TY - JOUR
T1 - Epigenetic modifications in mouse cerebellar Purkinje cells: effects of aging, caloric restriction, and overexpression of superoxide dismutase 1 on 5-methylcytosine and 5-hydroxymethylcytosine
AU - Lardenoije, Roy
AU - van den Hove, Daniel L. A.
AU - Vaessen, Thomas S. J.
AU - Iatrou, Artemis
AU - Meuwissen, Koen P. V.
AU - van Hagen, Britt T. J.
AU - Kenis, Gunter
AU - Steinbusch, Harry W. M.
AU - Schmitz, Christoph
AU - Rutten, Bart P. F.
PY - 2015/11
Y1 - 2015/11
N2 - 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-monthand 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.
AB - 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-monthand 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.
KW - DNA methylation
KW - DNA hydroxymethylation
KW - Purkinje cells
KW - Aging
KW - Caloric restriction
KW - Antioxidant overexpression
U2 - 10.1016/j.neurobiolaging.2015.08.001
DO - 10.1016/j.neurobiolaging.2015.08.001
M3 - Article
C2 - 26476235
SN - 0197-4580
VL - 36
SP - 3079
EP - 3089
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 11
ER -