{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T15:02:03Z","timestamp":1778511723881,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Heart failure (HF) is a major cause of hospitalisation in the elderly. Its incidence increases with aging and the presence of risk factors such as hypertension and diabetes. Aging\u2010related myocardial fibrosis, characterised by alterations in the extracellular matrix and myocardial structure, leads to impairment of cardiac function. However, the specific mechanisms linking mitochondrial oxidative stress to cardiac remodelling in aging remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To elucidate the mechanisms underlying aging\u2010related ventricular electrical and structural remodelling and to determine the role of mitochondrial dysfunction in modulating aging\u2010associated HF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>\n                      We developed third\u2010generation homozygous telomerase reverse transcriptase deficient (TERT\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) progeria mice to model accelerated aging. Compared to wild\u2010type controls, these mice exhibited marked upregulation of aging\u2010associated genes and proteins such as p53 in ventricular tissue. Echocardiographic analysis revealed significant reductions in left ventricular ejection fraction and fractional shortening, indicating both systolic and diastolic dysfunction. Histological staining showed increased interstitial fibrosis and inflammatory cell infiltration, which correlated with elevated expression of fibrosis markers including collagen type I and TGF\u2010\u03b2. Electrocardiography and epicardial mapping demonstrated prolonged QRS duration and slowed ventricular conduction velocity. These findings, together with increased conduction heterogeneity, are indicative of electrical remodelling. Furthermore, RNA sequencing and biochemical assays identified upregulation of mitochondrial oxidative stress pathways and elevated levels of malondialdehyde and MnSOD, alongside disrupted mitochondrial ultrastructure and downregulation of mitochondrial dynamics\u2010related proteins such as MFN2 and Drp1. These findings highlight the central role of mitochondrial dysfunction in driving structural and electrical cardiac remodelling in aging.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The findings demonstrate that third\u2010generation TERT\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      senescent mice exhibit significant cardiac impairments, including electrical remodelling, structural changes, and mitochondrial dysfunction, suggesting mitochondrial oxidative stress may be related to aging\u2010related HF. These insights underscore the potential of targeting mitochondrial dysfunction for therapeutic strategies in aging\u2010related HF. Collectively, these data demonstrate that telomerase deficiency drives cardiac structural and electrical remodelling through mitochondrial oxidative stress, underscoring mitochondrial quality control as a potential therapeutic target in aging\u2010related HF.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1440-1681.70082","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T04:52:13Z","timestamp":1760417533000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mitochondrial Oxidative Stress and Cardiac Dysfunction in\n                    <scp>TERT<\/scp>\n                    Deficient Progeria Mice"],"prefix":"10.1111","volume":"52","author":[{"given":"Zandong","family":"Zhou","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory of Ionic\u2010Molecular Function of Cardiovascular Disease, Department of Cardiology Tianjin Institute of Cardiology, the Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunpeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Ionic\u2010Molecular Function of Cardiovascular Disease, Department of Cardiology Tianjin Institute of Cardiology, the Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Genetics and Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences Tianjin Medical University  Tianjin China"},{"name":"Tianjin Medical University School of Stomatology Tianjin Medical University  Tianjin China"},{"name":"Tianjin Academy of Traditional Chinese Medicine  Tianjin China"},{"name":"Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daiqi","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Ionic\u2010Molecular Function of Cardiovascular Disease, Department of Cardiology Tianjin Institute of Cardiology, the Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingxin","family":"Xie","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Ionic\u2010Molecular Function of Cardiovascular Disease, Department of Cardiology Tianjin Institute of Cardiology, the Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Ionic\u2010Molecular Function of Cardiovascular Disease, Department of Cardiology Tianjin Institute of Cardiology, the Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Tse","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Ionic\u2010Molecular Function of Cardiovascular Disease, Department of Cardiology Tianjin Institute of Cardiology, the Second Hospital of Tianjin Medical University  Tianjin China"},{"name":"School of Nursing and Health Studies Hong Kong Metropolitan University  Hong Kong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Genetics and Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences Tianjin Medical University  Tianjin China"},{"name":"Tianjin Medical University School of Stomatology Tianjin Medical University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Ionic\u2010Molecular Function of Cardiovascular Disease, Department of Cardiology Tianjin Institute of Cardiology, the Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"issue":"1","key":"e_1_2_10_2_1","first-page":"4","article-title":"ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure: Developed by the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC). With the Special Contribution of the Heart Failure Association (HFA) of the ESC","volume":"24","author":"McDonagh T. A.","year":"2021","journal-title":"European Journal of Heart Failure"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001123"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.15212\/CVIA.2023.0085"},{"issue":"18","key":"e_1_2_10_5_1","first-page":"e895","article-title":"2022 AHA\/ACC\/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"145","author":"Heidenreich P. A.","year":"2022","journal-title":"Circulation"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab368"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-021-10095-9"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.09.114"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.302929"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-020-00504-1"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.20517\/2574\u20101209.2018.48"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00411-4"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-020-09965-8"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11091745"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118290"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.658362"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119240"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.20517\/2574\u20101209.2022.22"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.106038"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-020-07002-z"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102289"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.024582"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2018.06.009"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-021-00626-7"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.16463"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-00320-4"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.006615"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09787"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12979-022-00273-0"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2017.02.125"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101707"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.22599"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2020-318654"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaw8330"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101231"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.12.024"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.268680"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10840-019-00623-x"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204149"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.908037"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacep.2022.10.031"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-019-0084-z"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2017.09.002"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1004181"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2022.03.008"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-023-01908-0"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102329"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03238-7"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2024.111238"}],"container-title":["Clinical and Experimental Pharmacology and Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1440-1681.70082","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T04:33:56Z","timestamp":1764218036000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1440-1681.70082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,13]]},"references-count":48,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1111\/1440-1681.70082"],"URL":"https:\/\/doi.org\/10.1111\/1440-1681.70082","archive":["Portico"],"relation":{},"ISSN":["0305-1870","1440-1681"],"issn-type":[{"value":"0305-1870","type":"print"},{"value":"1440-1681","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,13]]},"assertion":[{"value":"2025-04-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70082"}}