Department of Biomedical Sciences, University of Padova, Via U. Bassi 58/B, Padova 35131, Italy.
Department of Biomedical Sciences, University of Padova, Via U. Bassi 58/B, Padova 35131, Italy; CIR-MYO Myology Center, University of Padova, Via U. Bassi 58/B, Padova 35131, Italy.
Ageing Res Rev. 2024 Dec;102:102586. doi: 10.1016/j.arr.2024.102586. Epub 2024 Nov 17.
Inactivity and ageing can have a detrimental impact on skeletal muscle and the neuromuscular junction (NMJ). Decreased physical activity results in muscle atrophy, impaired mitochondrial function, and NMJ instability. Ageing is associated with a progressive decrease in muscle mass, deterioration of mitochondrial function in the motor axon terminals and in myofibres, NMJ instability and loss of motor units. Focusing on the impact of inactivity and ageing, this review examines the consequences on NMJ stability and the role of mitochondrial dysfunction, delving into their complex relationship with ageing and disuse. Evidence suggests that mitochondrial dysfunction can be a pathogenic driver for NMJ alterations, with studies revealing the role of mitochondrial defects in motor neuron degeneration and NMJ instability. Two perspectives behind NMJ instability are discussed: one is that mitochondrial dysfunction in skeletal muscle triggers NMJ deterioration, the other envisages dysfunction of motor terminal mitochondria as a primary contributor to NMJ instability. While evidence from these studies supports both perspectives on the relationship between NMJ dysfunction and mitochondrial impairment, gaps persist in the understanding of how mitochondrial dysfunction can cause NMJ deterioration. Further research, both in humans and in animal models, is essential for unravelling the mechanisms and potential interventions for age- and inactivity-related neuromuscular and mitochondrial alterations.
不活动和衰老会对骨骼肌和神经肌肉接头（NMJ）产生有害影响。体力活动减少会导致肌肉萎缩、线粒体功能受损和 NMJ 不稳定。衰老与肌肉质量的逐渐减少、运动轴突末梢和肌纤维中线粒体功能的恶化、NMJ 不稳定以及运动单位的丧失有关。本综述重点关注不活动和衰老的影响，研究了 NMJ 稳定性的后果以及线粒体功能障碍的作用，深入探讨了它们与衰老和废用之间的复杂关系。有证据表明，线粒体功能障碍可能是 NMJ 改变的致病驱动因素，研究揭示了线粒体缺陷在运动神经元退化和 NMJ 不稳定中的作用。讨论了 NMJ 不稳定的两个观点：一种观点是骨骼肌中线粒体功能障碍触发 NMJ 恶化，另一种观点则认为运动终末线粒体功能障碍是 NMJ 不稳定的主要原因。尽管这些研究为 NMJ 功能障碍与线粒体损伤之间的关系提供了支持，但对于线粒体功能障碍如何导致 NMJ 恶化的理解仍存在差距。进一步的研究，无论是在人类还是在动物模型中，对于揭示与年龄和不活动相关的神经肌肉和线粒体改变的机制以及潜在的干预措施都是至关重要的。
