The role of the cell-matrix interface in aging and its interaction with the renin-angiotensin system in the aged vasculature

Abstract

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.

Constitutive interpretation of arterial stiffness in clinical studies: a methodological review

“…In contrast, arterial stiffness measurements in an (interventional) study context invariably evoke mechanistic interpretation, where measured changes are considered in relation to the existing knowledge and insights at the level of the extracellular matrix (ECM) and smooth muscle cells (27,46,73,77). In the last decade, a vast knowledge base has been developing from the molecular scale and genetic level toward the mechanobiological and biomechanical interactions between cells and the ECM (31,58,66).…”

Age-Associated Dysregulation of Integrin Function in Vascular Smooth Muscle

“…This indicates that angiotensin receptor-mediated constriction in old SFA was mostly dependent on integrin signaling. Since Ang II levels are increased with aging ( Yoon et al, 2016 ), integrin activation via AT1 receptor plays an important role in regulating SFA contractility and stiffness in old vessels ( De Luca 2019 ). This observation is in good agreement with other studies showing a positive correlation between Ang II effects via AT1 receptor and integrin activation in different vascular beds ( Kawano et al, 2000 ; Jia et al, 2003 ; Brassard et al, 2006 ; Bunni et al, 2011 ).…”

Age-Dependent Remodeling in Infrapatellar Fat Pad Adipocytes and Extracellular Matrix: A Comparative Study

“…A cell cannot be fully investigated without considering its environment ( 43 ). Cellular senescence likely descends from age-related changes in the ECM ( 44 ), hence, its features are another valuable aspect to consider when focusing on tissue age-related development. As stated by Rittié et al ( 45 ), tissue remodeling may be assessed focusing on variations in collagen matrix content; here, collagen I and III were both specifically analyzed through a histological approach.…”