Nicotinamide riboside augments the aged human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures

Elhassan, YS, Kluckova, K, Fletcher, RS, Schmidt, MS, Garten, A, Doig, CL ORCID: https://orcid.org/0000-0001-9694-4230, Cartwright, DM, Oakey, L, Burley, CV, Jenkinson, N, Wilson, M, Lucas, SJ, Akerman, I, Seabright, A, Lai, Y, Tennant, DA, Nightingale, P, Wallis, GA, Manolopoulos, KN, Brenner, C, Philp, A and Lavery, GG, 2019. Nicotinamide riboside augments the aged human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures. Cell Reports, 28 (7), pp. 1717-1728. ISSN 2211-1247

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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.

Item Type:	Journal article
Publication Title:	Cell Reports
Creators:	Elhassan, Y.S., Kluckova, K., Fletcher, R.S., Schmidt, M.S., Garten, A., Doig, C.L., Cartwright, D.M., Oakey, L., Burley, C.V., Jenkinson, N., Wilson, M., Lucas, S.J., Akerman, I., Seabright, A., Lai, Y., Tennant, D.A., Nightingale, P., Wallis, G.A., Manolopoulos, K.N., Brenner, C., Philp, A. and Lavery, G.G.
Publisher:	Cell Press
Date:	13 August 2019
Volume:	28
Number:	7
ISSN:	2211-1247
Identifiers:	Number Type 10.1016/j.celrep.2019.07.043 DOI 1215133 Other S2211124719309404 Publisher Item Identifier
Rights:	© 2019 the author(s). This is an open access article under the CC BY license http://creativecommons.org/licenses/by/4.0/
Divisions:	Schools > School of Science and Technology
Record created by:	Jonathan Gallacher
Date Added:	11 Nov 2019 11:28
Last Modified:	17 Dec 2019 15:10
URI:	https://irep.ntu.ac.uk/id/eprint/38196

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