Cited by 390Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsChromosomal and Genetic Variations

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Resurrection of endogenous retroviruses during aging reinforces senescence

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Liu, Xiaoqian, Liu, Zunpeng, Wu, Zeming, Ren, Jie, Fan, Yanling, Sun, Liang, Cao, Gang, Niu, Yuyu, Zhang, Baohu, Ji, Qianzhao, Jiang, Xiaoyu, Wang, Cui, Wang, Qiaoran, Ji, Zhejun, Li, Lanzhu, Esteban, Concepcion Rodriguez, Yan, Kaowen, Li, Wei, Cai, Yusheng, Wang, Si, Zheng, Aihua, Zhang, Yong E., Tan, Shengjun, Cai, Yingao, Song, Moshi, Lu, Falong, Tang, Fuchou, Ji, Weizhi, Zhou, Qi, Belmonte, Juan Carlos Izpisua, Zhang, Weiqi, Qu, Jing, Liu, Guang-Hui·2023·Cell

DOI 10.1016/j.cell.2022.12.017

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Abstract

SUMMARY 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 brief Liu 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. Highlights Derepression of the endogenous retrovirus contributes to programmed aging Upregulation of HERVK triggers the innate immune response and cellular senescence Extracellular HERVK retrovirus-like particles induce senescence in young cells Endogenous retrovirus serves as a potential target to alleviate agings Graphical abstract

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Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
NIH Image to ImageJ: 25 years of image analysis
Schneider, C. A., Rasband, W. S., & Eliceiri, K. W. (2012) · Nature Methods · doi:10.1038/nmeth.2089 · Cited by 64,638
The Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709
fastp: an ultra-fast all-in-one FASTQ preprocessor
Chen, S., Zhou, Y., Chen, Y., & Gu, J. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty560 · Cited by 29,721
featureCounts: an efficient general purpose program for assigning sequence reads to genomic features
Liao, Y., Smyth, G. K., & Shi, W. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btt656 · Cited by 27,219
HISAT: a fast spliced aligner with low memory requirements
Kim, D., Langmead, B., & Salzberg, S. L. (2015) · Nature Methods · doi:10.1038/nmeth.3317 · Cited by 24,112
HTSeq—a Python framework to work with high-throughput sequencing data
Anders, S., Pyl, P. T., & Huber, W. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btu638 · Cited by 21,464
The Hallmarks of Aging
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982
Salmon provides fast and bias-aware quantification of transcript expression
Patro, R., Duggal, G., Love, M. I., Irizarry, R. A., & Kingsford, C. (2017) · Nature Methods · doi:10.1038/nmeth.4197 · Cited by 12,700
Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration
Thorvaldsdottir, H., Robinson, J. T., & Mesirov, J. P. (2013) · Briefings in Bioinformatics · doi:10.1093/bib/bbs017 · Cited by 9,049
Identification and Characterization of MAVS, a Mitochondrial Antiviral Signaling Protein that Activates NF-κB and IRF3
Seth, R. B., Sun, L., Ea, C.-K., & Chen, Z. J. (2005) · Cell · doi:10.1016/j.cell.2005.08.012 · Cited by 3,329
Self-citation
DNA methylation-based biomarkers and the epigenetic clock theory of ageing
Horvath, S., & Raj, K. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0004-3 · Cited by 3,095
High-throughput droplet digital PCR system for absolute quantitation of DNA copy number
Hindson, B. J., Ness, K. D., Masquelier, D. A., Belgrader, P., Heredia, N. J., Makarewicz, A. J., Bright, I. J., Lucero, M. Y., Hiddessen, A. L., Legler, T. C., et al. (2011) · Analytical Chemistry · doi:10.1021/ac202028g · Cited by 2,792
Self-citation
Geroscience: Linking Aging to Chronic Disease
Kennedy, B. K., Berger, S. L., Brunet, A., Campisi, J., Cuervo, A. M., Epel, E. S., Franceschi, C., Lithgow, G. J., Morimoto, R. I., Pessin, J. E., et al. (2014) · Cell · doi:10.1016/j.cell.2014.10.039 · Cited by 2,764
Immunopathology of multiple sclerosis
Dendrou, C. A., Fugger, L., & Friese, M. A. (2015) · Nature Reviews Immunology · doi:10.1038/nri3871 · Cited by 2,215
mTOR Signaling in Growth, Metabolism, and Disease
Saxton, R. A., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.03.035 · Cited by 2,112
Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses
