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.
