Alcohol (and biological aging)

Alcohol (ethanol, C₂H₅OH) is a Group 1 human carcinogen whose chronic exposure accelerates biological aging through multiple molecular mechanisms. Ethanol is oxidized to acetaldehyde — a reactive intermediate — by alcohol dehydrogenase (ADH), then to acetate by mitochondrial aldehyde dehydrogenase (ALDH2). When impaired — through excess consumption or the ALDH2*2 loss-of-function variant prevalent in East Asian populations — acetaldehyde forms covalent DNA adducts, driving strand breaks, mutations, and genomic instability. Studies of alcohol use disorder (AUD) find approximately 2–4 years of accelerated biological age on DNA-methylation clocks (Horvath, GrimAge), scaling with severity and partially reversing after abstinence (Zindler et al. 2022, Addiction Biology). Mendelian randomization using ADH1B rs1229984 as an instrumental variable shows genetically-predicted higher alcohol exposure causally shortens leukocyte telomere length (Topiwala et al. 2022, Molecular Psychiatry). A 2024 non-linear MR study of 300,000+ UK Biobank participants found no protective threshold against dementia at any consumption level, contradicting the earlier observational J-curve (Zheng et al. 2024, eClinicalMedicine). IARC concluded in 2023 that no safe consumption level for cancer exists, with strongest causal evidence for cancers of the oral cavity, pharynx, larynx, oesophagus, liver, colorectum, and breast (Gapstur et al. 2023, NEJM); ethanol and acetaldehyde are the primary carcinogens, independent of beverage type.