Nicotinamide Riboside Improves Cardiac Function and Prolongs Survival After Disruption of the Cardiomyocyte Clock
Pieterjan Dierickx, Bryce J. Carpenter, Isaac J. Celwyn, Daniel P. Kelly, Joseph A. Baur, Mitchell A. Lazar
Abstract
The REV-ERB nuclear receptors are key components of the circadian clock. Loss of REV-ERBs in the mouse heart causes dilated cardiomyopathy and premature lethality. This is associated with a marked reduction in NAD + production, but whether this plays a role in the pathophysiology of this heart failure model is not known. Here, we show that supplementation with the NAD + precursor NR as a dietary supplement improves heart function and extends the lifespan of female mice lacking cardiac REV-ERBs. Thus, boosting NAD + levels can improve cardiac function in a setting of heart failure caused by disruption of circadian clock factors, providing new insights into the links between the circadian clock, energy metabolism, and cardiac function.