Chiappinelli, K. B., Strissel, P. L., Desrichard, A., Li, H., Henke, C., Akman, B., Hein, A., Rote, N. S., Cope, L. M., Snyder, A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.07.011 · Cited by 2,022
Protocols to detect senescence-associated beta-galactosidase (SA-βgal) activity, a biomarker of senescent cells in culture and in vivo
Debacq-Chainiaux, F., Erusalimsky, J. D., Campisi, J., & Toussaint, O. (2009) · Nature Protocols · doi:10.1038/nprot.2009.191 · Cited by 1,668
DNA-Demethylating Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry by Endogenous Transcripts
Roulois, D., Loo Yau, H., Singhania, R., Wang, Y., Danesh, A., Shen, S. Y., Han, H., Liang, G., Jones, P. A., Pugh, T. J., et al. (2015) · Cell · doi:10.1016/j.cell.2015.07.056 · Cited by 1,527
GSEA-P : a desktop application for Gene Set Enrichment Analysis
Subramanian, A., Kuehn, H., Gould, J., Tamayo, P., & Mesirov, J. P. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm369 · Cited by 1,399
From discoveries in ageing research to therapeutics for healthy ageing
Campisi, J., Kapahi, P., Lithgow, G. J., Melov, S., Newman, J. C., & Verdin, E. (2019) · Nature · doi:10.1038/s41586-019-1365-2 · Cited by 1,389
L1 drives IFN in senescent cells and promotes age-associated inflammation
De Cecco, M., Ito, T., Petrashen, A. P., Elias, A. E., Skvir, N. J., Criscione, S. W., Caligiana, A., Brocculi, G., Adney, E. M., Boeke, J. D., et al. (2019) · Nature · doi:10.1038/s41586-018-0784-9 · Cited by 1,255
Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences
Balaj, L., Lessard, R., Dai, L., Cho, Y., Pomeroy, S. L., Breakefield, X. O., & Skog, J. (2011) · Nature Communications · doi:10.1038/ncomms1180 · Cited by 1,227
BSMAP: whole genome bisulfite sequence MAPping program
Xi, Y., & Li, W. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-232 · Cited by 1,216
Self-citation
Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity
Schoggins, J. W., MacDuff, D. A., Imanaka, N., Gainey, M. D., Shrestha, B., Eitson, J. L., Mar, K. B., Richardson, R. B., Ratushny, A. V., Litvak, V., et al. (2014) · Nature · doi:10.1038/nature12862 · Cited by 896
TEtranscripts: a package for including transposable elements in differential expression analysis of RNA-seq datasets
Jin, Y., Tam, O. H., Paniagua, E., & Hammell, M. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv422 · Cited by 753
Epigenetic regulation of aging: implications for interventions of aging and diseases
Kang, W., Liu, H., Hu, Q., Wang, L., Liu, J., Zheng, Z., Zhang, W., Ren, J., Zhu, F., & Liu, G. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01211-8 · Cited by 732
Self-citation
Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells
Grow, E. J., Flynn, R. A., Chavez, S. L., Bayless, N. L., Wossidlo, M., Wesche, D. J., Martin, L., Ware, C. B., Blish, C. A., Chang, H. Y., et al. (2015) · Nature · doi:10.1038/nature14308 · Cited by 666
Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome
Liu, G.-H., Barkho, B. Z., Ruiz, S., Diep, D., Qu, J., Yang, S.-L., Panopoulos, A. D., Suzuki, K., Kurian, L., Walsh, C., et al. (2011) · Nature · doi:10.1038/nature09879 · Cited by 575
Self-citation
A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging
Zhang, W., Li, J., Suzuki, K., Qu, J., Wang, P., Zhou, J., Liu, X., Ren, R., Xu, X., Ocampo, A., et al. (2015) · Science · doi:10.1126/science.aaa1356 · Cited by 551
Self-citation
Hallmarks of Health
López-Otín, C., & Kroemer, G. (2021) · Cell · doi:10.1016/j.cell.2020.11.034 · Cited by 499
LINE1 Derepression in aged wild-type and SIRT6-deficient mice drives inflammation
Simon, M., Van Meter, M., Ablaeva, J., Ke, Z., Gonzalez, R. S., Taguchi, T., De Cecco, M., Leonova, K. I., Kogan, V., Helfand, S. L., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.02.014 · Cited by 498
Human endogenous retrovirus-K contributes to motor neuron disease
Li, W., Lee, M.-H., Henderson, L., Tyagi, R., Bachani, M., Steiner, J., Campanac, E., Hoffman, D. A., von Geldern, G., Johnson, K., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aac8201 · Cited by 482
Self-citation
Genomes of replicatively senescent cells undergo global epigenetic changes leading to gene silencing and activation of transposable elements
