RT Journal Article SR Electronic T1 Nicotinamide riboside augments the human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures in aged subjects: a placebo-controlled, randomized trial JF bioRxiv FD Cold Spring Harbor Laboratory SP 680462 DO 10.1101/680462 A1 Yasir S Elhassan A1 Katarina Kluckova A1 Rachel S Fletcher A1 Mark Schmidt A1 Antje Garten A1 Craig L Doig A1 David M Cartwright A1 Lucy Oakey A1 Claire V Burley A1 Ned Jenkinson A1 Martin Wilson A1 Samuel J E Lucas A1 Ildem Akerman A1 Alex Seabright A1 Yu-Chiang Lai A1 Daniel A Tennant A1 Peter Nightingale A1 Gareth A Wallis A1 Konstantinos N Manolopoulos A1 Charles Brenner A1 Andrew Philp A1 Gareth G Lavery YR 2019 UL http://biorxiv.org/content/early/2019/06/28/680462.abstract AB NAD+ is modulated by conditions of metabolic stress and has been reported to decline with aging, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD+ metabolome, and questioned if tissue NAD+ levels are depressed with aging. We supplemented 12 aged men with NR 1g per day for 21-days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD+ metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways. NR also depressed levels of circulating inflammatory cytokines. In an additional study, 31P magnetic resonance spectroscopy-based NAD+ measurement in muscle and brain showed no difference between young and aged individuals. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR, while suggesting that NAD+ decline is not associated with chronological aging per se in human muscle or brain.