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

Zhengyuan Bao; Can Cui; Simon Kwoon-Ho Chow; Ling Qin; Ronald Man Yeung Wong; Wing-Hoi Cheung

doi:10.3389/fnagi.2020.597811

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

Front Aging Neurosci. 2020 Dec 10:12:597811. doi: 10.3389/fnagi.2020.597811. eCollection 2020.

Authors

Zhengyuan Bao¹, Can Cui¹, Simon Kwoon-Ho Chow^{1

2}, Ling Qin¹, Ronald Man Yeung Wong¹, Wing-Hoi Cheung^{1

2}

Affiliations

¹ Department of Orthopaedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
² The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, China.

Abstract

Sarcopenia is an aging process with a decline of skeletal muscle mass and function, which is a challenging public health problem with reduced quality of life in patients. The endplate, the post-synaptic part of the neuromuscular junction (NMJ), occupies 0.1% of the myofiber surface area only, but is composed of millions of acetylcholine receptors (AChRs) that are efficient in binding to acetylcholine (ACh) and triggering skeletal muscle contraction. This systematic review aims to examine aging-associated alterations of post-synaptic AChRs, including morphology, function and related gene expression. A systematic literature search was conducted in PubMed, Embase and Web of Science with relevant keywords by two independent reviewers. Original pre-clinical and clinical studies regarding AChRs changes during aging with available full text and written in English were included. Information was extracted from the included studies for further review. In total, 30 articles were included. Various parameters assessing AChRs alterations by radioassay, immunofluorescence, electrophysiology and mechanical test were reported. Endplate fragmentation and denervation were common in old skeletal muscles during aging. To ensure efficient NMJ transmission and force generation, type I or IIb muscle fibers tended to have increased ACh quanta releasing after electrical stimulations, while type IIa muscle fibers tended to have stronger binding between ACh and AChRs, but the overall function of AChRs was reduced during aging. Alterations of AChRs area depended on muscle type, species and the progress of muscle atrophy and type I muscles fibers tended to demonstrate enlarging AChRs areas. Myogenic regulator factors (MRFs) can regulate the expression of AChRs subunits, while decreased MRF4 may lead to expression changes of AChRs subunits during aging. Sarcoglycan-α can delay low-density lipoprotein receptor-related protein 4 (LRP4) degradation. This protein was increased in old muscles but still cannot suppress the degradation of LRP4. Investigating the role of these AChRs-related genes in the process of aging may provide a potential target to treat sarcopenia.

Keywords: acetylcholine receptors; aging; sarcopenia; skeletal muscle; systematic review.

Publication types

Systematic Review