期刊
NEUROBIOLOGY OF AGING
卷 36, 期 11, 页码 3079-3089出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2015.08.001
关键词
DNA methylation; DNA hydroxymethylation; Purkinje cells; Aging; Caloric restriction; Antioxidant overexpression
资金
- Internationale Stichting Alzheimer Onderzoek (ISAO) [07551, 11532, 09552, 13515]
- Netherlands Organization for Scientific Research (NWO) [916.11.086]
- NWO [911.06.086, 022.005.019]
- Maastricht University Medical Centre + (Koostra Talent Fellowship)
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. (C) 2015 Elsevier Inc. All rights reserved.
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