{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T14:22:56Z","timestamp":1789395776806,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["478053"],"award-info":[{"award-number":["478053"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004411","name":"Heart and Stroke Foundation of Canada","doi-asserted-by":"publisher","award":["23\u20100035141"],"award-info":[{"award-number":["23\u20100035141"]}],"id":[{"id":"10.13039\/100004411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Senescent cells are characterized by expression of markers like p16 and secretion of profibrotic and proinflammatory factors. The role of cellular senescence in age\u2010related cardiac remodeling and dysfunction is incompletely understood. This study aimed to: (i) evaluate the effect of p16\u2010 positive cell clearance on cardiac function and structure in aging mice, and (ii) assess the role of different cardiac cell\u2010types in the response. Hypertrophy markers, ion channels and calcium handling protein gene expression. Statistical analysis for all panels: one\u2010way ANOVA followed by Tukey\u2019s test, significance level P&lt;0.05 (N=6 for each group). Each point represents results from one mouse; bars and horizontal lines are means and SD. NK\u2010ATTAC mice, permitting targeted clearance of p16\u2010positive cells upon exposure to the dimerizing agent AP20187 (AP), were treated with AP or vehicle from 12 to 18 months of age. Cardiac function and structure were assessed with echocardiography, hemodynamics with a Millar catheter. p16\u2010positive cells in various cardiac cell populations were analyzed with Fluorescence\u2010Activated Cell Sorting (FACS) and immunofluorescence imaging. Echocardiography revealed significant attenuation of aging\u2010associated increases in left ventricular mass to diameter at end\u2010diastole (LVDd) and anterior wall thickness at end diastole (LVAWTd) in Aged\u2010AP mice versus Aged\u2010Vehicle. Diastolic dysfunction in vehicle mice normalized with AP treatment. FACS results indicated clearance of p16\u2010positive fibroblasts with AP. Immunofluorescence imaging indicated reduced p16\u2010positive fibroblasts and cardiomyocytes with AP, implicating them in the effects of p16\u2010positive cell clearance on age\u2010related cardiac remodeling. Exposure of cardiomyocytes to senescent fibroblast products led to upregulation of hypertrophy markers, pointing to paracrine effects on cardiomyocytes. This study highlights the potential contribution of senescent fibroblasts and cardiomyocytes to age\u2010related cardiac remodeling. Modulating senescence might provide a new approach to age\u2010related cardiac diseases like heart failure.<\/jats:p>","DOI":"10.1113\/ep093551","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:57:31Z","timestamp":1789394251000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clearance of p16\u2010positive cardiac cells improves age\u2010related cardiac remodeling in mice"],"prefix":"10.1113","author":[{"given":"Mozhdeh","family":"Mehdizadeh","sequence":"first","affiliation":[{"name":"Research Center Montreal Heart Institute Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Department of Pharmacology and Therapeutics McGill University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Mackasey","sequence":"additional","affiliation":[{"name":"Research Center Montreal Heart Institute Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Department of Pharmacology and Therapeutics McGill University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimia","family":"Gharagozloo","sequence":"additional","affiliation":[{"name":"Research Center Montreal Heart Institute Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Department of Pharmacology and Therapeutics McGill University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Research Center Montreal Heart Institute Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Department of Medicine Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Naud","sequence":"additional","affiliation":[{"name":"Research Center Montreal Heart Institute Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Department of Medicine Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7300-8649","authenticated-orcid":false,"given":"Allan","family":"Ochs","sequence":"additional","affiliation":[{"name":"Research Center Montreal Heart Institute Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Department of Pharmacology and Therapeutics McGill University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nhung","family":"Vuong\u2010Robillard","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Universit\u00e9 de Montr\u00e9al and CRCHUM  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Thorin","sequence":"additional","affiliation":[{"name":"Department of Surgery Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Ferbeyre","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Universit\u00e9 de Montr\u00e9al and CRCHUM  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Claude","family":"Tardif","sequence":"additional","affiliation":[{"name":"Research Center Montreal Heart Institute Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin G.","family":"Sirois","sequence":"additional","affiliation":[{"name":"Research Center Montreal Heart Institute Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Department of Pharmacology and Physiology Faculty of Medicine Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Francois","family":"Tanguay","sequence":"additional","affiliation":[{"name":"Research Center Montreal Heart Institute Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5565-3311","authenticated-orcid":false,"given":"Stanley","family":"Nattel","sequence":"additional","affiliation":[{"name":"Research Center Montreal Heart Institute Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Department of Pharmacology and Therapeutics McGill University  Montreal Canada"},{"name":"Department of Medicine Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Department of Pharmacology and Physiology Faculty of Medicine Universit\u00e9 de Montr\u00e9al  Montreal Canada"},{"name":"Institute of Pharmacology West German Heart and Vascular Center University Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"issue":"2","key":"e_1_2_11_2_1","first-page":"204","article-title":"Characterization of a unique form of arrhythmic cardiomyopathy caused by recessive mutation in LEMD2","volume":"4","author":"Abdelfatah N.","year":"2019","journal-title":"JACC: Basic to Translational Science"},{"issue":"7","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1161\/CIRCRESAHA.115.303794","article-title":"Developmental heterogeneity of cardiac fibroblasts does not predict pathological proliferation and activation","volume":"115","author":"Ali S. 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