Effect of Collagen Turnover on the Accumulation of Advanced Glycation End Products*

By N. Verzijl, J. DeGroot, S. Thorpe, R. Bank, J. Shaw, T. Lyons, J. Bijlsma, F. Lafeber, J. Baynes, J. Tekoppele. Journal of Biological Chemistry, 2000

887 citations recorded by the source corpus.

Collagen molecules in articular cartilage have an exceptionally long lifetime, 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 pentosidine. To test the hypothesis that this higher AGE accumulation is primarily the result of the slow turnover of cartilage collagen, AGE levels in cartilage and skin collagen were compared with the degree of racemization of aspartic acid (% d-Asp, a measure of the residence time of a protein). AGE (N ε-(carboxymethyl)lysine,N ε-(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 higher in cartilage collagen than in skin collagen (p< 0.0001), indicating that cartilage collagen has a longer residence time in the tissue, and thus a slower turnover, than skin collagen. In both types of collagen, AGE concentrations 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 collagen. The present study thus provides the first experimental evidence that protein turnover is a major determinant in AGE accumulation in different collagen types. From the age-related increases in % d-Asp the half-life of cartilage collagen was calculated to be 117 years and that of skin collagen 15 years, thereby providing the first reasonable estimates of the half-lives of these collagens.

Subfields: Clinical Biochemistry, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/a195437b0d2ed49798501c1a9c0365cba139f8de

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In Clinical Biochemistry

1. M. Davies

In Molecular Biology

1. M. Goldring
2. M. Adams
3. M. Davies
4. A. Anderson
5. Richard F. Loeser
6. P. Roughley

In Physiology

1. M. Davies
2. A. Anderson
3. Richard F. Loeser

Citations in the corpus

• Protein oxidation and peroxidation (2016, background): “The slow turnover of large (and often heavily cross-linked) matrix proteins results in long half-lives [245,260], and this is likely to contribute to the accumulation of modifications on these materials [261–263].”
• The role of cytokines in cartilage matrix degeneration in osteoarthritis. (2004, background): “remodeling of the matrix components is reported to be very low.(83,84,145) However, it is possible that there are regional differences in the remodeling activities of chon-”
• What is Intervertebral Disc Degeneration, and What Causes It? (2006, background): “[32] Collagen turnover time in articular cartilage is approximately 100 years[33] and could be even longer in the disc.”
• Autophagy is a Protective Mechanism in Normal Cartilage and its Aging-related Loss is Linked with Cell Death and Osteoarthritis (2010, background): “It has been estimated that the half-life of type II collagen is 117 years (31), and various measurements in mature cartilage revealed only a very small fraction of proliferating cells (32).”
• The myofibroblast matrix: implications for tissue repair and fibrosis (2013, neutral): “Collagen crosslinking also occurs without enzymatic support by glycation; although this process iscomparably slow, it is physiologically relevant given the low turnover time of collagen with a half-life of 15 years in skin and one order of magnitude longer in cartilage [209,210].”
• Why is Osteoarthritis an Age-Related Disease? (2010, background): “The most common AGE-related cross link is pentosidine which has been found to be present in cartilage in increasing amounts with age [85,87,88].”
• International Consensus on Use of Continuous Glucose Monitoring (2017, background): “5% for adults (9) [E] and children (10) [E].”