Summary
The scientific perception of blood vessels has changed substantially in recent years. They are no longer considered passive conduits of blood that respond to exogenous cues. Now, the vascular endothelium is considered to act as an instructive gatekeeper to actively control organ function (1). Although mechanisms of local regulation by the vasculature have been identified for most organs and many disease states, including cancer, the study of systemic instructive vascular signaling is still in its infancy. On page 533 of this issue, Grunewald et al. (2) report that low-dose systemic increase of vascular endothelial growth factor–A (VEGFA) in the circulation leads to a notable life span extension in mice. The complex multiorgan rejuvenation phenotype of these mice yields insight into the mechanisms of organism aging and highlights the critical role of the vasculature as a gatekeeper of life span and health span.
