NAD+ metabolism as a target for metabolic health: have we found the silver bullet?

Abstract

NAD + has gone in and out of fashion within the scientific community a number of times since its discovery in the early 1900s. Over the last decade, NAD + has emerged as a potential target for combatting metabolic disturbances and the mitochondrial dysfunction that is mediated through sirtuin (SIRT) enzymes. The beneficial metabolic effects of the NAD + /SIRT axis have triggered an increased interest in NAD + as an enhancer of energy metabolism. As a result, a myriad of publications have focused on NAD + metabolism, with the majority of the work having been performed using in vitro models, and in vivo work largely consisting of interventions in Caenorhabditis elegans and rodents. Human intervention trials, on the other hand, are scarce. The aim of this review is to provide an overview of the state-of-the-art on influencing NAD + metabolism in humans and to set the stage for what the future of this exciting field may hold. Electronic supplementary material The online version of this article (10.1007/s00125-019-4831-3) contains a slideset of the figures for download, which is available to authorised users.

Subcellular Characterization of Nicotinamide Adenine Dinucleotide Biosynthesis in Metastatic Melanoma by Using Organelle-Specific Biosensors

“…Because of its essential role and ubiquitous presence, alterations of NAD + concentrations are associated with a large number of pathological conditions, including metabolic diseases like obesity, diabetes and insulin resistance, inflammation and immune responses(16,46,64). A decrease in NAD + levels is also a hallmark of aging and aging-associated pathologies, such as neurodegeneration and motor function decline.…”

Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes

“…Generation of precursors (glyceraldehyde 3-phosphate, ribose-5-phosphate and erythrose 4-phosphate) for nucleotide biosynthesis is a main function of PPP. In situations of intracellular fuel overload, shunting glycolytic intermediates into the PPP yields a relative energy loss in combination with an improved antioxidant and restorative capacity, via elevated cellular NADPH levels 24 .…”

Implications of NAD+ Metabolism in the Aging Retina and Retinal Degeneration

“…The potential therapeutic utility of NAD + supplementation was demonstrated as early as 1937 when it was demonstrated that it could cure the black tongue in the canine and successfully treat pellagra in the human [26][27][28]. Accordingly, more recent studies have shown that supplementation with NAD + precursors improves NAD + levels in aged tissues and thereby protects against aging and the development and progression of aging-related diseases [14,[29][30][31][32][33]. Indeed, boosting NAD + metabolism has been shown to extend the lifespan of various organisms, such as yeast, worms, flies, and rodents [11].…”