Tracking NAD+ Production and Breakdown Pathways: Preclinical Findings

Synopsis

NAD+ (nicotinamide adenine dinucleotide) is a key molecule for metabolism and is used by important signaling enzymes like PARPs and sirtuins. NAD+ levels decline with age, so scientists are interested in ways to boost NAD+. Traditionally, studies have measured NAD+ levels, but this doesn’t show how fast NAD+ is made and used. Researchers developed isotope-tracer methods to track NAD+ production and consumption. In cell studies, NAD+ was made from nicotinamide and mostly used by PARPs and sirtuins. In mice, NAD+ was made from tryptophan mainly in the liver, which then released nicotinamide. NAD+ production and use varied by tissue, being high in the small intestine and spleen but low in skeletal muscle. Giving nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN) intravenously delivered intact molecules to many tissues, but oral administration was mostly converted to nicotinamide in the liver. This study shows that tracking NAD+ flux reveals how different tissues produce and use NAD+, which is important for designing NAD-boosting strategies.

Journal

Cell Metabolism