Wu Shuangchan, Chen Jun
Sanhang Institute for Brain Science and Technology (SiBST), School of Medical Research, Northwestern Polytechnical University, Xi'an, Shaanxi Province, China.
Shenzhen Research Institute of Northwestern Polytechnical University, Shenzhen, Guangdong Province, China.
Neural Regen Res. 2026 Feb 1;21(2):648-658. doi: 10.4103/NRR.NRR-D-24-00848. Epub 2025 Jan 13.
Myelination, the continuous ensheathment of neuronal axons, is a lifelong process in the nervous system that is essential for the precise, temporospatial conduction of action potentials between neurons. Myelin also provides intercellular metabolic support to axons. Even minor disruptions in the integrity of myelin can impair neural performance and increase susceptibility to neurological diseases. In fact, myelin degeneration is a well-known neuropathological condition that is associated with normal aging and several neurodegenerative diseases, including multiple sclerosis and Alzheimer's disease. In the central nervous system, compact myelin sheaths are formed by fully mature oligodendrocytes. However, the entire oligodendrocyte lineage is susceptible to changes in the biological microenvironment and other risk factors that arise as the brain ages. In addition to their well-known role in action potential propagation, oligodendrocytes also provide intercellular metabolic support to axons by transferring energy metabolites and delivering exosomes. Therefore, myelin degeneration in the aging central nervous system is a significant contributor to the development of neurodegenerative diseases. Interventions that mitigate age-related myelin degeneration can improve neurological function in aging individuals. In this review, we investigate the changes in myelin that are associated with aging and their underlying mechanisms. We also discuss recent advances in understanding how myelin degeneration in the aging brain contributes to neurodegenerative diseases and explore the factors that can prevent, slow down, or even reverse age-related myelin degeneration. Future research will enhance our understanding of how reducing age-related myelin degeneration can be used as a therapeutic target for delaying or preventing neurodegenerative diseases.
髓鞘形成，即神经元轴突的持续包裹，是神经系统中一个贯穿终生的过程，对于神经元之间动作电位的精确时空传导至关重要。髓鞘还为轴突提供细胞间代谢支持。即使髓鞘完整性出现轻微破坏也会损害神经功能，并增加患神经疾病的易感性。事实上，髓鞘变性是一种众所周知的神经病理状况，与正常衰老以及包括多发性硬化症和阿尔茨海默病在内的几种神经退行性疾病相关。在中枢神经系统中，紧密的髓鞘由完全成熟的少突胶质细胞形成。然而，整个少突胶质细胞谱系易受生物微环境变化以及随着大脑衰老而出现的其他风险因素的影响。除了在动作电位传播中众所周知的作用外，少突胶质细胞还通过转移能量代谢物和传递外泌体为轴突提供细胞间代谢支持。因此，衰老中枢神经系统中的髓鞘变性是神经退行性疾病发展的一个重要因素。减轻与年龄相关的髓鞘变性的干预措施可以改善老年人的神经功能。在这篇综述中，我们研究了与衰老相关的髓鞘变化及其潜在机制。我们还讨论了在理解衰老大脑中的髓鞘变性如何导致神经退行性疾病方面的最新进展，并探索可以预防、减缓甚至逆转与年龄相关的髓鞘变性的因素。未来的研究将增进我们对如何将减少与年龄相关的髓鞘变性用作延迟或预防神经退行性疾病的治疗靶点的理解。
