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ever-changing demands on our body. It adapts to physiological and pathological changes, including exercise and emotional state, as well as metabolic, respiratory, and vascular abnormalities. The pumping action of the heart is determined by the health of the myocardium, which undergoes changes with ageing that are both under-investigated and incompletely understood, potentially impacting our approach to pathological conditions. Here, the alterations in cellular, tissue, and gross physiological function of the heart with age are discussed. At the molecular level, non-coding RNAs influence cellular senescence, and extracellular vesicles induce fibrosis through matrix remodelling. Mitochondrial dysfunction and altered fatty acid oxidation reduce cellular energetics, whilst accumulation of reactive oxygen species and steatosis, as well as telomere shortening coupled with reduced autophagy, limit the myocardium\u2019s regenerative capability. Loss of cardiomyocytes, combined with senescence, requires compensatory hypertrophy, inducing myocardial stiffness and altered muscle function. In addition to these direct alterations in myocardial characteristics with ageing, other factors that can affect the myocardium indirectly are addressed, including valve calcification, resulting in regurgitation and\/or stenosis; vascular abnormalities, reducing compliance and exacerbating hypertension; fibrosis leading to cardiac arrhythmias; and autonomic dysregulation, reducing cardiac adaptability. Finally, potential modulation of cardiac ageing is discussed whilst also addressing which senescent modifications should be considered as ageing-related physiological changes of the myocardium. A better understanding of myocardial ageing will differentiate physiological changes from early, preventable, and reversible pathological changes, consequently helping to optimize management of individuals with or at risk of myocardial disease by taking into account diverse trajectories of myocardial ageing.<\/jats:p>","DOI":"10.1093\/eurheartj\/ehag095","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T12:09:09Z","timestamp":1769515749000},"source":"Crossref","is-referenced-by-count":11,"title":["Senescence-related myocardial dysfunction: keeping a young heart"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1636-3725","authenticated-orcid":false,"given":"Ramzi A","family":"Ajjan","sequence":"first","affiliation":[{"name":"Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds , Leeds ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4410-3397","authenticated-orcid":false,"given":"Robert T R","family":"Huckstepp","sequence":"additional","affiliation":[{"name":"School of Life Sciences, University of Warwick , CoventryCV4 7AL ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4620-6373","authenticated-orcid":false,"given":"Naveed","family":"Akbar","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford , Oxford ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9341-117X","authenticated-orcid":false,"given":"Johann","family":"Bauersachs","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology, Hannover Medical School , Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesher Ching Wai","family":"Lok","sequence":"additional","affiliation":[{"name":"Medical School, University of East Anglia , Norwich \u00a0","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juel","family":"Choppy-Madeleine","sequence":"additional","affiliation":[{"name":"Medical School, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7175-6644","authenticated-orcid":false,"given":"Gary","family":"Christopher","sequence":"additional","affiliation":[{"name":"Centre for Ageing and Dementia Research, Swansea University , Swansea ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7091-7880","authenticated-orcid":false,"given":"Mayank","family":"Dalakoti","sequence":"additional","affiliation":[{"name":"Department of 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,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3736-0099","authenticated-orcid":false,"given":"Claudio","family":"Mauro","sequence":"additional","affiliation":[{"name":"College of Medicine and Health, University of Birmingham , Birmingham ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7273-639X","authenticated-orcid":false,"given":"Fiona","family":"Lewis-McDougall","sequence":"additional","affiliation":[{"name":"Centre for Microvascular Research, William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0929-9315","authenticated-orcid":false,"given":"Andrew J","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development and Neuroscience, University of Cambridge , Cambridge ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renita Peter","family":"Damien Genetus","sequence":"additional","affiliation":[{"name":"Medical School, University of Birmingham, Birmingham ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5050-589X","authenticated-orcid":false,"given":"Emma","family":"Short","sequence":"additional","affiliation":[{"name":"Cardiff Metropolitan University Cardiff School of Technologies, , Cardiff ,","place":["UK"]},{"name":"Department of Cellular Pathology, Swansea Bay University Health Board, Swansea ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0104-4799","authenticated-orcid":false,"given":"Mark A","family":"Sussman","sequence":"additional","affiliation":[{"name":"Biology Department and Integrated Regenerative Research Institute, San Diego State University , San Diego, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7505-9144","authenticated-orcid":false,"given":"Adriana A S","family":"Tavares","sequence":"additional","affiliation":[{"name":"University-BHF Centre for Cardiovascular Science, Queen\u2019s Medical Research Institute, University of Edinburgh , Edinburgh ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Thompson","sequence":"additional","affiliation":[{"name":"New College, Oxford University , Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morya","family":"Wadodkar","sequence":"additional","affiliation":[{"name":"Medical School, University of Bristol , Bristol ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0085-0385","authenticated-orcid":false,"given":"Stuart R G","family":"Calimport","sequence":"additional","affiliation":[{"name":"Cardiff Metropolitan University Cardiff School of Technologies, , Cardiff ,","place":["UK"]},{"name":"Collaboration for the Advancement of Sustainable Medical Innovation (CASMI), University College London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4360-5902","authenticated-orcid":false,"given":"Barry L","family":"Bentley","sequence":"additional","affiliation":[{"name":"Cardiff Metropolitan University Cardiff School of Technologies, , Cardiff ,","place":["UK"]},{"name":"Harvard Medical School , Harvard University, Boston, MA ,","place":["USA"]},{"name":"Massachusetts General Hospital Department of Surgery, , Boston, MA 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