Aged human serum induces changes in barrier function in an isogenic venule model

Vascular aging and dysfunction are significant contributors to age-related cardiovascular and neurodegenerative diseases, both of which encompass major causes of death in the aged population. In particular, aging heavily impacts small vessels, damages vascular integrity leading to leakage events and inflammation, and can be further exacerbated by environmental factors that may result in more severe symptomatic presentation of disease. Here, we evaluate generalized, isogenic, co-culture in vitro models of microvasculature under perfusion with aged human serum over just four days, which results in a transcriptomic recapitulation of an aging phenotype, transcript and protein changes in junctional mediators, and functional loss of paracellular and transcellular barrier integrity. Additionally, in comparison with endothelial monoculture, we identify critical changes to basement membrane composition and aging-cue-mediated cell cycle shifts with pericyte co-culture. This modular approach reveals key impacts to further our understanding of vascular aging to leverage in designing therapeutic and preventative approaches.