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Epigenetic Aging and Rheumatoid Arthritis.

Nandini Mukherjee1, Tracie C Harrison2

  • 1Department of Epidemiology, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.

The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
|September 12, 2023
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Summary

This study found that advanced epigenetic age, particularly using second-generation clocks like GrimAge, is associated with rheumatoid arthritis (RA) prevalence. Higher epigenetic age acceleration was observed in RA cases compared to controls.

Keywords:
Biological agingGrimAgeInflammationPhenoAge

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Area of Science:

  • Epigenetics
  • Rheumatology
  • Aging Research

Background:

  • Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex etiology.
  • Epigenetic age estimation offers a molecular measure of biological aging.
  • Previous research has not comparatively assessed various epigenetic age measures against RA prevalence.

Purpose of the Study:

  • To conduct the first comparative assessment of multiple epigenetic age estimates and their association with rheumatoid arthritis (RA) prevalence.
  • To investigate the utility of different epigenetic clocks, including first and second-generation measures, as potential biomarkers for RA.

Main Methods:

  • Utilized DNA methylation (DNAm) data from the Swedish Epidemiological Investigation of Rheumatoid Arthritis study (GSE42861).
  • Calculated multiple epigenetic age estimates: DNAmTL, Hannum, Horvath 2013, Horvath 2018, PhenoAge, and GrimAge, along with their acceleration measures.
  • Assessed associations with RA prevalence using linear regression, adjusting for sex and smoking, with FDR correction for multiple testing.

Main Results:

  • Statistically significant associations were found between RA prevalence and several epigenetic age acceleration measures, notably PhenoAge acceleration and GrimAge acceleration.
  • Higher epigenetic age acceleration was observed in RA cases compared to healthy controls.
  • GrimAge and its acceleration were strongly associated with RA, with higher GrimAge surrogate DNAm protein components in RA cases.

Conclusions:

  • Second-generation epigenetic clocks, particularly PhenoAge and GrimAge, show promise as markers of biological aging in the context of rheumatoid arthritis.
  • Epigenetic age acceleration is a potential indicator associated with RA prevalence.
  • Further research is warranted to explore the clinical utility of these epigenetic markers in RA.