Publication Date:
2016-04-30
Description:
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 impact 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 (UPRmt) and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice. NR also prevented MuSC senescence in the Mdx mouse model of muscular dystrophy. We furthermore demonstrate that NR delays senescence of neural SCs (NSCs) and melanocyte SCs (McSCs), and increased mouse lifespan. Strategies that conserve cellular NAD+ may reprogram dysfunctional SCs and improve lifespan in mammals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Hongbo -- Ryu, Dongryeol -- Wu, Yibo -- Gariani, Karim -- Wang, Xu -- Luan, Peiling -- D'Amico, Davide -- Ropelle, Eduardo R -- Lutolf, Matthias P -- Aebersold, Ruedi -- Schoonjans, Kristina -- Menzies, Keir J -- Auwerx, Johan -- New York, N.Y. -- Science. 2016 Apr 28. pii: aaf2693.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland. ; Department of Biology, Institute of Molecular Systems Biology, Eidgenossische Technische Hochschule Zurich (ETHZ), Zurich 8093, Switzerland. ; Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland. Laboratory of Molecular Biology of Exercise, School of Applied Science, University of Campinas, CEP 13484-350 Limeira, Sao Paulo, Brazil. ; Laboratory of Stem Cell Bioengineering, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland. ; Department of Biology, Institute of Molecular Systems Biology, Eidgenossische Technische Hochschule Zurich (ETHZ), Zurich 8093, Switzerland. Faculty of Science, University of Zurich, Zurich, Switzerland. ; Metabolic Signaling, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland. ; Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland. Interdisciplinary School of Health Sciences, University of Ottawa Brain and Mind Research Institute, 451 Smyth Rd, K1H 8M5, Ottawa, Canada. kmenzies@uottawa.ca admin.auwerx@epfl.ch. ; Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland. kmenzies@uottawa.ca admin.auwerx@epfl.ch.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27127236" target="_blank"〉PubMed〈/a〉
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
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Chemistry and Pharmacology
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Computer Science
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Medicine
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Natural Sciences in General
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Physics
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