title: Epigenetic modifications in mouse cerebellar Purkinje cells: effects of aging, caloric restriction, and overexpression of superoxide dismutase 1 on 5-methylcytosine and 5-hydroxymethylcytosine.
abstract: The aim of the present study was to assess alterations in DNA methylation and hydroxymethylation during aging in cerebellar Purkinje cells and to determine the effects of putatively preventative measures to such age-related changes. Using immunohistochemical techniques, 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) immunoreactivity in cerebellar Purkinje cells of 12-month- and 24-month-old mice was interrogated. Additionally, the modulatory effects of caloric restriction (CR) and normal human Cu/Zn super oxide dismutase 1 overexpression on these changes were assessed. We show that aging is associated with an increase of 5-mC and 5-hmC immunoreactivity in mouse cerebellar Purkinje cells. These age-related increases were mitigated by CR but not super oxide dismutase 1 overexpression. Additionally, the ratio between 5-mC and 5-hmC decreased with age and CR treatment, suggesting that CR has a stronger effect on DNA methylation than DNA hydroxymethylation. These findings enforce the notion that aging is closely connected to marked epigenetic changes, affecting multiple brain regions, and that CR is an effective means to prevent or counteract deleterious age-related epigenetic alterations.
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Faculty of Health, Medicine and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Roy
authors.initials: R
authors.lastname: Lardenoije
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Faculty of Health, Medicine and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Daniël L A
authors.initials: DLA
authors.lastname: van den Hove
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Faculty of Health, Medicine and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Thomas S J
authors.initials: TSJ
authors.lastname: Vaessen
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Faculty of Health, Medicine and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Artemis
authors.initials: A
authors.lastname: Iatrou
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Faculty of Health, Medicine and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Koen P V
authors.initials: KPV
authors.lastname: Meuwissen
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Faculty of Health, Medicine and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Britt T J
authors.initials: BTJ
authors.lastname: van Hagen
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Faculty of Health, Medicine and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Gunter
authors.initials: G
authors.lastname: Kenis
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Faculty of Health, Medicine and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Harry W M
authors.initials: HWM
authors.lastname: Steinbusch
authors.affiliation: Department of Neuroanatomy, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmitz
authors.affiliation: School for Mental Health and Neuroscience (MHeNS), Faculty of Health, Medicine and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, Maastricht, The Netherlands. Electronic address: b.rutten@maastrichtuniversity.nl.
authors.forename: Bart P F
authors.initials: BPF
authors.lastname: Rutten
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism* / Q000031:analogs & derivatives; D000375:Aging; D000818:Animals; D031204:Caloric Restriction; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000502:physiology*; D015870:Gene Expression; D007150:Immunohistochemistry / Q000379:methods; D008810:Mice, Inbred C57BL; D011689:Purkinje Cells / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000502:physiology; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Aging; Antioxidant overexpression; Caloric restriction; DNA hydroxymethylation; DNA methylation; Purkinje cells