Epigenetics of Aging

Trygve O. TollefsbolEditor

Epigenetics of Aging

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EditorTrygve O. TollefsbolDepartment of BiologyUniversity of Alabama at Birmingham1300 University Blvd.Birmingham, AL 35294-1170USAtrygve@uab.edu

ISBN 978-1-4419-0638-0 e-ISBN 978-1-4419-0639-7DOI 10.1007/978-1-4419-0639-7Springer New York Dordrecht Heidelberg London

Library of Congress Control Number: 2009932905

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Preface

Numerous studies have indicated that epigenetic mechanisms may play a majorrole in both cellular and organismal aging. These epigenetic processes not onlyinclude DNA methylation and histone modifications but also extend to many otherepigenetic mediators such as the polycomb group proteins, chromosomal positioneffects, and noncoding RNA. The topics of this seminal book on aging epigeneticsrange from fundamental changes in DNA methylation in aging to the most recentresearch on intervention into epigenetic modifications to modulate the aging pro-cess and age-associated disorders. The major topics of aging epigenetics coveredin this book are (1) DNA methylation and histone modifications in aging, (2) otherepigenetic processes and aging, (3) impact of epigenetics on aging, (4) epigenet-ics of age-related diseases, (5) epigenetic interventions and aging, and (6) futuredirections/perspectives in aging epigenetics.

The most studied of epigenetic processes, DNA methylation, has been associatedwith cellular aging and aging of organisms for many years. It is now apparent thatboth global and gene-specific alterations occur not only in DNA methylation duringaging but also in several types of histone modifications. Many epigenetic aberrationsmay have an impact on aging processes through control of telomerase, modificationsof telomeres, and epigenetic drift. The latter is evident in the recent studies of agingmonozygotic twins.

Numerous age-related diseases are affected by epigenetic mechanisms. Forexample, recent studies have shown that DNA methylation is altered in Alzheimer’sdisease and autoimmunity. Other prevalent diseases that have been associated withage-related epigenetic changes include cancer and osteoarthritis. Epigenetic alter-ations appear to have an effect on several of the progeroid syndromes of prematureaging as well. Moreover, the impact of dietary or drug intervention into epigeneticprocesses as they affect normal aging or age-related diseases is becoming increas-ingly feasible.

This book is intended for those with interests ranging from the fundamental basisof aging to interventions in slowing the aging process or treating age-related disor-ders. The study of epigenetics as it relates to aging and age-related diseases is arelatively new field that is showing considerable promise in revolutionizing how theaging process is viewed. The purpose of this book on aging epigenetics is to provide

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coverage of not only established aspects of epigenetics as applied to the aging pro-cess but also new approaches and perceptions in this important area of research.

Trygve O. TollefsbolBirmingham, AL, USA

Contents

Epigenetics and the Aging Process . . . . . . . . . . . . . . . . . . . . . 1Trygve O. Tollefsbol

Part I DNA Methylation and Histone Modifications in Aging

Age-Related Genomic Hypomethylation . . . . . . . . . . . . . . . . . . 11Igor P. Pogribny and Boris F. Vanyushin

Gene-Specific Hypermethylation in Aging . . . . . . . . . . . . . . . . . 29Adebayo D. Akintola and Alan R. Parrish

Aging and Non-sirtuin Histone Modifications . . . . . . . . . . . . . . . 41Inga Kadish

Sirtuins and Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51Yuqing Dong and Sige Zou

Chromatin in Senescent Cells: A Conduit for the Anti-AgingEffects of Wnt Signaling? . . . . . . . . . . . . . . . . . . . . . . . . . . 77Gowrishankar Banumathy and Peter D. Adams

S-Adenosylmethionine: Simple Agent of Methylation and Secretto Aging and Metabolism? . . . . . . . . . . . . . . . . . . . . . . . . . 107Wil A.M. Loenen

Part II Other Epigenetic Processes and Aging

Polycomb Group of Genes and the Epigenetics of Aging . . . . . . . . . 135Krishnaveni Mishra and Rakesh K. Mishra

Chromosomal Position Effect and Aging . . . . . . . . . . . . . . . . . . 151Eric Gilson and Frédérique Magdinier

Noncoding RNA for Presymptomatic Diagnosisof Age-Dependent Disease . . . . . . . . . . . . . . . . . . . . . . . . . . 177Eugenia Wang

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Part III Impact of Epigenetics on Aging

Telomerase Control by Epigenetic Processes in Cellular Senescence . . 191Huaping Chen and Trygve O. Tollefsbol

Telomeres, Epigenetics, and Aging . . . . . . . . . . . . . . . . . . . . . 205J. Arturo Londoño-Vallejo

Contributions of Tumor Suppressors to the EpigeneticRegulation of Aging Cells . . . . . . . . . . . . . . . . . . . . . . . . . . 227Pinaki Bose, Amudha Ganapathy, and Karl Riabowol

Epigenetic Drift and Aging . . . . . . . . . . . . . . . . . . . . . . . . . 257Ester Lara, Vincenzo Calvanese, and Mario F. Fraga

