Senescent cells (SnCs) accumulate in many vertebrate tissues with age and contribute to age-related pathologies^,,, presumably through their secretion of factors contributing to the senescence-associated secretory phenotype (SASP)^,,. Removal of SnCs delays several pathologies^,, and increases healthy lifespan. Aging and trauma are risk factors for the development of osteoarthritis (OA), a chronic disease characterized by degeneration of articular cartilage leading to pain and physical disability. Senescent chondrocytes are found in cartilage tissue isolated from patients undergoing joint replacement surgery^,,,, yet their role in disease pathogenesis is unknown. To test the idea that SnCs might play a causative role in OA, we used the p16-3MR transgenic mouse, which harbors a p16^INK4a (Cdkn2a) promoter driving the expression of a fusion protein containing synthetic Renilla luciferase and monomeric red …