Resurrection of endogenous retroviruses during aging reinforces senescence
Year: 2023
Type: article
Abstract: SUMMARY Whether and how certain transposable elements with viral origins, such as endogenous retroviruses (ERVs) dormant in our genomes, can become awakened and contribute to the aging process are largely unknown. In human senescent cells, we found that HERVK (HML-2), the most recently integrated human ERVs, are unlocked to transcribe viral genes and produce retrovirus-like particles (RVLPs). These HERVK RVLPs constitute a transmissible message to elicit senescence phenotypes in young cells, which can be blocked by neutralizing antibodies. Activation of ERVs was also observed in organs of aged primates and mice, as well as in human tissues and serum from the elderly. Their repression alleviates cellular senescence and tissue degeneration and, to some extent, organismal aging. These findings indicate that the resurrection of ERVs is a hallmark and driving force of cellular senescence and tissue aging. In brief Liu and colleagues uncover the ways in which de-repression of human endogenous retrovirus triggers cellular senescence and tissue aging; the findings provide fresh insights into therapeutic strategies for alleviating aging. Highlights Derepression of the endogenous retrovirus contributes to programmed aging Upregulation of HERVK triggers the innate immune response and cellular senescence Extracellular HERVK retrovirus-like particles induce senescence in young cells Endogenous retrovirus serves as a potential target to alleviate agings Graphical abstract
Source: Cell
Authors: Xiaoqian Liu, Zunpeng Liu, Zeming Wu, Jie Ren, Yanling Fan, Liang Sun, Gang Cao, Yuyu Niu, Baohu Zhang, Qianzhao Ji, Xiaoyu Jiang, Cui Wang, Qiaoran Wang, Zhejun Ji, Lanzhu Li, Concepcion Rodriguez Esteban, Kaowen Yan, Wei Li, Yusheng Cai, Si Wang, Aihua Zheng, Yong E. Zhang, Shengjun Tan, Yingao Cai, Moshi Song, Falong Lu, Fuchou Tang, Weizhi Ji, Qi Zhou, Juan Carlos Izpisua Belmonte, Weiqi Zhang, Jing Qu, Guang-Hui Liu
Institutions: Chinese Academy of Sciences, University of Chinese Academy of Sciences, Institute of Zoology, State Key Laboratory of Stem Cell and Reproductive Biology, Beijing Institute for Stem Cell and Regenerative Medicine, State Key Laboratory of Membrane Biology, Beijing Institute of Genomics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Hospital, Huazhong Agricultural University, State Key Laboratory of Agricultural Microbiology, Kunming University of Science and Technology, Altos Labs, Capital Medical University, Xuan Wu Hospital of the Capital Medical University, Key Laboratory of Zoological Systematics and Evolution, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Genetics and Developmental Biology, State Key Laboratory of Molecular Developmental Biology, Peking University, Center for Life Sciences
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $10,100
Funder: Tsinghua University
OpenAlex ID: W4313638435