The NAD-mitophagy axis in healthy longevity and in artificial intelligence-based clinical applications.

Journal: Mechanisms of ageing and development
PMID: 31812486

Abstract

Nicotinamide adenine dinucleotide (NAD) is an important natural molecule involved in fundamental biological processes, including the TCA cycle, OXPHOS, β-oxidation, and is a co-factor for proteins promoting healthy longevity. NAD depletion is associated with the hallmarks of ageing and may contribute to a wide range of age-related diseases including metabolic disorders, cancer, and neurodegenerative diseases. One of the central pathways by which NAD promotes healthy ageing is through regulation of mitochondrial homeostasis via mitochondrial biogenesis and the clearance of damaged mitochondria via mitophagy. Here, we highlight the contribution of the NAD-mitophagy axis to ageing and age-related diseases, and evaluate how boosting NAD levels may emerge as a promising therapeutic strategy to counter ageing as well as neurodegenerative diseases including Alzheimer's disease. The potential use of artificial intelligence to understand the roles and molecular mechanisms of the NAD-mitophagy axis in ageing is discussed, including possible applications in drug target identification and validation, compound screening and lead compound discovery, biomarker development, as well as efficacy and safety assessment. Advances in our understanding of the molecular and cellular roles of NAD in mitophagy will lead to novel approaches for facilitating healthy mitochondrial homoeostasis that may serve as a promising therapeutic strategy to counter ageing-associated pathologies and/or accelerated ageing.

Authors

  • Yahyah Aman
    Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1478, Lørenskog, Norway.
  • Johannes Frank
    Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1478, Lørenskog, Norway.
  • Sofie Hindkjær Lautrup
    Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1478, Lørenskog, Norway.
  • Adrian Matysek
    Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1478, Lørenskog, Norway; School of Pharmacy and Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, 40-055, Katowice, Poland.
  • Zhangming Niu
    Aladdin Healthcare Technologies Ltd., 24-26 Baltic Street West, London, EC1Y OUR, UK.
  • Guang Yang
    National Heart and Lung Institute, Imperial College London, London, UK.
  • Liu Shi
    Department of Psychiatry, University of Oxford, Oxford, UK.
  • Linda H Bergersen
    The Brain and Muscle Energy Group, Electron Microscopy Laboratory, Department of Oral Biology, University of Oslo, NO-0316, Oslo, Norway; Amino Acid Transporters, 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 Aging, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, DK-2200, Copenhagen N, Denmark; The Norwegian Centre on Healthy Ageing (NO-Age), Oslo, Norway.
  • Jon Storm-Mathisen
    Amino Acid Transporters, 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; The Norwegian Centre on Healthy Ageing (NO-Age), Oslo, Norway.
  • Lene J Rasmussen
    The Norwegian Centre on Healthy Ageing (NO-Age), Oslo, Norway; Center for Healthy Aging, Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, DK-2200, Copenhagen N, Denmark.
  • Vilhelm A Bohr
    Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, United States; The Norwegian Centre on Healthy Ageing (NO-Age), Oslo, Norway; Center for Healthy Aging, Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, DK-2200, Copenhagen N, Denmark.
  • Hilde Nilsen
    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.
  • Evandro F Fang
    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.

Keywords

External Resources

Popular Topics
Recent Journals