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

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@article{03d8074b9e0243d69239d7a96b146f6d,
title = "Nicotinamide riboside augments the aged human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures",
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 = "nicotinamide adenine dinucleotide, metabolism, aging, inflammation, cell adhesion",
author = "Elhassan, {Yasir S.} and Katarina Kluckova and Fletcher, {Rachel S.} and Schmidt, {Mark S.} and Antje Garten and Doig, {Craig L.} and Cartwright, {David M.} and Lucy Oakey and Burley, {Claire V.} and Ned Jenkinson and Martin Wilson and Lucas, {Samuel J.e.} and Ildem Akerman and Alex Seabright and Yu-chiang Lai and Tennant, {Daniel A.} and Peter Nightingale and Wallis, {Gareth A.} and Manolopoulos, {Konstantinos N.} and Charles Brenner and Andrew Philp and Lavery, {Gareth G.}",
year = "2019",
month = aug,
day = "13",
doi = "10.1016/j.celrep.2019.07.043",
language = "English",
volume = "28",
pages = "1717--1728.e6",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Elsevier",
number = "7",

}

RIS

TY - JOUR

T1 - Nicotinamide riboside augments the aged human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures

AU - Elhassan, Yasir S.

AU - Kluckova, Katarina

AU - Fletcher, Rachel S.

AU - Schmidt, Mark S.

AU - Garten, Antje

AU - Doig, Craig L.

AU - Cartwright, David M.

AU - Oakey, Lucy

AU - Burley, Claire V.

AU - Jenkinson, Ned

AU - Wilson, Martin

AU - Lucas, Samuel J.e.

AU - Akerman, Ildem

AU - Seabright, Alex

AU - Lai, Yu-chiang

AU - Tennant, Daniel A.

AU - Nightingale, Peter

AU - Wallis, Gareth A.

AU - Manolopoulos, Konstantinos N.

AU - Brenner, Charles

AU - Philp, Andrew

AU - Lavery, Gareth G.

PY - 2019/8/13

Y1 - 2019/8/13

N2 - 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.

AB - 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.

KW - nicotinamide adenine dinucleotide

KW - metabolism

KW - aging

KW - inflammation

KW - cell adhesion

U2 - 10.1016/j.celrep.2019.07.043

DO - 10.1016/j.celrep.2019.07.043

M3 - Article

C2 - 31412242

VL - 28

SP - 1717-1728.e6

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 7

ER -