Specific premature epigenetic aging of cartilage in osteoarthritis

Abstract

Osteoarthritis (OA) is a disease affecting multiple tissues of the joints in the elderly, but most notably articular cartilage. Premature biological aging has been described in this tissue and in blood cells, suggesting a systemic component of premature aging in the pathogenesis of OA. Here, we have explored epigenetic aging in OA at the local (cartilage and bone) and systemic (blood) levels. Two DNA methylation age-measures (DmAM) were used: the multi-tissue age estimator for cartilage and bone; and a blood-specific biomarker for blood. Differences in DmAM between OA patients and controls showed an accelerated aging of 3.7 years in articular cartilage (95% CI = 1.1 to 6.3, P = 0.008) of OA patients. By contrast, no difference in epigenetic aging was observed in bone (0.04 years; 95% CI = -1.8 to 1.9, P = 0.3) and in blood (-0.6 years; 95% CI = -1.5 to 0.3, P = 0.2) between OA patients and controls. Therefore, premature epigenetic aging according to DNA methylation changes was specific of OA cartilage, adding further evidence and insight on premature aging of cartilage as a component of OA pathogenesis that reflects damage and vulnerability.

Keywords: DNA methylation; biological age; epigenetics; osteoarthritis; telomere length shortening.

Figure 1. Comparison of epigenetic age in joint tissues from controls and patients with OA

(A) Accelerated aging in OA cartilage samples (n = 31) in comparison with control cartilage (n = 36) with ΔDmAM = 3.7 years (P = 0.008); and (B) no difference (ΔDmAM = 0.04 years, P = 0.3) in bone samples between OA patients (n = 33) and controls (n = 45). Epigenetic ages are represented as age- and sex-adjusted values with horizontal lines for the mean of each group.

Figure 2. Lack of accelerated epigenetic aging in blood cells of OA patients

The scatterplots represent age in the horizontal axis against epigenetic age in the vertical axis from the controls without OA (empty circles, n =182) together with (A) the hand OA (n = 206), (B) the knee OA (n = 229), and (C) the hip OA (n = 273) patients (filled circles). Straight lines represent least squares regression fit to the data.