ArticleNature communications2023
GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21.
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Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 26 citations in OpenAlex.
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- PTP1B in astrocytes drives pathogen-induced neurodegeneration.Journal of neuroinflammation · 2026Article
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- Kill two birds with one stone: Reprogramming tumor microenvironment with growth differentiation factor 11.World journal of gastroenterology · 2026Article
- Investigating and correcting a rare pathogenic mutation in GDF11.HGG advances · 2026Article
- GDF11 alleviates glucocorticoid-induced osteonecrosis of the femoral head by regulating angiogenesis via the PI3K-AKT-eNOS pathway.Communications biology · 2025Article
- GDF11-secreting cell transplant efficiently ameliorates age-related pulmonary fibrosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
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- DNMT3a Deficiency Contributes to Anesthesia/Surgery-Induced Synaptic Dysfunction and Cognitive Impairment in Aged Mice.Aging cell · 2025Article
- Senescent brain cell types in Alzheimer's disease: Pathological mechanisms and therapeutic opportunities.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- GDF11 Mitigates Neuropathic Pain via Regulation of Microglial Polarization and Neuroinflammation through TGF-βR1/SMAD2/NF-κB Pathway in Male Mice.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Development of Calcium-Dependent Phospholipase A2 Inhibitors to Target Cellular Senescence and Oxidative Stress in Neurodegenerative Diseases.Antioxidants & redox signaling · 2024Review
- Therapeutic targeting of senescent cells in the CNS.Nature reviews. Drug discovery · 2024Review
- Growth differentiation factor 11 alleviates oxidative stress-induced senescence of endothelial progenitor cells via activating autophagy.Stem cell research & therapy · 2024Article
- Role of Hippocampal Glutamatergic Synaptic Alterations in Sevoflurane-Induced Cognitive Dysfunction in Aged Mice.CNS neuroscience & therapeutics · 2024Article
- The role of cellular senescence in neurodegenerative diseases.Archives of toxicology · 2024Review
- Neutrophil Extracellular Traps Upregulate p21 and Suppress Cell Cycle Progression to Impair Endothelial Regeneration after Inflammatory Lung Injury.Journal of clinical medicine · 2024Article
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Authors and funding
31 authors at 8 institutions in 1 country.
Di-Xian Wang *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.ORCID 0000-0002-8065-9782
Zhao-Jun Dong *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.ORCID 0000-0002-9387-2937
Sui-Xin Deng *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.ORCID 0000-0003-4795-2570
Ying-Ming TianBGI Research, 310030, Hangzhou, China.ORCID 0000-0002-7608-3549
Yu-Jie XiaoDepartment 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.
Xinran LiThe 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.ORCID 0000-0003-2805-3510
Xiao-Ru MaDepartment 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.ORCID 0000-0001-5337-7272
Liang LiDepartment 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.
Pengxiao LiKey Laboratory of Systems Biomedicine (Ministry of Education), Shanghai; Center for Systems Biomedicine, Shanghai Jiao Tong University, 200240, Shanghai, China.
Hui-Zhong ChangBGI Research, 310030, Hangzhou, China.ORCID 0000-0002-9925-1138
Longqi LiuBGI Research, 310030, Hangzhou, China.ORCID 0000-0002-5828-5542
Fan WangDepartment 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.ORCID 0000-0003-1197-0531
Yang WuDepartment 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.ORCID 0000-0002-3350-952X
Xiang GaoDepartment 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.ORCID 0009-0006-7773-5840
Shuang-Shuang ZhengDepartment 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.
Hui-Min GuDepartment 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.
Ya-Nan ZhangZhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.
Jian-Bin WuDepartment 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.ORCID 0009-0003-0160-7429
Fan WuDepartment of Neurosurgery, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, 310003, Hangzhou, China.ORCID 0000-0002-6671-5282
Yonglin PengKey Laboratory of Systems Biomedicine (Ministry of Education), Shanghai; Center for Systems Biomedicine, Shanghai Jiao Tong University, 200240, Shanghai, China.ORCID 0000-0003-3446-3030
Xiao-Wen ZhangDepartment 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.ORCID 0009-0003-8728-1414
Ren-Ya ZhanDepartment of Neurosurgery, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, 310003, Hangzhou, China.ORCID 0000-0002-0619-6257
Li-Xia GaoDepartment of Neurology of the Second Affiliated Hospital, Interdisciplinary Institute of Neuroscience and Technology, Zhejiang University School of Medicine, 310020, Hangzhou, China.ORCID 0000-0002-1884-0257
Qiming SunDepartment of Biochemistry, and Department of Cardiology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.ORCID 0000-0003-4988-9886
Xing GuoZhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.ORCID 0000-0002-9794-1725
Xiao-Dong ZhaoKey Laboratory of Systems Biomedicine (Ministry of Education), Shanghai; Center for Systems Biomedicine, Shanghai Jiao Tong University, 200240, Shanghai, China.ORCID 0000-0002-2630-7161
Jian-Hong LuoDepartment of Neurobiology and Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 310058, Hangzhou, Zhejiang, China.
Ruhong ZhouInstitute of Quantitative Biology, College of Life Sciences, Zhejiang University, Hangzhou, China.ORCID 0000-0001-8624-5591
Lei HanBGI Research, 310030, Hangzhou, China. hanlei2@genomics.cn.
Yousheng ShuDepartment 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. yousheng@fudan.edu.cn.ORCID 0000-0002-2834-2876
Jing-Wei ZhaoDepartment 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. jingweizhao@zju.edu.cn.ORCID 0000-0002-1135-9743
Sir Run Run Shaw Hospital · CNFudan University · CNZhejiang University · CNBGI Research · CNMinistry of Education of the People's Republic of China · CNFirst Affiliated Hospital Zhejiang University · CNSecond Affiliated Hospital of Zhejiang University · CNBGI Group (China) · CN
Funding
National Natural Science Foundation of China (National Science Foundation of China) 81971144
Abstract
As a major neuron type in the brain, the excitatory neuron (EN) regulates the lifespan in C. elegans. How the EN acquires senescence, however, is unknown. Here, we show that growth differentiation factor 11 (GDF11) is predominantly expressed in the EN in the adult mouse, marmoset and human brain. In mice, selective knock-out of GDF11 in the post-mitotic EN shapes the brain ageing-related transcriptional profile, induces EN senescence and hyperexcitability, prunes their dendrites, impedes their synaptic input, impairs object recognition memory and shortens the lifespan, establishing a functional link between GDF11, brain ageing and cognition. In vitro GDF11 deletion causes cellular senescence in Neuro-2a cells. Mechanistically, GDF11 deletion induces neuronal senescence via Smad2-induced transcription of the pro-senescence factor p21. This work indicates that endogenous GDF11 acts as a brake on EN senescence and brain ageing.
Indexed as
Caenorhabditis elegansGrowth Differentiation FactorsAdultAgingAnimalsBone Morphogenetic ProteinsBrainHumansMiceNeuronsBone Morphogenetic ProteinsGDF11 protein, humanGrowth Differentiation Factors
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