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, Jing-Wei Zhao
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...
November 17, 2023: Nature Communications