Age-dependent motor unit remodelling in human limb muscles

Abstract

Voluntary control of skeletal muscle enables humans to interact with and manipulate the environment. Lower muscle mass, weakness and poor coordination are common complaints in older age and reduce physical capabilities. Attention has focused on ways of maintaining muscle size and strength by exercise, diet or hormone replacement. Without appropriate neural innervation, however, muscle cannot function. Emerging evidence points to a neural basis of muscle loss. Motor unit number estimates indicate that by age around 71 years, healthy older people have around 40 % fewer motor units. The surviving low- and moderate-threshold motor units recruited for moderate intensity contractions are enlarged by around 50 % and show increased fibre density, presumably due to collateral reinnervation of denervated fibres. Motor unit potentials show increased complexity and the stability of neuromuscular junction transmissions is decreased. The available evidence is limited by a lack of longitudinal studies, relatively small sample sizes, a tendency to examine the small peripheral muscles and relatively few investigations into the consequences of motor unit remodelling for muscle size and control of movements in older age. Loss of motor neurons and remodelling of surviving motor units constitutes the major change in ageing muscles and probably contributes to muscle loss and functional impairments. The deterioration and remodelling of motor units likely imposes constraints on the way in which the central nervous system controls movements.

Coupling between skeletal muscle fiber size and capillarization is maintained during healthy aging

“…However, we did not find a significant difference in the percentage of NCT in the muscle biopsies. The increased variation in the size of type I fibres and incidence of angular type II fibres observed in our samples and others studying ageing,27 disuse,2 denervation,38 and reinnervation39 is likely a feature of the ongoing denervation–reinnervation process of motor unit remodelling 40. A 12 year follow‐up of older individuals also showed that the decrease in muscle volume was not associated with fibre atrophy,41 adding further evidence that fibre loss is the primary cause of the age‐related decrease in vastus lateralis muscle volume 35…”

Age- and Activity-Related Differences in the Abundance of Myosin Essential and Regulatory Light Chains in Human Muscle

“…Consistent with this, percentage MyHCI and MyHCIIa levels were greater and lower, respectively, in trained compared with untrained participants (Table 1), irrespective of age [7]. Type IIa and Type IIx muscle fibers are preferentially lost with age as a consequence of failed re-innervation [2]. Accordingly, we report MyHCIIa levels were lower in older compared with younger participants, regardless of training status (Table 1).…”

“…Each MU comprises a presynaptic motor neuron and a postsynaptic population of mono-innervated skeletal muscle fibers [2]. MUs are, typically but not always [3], defined by uniform skeletal muscle fiber isoform (Type I, Type II) content [4].…”

“…MUs are, typically but not always [3], defined by uniform skeletal muscle fiber isoform (Type I, Type II) content [4]. Type II MUs are preferentially lost with age, owing to failed re-innervation [2]. Functionally, type II MU loss underpins age-related phenotypical alterations (e.g., reduced skeletal muscle power [5]), owing to the distinct contractile and metabolic properties associated with each fiber type (reviewed in [4,6]).…”

Neuromuscular junction degeneration in muscle wasting

“…Accordingly, autophagy was found to be dysregulated in skeletal muscle of aging dogs [12] and humans [11]. It has been determined that caloric restriction and physical exercise are beneficial for rescuing neuromuscular junction fragmentation [2,13,8] and innervation status [2,14], and at the same time reduce impairment of autophagy [11] as well as sarcopenia onset or progression [15–18]. This suggests autophagy modulation to be a potential therapeutic target in neuromuscular transmission disorders (Fig.…”