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-...

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Bibliographic Details
Published in:Neurobiology of aging 2015-11, Vol.36 (11), p.3079-3089
Main Authors: Lardenoije, Roy, van den Hove, Daniël L.A, Vaessen, Thomas S.J, Iatrou, Artemis, Meuwissen, Koen P.V, van Hagen, Britt T.J, Kenis, Gunter, Steinbusch, Harry W.M, Schmitz, Christoph, Rutten, Bart P.F
Format: Article
Language:English
Subjects:
5-Methylcytosine - metabolism
Aging
Animals
Antioxidant overexpression
Caloric Restriction
Cytosine - analogs & derivatives
Cytosine - metabolism
DNA hydroxymethylation
DNA methylation
DNA Methylation - genetics
Epigenesis, Genetic - physiology
Gene Expression
Immunohistochemistry - methods
Internal Medicine
Mice, Inbred C57BL
Neurology
Purkinje cells
Purkinje Cells - metabolism
Superoxide Dismutase - genetics
Superoxide Dismutase - physiology
Superoxide Dismutase-1
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Summary: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.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2015.08.001