The key pathology of multiple sclerosis (MS) comprises demyelination, axonal damage, and neuronal loss, and when MS develops into the progressive phase it is essentially untreatable. Identifying new targets in both axons and oligodendrocyte progenitor cells (OPCs) and rejuvenating the aged OPCs holds promise for this unmet medical need. We summarize here the recent evidence showing that mitochondria in both axons and OPCs are impaired, and lipid metabolism of OPCs within demyelinated lesion and in the aged CNS is disturbed. Given that emerging evidence shows that rewiring cellular metabolism regulates stem cell aging, to protect axons from degeneration and promote differentiation of OPCs, we propose that restoring the impaired metabolism of both OPCs and axons in the aged CNS in a synergistic way could be a promising strategy to enhance remyelination in the aged CNS, leading to novel drug-based approaches to treat the progressive phase of MS.

多发性硬化症 (MS) 的关键病理学包括脱髓鞘、轴突损伤和神经元丢失，当 MS 发展到进行性阶段时，它基本上是无法治愈的。识别轴突和少突胶质祖细胞 (OPCs) 中的新靶标并恢复老化的 OPCs 有望满足这一未满足的医疗需求。我们在此总结了最近的证据，表明轴突和 OPCs 中的线粒体均受损，脱髓鞘病变和老年中枢神经系统中 OPCs 的脂质代谢受到干扰。鉴于新出现的证据表明，重新布线的细胞代谢调节干细胞衰老，保护轴突免于退化并促进 OPCs 的分化，