title: NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice.
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.
authors.affiliation: Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Dongryeol
authors.initials: D
authors.lastname: Ryu
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule Zürich (ETHZ), 8093 Zurich, Switzerland.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Karim
authors.initials: K
authors.lastname: Gariani
authors.affiliation: Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Peiling
authors.initials: P
authors.lastname: Luan
authors.affiliation: Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Davide
authors.initials: D
authors.lastname: D'Amico
authors.affiliation: 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.
authors.forename: Eduardo R
authors.initials: ER
authors.lastname: Ropelle
authors.affiliation: Laboratory of Stem Cell Bioengineering, EPFL, 1015 Lausanne, Switzerland.
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Lutolf
authors.affiliation: 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.
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.affiliation: Metabolic Signaling, EPFL, 1015 Lausanne, Switzerland.
authors.forename: Kristina
authors.initials: K
authors.lastname: Schoonjans
authors.affiliation: 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.
authors.forename: Keir J
authors.initials: KJ
authors.lastname: Menzies
authors.affiliation: Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. kmenzies@uottawa.ca admin.auwerx@epfl.ch.
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming; D016922:Cellular Senescence / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D008136:Longevity / Q000187:drug effects* / Q000502:physiology; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D009136:Muscular Dystrophies / Q000628:therapy; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009243:NAD / Q000378:metabolism / Q000494:pharmacology*; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009536:Niacinamide / Q000031:analogs & derivatives / Q000378:metabolism; D018384:Oxidative Stress; D000091402:Prohibitins; D011726:Pyridinium Compounds; D012097:Repressor Proteins / Q000096:biosynthesis; D056811:Unfolded Protein Response / Q000187:drug effects
chemical_list: D000091402:Prohibitins; D011726:Pyridinium Compounds; D012097:Repressor Proteins; C018613:nicotinamide-beta-riboside; D009243:NAD; D009536:Niacinamide