Background/Purpose: Accelerated biological aging of blood cells could contribute to the pathogenesis of RA. However, biological age has multiple facets, some as epigenetic aging not yet addressed in RA, and the most studied, shortened telomere length, not replicated in all studies. Recently, DNA methylation age measures (DmAM) have been developed as biomarkers of epigenetic aging that correlate with survival, diseases of old age and fitness in the elderly. We aimed to address biological aging in RA with DmAM and telomere length.

Methods: DNA from blood of 365 patients meeting ACR classification criteria for RA and 375 healthy age-matched controls were analyzed. A DmAM based in 8 CpG sites was assayed by minisequencing after bisulfite modification (1). qPCR was used for evaluation of relative telomere length (2). A second set of 354 ACPA positive RA patients and 335 controls was used for replication of the DmAM results (3). Differences in DmAM and telomere length between patients and controls were evaluated with ANOVA. Cox proportional hazards regression models were used for survival analysis. All analyses were adjusted for age and sex.

Results: The 8 CpG DmAM showed a small premature aging in patients with RA in comparison with controls in the two sample collections analyzed (Table 1). However, premature aging did not persist after correction for changes in blood cell subpopulations (Table 1), and it was not consistently observed with other DmAM (Table 1). In addition, telomere length attrition was not observed in RA patients (Table 1). No association was observed between any of the two age biomarkers and time since disease onset, antibody status, and prevalence of erosions, shared epitope or smoking (not shown). At the end of data collection, 246 of 734 subjects have died (33.51%). Hazard Ratio (HR) for all-cause mortality was higher for RA patients than for controls (HR = 1.89; 95% CI = 1.45 to 2.45; P = 2.0 x 10^-6). However, mortality was not associated with age biomarkers, neither the DmAM, nor telomere length, after adjusting for chronological age.

Conclusion: We observed premature epigenetic aging of small magnitude in blood cells of patients with RA, but the difference is most likely irrelevant as it could be due to changes in blood cell subpopulations or to particularities of the specific DmAM. In addition, we did not observe the reported shortening of telomere length, further questioning the concept of premature biological aging in RA blood cells as a whole. Table 1. Differences in biological age

* Adjusted for blood cell composition according to Houseman et al. BMC Bioinformatics 13:86 (2012). ** Alternative DmAM from Horvath, S. Genome Biology14:R115 (2013) References: 1. Vidal-Bralo, L. Submitted 2. Cawthon, R. M. Nucleic Acids Res. 30, e47 (2002) 3. Liu, Y. et al. Nat Biotechnol 31,142–147 (2013) Funded by Instituto de Salud Carlos III (Spain) with participation of the European Regional Development Fund of the EU (grants PI14/01651 and RD12/009/008)

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/study-of-two-biomarkers-of-biological-age-in-the-blood-of-patients-with-rheumatoid-arthritis/