The MVC, quadriceps volume, and specific force were 39%, 28%, and 17% lower, respectively, in old compared with young, but voluntary activation was not different. The difference in muscle size was due in almost equal proportions to lower type II FCSA and fewer fibers. Five years later (n = 23) the MVC, muscle volume and voluntary activation in old decreased an additional 12%, 6%, and 4%, respectively, but there was no further change in specific force. In situ specific force declines relatively early in older age and reduced voluntary activation occurs later, but the overall weakness in sarcopenia is mainly related to loss of both type I and II fibers and type II fiber atrophy.

The reliability of methods to estimate the number and size of human motor units and their use with large limb muscles

PurposeCurrent methods for estimating muscle motor unit (MU) number provide values which are remarkably similar for muscles of widely differing size, probably because surface electrodes sample from similar and relatively small volumes in each muscle. We have evaluated an alternative means of estimating MU number that takes into account differences in muscle size.MethodsIntramuscular motor unit potentials (MUPs) were recorded and muscle cross-sectional area (CSA) was measured using MRI to provide a motor unit number estimate (iMUNE). This was compared to the traditional MUNE method, using compound muscle action potentials (CMAP) and surface motor unit potentials (sMUPs) recorded using surface electrodes. Data were collected from proximal and distal regions of the vastus lateralis (VL) in young and old men while test–retest reliability was evaluated with VL, tibialis anterior and biceps brachii.ResultsMUPs, sMUPs and CMAPs were highly reliable (r = 0.84–0.91). The traditional MUNE, based on surface recordings, did not differ between proximal and distal sites of the VL despite the proximal CSA being twice the distal CSA. iMUNE, however, gave values that differed between young and old and were proportional to the muscle size.ConclusionWhen evaluating the contribution that MU loss makes to muscle atrophy, such as in disease or ageing, it is important to have a method such as iMUNE, which takes into account any differences in total muscle size.

The strength of weight‐bearing bones is similar in amenorrheic and eumenorrheic elite long‐distance runners

Regular intense endurance exercise can lead to amenorrhea with possible adverse consequences for bone health. We compared whole body and regional bone strength and skeletal muscle characteristics between amenorrheic (AA: n = 14) and eumenorrheic (EA: n = 15) elite adult female long‐distance runners and nonathletic controls (C: n = 15). Participants completed 3‐day food diaries, dual‐energy X‐ray absorptiometry (DXA), magnetic resonance imaging (MRI), peripheral quantitative computed tomography (pQCT), and isometric maximal voluntary knee extension contraction (MVC). Both athlete groups had a higher caloric intake than controls, with no significant difference between athlete groups. DXA revealed lower bone mineral density (BMD) at the trunk, rib, pelvis, and lumbar spine in the AA than EA and C. pQCT showed greater bone size in the radius and tibia in EA and AA than C. The radius and tibia of AA had a larger endocortical circumference than C. Tibia bone mass and moments of inertia (Ix and Iy) were greater in AA and EA than C, whereas in the radius, only the proximal Iy was larger in EA than C. Knee extensor MVC did not differ significantly between groups. Amenorrheic adult female elite long‐distance runners had lower BMD in the trunk, lumbar spine, ribs, and pelvis than eumenorrheic athletes and controls. The radius and tibia bone size and strength indicators were similar in amenorrheic and eumenorrheic athletes, suggesting that long bones of the limbs differ in their response to amenorrhea from bones in the trunk.