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Restoring nuclear entry of Sirtuin 2 in oligodendrocyte progenitor cells promotes remyelination during ageing

Author

Listed:
  • Xiao-Ru Ma

    (Zhejiang University School of Medicine)

  • Xudong Zhu

    (Hangzhou Normal University)

  • Yujie Xiao

    (Fudan University)

  • Hui-Min Gu

    (Zhejiang University School of Medicine)

  • Shuang-Shuang Zheng

    (Zhejiang University School of Medicine)

  • Liang Li

    (Fudan University)

  • Fan Wang

    (Zhejiang University School of Medicine)

  • Zhao-Jun Dong

    (Zhejiang University School of Medicine)

  • Di-Xian Wang

    (Zhejiang University School of Medicine)

  • Yang Wu

    (Zhejiang University School of Medicine)

  • Chenyu Yang

    (Zhejiang University)

  • Wenhong Jiang

    (Zhejiang University School of Medicine)

  • Ke Yao

    (Tsinghua University)

  • Yue Yin

    (Shanghai Advanced Research Institute, Chinese Academy of Sciences)

  • Yang Zhang

    (Zhongshan Hospital of Fudan University)

  • Chao Peng

    (Shanghai Advanced Research Institute, Chinese Academy of Sciences)

  • Lixia Gao

    (Zhejiang University School of Medicine)

  • Zhuoxian Meng

    (Zhejiang University School of Medicine)

  • Zeping Hu

    (Tsinghua University
    Tsinghua University)

  • Chong Liu

    (Zhejiang University School of Medicine)

  • Li Li

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Hou-Zao Chen

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Yousheng Shu

    (Beijing Normal University)

  • Zhenyu Ju

    (Jinan University)

  • Jing-Wei Zhao

    (Zhejiang University School of Medicine
    Zhejiang University)

Abstract

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.

Suggested Citation

  • Xiao-Ru Ma & Xudong Zhu & Yujie Xiao & Hui-Min Gu & Shuang-Shuang Zheng & Liang Li & Fan Wang & Zhao-Jun Dong & Di-Xian Wang & Yang Wu & Chenyu Yang & Wenhong Jiang & Ke Yao & Yue Yin & Yang Zhang & C, 2022. "Restoring nuclear entry of Sirtuin 2 in oligodendrocyte progenitor cells promotes remyelination during ageing," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28844-1
    DOI: 10.1038/s41467-022-28844-1
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    3. Stefan G. Tullius & Hector Rodriguez Cetina Biefer & Suyan Li & Alexander J. Trachtenberg & Karoline Edtinger & Markus Quante & Felix Krenzien & Hirofumi Uehara & Xiaoyong Yang & Haydn T. Kissick & Wi, 2014. "NAD+ protects against EAE by regulating CD4+ T-cell differentiation," Nature Communications, Nature, vol. 5(1), pages 1-17, December.
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    Cited by:

    1. Raúl F. Pérez & Patricia Tezanos & Alfonso Peñarroya & Alejandro González-Ramón & Rocío G. Urdinguio & Javier Gancedo-Verdejo & Juan Ramón Tejedor & Pablo Santamarina-Ojeda & Juan José Alba-Linares & , 2024. "A multiomic atlas of the aging hippocampus reveals molecular changes in response to environmental enrichment," Nature Communications, Nature, vol. 15(1), pages 1-26, December.
    2. John N. Mariani & Benjamin Mansky & Pernille M. Madsen & Dennis Salinas & Deniz Kesmen & Nguyen P. T. Huynh & Nicholas J. Kuypers & Erin R. Kesel & Janna Bates & Casey Payne & Devin Chandler-Militello, 2024. "Repression of developmental transcription factor networks triggers aging-associated gene expression in human glial progenitor cells," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Di-Xian Wang & Zhao-Jun Dong & Sui-Xin Deng & Ying-Ming Tian & Yu-Jie Xiao & Xinran Li & Xiao-Ru Ma & Liang Li & Pengxiao Li & Hui-Zhong Chang & Longqi Liu & Fan Wang & Yang Wu & Xiang Gao & Shuang-Sh, 2023. "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21," Nature Communications, Nature, vol. 14(1), pages 1-24, December.

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