Enzymic and non‐enzymic cross‐linking mechanisms in relation to turnover of collagen: relevance to aging and exercise

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.