Age-related changes in articular cartilage and chondrocyte senescence

This review delineates age-related changes in articular hyaline cartilage and chondrocyte senescence, distinguishing physiological aging processes from osteoarthritis (OA) pathogenesis — a distinction frequently conflated in the scientific literature. Aging cartilage exhibits impaired homeostasis and progressive macroscopic alterations — including thinning and ectopic calcification — as well as molecular hallmarks such as glycosaminoglycan (GAG) depletion, advanced glycation end-product (AGE) accumulation, and inflammaging. These alterations predispose joints to degeneration and elevate OA risk, yet do not inevitably precipitate disease. Chondrocyte senescence is further examined in tissue aging, OA pathology, and two-dimensional culture models, emphasizing tissue-specific triggers, including mechanical overload (e.g., Piezo1-mediated), oxidative stress, mitochondrial dysfunction (impaired mitophagy and ROS surge), and replicative exhaustion (including passaging). Emerging evidence establishes chondrocyte senescence as a modifiable driver of joint degeneration, thereby supporting the development of targeted interventions to attenuate cartilage aging and forestall early OA development.