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GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10656444/ https://www.ncbi.nlm.nih.gov/pubmed/37978295 http://dx.doi.org/10.1038/s41467-023-43292-1 |
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author | Wang, Di-Xian Dong, Zhao-Jun Deng, Sui-Xin Tian, Ying-Ming Xiao, Yu-Jie Li, Xinran Ma, Xiao-Ru Li, Liang Li, Pengxiao Chang, Hui-Zhong Liu, Longqi Wang, Fan Wu, Yang Gao, Xiang Zheng, Shuang-Shuang Gu, Hui-Min Zhang, Ya-Nan Wu, Jian-Bin Wu, Fan Peng, Yonglin Zhang, Xiao-Wen Zhan, Ren-Ya Gao, Li-Xia Sun, Qiming Guo, Xing Zhao, Xiao-Dong Luo, Jian-Hong Zhou, Ruhong Han, Lei Shu, Yousheng Zhao, Jing-Wei |
author_facet | Wang, Di-Xian Dong, Zhao-Jun Deng, Sui-Xin Tian, Ying-Ming Xiao, Yu-Jie Li, Xinran Ma, Xiao-Ru Li, Liang Li, Pengxiao Chang, Hui-Zhong Liu, Longqi Wang, Fan Wu, Yang Gao, Xiang Zheng, Shuang-Shuang Gu, Hui-Min Zhang, Ya-Nan Wu, Jian-Bin Wu, Fan Peng, Yonglin Zhang, Xiao-Wen Zhan, Ren-Ya Gao, Li-Xia Sun, Qiming Guo, Xing Zhao, Xiao-Dong Luo, Jian-Hong Zhou, Ruhong Han, Lei Shu, Yousheng Zhao, Jing-Wei |
author_sort | Wang, Di-Xian |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10656444 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-106564442023-11-17 GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21 Wang, Di-Xian Dong, Zhao-Jun Deng, Sui-Xin Tian, Ying-Ming Xiao, Yu-Jie Li, Xinran Ma, Xiao-Ru Li, Liang Li, Pengxiao Chang, Hui-Zhong Liu, Longqi Wang, Fan Wu, Yang Gao, Xiang Zheng, Shuang-Shuang Gu, Hui-Min Zhang, Ya-Nan Wu, Jian-Bin Wu, Fan Peng, Yonglin Zhang, Xiao-Wen Zhan, Ren-Ya Gao, Li-Xia Sun, Qiming Guo, Xing Zhao, Xiao-Dong Luo, Jian-Hong Zhou, Ruhong Han, Lei Shu, Yousheng Zhao, Jing-Wei Nat Commun Article 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. Nature Publishing Group UK 2023-11-17 /pmc/articles/PMC10656444/ /pubmed/37978295 http://dx.doi.org/10.1038/s41467-023-43292-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Wang, Di-Xian Dong, Zhao-Jun Deng, Sui-Xin Tian, Ying-Ming Xiao, Yu-Jie Li, Xinran Ma, Xiao-Ru Li, Liang Li, Pengxiao Chang, Hui-Zhong Liu, Longqi Wang, Fan Wu, Yang Gao, Xiang Zheng, Shuang-Shuang Gu, Hui-Min Zhang, Ya-Nan Wu, Jian-Bin Wu, Fan Peng, Yonglin Zhang, Xiao-Wen Zhan, Ren-Ya Gao, Li-Xia Sun, Qiming Guo, Xing Zhao, Xiao-Dong Luo, Jian-Hong Zhou, Ruhong Han, Lei Shu, Yousheng Zhao, Jing-Wei GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21 |
title | GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21 |
title_full | GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21 |
title_fullStr | GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21 |
title_full_unstemmed | GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21 |
title_short | GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21 |
title_sort | gdf11 slows excitatory neuronal senescence and brain ageing by repressing p21 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10656444/ https://www.ncbi.nlm.nih.gov/pubmed/37978295 http://dx.doi.org/10.1038/s41467-023-43292-1 |
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