Top Publication: Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging

Endothelial SIRT1 regulates proangiogenic signals secreted from myocytes and improves muscle health. Treatment of mice with NAD precursor nicotinamide mononucleotide improves vascular and increases endurance in aging mice.

A decline in capillary density and blood flow with age is a major cause of mortality and morbidity. Understanding why this occurs is key to futuregains in human health. NAD precursors reverse aspects of aging, in part, by activating sirtuin deacylases (SIRT1–SIRT7) that mediate the benefitsof exercise and dietary restriction (DR). We show that SIRT1 in endothelial cells is a key mediator of pro-angiogenic signals secreted from myocytes.Treatment of mice with the NAD+ booster nicotinamide mononucleotide (NMN) improves blood flow and increases endurance in elderly mice bypromoting SIRT1-dependent increases in capillary density, an effect augmented by exercise or increasing the levels of hydrogen sulfide (H2S), aDR mimetic and regulator of endothelial NAD+ levels. These findings have implications for improving blood flow to organs and tissues,increasing human performance, and reestablishing a virtuous cycle of mobility in the elderly.