Role of Epigenetics in Age-Related Long-Term Memory Loss . . . . . . 275J. Tyson DeAngelis and Trygve O. Tollefsbol

Part IV Epigenetics of Age-Related Diseases

The Epigenetics of Age-Related Cancers . . . . . . . . . . . . . . . . . . 285Kristen H. Taylor, Lynda B. Bennett, Gerald L. Arthur,Huidong Shi,and Charles W. Caldwell

DNA Methylation and Alzheimer’s Disease . . . . . . . . . . . . . . . . 315Thomas van Groen

DNA Methylation, Age-Related Immune Defects, and Autoimmunity . . 327Jörg J. Goronzy, Guangjin Li, and Cornelia M. Weyand

Epigenetic Silencing of Progeroid Syndromes . . . . . . . . . . . . . . . 345Ruben Agrelo

DNA Methylation and Osteoarthritis . . . . . . . . . . . . . . . . . . . . 371Helmtrud I. Roach

Part V Epigenetic Interventions and Aging

Histone-Modifying Drugs in Aging . . . . . . . . . . . . . . . . . . . . . 395Ulrich Mahlknecht and Barbara Zschoernig

Dietary Effect on Epigenetics During the Aging Process . . . . . . . . . 407Yuanyuan Li and Trygve O. Tollefsbol

Environmental Effects on Age-Associated Epigenetics . . . . . . . . . . 417Sabita N. Saldanha, Ashley McCollum, and Trygve O. Tollefsbol

Part VI Future Directions/Perspectives

Future Directions in Research on the Epigenetics of Aging . . . . . . . . 433Huidong Shi and Charles W. Caldwell

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Perspectives in Aging and Epigenetics . . . . . . . . . . . . . . . . . . . 447Robin Holliday

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 457

Contributors

Peter D. Adams Fox Chase Cancer Center, Philadelphia, PA 19111, USA,peter.adams@fccc.edu

Ruben Agrelo Research Institute of Molecular Pathology (IMP), Dr. Bohr-Gasse7, 1030 Vienna, Austria, agrelo@imp.univie.ac.at, ragrelo@adinet.com.uy

Adebayo D. Akintola Systems Biology and Translational Medicine, Texas A&MHealth Science Center, College of Medicine, College Station, TX 77847-1114,USA

Gerald L. Arthur Department of Pathology and Anatomical Sciences, EllisFischel Cancer Center, University of Missouri School of Medicine, Columbia,MO 65212, USA

Gowrishankar Banumathy Fox Chase Cancer Center, Philadelphia, PA19111, USA

Lynda B. Bennett Department of Pathology and Anatomical Sciences, EllisFischel Cancer Center, University of Missouri School of Medicine, Columbia,MO 65212, USA

Pinaki Bose Department of Biochemistry and Molecular Biology, SouthernAlberta Cancer Research Institute, University of Calgary, 3330 Hospital Drive NW,Calgary, Alberta, Canada 42N 4N1

Charles W. Caldwell Department of Pathology and Anatomical Sciences, EllisFischel Cancer Center, University of Missouri School of Medicine, Columbia,MO 65212, USA, caldwellc@health.missouri.edu

Vincenzo Calvanese Department of Immunology and Oncology, National Centerfor Biotechnology, CNB-CSIC, Cantoblanco, Madrid E-28049, Spain

Huaping Chen Department of Biology, 175 CH, 1300 University Boulevard,University of Alabama, Birmingham, AL 35294-1170, USA

J. Tyson DeAngelis Department of Biology, 175 CH, 1300 University Boulevard,University of Alabama, Birmingham, AL 35294-1170, USA

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xii Contributors

Yuqing Dong Department of Biological Sciences, Clemson University, Clemson,SC 29634, USA,

Mario F. Fraga Department of Immunology and Oncology, National Center forBiotechnology, CNB-CSIC, Cantoblanco, Madrid E-28049, Spain; Laboratorio deEpigenética del Cáncer, Instituto Universitario de Oncología del Principado deAsturias (IUOPA), Universidad de Oviedo, Oviedo, Spain, mffraga@cnio.es

Amudha Ganapathy Department of Biochemistry and Molecular Biology,Southern Alberta Cancer Research Institute, University of Calgary, 3330 HospitalDrive NW, Calgary, Alberta, Canada 42N 4N1

Eric Gilson Laboratoire de Biologie Moleculaire de la Cellule, CNRS UMR5239, Ecole Normale Superieure de Lyon, UCBL1, IFR 128, 46 allee d-Italie,69364 Lyon Cedex 07, France

Jorg J. Goronzy Department of Medicine, Kathleen B. and Mason I. LowanceCenter for Human Immunology, Emory University School of Medicine, WoodruffMemorial Research Building, Atlanta, GA, USA, jgoronz@emory.edu

Robin Holliday Australian Academy of Science, Canberra, Australia,randl.holliday@bigpond.com

Inga Kadish Department of Cell Biology, THT 912, University of Alabama,Birmingham, AL 35294-0006, USA; Center for Aging, University of Alabama,Birmingham, AL, USA, ikadisha@uab.edu

