{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:02:10Z","timestamp":1792735330624,"version":"4.5.0"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2014,6,24]],"date-time":"2014-06-24T00:00:00Z","timestamp":1403568000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2014,6,24]],"date-time":"2014-06-24T00:00:00Z","timestamp":1403568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the\n                    <jats:italic>nfkb1<\/jats:italic>\n                    subunit of the transcription factor NF-\u03baB induces premature ageing in mice. We also show that these mice have reduced regeneration in liver and gut.\n                    <jats:italic>nfkb1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    fibroblasts exhibit aggravated cell senescence because of an enhanced autocrine and paracrine feedback through NF-\u03baB, COX-2 and ROS, which stabilizes DNA damage. Preferential accumulation of telomere-dysfunctional senescent cells in\n                    <jats:italic>nfkb1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    tissues is blocked by anti-inflammatory or antioxidant treatment of mice, and this rescues tissue regenerative potential. Frequencies of senescent cells in liver and intestinal crypts quantitatively predict mean and maximum lifespan in both short- and long-lived mice cohorts. These data indicate that systemic chronic inflammation can accelerate ageing via ROS-mediated exacerbation of telomere dysfunction and cell senescence in the absence of any other genetic or environmental factor.\n                  <\/jats:p>","DOI":"10.1038\/ncomms5172","type":"journal-article","created":{"date-parts":[[2014,6,24]],"date-time":"2014-06-24T11:01:12Z","timestamp":1403607672000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":732,"title":["Chronic inflammation induces telomere dysfunction and accelerates ageing in mice"],"prefix":"10.1038","volume":"5","author":[{"given":"Diana","family":"Jurk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o F.","family":"Passos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Oakley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Correia-Melo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Greaves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Saretzki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Fox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor","family":"Lawless","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhys","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Hewitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia LF","family":"Pender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Fullard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glyn","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Mann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"van de Sluis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek A.","family":"Mann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"von Zglinicki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,6,24]]},"reference":[{"key":"BFncomms5172_CR1","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.arr.2008.07.002","volume":"8","author":"HY Chung","year":"2009","unstructured":"Chung, H. Y. et al. Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res Rev. 8, 18\u201330 (2009).","journal-title":"Ageing Res Rev."},{"key":"BFncomms5172_CR2","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.mad.2006.11.016","volume":"128","author":"C Franceschi","year":"2007","unstructured":"Franceschi, C. et al. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech. Ageing Dev. 128, 92\u2013105 (2007).","journal-title":"Mech. Ageing Dev."