NAD⁺ metabolism as a target for anti-aging

Abstract

Aging is a physiological process caused by various genetic and environmental factors. Recently, it has been proposed that the disturbance of the nutritional-metabolic sensing pathway is one of the aging characteristics. In particular, nicotinamide adenine dinucleotide (NAD⁺) plays an important role in this pathway and is considered the regulator of aging. NAD⁺ regulates an energy metabolism as a co-factor and is also involved in various biological processes including transcription, stress responses, DNA repair, inflammatory responses as well as post-transcriptional modifications, as a substrate for sirtuins, poly ADP-ribose polymerase (PARP), and CD38. With age, DNA damage and chronic inflammation increase in organs, resulting in overconsumption of NAD⁺ via PARP and CD38. The reduced NAD⁺ levels decrease the activity of sirtuins and PARPs and impair energy metabolism, ultimately leading to aging and aging-related diseases. However, the precise metabolism of NAD⁺ in vivo and the mechanism of how NAD⁺ regulates aging remain elusive. Moreover, the clinical application of NAD⁺ supplementation therapy is still under development. In this review, we overview the NAD⁺ metabolism and its relation to aging. In addition, we describe the current issue and perspective of NAD⁺ supplementation therapy to promote a healthy lifespan.