Aging, considered as a chronological and/or biological event, is an extremely complex and multifactorial process, which may represent the consequences of environmental noxae interfering with genetic and developmental programs.The extracellular matrix plays a crucial role in age-related degenerations, and the so-called "premature aging syndromes" give further evidence for the complexity of the relationships between connective tissue, age and diseases. Several reports already focused on the correlations between age and phenotypic expression of mesenchimal cells in vitro; moreover, it was also pointed out that morphological and functional alterations of connective tissues, at some extent, might be related in vivo to increasing age. Correlation between morphologic data and proteomic analyses sustains the hypothesis that senescence is the result of both genetic and epigenetic factors.