Prevention of age-related changes in hippocampal levels of 5-methylcytidine by caloric restriction
Abstract 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 coho...
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| Veröffentlicht in: | Neurobiology of aging 2012-08, Vol.33 (8), p.1672-1681 |
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| creator | Chouliaras, Leonidas van den Hove, Daniel L.A Kenis, Gunter Keitel, Stella Hof, Patrick R van Os, Jim Steinbusch, Harry W.M Schmitz, Christoph Rutten, Bart P.F |
| description | Abstract 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. |
| doi_str_mv | 10.1016/j.neurobiolaging.2011.06.003 |
| format | Article |
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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.</description><identifier>ISSN: 0197-4580</identifier><identifier>EISSN: 1558-1497</identifier><identifier>DOI: 10.1016/j.neurobiolaging.2011.06.003</identifier><identifier>PMID: 21764481</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>5-methylcytidine (5-mC) ; Age ; Aging ; Aging - metabolism ; Animals ; Antioxidants ; Brain ; Caloric restriction ; Caloric Restriction - methods ; Cytidine - analogs & derivatives ; Cytidine - metabolism ; Dentate gyrus ; Dietary restrictions ; Diets ; DNA Methylation ; DNA methyltransferase ; DNA Methyltransferase 3A ; Epigenesis ; Epigenetics ; Hippocampus ; Hippocampus - metabolism ; Immunoreactivity ; Internal Medicine ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nervous system ; Neurology ; Superoxide dismutase ; Superoxide dismutase (SOD) ; Superoxide Dismutase - genetics ; Superoxide Dismutase - metabolism ; Superoxide Dismutase-1</subject><ispartof>Neurobiology of aging, 2012-08, Vol.33 (8), p.1672-1681</ispartof><rights>Elsevier Inc.</rights><rights>2012 Elsevier Inc.</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><rights>2011 Elsevier Inc. All rights reserved. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c583t-7625c35339986283a07f15f4cf13d9253815b0a8c35cf49a7fd1dd067d4475503</citedby><cites>FETCH-LOGICAL-c583t-7625c35339986283a07f15f4cf13d9253815b0a8c35cf49a7fd1dd067d4475503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.neurobiolaging.2011.06.003$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21764481$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chouliaras, Leonidas</creatorcontrib><creatorcontrib>van den Hove, Daniel L.A</creatorcontrib><creatorcontrib>Kenis, Gunter</creatorcontrib><creatorcontrib>Keitel, Stella</creatorcontrib><creatorcontrib>Hof, Patrick R</creatorcontrib><creatorcontrib>van Os, Jim</creatorcontrib><creatorcontrib>Steinbusch, Harry W.M</creatorcontrib><creatorcontrib>Schmitz, Christoph</creatorcontrib><creatorcontrib>Rutten, Bart P.F</creatorcontrib><title>Prevention of age-related changes in hippocampal levels of 5-methylcytidine by caloric restriction</title><title>Neurobiology of aging</title><addtitle>Neurobiol Aging</addtitle><description>Abstract 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.</description><subject>5-methylcytidine (5-mC)</subject><subject>Age</subject><subject>Aging</subject><subject>Aging - metabolism</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Brain</subject><subject>Caloric restriction</subject><subject>Caloric Restriction - methods</subject><subject>Cytidine - analogs & derivatives</subject><subject>Cytidine - metabolism</subject><subject>Dentate gyrus</subject><subject>Dietary restrictions</subject><subject>Diets</subject><subject>DNA Methylation</subject><subject>DNA methyltransferase</subject><subject>DNA Methyltransferase 3A</subject><subject>Epigenesis</subject><subject>Epigenetics</subject><subject>Hippocampus</subject><subject>Hippocampus - metabolism</subject><subject>Immunoreactivity</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Nervous system</subject><subject>Neurology</subject><subject>Superoxide dismutase</subject><subject>Superoxide dismutase (SOD)</subject><subject>Superoxide Dismutase - genetics</subject><subject>Superoxide Dismutase - metabolism</subject><subject>Superoxide