Fig. 7.

Proposed scheme for the mechanisms contributing to young blood–mediated vascular rejuvenation in aged heterochonic parabionts. The model, based on our present and previous findings and earlier data from the literature (Ungvari et al. 2018a; Tarantini et al. 2018; Tarantini et al. 2019b; Csiszar et al. 2019b; Van Skike et al. 2018), predicts that circulating anti-geronic factors present in young blood (derived from heterochronic parabiont young mice [Y-(A)]) restore cellular NAD+, activate sirtuins/PGC-1α and/or inhibit mTOR mediated pathways, promoting transcriptomic changes, which rescue a youthful vascular phenotype in and heterochronic parabiont aged mice [A-(Y)]. Young blood–mediated vascular rejuvenation is associated with restored mitochondrial function, attenuation of cellular and mitochondrial ROS production, increased bioavailability of NO and improved endothelium-mediated vasodilation. All of these effects are predicted to act to improve vascular health, preventing the pathogenesis of age-related vascular diseases. CVD: cardiovascular diseases; Y-(A)