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Cell Rep. 2019 Aug 13;28(7):1717-1728.e6. doi: 10.1016/j.celrep.2019.07.043.

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

Author information

1
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.
2
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
3
Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
4
School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK; Centre for Human Brain Health, University of Birmingham, Birmingham, UK.
5
Centre for Human Brain Health, University of Birmingham, Birmingham, UK; School of Psychology, University of Birmingham, Birmingham, UK.
6
School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK.
7
Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
8
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK.
9
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.
10
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. Electronic address: g.g.lavery@bham.ac.uk.

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.

KEYWORDS:

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

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