Targeting NAD+ in translational research to relieve diseases and conditions of metabolic stress and ageing

Brian C Gilmour; Ruben Gudmundsrud; Johannes Frank; Amund Hov; Sofie Lautrup; Yahyah Aman; Helge Røsjø; Charles Brenner; Mathias Ziegler; Ole-Bjørn Tysnes; Charalampos Tzoulis; Torbjørn Omland; Arne Søraas; Trygve Holmøy; Linda H Bergersen; Jon Storm-Mathisen; Hilde Nilsen; Evandro F Fang

doi:10.1016/j.mad.2020.111208

Targeting NAD⁺ in translational research to relieve diseases and conditions of metabolic stress and ageing

Mech Ageing Dev. 2020 Mar:186:111208. doi: 10.1016/j.mad.2020.111208. Epub 2020 Jan 15.

Authors

Brian C Gilmour¹, Ruben Gudmundsrud¹, Johannes Frank², Amund Hov¹, Sofie Lautrup², Yahyah Aman², Helge Røsjø³, Charles Brenner⁴, Mathias Ziegler⁵, Ole-Bjørn Tysnes⁶, Charalampos Tzoulis⁶, Torbjørn Omland⁷, Arne Søraas⁸, Trygve Holmøy⁹, Linda H Bergersen¹⁰, Jon Storm-Mathisen¹¹, Hilde Nilsen¹², Evandro F Fang¹³

Affiliations

¹ The Norwegian Centre on Healthy Ageing (NO-Age), Oslo, Norway.
² Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1478 Lørenskog, Norway.
³ Division of Research and Innovation, Akershus University Hospital, 1478 Lørenskog, Norway; Institute for Clinical Medicine, University of Oslo, Oslo, Norway.
⁴ Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
⁵ Department of Biomedicine, University of Bergen, 5009 Bergen, Norway.
⁶ Neuro-SysMed, Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.
⁷ Institute for Clinical Medicine, University of Oslo, Oslo, Norway; Department of Cardiology, Division of Medicine, Akershus University Hospital, 1478 Lørenskog, Norway.
⁸ Department of Microbiology, Oslo University Hospital, Oslo, Norway.
⁹ Department of Neurology, Akershus University Hospital, Lørenskog, Norway; Department of Clinical Medicine, University of Oslo, Oslo, Norway.
¹⁰ The Norwegian Centre on Healthy Ageing (NO-Age), Oslo, Norway; The Brain and Muscle Energy Group, Electron Microscopy Laboratory, Department of Oral Biology, University of Oslo, NO-0316 Oslo, Norway; Synaptic Neurochemistry and Amino Acid Transporters Labs, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences (IMB) and Healthy Brain Ageing Centre (SERTA), University of Oslo, NO-0317 Oslo, Norway; Center for Healthy Ageing, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
¹¹ The Norwegian Centre on Healthy Ageing (NO-Age), Oslo, Norway; Synaptic Neurochemistry and Amino Acid Transporters Labs, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences (IMB) and Healthy Brain Ageing Centre (SERTA), University of Oslo, NO-0317 Oslo, Norway.
¹² Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1478 Lørenskog, Norway; The Norwegian Centre on Healthy Ageing (NO-Age), Oslo, Norway.
¹³ Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1478 Lørenskog, Norway; The Norwegian Centre on Healthy Ageing (NO-Age), Oslo, Norway. Electronic address: e.f.fang@medisin.uio.no.

PMID: 31953124
DOI: 10.1016/j.mad.2020.111208

Abstract

Nicotinamide adenine dinucleotide (NAD⁺) plays a fundamental role in life and health through the regulation of energy biogenesis, redox homeostasis, cell metabolism, and the arbitration of cell survival via linkages to apoptosis and autophagic pathways. The importance of NAD⁺ in ageing and healthy longevity has been revealed from laboratory animal studies and early-stage clinical testing. While basic researchers and clinicians have investigated the molecular mechanisms and translation potential of NAD⁺, there are still major gaps in applying laboratory science to design the most effective trials. This mini-review was based on the programme and discussions of the 3rd NO-Age Symposium held at the Akershus University Hospital, Norway on the 28th October 2019. This symposium brought together leading basic researchers on NAD⁺ and clinicians who are leading or are going to perform NAD⁺ augmentation-related clinical studies. This meeting covered talks about NAD⁺ synthetic pathways, subcellular homeostasis of NAD⁺, the benefits of NAD⁺ augmentation from maternal milk to offspring, current clinical trials of the NAD⁺ precursor nicotinamide riboside (NR) on Ataxia-Telangiectasia (A-T), Parkinson's disease (PD), post-sepsis fatigue, as well as other potential NR-based clinical trials. Importantly, a consensus is emerging with respect to the design of clinical trials in order to measure meaningful parameters and ensure safety.

Keywords: Ageing; Alzheimer’s disease; Clinical trials; NAD(+); Parkinson’s disease.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Aging / physiology*
Humans
NAD / metabolism*
Translational Research, Biomedical* / methods
Translational Research, Biomedical* / trends

Substances

NAD