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J Physiol. 2016 Apr 15;594(8):1965-78. doi: 10.1113/JP270561. Epub 2015 Dec 21.

Innervation and neuromuscular control in ageing skeletal muscle.

Hepple RT1,2,3, Rice CL4,5,6.

Author information

1
Department of Kinesiology & Physical Education, McGill University, Montreal, Québec, Canada.
2
McGill Research Centre for Physical Activity and Health, Montreal, Québec, Canada.
3
Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montreal, Québec, Canada.
4
School of Kinesiology, University of Western Ontario, London, Ontario, Canada.
5
Canadian Centre for Activity and Aging, London, Ontario, Canada.
6
Department of Anatomy & Cell Biology, University of Western Ontario, London, Ontario, Canada.

Abstract

Changes in the neuromuscular system affecting the ageing motor unit manifest structurally as a reduction in motor unit number secondary to motor neuron loss; fibre type grouping due to repeating cycles of denervation-reinnervation; and instability of the neuromuscular junction that may be due to either or both of a gradual perturbation in postsynaptic signalling mechanisms necessary for maintenance of the endplate acetylcholine receptor clusters or a sudden process involving motor neuron death or traumatic injury to the muscle fibre. Functionally, these changes manifest as a reduction in strength and coordination that precedes a loss in muscle mass and contributes to impairments in fatigue. Regular muscle activation in postural muscles or through habitual physical activity can attenuate some of these structural and functional changes up to a point along the ageing continuum. On the other hand, regular muscle activation in advanced age (>75 years) loses its efficacy, and at least in rodents may exacerbate age-related motor neuron death. Transgenic mouse studies aimed at identifying potential mechanisms of motor unit disruptions in ageing muscle are not conclusive due to many different mechanisms converging on similar motor unit alterations, many of which phenocopy ageing muscle. Longitudinal studies of ageing models and humans will help clarify the cause and effect relationships and thus, identify relevant therapeutic targets to better preserve muscle function across the lifespan.

PMID:
26437581
PMCID:
PMC4933121
DOI:
10.1113/JP270561
[Indexed for MEDLINE]
Free PMC Article

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