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Nuclear lamina erosion-induced resurrection of endogenous retroviruses underlies neuronal aging.
Zhang, Hui; Li, Jiaming; Yu, Yang; Ren, Jie; Liu, Qiang; Bao, Zhaoshi; Sun, Shuhui; Liu, Xiaoqian; Ma, Shuai; Liu, Zunpeng; Yan, Kaowen; Wu, Zeming; Fan, Yanling; Sun, Xiaoyan; Zhang, Yixin; Ji, Qianzhao; Cheng, Fang; Wei, Peng-Hu; Ma, Xibo; Zhang, Shiqiang; Xie, Zhengwei; Niu, Yuyu; Wang, Yan-Jiang; Han, Jing-Dong J; Jiang, Tao; Zhao, Guoguang; Ji, Weizhi; Izpisua Belmonte, Juan Carlos; Wang, Si; Qu, Jing; Zhang, Weiqi; Liu, Guang-Hui.
Afiliación
  • Zhang H; State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Li J; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Yu Y; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology and Key Laboratory of Assisted Reproduction, Ministry of Education, Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China; Clinical Stem Cell
  • Ren J; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; Institute for Stem Cell and Regeneration, CAS, Beijing 100101, China; University of Chinese Academy of Sciences, Beiji
  • Liu Q; Department of Neurology, Tianjin Medical University General Hospital, Tianjin 300052, China.
  • Bao Z; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; Chinese Glioma Genome Atlas Network & Asian Glioma Genome Atlas Network, Beijing 100070, China.
  • Sun S; State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, CAS, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.
  • Liu X; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, CAS, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.
  • Ma S; State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, CAS, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.
  • Liu Z; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Yan K; State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, CAS, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.
  • Wu Z; State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, CAS, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.
  • Fan Y; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Sun X; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Zhang Y; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Ji Q; State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Cheng F; University of Chinese Academy of Sciences, Beijing 100049, China; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • Wei PH; Beijing Municipal Geriatric Medical Research Center, Beijing 100053, China; MAIS, State Key Laboratory of Multimodal Artificial Intelligence Systems, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; School of Artificial Intelligence, University of Chinese Academy of Scien
  • Ma X; MAIS, State Key Laboratory of Multimodal Artificial Intelligence Systems, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing 100049, China.
  • Zhang S; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology (CQB), Peking University, Beijing 100871, China.
  • Xie Z; Peking University International Cancer Institute, Peking University Health Science Center, Peking University, Beijing 100191, China.
  • Niu Y; State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.
  • Wang YJ; Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China; State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
  • Han JJ; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology (CQB), Peking University, Beijing 100871, China.
  • Jiang T; Beijing Neurosurgical Institute, Beijing 100070, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; Chinese Glioma Genome Atlas Network & Asian Glioma Genome Atlas Network, Beijing 100070, China.
  • Zhao G; Department of Neurosurgery, Xuanwu Hospital Capital Medical University, Beijing 100053, China; Clinical Research Center for Epilepsy Capital Medical University, Beijing 100053, China; Beijing Municipal Geriatric Medical Research Center, Beijing 100053, China.
  • Ji W; State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.
  • Izpisua Belmonte JC; Altos Labs, Inc., San Diego, CA, USA.
  • Wang S; Advanced Innovation Center for Human Brain Protection, and National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China; Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical
  • Qu J; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, CAS, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Institute for Stem Cel
  • Zhang W; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; Institute for Stem Cell and Regeneration, CAS, Beijing 100101, China; University of Chinese Academy of Sciences, Beiji
  • Liu GH; State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, CAS, Beijing 100101, China; Advanced Innovation Center for Human Brain Protection, and National Clinical Research Center for Geriatric Disorde
Cell Rep ; 42(6): 112593, 2023 06 27.
Article en En | MEDLINE | ID: mdl-37261950
ABSTRACT
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 primates (NHPs), we depicted a comprehensive landscape of FL aging with multidimensional profiling encompassing 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-inflammatory 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.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Retrovirus Endógenos Límite: Animals Idioma: En Revista: Cell Rep Año: 2023 Tipo del documento: Article País de afiliación: China
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Retrovirus Endógenos Límite: Animals Idioma: En Revista: Cell Rep Año: 2023 Tipo del documento: Article País de afiliación: China