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Resurrection of endogenous retroviruses during aging reinforces senescence
Xiaoqian Liu 1, Zunpeng Liu 2, Zeming Wu 3, Jie Ren 4, Yanling Fan 5, Liang Sun 6, Gang Cao 7, Yuyu Niu 8, Baohu Zhang 9, Qianzhao Ji 10, Xiaoyu Jiang 10, Cui Wang 5, Qiaoran Wang 5, Zhejun Ji 2, Lanzhu Li 10, Concepcion Rodriguez Esteban 11, Kaowen Yan 3, Wei Li 12, Yusheng Cai 3, Si Wang 13, Aihua Zheng 14, Yong E Zhang 15, Shengjun Tan 16, Yingao Cai 15, Moshi Song 17, Falong Lu 18, Fuchou Tang 19, Weizhi Ji 20, Qi Zhou 1, Juan Carlos Izpisua Belmonte 11, Weiqi Zhang 21, Jing Qu 22, Guang-Hui Liu 23
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.