De Cecco, M., Criscione, S. W., Peckham, E. J., Hillenmeyer, S., Hamm, E. A., Manivannan, J., Peterson, A. L., Kreiling, J. A., Neretti, N., & Sedivy, J. M. (2013) · Aging Cell · doi:10.1111/acel.12047 · Cited by 459
The ageing epigenome and its rejuvenation
Zhang, W., Qu, J., Liu, G.-H., & Belmonte, J. C. I. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0204-5 · Cited by 458
Self-citation
SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age
Van Meter, M., Kashyap, M., Rezazadeh, S., Geneva, A. J., Morello, T. D., Seluanov, A., & Gorbunova, V. (2014) · Nature Communications · doi:10.1038/ncomms6011 · Cited by 456
The landscape of aging
Cai, Y., Song, W., Li, J., Jing, Y., Liang, C., Zhang, L., Zhang, X., Zhang, W., Liu, B., An, Y., et al. (2022) · Science China Life Sciences · doi:10.1007/s11427-022-2161-3 · Cited by 450
Self-citation
The role of retrotransposable elements in ageing and age-associated diseases
Gorbunova, V., Seluanov, A., Mita, P., McKerrow, W., Fenyö, D., Boeke, J. D., Linker, S. B., Gage, F. H., Kreiling, J. A., Petrashen, A. P., et al. (2021) · Nature · doi:10.1038/s41586-021-03542-y · Cited by 446
Identification, characterization, and comparative genomic distribution of the HERV-K (HML-2) group of human endogenous retroviruses
Subramanian, R. P., Wildschutte, J. H., Russo, C., & Coffin, J. M. (2011) · Retrovirology · doi:10.1186/1742-4690-8-90 · Cited by 439
Origins and evolutionary consequences of ancient endogenous retroviruses
Johnson, W. E. (2019) · Nature Reviews Microbiology · doi:10.1038/s41579-019-0189-2 · Cited by 425
Mammalian Retrovirus-like Protein PEG10 Packages Its Own MRNA and Can Be Pseudotyped for MRNA Delivery
Segel, M., Lash, B., Song, J., Ladha, A., Liu, C. C., Jin, X., Mekhedov, S. L., Macrae, R. K., Koonin, E. V., & Zhang, F. (2021) · Science · doi:10.1126/science.abg6155 · Cited by 423
Chromatin immunoprecipitation (ChIP) of plant transcription factors followed by sequencing (ChIP-SEQ) or hybridization to whole genome arrays (ChIP-CHIP)
Kaufmann, K., Muiño, J. M., Østerås, M., Farinelli, L., Krajewski, P., & Angenent, G. C. (2010) · Nature Protocols · doi:10.1038/nprot.2009.244 · Cited by 417
A Single-Cell Transcriptomic Atlas of Human Skin Aging
Zou, Z., Long, X., Zhao, Q., Zheng, Y., Song, M., Ma, S., Jing, Y., Wang, S., He, Y., Esteban, C. R., et al. (2021) · Developmental Cell · doi:10.1016/j.devcel.2020.11.002 · Cited by 402
Self-citation
Transposable elements become active and mobile in the genomes of aging mammalian somatic tissues
De Cecco, M., Criscione, S. W., Peterson, A. L., Neretti, N., Sedivy, J. M., & Kreiling, J. A. (2013) · Aging · doi:10.18632/aging.100621 · Cited by 365
Studies of endogenous retroviruses reveal a continuing evolutionary saga
Stoye, J. P. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2783 · Cited by 350
Downregulation of cytoplasmic DNases is implicated in cytoplasmic DNA accumulation and SASP in senescent cells
Takahashi, A., Loo, T. M., Okada, R., Kamachi, F., Watanabe, Y., Wakita, M., Watanabe, S., Kawamoto, S., Miyata, K., Barber, G. N., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03555-8 · Cited by 350
Activation of transposable elements during aging and neuronal decline in Drosophila
Li, W., Prazak, L., Chatterjee, N., Grüninger, S., Krug, L., Theodorou, D., & Dubnau, J. (2013) · Nature Neuroscience · doi:10.1038/nn.3368 · Cited by 346
Self-citation
Repetitive sequences in complex genomes: Structure and evolution
Jurka, J., Kapitonov, V. V., Kohany, O., & Jurka, M. V. (2007) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.8.080706.092416 · Cited by 331
Identification of active loci of a human endogenous retrovirus in neurons of patients with amyotrophic lateral sclerosis
Douville, R. N., Liu, J., Rothstein, J., & Nath, A. (2010) · Annals of Neurology · doi:10.1002/ana.22149 · Cited by 327
Impact of senescence-associated secretory phenotype and its potential as a therapeutic target for senescence-associated diseases
Watanabe, S., Kawamoto, S., Ohtani, N., & Hara, E. (2017) · Cancer Science · doi:10.1111/cas.13184 · Cited by 321
Classification and characterization of human endogenous retroviruses; mosaic forms are common
Vargiu, L., Rodriguez-Tomé, P., Sperber, G. O., Cadeddu, M., Grandi, N., Blikstad, V., Tramontano, E., & Blomberg, J. (2016) · Retrovirology · doi:10.1186/s12977-015-0232-y · Cited by 315
