A new monocyte epigenetic clock reveals nonlinear effects of alcohol consumption on biological aging in three independent cohorts (N = 2242)
Year: 2022
Type: article
Study design: Observational Study
Abstract: Background Assessing the effect of alcohol consumption on biological age is essential for understanding alcohol use‐related comorbidities and mortality. Previously developed epigenetic clocks are mainly based on DNA methylation in heterogeneous cell types, which provide limited knowledge on the impacts of alcohol consumption at the individual cellular level. Evidence shows that monocytes play an important role in both alcohol‐induced pathophysiology and the aging process. In this study, we developed a novel monocyte‐based DNA methylation clock (MonoDNAmAge) to assess the impact of alcohol consumption on monocyte age. Methods A machine learning method was applied to select a set of chronological age‐associated DNA methylation CpG sites from 1202 monocyte methylomes. Pearson correlation was tested between MonoDNAmAge and chronological age in three independent cohorts (Ntotal = 2242). Using the MonoDNAmAge clock and four established clocks (i.e., HorvathDNAmAge, HannumDNAmAge, PhenoDNAmAge, GrimDNAmAge), we then evaluated the effect of alcohol consumption on epigenetic aging in the three cohorts [i.e., Yale Stress Center Community Study (YSCCS), Veteran Aging Cohort Study (VACS), Women's Interagency HIV Study (WIHS)] using linear and quadratic models. Results The MonoDNAmAge, comprised of 186 CpG sites, was moderately to strongly correlated with chronological age in the three cohorts (r = 0.90, p = 3.12E−181 in YSCCS; r = 0.54, p = 1.75E−96 in VACS; r = 0.66, p = 1.50E−60 in WIHS). More importantly, we found a nonlinear association between MonoDNAmAge and alcohol consumption (pmodel = 4.55E−08, = 7.80E−08 in YSCCS; pmodel = 1.85E−02, = 3.46E−02 in VACS). Heavy alcohol consumption increased EAAMonoDNAmAge up to 1.60 years while light alcohol consumption decreased EAAMonoDNAmAge up to 2.66 years. These results were corroborated by the four established epigenetic clocks (i.e., HorvathDNAmAge, HannumDNAmAge, PhenoDNAmAge, GrimDNAmAge). Conclusions The results suggest a nonlinear relationship between alcohol consumption and its effects on epigenetic age. Considering adverse effects of alcohol consumption on health, nonlinear effects of alcohol use should be interpreted with caution. The findings, for the first time, highlight the complex effects of alcohol consumption on biological aging.
DOI: 10.1111/acer.14803
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,800
Funders: U.S. Department of Veterans Affairs, Yale University, Georgia Clinical and Translational Science Alliance, National Institutes of Health, University of California, San Francisco, Center for AIDS Research, University of Alabama at Birmingham, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Nursing Research, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Dental and Craniofacial Research, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities, Center for AIDS Research, University of North Carolina at Chapel Hill
Awards: G1158786059, A clinical trial of DOT for HAART in jailed drug users, 4/6 COMpAAAS U01: Operations Research Study, G1913134163, Using the VACS Index to track health outcomes associated with changes in drug use, G2615631298, Feature selection of DNA methylation biosignatures for neuropathy with comorbid drug abuse in the setting of HIV infection, G311558797, 2/6 COMpAAAS U01: Observation Study, Defining the impact of injection drug use on antiretroviral therapy and HIV treatment outcomes: an (epi)genomic approach, G3631044079, G3673658808, G3869857964, 3/6 COMpAAAS U01: Intervention Study, G4228988029, G4277369897, G4418003357, Genome-wide DNA methylation in HIV infected drug users, G4903055321, G4953964255, Alcohol Associated Outcomes Among HIV+/- Aging Veterans, G5109693148, G5699974340, Clinical and Translational Science Institute, G5900455136, 1/6 COMpAAAS U24: Coordinating Center, G6384504179, G6509896931, G6759032351, G6990385686, G7000692498, G7454986501, G775892330, G7807729167, Human Subjects Core: Protocols, Statistics, Collaborative Method Development and, G8029522133, Alcohol Associated Outcomes Among HIV+/-Aging Veterans, G833165568, Alcohol Associated Outcomes Among HIV+/-Aging Veterans, Enhancing Discovery of HIV Host Genetics using Drug Abuse and other Interactions, MACS/WIHS -CCS, SF Bay Area MACS/WIHS Combined Cohort Study, UNC MACS/WIHS Combined Cohort Study Clinical Research Site, Surviving the HIV Epidemic (S/HE) in metropolitan Washington DC - Advancing knowledge through cohort studies, Center for AIDS Research at Emory University, Data Analysis and Coordination Center for the MACS-WIHS Combined Cohort Study, MACS/WIHS Combined Cohort Study: Cook County Clinical Research Site (CC_CRS), The University of North Carolina Center for AIDS Research, MACS/WIHS Combined Cohort Study: Brooklyn Clinical Research Site (Bklyn CRS), Atlanta MACS/WIHS Combined Cohort Study Clinical Research Site, UAB-MISS MACS/WIHS Combined Cohort Study, Clinical Research Sites for the MACS/WIHS Combined Cohort Study (MACS/WIHS-CCS), UAB Center for AIDS Research (CFAR), G929137571
OpenAlex ID: W4221072955