Effect of collagen turnover on the accumulation of advanced glycation end products

Collagen molecules in articular cartilage have an exceptionally long lifeti me, which makes them susceptible to the accumulation of advanced glycation end products (AGEs). In fact, in comparison to other collagen-rich tissues, articular cartilage contains relatively high amounts of the AGE pentosidin e. To test the hypothesis that this higher AGE accumulation is primarily th e result of the slow turnover of cartilage collagen, AGE levels in cartilag e and skin collagen were compared with the degree of racemization of aspart ic acid (% D-Asp, a measure of the residence time of a protein). AGE (N-eps ilon-(carboxymethyl)lysine, N-epsilon-(carboxyethyl)lysine, and pentosidine ) and % D-Asp concentrations increased linearly with age in both cartilage and skin collagen (p < 0.0001), The rate of increase in AGEs was greater in cartilage collagen than in skin collagen (p < 0.0001). % D-Asp was also hi gher in cartilage collagen than in skin collagen (p < 0.0001), indicating t hat cartilage collagen has a longer residence time in the tissue, and thus a slower turnover, than skin collagen. In both types of collagen, AGE conce ntrations increased linearly with % D-Asp (p < 0.0005). Interestingly, the slopes of the curves of AGEs versus % D-Asp, i.e. the rates of accumulation of AGEs corrected for turnover, were identical for cartilage and skin coll agen. The present study thus provides the first experimental evidence that protein turnover is a major determinant in AGE accumulation in different co llagen types. From the age-related increases in % D-Asp the half-life of ca rtilage collagen was calculated to be 117 years and that of skin collagen 1 5 years, thereby providing the first reasonable estimates of the half-lives of these collagens.