骨骼肌具备卓越的重新排列和高效再生能力。然而，在衰老、严重损伤或病理情况下，完整的再生程序受到严重影响，导致肌肉质量和功能逐渐丧失，这种情况被称为肌肉萎缩。组织修复程序受损主要归因于干细胞逐渐枯竭和调节信号的改变。肌肉再生缺陷会严重影响运动神经轴索的重新内布和神经肌肉连接的发展，最终导致骨骼肌萎缩。在衰老过程中，神经肌肉连接的形成和维持出现缺陷，这是多种神经肌肉疾病发病机制的原因。然而，如何在再生纤维上恢复神经肌肉连接仍然大部分未知。有人认为，用于轴突引导的引力和排斥信号可能参与了这个过程，尤其是被称为神经元素的引导分子在其中起到关键作用。神经元素是一类广泛的细胞间通信的胞外调节信号，最初被发现时是作为轴突引导因子，已被证明在癌症进展、胚胎器官生成、骨骼肌内布和其他不同组织的生理和发育功能中发挥着多方面的作用。特别是在骨骼肌中，特定的神经元素分子参与了神经-肌肉连接的恢复和重塑，突出了它们在确保肌肉再生成功方面的可能角色。本综述旨在讨论衰老对骨骼肌再生和神经肌肉连接重塑的影响，并重点介绍神经元素在这一背景下的最新研究进展。

Skeletal muscle is characterized by a remarkable capacity to rearrange after physiological changes and efficiently regenerate. However, during aging, extensive injury, or pathological conditions, the complete regenerative program is severely affected, with a progressive loss of muscle mass and function, a condition known as sarcopenia. The compromised tissue repair program is attributable to the gradual depletion of stem cells and to altered regulatory signals. Defective muscle regeneration can severely affect re-innervation by motor axons, and neuromuscular junctions (NMJs) development, ultimately leading to skeletal muscle atrophy. Defects in NMJ formation and maintenance occur physiologically during aging and are responsible for the pathogenesis of several neuromuscular disorders. However, it is still largely unknown how neuromuscular connections are restored on regenerating fibers. It has been suggested that attractive and repelling signals used for axon guidance could be implicated in this process; in particular, guidance molecules called semaphorins play a key role. Semaphorins are a wide family of extracellular regulatory signals with a multifaceted role in cell-cell communication. Originally discovered as axon guidance factors, they have been implicated in cancer progression, embryonal organogenesis, skeletal muscle innervation, and other physiological and developmental functions in different tissues. In particular, in skeletal muscle, specific semaphorin molecules are involved in the restoration and remodeling of the nerve-muscle connections, thus emphasizing their plausible role to ensure the success of muscle regeneration. This review article aims to discuss the impact of aging on skeletal muscle regeneration and NMJs remodeling and will highlight the most recent insights about the role of semaphorins in this context.