Obesity accelerates epigenetic aging of human liver

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Aging / pathology
  • Body Mass Index
  • Cross-Sectional Studies
  • DNA Methylation / genetics
  • Databases, Genetic
  • Epigenesis, Genetic*
  • Humans
  • Liver / metabolism*
  • Liver / pathology*
  • Models, Genetic
  • Non-alcoholic Fatty Liver Disease / genetics
  • Non-alcoholic Fatty Liver Disease / pathology
  • Obesity / genetics*
  • Obesity / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reproducibility of Results
  • Time Factors
  • Transcription, Genetic
  • Weight Loss / genetics

Substances

  • RNA, Messenger

Associated data

  • GEO/GSE61256