Human aortic smooth muscle cells (AoSMCs) change their extracellular matrix composition during aging, with direct effects on cellular events and cell migration. For example, active matrix metalloproteinase-2 (MMP-2) is synthesized only by young AoSMCs, whereas aged cells produce only the inactive zymogen form. The pro-MMP-2 activation in young cells depends on an increase in membrane type 1 matrix metalloproteinase content. Furthermore, transcripts coding for tissue inhibitor of metalloproteinases (TIMPs) were upregulated in aged cells, and the increase of TIMPs also could prevent pro-MMP-2 activation. As consequence of these situations, young AoSMCs possess a higher migratory capability than aged cells on gelatin support. These data are confirmed by adding TIMP-1 and TIMP-2 to young cells which reproduces aged AoSMCs migratory behavior. The opposite effect was obtained in young cells silencing MMP-2 and TIMP-2.