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Nuclear lamina erosion-induced resurrection of endogenous retroviruses underlies neuronal aging

文献类型：期刊论文

作者Zhang, Hui18; Li, Jiaming1,16; Yu, Yang27; Ren, Jie1,12,15,16; Liu, Qiang; Bao, Zhaoshi8,23; Sun, Shuhui15,18; Liu, Xiaoqian11,15,17; Ma, Shuai11,15,18; Liu, Zunpeng12
刊名CELL REPORTS
出版日期2023-06-27
卷号42期号:6页码:31
ISSN号2211-1247
DOI10.1016/j.celrep.2023.112593
通讯作者Wang, Si(wangsi@xwh.ccmu.edu.cn) ; Qu, Jing(qujing@ioz.ac.cn) ; Zhang, Weiqi(zhangwq@big.ac.cn) ; Liu, Guang-Hui(ghliu@ioz.ac.cn)
英文摘要The primate frontal lobe (FL) is sensitive to aging-related neurocognitive decline. However, the aging -associated molecular mechanisms remain unclear. Here, using physiologically aged non-human pri-mates (NHPs), we depicted a comprehensive landscape of FL aging with multidimensional profiling en-compassing bulk and single-nucleus transcriptomes, quantitative proteome, and DNA methylome. Conjoint analysis across these molecular and neuropathological layers underscores nuclear lamina and heterochromatin erosion, resurrection of endogenous retroviruses (ERVs), activated pro -inflamma-tory cyclic GMP-AMP synthase (cGAS) signaling, and cellular senescence in post-mitotic neurons of aged NHP and human FL. Using human embryonic stem-cell-derived neurons recapitulating cellular aging in vitro, we verified the loss of B-type lamins inducing resurrection of ERVs as an initiating event of the aging-bound cascade in post-mitotic neurons. Of significance, these aging-related cellular and molecular changes can be alleviated by abacavir, a nucleoside reverse transcriptase inhibitor, either through direct treatment of senescent human neurons in vitro or oral administration to aged mice.
WOS关键词CELLULAR SENESCENCE ; SECRETORY PHENOTYPE ; ALZHEIMERS-DISEASE ; PREFRONTAL CORTEX ; HUMAN BRAIN ; DNA-DAMAGE ; STEM-CELLS ; RNA-SEQ ; GENOME ; BETA
资助项目National Key Research and Development Program of China[2020YFA0804000] ; National Key Research and Development Program of China[2022YFA1103700] ; National Key Research and Development Program of China[2020YFA0112200] ; National Key Research and Development Program of China[2021YFF1201005] ; National Key Research and Development Program of China[2021ZD0202400] ; National Key Research and Development Program of China[2019YFA0802202] ; National Key Research and Development Program of China[2020YF A0803401] ; National Key Research and Development Program of China[2022YFA1103800] ; National Key Research and Development Program of China[2019YFA0110100] ; National Natural Science Foundation of China[81921006] ; National Natural Science Foundation of China[82125011] ; National Natural Science Foundation of China[92149301] ; National Natural Science Foundation of China[92168201] ; National Natural Science Foundation of China[91949209] ; National Natural Science Foundation of China[92049304] ; National Natural Science Foundation of China[92049116] ; National Natural Science Foundation of China[32121001] ; National Natural Science Foundation of China[82192863] ; National Natural Science Foundation of China[82122024] ; National Natural Science Foundation of China[82071588] ; National Natural Science Foundation of China[31970597] ; National Natural Science Foundation of China[32000500] ; National Natural Science Foundation of China[82271600] ; National Natural Science Foundation of China[32100937] ; National Natural Science Foundation of China[81972337] ; National Natural Science Foundation of China[81802994] ; National Natural Science Foundation of China[82090051] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA16000000] ; Program of the Beijing Natural Science Foun[Z190019] ; Program