Restoring nuclear entry of Sirtuin 2 in oligodendrocyte progenitor cells promotes remyelination during ageing.
Restoring nuclear entry of Sirtuin 2 in oligodendrocyte progenitor cells promotes remyelination during ageing.
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DOI：
10.1038/s41467-022-28844-1
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发表时间：
2022-03-09
影响因子：
16.6
通讯作者：
Zhao JW
中科院分区：
文献类型：
--
作者：
Ma XR;Zhu X;Xiao Y;Gu HM;Zheng SS;Li L;Wang F;Dong ZJ;Wang DX;Wu Y;Yang C;Jiang W;Yao K;Yin Y;Zhang Y;Peng C;Gao L;Meng Z;Hu Z;Liu C;Li L;Chen HZ;Shu Y;Ju Z;Zhao JW
衰老过程中中枢神经系统髓鞘再生能力的年龄依赖性下降与少突胶质祖细胞（OPCs）分化能力下降有关。能够增强OPC分化或使OPC恢复活力的分子参与者尚不清楚。在这里，我们表明，在小鼠OPCs中，SIRT 2的核进入受损，NAD+水平在衰老过程中降低。当我们补充β-烟酰胺单核苷酸（β-NMN）时，NAD+前体，SIRT 2进入OPC的核，OPC分化和髓鞘再生在老年动物中得到拯救。我们表明，对髓鞘形成的影响是通过NAD+-SIRT 2-H3 K18 Ac-ID 4轴介导的，SIRT 2是再生OPCs所必需的。我们的研究结果表明，SIRT 2和NAD+水平拯救老年OPC分化潜力的水平与年轻的年龄，提供潜在的目标，以提高髓鞘再生在老化过程中。中枢神经系统髓鞘再生的年龄依赖性下降与少突胶质祖细胞（OPCs）分化能力的下降有关。在这里，作者表明，在小鼠OPCs的衰老过程中，SIRT 2的核进入受损，NAD+水平降低。β-烟酰胺单甘肽（β-NMN）补充剂延缓了老年小鼠的髓鞘老化并增强了髓鞘再生。
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. Age-dependent decline in remyelination in the CNS is associated with declined differentiation capacity of oligodendrocyte progenitor cells (OPCs). Here, the authors show nuclear entry of SIRT2 is impaired and NAD+ levels are reduced during ageing in mouse OPCs. β-nicotinamide mononucleotide (β-NMN) supplement delays myelin aging and enhances remyelination in the aged mice.
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影响因子：
14.8
作者：
Beyer BA;Fang M;Sadrian B;Montenegro-Burke JR;Plaisted WC;Kok BPC;Saez E;Kondo T;Siuzdak G;Lairson LL
通讯作者：
Lairson LL
DOI：
10.1038/s41580-020-00313-x
发表时间：
2021-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Covarrubias AJ;Perrone R;Grozio A;Verdin E
通讯作者：
Verdin E
影响因子：
25
作者：
Kang, Shin H.;Li, Ying;Fukaya, Masahiro;Lorenzini, Ileana;Cleveland, Don W.;Ostrow, Lyle W.;Rothstein, Jeffrey D.;Bergles, Dwight E.
通讯作者：
Bergles, Dwight E.
影响因子：
5.5
作者：
Ji, Shaoping;Doucette, J. Ronald;Nazarali, Adil J.
通讯作者：
Nazarali, Adil J.
Gadd45a介导的端粒表观遗传反应调节干细胞衰老和寿命
影响因子：
7.7
作者：
Diao, Daojun;Wang, Hu;Ju, Zhenyu
通讯作者：
Ju, Zhenyu