},{"key":"BFncomms5172_CR3","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/nature12143","volume":"497","author":"G Zhang","year":"2013","unstructured":"Zhang, G. et al. Hypothalamic programming of systemic ageing involving IKK-beta, NF-kappaB and GnRH. Nature 497, 211\u2013216 (2013).","journal-title":"Nature"},{"key":"BFncomms5172_CR4","doi-asserted-by":"publisher","first-page":"3244","DOI":"10.1101\/gad.1588507","volume":"21","author":"AS Adler","year":"2007","unstructured":"Adler, A. S. et al. Motif module map reveals enforcement of aging by continual NF-kB activity. Genes Dev. 21, 3244\u20133257 (2007).","journal-title":"Genes Dev."},{"key":"BFncomms5172_CR5","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.cell.2008.10.052","volume":"136","author":"TLA Kawahara","year":"2009","unstructured":"Kawahara, T. L. A. et al. SIRT6 links histone H3 lysine 9 deacetylation to NF-\u03baB-dependent gene expression and organismal life span. Cell 136, 62\u201374 (2009).","journal-title":"Cell"},{"key":"BFncomms5172_CR6","doi-asserted-by":"publisher","first-page":"2311","DOI":"10.1101\/gad.197954.112","volume":"26","author":"FG Osorio","year":"2012","unstructured":"Osorio, F. G. et al. Nuclear lamina defects cause ATM-dependent NF-\u03baB activation and link accelerated aging to a systemic inflammatory response. Genes Dev. 26, 2311\u20132324 (2012).","journal-title":"Genes Dev."},{"key":"BFncomms5172_CR7","doi-asserted-by":"publisher","first-page":"2601","DOI":"10.1172\/JCI45785","volume":"122","author":"JS Tilstra","year":"2012","unstructured":"Tilstra, J. S. et al. NF-\u03baB inhibition delays DNA damage\u2013induced senescence and aging in mice. Clin. Invest. 122, 2601\u20132612 (2012).","journal-title":"Clin. Invest."},{"key":"BFncomms5172_CR8","doi-asserted-by":"publisher","first-page":"e125","DOI":"10.1371\/journal.pgen.0030125","volume":"3","author":"GM Martin","year":"2007","unstructured":"Martin, G. M., Bergman, A. & Barzilai, N. Genetic determinants of human health span and life span: progress and new opportunities. PLoS Genet. 3, e125 (2007).","journal-title":"PLoS Genet."},{"key":"BFncomms5172_CR9","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/nature02118","volume":"426","author":"F d\u2019Adda di Fagagna","year":"2003","unstructured":"d\u2019Adda di Fagagna, F. et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 426, 194\u2013198 (2003).","journal-title":"Nature"},{"key":"BFncomms5172_CR10","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/ng1937","volume":"39","author":"AR Choudhury","year":"2007","unstructured":"Choudhury, A. R. et al. Cdkn1a deletion improves stem cell function and lifespan of mice with dysfunctional telomeres without accelerating cancer formation. Nat. Genet. 39, 99\u2013105 (2007).","journal-title":"Nat. Genet."},{"key":"BFncomms5172_CR11","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1038\/ncomms1708","volume":"3","author":"G Hewitt","year":"2012","unstructured":"Hewitt, G. et al. Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence. Nat Commun. 3, 708 (2012).","journal-title":"Nat Commun."},{"key":"BFncomms5172_CR12","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1038\/msb.2010.5","volume":"6","author":"JF Passos","year":"2010","unstructured":"Passos, J. F. et al. Feedback between p21 and reactive oxygen production is necessary for cell senescence. Mol. Syst. Biol. 6, 347 (2010).","journal-title":"Mol. Syst. Biol."},{"key":"BFncomms5172_CR13","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1016\/j.cell.2008.03.039","volume":"133","author":"T Kuilman","year":"2008","unstructured":"Kuilman, T. et al. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133, 1019\u20131031 (2008).","journal-title":"Cell"},{"key":"BFncomms5172_CR14","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1016\/j.cell.2008.03.038","volume":"133","author":"JC Acosta","year":"2008","unstructured":"Acosta, J. C. et al. Chemokine signalling via the CXCR2 receptor reinforces senescence. Cell 133, 1006\u20131018 (2008).","journal-title":"Cell"},{"key":"BFncomms5172_CR15","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1038\/ncb1909","volume":"11","author":"F Rodier","year":"2009","unstructured":"Rodier, F. et al. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat. Cell Biol. 11, 973\u2013979 (2009).","journal-title":"Nat. Cell Biol."},{"key":"BFncomms5172_CR16","doi-asserted-by":"publisher","first-page":"2125","DOI":"10.1101\/gad.17276711","volume":"25","author":"Y Chien","year":"2011","unstructured":"Chien, Y. et al. Control of the senescence-associated secretory phenotype by NF-\u03baB promotes senescence and enhances chemosensitivity. Genes Dev. 25, 2125\u20132136 (2011).","journal-title":"Genes Dev."},{"key":"BFncomms5172_CR17","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1038\/emboj.2011.69","volume":"30","author":"A Freund","year":"2011","unstructured":"Freund, A., Patil, C. K. & Campisi, J. p38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype. EMBO J. 30, 1536\u20131548 (2011).","journal-title":"EMBO J."},{"key":"BFncomms5172_CR18","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/nature10600","volume":"479","author":"DJ Baker","year":"2011","unstructured":"Baker, D. J. et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479, 232\u2013236 (2011).","journal-title":"Nature"},{"key":"BFncomms5172_CR19","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.arr.2007.09.002","volume":"7","author":"A Salminen","year":"2008","unstructured":"Salminen, A. et al. Activation of innate immunity system during aging: NF-kB signaling is the molecular culprit of inflamm-aging. Ageing Res. Rev. 7, 83\u2013105 (2008).","journal-title":"Ageing Res. Rev."},{"key":"BFncomms5172_CR20","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.jhep.2010.03.025","volume":"53","author":"AM Elsharkawy","year":"2010","unstructured":"Elsharkawy, A. M. et al. The NF-\u03baB p50:p50:HDAC-1 repressor complex orchestrates transcriptional inhibition of multiple pro-inflammatory genes. Hepatology 53, 519\u2013527 (2010).","journal-title":"Hepatology"},{"key":"BFncomms5172_CR21","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/S0002-9440(10)62291-2","volume":"166","author":"F Oakley","year":"2005","unstructured":"Oakley, F. et al. Nuclear factor-\u03baB1 (p50) limits the inflammatory and fibrogenic responses to chronic injury. Am. J. Pathol. 166, 695\u2013708 (2005).","journal-title":"Am. J. Pathol."},{"key":"BFncomms5172_CR22","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1164\/rccm.200303-412OC","volume":"168","author":"JP Mizgerd","year":"2003","unstructured":"Mizgerd, J. P. et al. Nuclear factor-\u03baB p50 limits inflammation and prevents lung injury during Escherichia coli pneumonia. Am. Respir. Crit. Care Med. 168, 810\u2013817 (2003).","journal-title":"Am. Respir. Crit. Care Med."},{"key":"BFncomms5172_CR23","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1097\/NEN.0b013e3181654957","volume":"67","author":"S Campbell","year":"2008","unstructured":"Campbell, S. et al. Hepatic nuclear factor kappa B regulates neutrophil recruitment to the injured brain. J. Neuropathol. Exp. Neurol. 67, 223\u2013230 (2008).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"BFncomms5172_CR24","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1111\/j.1474-9726.2011.00702.x","volume":"10","author":"CY Liao","year":"2011","unstructured":"Liao, C. Y. et al. Fat maintenance is a predictor of the murine lifespan response to dietary restriction. Aging Cell 10, 629\u2013639 (2011).","journal-title":"Aging Cell"},{"key":"BFncomms5172_CR25","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/nrd2781","volume":"8","author":"V Baud","year":"2009","unstructured":"Baud, V. & Karin, M. Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls. Nat. Rev. Drug Discov. 8, 33\u201340 (2009).","journal-title":"Nat. Rev. Drug Discov."