Reconstitution of an Infectious Human Endogenous Retrovirus
Lee, Y. N., & Bieniasz, P. D. (2007) · PLoS Pathogens · doi:10.1371/journal.ppat.0030010 · Cited by 311
Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements
Dewannieux, M., Harper, F., Richaud, A., Letzelter, C., Ribet, D., Pierron, G., & Heidmann, T. (2006) · Genome Research · doi:10.1101/gr.5565706 · Cited by 309
Werner and Hutchinson–Gilford progeria syndromes: mechanistic basis of human progeroid diseases
Kudlow, B. A., Kennedy, B. K., & Monnat, R. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2161 · Cited by 304
Epigenetic Modifications in Cardiovascular Aging and Diseases
Zhang, W., Song, M., Qu, J. T., & Liu, G. (2018) · Circulation Research · doi:10.1161/circresaha.118.312497 · Cited by 296
Self-citation
Regulation of Stem Cell Aging by Metabolism and Epigenetics
Ren, R., Ocampo, A., Liu, G., & Belmonte, J. C. I. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.07.019 · Cited by 286
Self-citation
Loss of Nuclear TDP-43 Is Associated with Decondensation of LINE Retrotransposons
Liu, E. Y., Russ, J., Cali, C. P., Phan, J. M., Amlie-Wolf, A., & Lee, E. B. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.003 · Cited by 231
Human Endogenous Retrovirus K (HML-2) Elements in the Plasma of People with Lymphoma and Breast Cancer
Contreras-Galindo, R., Kaplan, M. H., Leissner, P., Verjat, T., Ferlenghi, I., Bagnoli, F., Giusti, F., Dosik, M. H., Hayes, D. F., Gitlin, S. D., et al. (2008) · Journal of Virology · doi:10.1128/jvi.00646-08 · Cited by 222
Human endogenous retrovirus-K (HML-2): a comprehensive review
Montojo, M. G., Doucet-O’Hare, T. T., Henderson, L. J., & Nath, A. (2018) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2018.1501345 · Cited by 219
Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells
Garcia-Perez, J. L., Morell, M. H., Scheys, J. O., Kulpa, D. A., Morell, S., Carter, C. C., Hammer, G. D., Collins, K. L., O’Shea, K. S., Menéndez, P. R., et al. (2010) · Nature · doi:10.1038/nature09209 · Cited by 186
Immunotherapeutic Potential of Anti-Human Endogenous Retrovirus-K Envelope Protein Antibodies in Targeting Breast Tumors
Wang‐Johanning, F., Rycaj, K., Plummer, J. B., Li, M., Yin, B., Frerich, K., Garza, J. G., Shen, J., Lin, K., Yan, P., et al. (2012) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djr540 · Cited by 182
A genome-wide CRISPR-based screen identifies KAT7 as a driver of cellular senescence
Wang, W., Zheng, Y., Sun, S., Li, W., Song, M., Ji, Q., Wu, Z., Liu, Z., Fan, Y., Liu, F., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abd2655 · Cited by 178
Self-citation
A single-cell transcriptomic landscape of primate arterial aging
Zhang, W., Zhang, S., Yan, P., Ren, J., Song, M., Li, J., Lei, J., Pan, H., Wang, S., Ma, X., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15997-0 · Cited by 165
Self-citation
SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer
Bi, S., Liu, Z., Wu, Z., Wang, Z., Liu, X., Wang, S., Ren, J., Yao, Y., Zhang, W., Song, M., et al. (2020) · Protein & Cell · doi:10.1007/s13238-020-00728-4 · Cited by 162
Self-citation
Up-regulation of FOXD1 by YAP alleviates senescence and osteoarthritis
Fu, L., Hu, Y., Song, M., Liu, Z., Zhang, W., Yu, F., Wu, J., Wang, S., Belmonte, J. C. I., Chan, P., et al. (2019) · PLoS Biology · doi:10.1371/journal.pbio.3000201 · Cited by 162
Self-citation
Characterization of novel reverse transcriptase encoding human endogenous retroviral sequences similar to type A and type B retroviruses: differential transcription in normal human tissues
Medstrand, P., & Blomberg, J. (1993) · Journal of Virology · doi:10.1128/jvi.67.11.6778-6787.1993 · Cited by 154
Epigenetic Control of Human Endogenous Retrovirus Expression: Focus on Regulation of Long-Terminal Repeats (LTRs)
Hurst, T. P., & Magiorkinis, G. (2017) · Viruses · doi:10.3390/v9060130 · Cited by 154
Single-cell transcriptomic atlas of primate cardiopulmonary aging
Ma, S., Sun, S., Li, J., Fan, Y., Qu, J. T., Sun, L., Wang, S., Zhang, Y., Yang, S., Liu, Z., et al. (2020) · Cell Research · doi:10.1038/s41422-020-00412-6 · Cited by 152
Self-citation
Unfixed Endogenous Retroviral Insertions in the Human Population
