Cell–matrix interactions in aging: role of receptors and matricryptins

Extracellular matrix (ECM) has been a central topic in aging research for several years. Cell–matrix interactions extend the interest in this topic both for normal tissue homeostatic regulation as well as for its dysregulation in age-related diseases. A relatively new extension of this ever-increasing field of aging research concerns the recognition of the original biological activities exhibited by proteolytic fragments of matrix macromolecules. A number of such matricryptins were recently identified, some of them endowed with harmful effects for tissue function. Some of the breakdown products exert a positive feedback effect by upregulating the biosynthesis of the original macromolecule synthesis and/or the expression of degrading enzymes. This results in vicious circles which might well be involved in tissue aging. The examples detailed in this review concern fibronectin (FN) and elastin. A number of fibronectin fragments (Fn-fr) were shown to exhibit diverse activities including increasing tissue degradation, inflammation and tumor progression. Elastin degradation products acting as agonists on the elastin-laminin receptor can trigger harmful effects such as up-regulation of proteases and free radical production. Both macromolecules are at the center of autoamplifying vicious circles of potential importance for age-dependent modification of tissue function.