},{"key":"BFncomms5172_CR26","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1053\/jhep.2003.08052","volume":"38","author":"K Krupczak-Hollis","year":"2003","unstructured":"Krupczak-Hollis, K., Wang, X., Dennewitz, M. B. & Costa, R. H. Growth hormone stimulates proliferation of old-aged regenerating liver through forkhead box m1b. Hepatology 38, 1552\u20131562 (2003).","journal-title":"Hepatology"},{"key":"BFncomms5172_CR27","doi-asserted-by":"publisher","first-page":"1939","DOI":"10.1016\/j.cellsig.2013.06.007","volume":"25","author":"A Kauppinen","year":"2013","unstructured":"Kauppinen, A., Suuronen, T., Ojala, J., Kaarniranta, K. & Salminen, A. Antagonistic crosstalk between NF-kappaB and SIRT1 in the regulation of inflammation and metabolic disorders. Cell. Signal. 25, 1939\u20131948 (2013).","journal-title":"Cell. Signal."},{"key":"BFncomms5172_CR28","doi-asserted-by":"publisher","first-page":"B129","DOI":"10.1093\/geronj\/45.4.B129","volume":"45","author":"TS Chen","year":"1990","unstructured":"Chen, T. S., Currier, G. J. & Wabner, C. L. Intestinal transport during the lifespan of the mouse. J. Gerontol. Biol. Sci. 45, B129\u2013B133 (1990).","journal-title":"J. Gerontol. Biol. Sci."},{"key":"BFncomms5172_CR29","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1038\/ncb1024","volume":"5","author":"S Parrinello","year":"2003","unstructured":"Parrinello, S. et al. Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nat. Cell Biol. 5, 741\u2013747 (2003).","journal-title":"Nat. Cell Biol."},{"key":"BFncomms5172_CR30","doi-asserted-by":"publisher","first-page":"e301","DOI":"10.1371\/journal.pbio.0060301","volume":"6","author":"J-P Coppe","year":"2008","unstructured":"Coppe, J.-P. et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 6, e301 (2008).","journal-title":"PLoS Biol."},{"key":"BFncomms5172_CR31","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1038\/cr.2010.179","volume":"21","author":"S Miyamoto","year":"2010","unstructured":"Miyamoto, S. Nuclear initiated NF-kappaB signaling: NEMO and ATM take center stage. Cell Res. 21, 116\u2013130 (2010).","journal-title":"Cell Res."},{"key":"BFncomms5172_CR32","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.molmed.2010.03.003","volume":"16","author":"A Freund","year":"2010","unstructured":"Freund, A., Orjalo, A. V., Desprez, P. Y. & Campisi, J. Inflammatory networks during cellular senescence: causes and consequences. Trends Mol. Med. 16, 238\u2013246 (2010).","journal-title":"Trends Mol. Med."},{"key":"BFncomms5172_CR33","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/nature09787","volume":"470","author":"E Sahin","year":"2011","unstructured":"Sahin, E. et al. Telomere dysfunction induces metabolic and mitochondrial compromise. Nature 470, 359\u2013365 (2011).","journal-title":"Nature"},{"key":"BFncomms5172_CR34","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/1-4020-5688-5_1","volume":"42","author":"KD Rainsford","year":"2007","unstructured":"Rainsford, K. D. Anti-inflammatory drugs in the 21st century. Subcell. Biochem. 42, 3\u201327 (2007).","journal-title":"Subcell. Biochem."},{"key":"BFncomms5172_CR35","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1016\/j.bbalip.2013.04.005","volume":"1831","author":"S Martien","year":"2013","unstructured":"Martien, S. et al. Cellular senescence involves an intracrine prostaglandin E2 pathway in human fibroblasts. Biochim. Biophys. Acta Mol, Cell Biol. Lipids 1831, 1217\u20131227 (2013).","journal-title":"Biochim. Biophys. Acta Mol, Cell Biol. Lipids"},{"key":"BFncomms5172_CR36","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1111\/j.1474-9726.2012.00795.x","volume":"11","author":"G Nelson","year":"2012","unstructured":"Nelson, G. et al. A senescent cell bystander effect: senescence-induced senescence. Aging Cell 11, 345\u2013349 (2012).","journal-title":"Aging Cell"},{"key":"BFncomms5172_CR37","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1038\/ncb2784","volume":"15","author":"JC Acosta","year":"2013","unstructured":"Acosta, J. C. et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat. Cell Biol. 15, 978\u2013990 (2013).","journal-title":"Nat. Cell Biol."