{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T01:08:23Z","timestamp":1783818503938,"version":"3.55.0"},"reference-count":52,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:00:00Z","timestamp":1783728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:00:00Z","timestamp":1783728000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001030","name":"National Heart Foundation of Australia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001030","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>Atrial fibrillation (AF) prevalence rises sharply with age due to two independent mechanisms. Ageing produces irreversible arrhythmogenic substrate changes through progressive fibrosis, cellular senescence and mitochondrial dysfunction, while modifiable risk factors such as obesity, hypertension, sleep apnoea, diabetes and alcohol use promote atrial remodelling through inflammatory, haemodynamic and metabolic pathways. These comorbidities accumulate with age but operate through distinct mechanisms. Late gadolinium enhancement magnetic resonance imaging now quantifies fibrosis burden, while circulating biomarkers track inflammation, fibrosis and disease activity, and these measures respond to treatment, providing objective evidence of substrate modification. Landmark trials have transformed management. Weight loss of 10% or more when maintained is associated with reduced AF burden. Structured risk\u2010factor management may improve ablation outcomes and is associated with regression of AF type, with some patients moving from persistent back to paroxysmal patterns. These benefits occur across age groups, preventing arrhythmogenic substrate formation in younger patients and likely enabling reduction in AF burden in older adults. Collectively, this evidence positions risk\u2010factor management as the fourth pillar of AF care and shifts AF from an inevitable consequence of ageing to a modifiable chronic disease when delivered effectively.<\/jats:p>","DOI":"10.1113\/ep093597","type":"journal-article","created":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:41:32Z","timestamp":1783816892000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A new approach to an old disease: Ageing, arrhythmogenic substrate and the role of risk\u2010factor modification in atrial fibrillation"],"prefix":"10.1113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2159-5424","authenticated-orcid":false,"given":"Udit","family":"Thakur","sequence":"first","affiliation":[{"name":"Department of Cardiology Royal Melbourne Hospital  Melbourne Victoria Australia"},{"name":"Department of Medicine University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6618-7184","authenticated-orcid":false,"given":"Jonathan M.","family":"Kalman","sequence":"additional","affiliation":[{"name":"Department of Cardiology Royal Melbourne Hospital  Melbourne Victoria Australia"},{"name":"Department of Medicine University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.280521"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2021.0619"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101412"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.15420\/aer.2021.36"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11247400"},{"issue":"2","key":"e_1_2_11_7_1","first-page":"145","article-title":"Age\u2010related changes in the structure of myocardial collagen network of auricle of the right atrium in healthy persons and ischemic heart disease patients","volume":"41","author":"Burkauskiene A.","year":"2005","journal-title":"Medicina (Kaunas, Lithuania)"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.09.064"},{"key":"e_1_2_11_9_1","doi-asserted-by":"crossref","unstructured":"Chen C. 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