Exploring motor unit and neuromuscular junction dysfunction in aging and sarcopenia: insights from electromyography...

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.