Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 43, Pages 15538-15543Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1412759111
Keywords
obesity; epigenetics; aging; biological age; DNA methylation
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Funding
- National Institutes of Health (NIA/NIH) [5R01AG042511-02]
- German ministry of education and research (BmBF) through the Virtual Liver Network (VLN) [0315763]
- Christian-Albrechts-University Kiel
- University Hospitals Schleswig-Holstein and Dresden in Germany
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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 x 10(-4) in dataset 1 and r = 0.42, P = 1.2 x 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 x 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.
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