Effects of age and diabetes mellitus on the solubility and nonenzymatic glucosylation of human skin collagen.

Abstract

A B S T R A C T Collagen from human skin was fractionated into neutral salt-soluble, acid-soluble, pepsinreleased, and insoluble fractions. No age-related changes were observed in the proportion ofcollagen extracted by neutral salt. A significant age-related decrease in the proportion of acid-soluble collagen was found. A highly significant (P < 0.001) agerelated decrease in the amount of collagen released by pepsini digestion was observed, with a concomitant age-related increase in the fraction of insoluble collagen. The amount of ketoamine-linked glucose bound to this insoluble collagen also increased significantly with age.Skin collagen from three juvenile onset diabetics (JOD) and one young maturity onset diabetic (MOD) appeared to have undergone accelerated aging. JOD and the young MOD had significantly less collagen released by pepsin digestion and significantly more insoluble collagen than would be predicted by their ages. The collagen released by pepsin digestion of the diabetic samples had more high molecular weight components than similar fractions obtained from agematched nondiabetic controls. There was also more ketoamine-linked glucose bound to the insoluble collagen of JOD than to that fraction from comparably aged control subjects. The apparent acceleration of collagen aging in diabetes mellitus may play a role in complications of diabetes that occur in collagenrich tissues.

Age-related accumulation of Maillard reaction products in human articular cartilage collagen

“…The fact that the solubility of human skin collagen by enzymic digestion with pepsin decreases with age is attributed to the increased AGE cross-linking with advancing age [11,37]. Similarly, our data show that the digestibility of articular cartilage collagen by bacterial collagenase decreases substantially with age : from approx.…”

“…In subsequent Maillard or browning reactions, products known as advanced glycation end products (AGEs) are formed from FL [3,4], and accumulate with age in long-lived proteins [1,2,[5][6][7][8]. These AGEs include structurally characterized adducts, such as N ε -(carboxymethyl)lysine (CML) [1][2][3] and N ε -(carboxyethyl)-lysine (CEL) [9], fluorescent cross-links, such as pentosidine formed between lysine and arginine residues [5,10], as well as chemically unidentified compounds which result in proteinbound browning or fluorescence, and cross-linking [11][12][13][14].In comparison with other collagen-rich tissues such as skin, cartilage contains relatively large amounts of pentosidine [5,15]. Pentosidine levels in articular cartilage increase linearly with age [6-8], as was previously described for skin collagen [16] and lens proteins [10].…”

Non-enzymatic glycosylation and the chronic complications of diabetes: an overview

“…Increased non-enzymatic glycosylation of diaphragmatic tendon and skin collagens is observed with both age and diabetes in man [59,60]; and, in rats similar effects were noted with aortic and glomerular basement membrane collagens [61,62]. The increased glycosylation of collagen in vivo has been correlated with its decreased solubility, elasticity and sensitivity to protease digestion [60], and increased thermal stability [63], all of which suggest increased crosslinking of collagen in diabetes. Incubation of collagen (and other proteins) with glucose in vitro also inhibits their degradation by proteases [64], possibly because of cross-linking, but perhaps also because glycosylation of lysine residues renders them resistant to trypsin enzymes.…”

Advanced Glycation End Products Enhance Expression of Pro-apoptotic Genes and Stimulate Fibroblast Apoptosis through Cytoplasmic and Mitochondrial Pathways

“…It is well known that AGEs form in the skin as part of the aging process and as a result of diabetes (31)(32)(33). Accumulation of AGEs in skin has been related to tissue stiffening and lack of elasticity during aging (5,31,32).…”