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

Yasir S Elhassan | Katarina Kluckova | Rachel S Fletcher | Mark S Schmidt | Antje Garten | Craig L Doig | David M Cartwright | Lucy Oakey | Claire V Burley | Ned Jenkinson | Martin Wilson | Samuel J E Lucas | Ildem Akerman | Alex Seabright | Yu-Chiang Lai | Daniel A Tennant | Peter Nightingale | Gareth A Wallis | Konstantinos N Manolopoulos | Charles Brenner | Andrew Philp | Gareth G Lavery
Cell reports | 2019

Nicotinamide adenine dinucleotide (NAD+) is modulated by conditions of metabolic stress and has been reported to decline with aging in preclinical models, 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 if it can alter muscle mitochondrial bioenergetics. We supplemented 12 aged men with 1 g NR 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, without altering mitochondrial bioenergetics. NR also depressed levels of circulating inflammatory cytokines. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR.

Pubmed ID: 31412242

Associated grants

  • Agency: Medical Research Council, United Kingdom
    Id: MC_PC_15032
  • Agency: Arthritis Research UK, United Kingdom
  • Agency: Wellcome Trust, United Kingdom
    Id: 104612/Z/14/Z
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL147545

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