Effect of collagen turnover on the accumulation of advanced glycation end products.
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(epsilon)-(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 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.
Verzijl
N
N
Gaubius Laboratory, TNO Prevention and Health, P. O. Box 2215, 2301 CE Leiden, the Netherlands.
DeGroot
J
J
Thorpe
S R
SR
Bank
R A
RA
Shaw
J N
JN
Lyons
T J
TJ
Bijlsma
J W
JW
Lafeber
F P
FP
Baynes
J W
JW
TeKoppele
J M
JM
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D001224:Aspartic Acid / Q000737:chemistry; D002358:Cartilage, Articular / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D019902:Chondrocytes / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000493:pharmacokinetics*; D006801:Humans; D007700:Kinetics; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D008875:Middle Aged; D012867:Skin / Q000378:metabolism
D017127:Glycation End Products, Advanced; D001224:Aspartic Acid; C054688:N(6)-(1-carboxyethyl)lysine; C048496:N(6)-carboxymethyllysine; D003094:Collagen; D001120:Arginine; C062187:pentosidine; D008239:Lysine