{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:41:25Z","timestamp":1789015285836,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcohol, Clinical and Experimental Research"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic heavy alcohol use is a major risk factor for premature aging and age\u2010related diseases. DNA methylation (DNAm)\u2010based epigenetic clocks are novel tools for predicting biological age. However, the newest configurations, causality\u2010enriched epigenetic clocks, have not been assessed in the context of alcohol consumption and alcohol use disorder (AUD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Epigenetic aging was evaluated in a sample of 615 individuals (372 AUD patients and 243 healthy controls) by applying the GrimAge Version 1 (V1) and Version 2 (V2) clocks alongside three causality\u2010enriched clocks (CausAge, DamAge, and AdaptAge). A linear model controlling for AUD diagnosis, sex, race, BMI, smoking status, and five blood cell types was leveraged to test associations between alcohol\u2010related metrics and age\u2010adjusted epigenetic clocks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GrimAge V1 and V2 maintained significant associations with AUD and drinking behavior measures within the total sample and both the young (&lt;40\u2009years old) and old (\u226540\u2009years old) subgroups. Generally, GrimAge V2 slightly outperformed GrimAge V1, while none of the causality\u2010enriched epigenetic clocks demonstrated significant associations with AUD. However, in the young subgroup, DamAge had a significant association with the total number of drinks. Across the total sample and age subgroups, with liver function enzymes, GrimAge V2 consistently sustained stronger associations compared with GrimAge V1. Among fourth\u2010generation clocks, DamAge exhibited significant associations with gamma\u2010glutamyl transferase (GGT) and aspartate aminotransferase in the total sample and young subgroup; CausAge displayed a significant association with GGT in the total sample. Examining clinical biomarkers, GrimAge V2 showed improved associations with C\u2010reactive protein compared to GrimAge V1 in the total sample and age subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Overall, we observed moderately improved performance of GrimAge V2 compared with GrimAge V1 with the majority of the parameters tested. The causality\u2010enriched epigenetic clocks lacked significant associations but demonstrate the complexities of aging and inspire further research of AUD and drinking dynamics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.70020","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T14:56:44Z","timestamp":1743346604000},"page":"829-842","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Alcohol and aging: Next\u2010generation epigenetic clocks predict biological age acceleration in individuals with alcohol use disorder"],"prefix":"10.1111","volume":"49","author":[{"given":"Tyler A.","family":"Perlstein","sequence":"first","affiliation":[{"name":"Section on Clinical Genomics and Experimental Therapeutics National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeesun","family":"Jung","sequence":"additional","affiliation":[{"name":"Section on Clinical Genomics and Experimental Therapeutics National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6075-6848","authenticated-orcid":false,"given":"Alexandra C.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Section on Clinical Genomics and Experimental Therapeutics National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1041-6602","authenticated-orcid":false,"given":"Joshua","family":"Reitz","sequence":"additional","affiliation":[{"name":"Section on Clinical Genomics and Experimental Therapeutics National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephin","family":"Wagner","sequence":"additional","affiliation":[{"name":"Section on Clinical Genomics and Experimental Therapeutics National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel B.","family":"Rosoff","sequence":"additional","affiliation":[{"name":"Section on Clinical Genomics and Experimental Therapeutics National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Bethesda Maryland USA"},{"name":"NIH Oxford\u2010Cambridge Scholars Program, Radcliffe Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0480-7755","authenticated-orcid":false,"given":"Falk W.","family":"Lohoff","sequence":"additional","affiliation":[{"name":"Section on Clinical Genomics and Experimental Therapeutics National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"American Psychiatric Association.Substance\u2010related and addictive disorders. 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