{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T09:37:52Z","timestamp":1789033072783,"version":"build-2803163510"},"reference-count":153,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Aging is a multidimensional process regulated by the interplay of genetic and environmental factors, with epigenetic alterations serving as a central regulatory hub. Aberrant DNA methylation patterns, dysregulation of histone-modifying enzymes (e.g., SIRT1, EZH2), and non-coding RNA-mediated mechanisms collectively remodel gene expression networks, impacting critical pathways such as cellular senescence and mitochondrial homeostasis. This establishes an \u201cenvironment-epigenome-disease\u201d causal axis, closely associated with pathologies including \u03b2-amyloid deposition in Alzheimer\u2019s disease, atherosclerosis, immunosenescence, osteoporosis, sarcopenia, and tumorigenesis. Capitalizing on the reversible nature of epigenetic modifications, pharmacological epigenetics has emerged as a cutting-edge field for intervening in aging and age-related diseases. Targeting key epigenetic modifiers such as DNA methyltransferases and histone deacetylases enables the modulation of disease-associated epigenetic states, providing a promising avenue for therapeutic intervention in aging and age-related diseases. This review synthesizes the molecular mechanisms of epigenetic regulation in aging, their role in age-related diseases, and advances in pharmacological epigenetics\u2014from basic research to clinical translation. It further situates key challenges such as target specificity, long-term safety, and tissue-specific delivery within a translational framework, aiming to inform strategies for the diagnosis and intervention of age-related conditions.<\/jats:p>","DOI":"10.3389\/fphar.2025.1699296","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T06:23:22Z","timestamp":1761805402000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Epigenetic pharmacology in aging: from mechanisms to therapies for age-related disorders"],"prefix":"10.3389","volume":"16","author":[{"given":"Haikuan","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taojin","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhouguang","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenkai","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongxian","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dewen","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fubing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e13231","DOI":"10.1111\/srt.13231","article-title":"Prediction and association analyses of skin phenotypes in Japanese females using genetic, environmental, and physical features","volume":"29","author":"Amano","year":"2023","journal-title":"Skin. 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