Mitochondrial DNA Hypomethylation Is a Biomarker Associated with Induced Senescence in Human Fetal Heart Mesenchymal Stem Cells

Background. Fetal heart can regenerate to restore its normal anatomy and function in response to injury, but this regenerative capacity is lost within the first week of postnatal life. Although the specific molecular mechanisms remain to be defined, it is presumed that aging of cardiac stem or proge...

Full description

Saved in:
Bibliographic Details
Published in:Stem Cells International 2017-01, Vol.2017 (2017), p.277-288-022
Main Authors: Cui, Jiuwei, Hoffman, Andrew R., Hu, Jifan, Xiao, Jialin, Kim, Su-Jeong, Li, Wei, Wen, Xue, Li, Tao, Pian, Lingling, Du, Zhonghua, Yu, Dehai, Cohen, Pinchas
Format: Article
Language:English
Subjects:
Aging
Analysis
Biological markers
Biomarkers
Cardiomyocytes
Colleges & universities
Deoxyribonucleic acid
DNA
DNA methylation
Epigenetics
Gene expression
Genomes
Health aspects
Heart attacks
Laboratories
Mammals
Methylation
Mitochondrial DNA
Oxidative stress
Science
Senescence
Stem cells
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-a741t-21065c145b6c71af9b2bc76022459e73caaa7a933b858cae3c92a548f1766aa93
cites cdi_FETCH-LOGICAL-a741t-21065c145b6c71af9b2bc76022459e73caaa7a933b858cae3c92a548f1766aa93
container_end_page 288-022
container_issue 2017
container_start_page 277
container_title Stem Cells International
container_volume 2017
creator Cui, Jiuwei
Hoffman, Andrew R.
Hu, Jifan
Xiao, Jialin
Kim, Su-Jeong
Li, Wei
Wen, Xue
Li, Tao
Pian, Lingling
Du, Zhonghua
Yu, Dehai
Cohen, Pinchas
description Background. Fetal heart can regenerate to restore its normal anatomy and function in response to injury, but this regenerative capacity is lost within the first week of postnatal life. Although the specific molecular mechanisms remain to be defined, it is presumed that aging of cardiac stem or progenitor cells may contribute to the loss of regenerative potential. Methods. To study this aging-related dysfunction, we cultured mesenchymal stem cells (MSCs) from human fetal heart tissues. Senescence was induced by exposing cells to chronic oxidative stress/low serum. Mitochondrial DNA methylation was examined during the period of senescence. Results. Senescent MSCs exhibited flattened and enlarged morphology and were positive for the senescence-associated beta-galactosidase (SA-β-Gal). By scanning the entire mitochondrial genome, we found that four CpG islands were hypomethylated in close association with senescence in MSCs. The mitochondrial COX1 gene, which encodes the main subunit of the cytochrome c oxidase complex and contains the differentially methylated CpG island 4, was upregulated in MSCs in parallel with the onset of senescence. Knockdown of DNA methyltransferases (DNMT1, DNMT3a, and DNMT3B) also upregulated COX1 expression and induced cellular senescence in MSCs. Conclusions. This study demonstrates that mitochondrial CpG hypomethylation may serve as a critical biomarker associated with cellular senescence induced by chronic oxidative stress.
