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

Collagen from human skin was fractionated into neutral salt-soluble, acid-soluble, pepsin-released, and insoluble fractions. No age-related changes were observed in the proportion of collagen extracted by neutral salt. A significant age-related decrease in the proportion of acid-soluble collagen was found. A highly significant (P less than 0.001) age-related decrease in the amount of collagen released by pepsin 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 age-matched 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 collagen-rich tissues.