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 humanERVs, are unlocked to transcribe viral genes and produce retrovirus-like particles (RVLPs). TheseHERVK 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 organsof 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 findingsindicate that the resurrection of ERVs is a hallmark and driving force of cellular senescence and tissue aging.
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