doi_str_mv 10.1155/2017/1764549
format article
fullrecord <record><control><sourceid>gale_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_07dec69941f04ed59bcb331eae797b77</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A555409672</galeid><airiti_id>P20150730003_201712_201801170015_201801170015_277_288_022</airiti_id><doaj_id>oai_doaj_org_article_07dec69941f04ed59bcb331eae797b77</doaj_id><sourcerecordid>A555409672</sourcerecordid><originalsourceid>FETCH-LOGICAL-a741t-21065c145b6c71af9b2bc76022459e73caaa7a933b858cae3c92a548f1766aa93</originalsourceid><addsrcrecordid>eNqNk0Fv1DAQhSMEolXpjTOKhISQYFs7tmP7UmkplF2phUoFiZvlOJPGJYlLnFDtib_OpFvabsWhycHxzOeXmclLkrykZI9SIfYzQuU-lTkXXD9Jtmmu5EznUj29fc5_bCW7MV4QvJgmnGTPk61MccW5FtvJnxM_BFeHruy9bdKPX-bpYnUZWhjqVWMHH7p0GVObfvChtf1P6NN5jMF5O0CZXvmhTpddOTrcnEEH0UHnIPVduhhb26VHMKDoAmw_pCcQMVmvWoycDdCmh9A08UXyrLJNhN2bdSf5fvTp2-Fidvz18_JwfjyzktNhllGSC0e5KHInqa10kRVO5iTLuNAgmbPWSqsZK5RQzgJzOrOCqwpnk1tM7CTLtW4Z7IW57D12szLBenMdCP25wSK9a8AQWYLLtea0IhxKoQtXMEbBgtSykBK1DtZal2PRQok9D71tNkQ3M52vzXn4bQTT-KkUCry9EejDrxHiYFqPo2sa20EYo6FKS6akktlj0FxpoXKB6OsH6EUY-w6nipTSLOc8I3fUucVefVcFLNFNomYuhOAE7TO9du8_FN4ltN6FDiqP8Y0Db-4dqME2Qx1DM04Oipvg-zXo-hBjD9Xt3Cgxk6fN5Glz42nEX92f9S38z8EIvFsDte9Ke-UfKQfIQGXv6IwQxRkCp2vA-t4P_m6Ep6gjiGTTb3StSbNpUYRSSTD1YCMllqgMGpT9BaTMGxU</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1889364420</pqid></control><display><type>article</type><title>Mitochondrial DNA Hypomethylation Is a Biomarker Associated with Induced Senescence in Human Fetal Heart Mesenchymal Stem Cells</title><source>Open Access: PubMed Central</source><source>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</source><source>Wiley Open Access</source><creator>Cui, Jiuwei ; Hoffman, Andrew R. ; Hu, Jifan ; Xiao, Jialin ; Kim, Su-Jeong ; Li, Wei ; Wen, Xue ; Li, Tao ; Pian, Lingling ; Du, Zhonghua ; Yu, Dehai ; Cohen, Pinchas</creator><contributor>Stimpfel, Martin</contributor><creatorcontrib>Cui, Jiuwei ; Hoffman, Andrew R. ; Hu, Jifan ; Xiao, Jialin ; Kim, Su-Jeong ; Li, Wei ; Wen, Xue ; Li, Tao ; Pian, Lingling ; Du, Zhonghua ; Yu, Dehai ; Cohen, Pinchas ; Stimpfel, Martin</creatorcontrib><description>Background. Fetal heart can regenerate to restore its normal anatomy and function in response to injury, but this regenerative capacity is lost within the first week of postnatal life. Although the specific molecular mechanisms remain to be defined, it is presumed that aging of cardiac stem or progenitor cells may contribute to the loss of regenerative potential. Methods. To study this aging-related dysfunction, we cultured mesenchymal stem cells (MSCs) from human fetal heart tissues. Senescence was induced by exposing cells to chronic oxidative stress/low serum. Mitochondrial DNA methylation was examined during the period of senescence. Results. Senescent MSCs exhibited flattened and enlarged morphology and were positive for the senescence-associated beta-galactosidase (SA-β-Gal). By scanning the entire mitochondrial genome, we found that four CpG islands were hypomethylated in close association with senescence in MSCs. The mitochondrial COX1 gene, which encodes the main subunit of the cytochrome c oxidase complex and contains the differentially methylated CpG island 4, was upregulated in MSCs in parallel with the onset of senescence. Knockdown of DNA methyltransferases (DNMT1, DNMT3a, and DNMT3B) also upregulated COX1 expression and induced cellular senescence in MSCs. Conclusions. This study demonstrates that mitochondrial CpG hypomethylation may serve as a critical biomarker associated with cellular senescence induced by chronic oxidative stress.