The mechanisms and consequences of the maturation and ageing of collagen

The stabilisation of collagen fibres during development and through growth to maturation is now fairly well understood. It is a carefully controlled enzymic process which produces intermolecular cross-links at specific locations. In marked contrast, the changes in the physical properties that occur towards old age are stochastic and involve oxidative reactions that result in the formation of glucose mediated cross-links. This excessive and random cross-linking leads to a devastating loss of tissue functionality and deterioration of vital organs. In addition, specific residues involved in cell-matrix interactions may become modified. This can affect the expression of cells and lead to the formation of an inappropriate collagen matrix during its slower turnover in old age. This is exemplified in the ubiquitous disorders osteoporosis and osteoarthritis, age-related diseases in which we have noted gene regulated changes in the collagen deposited and also post-translational changes such as over-hydroxylation of lysine residues. Both of these effects can have a profound deleterious effect on the function of the matrix tissue.