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
Affiliations
Yasir S. Elhassan
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK; MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
Katarina Kluckova
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Rachel S. Fletcher
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Mark S. Schmidt
Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Antje Garten
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Craig L. Doig
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
David M. Cartwright
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Lucy Oakey
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Claire V. Burley
School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK; Centre for Human Brain Health, University of Birmingham, Birmingham, UK
Ned Jenkinson
School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK; Centre for Human Brain Health, University of Birmingham, Birmingham, UK
Martin Wilson
Centre for Human Brain Health, University of Birmingham, Birmingham, UK; School of Psychology, University of Birmingham, Birmingham, UK
Samuel J.E. Lucas
School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK; Centre for Human Brain Health, University of Birmingham, Birmingham, UK
Ildem Akerman
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Alex Seabright
School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK
Yu-Chiang Lai
School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK
Daniel A. Tennant
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Peter Nightingale
Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Gareth A. Wallis
School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK
Konstantinos N. Manolopoulos
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
Charles Brenner
Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Andrew Philp
School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK; Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW, Australia; Faculty of Medicine, St. Vincent’s Clinical School, Sydney, UNSW, Australia
Gareth G. Lavery
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK; MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; Corresponding author
Summary: 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. : Elhassan et al. show that oral nicotinamide riboside increases the NAD+ metabolome in aged human skeletal muscle, without apparently altering mitochondrial bioenergetics. Measures of muscle and whole-body metabolism are also unchanged. Nicotinamide riboside reduces the levels of circulating inflammatory cytokines. Studies in relevant human disease models are warranted. Keywords: nicotinamide adenine dinucleotide, metabolism, aging, inflammation, cell adhesion
