Resurrection of endogenous retroviruses during aging reinforces senescence

作者：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, Lan‐Zhu Li, Concepción Rodrı́guez 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 Izpisúa Belmonte, Weiqi Zhang, Jing Qu, Guang‐Hui Liu · 发表于：Cell · 年份：2023 · DOI：10.1016/j.cell.2022.12.017 · 被引用次数：380 · 研究领域：Chromosomal and Genetic Variations、Cytomegalovirus and herpesvirus research、CRISPR and Genetic Engineering

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 is 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. The 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.