},{"key":"BFncomms5172_CR38","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/j.semcancer.2011.10.001","volume":"21","author":"JW Shay","year":"2011","unstructured":"Shay, J. W. & Wright, W. E. Roles of telomeres and telomerase in cancer. Semin. Cancer Biol. 21, 349\u2013353 (2011).","journal-title":"Semin. Cancer Biol."},{"key":"BFncomms5172_CR39","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/ncb2466","volume":"14","author":"M Fumagalli","year":"2012","unstructured":"Fumagalli, M. et al. Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat. Cell Biol. 14, 355\u2013365 (2012).","journal-title":"Nat. Cell Biol."},{"key":"BFncomms5172_CR40","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1126\/science.1122446","volume":"311","author":"U Herbig","year":"2006","unstructured":"Herbig, U., Ferreira, M., Condel, L., Carey, D. & Sedivy, J. M. Cellular Senescence in Aging Primates. Science 311, 1257 (2006).","journal-title":"Science"},{"key":"BFncomms5172_CR41","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1101\/gad.235184.113","volume":"28","author":"R Salama","year":"2014","unstructured":"Salama, R., Sadaie, M., Hoare, M. & Narita, M. Cellular senescence and its effector programs. Genes Dev. 28, 99\u2013114 (2014).","journal-title":"Genes Dev."},{"key":"BFncomms5172_CR42","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1016\/j.exger.2010.01.018","volume":"45","author":"C Lawless","year":"2010","unstructured":"Lawless, C. et al. Quantitative assessment of markers for cell senescence. Exp. Gerontol. 45, 772\u2013778 (2010).","journal-title":"Exp. Gerontol."},{"key":"BFncomms5172_CR43","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1111\/j.1474-9726.2009.00481.x","volume":"8","author":"C Wang","year":"2009","unstructured":"Wang, C., Jurk, D., Nelson, G., Martin-Ruiz, C. & von Zglinicki, T. DNA damage response and cellular senescence in aging mice. Aging Cell 8, 311\u2013323 (2009).","journal-title":"Aging Cell"},{"key":"BFncomms5172_CR44","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1111\/j.1348-0421.2010.00249.x","volume":"54","author":"YJ Lee","year":"2010","unstructured":"Lee, Y. J. & Chuang, Y. C. Ibuprofen augments pro-inflammatory cytokine release in a mouse model of Vibrio vulnificus infection. Microbiol. Immunol. 54, 542\u2013550 (2010).","journal-title":"Microbiol. Immunol."},{"key":"BFncomms5172_CR45","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.bbi.2009.11.006","volume":"24","author":"JL Teeling","year":"2009","unstructured":"Teeling, J. L., Cunningham, C., Newman, T. A. & Perry, V. H. The effect of non-steroidal anti-inflammatory agents on behavioural changes and cytokine production following systemic inflammation: Implications for a role of COX-1. Brain Behav. Immun. 24, 409\u2013419 (2009).","journal-title":"Brain Behav. Immun."},{"key":"BFncomms5172_CR46","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1002\/hep.26046","volume":"57","author":"M Aparicio-Vergara","year":"2013","unstructured":"Aparicio-Vergara, M. et al. TNF receptor 1 gain-of-function mutation aggravates non-alcoholic fatty liver disease but does not cause insulin resistance in a murine model. Hepatology 57, 566\u2013576 (2013).","journal-title":"Hepatology"},{"key":"BFncomms5172_CR47","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1038\/ncb2621","volume":"14","author":"A Ghosh","year":"2012","unstructured":"Ghosh, A. et al. Telomerase directly regulates NF-kappaB-dependent transcription. Nat. Cell Biol. 14, 1270\u20131281 (2012).","journal-title":"Nat. Cell Biol."},{"key":"BFncomms5172_CR48","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/S0968-0004(02)02110-2","volume":"27","author":"T von Zglinicki","year":"2002","unstructured":"von Zglinicki, T. Oxidative stress shortens telomeres. Trends Biochem. Sci. 27, 339\u2013344 (2002).","journal-title":"Trends Biochem. Sci."