**Key Components of Human Myofibre Denervation and Neuromuscular Junction Stability are Modulated by Age and Exercise**

**Casper Soendenbroe 1,2, Cecilie J. L. Bechshøft 1,3, Mette F. Heisterberg 1, Simon M. Jensen 1, Emma Bomme 1, Peter Schjerling 1,3, Anders Karlsen 1,3, Michael Kjaer 1,3, Jesper L. Andersen 1,3 and Abigail L. Mackey 1,2,3,\***


Received: 28 February 2020; Accepted: 3 April 2020; Published: 6 April 2020

**Abstract:** The decline in muscle mass and function with age is partly caused by a loss of muscle fibres through denervation. The purpose of this study was to investigate the potential of exercise to influence molecular targets involved in neuromuscular junction (NMJ) stability in healthy elderly individuals. Participants from two studies (one group of 12 young and 12 elderly females and another group of 25 elderly males) performed a unilateral bout of resistance exercise. Muscle biopsies were collected at 4.5 h and up to 7 days post exercise for tissue analysis and cell culture. Molecular targets related to denervation and NMJ stability were analysed by immunohistochemistry and real-time reverse transcription polymerase chain reaction. In addition to a greater presence of denervated fibres, the muscle samples and cultured myotubes from the elderly individuals displayed altered gene expression levels of acetylcholine receptor (AChR) subunits. A single bout of exercise induced general changes in AChR subunit gene expression within the biopsy sampling timeframe, suggesting a sustained plasticity of the NMJ in elderly individuals. These data support the role of exercise in maintaining NMJ stability, even in elderly inactive individuals. Furthermore, the cell culture findings suggest that the transcriptional capacity of satellite cells for AChR subunit genes is negatively affected by ageing.

**Keywords:** sarcopenia; denervation; neuromuscular junction; heavy resistance exercise; acetylcholine receptor; cell culture; myogenesis; neonatal myosin; neural cell adhesion molecule
