© 2018 Elsevier B.V. The extracellular matrix (ECM) is an intricate network that provides structural and anchoring support to cells in order to stabilize cell morphology and tissue architecture. The ECM also controls many aspects of the cell's dynamic behavior and fate through its ongoing, bidirectional interaction with cells. These interactions between the cell and components of the surrounding ECM are implicated in several biological processes, including development and adult tissue repair in response to injury, throughout the lifespan of multiple species. The present review gives an overview of the growing evidence that cell-matrix interactions play a pivotal role in the aging process. The focus of the first part of the article is on recent studies using cell-derived decellularized ECM, which strongly suggest that age-related changes in the ECM induce cellular senescence, a well-recognized hallmark of aging. This is followed by a review of findings from genetic studies indicating that changes in genes involved in cell–ECM adhesion and matrix-mediated intracellular signaling cascades affect longevity. Finally, mention is made of novel data proposing an intricate interplay between cell-matrix interactions and the renin-angiotensin system that may have a significant impact on mammalian arterial stiffness with age.