The molecular mechanisms involved in the aging of collagen and consequent increase in mechanical strength and stiffness occur in a series of enzymic and non-enzymic intermolecular cross-links. The enzymic mechanism involves divalent aldimine intermolecular cross-links derived from the reaction of aldehydes which then mature to trivalent cross-links and further stabilize the collagen fiber and is now well known. Recent studies have demonstrated that the rate of turnover and level of telopeptide lysyl hydroxylation modifies the nature of the cross-link and hence the mechanical strength of the fiber.
The slow turnover of mature collagen subsequently allows accumulation of the products of the adventitious non-enzymic reaction of glucose with the lysines in the triple helix to form glucosyl lysine and its Amadori product, that is, the Maillard reaction. These products are subsequently oxidized to a complex series of advanced glycation end-products, some of which are intermolecular cross-links between the triple helices rendering the fiber too stiff for optimal functioning of the collagen fibers, and consequently of the particular tissue involved. The glycation reactions following maturation are true aging processes, and attempts at their specific inhibition involve competitive inhibition of the Maillard reaction and chemical cleavage of the glycation cross-links.
It is clear that the nature of the age-related cross-links and hence tissue strength depends on the rate of turnover of the collagen. An examination of the particular effect of strenuous exercise on the rate of turnover of collagen and hence cross-linking in different tissues could lead to a better understanding of optimal sports training regimes.