Matrix biology expanded its sphere of interest over the recent decades from its original rheological-morphological functions to incorporate control of cell phenotype during development and maturation. Aging and age-related pathologies are accompanied by matrix remodeling, loss of phenotypic traits as during atherogenesis or tumor growth. Most of these recently discovered functions are related to signaling by matrix components to cells through cell-membrane receptors. Some of the signaling molecules are produced by proteolytic degradation of macromolecules of the extracellular matrix. Such peptides (matrikins or matricryptins) exhibit biological functions absent in the native molecule from which these peptides were derived. Some of these novel activities are potentially harmful and appear to be involved in the age-dependent alterations of tissue structure and functions as well as in related pathologies.