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Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15538-43. doi: 10.1073/pnas.1412759111. Epub 2014 Oct 13.

Obesity accelerates epigenetic aging of human liver.

Author information

1
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.
2
Department of Internal Medicine I.
3
Medical Department 1, University Hospital Dresden, Technical University Dresden, 01307 Dresden, Germany;
4
Institute of Human Genetics, Christian-Albrechts-University Kiel, and.
5
Department of Visceral and Thoracic Surgery.
6
Department of Twin Research and Genetic Epidemiology, Kings College London, London SE1 7EH, United Kingdom;
7
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.
8
Institute of Pathology, University Hospital Tübingen, 72074 Tübingen, Germany.
9
Institute of Pathology, University Hospital Schleswig-Holstein, 24015 Kiel, Germany;

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.

KEYWORDS:

DNA methylation; aging; biological age; epigenetics; obesity

PMID:
25313081
PMCID:
PMC4217403
DOI:
10.1073/pnas.1412759111
[Indexed for MEDLINE]
Free PMC Article

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