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 OA and include the accumulation of proteins modified by non-enzymatic glycation.


CONCLUSIONS
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.
Loeser
R F
RF
Section of Molecular Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. rloeser@wfubmc.edu
D000375:Aging / Q000502:physiology*; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000502:physiology*; D019902:Chondrocytes / Q000502:physiology*; D006801:Humans; D010003:Osteoarthritis / Q000235:genetics / Q000503:physiopathology*; D018384:Oxidative Stress / Q000502:physiology