PMID- 21764481 OWN - NLM STAT- MEDLINE DCOM- 20121024 LR - 20240417 IS - 1558-1497 (Electronic) IS - 0197-4580 (Print) IS - 0197-4580 (Linking) VI - 33 IP - 8 DP - 2012 Aug TI - Prevention of age-related changes in hippocampal levels of 5-methylcytidine by caloric restriction. PG - 1672-81 LID - 10.1016/j.neurobiolaging.2011.06.003 [doi] AB - Aberrant DNA methylation patterns have been linked to molecular and cellular alterations in the aging brain. Caloric restriction (CR) and upregulation of antioxidants have been proposed as interventions to prevent or delay age-related brain pathology. Previously, we have shown in large cohorts of aging mice, that age-related increases in DNA methyltransferase 3a (Dnmt3a) immunoreactivity in the mouse hippocampus were attenuated by CR, but not by overexpression of superoxide dismutase 1 (SOD1). Here, we investigated age-related alterations of 5-methylcytidine (5-mC), a marker of DNA methylation levels, in a hippocampal subregion-specific manner. Examination of 5-mC immunoreactivity in 12- and 24-month-old wild type (WT) mice on control diet, mice overexpressing SOD1 on control diet, wild type mice on CR, and SOD1 mice on CR, indicated an age-related increase in 5-mC immunoreactivity in the hippocampal dentate gyrus, CA3, and CA1-2 regions, which was prevented by CR but not by SOD1 overexpression. Moreover, positive correlations between 5-mC and Dnmt3a immunoreactivity were observed in the CA3 and CA1-2. These findings suggest a crucial role for DNA methylation in hippocampal aging and in the mediation of the beneficial effects of CR on aging. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Chouliaras, Leonidas AU - Chouliaras L AD - School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, European Graduate School of Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands. FAU - van den Hove, Daniel L A AU - van den Hove DL FAU - Kenis, Gunter AU - Kenis G FAU - Keitel, Stella AU - Keitel S FAU - Hof, Patrick R AU - Hof PR FAU - van Os, Jim AU - van Os J FAU - Steinbusch, Harry W M AU - Steinbusch HW FAU - Schmitz, Christoph AU - Schmitz C FAU - Rutten, Bart P F AU - Rutten BP LA - eng GR - P50 AG005138/AG/NIA NIH HHS/United States GR - P50 AG005138-27/AG/NIA NIH HHS/United States GR - P50AG05138/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110718 PL - United States TA - Neurobiol Aging JT - Neurobiology of aging JID - 8100437 RN - 0 (Dnmt3a protein, mouse) RN - 5CSZ8459RP (Cytidine) RN - EC 1.15.1.1 (Sod1 protein, mouse) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 1.15.1.1 (Superoxide Dismutase-1) RN - EC 2.1.1.37 (DNA Methyltransferase 3A) RN - TL9PB228DC (5-methylcytidine) SB - IM MH - Aging/*metabolism MH - Animals MH - Caloric Restriction/*methods MH - Cytidine/*analogs & derivatives/metabolism MH - *DNA Methylation MH - DNA Methyltransferase 3A MH - Hippocampus/*metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Superoxide Dismutase/genetics/*metabolism MH - Superoxide Dismutase-1 PMC - PMC3355211 MID - NIHMS351427 COIS- Disclosure statement The authors declare no actual or potential conflicts of interest relating to this work. All experiments were conducted in compliance with the Principles of Laboratory Animal Care (NIH publication no. 86-23, revised 1985) and the Dutch animal protection law, considering international standards. The experimental protocols were approved by the Animal Subjects Ethics Committee of The Maastricht University. EDAT- 2011/07/19 06:00 MHDA- 2012/10/25 06:00 PMCR- 2012/08/01 CRDT- 2011/07/19 06:00 PHST- 2011/01/26 00:00 [received] PHST- 2011/05/24 00:00 [revised] PHST- 2011/06/04 00:00 [accepted] PHST- 2011/07/19 06:00 [entrez] PHST- 2011/07/19 06:00 [pubmed] PHST- 2012/10/25 06:00 [medline] PHST- 2012/08/01 00:00 [pmc-release] AID - S0197-4580(11)00212-0 [pii] AID - 10.1016/j.neurobiolaging.2011.06.003 [doi] PST - ppublish SO - Neurobiol Aging. 2012 Aug;33(8):1672-81. doi: 10.1016/j.neurobiolaging.2011.06.003. Epub 2011 Jul 18.