Nicotinamide Phosphoribosyltransferase as a Key Molecule of the Aging/Senescence Process

Aging is a phenomenon underlined by complex molecular and biochemical changes that occur over time. One of the metabolites that is gaining strong research interest is nicotinamide adenine dinucleotide, NAD(+), whose cellular level has been shown to decrease with age in various tissues of model animals and humans. Administration of NAD(+) precursors, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), to supplement NAD(+) production through the NAD(+) salvage pathway has been demonstrated to slow down aging processes in mice. Therefore, NAD(+) is a critical metabolite now understood to mitigate age-related tissue function decline and prevent age-related diseases in aging animals. In human clinical trials, administration of NAD(+) precursors to the elderly is being used to address systemic age-associated physiological decline. Among NAD(+) biosynthesis pathways in mammals, the NAD(+) salvage pathway is the dominant pathway in most of tissues, and NAMPT is the rate limiting enzyme of this pathway. However, only a few activators of NAMPT, which are supposed to increase NAD(+), have been developed so far. In this review, we will focus on the importance of NAD(+) and the possible application of an activator of NAMPT to promote successive aging.