Experimental model systems to study vascular aging.

Vascular aging contributes to systemic dysfunction and underlies many age-related diseases, driven by structural and functional changes across various cell types, including endothelial cells, vascular smooth muscle cells, pericytes, and cardiomyocytes. This review highlights experimental models that facilitate mechanistic insights and the development of novel therapeutic approaches for vascular aging, emphasizing both in vitro and in vivo methodologies. This review discusses in vitro models utilizing primary and induced pluripotent stem cell (iPSC)-derived cultures across two-dimensional (2D) and three-dimensional (3D) systems, such as spheroids, organoids, and vessel-on-chip platforms, which allow for a more physiological investigation of aging-associated processes. Moreover, currently used in vivo models, including genetically engineered mice, and disease models mimicking human vascular aging, as well as state-of-the-art readouts, including flow-mediated dilation (FMD) and pulse wave velocity (PWV), are also reviewed. Lastly, an overview of the most prominent hurdles and shortcomings associated with modeling vascular aging is provided, underscoring the need for continued refinement to drive therapeutic innovation.