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

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.

Macrophage Subpopulations and the Acute Inflammatory Response of Elderly Human Skeletal Muscle to Physiological Resistance Exercise

“…Indeed it is possible that muscle damage is the main driver of the macrophage response. However, we detected similar increases in circulating creatine kinase in the young and elderly females at 5 days post exercise, together with similar numbers of fibers positive for neonatal myosin at this time point (Bechshøft et al, 2019;Soendenbroe et al, 2020) suggesting that muscle damage leading to necrosis was absent. This is further supported by the complete lack of fibers containing macrophages in the present study.…”

“…This study is based on muscle biopsy analyses from two studies, one on 25 elderly men (Heisterberg et al, 2018) and one on 12 young and 12 elderly women (Bechshøft et al, 2019;Soendenbroe et al, 2020). Both studies were approved by The Committees on Health Research Ethics for The Capital Region of Denmark (Ref: H-15017223, H-3-2012-081).…”

“…RPLP0 mRNA was chosen as internal control. To validate this use, another unrelated "constitutive" mRNA, GAPDH, was measured and normalized with RPLP0 (Heisterberg et al, 2018;Soendenbroe et al, 2020).…”

AChRs Degeneration at NMJ in Aging-Associated Sarcopenia–A Systematic Review

“…After further screening of remaining articles, 49 were excluded, in which 23 had no comparisons among different ages, 20 were review papers 4 were conference reports and 2 had no full text access. Therefore, 30 manuscripts were included for the systematic review (Courtney and Steinbach, 1981;Banker et al, 1983;Oda, 1984;Herscovich and Gershon, 1987;Smith and Chapman, 1987;Anis and Robbins, 1988;Smith et al, 1990;Prakash and Sieck, 1998;Connor et al, 2002;Deschenes and Wilson, 2003;Apel et al, 2009;Mcmullen and Andrade, 2009;Suzuki et al, 2009;Kulakowski et al, 2011;Li et al, 2011;Samuel et al, 2012;Cheng et al, 2013;Deschenes et al, 2013;Personius and Parker, 2013;Aare et al, 2016;Willadt et al, 2016;Xie et al, 2016Xie et al, , 2018Hughes et al, 2017;Liu et al, 2017;Snyder-Warwick et al, 2018;Zhao et al, 2018;Soendenbroe et al, 2019Soendenbroe et al, , 2020Uchitomi et al, 2019). The flow chart presenting the selection process is shown in Figure 1.…”

Muscle Homeostasis and Regeneration: From Molecular Mechanisms to Therapeutic Opportunities

“…The study by Soendenbroe et al, supported the role of exercise in maintaining NMJ stability, even in elderly inactive individuals [18], whereas Jin and co-workers demonstrated that the functions of Lysine (Lys), the first limiting essential amino acid for mammals, in muscle mass accumulation are mediated by satellite cells and the mTORC1 pathway [19].…”