Physiological and structural changes in skeletal muscle and nerve-muscle interactions: the effects of ROS and ageing

Future Physiology 2019 (Liverpool, UK) (2019) Proc Physiol Soc 45, SA04

Research Symposium: Physiological and structural changes in skeletal muscle and nerve-muscle interactions: the effects of ROS and ageing

N. Pollock1,2, C. A. Staunton1,2, M. Scalabrin1,2, E. Owen1,2, K. Hemmings1,2, A. Vasilaki1,2, A. McArdle1,2, M. J. Jackson1,2

1. Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom. 2. MRC- Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing (CIMA), Liverpool, United Kingdom.

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With an ever growing population, and the fastest growing group being elderly, we need to understand and treat those factors which affect quality of life in later years. It is well established that there is an age-related decline in muscle mass and function with increasing age (termed sarcopenia) and this is associated with increased falls and hospital admissions. There are many factors which have been associated with sarcopenia. Substantial alteration of motor neurons and changes in reactive oxygen species (ROS) with advancing age are widely described in rodent models. We have utilised several mouse models, deficient in the antioxidant enzyme superoxide dismutase 1 (SOD1), to examine to role of aberrant redox homeostasis on nerve-muscle interactions. Whole body knock out of Sod1 in mice causes accelerated age-related muscle wasting, a decline in force production and alterations in neuromuscular junctions (NMJs). The NMJ is composed of the pre-synaptic nerve terminal, the acetylcholine receptor clusters on the muscle and terminal Schwann cells that encase this region. It is a dynamic structure and multiple cycles of denervation and re-innervation throughout life are thought to result in structural changes which accumulate. When re-innervation fails the muscle fibre remains denervated and the incidence of denervated fibres is increased with advancing age which correlates with reduced muscle mass and function. Using a surgical model of nerve transection we have shown that there is an increase in mitochondrial generation of hydrogen peroxide and other peroxides in denervated muscle fibres which also occurs in neighbouring fibres which have a “normal” NMJ structure. We speculate that the initial increase in peroxide production may stimulate adaptations to protect the muscle fibre. More chronic production of peroxides has also been shown to activate several degenerative processes preceding loss of muscle mass. Recent in vivo imaging of HyPer2 transduced skeletal muscle from our lab has also drawn strong links between innervation status and peroxide production in nerve crush models Ongoing work seeks to understand the complex relationship between the redox status of motor nerves and skeletal muscle in the Sod1KO mouse model and in ageing of wild type mice together with the role that Schwann cells, which are responsible for NMJ stability, are playing in these situations.



Where applicable, experiments conform with Society ethical requirements.

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