Episodic denervation as a driver of loss of skeletal muscle redox homeostasis and muscle weakness in sarcopenia: Possible amelioration by exercise

Abstract

Substantial reductions in muscle motor unit numbers accompany ageing and occur in parallel the age-related changes in skeletal muscle mass and fibre number. These motor unit changes are reflected in reduced motor neuron numbers and size, axonal integrity and disrupted pre-and post-synaptic neuromuscular junctions (NMJ). Conversely, data indicate that the effects of ageing on neuromuscular transmission are relatively minor. Some authors have therefore argued that structural degeneration of motor axons and NMJ are unimportant in the pathogenesis of sarcopenia and for a non-neurogenic origin for ageing-induced muscle loss. Increased Reactive Oxygen Species (ROS) activities and changes in redox status are a feature of ageing and may play a key role in muscle loss through increased mitochondrial peroxide generation. This article will review the changes in motor units and NMJ seen during ageing and develop the argument that the changes in muscle mitochondrial peroxide generation and redox status may be caused by age-related changes in neuromuscular structure, but are not directly related to neuromuscular transmission. This provides an alternative explanation on how age-related changes in neural tissue might drive skeletal muscle fibre loss and weakness. Exercise interventions are known to reduce muscle loss and weakness in the elderly, but studies of such interventions on age-related changes in motor units, motor neurons or NMJ structure and function provide conflicting data. A further aim is therefore to identify areas where there is a need for novel research to understand whether, and how, targeted or long-term exercise might influence neuromuscular changes in ageing.

Keywords

Neuromuscular junction / Mitochondria / Reactive oxygen species / Muscle fibre

Declaration of competing interest

I, Malcolm J Jackson, am an Editorial Board Member for Sports Medicine and Health Science and was not involved in the editorial review or the decision to publish this article.

I confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

I confirm that I have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing I confirm that we have fol- lowed the regulations of my institution concerning intellectual property.

Acknowledgements

The author would like to thank his many collaborators and colleagues who have contributed to this work over a number of years and to acknowledge the generous financial support for a variety of agencies including the UKRI Medical Research Council, Biotechnology and Bio- logical Sciences Research Council, the MRC-Versus Arthritis Centre for Integrated Research into Musculoskeletal Ageing (CIMA) and US Na- tional Institute on Aging.

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