of the Beijing Natural Science Foun[JQ20030] ; CAS Project for Young Scientists in Basic Research[YSBR-076] ; CAS Project for Young Scientists in Basic Research[YSBR-012] ; Pilot Project for Public Welfare Devel- opment and Reform of Beijing -affiliated Medical Research Institutes[11000022T000000461062] ; Young Elite Scientists Sponsorship Program by CAST[YESS20200012] ; Young Elite Scientists Sponsorship Program by CAST[YESS20210002] ; Youth Innovation Promotion Associ- ation of CAS[E1CAZW0401] ; Youth Innovation Promotion Associ- ation of CAS[2023092] ; Youth Innovation Promotion Associ- ation of CAS[2022083] ; Informatization Plan of Chinese Academy of Sciences[CAS-WX2021SF-0301] ; Informatization Plan of Chinese Academy of Sciences[CAS-WX2022SDC- XK14] ; Informatization Plan of Chinese Academy of Sciences[CAS-WX2021SF-0101] ; Tencent Foundation[2021-1045] ; Outstanding Young Talents Program of the Capital Medical University[B2101] ; Excellent Young Talents Program of Capital Medical University[12300927] ; Excellent Young Talents Training Program for the Construc- tion of Beijing Municipal University Teacher Team[BPHR202203105]
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:001014778300001
出版者CELL PRESS
资助机构National Key Research and Development Program of China ; National Natural Science Foundation of China ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Program of the Beijing Natural Science Foun ; CAS Project for Young Scientists in Basic Research ; Pilot Project for Public Welfare Devel- opment and Reform of Beijing -affiliated Medical Research Institutes ; Young Elite Scientists Sponsorship Program by CAST ; Youth Innovation Promotion Associ- ation of CAS ; Informatization Plan of Chinese Academy of Sciences ; Tencent Foundation ; Outstanding Young Talents Program of the Capital Medical University ; Excellent Young Talents Program of Capital Medical University ; Excellent Young Talents Training Program for the Construc- tion of Beijing Municipal University Teacher Team
源URL[http://ir.ia.ac.cn/handle/173211/53531]  
专题多模态人工智能系统全国重点实验室
通讯作者Wang, Si; Qu, Jing; Zhang, Weiqi; Liu, Guang-Hui
作者单位1.Chinese Acad Sci, Beijing Inst Genom, CAS Key Lab Genom & Precis Med, Beijing 100101, Peoples R China
2.Univ Chinese Acad Sci, Sch Artificial Intelligence, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Inst Automat, State Key Lab Multimodal Artificial Intelligence S, MAIS, Beijing 100190, Peoples R China
4.Beijing Municipal Geriatr Med Res Ctr, Beijing 100053, Peoples R China
5.Capital Med Univ, Clin Res Ctr Epilepsy, Beijing 100053, Peoples R China
6.Capital Med Univ, Dept Neurosurg, Xuanwu Hosp, Beijing 100053, Peoples R China
7.Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing 100101, Peoples R China
8.Chinese Glioma Genome Atlas Network, Beijing 100070, Peoples R China
9.Kunming Univ Sci & Technol, Inst Primate Translat Med, State Key Lab Primate Biomed Res, Kunming 650500, Yunnan, Peoples R China
10.Capital Med Univ, Beijing Municipal Geriatr Med Res Ctr Hosp, Aging Translat Med Ctr, Int Ctr Aging & Canc, Beijing 100053, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Hui,Li, Jiaming,Yu, Yang,et al. Nuclear lamina erosion-induced resurrection of endogenous retroviruses underlies neuronal aging[J]. CELL REPORTS,2023,42(6):31.
APA Zhang, Hui.,Li, Jiaming.,Yu, Yang.,Ren, Jie.,Liu, Qiang.,...&Liu, Guang-Hui.(2023).Nuclear lamina erosion-induced resurrection of endogenous retroviruses underlies neuronal aging.CELL REPORTS,42(6),31.
MLA Zhang, Hui,et al."Nuclear lamina erosion-induced resurrection of endogenous retroviruses underlies neuronal aging".CELL REPORTS 42.6(2023):31.

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