GDF11 通过抑制 p21 减缓兴奋性神经元衰老和大脑衰老,Nature Communications

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GDF11 通过抑制 p21 减缓兴奋性神经元衰老和大脑衰老
Nature Communications ( IF 14.7 ) Pub Date : 2023-11-17 , DOI: 10.1038/s41467-023-43292-1
Di-Xian Wang _{1,

2} , Zhao-Jun Dong _{1,

2} , Sui-Xin Deng ₃ , Ying-Ming Tian ₄ , Yu-Jie Xiao ₃ , Xinran Li ₅ , Xiao-Ru Ma _{1,

2} , Liang Li ₃ , Pengxiao Li ₆ , Hui-Zhong Chang ₄ , Longqi Liu ₄ , Fan Wang _{1,

2} , Yang Wu _{1,

2} , Xiang Gao _{1,

2} , Shuang-Shuang Zheng _{1,

2} , Hui-Min Gu _{1,

2} , Ya-Nan Zhang ₇ , Jian-Bin Wu _{1,

2} , Fan Wu ₈ , Yonglin Peng ₆ , Xiao-Wen Zhang _{1,

2} , Ren-Ya Zhan ₈ , Li-Xia Gao ₉ , Qiming Sun ₁₀ , Xing Guo ₇ , Xiao-Dong Zhao ₆ , Jian-Hong Luo _{11,

12} , Ruhong Zhou ₁₃ , Lei Han ₄ , Yousheng Shu ₃ , Jing-Wei Zhao _{1,

2}

Affiliation

Department of Pathology of Sir Run Run Shaw Hospital, and Department of Human Anatomy, Histology and Embryology, System Medicine Research Center, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, 310058, Hangzhou, Zhejiang, China.
Center of Cryo-Electron Microscopy, Zhejiang University, 310058, Hangzhou, Zhejiang, China.
Department of Neurosurgery, Jinshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, 201508, Shanghai, China.
BGI Research, 310030, Hangzhou, China.
The Global Scientific and Technological Innovation Center and the MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, 310058, Hangzhou, Zhejiang, China.
Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai; Center for Systems Biomedicine, Shanghai Jiao Tong University, 200240, Shanghai, China.
Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.
Department of Neurosurgery, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, 310003, Hangzhou, China.
Department of Neurology of the Second Affiliated Hospital, Interdisciplinary Institute of Neuroscience and Technology, Zhejiang University School of Medicine, 310020, Hangzhou, China.
Department of Biochemistry, and Department of Cardiology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Neurobiology and Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 310058, Hangzhou, Zhejiang, China.
NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Zhejiang, China.
Institute of Quantitative Biology, College of Life Sciences, Zhejiang University, Hangzhou, China.

作为大脑中的主要神经元类型，兴奋性神经元（EN）调节线虫的寿命。然而，EN 如何衰老尚不清楚。在这里，我们发现生长分化因子 11 (GDF11) 主要在成年小鼠、狨猴和人脑的 EN 中表达。在小鼠中，有丝分裂后 EN 中 GDF11 的选择性敲除塑造了大脑衰老相关的转录谱，诱导 EN 衰老和过度兴奋，修剪其树突，阻碍其突触输入，损害物体识别记忆并缩短寿命，从而建立了一种GDF11、大脑衰老和认知之间的功能联系。体外 GDF11 缺失会导致 Neuro-2a 细胞衰老。从机制上讲，GDF11 缺失通过 Smad2 诱导促衰老因子 p21 的转录来诱导神经元衰老。这项工作表明内源性 GDF11 可以抑制 EN 衰老和大脑老化。

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更新日期：2023-11-18

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