A high-fat diet and NAD(+) activate Sirt1 to rescue premature aging in cockayne syndrome

Cell Metabolism
Morten Scheibye-KnudsenVilhelm A Bohr

Abstract

Cockayne syndrome (CS) is an accelerated aging disorder characterized by progressive neurodegeneration caused by mutations in genes encoding the DNA repair proteins CS group A or B (CSA or CSB). Since dietary interventions can alter neurodegenerative processes, Csb(m/m) mice were given a high-fat, caloric-restricted, or resveratrol-supplemented diet. High-fat feeding rescued the metabolic, transcriptomic, and behavioral phenotypes of Csb(m/m) mice. Furthermore, premature aging in CS mice, nematodes, and human cells results from aberrant PARP activation due to deficient DNA repair leading to decreased SIRT1 activity and mitochondrial dysfunction. Notably, β-hydroxybutyrate levels are increased by the high-fat diet, and β-hydroxybutyrate, PARP inhibition, or NAD(+) supplementation can activate SIRT1 and rescue CS-associated phenotypes. Mechanistically, CSB can displace activated PARP1 from damaged DNA to limit its activity. This study connects two emerging longevity metabolites, β-hydroxybutyrate and NAD(+), through the deacetylase SIRT1 and suggests possible interventions for CS.

References

Oct 4, 2000·The Journal of Biological Chemistry·J M PleschkeF R Althaus
Mar 30, 2004·Annals of Neurology·Patrick G SullivanJong M Rho
Jun 27, 2006·Trends in Genetics : TIG·Jean-Philippe Lainé, Jean-Marc Egly
Jun 30, 2006·Annals of Neurology·Kristopher J BoughRaymond J Dingledine
Jan 31, 2007·Stroke; a Journal of Cerebral Circulation·Aaron M HambyRaymond A Swanson
Oct 11, 2008·Brain Research Reviews·Marwan MaaloufMark P Mattson
Nov 22, 2008·Nature Reviews. Molecular Cell Biology·Philip C Hanawalt, Graciela Spivak
Feb 4, 2009·Molecular and Cellular Biology·Natalia PediconiMassimo Levrero
Aug 4, 2009·Mechanisms of Ageing and Development·Karen M WeidenheimIsabelle Rapin
Jun 5, 2010·AJNR. American Journal of Neuroradiology·M KoobJ-L Dietemann
Mar 8, 2012·Nature Reviews. Molecular Cell Biology·Riekelt H HoutkooperJohan Auwerx
Mar 13, 2012·Pathology·Robin FraserDavid G Le Couteur
Dec 21, 2012·The Journal of Cell Biology·Hervé MenoniWim Vermeulen
Jan 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Mihaela RobuGirish M Shah
Feb 26, 2013·Mechanisms of Ageing and Development·Morten Scheibye-KnudsenVilhelm A Bohr

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Citations

Dec 1, 2015·Journal of Molecular Biology·Teruaki Iyama, David M Wilson
Jul 1, 2015·Proceedings of the National Academy of Sciences of the United States of America·Christopher E WallRonald M Evans
Oct 31, 2015·Annual Review of Pharmacology and Toxicology·Wilbert P VermeijJoris Pothof
Dec 3, 2015·Molecular Cell·Jennine M Dawicki-McKennaJohn M Pascal
Jun 24, 2015·Proceedings of the National Academy of Sciences of the United States of America·Leizhen WeiLi Lan
Mar 5, 2016·Molecular Cell·Nuo SunToren Finkel
Dec 3, 2014·Cell Metabolism·Leonard Guarente
Mar 10, 2016·Nature Reviews. Molecular Cell Biology·Evandro Fei FangVilhelm A Bohr
Aug 27, 2015·Medical Hypotheses·Mark F McCartyJames H O'Keefe
Sep 12, 2015·Annual Review of Cell and Developmental Biology·Ryan JankeJasper Rine
Sep 19, 2015·Nature Reviews. Cancer·Angeliki Chalkiadaki, Leonard Guarente
Mar 18, 2016·Human Molecular Genetics·Weiliang TangRaymond J Monnat
May 24, 2015·DNA Repair·Mansour AkbariVilhelm A Bohr
May 23, 2015·Future Medicinal Chemistry·Julien LancelotRaymond J Pierce
Apr 25, 2015·Protein & Cell·Shrestha Ghosh, Zhongjun Zhou
Feb 18, 2015·Nature Chemical Biology·Florian J Bock, Paul Chang
May 11, 2016·International Journal of Molecular Sciences·Mei-Ren PanWen-Chun Hung
Jun 30, 2016·Ageing Research Reviews·João Pinto da CostaTeresa Rocha-Santos
Oct 21, 2016·Biochimica Et Biophysica Acta·Yue Yang, Anthony A Sauve
Sep 14, 2016·Maturitas·Joop S E LavenJan H J Hoeijmakers
Oct 22, 2016·Ageing Research Reviews·Ajoy C KarikkinethVilhelm A Bohr
Aug 16, 2016·Cell·Carlos López-OtínGuido Kroemer
Oct 21, 2016·Nature Reviews. Molecular Cell Biology·Michael S Bonkowski, David A Sinclair
Oct 13, 2016·Cell Metabolism·Leonard Guarente
Nov 3, 2016·Proceedings of the National Academy of Sciences of the United States of America·Morten Scheibye-KnudsenVilhelm A Bohr
Oct 16, 2016·Journal of Neurochemistry·Krisztina MarosiMark P Mattson
Feb 2, 2017·Cell Cycle·Deborah L CroteauVilhelm A Bohr
Apr 27, 2017·International Journal of Molecular Sciences·Víctor MicóLidia Daimiel
Feb 16, 2018·The Journal of Clinical Investigation·Mehdi TouatSophie Postel-Vinay
Dec 3, 2017·Archives of Toxicology·Jan M F FischerAswin Mangerich
Oct 28, 2017·Antioxidants & Redox Signaling·Jessica M BerthiaumeMariana G Rosca
Dec 1, 2017·Frontiers in Molecular Neuroscience·Marwa ElaminPaola Sacchetti
Nov 28, 2017·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Fiqri D KhaidizarYasumasa Bessho
Mar 7, 2017·World Journal of Experimental Medicine·Abu Shufian Ishtiaq AhmedKin-Hing William Lau
Dec 23, 2017·Cell Biology International·Mateus Prates Mori, Nadja Cristhina de Souza-Pinto

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