Marchi, E., Kanapin, A. A., Magiorkinis, G., & Belshaw, R. D. (2014) · Journal of Virology · doi:10.1128/jvi.00919-14 · Cited by 144
Maintenance of Nucleolar Homeostasis by CBX4 Alleviates Senescence and Osteoarthritis
Ren, X., Hu, B., Song, M., Ding, Z., Dang, Y., Liu, Z., Zhang, W., Ji, Q., Ren, R., Ding, J., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.02.088 · Cited by 139
Self-citation
Stabilizing heterochromatin by DGCR8 alleviates senescence and osteoarthritis
Deng, L., Ren, R., Liu, Z., Song, M., Li, J., Wu, Z., Ren, X., Fu, L., Li, W., Zhang, W., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10831-8 · Cited by 138
Self-citation
Identification of a Functional Envelope Protein from the HERV-K Family of Human Endogenous Retroviruses
Dewannieux, M., Blaise, S., & Heidmann, T. (2005) · Journal of Virology · doi:10.1128/jvi.79.24.15573-15577.2005 · Cited by 137
Cross-species metabolomic analysis identifies uridine as a potent regeneration promoting factor
Liu, Z., Li, W., Geng, L., Sun, L., Wang, Q., Yu, Y., Yan, P., Liang, C., Ren, J., Song, M., et al. (2022) · Cell Discovery · doi:10.1038/s41421-021-00361-3 · Cited by 137
Self-citation
Chemical screen identifies a geroprotective role of quercetin in premature aging
Geng, L., Liu, Z., Zhang, W., Li, W., Wu, Z., Wang, W., Ren, R., Su, Y., Wang, P., Sun, L., et al. (2018) · Protein & Cell · doi:10.1007/s13238-018-0567-y · Cited by 131
Self-citation
Downregulation of Human Endogenous Retrovirus Type K (HERV-K) Viral env RNA in Pancreatic Cancer Cells Decreases Cell Proliferation and Tumor Growth
Li, M., Radvanyi, L. G., Yin, B., Rycaj, K., Li, J., Chivukula, R., Lin, K., Lu, Y., Shen, J., Chang, D. Z., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-0001 · Cited by 130
New Horizons: Novel Approaches to Enhance Healthspan Through Targeting Cellular Senescence and Related Aging Mechanisms
Tchkonia, T., Palmer, A. K., & Kirkland, J. L. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa728 · Cited by 129
Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses
Chiappinelli, K. B., Strissel, P. L., Desrichard, A., Li, H., Henke, C., Akman, B., Hein, A., Rote, N. S., Cope, L., Snyder, A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.03.036 · Cited by 126
Genetic Engineering of T Cells to Target HERV-K, an Ancient Retrovirus on Melanoma
Krishnamurthy, J., Rabinovich, B. A., Mi, T., Switzer, K. C., Olivares, S., Maiti, S. N., Plummer, J. B., Singh, H., Kumaresan, P. R., Huls, H. M., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-3197 · Cited by 125
The conundrum of human immune system “senescence”
Pawelec, G., Bronikowski, A. M., Cunnane, S. C., Ferrucci, L., Franceschi, C., Fülöp, T., Gaudreau, P., Gladyshev, V. N., Gonos, E. S., Gorbunova, V. A., et al. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111357 · Cited by 121
Self-citation
Stabilization of heterochromatin by CLOCK promotes stem cell rejuvenation and cartilage regeneration
Liang, C., Liu, Z., Song, M., Li, W., Wu, Z., Wang, Z., Wang, Q., Wang, S., Yan, K., Sun, L., et al. (2020) · Cell Research · doi:10.1038/s41422-020-0385-7 · Cited by 119
Self-citation
Endogenous retroviruses
Blikstad, V., Benachenhou, F., Sperber, G. O., & Blomberg, J. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8495-2 · Cited by 117
Epigenetic regulation of an IAP retrotransposon in the aging mouse: progressive demethylation and de-silencing of the element by its repetitive induction
Barbot, W. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.11.2365 · Cited by 116
A role for human endogenous retrovirus-K (HML-2) in rheumatoid arthritis: investigating mechanisms of pathogenesis
Freimanis, G., Hooley, P., Ejtehadi, H. D., Ali, H. A., Veitch, A. M., Rylance, P. B., Alawi, A., Axford, J. S., Nevill, A. M., Murray, P. G., et al. (2010) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2010.04110.x · Cited by 116
Phenotypic heterogeneity of human endogenous retrovirus particles produced by teratocarcinoma cell lines
Bieda, K., Hoffmann, A., & Boller, K. (2001) · Journal of General Virology · doi:10.1099/0022-1317-82-3-591 · Cited by 113
A stem cell aging framework, from mechanisms to interventions
