{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:44:07Z","timestamp":1792669447500,"version":"4.5.0"},"reference-count":0,"publisher":"Portland Press Ltd.","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2019\/17031-2"],"award-info":[{"award-number":["2019\/17031-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["PPQ"],"award-info":[{"award-number":["PPQ"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2022\/00840-8"],"award-info":[{"award-number":["2022\/00840-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Cardiac aging increases susceptibility to cardiovascular diseases, particularly myocardial infarction. Although evidence suggest association between activation of the AIM2 inflammasome and cardiovascular diseases, its contribution to age-related cardiac complications remains unknown. We investigated the role of the AIM2 inflammasome and the cardiac response to ischemia\u2013reperfusion (I\/R) injury in aged mice. Male wildtype (C57BL\/6) and AIM2-deficient (AIM2-\/-) mice were subjected to natural aging (21 months), using 3-month-old mice as controls, and human cardiomyocytes (AC16) were stressed by hydrogen peroxide to mimic senescent. AIM2 expression was upregulated in the aged myocardium and senescent AC16 cells, coinciding with increased levels of cleaved caspase-1 (p20), IL-1\u03b2, and IL-18. Functional assays in Langendorff-perfused hearts revealed that AIM2 deficiency significantly attenuated post-I\/R dysfunction in aged mice, restoring left ventricular developed pressure (LVDP) and pressure derivatives (+dP\/dTmax and \u2212dP\/dTmin) toward pre-ischemic levels. While AIM2 absence did not alter age-associated hypertrophy, fibrosis, longevity, or senescence markers (p53 and p21), it reduced the baseline pro-inflammatory and pro-pyroptotic profile of the aged heart (IL-1\u03b2, IL-18, GSDMD-N, and ASC speck). In vitro, AIM2 activation using Poly(dA:dT) elevated IL-1\u03b2, GSDMD-N, ASC speck, and cell death in senescent cells, whereas pharmacological inhibition with A151 prevented these effects. Concurrently, age-dependent AIM2 upregulation was confirmed in human cardiac datasets. Together, these findings suggest that age-dependent AIM2 induction primes a pro-inflammatory cardiac microenvironment, exacerbating post-I\/R injury and highlighting this pathway for future investigation in the context of cardiac aging.<\/jats:p>","DOI":"10.1042\/cs20260997","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:20:03Z","timestamp":1792668003000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The AIM2 inflammasome drives age-dependent cardiac dysfunction following ischemia-reperfusion in mice"],"prefix":"10.1042","author":[{"given":"Nathalia","family":"Senger","sequence":"first","affiliation":[{"name":"University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denival Nascimento","family":"Vieira-Junior","sequence":"additional","affiliation":[{"name":"Universidade de Sao Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T\u00e1batha","family":"de Oliveira Silva","sequence":"additional","affiliation":[{"name":"Universidade de Sao Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela Cavazza","family":"Cerri","sequence":"additional","affiliation":[{"name":"Universidade de Sao Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline Cristina","family":"Parletta","sequence":"additional","affiliation":[{"name":"Universidade de Sao Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme","family":"Lunardon","sequence":"additional","affiliation":[{"name":"Universidade de Sao Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa Maria","family":"Zacarias-Rodrigues","sequence":"additional","affiliation":[{"name":"Universidade de Sao Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabela","family":"Martins de Carvalho","sequence":"additional","affiliation":[{"name":"Universidade de Sao Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia Vanzo","family":"Ubi","sequence":"additional","affiliation":[{"name":"Universidade de Sao Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina Reingruber","family":"Fevereiro","sequence":"additional","affiliation":[{"name":"Universidade de Sao Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luiza Morais","family":"Barreto-Chaves","sequence":"additional","affiliation":[{"name":"Universidade de Sao Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,10,22]]},"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/doi\/10.1042\/CS20260997\/993145\/cs-2026-0997.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/doi\/10.1042\/CS20260997\/993145\/cs-2026-0997.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:20:04Z","timestamp":1792668004000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/doi\/10.1042\/CS20260997\/238213\/The-AIM2-inflammasome-drives-age-dependent-cardiac"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1042\/cs20260997","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]},"article-number":"CS20260997"}}