Fig. 3.

Proposed scheme for the mechanisms by which restoration of NAD+ levels in the aged vasculature by NMN supplementation promotes anti-aging miRNA expression profile, rescues endothelial function, and prevents atherogenesis. The model, based on our present and previous findings and earlier data from the literature (Tarantini et al. 2019; Csiszar et al. 2019), predicts that increased NAD+ activates sirtuin-mediated pathways, restores cellular energetics and attenuates mitochondrial ROS (mtROS) production, which lead to epigenetic changes promoting youthful gene/miRNA expression, restore Dicer1-mediated miRNA processing, increase NO bioavailability, decrease inflammation, and improve protein homeostasis. All of these effects are predicted to act to decrease large artery stiffness, inhibit atherogenesis, improve vasodilation, and promote angiogenesis at the level of the microcirculation