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The toxicity is partly dependent on age, as older individuals metabolize alcohol more slowly leading to increased cellular injury. This study aimed to investigate the effects of moderate binge drinking on the liver of young and aged mice in a genome\u2010wide multi\u2010omics approach. We determined DNA methylation (DNAm) using the Illumina MouseMethylation array and gene expression by RNA sequencing in 18 female Balb\/c mice in a 2\u2009\u00d7\u20092 design. The animals underwent three moderate binge drinking cycles (ethanol vs. vehicle) and liver tissue was harvested at 4 or 19\u2009months of age. We tested differential gene expression (DE) and DNAm associated with ethanol intake in linear models separately in young and aged mice, performed enrichment analyses for pathways and GWAS signatures of problematic alcohol use, and analysed the overlap of DNAm and gene expression. We observed DE in young and aged animals and substantial overlap in genes such as <jats:italic>Bhlhe40<\/jats:italic>, <jats:italic>Klf10<\/jats:italic>, and <jats:italic>Frmd8<\/jats:italic>. DE genes in aged animals were enriched for biological processes related to alcohol metabolism, inflammation, liver fibrosis, and GWAS signatures of problematic alcohol use. We identified overlapping signatures from DNAm and gene expression, for example, <jats:italic>Frmd8<\/jats:italic> in aged and <jats:italic>St6galnac4<\/jats:italic> in young mice. This study offers converging evidence of novel age\u2010related targets in a moderate alcohol consumption model highlighting dysregulations in genes related to alcohol metabolism, inflammation, and liver fibrosis. Future studies are needed to confirm these results and elucidate the underlying mechanisms.<\/jats:p>","DOI":"10.1111\/adb.13342","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T14:33:03Z","timestamp":1699972383000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Multi\u2010omics analysis of alcohol effects on the liver in young and aged mice"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7457-374X","authenticated-orcid":false,"given":"Lea","family":"Zillich","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"},{"name":"Department of Genetic Epidemiology in Psychiatry Central Institute of Mental Health  Mannheim 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