Liu, B., Qu, J. T., Zhang, W., Belmonte, J. C. I., & Liu, G. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111451 · Cited by 110
Self-citation
Large-scale chromatin reorganization reactivates placenta-specific genes that drive cellular aging
Liu, Z., Ji, Q., Ren, J., Yan, P., Wu, Z., Wang, S., Sun, L., Wang, Z., Li, J., Sun, G., et al. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.05.004 · Cited by 109
Self-citation
Exosomes from antler stem cells alleviate mesenchymal stem cell senescence and osteoarthritis
Lei, J., Jiang, X., Li, W., Ren, J., Wang, D., Ji, Z., Wu, Z., Cheng, F., Cai, Y., Yu, Z., et al. (2021) · Protein & Cell · doi:10.1007/s13238-021-00860-9 · Cited by 109
Self-citation
Targeting senescent cells for a healthier longevity: the roadmap for an era of global aging
Sun, Y., Li, Q., & Kirkland, J. L. (2022) · Life Medicine · doi:10.1093/lifemedi/lnac030 · Cited by 105
Safety and tolerability of Triumeq in amyotrophic lateral sclerosis: the Lighthouse trial
Gold, J., Rowe, D. B., Kiernan, M. C., Vucic, S., Mathers, S., van Eijk, R. P. A., Nath, A., Montojo, M. G., Norato, G., Santamaria, U. A., et al. (2019) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2019.1632899 · Cited by 102
Generation of a Hutchinson–Gilford progeria syndrome monkey model by base editing
Wang, F., Zhang, W., Yang, Q., Kang, Y., Fan, Y., Wei, J., Liu, Z., Dai, S., Li, H., Li, Z., et al. (2020) · Protein & Cell · doi:10.1007/s13238-020-00740-8 · Cited by 93
Self-citation
Endogenous β-Galactosidase Activity in Continuously Nonproliferating Cells
Yegorov, Y. E., Akimov, S. S., Hass, R., Zelenin, A. V., & Prudovsky, I. A. (1998) · Experimental Cell Research · doi:10.1006/excr.1998.4169 · Cited by 90
Differential stem cell aging kinetics in Hutchinson-Gilford progeria syndrome and Werner syndrome
Wu, Z., Zhang, W., Song, M., Wang, W., Wei, G., Li, W., Lei, J., Huang, Y., Sang, Y., Chan, P., et al. (2018) · Protein & Cell · doi:10.1007/s13238-018-0517-8 · Cited by 89
Self-citation
ZKSCAN3 counteracts cellular senescence by stabilizing heterochromatin
Hu, H., Ji, Q., Song, M., Ren, J., Liu, Z., Wang, Z., Liu, X., Yan, K., Hu, J., Jing, Y., et al. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa425 · Cited by 89
Self-citation
Primate-restricted KRAB zinc finger proteins and target retrotransposons control gene expression in human neurons
Turelli, P., Playfoot, C. J., Grun, D., Raclot, C., Pontis, J., Coudray, A., Thorball, C. W., Duc, J., Pankevich, E. V., Deplancke, B., et al. (2020) · Science Advances · doi:10.1126/sciadv.aba3200 · Cited by 85
Crosstalk between the Rb pathway and AKT signaling forms a quiescence-senescence switch.
Imai, Y., Takahashi, A., Hanyu, A., Hori, S., Sato, S., Naka, K., Hirao, A., Ohtani, N., & Hara, E. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.006 · Cited by 84
Genome-wide R-loop Landscapes during Cell Differentiation and Reprogramming
Yan, P., Liu, Z., Song, M., Wu, Z., Xu, W. M., Li, K., Ji, Q., Wang, S., Liu, X., Yan, K., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107870 · Cited by 81
Self-citation
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Li, Y., Zhang, W., Chang, L., Han, Y., Sun, L., Gong, X., Tang, H., Liu, Z., Deng, H., Ye, Y., et al. (2016) · Protein & Cell · doi:10.1007/s13238-016-0278-1 · Cited by 79
Self-citation
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Zhang, M., Liang, Q., & Zheng, S. S. (2019) · Reviews in Medical Virology · doi:10.1002/rmv.2025 · Cited by 79
Inhibition of human endogenous retrovirus-K by antiretroviral drugs
Tyagi, R., Li, W., Parades, D., Bianchet, M. A., & Nath, A. (2017) · Retrovirology · doi:10.1186/s12977-017-0347-4 · Cited by 78
Self-citation
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Li, J., Zheng, Y., Yan, P., Song, M., Wang, S., Sun, L., Liu, Z., Ma, S., Belmonte, J. C. I., Chan, P., et al. (2020) · National Science Review · doi:10.1093/nsr/nwaa127 · Cited by 78
Self-citation
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Balestrieri, E., Pica, F., Matteucci, C., Zenobi, R., Sorrentino, R., Argaw-Denboba, A., Cipriani, C., Bucci, I., & Vallebona, P. S. (2015) · BioMed Research International · doi:10.1155/2015/164529 · Cited by 76
Regulation of stem cell function and neuronal differentiation by HERV-K via mTOR pathway