},{"key":"BFncomms5172_CR49","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1111\/j.1474-9726.2012.00870.x","volume":"11","author":"D Jurk","year":"2012","unstructured":"Jurk, D. et al. Postmitotic neurons develop a p21-dependent senescence-like phenotype driven by a DNA damage response. Aging Cell 11, 996\u20131004 (2012).","journal-title":"Aging Cell"},{"key":"BFncomms5172_CR50","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/ncb2388","volume":"14","author":"T Sperka","year":"2012","unstructured":"Sperka, T. et al. Puma and p21 represent cooperating checkpoints limiting self-renewal and chromosomal instability of somatic stem cells in response to telomere dysfunction. Nat. Cell Biol. 14, 73\u201379 (2012).","journal-title":"Nat. Cell Biol."},{"key":"BFncomms5172_CR51","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1038\/nature05862","volume":"447","author":"DJ Rossi","year":"2007","unstructured":"Rossi, D. J. et al. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature 447, 725\u2013729 (2007).","journal-title":"Nature"},{"key":"BFncomms5172_CR52","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1016\/j.cell.2012.01.040","volume":"148","author":"J Wang","year":"2012","unstructured":"Wang, J. et al. A differentiation checkpoint limits hematopoietic stem cell self-renewal in response to DNA damage. Cell 148, 1001\u20131014 (2012).","journal-title":"Cell"},{"key":"BFncomms5172_CR53","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.dnarep.2010.09.008","volume":"10","author":"DB Rhee","year":"2011","unstructured":"Rhee, D. B., Ghosh, A., Lu, J., Bohr, V. A. & Liu, Y. Factors that influence telomeric oxidative base damage and repair by DNA glycosylase OGG1. DNA Repair (Amst) 10, 34\u201344 (2011).","journal-title":"DNA Repair (Amst)"},{"key":"BFncomms5172_CR54","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1006\/excr.1997.3893","volume":"239","author":"S Petersen","year":"1998","unstructured":"Petersen, S., Saretzki, G. & von Zglinicki, T. Preferential accumulation of single-stranded regions in telomeres of human fibroblasts. Exp. Cell Res. 239, 152\u2013160 (1998).","journal-title":"Exp. Cell Res."},{"key":"BFncomms5172_CR55","doi-asserted-by":"publisher","first-page":"e110","DOI":"10.1371\/journal.pbio.0050110","volume":"5","author":"JF Passos","year":"2007","unstructured":"Passos, J. F. et al. Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence. PLoS Biol. 5, e110 (2007).","journal-title":"PLoS Biol."},{"key":"BFncomms5172_CR56","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1111\/j.1474-9726.2008.00414.x","volume":"7","author":"R Strong","year":"2008","unstructured":"Strong, R. et al. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice. Aging Cell 7, 641\u2013650 (2008).","journal-title":"Aging Cell"},{"key":"BFncomms5172_CR57","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1172\/JCI64098","volume":"123","author":"T Tchkonia","year":"2013","unstructured":"Tchkonia, T., Zhu, Y., van Deursen, J., Campisi, J. & Kirkland, J. L. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J. Clin. Invest. 123, 966\u2013972 (2013).","journal-title":"J. Clin. Invest."},{"key":"BFncomms5172_CR58","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1161\/CIRCULATIONAHA.105.580506","volume":"113","author":"HL Hillege","year":"2006","unstructured":"Hillege, H. L. et al. Renal function as a predictor of outcome in a broad spectrum of patients with heart failure. Circulation 113, 671\u2013678 (2006).","journal-title":"Circulation"},{"key":"BFncomms5172_CR59","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1111\/acel.12068","volume":"12","author":"L Fontana","year":"2013","unstructured":"Fontana, L. et al. Identification of a metabolic signature for multidimensional impairment and mortality risk in hospitalized older patients. Aging Cell 12, 459\u2013466 (2013).","journal-title":"Aging Cell"},{"key":"BFncomms5172_CR60","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.mad.2012.05.005","volume":"133","author":"J Collerton","year":"2012","unstructured":"Collerton, J. et al. Frailty and the role of inflammation, immunosenescence and cellular ageing in the very old: cross-sectional findings from the Newcastle 85+ Study. Mech. Ageing Dev. 133, 456\u2013466 (2012).","journal-title":"Mech. Ageing Dev."