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NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice.

  • Zhang H Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
  • Ryu D Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
  • Wu Y Department of Biology, Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule Zürich (ETHZ), 8093 Zurich, Switzerland.
  • Gariani K Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
  • Wang X Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
  • Luan P Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
  • D'Amico D Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
  • Ropelle ER Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. Laboratory of Molecular Biology of Exercise, School of Applied Science, University of Campinas, CEP 13484-350 Limeira, São Paulo, Brazil.
  • Lutolf MP Laboratory of Stem Cell Bioengineering, EPFL, 1015 Lausanne, Switzerland.
  • Aebersold R Department of Biology, Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule Zürich (ETHZ), 8093 Zurich, Switzerland. Faculty of Science, University of Zurich, 8057 Zurich, Switzerland.
  • Schoonjans K Metabolic Signaling, EPFL, 1015 Lausanne, Switzerland.
  • Menzies KJ Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. Interdisciplinary School of Health Sciences, University of Ottawa Brain and Mind Research Institute, 451 Smyth Road, K1H 8M5 Ottawa, Ontario, Canada. kmenzies@uottawa.ca admin.auwerx@epfl.ch.
  • Auwerx J Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. kmenzies@uottawa.ca admin.auwerx@epfl.ch.
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  • 2016-04-30
Published in:
  • Science (New York, N.Y.). - 2016
Animals
Cellular Reprogramming
Cellular Senescence
Disease Models, Animal
Longevity
Melanocytes
Mice
Mice, Inbred C57BL
Mice, Inbred mdx
Mitochondria
Muscular Dystrophies
Myoblasts, Skeletal
NAD
Neural Stem Cells
Niacinamide
Oxidative Stress
Repressor Proteins
Unfolded Protein Response
English Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD(+)) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence. Treatment with the NAD(+) precursor nicotinamide riboside (NR) induced the mitochondrial unfolded protein response and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice. NR also prevented MuSC senescence in the mdx (C57BL/10ScSn-Dmd(mdx)/J) mouse model of muscular dystrophy. We furthermore demonstrate that NR delays senescence of neural SCs and melanocyte SCs and increases mouse life span. Strategies that conserve cellular NAD(+) may reprogram dysfunctional SCs and improve life span in mammals.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/168071
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