Wang, T., Medynets, M., Johnson, K. R., Doucet-O’Hare, T. T., Disanza, B., Li, W., Xu, Y., Bagnell, A. M., Tyagi, R., Sampson, K., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2002427117 · Cited by 74
Self-citation
Human endogenous retroviral elements promote genome instability via non-allelic homologous recombination
Campbell, I. M., Gambin, T., Dittwald, P., Beck, C. R., Shuvarikov, A., Hixson, P. M., Patel, A., Gambin, A., Shaw, C. A., Rosenfeld, J. A., et al. (2014) · BMC Biology · doi:10.1186/s12915-014-0074-4 · Cited by 74
Mental health starts with physical health: current status and future directions of non-pharmacological interventions to improve physical health in first-episode psychosis
Gates, J., Killackey, E., Phillips, L., & Álvarez-Jiménez, M. (2015) · The Lancet Psychiatry · doi:10.1016/s2215-0366(15)00213-8 · Cited by 72
Isolation and phylogeny of endogenous retrovirus sequences belonging to the HERV-W family in primates
Kim, H., Takenaka, O., & Crow, T. J. (1999) · Journal of General Virology · doi:10.1099/0022-1317-80-10-2613 · Cited by 70
Human Endogenous Retrovirus Type K (HERV-K) Particles Package and Transmit HERV-K–Related Sequences
Contreras-Galindo, R., Kaplan, M. H., Dube, D., Gonzalez-Hernandez, M. J., Chan, S., Meng, F., Dai, M., Omenn, G. S., Gitlin, S. D., & Markovitz, D. M. (2015) · Journal of Virology · doi:10.1128/jvi.00544-15 · Cited by 64
Inhibition of HERV-K (HML-2) in amyotrophic lateral sclerosis patients on antiretroviral therapy
Montojo, M. G., Fathi, S., Norato, G., Smith, B., Rowe, D. B., Kiernan, M. C., Vucic, S., Mathers, S., van Eijk, R. P. A., Santamaria, U. A., et al. (2021) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2021.117358 · Cited by 58
Identification of a HERV‐K env surface peptide highly recognized in Rheumatoid Arthritis (RA) patients: a cross‐sectional case–control study
Mameli, G., Erre, G., Caggiu, E., Mura, S., Cossu, D., Bo, M., Cadoni, M., Piras, A., Mundula, N., Colombo, E., et al. (2017) · Clinical and Experimental Immunology · doi:10.1111/cei.12964 · Cited by 56
Are human endogenous retroviruses triggers of autoimmune diseases? Unveiling associations of three diseases and viral loci
Nexø, B. A., Villesen, P., Nissen, K. K., Lindegaard, H., Rossing, P. R., Petersen, T., Tarnow, L., Hansen, B. D., Lorenzen, T., Hørslev‐Petersen, K., et al. (2015) · Immunologic Research · doi:10.1007/s12026-015-8671-z · Cited by 53
Aging-associated accumulation of mitochondrial DNA mutations in tumor origin
Kong, M., Guo, L., Xu, W., He, C., Jia, X., Zhao, Z., & Gu, Z. (2022) · Life Medicine · doi:10.1093/lifemedi/lnac014 · Cited by 51
Activation of HERV-K(HML-2) disrupts cortical patterning and neuronal differentiation by increasing NTRK3
Nair, V. P., Liu, H., Ciceri, G., Jungverdorben, J., Frishman, G., Tchieu, J. H., Cederquist, G., Rothenaigner, I., Schorpp, K., Klepper, L., et al. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.04.009 · Cited by 50
Endogenous retroviruses are associated with hippocampus-based memory impairment
Sankowski, R., Strohl, J. J., Huerta, T. S., Nasiri, E., Mazzarello, A. N., d’Abramo, C., Cheng, K. F., Staszewski, O., Prinz, M., Huerta, P. T., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1822164116 · Cited by 49
Human endogenous retrovirus HERV-K(HML-2) encodes a stable signal peptide with biological properties distinct from Rec
Ruggieri, A., Maldener, E., Sauter, M., Mueller‐Lantzsch, N., Meese, E. U., Fackler, O., & Mayer, J. M. (2009) · Retrovirology · doi:10.1186/1742-4690-6-17 · Cited by 42
Preferential retrotransposition in aging yeast mother cells is correlated with increased genome instability
Patterson, M. N., Scannapieco, A. E., Au, P. H., Dorsey, S. B., Royer, C. A., & Maxwell, P. H. (2015) · DNA repair · doi:10.1016/j.dnarep.2015.07.004 · Cited by 41
Human Endogenous Retrovirus K Homologous Sequences and Their Coding Capacity in Old World Primates
Mayer, J. M., Meese, E. U., & Mueller‐Lantzsch, N. (1998) · Journal of Virology · doi:10.1128/jvi.72.3.1870-1875.1998 · Cited by 39
Physiological and Pathological Aging Affects Chromatin Dynamics, Structure and Function at the Nuclear Edge
Robin, J. D., & Magdinier, F. (2016) · Frontiers in Genetics · doi:10.3389/fgene.2016.00153 · Cited by 39
