{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:51:22Z","timestamp":1790729482155,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T00:00:00Z","timestamp":1644883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700254"],"award-info":[{"award-number":["81700254"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070410"],"award-info":[{"award-number":["82070410"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Aging is an important risk factor for cardiovascular diseases, and aging\u2010related cardiac dysfunction serves as\u00a0a\u00a0major\u00a0determinant of morbidity and\u00a0mortality in elderly populations. Our previous study has identified fibronectin type III domain\u2010containing 5 (FNDC5) and its cleaved form, irisin, as the cardioprotectant against doxorubicin\u2010induced cardiomyopathy. Herein, aging or matched young mice were overexpressed with FNDC5 by adeno\u2010associated virus serotype 9 (AAV9) vectors, or subcutaneously infused with irisin to uncover the role of FNDC5 in aging\u2010related cardiac dysfunction. To verify the involvement of nucleotide\u2010binding oligomerization domain\u2010like receptor with a pyrin domain 3 (NLRP3) and AMP\u2010activated protein kinase \u03b1 (AMPK\u03b1), <jats:italic>Nlrp3<\/jats:italic> or <jats:italic>Ampk\u03b12<\/jats:italic>\u00a0global knockout mice were used. Besides, young mice were injected with AAV9\u2010FNDC5 and maintained for 12\u00a0months to determine the preventive effect of FNDC5. Moreover, neonatal rat cardiomyocytes were stimulated with tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) to examine the role of FNDC5 <jats:italic>in vitro<\/jats:italic>. We found that FNDC5 was downregulated in aging hearts. Cardiac\u2010specific overexpression of FNDC5 or irisin infusion significantly suppressed NLRP3 inflammasome and cardiac inflammation, thereby attenuating aging\u2010related cardiac remodeling and dysfunction. In addition, irisin treatment also inhibited cellular senescence in TNF\u2010\u03b1\u2010stimulated cardiomyocytes <jats:italic>in vitro<\/jats:italic>. Mechanistically, FNDC5 activated AMPK\u03b1 through blocking the lysosomal degradation of glucagon\u2010like peptide\u20101 receptor. More importantly, FNDC5\u00a0gene transfer in early life could delay the onset of cardiac dysfunction during aging process. We prove that FNDC5 improves aging\u2010related cardiac dysfunction by activating AMPK\u03b1, and it might be a promising therapeutic target to support cardiovascular health in elderly populations.<\/jats:p>","DOI":"10.1111\/acel.13556","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T08:47:04Z","timestamp":1644914824000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Fibronectin type III domain\u2010containing 5 improves aging\u2010related cardiac dysfunction in mice"],"prefix":"10.1111","volume":"21","author":[{"given":"Can","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Pei","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Yan","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si\u2010Chi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen\u2010Guo","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2210-3169","authenticated-orcid":false,"given":"Qi\u2010Zhu","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000105680.92873.70"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10777"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/db17\u20100639"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2018.03.004"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2017.08.003"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2016.6648"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.176024"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.03743"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1321942111"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000749"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4267"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0735\u20101097(00)00582\u20109"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/RES.0000000000000110"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003\u20100007"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15462"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI98287"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101747"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2019.03.003"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.124"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014\u20101437"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz566"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201003941\u20102"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.06.028"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz768"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz961"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2021.06.013"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010018\u20100275\u20104"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13449"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010017\u20104232\u20104"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvy279"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.313940"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13050"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700761RR"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.300171"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00871"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20190139"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2011.12.005"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2020.02.011"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0710402105"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.06.053"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474\u20109726.2010.00586.x"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000057810.48709.f6"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3100203"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.05.023"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.29680"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010019\u20100372\u2010z"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401\u2010020\u201000557\u20105"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010021\u201003922\u20102"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10565\u2010021\u201009581\u20105"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401\u2010020\u20100473\u20108"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010017\u20100123\u20103"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.29907"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13556","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.13556","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13556","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T22:47:49Z","timestamp":1749163669000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.13556"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,15]]},"references-count":52,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1111\/acel.13556"],"URL":"https:\/\/doi.org\/10.1111\/acel.13556","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,15]]},"assertion":[{"value":"2021-06-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13556"}}