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bioRxiv · 10.1101/2021.02.22.432260

Resurrection of human endogenous retroviruses during aging reinforces senescence

Liu, X.·Liu, Z.·Sun, L.·Ren, J.·Wu, Z.·Jiang, X.·Ji, Q.·Wang, Q.·Fan, Y.·Cai, Y.·Wang, S.·Li, W.·Cao, G.·Song, M.·Lu, F.·Zhang, W.·Qu, J.·liu, g.
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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 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 briefLiu 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. HighlightsO_LIDerepression of the endogenous retrovirus contributes to programmed aging C_LIO_LIUpregulation of HERVK triggers the innate immune response and cellular senescence C_LIO_LIExtracellular HERVK retrovirus-like particles induce senescence in young cells C_LIO_LIEndogenous retrovirus serves as a potential target to alleviate agings C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=194 SRC="FIGDIR/small/432260v2_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@31d384org.highwire.dtl.DTLVardef@13594c0org.highwire.dtl.DTLVardef@b8e070org.highwire.dtl.DTLVardef@196e5be_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Liu, X., Liu, Z., Sun, L., Ren, J., Wu, Z., Jiang, X., Ji, Q., Wang, Q., Fan, Y., Cai, Y., Wang, S., Li, W., Cao, G., Song, M., Lu, F., Zhang, W., Qu, J., liu, g.. 2021-02-22. Resurrection of human endogenous retroviruses during aging reinforces senescence. https://doi.org/10.1101/2021.02.22.432260

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