Identification of endogenous retroviral reading frames in the human genome
Villesen, P., Aagaard, L., Wiuf, C., & Pedersen, F. (2004) · Retrovirology · doi:10.1186/1742-4690-1-32 · Cited by 37
Demethylation and derepression of genomic retroelements in the skeletal muscles of aged mice
Min, B., Jeon, K., Park, J. S., & Kang, Y. (2019) · Aging Cell · doi:10.1111/acel.13042 · Cited by 29
CRISPR/Cas9-mediated gene knockout reveals a guardian role of NF-κB/RelA in maintaining the homeostasis of human vascular cells
Wang, P., Liu, Z., Zhang, X., Li, J., Sun, L., Ju, Z., Li, J., Chan, P., Liu, G., Zhang, W., et al. (2018) · Protein & Cell · doi:10.1007/s13238-018-0560-5 · Cited by 28
Self-citation
The Retrotransposon storm and the dangers of a Collyer's genome
Dubnau, J. (2018) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2018.04.004 · Cited by 24
Failures at every level: breakdown of the epigenetic machinery of aging
Zhao, D., & Chen, S. (2022) · Life Medicine · doi:10.1093/lifemedi/lnac016 · Cited by 23
Expression Profiles of Endogenous Retroviruses in Old World Monkeys
Stengel, A., Roos, C., Hunsmann, G., Seifarth, W., Leib‐Mösch, C., & Greenwood, A. D. (2006) · Journal of Virology · doi:10.1128/jvi.80.9.4415-4421.2006 · Cited by 14
Epigenetic control of retrotransposons in adult tissues: implications for immune regulation
Tie, C. H. C., & Rowe, H. M. (2017) · Current Opinion in Virology · doi:10.1016/j.coviro.2017.06.007 · Cited by 12
Retrotransposon: a versatile player in human preimplantation development and health
Qu, Y., Izsvák, Z., & Wang, J. (2022) · Life Medicine · doi:10.1093/lifemedi/lnac041 · Cited by 7
A protocol for CRISPR-mediated activation and repression of human endogenous retroviruses in human pluripotent stem cells
Nair, V. P., Mayer, J. M., & Vincendeau, M. (2022) · STAR Protocols · doi:10.1016/j.xpro.2022.101281 · Cited by 4
Age-related cardiopathies gene editing
Song, M., Belmonte, J. C. I., & Liu, G. (2019) · Aging · doi:10.18632/aging.101853 · Cited by 2
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Liang, 2022, BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in primates, Nucleic Acids Res., 50, 3323

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See all 390

Authors: Liu, X., Liu, Z., Wu, Z., Ren, J., Fan, Y., Sun, L., Cao, G., Niu, Y., Zhang, B., Ji, Q., Jiang, X., Wang, C., Wang, Q., Ji, Z., Li, L., Esteban, C. R., Yan, K., Li, W., Cai, Y., Wang, S., Zheng, A., Zhang, Y. E., Tan, S., Cai, Y., Song, M., Lu, F., Tang, F., Ji, W., Zhou, Q., Belmonte, J. C. I., Zhang, W., Qu, J., & Liu, G.-H.
Affiliations: Chinese Academy of Sciences (CN)
Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
Huazhong Agricultural University (CN)
Kunming University of Science and Technology (CN)
Capital Medical University (CN)
Peking University (CN)
Corresponding author: Zhang, Weiqi
Qu, Jing
Liu, Guang-Hui
ORCID: Liu, Xiaoqian
Liu, Zunpeng
Wu, Zeming
Ren, Jie
Sun, Liang
Cao, Gang
Niu, Yuyu
Zhang, Baohu
Ji, Qianzhao
Jiang, Xiaoyu
Wang, Cui
Wang, Qiaoran
Yan, Kaowen
Li, Wei
Cai, Yusheng
Wang, Si
Zheng, Aihua
Zhang, Yong E.
Tan, Shengjun
Cai, Yingao
Song, Moshi
Lu, Falong
Tang, Fuchou
Ji, Weizhi
Zhou, Qi
Zhang, Weiqi
Qu, Jing
Liu, Guang-Hui
Venue: Cell
Publisher: Elsevier BV
Published: 2023-01
Volume: 186
Issue: 2
Pages: 287-304.e26
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2022.12.017
OpenAlex: W4313638435
Cited by: 390
References: 111
Citations by year: 2026: 89 · 2025: 119 · 2024: 97 · 2023: 74
FWCI: 67.31
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc/4.0/ (vor)
Locations: Cell (publishedVersion, cc-by-nc)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Funders: Tsinghua University
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
Keywords: endogenous retroviruses, cellular senescence, aging, retrovirus-like particles, transposable elements, viral transcription, neutralizing antibodies, tissue degeneration, primates, mice
MeSH terms: Aged, Aging, Animals, Humans, Primates, Cellular Senescence, Endogenous Retroviruses, Mice

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Resurrection of endogenous retroviruses during aging reinforces senescence

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