AGEing and osteoarthritis: a different perspective

Across the world, osteoarthritis is the most commonly occurring musculoskeletal disease of the elderly, affecting more than 25% of the population older than 60 years of age. By far the single greatest risk factor for the development of osteoarthritis is age, but a mechanism to explain this relation has not yet been identified. If such a mechanism is identified, this potentially also provides a novel target for osteoarthritis therapy. The identification of new therapeutic targets is of utmost importance, because a disease-modifying treatment for osteoarthritis is not available and, because of the graying of the population, the number of patients with osteoarthritis will continue to increase, which will pose an enormous social and economic burden on society.

Advanced glycation end products accumulate in human articular cartilage with increasing age, and affect biomechanical, biochemical, and cellular characteristics of the tissue. As an illustration, accumulation of advanced glycation end products increase cartilage stiffness and brittleness while decreasing the synthesis and degradation of cartilage matrix constituents. Articular cartilage becomes more prone to damage, and thus osteoarthritis, at elevated concentrations of advanced glycation end products.

The reviewed literature demonstrates that the age-related accumulation of advanced glycation end products in articular cartilage may provide a molecular mechanism capable of (at least in part) explaining the age-related increase in the incidence of osteoarthritis. This conclusion paves the way for new strategies to prevent or treat osteoarthritis via inhibition and/or reversal of this process.