{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T10:40:13Z","timestamp":1789382413771,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL107304"],"award-info":[{"award-number":["HL107304"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL081753"],"award-info":[{"award-number":["HL081753"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n While\n BAG3<\/jats:italic>\n has been identified as a causative gene for dilated cardiomyopathy, the major pathological events in\n BAG3\u2010<\/jats:italic>\n related cardiomyopathy that could be targeted for therapeutic benefit remain to be discovered. Here, we aim to uncover novel pathological events through genetic studies in a zebrafish\n bag3<\/jats:italic>\n cardiomyopathy model. Given the known cardioprotective effects of\n mtor<\/jats:italic>\n inhibition and the fact that\n transcription factor EB (tfeb<\/jats:italic>\n ) encodes a direct downstream phosphorylation target of mTOR signaling, we generated a cardiomyocyte\u2010specific transgenic line overexpressing\n tfeb<\/jats:italic>\n (\n Tg[cmlc2:tfeb]<\/jats:italic>\n ). This overexpression was sufficient to restore defective proteostasis and rescue cardiac dysfunction in the\n bag3<\/jats:italic>\n cardiomyopathy model. Importantly, we detected accelerated cardiac senescence in the\n bag3<\/jats:italic>\n cardiomyopathy model, which can be mitigated by\n Tg(cmlc2:tfeb)<\/jats:italic>\n . We compared cardiac transcriptomes between the\n Tg(cmlc2:tfeb)<\/jats:italic>\n transgenic fish and the\n mtor<\/jats:italic>\n \n xu015\/+<\/jats:italic>\n <\/jats:sup>\n mutant and found that inhibition of the fatty acid binding protein a (\n fabp7a<\/jats:italic>\n ) gene exerts therapeutic effects. Consistent with this genetic evidence, we detected elevated\n fabp7a<\/jats:italic>\n expression in the\n bag3<\/jats:italic>\n cardiomyopathy model, whereas cardiomyocyte\u2010specific overexpression of\n fabp7a<\/jats:italic>\n induced dysregulated proteostasis, accelerated cardiac senescence, and cardiac dysfunction. To elucidate the functions of Fabp7a in normative cardiac aging, we turned to the African Turquoise Killifish. We noted elevated Fabp7a expression in the hearts of aged killifish, and pharmacological inhibition of Fabp7a mitigated the cardiac aging process. Together, this study uncovered accelerated cardiac senescence as a key pathological event in\n bag3<\/jats:italic>\n cardiomyopathy and reveals that manipulating the mTOR\u2010Tfeb\u2010Fabp7a axis can mitigate this pathology and confer cardioprotective effects.\n <\/jats:p>","DOI":"10.1111\/acel.70216","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T06:47:41Z","timestamp":1757400461000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["An\n mTOR<\/scp>\n \u2010Tfeb\u2010Fabp7a Axis Ameliorates\n bag3<\/i>\n Cardiomyopathy via Decelerating Cardiac Aging"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4531-1721","authenticated-orcid":false,"given":"Yonghe","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Department of Cardiovascular Medicine Mayo Clinic Rochester Minnesota 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Department of Cardiovascular Medicine Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health University of Maryland School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueying","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Department of Cardiovascular Medicine Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Department of Cardiovascular Medicine Mayo 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