Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix

Objective: Age-related changes in multiple components of the musculoskeletal system may contribute to the well established link between aging and osteoarthritis (OA). This review focused on potential mechanisms by which age-related changes in the articular cartilage could contribute to the development of OA. Methods: The peer-reviewed literature published prior to February 2009 in the PubMed database was searched using pre-defined search criteria. Articles, selected for their relevance to aging and articular chondrocytes or cartilage, were summarized. Results: Articular chondrocytes exhibit an age-related decline in proliferative and synthetic capacity while maintaining the ability to produce pro-inflammatory mediators and matrix degrading enzymes. These findings are characteristic of the senescent secretory phenotype and are most likely a consequence of extrinsic stress-induced senescence driven by oxidative stress rather than intrinsic replicative senescence. Extracellular matrix changes with aging also contribute to the propensity to develop CA and include the accumulation of proteins modified by non-enzymatic glycation. Conclusion: The effects of aging on chondrocytes and their matrix result in a tissue that is less able to maintain homeostasis when stressed, resulting in breakdown and loss of the articular cartilage, a hallmark of OA. A better understanding of the basic mechanisms underlying senescence and how the process may be modified could provide novel ways to slow the development of OA. (C) 2009 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.