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SAT0002 Specific Premature Epigenetic Aging of Cartilage in Osteoarthritis

Background Accelerated aging may be a component of osteoarthritis (OA) as shown by changes observed at the level of cartilage (local) in multiple studies. Systemic changes of biological aging have been much less studied, but accelerated telomere shortening (a biomarker of biological aging) has been described in the blood of patients with hand OA (1). In addition, some studies report increases in age-related comorbidities, frailty and mortality in patients with OA, which are consistent with sytemic premature aging. The recent discovery of an epigenetic biomarker of biological age consisting in DNA methylation age measures (DmAM) provides a new opportunity to address these questions. Objectives We aimed to explore the local and the systemic components of biological aging in OA using epigenetic DmAM biomarkers. Methods Three tissues were investigated: blood with 890 samples (182 controls without OA, 206 clinical hand OA, 229 severe knee OA and 273 severe hip OA), bone from femoral heads (45 controls without OA and 33 severe hip OA) and cartilage from tibial plateau or femoral heads (31 controls without OA and 36 severe OA). Two DmAM were used: a novel DmAM based on 8 CpG selected from previous work (2) and analyzed by quantitative minisequencing for blood; and the multi-tissue age estimator by Horvath (3), which is based on 353 CpGs analyzed with Illumina Methylation arrays, for bone and cartilage. Accuracy of the 8 CpG DmAM was evaluated with correlation and mean absolute difference (MAD) to age. Differences in DmAM (ΔDmAM) between OA patients and controls were evaluated with ANOVA adjusting for age and sex. Results OA cartilage showed an accelerated epigenetic aging of 3.7 years in relation with cartilage from controls without OA (Table 1). By contrast, no significant difference was observed in bone from OA patients (Table 1). The new DmAM for blood based on 8 CpG was accurate as shown in data sets from controls, two from previous studies and the 182 controls without OA from the current study (R2≥0.52, p<10–16, MAD≤7.3 years). Therefore, it was applied to compare the controls without OA with the OA patients. None of the three groups of patients, hand OA, knee OA or hip OA, showed accelerated aging in blood (Table 1).Table 1. Specific accelerated DmAM in OA cartilage compared with control cartilage Tissue OA set ΔDmAM (95% CI) P-value Cartilage Knee/hip 3.66 (1.06 to 6.26) 0.008 Bone Hip 0.04 (−1.80 to 1.87) 0.34 Blood Hand 0.01 (−1.10 to 1.12) 0.98 Knee 0.04 (−0.94 to 1.02) 0.93 Hip −0.72 (−1.70 to 0.25) 0.11 Conclusions OA cartilage showed premature biological (epigenetic) aging according to DNA methylation changes. This effect was cartilage-specific, excluding a systemic component, since it was not observed in bone tissue or in blood. References Zhai G, et al. Ann Rheum Dis. 2006;65:1444 Weidner CI, et al. Genome biology. 2014;15:R24 Horvath S. Genome biology. 2013;14:R115 Acknowledgement Funding was provided by the Instituto de Salud Carlos III (Spain) through grants PI12/01909, PI15/01651, RD12/009/008, and P12/615, which are partially financed by the European Regional Development Fund of the EU. Disclosure of Interest None declared