Mechanisms of maturation and ageing of collagen

The deleterious age-related changes in collagen that manifest in the stiffe ning of the joints, the vascular system and the renal and retinal capillari es are primarily due to the intermolecular cross-linking of the collagen mo lecules within the tissues. The formation of cross-links was elegantly demo nstrated by Verzar over 40 years ago but the nature and mechanisms are only now being unravelled. Cross-linking involves two different mechanisms, one a precise enzymically controlled cross-linking during development and matu ration and the other an adventitious non-enzymic mechanism following matura tion of the tissue. It is this additional non-enzymic cross-linking, known as glycation, involving reaction with glucose and subsequent oxidation prod ucts of the complex, that is the major cause of dysfunction of collagenous tissues in old age. The process is accelerated in diabetic subjects due to the higher levels of glucose. The effect of glycation on cell-matrix intera ctions is now being studied and may be shown to be an equally important asp ect of ageing of collagen. An understanding of these mechanisms is now lead ing to the development of inhibitors of glycation and compounds capable of cleaving the cross-links, thus alleviating the devastating effects of agein g. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.