title: The epigenetics of aging and neurodegeneration.
abstract: Epigenetics is a quickly growing field encompassing mechanisms regulating gene expression that do not involve changes in the genotype. Epigenetics is of increasing relevance to neuroscience, with epigenetic mechanisms being implicated in brain development and neuronal differentiation, as well as in more dynamic processes related to cognition. Epigenetic regulation covers multiple levels of gene expression; from direct modifications of the DNA and histone tails, regulating the level of transcription, to interactions with messenger RNAs, regulating the level of translation. Importantly, epigenetic dysregulation currently garners much attention as a pivotal player in aging and age-related neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, where it may mediate interactions between genetic and environmental risk factors, or directly interact with disease-specific pathological factors. We review current knowledge about the major epigenetic mechanisms, including DNA methylation and DNA demethylation, chromatin remodeling and non-coding RNAs, as well as the involvement of these mechanisms in normal aging and in the pathophysiology of the most common neurodegenerative diseases. Additionally, we examine the current state of epigenetics-based therapeutic strategies for these diseases, which either aim to restore the epigenetic homeostasis or skew it to a favorable direction to counter disease pathology. Finally, methodological challenges of epigenetic investigations and future perspectives are discussed.
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands.
authors.forename: Roy
authors.initials: R
authors.lastname: Lardenoije
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands.
authors.forename: Artemis
authors.initials: A
authors.lastname: Iatrou
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands.
authors.forename: Gunter
authors.initials: G
authors.lastname: Kenis
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Genopode Building, 1015 Lausanne-Dorigny, Switzerland.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kompotis
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands.
authors.forename: Harry W M
authors.initials: HW
authors.lastname: Steinbusch
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands; L.J. Roberts Alzheimer's Disease Center, Banner Sun Health Research Institute, 10515 W. Santa Fe Drive, Sun City, AZ 85351, USA.
authors.forename: Diego
authors.initials: D
authors.lastname: Mastroeni
authors.affiliation: L.J. Roberts Alzheimer's Disease Center, Banner Sun Health Research Institute, 10515 W. Santa Fe Drive, Sun City, AZ 85351, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Coleman
authors.affiliation: Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Lemere
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Hof
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands; Laboratory of Translational Neuroscience, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Fuechsleinstrasse 15, 97080 Wuerzburg, Germany.
authors.forename: Daniel L A
authors.initials: DL
authors.lastname: van den Hove
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands. Electronic address: b.rutten@maastrichtuniversity.nl.
authors.forename: Bart P F
authors.initials: BP
authors.lastname: Rutten
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D019636:Neurodegenerative Diseases / Q000235:genetics*; D022661:RNA, Untranslated / Q000378:metabolism
chemical_list: D022661:RNA, Untranslated
keywords: Aging; Alzheimer's disease; Epigenetics; Huntington's disease; Neurodegeneration; Parkinson's disease