Postmortem p16INK4a-positive senescent cell burden in zone II articular cartilage of older adult males with a history of youth high-impact athletics

Background Previous studies have shown that p16INK4a-expressing senescent chondrocytes accumulate in zone II of articular cartilage with advancing age, are enriched in primary age-related cartilage degeneration, are observed in early osteoarthritic change, and are prominent after repetitive joint microtrauma. Objective To determine whether preferential p16INK4a accumulation in zone II articular cartilage is associated with a documented history of high-impact athletic participation during secondary school. Methods Postmortem knee joint specimens were obtained from a musculoskeletal tissue repository for 174 male donors (median age at death = 65 years; range = 50–96). One hundred twenty-six had no known contact-sport exposure, whereas forty-eight (27.6 %) reported high-impact athletics in adolescence. Cartilage degeneration was graded using modified OARSI and modified Mankin scales. Immunohistochemistry quantified p16INK4a-positive cells across cartilage zones; preferential accumulation was defined as ≥2-fold enrichment in zone II relative to zones I and III. Results Nearly half of the cohort was classified as modified OARSI grade I (47.1 %) and modified Mankin score 0 (52.0 %). Preferential zone II p16INK4a accumulation was present in 29.9 % of samples. Mean age of donors with versus without preferential accumulation was 75 and 63 years, respectively (Cohen’s d = −1.27, large effect). Athletic-history and non-athletic groups did not differ in age (p = 0.607). In both univariate and multivariate logistic models, older age brackets (odds ratio [OR] = 3.42 and 3.23) and higher modified Mankin scores (OR = 1.78 and 1.48) were significantly associated with preferential zone II p16INK4a accumulation. No significant association was observed between youth high-impact athletics and preferential zone II senescence. Conclusions Participation in secondary-school high-impact athletics was not associated with preferential zone II p16INK4a accumulation at autopsy. These findings support existing hypotheses that zone-specific chondrocyte senescence is predominantly linked to aging and osteoarthritic degeneration rather than to isolated adolescent mechanical loading.