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 BrennerAndrew Philp, Gareth G. Lavery

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)
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Abstract

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.
Original languageEnglish
Pages (from-to)1717-1728.e6
Number of pages19
JournalCell Reports
Volume28
Issue number7
Early online date13 Aug 2019
DOIs
Publication statusPublished - 13 Aug 2019

Keywords

  • nicotinamide adenine dinucleotide
  • metabolism
  • aging
  • inflammation
  • cell adhesion

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