Nuclear lamina erosion-induced resurrection of endogenous retroviruses underlies neuronal aging
Summary: 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 profilin...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723006046 |
| _version_ | 1827935582812110848 |
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| author | Hui Zhang Jiaming Li Yang Yu Jie Ren Qiang Liu Zhaoshi Bao Shuhui Sun Xiaoqian Liu Shuai Ma Zunpeng Liu Kaowen Yan Zeming Wu Yanling Fan Xiaoyan Sun Yixin Zhang Qianzhao Ji Fang Cheng Peng-Hu Wei Xibo Ma Shiqiang Zhang Zhengwei Xie Yuyu Niu Yan-Jiang Wang Jing-Dong J. Han Tao Jiang Guoguang Zhao Weizhi Ji Juan Carlos Izpisua Belmonte Si Wang Jing Qu Weiqi Zhang Guang-Hui Liu |
| author_facet | Hui Zhang Jiaming Li Yang Yu Jie Ren Qiang Liu Zhaoshi Bao Shuhui Sun Xiaoqian Liu Shuai Ma Zunpeng Liu Kaowen Yan Zeming Wu Yanling Fan Xiaoyan Sun Yixin Zhang Qianzhao Ji Fang Cheng Peng-Hu Wei Xibo Ma Shiqiang Zhang Zhengwei Xie Yuyu Niu Yan-Jiang Wang Jing-Dong J. Han Tao Jiang Guoguang Zhao Weizhi Ji Juan Carlos Izpisua Belmonte Si Wang Jing Qu Weiqi Zhang Guang-Hui Liu |
| author_sort | Hui Zhang |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-13T07:56:53Z |
| format | Article |
| id | doaj.art-32a7e9db6c1b41628f79aca1dfc42490 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-13T07:56:53Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-32a7e9db6c1b41628f79aca1dfc424902023-06-02T04:23:02ZengElsevierCell Reports2211-12472023-06-01426112593Nuclear lamina erosion-induced resurrection of endogenous retroviruses underlies neuronal agingHui Zhang0Jiaming Li1Yang Yu2Jie Ren3Qiang Liu4Zhaoshi Bao5Shuhui Sun6Xiaoqian Liu7Shuai Ma8Zunpeng Liu9Kaowen Yan10Zeming Wu11Yanling Fan12Xiaoyan Sun13Yixin Zhang14Qianzhao Ji15Fang Cheng16Peng-Hu Wei17Xibo Ma18Shiqiang Zhang19Zhengwei Xie20Yuyu Niu21Yan-Jiang Wang22Jing-Dong J. Han23Tao Jiang24Guoguang Zhao25Weizhi Ji26Juan Carlos Izpisua Belmonte27Si Wang28Jing Qu29Weiqi Zhang30Guang-Hui Liu31State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaCAS 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, ChinaBeijing 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 Research Center, Peking University Third Hospital, Beijing, ChinaCAS 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, Beijing 100049, ChinaDepartment of Neurology, Tianjin Medical University General Hospital, Tianjin 300052, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; Chinese Glioma Genome Atlas Network & Asian Glioma Genome Atlas Network, Beijing 100070, ChinaState 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, ChinaState 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, ChinaState 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, ChinaState 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, ChinaState 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, ChinaState 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, ChinaCAS 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, ChinaCAS 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, ChinaState 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, ChinaState Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaUniversity 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, ChinaBeijing 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 Sciences, Beijing 100049, ChinaMAIS, 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, ChinaPeking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology (CQB), Peking University, Beijing 100871, ChinaPeking University International Cancer Institute, Peking University Health Science Center, Peking University, Beijing 100191, ChinaState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, ChinaDepartment 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, ChinaPeking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology (CQB), Peking University, Beijing 100871, ChinaBeijing 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, ChinaDepartment 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, ChinaState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, ChinaAltos Labs, Inc., San Diego, CA, USAAdvanced 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 Research Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; The Fifth People’s Hospital of Chongqing, Chongqing 400062, China; Corresponding authorState 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 Cell and Regenerative Medicine, Beijing 100101, China; Corresponding authorCAS 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, Beijing 100049, China; Corresponding authorState 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 Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China; University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723006046CP: NeuroscienceCP: Cell biology |
| spellingShingle | Hui Zhang Jiaming Li Yang Yu Jie Ren Qiang Liu Zhaoshi Bao Shuhui Sun Xiaoqian Liu Shuai Ma Zunpeng Liu Kaowen Yan Zeming Wu Yanling Fan Xiaoyan Sun Yixin Zhang Qianzhao Ji Fang Cheng Peng-Hu Wei Xibo Ma Shiqiang Zhang Zhengwei Xie Yuyu Niu Yan-Jiang Wang Jing-Dong J. Han Tao Jiang Guoguang Zhao Weizhi Ji Juan Carlos Izpisua Belmonte Si Wang Jing Qu Weiqi Zhang Guang-Hui Liu Nuclear lamina erosion-induced resurrection of endogenous retroviruses underlies neuronal aging Cell Reports CP: Neuroscience CP: Cell biology |
| title | Nuclear lamina erosion-induced resurrection of endogenous retroviruses underlies neuronal aging |
| title_full | Nuclear lamina erosion-induced resurrection of endogenous retroviruses underlies neuronal aging |
| title_fullStr | Nuclear lamina erosion-induced resurrection of endogenous retroviruses underlies neuronal aging |
| title_full_unstemmed | Nuclear lamina erosion-induced resurrection of endogenous retroviruses underlies neuronal aging |
| title_short | Nuclear lamina erosion-induced resurrection of endogenous retroviruses underlies neuronal aging |
| title_sort | nuclear lamina erosion induced resurrection of endogenous retroviruses underlies neuronal aging |
| topic | CP: Neuroscience CP: Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723006046 |
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