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

doi:10.1126/science.aaf2693

. 2016 Jun 17;352(6292):1436-43.

doi: 10.1126/science.aaf2693. Epub 2016 Apr 28.

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

Affiliations

¹ Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
² Department of Biology, Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule Zürich (ETHZ), 8093 Zurich, Switzerland.
³ 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.
⁴ Laboratory of Stem Cell Bioengineering, EPFL, 1015 Lausanne, Switzerland.
⁵ 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.
⁶ Metabolic Signaling, EPFL, 1015 Lausanne, Switzerland.
⁷ 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. [email protected] [email protected].
⁸ Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. [email protected] [email protected].

PMID: 27127236
DOI: 10.1126/science.aaf2693

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

Hongbo Zhang et al. Science. 2016.

. 2016 Jun 17;352(6292):1436-43.

doi: 10.1126/science.aaf2693. Epub 2016 Apr 28.

Authors

Affiliations

¹ Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
² Department of Biology, Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule Zürich (ETHZ), 8093 Zurich, Switzerland.
³ 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.
⁴ Laboratory of Stem Cell Bioengineering, EPFL, 1015 Lausanne, Switzerland.
⁵ 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.
⁶ Metabolic Signaling, EPFL, 1015 Lausanne, Switzerland.
⁷ 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. [email protected] [email protected].
⁸ Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. [email protected] [email protected].

PMID: 27127236
DOI: 10.1126/science.aaf2693

Abstract

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.

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Comment in

Ageing: The yin and yang of mitochondrial dysfunction.
Baumann K. Baumann K. Nat Rev Mol Cell Biol. 2016 May 23;17(6):331. doi: 10.1038/nrm.2016.71. Nat Rev Mol Cell Biol. 2016. PMID: 27211483 No abstract available.
CELL METABOLISM. The resurgence of NAD⁺.
Guarente L. Guarente L. Science. 2016 Jun 17;352(6292):1396-7. doi: 10.1126/science.aag1718. Science. 2016. PMID: 27313027 No abstract available.
Restoring stem cells - all you need is NAD(.).
Wu LE, Sinclair DA. Wu LE, et al. Cell Res. 2016 Sep;26(9):971-2. doi: 10.1038/cr.2016.80. Epub 2016 Jun 24. Cell Res. 2016. PMID: 27339086 Free PMC article.

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

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

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