The scientific conception of blood vessels has modified significantly in most recent years. They are no longer regarded as passive conduits of blood that reply to exogenous cues. Now, the vascular endothelium is taken into legend to behave as an instructive gatekeeper to actively control organ purpose (1). Though mechanisms of local legislation by the vasculature had been identified for most organs and many disease states, including most cancers, the behold of systemic instructive vascular signaling is tranquil in its infancy. On page 533 of this topic, Grunewald et al. (2) document that low-dose systemic lengthen of vascular endothelial voice element–A (VEGFA) within the circulation ends in a notable life span extension in mice. The advanced multiorgan rejuvenation phenotype of those mice yields insight into the mechanisms of organism aging and highlights the serious purpose of the vasculature as a gatekeeper of life span and health span.