GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21

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-Shuang Zheng, Hui-Min Gu, Ya-Nan Zhang, Jian-Bin Wu, Fan Wu, Yonglin Peng, Xiao-Wen Zhang, Ren-Ya Zhan, Li-Xia Gao, Qiming Sun, Xing Guo, Xiao-Dong Zhao, Jian-Hong Luo, Ruhong Zhou, Lei Han (), Yousheng Shu () and Jing-Wei Zhao ()
Additional contact information
Di-Xian Wang: Zhejiang University School of Medicine
Zhao-Jun Dong: Zhejiang University School of Medicine
Sui-Xin Deng: Fudan University
Ying-Ming Tian: BGI Research
Yu-Jie Xiao: Fudan University
Xinran Li: Zhejiang University
Xiao-Ru Ma: Zhejiang University School of Medicine
Liang Li: Fudan University
Pengxiao Li: Shanghai Jiao Tong University
Hui-Zhong Chang: BGI Research
Longqi Liu: BGI Research
Fan Wang: Zhejiang University School of Medicine
Yang Wu: Zhejiang University School of Medicine
Xiang Gao: Zhejiang University School of Medicine
Shuang-Shuang Zheng: Zhejiang University School of Medicine
Hui-Min Gu: Zhejiang University School of Medicine
Ya-Nan Zhang: Zhejiang University
Jian-Bin Wu: Zhejiang University School of Medicine
Fan Wu: Zhejiang University School of Medicine
Yonglin Peng: Shanghai Jiao Tong University
Xiao-Wen Zhang: Zhejiang University School of Medicine
Ren-Ya Zhan: Zhejiang University School of Medicine
Li-Xia Gao: Zhejiang University School of Medicine
Qiming Sun: Zhejiang University School of Medicine
Xing Guo: Zhejiang University
Xiao-Dong Zhao: Shanghai Jiao Tong University
Jian-Hong Luo: Zhejiang University
Ruhong Zhou: Zhejiang University
Lei Han: BGI Research
Yousheng Shu: Fudan University
Jing-Wei Zhao: Zhejiang University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-24

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-43292-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43292-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-43292-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().