Resurrection of endogenous retroviruses during aging reinforces senescence
Xiaoqian Liu1, Zunpeng Liu2, Zeming Wu3
1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Abstract:
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.
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