Martin W. Hetzer1 and Simone Bersini2,3 1Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA 2Regenerative Medicine Technologies Laboratory, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland 3Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6900 Lugano, Switzerland Correspondence: hetzersalk.edu; simone.bersinieoc.ch

The vascular system is a key player for the maintenance of healthy tissues, suggesting how the physiological decline of blood vessel functionality during aging could be a major contributor of organ degeneration. While basic research studies have begun to pinpoint potential mechanisms of vascular aging, it is now critical to translate them into therapeutically relevant options. Microphysiological systems represent a powerful tool to precisely control which combinations of stimuli are provided to in vitro reconstructed blood vessels and to analyze their functional consequences. After highlighting key aspects of vascular aging, this review discusses in vitro models that are able to recapitulate relevant features of blood vessel damage during aging. Strategies to improve current in vitro systems so that they will more faithfully recapitulate vascular aging are proposed, emphasizing the importance of combining in vivo models with microphysiological systems for an effective translation of vascular aging biomarkers and therapies to the clinical level.