{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:07:57Z","timestamp":1790204877809,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T00:00:00Z","timestamp":1680220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T00:00:00Z","timestamp":1680220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["RO1 DK121527"],"award-info":[{"award-number":["RO1 DK121527"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R21 AA026922"],"award-info":[{"award-number":["R21 AA026922"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK100603"],"award-info":[{"award-number":["DK100603"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Our studies indicate that the longevity factor SIRT1 is implicated in metabolic disease; however, whether and how hepatocyte\u2010specific SIRT1 signaling is involved in liver fibrosis remains undefined. We characterized a functional link of age\u2010mediated defects in SIRT1 to the NLRP3 inflammasome during age\u2010related liver fibrosis. In multiple experimental murine models of liver fibrosis, we compared the development of liver fibrosis in young and old mice, as well as in liver\u2010specific SIRT1 knockout (SIRT1 LKO) mice and wild\u2010type (WT) mice. Liver injury, fibrosis, and inflammation were assessed histologically and quantified by real\u2010time PCR analysis. In a model of hepatotoxin\u2010induced liver fibrosis, old mice displayed more severe and persistent liver fibrosis than young mice during liver injury and after injury cessation, as characterized by inhibition of SIRT1, induction of NLRP3, infiltration of macrophages and neutrophils, activation of hepatic stellate cells (HSCs), and excessive deposition and remodeling of the extracellular matrix. Mechanistically, deletion of SIRT1 in hepatocytes resulted in NLRP3 and IL\u20101\u03b2 induction, pro\u2010inflammatory response, and severe liver fibrosis in young mice, mimicking the ability of aging to impair the resolution of established fibrosis. In an aging mouse model, chronic\u2010plus\u2010binge alcohol feeding\u2010induced liver fibrosis was attenuated by treatment with MCC950, a selective NLRP3 inhibitor. NLRP3 inhibition ameliorated alcoholic liver fibrosis in old mice by repressing inflammation and reducing hepatocyte\u2010derived danger signaling\u2014ASK1 and HMGB1.\u00a0In conclusion, age\u2010dependent SIRT1 defects lead to NLRP3 activation and inflammation, which in turn impairs the capacity to resolve fibrosis during aging.<\/jats:p>","DOI":"10.1111\/acel.13811","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T05:31:05Z","timestamp":1680240665000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Age\u2010dependent loss of hepatic\n                    <scp>SIRT1<\/scp>\n                    enhances NLRP3 inflammasome signaling and impairs capacity for liver fibrosis resolution"],"prefix":"10.1111","volume":"22","author":[{"given":"Jennifer","family":"Adjei\u2010Mosi","sequence":"first","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies, Center for Healthy Aging  San Antonio Texas USA"},{"name":"Department of Molecular Medicine The University of Texas Health San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Sun","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies, Center for Healthy Aging  San Antonio Texas USA"},{"name":"Department of Molecular Medicine The University of Texas Health San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0229-9360","authenticated-orcid":false,"given":"Steven Blake","family":"Smithson","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies, Center for Healthy Aging  San Antonio Texas USA"},{"name":"Department of Molecular Medicine The University of Texas Health San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavyn Lee","family":"Shealy","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies, Center for Healthy Aging  San Antonio Texas USA"},{"name":"Department of Molecular Medicine The University of Texas Health San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krupa Dhruvitha","family":"Amerineni","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies, Center for Healthy Aging  San Antonio Texas USA"},{"name":"Department of Molecular Medicine The University of Texas Health San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zerong","family":"Liang","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies, Center for Healthy Aging  San Antonio Texas USA"},{"name":"Department of Molecular Medicine The University of Texas Health San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanqing","family":"Chen","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies, Center for Healthy Aging  San Antonio Texas USA"},{"name":"Department of Molecular Medicine The University of Texas Health San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Wang","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies, Center for Healthy Aging  San Antonio Texas USA"},{"name":"Department of Molecular Medicine The University of Texas Health San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinggong","family":"Ping","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies, Center for Healthy Aging  San Antonio Texas USA"},{"name":"Department of Molecular Medicine The University of Texas Health San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyan","family":"Han","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Morita","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies, Center for Healthy Aging  San Antonio Texas USA"},{"name":"Department of Molecular Medicine The University of Texas Health San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrita","family":"Kamat","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies, Center for Healthy Aging  San Antonio Texas USA"},{"name":"Geriatric Research, Education and Clinical Center South Texas Veterans Health Care System  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Musi","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies, Center for Healthy Aging  San Antonio Texas USA"},{"name":"Geriatric Research, Education and Clinical Center South Texas Veterans Health Care System  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2502-2586","authenticated-orcid":false,"given":"Mengwei","family":"Zang","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies, Center for Healthy Aging  San Antonio Texas USA"},{"name":"Department of Molecular Medicine The University of Texas Health San Antonio  San Antonio Texas USA"},{"name":"Geriatric Research, Education and Clinical Center South Texas Veterans Health Care System  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,31]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.09.014"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29849"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.14338"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589\u2010019\u20100277\u20107"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3806"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.can\u201012\u20102233"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30866"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30093"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.90564.2008"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010019\u20100215\u20107"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3893"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.01.009"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M802187200"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2019.07.021"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2014.04.002"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci93563"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci88881"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.12.003"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700612R"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.10.059"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10\u2010173492"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2014.03.007"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci60777"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2017.12.006"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.11.004"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32152"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707914"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.08.017"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.149"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26592"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.01.056"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.00065"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13811","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.13811","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13811","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T08:17:58Z","timestamp":1773994678000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.13811"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,31]]},"references-count":32,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10.1111\/acel.13811"],"URL":"https:\/\/doi.org\/10.1111\/acel.13811","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,31]]},"assertion":[{"value":"2022-09-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13811"}}