</description><identifier>ISSN: 1687-966X</identifier><identifier>ISSN: 1687-9678</identifier><identifier>EISSN: 1687-9678</identifier><identifier>DOI: 10.1155/2017/1764549</identifier><identifier>PMID: 28484495</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Limiteds</publisher><subject>Aging ; Analysis ; Biological markers ; Biomarkers ; Cardiomyocytes ; Colleges &amp; universities ; Deoxyribonucleic acid ; DNA ; DNA methylation ; Epigenetics ; Gene expression ; Genomes ; Health aspects ; Heart attacks ; Laboratories ; Mammals ; Methylation ; Mitochondrial DNA ; Oxidative stress ; Science ; Senescence ; Stem cells</subject><ispartof>Stem Cells International, 2017-01, Vol.2017 (2017), p.277-288-022</ispartof><rights>Copyright © 2017 Dehai Yu et al.</rights><rights>COPYRIGHT 2017 John Wiley &amp; Sons, Inc.</rights><rights>Copyright © 2017 Dehai Yu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2017 Dehai Yu et al. 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a741t-21065c145b6c71af9b2bc76022459e73caaa7a933b858cae3c92a548f1766aa93</citedby><cites>FETCH-LOGICAL-a741t-21065c145b6c71af9b2bc76022459e73caaa7a933b858cae3c92a548f1766aa93</cites><orcidid>0000-0001-6496-7550 ; 0000-0002-0145-1917 ; 0000-0002-0035-8366 ; 0000-0002-2174-0361</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1889364420/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1889364420?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28484495$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Stimpfel, Martin</contributor><creatorcontrib>Cui, Jiuwei</creatorcontrib><creatorcontrib>Hoffman, Andrew R.</creatorcontrib><creatorcontrib>Hu, Jifan</creatorcontrib><creatorcontrib>Xiao, Jialin</creatorcontrib><creatorcontrib>Kim, Su-Jeong</creatorcontrib><creatorcontrib>Li, Wei</creatorcontrib><creatorcontrib>Wen, Xue</creatorcontrib><creatorcontrib>Li, Tao</creatorcontrib><creatorcontrib>Pian, Lingling</creatorcontrib><creatorcontrib>Du, Zhonghua</creatorcontrib><creatorcontrib>Yu, Dehai</creatorcontrib><creatorcontrib>Cohen, Pinchas</creatorcontrib><title>Mitochondrial DNA Hypomethylation Is a Biomarker Associated with Induced Senescence in Human Fetal Heart Mesenchymal Stem Cells</title><title>Stem Cells International</title><addtitle>Stem Cells Int</addtitle><description>Background. Fetal heart can regenerate to restore its normal anatomy and function in response to injury, but this regenerative capacity is lost within the first week of postnatal life. Although the specific molecular mechanisms remain to be defined, it is presumed that aging of cardiac stem or progenitor cells may contribute to the loss of regenerative potential. Methods. To study this aging-related dysfunction, we cultured mesenchymal stem cells (MSCs) from human fetal heart tissues. Senescence was induced by exposing cells to chronic oxidative stress/low serum. Mitochondrial DNA methylation was examined during the period of senescence. Results. Senescent MSCs exhibited flattened and enlarged morphology and were positive for the senescence-associated beta-galactosidase (SA-β-Gal). By scanning the entire mitochondrial genome, we found that four CpG islands were hypomethylated in close association with senescence in MSCs. The mitochondrial COX1 gene, which encodes the main subunit of the cytochrome c oxidase complex and contains the differentially methylated CpG island 4, was upregulated in MSCs in parallel with the onset of senescence. Knockdown of DNA methyltransferases (DNMT1, DNMT3a, and DNMT3B) also upregulated COX1 expression and induced cellular senescence in MSCs. Conclusions. This study demonstrates that mitochondrial CpG hypomethylation may serve as a critical biomarker associated with cellular senescence induced by chronic oxidative stress.