},{"key":"BFncomms5172_CR61","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/2046-2395-1-3","volume":"1","author":"KM Cameron","year":"2012","unstructured":"Cameron, K. M., Miwa, S., Walker, C. & von Zglinicki, T. Male mice retain a metabolic memory of improved glucose tolerance induced during adult onset, short-term dietary restriction. Longevity Healthspan 1, 3 (2012).","journal-title":"Longevity Healthspan"},{"key":"BFncomms5172_CR62","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.mad.2011.04.004","volume":"132","author":"KM Cameron","year":"2011","unstructured":"Cameron, K. M. et al. Gross energy metabolism in mice under late onset, short term caloric restriction. Mech. Ageing Dev. 132, 202\u2013209 (2011).","journal-title":"Mech. Ageing Dev."},{"key":"BFncomms5172_CR63","first-page":"186","volume":"12","author":"G Higgins","year":"1931","unstructured":"Higgins, G. & Anderson, R. Experimental pathology of the liver. I. Restoration of the liver of the white rat following partial surgical removal. Arch. Pathol. 12, 186\u2013202 (1931).","journal-title":"Arch. Pathol."},{"key":"BFncomms5172_CR64","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/j.cell.2008.09.034","volume":"135","author":"A Tomas-Loba","year":"2008","unstructured":"Tomas-Loba, A. et al. Telomerase reverse transcriptase delays aging in cancer-resistant mice. Cell 135, 609\u2013622 (2008).","journal-title":"Cell"},{"key":"BFncomms5172_CR65","doi-asserted-by":"publisher","first-page":"3379","DOI":"10.4161\/cc.8.20.9857","volume":"8","author":"G Nelson","year":"2009","unstructured":"Nelson, G., Buhmann, M. & von Zglinicki, T. DNA damage foci in mitosis are devoid of 53BP1. Cell Cycle 8, 3379\u20133383 (2009).","journal-title":"Cell Cycle"},{"key":"BFncomms5172_CR66","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1042\/BJ20082429","volume":"421","author":"H Sato","year":"2009","unstructured":"Sato, H. et al. Group III secreted phospholipase A2 transgenic mice spontaneously develop inflammation. Biochem J. 421, 17\u201327 (2009).","journal-title":"Biochem J."},{"key":"BFncomms5172_CR67","first-page":"319","volume":"49","author":"M Ullman-Cullere","year":"1999","unstructured":"Ullman-Cullere, M. & Foltz, C. Body condition scoring: a rapid and accurate method for assessing health status in mice. Lab. Anim. Sci. 49, 319\u2013323 (1999).","journal-title":"Lab. Anim. Sci."},{"key":"BFncomms5172_CR68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1258\/la.2010.010031","volume":"45","author":"P Hawkins","year":"2011","unstructured":"Hawkins, P. et al. A guide to defining and implementing protocols for the welfare assessment of laboratory animals: eleventh report of the BVAAWF\/FRAME\/RSPCA\/UFAW Joint Working Group on refinement. Lab. Anim. 45, 1\u201313 (2011).","journal-title":"Lab. Anim."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/ncomms5172.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms5172","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms5172.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T22:33:51Z","timestamp":1672958031000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms5172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6,24]]},"references-count":68,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2014,9,22]]}},"alternative-id":["BFncomms5172"],"URL":"https:\/\/doi.org\/10.1038\/ncomms5172","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718465301.793496659","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.718465301.793496566","asserted-by":"object"}]},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,6,24]]},"assertion":[{"value":"20 November 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 May 2014","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2014","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4172"}}