{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T15:06:52Z","timestamp":1781276812938,"version":"3.54.1"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["18gm0610007h0006"],"award-info":[{"award-number":["18gm0610007h0006"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["23K06638"],"award-info":[{"award-number":["23K06638"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Chronic inflammation is a key driver of aging\u2010related diseases, obesity\u2010associated metabolic disorders, and tumor progression. Aging and obesity contribute to the accumulation of senescent cells, which secrete senescence\u2010associated secretory phenotype (SASP) factors that promote tissue remodeling and chronic inflammation. Here, we investigated the pathological roles of angiopoietin\u2010like protein 2 (ANGPTL2), a potential SASP factor, in a mouse model of high\u2010fat diet\u2010induced premature aging. We found that ANGPTL2 deficiency shortened lifespan but attenuated systemic inflammation, indicating a complex role for ANGPTL2 in aging\u2010related processes. ANGPTL2 was required for maintaining intestinal homeostasis under metabolic stress; however, ANGPTL2 also exacerbated adipocyte hypertrophy and cardiac dysfunction. Furthermore, ANGPTL2\u2010mediated inflammation promoted kidney fibrosis but paradoxically protected against perivascular fibrosis in the liver, indicating its organ\u2010specific effects on fibrotic remodeling. In addition, ANGPTL2 influenced immune responses by driving bronchus\u2010associated lymphoid tissue formation. These findings suggest that ANGPTL2 has context\u2010dependent effects, balancing tissue homeostasis and inflammation\u2010driven pathologies. Our study provides novel insights into the dual roles of ANGPTL2 as a SASP factor in regulating inflammation, fibrosis, and tissue remodeling across different organ systems.<\/jats:p>","DOI":"10.1111\/acel.70370","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T06:06:34Z","timestamp":1767938794000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Context\u2010Dependent Roles of\n                    <scp>ANGPTL2<\/scp>\n                    \u2010Mediated Inflammaging in Tissue Homeostasis, Pathological Tissue Remodeling, and Longevity"],"prefix":"10.1111","volume":"25","author":[{"given":"Shinsei","family":"Yumoto","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"},{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruki","family":"Horiguchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"},{"name":"Department of Aging and Geriatric Medicine, Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keishi","family":"Miyata","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Kadomatsu","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"},{"name":"Center for Metabolic Regulation of Healthy Aging (CMHA), Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9339-1642","authenticated-orcid":false,"given":"Michio","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1396-1527","authenticated-orcid":false,"given":"Kimi","family":"Araki","sequence":"additional","affiliation":[{"name":"Center for Metabolic Regulation of Healthy Aging (CMHA), Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"},{"name":"Division of Developmental Genetics Institute of Resource Development and Analysis, Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Iwatsuki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Oike","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"},{"name":"Department of Aging and Geriatric Medicine, Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"},{"name":"Center for Metabolic Regulation of Healthy Aging (CMHA), Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2023.03.005"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17173"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13817"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01923-y"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.158207"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adj7050"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00314-w"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-023-00843-0"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.25259\/ijn_532_23"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2010.52"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-018-0059-4"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0675-0"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2007.10.003"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032158"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201695690"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.12554"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.329417.119"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388\u2010020\u201001505\u20107"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.16434"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-05338-4"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-024-00757-9"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-022-02405-8"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.113.303116"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2014.03.012"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modgep.2005.02.006"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-04243-6"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.11.001"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01792-5"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2014"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2015.12.021"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00005.2016"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1091"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2018.0601"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.70108"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1531901100"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/advances\/nmz061"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.1027116"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03122-4"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.08.003"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222212232"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13016"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nutd.2013.4"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-73828-4"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020\u2010025\u201001072\u20101"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-35985-4"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.16348"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12556"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70370","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70370","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70370","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T12:18:39Z","timestamp":1772972319000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70370"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,8]]},"references-count":47,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1111\/acel.70370"],"URL":"https:\/\/doi.org\/10.1111\/acel.70370","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,8]]},"assertion":[{"value":"2025-04-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70370"}}