{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T15:24:47Z","timestamp":1793287487924,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,25]],"date-time":"2020-01-25T00:00:00Z","timestamp":1579910400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["K99 AG049126"],"award-info":[{"award-number":["K99 AG049126"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P01 AG043376"],"award-info":[{"award-number":["P01 AG043376"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R00 AG057032"],"award-info":[{"award-number":["R00 AG057032"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG063543"],"award-info":[{"award-number":["R01 AG063543"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R56 AG059676"],"award-info":[{"award-number":["R56 AG059676"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U19 AG056278"],"award-info":[{"award-number":["U19 AG056278"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000965","name":"American Federation for Aging Research","doi-asserted-by":"publisher","award":["The Irene Diamond\u00a0Fund\/American Federation on Aging Research\u00a0Postdoctoral Transition Award"],"award-info":[{"award-number":["The Irene Diamond\u00a0Fund\/American Federation on Aging Research\u00a0Postdoctoral Transition Award"]}],"id":[{"id":"10.13039\/100000965","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Senescent cells accumulate with age in vertebrates and promote aging largely through their senescence\u2010associated secretory phenotype (SASP). Many types of stress induce senescence, including genotoxic stress. ERCC1\u2010XPF is a DNA repair endonuclease required for multiple DNA repair mechanisms that protect the nuclear genome. Humans or mice with reduced expression of this enzyme age rapidly due to increased levels of spontaneous, genotoxic stress. Here, we asked whether this corresponds to an increased level of senescent cells.\n                    <jats:italic>\n                      p16\n                      <jats:sup>Ink4a<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic>\n                      p21\n                      <jats:sup>Cip1<\/jats:sup>\n                    <\/jats:italic>\n                    mRNA were increased ~15\u2010fold in peripheral lymphocytes from 4\u2010 to 5\u2010month\u2010old\n                    <jats:italic>Ercc1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2206<\/jats:sup>\n                    and 2.5\u2010year\u2010old wild\u2010type (WT) mice, suggesting that these animals exhibit a similar biological age.\n                    <jats:italic>\n                      p16\n                      <jats:sup>Ink4a<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic>\n                      p21\n                      <jats:sup>Cip1<\/jats:sup>\n                    <\/jats:italic>\n                    mRNA were elevated in 10 of 13 tissues analyzed from 4\u2010 to 5\u2010month\u2010old\n                    <jats:italic>Ercc1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2206<\/jats:sup>\n                    mice, indicating where endogenous DNA damage drives senescence in vivo. Aged WT mice had similar increases of\n                    <jats:italic>\n                      p16\n                      <jats:sup>Ink4a<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic>\n                      p21\n                      <jats:sup>Cip1<\/jats:sup>\n                    <\/jats:italic>\n                    mRNA in the same 10 tissues as the mutant mice. Senescence\u2010associated \u03b2\u2013galactosidase activity and p21\n                    <jats:italic>\n                      <jats:sup>Cip1<\/jats:sup>\n                    <\/jats:italic>\n                    protein also were increased in tissues of the progeroid and aged mice, while Lamin B1 mRNA and protein levels were diminished. In\n                    <jats:italic>Ercc1<\/jats:italic>\n                    <jats:sup>\u2212\/\u0394<\/jats:sup>\n                    mice with a\n                    <jats:italic>\n                      p16\n                      <jats:sup>Ink4a<\/jats:sup>\n                    <\/jats:italic>\n                    luciferase reporter, bioluminescence rose steadily with age, particularly in lung, thymus, and pancreas. These data illustrate where senescence occurs with natural and accelerated aging in mice and the relative extent of senescence among tissues. Interestingly, senescence was greater in male mice until the end of life. The similarities between\n                    <jats:italic>Ercc1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2206<\/jats:sup>\n                    and aged WT\u00a0mice support the conclusion that the DNA repair\u2010deficient mice accurately model the\u00a0age\u2010related accumulation of senescent cells, albeit six\u2010times faster.\n                  <\/jats:p>","DOI":"10.1111\/acel.13094","type":"journal-article","created":{"date-parts":[[2020,1,25]],"date-time":"2020-01-25T12:39:43Z","timestamp":1579955983000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":334,"title":["Tissue specificity of senescent cell accumulation during physiologic and accelerated aging of mice"],"prefix":"10.1111","volume":"19","author":[{"given":"Matthew J.","family":"Yousefzadeh","sequence":"first","affiliation":[{"name":"Institute on the Biology of Aging and Metabolism University of Minnesota Minneapolis MN USA"},{"name":"Department of Biochemistry, Molecular Biology and Biophysics University of Minnesota Minneapolis MN USA"},{"name":"Department of Molecular Medicine Scripps Research Institute Jupiter FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Scripps Research Institute Jupiter FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Bukata","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Scripps Research Institute Jupiter FL USA"},{"name":"Harriet L. Wilkes Honors College Florida Atlantic University Jupiter FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin A.","family":"Wade","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Scripps Research Institute Jupiter FL USA"},{"name":"Harriet L. Wilkes Honors College Florida Atlantic University Jupiter FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara J.","family":"McGowan","sequence":"additional","affiliation":[{"name":"Institute on the Biology of Aging and Metabolism University of Minnesota Minneapolis MN USA"},{"name":"Department of Biochemistry, Molecular Biology and Biophysics University of Minnesota Minneapolis MN USA"},{"name":"Department of Molecular Medicine Scripps Research Institute Jupiter FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luise A.","family":"Angelini","sequence":"additional","affiliation":[{"name":"Institute on the Biology of Aging and Metabolism University of Minnesota Minneapolis MN USA"},{"name":"Department of Biochemistry, Molecular Biology and Biophysics University of Minnesota Minneapolis MN USA"},{"name":"Department of Molecular Medicine Scripps Research Institute Jupiter FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Bank","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Scripps Research Institute Jupiter FL USA"},{"name":"Charles E. Schmidt College of Medicine Florida Atlantic University Boca Raton FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditi U.","family":"Gurkar","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Scripps Research Institute Jupiter FL USA"},{"name":"Department of Medicine University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collin A.","family":"McGuckian","sequence":"additional","affiliation":[{"name":"Institute on the Biology of Aging and Metabolism University of Minnesota Minneapolis MN USA"},{"name":"Department of Biochemistry, Molecular Biology and Biophysics University of Minnesota Minneapolis MN USA"},{"name":"Department of Molecular Medicine Scripps Research Institute Jupiter FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariah F.","family":"Calubag","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Scripps Research Institute Jupiter FL USA"},{"name":"Harriet L. Wilkes Honors College Florida Atlantic University Jupiter FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan I.","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Scripps Research Institute Jupiter FL USA"},{"name":"Harriet L. Wilkes Honors College Florida Atlantic University Jupiter FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7919-3954","authenticated-orcid":false,"given":"Christin E.","family":"Burd","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Cancer Biology and Genetics The Ohio State University Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Robbins","sequence":"additional","affiliation":[{"name":"Institute on the Biology of Aging and Metabolism University of Minnesota Minneapolis MN USA"},{"name":"Department of Biochemistry, Molecular Biology and Biophysics University of Minnesota Minneapolis MN USA"},{"name":"Department of Molecular Medicine Scripps Research Institute Jupiter FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1074-1385","authenticated-orcid":false,"given":"Laura J.","family":"Niedernhofer","sequence":"additional","affiliation":[{"name":"Institute on the Biology of Aging and Metabolism University of Minnesota Minneapolis MN USA"},{"name":"Department of Biochemistry, Molecular Biology and Biophysics University of Minnesota Minneapolis MN USA"},{"name":"Department of Molecular Medicine Scripps Research Institute Jupiter FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00293-08"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16932"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1382"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.12.010"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2944"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-030212-183653"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4010"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4000"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-121808-102144"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10522-008-9179-x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.20.9363"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3402\/pba.v1i0.7219"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E11-10-0884"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24713"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2015.01.045"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300985815625169"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a025882"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5172"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa5612"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep39501"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI22475"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2006.00199.x"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1818313116"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2009.00489.x"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00032.x"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9728.2004.00081.x"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2016.00147"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05456"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-062917-012239"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199907)180:1<123:AID-JCP14>3.0.CO;2-W"},{"key":"e_1_2_10_32_1","volume-title":"Spontaneous DNA damage to the nuclear genome promotes senescence and aging","author":"Robinson A. R. Y.","year":"2018"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2015.143"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3960"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3898"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64098"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45785"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13193"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2009.00481.x"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2012.00828.x"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0047-6374(03)00008-3"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-8931-7_17"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12706"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.09.015"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12445"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12344"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Facel.13094","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13094","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.13094","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13094","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T05:28:56Z","timestamp":1726723736000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.13094"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,25]]},"references-count":45,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["10.1111\/acel.13094"],"URL":"https:\/\/doi.org\/10.1111\/acel.13094","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,25]]},"assertion":[{"value":"2017-08-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13094"}}