title: Obesity accelerates epigenetic aging of human liver.
abstract: Because of the dearth of biomarkers of aging, it has been difficult to test the hypothesis that obesity increases tissue age. Here we use a novel epigenetic biomarker of aging (referred to as an "epigenetic clock") to study the relationship between high body mass index (BMI) and the DNA methylation ages of human blood, liver, muscle, and adipose tissue. A significant correlation between BMI and epigenetic age acceleration could only be observed for liver (r = 0.42, P = 6.8 × 10(-4) in dataset 1 and r = 0.42, P = 1.2 × 10(-4) in dataset 2). On average, epigenetic age increased by 3.3 y for each 10 BMI units. The detected age acceleration in liver is not associated with the Nonalcoholic Fatty Liver Disease Activity Score or any of its component traits after adjustment for BMI. The 279 genes that are underexpressed in older liver samples are highly enriched (1.2 × 10(-9)) with nuclear mitochondrial genes that play a role in oxidative phosphorylation and electron transport. The epigenetic age acceleration, which is not reversible in the short term after rapid weight loss induced by bariatric surgery, may play a role in liver-related comorbidities of obesity, such as insulin resistance and liver cancer.
authors.affiliation: Departments of Human Genetics, David Geffen School of Medicine, and Biostatistics, School of Public Health, University of California Los Angeles, CA 90095; shorvath@mednet.ucla.edu.
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.affiliation: Department of Internal Medicine I.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Erhart
authors.affiliation: Medical Department 1, University Hospital Dresden, Technical University Dresden, 01307 Dresden, Germany;
authors.forename: Mario
authors.initials: M
authors.lastname: Brosch
authors.affiliation: Institute of Human Genetics, Christian-Albrechts-University Kiel, and.
authors.forename: Ole
authors.initials: O
authors.lastname: Ammerpohl
authors.affiliation: Department of Visceral and Thoracic Surgery.
authors.forename: Witigo
authors.initials: W
authors.lastname: von Schönfels
authors.affiliation: Department of Visceral and Thoracic Surgery.
authors.forename: Markus
authors.initials: M
authors.lastname: Ahrens
authors.affiliation: Department of Visceral and Thoracic Surgery.
authors.forename: Nils
authors.initials: N
authors.lastname: Heits
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London SE1 7EH, United Kingdom;
authors.forename: Jordana T
authors.initials: JT
authors.lastname: Bell
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London SE1 7EH, United Kingdom;
authors.forename: Pei-Chien
authors.initials: PC
authors.lastname: Tsai
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London SE1 7EH, United Kingdom;
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, EC1M 6BQ, United Kingdom; Wellcome Trust Sanger Institute, Hinxton CB10 1SA, United Kingdom; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah 21589, Saudi Arabia; and.
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.affiliation: Institute of Human Genetics, Christian-Albrechts-University Kiel, and.
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.affiliation: Institute of Pathology, University Hospital Tübingen, 72074 Tübingen, Germany.
authors.forename: Bence
authors.initials: B
authors.lastname: Sipos
authors.affiliation: Department of Visceral and Thoracic Surgery.
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.affiliation: Institute of Pathology, University Hospital Schleswig-Holstein, 24015 Kiel, Germany;
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
authors.affiliation: Department of Visceral and Thoracic Surgery.
authors.forename: Clemens
authors.initials: C
authors.lastname: Schafmayer
authors.affiliation: Medical Department 1, University Hospital Dresden, Technical University Dresden, 01307 Dresden, Germany;
authors.forename: Jochen
authors.initials: J
authors.lastname: Hampe
mesh_terms: D000375:Aging / Q000235:genetics* / Q000473:pathology; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D019175:DNA Methylation / Q000235:genetics; D030541:Databases, Genetic; D044127:Epigenesis, Genetic; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D008957:Models, Genetic; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000473:pathology; D009765:Obesity / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D013997:Time Factors; D014158:Transcription, Genetic; D015431:Weight Loss / Q000235:genetics
chemical_list: D012333:RNA, Messenger
keywords: DNA methylation; aging; biological age; epigenetics; obesity