英国剑桥大学Robin J.M. Franklin和Peter van Wijngaarden等研究人员合作发现，二甲双胍通过使衰老的干细胞恢复活力来重塑中枢神经系统的髓鞘再生能力。该研究,2019年10月3日发表于国际一流学术期刊《细胞—干细胞》。

研究人员发现，成年啮齿动物少突胶质祖细胞（OPC）的分化潜力随年龄的增长而降低。老化的OPC对分化前信号无反应，这表明那些旨在增强OPC分化的治疗方法存在固有限制。功能的下降与细胞衰老有关，包括代谢功能下降和DNA损伤增加。空腹或用二甲双胍治疗可以逆转这些变化并恢复衰老OPC的再生能力，从而改善局灶性脱髓鞘后老年动物的髓鞘再生。

用二甲双胍治疗的衰老OPC可以恢复对促分化信号的响应，这提示了恢复活力和促分化疗法的协同作用。这些发现提供了与衰老相关的髓鞘再生失败的见解，并建议了相关治疗措施来逆转这种慢性疾病的恶化。

据了解，由OPC产生少突胶质细胞与年龄相关的失败与多发性硬化症中不可逆的神经变性有关。因此，能够治疗慢性髓鞘疾病的再生方法具有巨大潜力。

附：英文原文

Title: Metformin Restores CNS Remyelination Capacity by Rejuvenating Aged Stem Cells

Author: Bjrn Neumann, Roey Baror, Chao Zhao, Michael Segel, Sabine Dietmann, Khalil S. Rawji, Sarah Foerster, Crystal R. McClain, Kevin Chalut, Peter van Wijngaarden, Robin J.M. Franklin

Issue&Volume: Volume 25 Issue 4

Abstract: The age-related failure to produce oligodendrocytes from oligodendrocyte progenitor cells (OPCs) is associated with irreversible neurodegeneration in multiple sclerosis (MS). Consequently, regenerative approaches have significant potential for treating chronic demyelinating diseases. Here, we show that the differentiation potential of adult rodent OPCs decreases with age. Aged OPCs become unresponsive to pro-differentiation signals, suggesting intrinsic constraints on therapeutic approaches aimed at enhancing OPC differentiation. This decline in functional capacity is associated with hallmarks of cellular aging, including decreased metabolic function and increased DNA damage. Fasting or treatment with metformin can reverse these changes and restore the regenerative capacity of aged OPCs, improving remyelination in aged animals following focal demyelination. Aged OPCs treated with metformin regain responsiveness to pro-differentiation signals, suggesting synergistic effects of rejuvenation and pro-differentiation therapies. These findings provide insight into aging-associated remyelination failure and suggest therapeutic interventions for reversing such declines in chronic disease.

DOI: 10.1016/j.stem.2019.08.015

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30350-9