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Cell Metab. 2018 Mar 6;27(3):513-528. doi: 10.1016/j.cmet.2017.11.002. Epub 2017 Dec 14.

NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR.

Author information

1
Center for Human Nutrition, Division of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, Campus Box 8103, 660 South Euclid Avenue, St. Louis, MO 63110, USA. Electronic address: jyoshino@wustl.edu.
2
Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, 12-114 Smilow Center for Translational Research, 3400 Civic Center Boulevard, Building 421, Philadelphia, PA 19104-5160, USA. Electronic address: baur@pennmedicine.upenn.edu.
3
Department of Developmental Biology, Department of Medicine (Joint), Washington University School of Medicine, Campus Box 8103, 660 South Euclid Avenue, St. Louis, MO 63110, USA; Japan Agency for Medical Research and Development, Project for Elucidating and Controlling Mechanisms of Aging and Longevity, Tokyo, Japan. Electronic address: imaishin@wustl.edu.

Abstract

Research on the biology of NAD+ has been gaining momentum, providing many critical insights into the pathogenesis of age-associated functional decline and diseases. In particular, two key NAD+ intermediates, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), have been extensively studied over the past several years. Supplementing these NAD+ intermediates has shown preventive and therapeutic effects, ameliorating age-associated pathophysiologies and disease conditions. Although the pharmacokinetics and metabolic fates of NMN and NR are still under intensive investigation, these NAD+ intermediates can exhibit distinct behavior, and their fates appear to depend on the tissue distribution and expression levels of NAD+ biosynthetic enzymes, nucleotidases, and presumptive transporters for each. A comprehensive concept that connects NAD+ metabolism to the control of aging and longevity in mammals has been proposed, and the stage is now set to test whether these exciting preclinical results can be translated to improve human health.

KEYWORDS:

NAD(+); NAMPT; NMN; NMN adenylyltransferases; NMNATs; NR; NR kinases; NRKs; PARPs; aging; metabolism; nicotinamide adenine dinucleotide; nicotinamide mononucleotide; nicotinamide phosphoribosyltransferase; nicotinamide riboside; poly-ADP-ribose polymerases; sirtuins

PMID:
29249689
PMCID:
PMC5842119
[Available on 2019-03-06]
DOI:
10.1016/j.cmet.2017.11.002

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