Cui Can, Hu Yong, Wong Ronald Man Yeung, Zhang Ning, Guan Yuzhou, Cheung Wing-Hoi
Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China.
Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
Geroscience. 2025 Jul 8. doi: 10.1007/s11357-025-01760-0.
The neuromuscular junction (NMJ) is a vital interface between motor neurons and muscle fibers, and alterations in its structure and function can substantially influence the onset and progression of sarcopenia. Electromyography (EMG) is a critical tool to assess motor unit and NMJ function, providing insights into neuromuscular activation patterns and the integrity of motor unit communication. However, its implications for aging and muscle performance during sarcopenia have not been fully discussed. Therefore, we conducted a systematic review using the PubMed, Embase, and Web of Science databases by employing relevant keywords. A total of 53 articles were included. This review explored the various alterations in the NMJ associated with aging, their functional implications, and potential interventions to mitigate these effects, highlighting the structural and functional alterations of the NMJ during aging and sarcopenia. Key findings include early NMJ transmission instability, motor unit loss and compensatory remodeling, and impaired neuromuscular activation preceding overt muscle atrophy and weakness. Notably, biomarkers such as C-terminal agrin fragment and neurofilament light chain, along with EMG-derived parameters (e.g., jitter, jiggle, MUNE), are sensitive indicators of NMJ deterioration. Both physical inactivity and hormonal changes (e.g., menopause) accelerate NMJ decline, while interventions such as resistance and endurance training, nutritional supplementation, and emerging gene therapies demonstrate potential to preserve or restore NMJ structure and function. In conclusion, this systematic review underscores the importance of NMJ dysfunction in aging and sarcopenia, advocating further research into diagnostic biomarkers and therapeutic strategies to enhance NMJ integrity. The interplay between aging, exercise, and NMJ function is complex and requires a nuanced approach to rehabilitation and exercise strategies tailored to the aging population. Future directions should prioritize the development of sensitive biomarkers, mechanistic studies of NMJ degeneration, and rigorous evaluation of multimodal interventions to mitigate neuromuscular decline and promote healthy aging.
神经肌肉接头（NMJ）是运动神经元与肌纤维之间的重要接口，其结构和功能的改变会显著影响肌肉减少症的发生和发展。肌电图（EMG）是评估运动单位和神经肌肉接头功能的关键工具，可深入了解神经肌肉激活模式以及运动单位通信的完整性。然而，其在肌肉减少症期间对衰老和肌肉性能的影响尚未得到充分讨论。因此，我们使用PubMed、Embase和Web of Science数据库，通过使用相关关键词进行了一项系统综述。共纳入53篇文章。本综述探讨了与衰老相关的神经肌肉接头的各种改变、其功能影响以及减轻这些影响的潜在干预措施，突出了衰老和肌肉减少症期间神经肌肉接头的结构和功能改变。主要发现包括神经肌肉接头早期传递不稳定、运动单位丧失和代偿性重塑，以及在明显的肌肉萎缩和无力之前神经肌肉激活受损。值得注意的是，生物标志物如C端集聚蛋白片段和神经丝轻链，以及肌电图衍生参数（如抖动、微颤、运动单位数目估计），是神经肌肉接头退化的敏感指标。缺乏身体活动和激素变化（如更年期）都会加速神经肌肉接头的衰退，而阻力训练、耐力训练、营养补充和新兴的基因疗法等干预措施显示出保留或恢复神经肌肉接头结构和功能的潜力。总之，这项系统综述强调了神经肌肉接头功能障碍在衰老和肌肉减少症中的重要性，主张进一步研究诊断生物标志物和治疗策略以增强神经肌肉接头的完整性。衰老、运动和神经肌肉接头功能之间的相互作用很复杂，需要针对老年人群制定细致入微的康复和运动策略。未来的方向应优先发展敏感的生物标志物、神经肌肉接头退化的机制研究，以及对多模式干预措施进行严格评估，以减轻神经肌肉衰退并促进健康衰老。