</description><subject>Aging</subject><subject>Analysis</subject><subject>Biological markers</subject><subject>Biomarkers</subject><subject>Cardiomyocytes</subject><subject>Colleges &amp; universities</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>Epigenetics</subject><subject>Gene expression</subject><subject>Genomes</subject><subject>Health aspects</subject><subject>Heart attacks</subject><subject>Laboratories</subject><subject>Mammals</subject><subject>Methylation</subject><subject>Mitochondrial DNA</subject><subject>Oxidative stress</subject><subject>Science</subject><subject>Senescence</subject><subject>Stem cells</subject><issn>1687-966X</issn><issn>1687-9678</issn><issn>1687-9678</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk0Fv1DAQhSMEolXpjTOKhISQYFs7tmP7UmkplF2phUoFiZvlOJPGJYlLnFDtib_OpFvabsWhycHxzOeXmclLkrykZI9SIfYzQuU-lTkXXD9Jtmmu5EznUj29fc5_bCW7MV4QvJgmnGTPk61MccW5FtvJnxM_BFeHruy9bdKPX-bpYnUZWhjqVWMHH7p0GVObfvChtf1P6NN5jMF5O0CZXvmhTpddOTrcnEEH0UHnIPVduhhb26VHMKDoAmw_pCcQMVmvWoycDdCmh9A08UXyrLJNhN2bdSf5fvTp2-Fidvz18_JwfjyzktNhllGSC0e5KHInqa10kRVO5iTLuNAgmbPWSqsZK5RQzgJzOrOCqwpnk1tM7CTLtW4Z7IW57D12szLBenMdCP25wSK9a8AQWYLLtea0IhxKoQtXMEbBgtSykBK1DtZal2PRQok9D71tNkQ3M52vzXn4bQTT-KkUCry9EejDrxHiYFqPo2sa20EYo6FKS6akktlj0FxpoXKB6OsH6EUY-w6nipTSLOc8I3fUucVefVcFLNFNomYuhOAE7TO9du8_FN4ltN6FDiqP8Y0Db-4dqME2Qx1DM04Oipvg-zXo-hBjD9Xt3Cgxk6fN5Glz42nEX92f9S38z8EIvFsDte9Ke-UfKQfIQGXv6IwQxRkCp2vA-t4P_m6Ep6gjiGTTb3StSbNpUYRSSTD1YCMllqgMGpT9BaTMGxU</recordid><startdate>20170101</startdate><enddate>20170101</enddate><creator>Cui, Jiuwei</creator><creator>Hoffman, Andrew R.</creator><creator>Hu, Jifan</creator><creator>Xiao, Jialin</creator><creator>Kim, Su-Jeong</creator><creator>Li, Wei</creator><creator>Wen, Xue</creator><creator>Li, Tao</creator><creator>Pian, Lingling</creator><creator>Du, Zhonghua</creator><creator>Yu, Dehai</creator><creator>Cohen, Pinchas</creator><general>Hindawi Limiteds</general><general>Hindawi Publishing Corporation</general><general>Hindawi</general><general>John Wiley &amp; Sons, Inc</general><general>Hindawi Limited</general><scope>188</scope><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QO</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M2O</scope><scope>MBDVC</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-6496-7550</orcidid><orcidid>https://orcid.org/0000-0002-0145-1917</orcidid><orcidid>https://orcid.org/0000-0002-0035-8366</orcidid><orcidid>https://orcid.org/0000-0002-2174-0361</orcidid></search><sort><creationdate>20170101</creationdate><title>Mitochondrial DNA Hypomethylation Is a Biomarker Associated with Induced Senescence in Human Fetal Heart Mesenchymal Stem Cells</title><author>Cui, Jiuwei ; Hoffman, Andrew R. ; Hu, Jifan ; Xiao, Jialin ; Kim, Su-Jeong ; Li, Wei ; Wen, Xue ; Li, Tao ; Pian, Lingling ; Du, Zhonghua ; Yu, Dehai ; Cohen, Pinchas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a741t-21065c145b6c71af9b2bc76022459e73caaa7a933b858cae3c92a548f1766aa93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aging</topic><topic>Analysis</topic><topic>Biological markers</topic><topic>Biomarkers</topic><topic>Cardiomyocytes</topic><topic>Colleges &amp; universities</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>Epigenetics</topic><topic>Gene expression</topic><topic>Genomes</topic><topic>Health aspects</topic><topic>Heart attacks</topic><topic>Laboratories</topic><topic>Mammals</topic><topic>Methylation</topic><topic>Mitochondrial DNA</topic><topic>Oxidative stress</topic><topic>Science</topic><topic>Senescence</topic><topic>Stem cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cui, Jiuwei</creatorcontrib><creatorcontrib>Hoffman, Andrew R.