恢复少突胶质前体细胞中 Sirtuin 2 的核内进入可促进衰老过程中的髓鞘再生。
Restoring nuclear entry of Sirtuin 2 in oligodendrocyte progenitor cells promotes remyelination during ageing.
机构信息
Department of Pathology of Sir Run Run Shaw Hospital and Department of Human Anatomy, Histology and Embryology, System Medicine Research Center, Center for Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang, China.
Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China.
出版信息
Nat Commun. 2022 Mar 9;13(1):1225. doi: 10.1038/s41467-022-28844-1.
The age-dependent decline in remyelination potential of the central nervous system during ageing is associated with a declined differentiation capacity of oligodendrocyte progenitor cells (OPCs). The molecular players that can enhance OPC differentiation or rejuvenate OPCs are unclear. Here we show that, in mouse OPCs, nuclear entry of SIRT2 is impaired and NAD levels are reduced during ageing. When we supplement β-nicotinamide mononucleotide (β-NMN), an NAD precursor, nuclear entry of SIRT2 in OPCs, OPC differentiation, and remyelination were rescued in aged animals. We show that the effects on myelination are mediated via the NAD-SIRT2-H3K18Ac-ID4 axis, and SIRT2 is required for rejuvenating OPCs. Our results show that SIRT2 and NAD levels rescue the aged OPC differentiation potential to levels comparable to young age, providing potential targets to enhance remyelination during ageing.
随着年龄的增长，中枢神经系统的髓鞘再生能力逐渐下降，这与少突胶质前体细胞（OPC）分化能力下降有关。目前尚不清楚哪些分子能够增强 OPC 的分化或使 OPC 年轻化。本研究表明，在小鼠 OPC 中，SIRT2 的核内易位在衰老过程中受损，NAD 水平降低。当我们补充烟酰胺单核苷酸（β-NMN），一种 NAD 前体时，OPC 中的 SIRT2 核内易位、OPC 分化和髓鞘再生在老年动物中得到挽救。我们表明，对髓鞘形成的影响是通过 NAD-SIRT2-H3K18Ac-ID4 轴介导的，SIRT2 是使 OPC 年轻化所必需的。我们的研究结果表明，SIRT2 和 NAD 水平可将衰老的 OPC 分化潜能恢复到与年轻时期相当的水平，为增强衰老过程中的髓鞘再生提供了潜在靶点。
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