Mechanisms of aging of the extracellular matrix: role of the elastin-laminin receptor.

Aging of connective tissues is important for the understanding of aging mechanisms of tissues rich in extracellular matrix and of age-dependent diseases often affecting such tissues. Aging mechanisms of such tissues can be divided as follows: (1) age-dependent modifications of matrix biosynthesis; (2) postsynthetic modifications of extracellular matrix, and (3) modifications of cell-matrix interactions. Examples are discussed for all three aspects of tissue aging, with special emphasis on the role of epigenetic reactions. These reactions include the Maillard reaction, uncontrolled proteolytic degradation, and free radical release. Proteolytic fragments of fibronectin and of elastic fibers were shown to produce noxious effects and to be engaged in vicious circles of autoentertained and self-amplified mechanisms. We studied in particular the role of the elastin-laminin receptor in tissue aging and in atherogenesis. The presence of saturating concentrations of elastin peptides in the circulation results in a chronic overstimulation of the receptor with sustained free radical and lytic enzyme production. Other examples of age-dependent uncoupling of receptors also illustrate the importance of altered receptor function in tissue aging and related pathologies.