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DNA methylation signatures reflect aging in patients with nonalcoholic steatohepatitis.

Publication ,  Journal Article
Loomba, R; Gindin, Y; Jiang, Z; Lawitz, E; Caldwell, S; Djedjos, CS; Xu, R; Chung, C; Myers, RP; Subramanian, GM; Goodman, Z; Charlton, M ...
Published in: JCI Insight
January 25, 2018

A DNA methylation (DNAm) signature (the "Horvath clock") has been proposed as a measure of human chronological and biological age. We determined peripheral blood DNAm in patients with nonalcoholic steatohepatitis (NASH) and assessed whether accelerated aging occurs in these patients. DNAm signatures were obtained in patients with biopsy-proven NASH and stage 2-3 fibrosis. The DNAm profile from one test and two validation cohorts served as controls. Age acceleration was calculated as the difference between DNAm age and the predicted age based on the linear model derived from controls. Hepatic collagen content was assessed by quantitative morphometry. The Horvath clock accurately predicts the chronological age of the entire cohort. Age acceleration was observed among NASH subjects compared with control data sets and our test controls. Age acceleration in NASH subjects did not differ by fibrosis stage but correlated with hepatic collagen content. A set of 152 differentially methylated CpG islands between NASH subjects and controls identified gene set enrichment for transcription factors and developmental pathways. Patients with NASH exhibit epigenetic age acceleration that correlates with hepatic collagen content.

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Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

January 25, 2018

Volume

3

Issue

2

Location

United States

Related Subject Headings

  • Severity of Illness Index
  • Randomized Controlled Trials as Topic
  • Non-alcoholic Fatty Liver Disease
  • Middle Aged
  • Male
  • Liver
  • Humans
  • Fibrosis
  • Female
  • Epigenesis, Genetic
 

Citation

APA
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ICMJE
MLA
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Loomba, R., Gindin, Y., Jiang, Z., Lawitz, E., Caldwell, S., Djedjos, C. S., … Diehl, A. M. (2018). DNA methylation signatures reflect aging in patients with nonalcoholic steatohepatitis. JCI Insight, 3(2). https://doi.org/10.1172/jci.insight.96685
Loomba, Rohit, Yevgeniy Gindin, Zhaoshi Jiang, Eric Lawitz, Stephen Caldwell, C Stephen Djedjos, Ren Xu, et al. “DNA methylation signatures reflect aging in patients with nonalcoholic steatohepatitis.JCI Insight 3, no. 2 (January 25, 2018). https://doi.org/10.1172/jci.insight.96685.
Loomba R, Gindin Y, Jiang Z, Lawitz E, Caldwell S, Djedjos CS, et al. DNA methylation signatures reflect aging in patients with nonalcoholic steatohepatitis. JCI Insight. 2018 Jan 25;3(2).
Loomba, Rohit, et al. “DNA methylation signatures reflect aging in patients with nonalcoholic steatohepatitis.JCI Insight, vol. 3, no. 2, Jan. 2018. Pubmed, doi:10.1172/jci.insight.96685.
Loomba R, Gindin Y, Jiang Z, Lawitz E, Caldwell S, Djedjos CS, Xu R, Chung C, Myers RP, Subramanian GM, Goodman Z, Charlton M, Afdhal NH, Diehl AM. DNA methylation signatures reflect aging in patients with nonalcoholic steatohepatitis. JCI Insight. 2018 Jan 25;3(2).

Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

January 25, 2018

Volume

3

Issue

2

Location

United States

Related Subject Headings

  • Severity of Illness Index
  • Randomized Controlled Trials as Topic
  • Non-alcoholic Fatty Liver Disease
  • Middle Aged
  • Male
  • Liver
  • Humans
  • Fibrosis
  • Female
  • Epigenesis, Genetic