Abstract
Life expectancy continues to extend, although frailty caused by loss of skeletal muscle mass continues unimpeded. Muscle atrophy caused by withdrawal of motor nerves is a feature of old age, as it is in amyotrophic lateral sclerosis (ALS) in which skeletal muscle denervation results from motoneuron death. In ALS, direct links have been established between motoneuron death and altered nucleocytoplasmic transport, so we ask whether similar defects accompany motoneuron death in normal ageing. We used immunohistochemistry on mouse tissues to explore potential links between neuromuscular junction (NMJ) degeneration, motoneuron death and nucleocytoplasmic transport regulatory proteins. Old age brought neuromuscular degeneration, motoneuron loss and reductions in immunodetectable levels of key nucleocytoplasmic transport proteins in lumbar motoneurons. We then asked whether exercise inhibited these changes and found that active elderly mice experienced less motoneuron death, improved neuromuscular junction morphology and retention of key nucleocytoplasmic transport proteins in lumbar motoneurons. Our results suggest that emergent defects in nucleocytoplasmic transport may contribute to motoneuron death and age-related loss of skeletal muscle mass, and that these defects may be reduced by exercise.
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Acknowledgements
Funding of the study reported in the article was provided by the Department of Physiology as part of a full PhD scholarship. AG was also the grateful recipient of a Universities New Zealand, Henry Kelsey Neurological scholarship, and a Hope Selwyn Foundation, ageing research scholarship.
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Gillon, A., Nielsen, K., Steel, C. et al. Exercise attenuates age-associated changes in motoneuron number, nucleocytoplasmic transport proteins and neuromuscular health. GeroScience 40, 177–192 (2018). https://doi.org/10.1007/s11357-018-0020-4
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DOI: https://doi.org/10.1007/s11357-018-0020-4