Dismutase-1</subject><issn>0197-4580</issn><issn>1558-1497</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNksFu1DAQhiMEokvhFVAOHLgkzNhxnEioEqooIFUCCThbjjPZ9eK1Fzu70r49jrZUlFNPc_A3vz3-pijeINQI2L7b1p4OMQw2OL22fl0zQKyhrQH4k2KFQnQVNr18WqwAe1k1ooOL4kVKWwCQjWyfFxcMZds0Ha6K4VukI_nZBl-GqdRrqiI5PdNYmo32a0ql9eXG7vfB6N1eu9Jl3qUFFtWO5s3JmdNsR-upHE6l0S5Ea8pIac51yX1ZPJu0S_Tqrl4WP28-_rj-XN1-_fTl-sNtZUTH50q2TBguOO_7rmUd1yAnFFNjJuRjzwTvUAygu8yYqem1nEYcR2jl2DRSCOCXxdU5d38YdjSaPFXUTu2j3el4UkFb9fDE241ah6PiXAiGmAPe3gXE8PuQB1A7mww5pz2FQ1IIPP9Z0zP5CJQBCICeZfT9GTUxpBRpun8RglqMqq16aFQtRhW0KhvN7a__neq--a_CDNycgWyFjpaiSsaSNzTaSGZWY7CPvenqvyDjrLfZ6C86UdqGQ_TZn0KVmAL1fdmuZbkQARgy4H8AJtDQyQ</recordid><startdate>20120801</startdate><enddate>20120801</enddate><creator>Chouliaras, Leonidas</creator><creator>van den Hove, Daniel L.A</creator><creator>Kenis, Gunter</creator><creator>Keitel, Stella</creator><creator>Hof, Patrick R</creator><creator>van Os, Jim</creator><creator>Steinbusch, Harry W.M</creator><creator>Schmitz, Christoph</creator><creator>Rutten, Bart P.F</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TK</scope><scope>5PM</scope></search><sort><creationdate>20120801</creationdate><title>Prevention of age-related changes in hippocampal levels of 5-methylcytidine by caloric restriction</title><author>Chouliaras, Leonidas ; van den Hove, Daniel L.A ; Kenis, Gunter ; Keitel, Stella ; Hof, Patrick R ; van Os, Jim ; Steinbusch, Harry W.M ; Schmitz, Christoph ; Rutten, Bart P.F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c583t-7625c35339986283a07f15f4cf13d9253815b0a8c35cf49a7fd1dd067d4475503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>5-methylcytidine (5-mC)</topic><topic>Age</topic><topic>Aging</topic><topic>Aging - metabolism</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Brain</topic><topic>Caloric restriction</topic><topic>Caloric Restriction - methods</topic><topic>Cytidine - analogs & derivatives</topic><topic>Cytidine - metabolism</topic><topic>Dentate gyrus</topic><topic>Dietary restrictions</topic><topic>Diets</topic><topic>DNA Methylation</topic><topic>DNA methyltransferase</topic><topic>DNA Methyltransferase 3A</topic><topic>Epigenesis</topic><topic>Epigenetics</topic><topic>Hippocampus</topic><topic>Hippocampus - metabolism</topic><topic>Immunoreactivity</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Nervous system</topic><topic>Neurology</topic><topic>Superoxide dismutase</topic><topic>Superoxide dismutase (SOD)</topic><topic>Superoxide Dismutase - genetics</topic><topic>Superoxide Dismutase - metabolism</topic><topic>Superoxide Dismutase-1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chouliaras, Leonidas</creatorcontrib><creatorcontrib>van den Hove, Daniel L.A</creatorcontrib><creatorcontrib>Kenis, Gunter</creatorcontrib><creatorcontrib>Keitel, Stella</creatorcontrib><creatorcontrib>Hof, Patrick R</creatorcontrib><creatorcontrib>van Os, Jim</creatorcontrib><creatorcontrib>Steinbusch, Harry W.M</creatorcontrib><creatorcontrib>Schmitz, Christoph</creatorcontrib><creatorcontrib>Rutten, Bart P.F</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neurobiology of aging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chouliaras, Leonidas</au><au>van den Hove, Daniel L.A</au><au>Kenis, Gunter</au><au>Keitel, Stella</au><au>Hof, Patrick R</au><au>van Os, Jim</au><au>Steinbusch, Harry W.M</au><au>Schmitz, Christoph</au><au>Rutten, Bart P.F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prevention of age-related changes in hippocampal levels of 5-methylcytidine by caloric restriction</atitle><jtitle>Neurobiology of aging</jtitle><addtitle>Neurobiol Aging</addtitle><date>2012-08-01</date><risdate>2012</risdate><volume>33</volume><issue>8</issue><spage>1672</spage><epage>1681</epage><pages>1672-1681</pages><issn>0197-4580</issn><eissn>1558-1497</eissn><abstract>Abstract 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. 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| subjects | 5-methylcytidine (5-mC) Age Aging Aging - metabolism Animals Antioxidants Brain Caloric restriction Caloric Restriction - methods Cytidine - analogs & derivatives Cytidine - metabolism Dentate gyrus Dietary restrictions Diets DNA Methylation DNA methyltransferase DNA Methyltransferase 3A Epigenesis Epigenetics Hippocampus Hippocampus - metabolism Immunoreactivity Internal Medicine Male Mice Mice, Inbred C57BL Mice, Transgenic Nervous system Neurology Superoxide dismutase Superoxide dismutase (SOD) Superoxide Dismutase - genetics Superoxide Dismutase - metabolism Superoxide Dismutase-1 |
| title | Prevention of age-related changes in hippocampal levels of 5-methylcytidine by caloric restriction |
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