Molecular mechanisms of ageing in connective tissues.

The outward manifestations of tissue ageing occurring in the elderly primarily involve the two major structural proteins of the body, collagen and elastin. The changes in these proteins are associated with intermolecular cross-linking and side-chain modifications. Cross-linking involves two different mechanisms, a precise enzymic process during development and maturation, and a subsequent non-enzymic adventitious reaction with glucose during ageing. The latter glycation reactions are the major cause of tissue dysfunction in the elderly due to cross-linking, which stiffens the tissues, and to side-chain modification, which alters normal cell-matrix interactions. Photoageing by UV involves two competing reactions, chain cleavage and cross-linking, the former predominating on long-term exposure. The molecular mechanisms involved are gradually being unravelled and will lead to the development of inhibitors of these deleterious effects of ageing.