Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures

摘要

Nicotinamide adenine dinucleotide (NAD+) is modulatedby conditions of metabolic stress and hasbeen reported to decline with aging in preclinicalmodels, but human data are sparse. Nicotinamideriboside (NR) supplementation ameliorates metabolicdysfunction in rodents. We aimed to establishwhether oral NR supplementation in aged participantscan increase the skeletal muscle NAD+ metabolomeand if it can alter muscle mitochondrialbioenergetics. We supplemented 12 aged men with1 g NR per day for 21 days in a placebo-controlled,randomized, double-blind, crossover trial. Targetedmetabolomics showed that NR elevated the muscleNAD+ metabolome, evident by increased nicotinicacid adenine dinucleotide and nicotinamide clearanceproducts. Muscle RNA sequencing revealedNR-mediated downregulation of energy metabolismand mitochondria pathways, without altering mitochondrialbioenergetics. NR also depressed levelsof circulating inflammatory cytokines. Our dataestablish that oral NR is available to aged humanmuscle and identify anti-inflammatory effects of NR.