Modulating NAD metabolism, from bench to bedside.

Discovered in the beginning of the 20 century, nicotinamide adenine dinucleotide (NAD) has evolved from a simple oxidoreductase cofactor to being an essential cosubstrate for a wide range of regulatory proteins that include the sirtuin family of NAD-dependent protein deacylases, widely recognized regulators of metabolic function and longevity. Altered NAD metabolism is associated with aging and many pathological conditions, such as metabolic diseases and disorders of the muscular and neuronal systems. Conversely, increased NAD levels have shown to be beneficial in a broad spectrum of diseases. Here, we review the fundamental aspects of NAD biochemistry and metabolism and discuss how boosting NAD content can help ameliorate mitochondrial homeostasis and as such improve healthspan and lifespan.