Ester Lara Department of Immunology and Oncology, National Center forBiotechnology, CNB-CSIC, Cantoblanco, Madrid E-28049, Spain

Guangjin Li Department of Medicine, Kathleen B. and Mason I. Lowance Centerfor Human Immunology, Emory University School of Medicine, WoodruffMemorial Research Building, Atlanta, GA, USA

Yuanyuan Li Department of Biology, 175 CH, 1300 University Boulevard,University of Alabama, Birmingham, AL 35294-1170, USA

Wil A.M. Loenen Department of Toxicogenetics, Leiden University MedicalCentre, Einthovenweg 20, Leiden, The Netherlands, w.a.m.loenen@lumc.nl

J. Arturo Loñdono-Vallejo UMR7147, Institut Curie-UPMC-CNRS, 26, rued’Ulm, 75248 Paris, France, arturo.londono@curie.fr

Frederique Magdinier Laboratoire de Biologie Moleculaire de la Cellule, CNRSUMR 5239, Ecole Normale Superieure de Lyon, UCBL1, IFR 128, 46 alleed-Italie, 69364 Lyon Cedex 07, France, frederique.magdinier@ens-lyon.fr

Ulrich Mahlknecht Department of Internal Medicine, Saarland UniversityMedical Center, Division of Immunotherapy and Gene Therapy, Jose CarrerasCenter for Immunotherapy and Gene Therapy, D-66421 Homburg/Saar, Germany,ulrich.mahlknecht@uks.eu

Contributors xiii

Ashley McCollum Alabama State University, Montgomery, AL 36104, USA

Krishnaveni Mishra Department of Biochemistry, School of Life Sciences,University of Hyderabad, Hyderabad, India, kmsl@uohyd.ernet.in

Rakesh K. Mishra Centre for Cellular and Molecular Biology, Uppal Road,Hyderabad 500007, India, mishra@ccmb.res.in

Alan R. Parrish Systems Biology and Translational Medicine, Texas A&MHealth Science Center, College of Medicine, College Station, TX 77847-1114,USA, parrish@medicine.tamhsc.edu

Igor P. Pogribny Division of Biochemical Toxicology, National Center forToxicological Research, Jefferson, AR 72079, USA, igor.pogribny@fda.hhs.gov

Karl Riabowol Departments of Biochemistry & Molecular Biology, SouthernAlberta Cancer Research Institute, University of Calgary, 3330 Hospital Drive NW,Calgary, Alberta, Canada 42 N 4N1; Departments of Oncology, Southern AlbertaCancer Research Institute, University of Calgary, 3330 Hospital DriveNW, Calgary, Alberta, Canada 42 N 4N1, karl@ucalgary.ca

Helmtrud I. Roach Bone and Joint Research Group, Southampton GeneralHospital, University of Southampton, Southampton, SO16 6YD, UK,h.roach@southampton.ac.uk

Sabita N. Saldanha Department of Biology, 175 CH, 1300 University Boulevard,University of Alabama, Birmingham, AL 35294-1170, USA

Huidong Shi Department of Pathology and Anatomical Sciences, Ellis FischelCancer Center, University of Missouri School of Medicine, Columbia, MO 65212,USA

Kristen H. Taylor Department of Pathology and Anatomical Sciences, EllisFischel Cancer Center, University of Missouri School of Medicine, Columbia, MO65212, USA

Trygve O. Tollefsbol Department of Biology, University of Alabama,Birmingham, AL 35294, USA; Center for Aging, University of Alabama,Birmingham, AL 35294, USA; Comprehensive Cancer Center, University ofAlabama, Birmingham, AL 35294, USA; Clinical Nutrition Research Center,University of Alabama, Birmingham, AL 35294, USA, trygve@uab.edu

Thomas van Groen Department of Cell Biology, THT 912, University ofAlabama, Birmingham, AL 35294-0006, USA; Department of Neurobiology,University of Alabama, Birmingham, AL. USA, vangroen@uab.edu

Boris F. Vanyushin Belozersky Institute of Physico-Chemical Biology,Lomonosov Moscow State University, Moscow 119899, Russia,vanyush@belozersky.msu.ru

xiv Contributors

Eugenia Wang Department of Biochemistry, , University of Louisville School ofMedicine, Louisville, KY 40202, USA; Gheens Center on Aging, University ofLouisville School of Medicine, Louisville, KY 40202, USA,eugenia.wang@louisville.edu

Cornelia M. Weyand Department of Medicine, Kathleen B. and Mason I.Lowance Center for Human Immunology, Emory University School of Medicine,Woodruff Memorial Research Building, Atlanta, GA, USA

Sige Zou Functional Genomics Unit, Laboratory of Experimental Gerontology,National Institute on Aging, Baltimore, MD 21224, USA, zous@grc.nia.nih.gov

Barbara Zschoernig Department of Internal Medicine, Saarland UniversityMedical Center, Division of Immunotherapy and Gene Therapy, Jose CarrerasCenter for Immunotherapy and Gene Therapy, D-66421 Homburg/Saar, Germany