Sirtuins and NAD+ in the Development and Treatment of Metabolic and Cardiovascular Diseases


Several studies suggest that increasing NAD+ may protect against hypertrophy. Increasing NAD+ in mice by either dosing with NMN or overexpressing NAMPT prevented hypertrophy induced by TAC and improved cardiac function63, by increasing energy production in the mitochondria and reducing mPTP opening. The addition of NAD+ prevented isoproterenol-induced hypertrophy in mice and interestingly this was mediated by SIRT3, but not SIRT1, through activation of LKB1-AMPK signaling.

NMN treatment protected against cardiac dysfunction in a Friedreich’s ataxia cardiomyopathy mouse model in a SIRT3-dependent manner and increased cardiac function in Ndufs4 knockout mice exposed to pressure overload64. NR treatment also reduced inflammation and fibrosis in aged MDX mice, a muscular dystrophy model that develops cardiomyopathy. Finally, PARP inhibitors protected against hypertrophy and improved cardiac function in several rodent models, possibly in part by increasing NAD+ levels.