{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:18:12Z","timestamp":1789708692223,"version":"4.0.1"},"reference-count":63,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,6,8]],"date-time":"2025-06-08T00:00:00Z","timestamp":1749340800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20\u2009K19520"],"award-info":[{"award-number":["20\u2009K19520"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["3P40OD021331\u201006S1"],"award-info":[{"award-number":["3P40OD021331\u201006S1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P40OD\u2010021331"],"award-info":[{"award-number":["P40OD\u2010021331"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Epigenetic drift, which is gradual age\u2010related changes in DNA methylation patterns, plays a significant role in aging and age\u2010related diseases. However, the relationship between exercise, epigenetics, and aging, and the molecular mechanisms underlying their interactions are poorly understood. Here, we investigated the relationship between cardiorespiratory fitness (CRF), epigenetic aging, and promoter methylation of individual genes across multiple organs in selectively bred low\u2010 and high\u2010capacity runner (LCR and HCR) aged rats. Epigenetic clocks, trained on available rat blood\u2010derived reduced representation bisulfite sequencing data, did not reflect differences in CRF between LCR and HCR rats across all four organs. However, we observed organ\u2010specific differences in global mean DNA methylation and mean methylation entropy between LCR and HCR rats, and the direction of these differences was the opposite compared to the age\u2010related changes in the rat blood. Notably, the soleus muscle exhibited the most pronounced differences in promoter methylation due to CRF. We also identified seven genes whose promoter methylation was consistently influenced by CRF in all four organs. Moreover, we found that age acceleration of the soleus muscle was significantly higher compared to the heart and the hippocampus, and significantly lower compared to the large intestine. Finally, we found that the age acceleration was not consistent across organs. Our data suggest that CRF associates with epigenetic aging in an organ\u2010specific and organ\u2010common manner. Our findings provide important insights into the biology of aging and emphasize the need to validate rejuvenation strategies in the context of the organ\u2010specific nature of epigenetic aging.<\/jats:p>","DOI":"10.1111\/acel.70110","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T10:47:14Z","timestamp":1749725234000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Organ Specificity and Commonality of Epigenetic Aging in Low\u2010 and High\u2010Running Capacity Rats"],"prefix":"10.1111","volume":"24","author":[{"given":"Takuji","family":"Kawamura","sequence":"first","affiliation":[{"name":"Research Center for Molecular Exercise Science Hungarian University of Sports Science  Budapest Hungary"},{"name":"Smart\u2010Aging Research Center Tohoku University  Sendai 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Hungary"},{"name":"Hungarian Centre of Excellence for Molecular Medicine \u2010 Semmelweis University (HCEMM\u2010SU), Neurobiology and Neurodegenerative Diseases Research Group  Budapest Hungary"},{"name":"Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren Gerard","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology The University of Toledo College of Medicine and Life Sciences  Toledo Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven Loyal","family":"Britton","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology University of Michigan  Ann Arbor Michigan 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