Role of NAD + and mitochondrial sirtuins in cardiac and renal diseases.

The coenzyme nicotinamide adenine dinucleotide (NAD ⁺ ) has key roles in the regulation of redox status and energy metabolism. NAD ⁺ depletion is emerging as a major contributor to the pathogenesis of cardiac and renal diseases and NAD ⁺ repletion strategies have shown therapeutic potential as a means to restore healthy metabolism and physiological function. The pleotropic roles of NAD ⁺ enable several possible avenues by which repletion of this coenzyme could have therapeutic efficacy. In particular, NAD ⁺ functions as a co-substrate in deacylation reactions carried out by the sirtuin family of enzymes. These NAD ⁺ -dependent deacylases control several aspects of metabolism and a wealth of data suggests that boosting sirtuin activity via NAD ⁺ supplementation might be a promising therapy for cardiac and renal pathologies. This Review summarizes the role of NAD ⁺ metabolism in the heart and kidney, and highlights the mitochondrial sirtuins as mediators of some of the beneficial effects of NAD ⁺ -boosting therapies in preclinical animal models. We surmise that modulating the NAD ⁺ -sirtuin axis is a clinically relevant approach to develop new therapies for cardiac and renal diseases.