{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T04:58:32Z","timestamp":1788238712693,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T00:00:00Z","timestamp":1696550400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T00:00:00Z","timestamp":1696550400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1651385"],"award-info":[{"award-number":["1651385"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1805157"],"award-info":[{"award-number":["1805157"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Aging is the main risk factor for cardiovascular disease (CVD). As the world's population ages rapidly and CVD rates rise, there is a growing need for physiologically relevant models of aging hearts to better understand cardiac aging. Translational research relies heavily on young animal models; however, these models correspond to early ages in human life, therefore cannot fully capture the pathophysiology of age\u2010related CVD. Here, we first investigated the transcriptomic and proteomic changes that occur with human cardiac aging. We then chronologically aged human induced pluripotent stem cell\u2010derived cardiomyocytes (iCMs) and showed that 14\u2010month\u2010old iCMs exhibited a similar aging profile to the human CMs and recapitulated age\u2010related disease hallmarks. Using aged iCMs, we studied the effect of cell age on the young extracellular matrix (ECM) therapy, an emerging approach for myocardial infarction (MI) treatment and prevention. Young ECM decreased oxidative stress, improved survival, and post\u2010MI beating in aged iCMs. In the absence of stress, young ECM improved beating and reversed aging\u2010associated expressions in 3\u2010month\u2010old iCMs while causing the opposite effect on 14\u2010month\u2010old iCMs. The same young ECM treatment surprisingly increased SASP and impaired beating in advanced aged iCMs. Overall, we showed that young ECM therapy had a positive effect on post\u2010MI recovery; however, cell age was determinant in the treatment outcomes without any stress conditions. Therefore, \u201cone\u2010size\u2010fits\u2010all\u201d approaches to ECM treatments fail, and cardiac tissue engineered models with age\u2010matched human iCMs are valuable in translational basic research for determining the appropriate treatment, particularly for the elderly.<\/jats:p>","DOI":"10.1111\/acel.13966","type":"journal-article","created":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T02:02:43Z","timestamp":1696644163000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["In need of\n                    <scp>age\u2010appropriate<\/scp>\n                    cardiac models: Impact of cell age on extracellular matrix therapy outcomes"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5210-8086","authenticated-orcid":false,"given":"S. Gulberk","family":"Ozcebe","sequence":"first","affiliation":[{"name":"Bioengineering Graduate Program University of Notre Dame  Notre Dame Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinar","family":"Zorlutuna","sequence":"additional","affiliation":[{"name":"Bioengineering Graduate Program University of Notre Dame  Notre Dame Indiana USA"},{"name":"Department of Aerospace and Mechanical Engineering University of Notre Dame  Notre Dame Indiana USA"},{"name":"Harper Cancer Research Institute University of Notre Dame  Notre Dame Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2019.05.064"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/gels7020070"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0100\u2010879X2006000300010"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201801217"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00059\u2010017\u20104668\u20109"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.08.020"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1600844"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.673044"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9102275"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.822816"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12576\u2010016\u20100509\u20105"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ\u201012\u20100987"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001444"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.10110"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.007230"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44161\u2010022\u201000028\u20106"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.70884"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/0963689718779346"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102797\u20104"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010019\u20101486\u20104"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4780\u201008.2009"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120554"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2017.94"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2004.09.003"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00586"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abo1984"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201022628\u20108"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.274.2.H627"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.612215"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/08820139.2018.1504300"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20110115"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201048948\u2010x"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.10.888"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477\u20107819\u201012\u2010230"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2008.05.008"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2016.09.034"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2019.07.012"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.045401"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000757"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010022\u201003021\u20109"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2022.08.050"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2019.01.062"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2013.08.037"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073294"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13966","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13966","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T07:15:44Z","timestamp":1700118944000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.13966"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,6]]},"references-count":44,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1111\/acel.13966"],"URL":"https:\/\/doi.org\/10.1111\/acel.13966","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.03.14.532565","asserted-by":"object"}]},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,6]]},"assertion":[{"value":"2023-03-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13966"}}