{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T10:07:43Z","timestamp":1785146863381,"version":"3.55.0"},"reference-count":126,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2022YFC3600201"],"award-info":[{"award-number":["2022YFC3600201"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005236","name":"Chinese Universities Scientific Fund","doi-asserted-by":"crossref","award":["2024JNPD001"],"award-info":[{"award-number":["2024JNPD001"]}],"id":[{"id":"10.13039\/501100005236","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Aging is driven by progressive epigenetic alterations\u2014DNA methylation drift, aberrant histone modifications, chromatin remodeling, and non-coding RNA dysregulation. Vitamin D, acting through its nuclear receptor vitamin D receptor (VDR), modulates the epigenetic landscape to potentially counteract these age-related changes. This review first describes age-related epigenetic alterations, then outlines vitamin D signaling and its interface with the epigenetic machinery. Next, tissue-specific epigenetic actions of vitamin D in the immune, musculoskeletal, and nervous systems are discussed. Finally, clinical trial evidence is examined, interindividual variability is highlighted, and future research directions are proposed. However, large randomized controlled trials (RCTs) consistently show limited benefits of vitamin D monotherapy, with measurable anti-aging effects observed when combined with exercise and nutritional interventions. Its efficacy is constrained by interindividual variability, J-shaped dose\u2013response, and tissue-specific barriers. For deficient individuals (serum 25-hydroxyvitamin D (25(OH)D) &lt; 50 nmol\/L), guided supplementation\u2014typically 800\u20132000 international units (IU)\/day\u2014is warranted to achieve tentative target serum concentrations of 75\u2013125 nmol\/L, the range linked to favorable epigenetic and immune effects. For those already sufficient (e.g., serum 25(OH)D \u2265 50 nmol\/L), indiscriminate supplementation without biochemical indication is not supported. Therefore, promoting healthy aging through vitamin D requires serum-monitored, individually titrated, and multimodal regimens, with supplementation reserved primarily for documented deficiency and integrated with lifestyle interventions.<\/jats:p>","DOI":"10.3390\/ijms27156578","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:36:13Z","timestamp":1784878573000},"page":"6578","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic Mechanisms of Vitamin D in the Aging Process: A Narrative Review"],"prefix":"10.3390","volume":"27","author":[{"given":"Yi","family":"Guo","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory of Sports Performance and Skill Assessment, Beijing Sport University, Beijing 100084, China"},{"name":"School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhen","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7049-880X","authenticated-orcid":false,"given":"Li","family":"Zhao","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Sports Performance and Skill Assessment, Beijing Sport University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1778-002X","authenticated-orcid":false,"given":"Shanshan","family":"Mao","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Sports Performance and Skill Assessment, Beijing Sport University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1093\/gerona\/glaa101","article-title":"Epigenetic Clock and Leukocyte Telomere Length Are Associated with Vitamin D Status but not with Functional Assessments and Frailty in the Berlin Aging Study II","volume":"75","author":"Vetter","year":"2020","journal-title":"J. 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