</creatorcontrib><creatorcontrib>Hu, Jifan</creatorcontrib><creatorcontrib>Xiao, Jialin</creatorcontrib><creatorcontrib>Kim, Su-Jeong</creatorcontrib><creatorcontrib>Li, Wei</creatorcontrib><creatorcontrib>Wen, Xue</creatorcontrib><creatorcontrib>Li, Tao</creatorcontrib><creatorcontrib>Pian, Lingling</creatorcontrib><creatorcontrib>Du, Zhonghua</creatorcontrib><creatorcontrib>Yu, Dehai</creatorcontrib><creatorcontrib>Cohen, Pinchas</creatorcontrib><collection>Airiti Library</collection><collection>الدوريات العلمية والإحصائية - e-Marefa Academic and Statistical Periodicals</collection><collection>معرفة - المحتوى العربي الأكاديمي المتكامل - e-Marefa Academic Complete</collection><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>ProQuest_Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>ProQuest research library</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Stem Cells International</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cui, Jiuwei</au><au>Hoffman, Andrew R.</au><au>Hu, Jifan</au><au>Xiao, Jialin</au><au>Kim, Su-Jeong</au><au>Li, Wei</au><au>Wen, Xue</au><au>Li, Tao</au><au>Pian, Lingling</au><au>Du, Zhonghua</au><au>Yu, Dehai</au><au>Cohen, Pinchas</au><au>Stimpfel, Martin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mitochondrial DNA Hypomethylation Is a Biomarker Associated with Induced Senescence in Human Fetal Heart Mesenchymal Stem Cells</atitle><jtitle>Stem Cells International</jtitle><addtitle>Stem Cells Int</addtitle><date>2017-01-01</date><risdate>2017</risdate><volume>2017</volume><issue>2017</issue><spage>277</spage><epage>288-022</epage><pages>277-288-022</pages><issn>1687-966X</issn><issn>1687-9678</issn><eissn>1687-9678</eissn><abstract>Background. Fetal heart can regenerate to restore its normal anatomy and function in response to injury, but this regenerative capacity is lost within the first week of postnatal life. Although the specific molecular mechanisms remain to be defined, it is presumed that aging of cardiac stem or progenitor cells may contribute to the loss of regenerative potential. Methods. To study this aging-related dysfunction, we cultured mesenchymal stem cells (MSCs) from human fetal heart tissues. Senescence was induced by exposing cells to chronic oxidative stress/low serum. Mitochondrial DNA methylation was examined during the period of senescence. Results. Senescent MSCs exhibited flattened and enlarged morphology and were positive for the senescence-associated beta-galactosidase (SA-β-Gal). By scanning the entire mitochondrial genome, we found that four CpG islands were hypomethylated in close association with senescence in MSCs. The mitochondrial COX1 gene, which encodes the main subunit of the cytochrome c oxidase complex and contains the differentially methylated CpG island 4, was upregulated in MSCs in parallel with the onset of senescence. Knockdown of DNA methyltransferases (DNMT1, DNMT3a, and DNMT3B) also upregulated COX1 expression and induced cellular senescence in MSCs. Conclusions. This study demonstrates that mitochondrial CpG hypomethylation may serve as a critical biomarker associated with cellular senescence induced by chronic oxidative stress.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Limiteds</pub><pmid>28484495</pmid><doi>10.1155/2017/1764549</doi><orcidid>https://orcid.org/0000-0001-6496-7550</orcidid><orcidid>https://orcid.org/0000-0002-0145-1917</orcidid><orcidid>https://orcid.org/0000-0002-0035-8366</orcidid><orcidid>https://orcid.org/0000-0002-2174-0361</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1687-966X
ispartof Stem Cells International, 2017-01, Vol.2017 (2017), p.277-288-022
issn 1687-966X
1687-9678
1687-9678
language eng
recordid cdi_doaj_primary_oai_doaj_org_article_07dec69941f04ed59bcb331eae797b77
source Open Access: PubMed Central; Publicly Available Content Database (Proquest) (PQ_SDU_P3); Wiley Open Access
subjects Aging
Analysis
Biological markers
Biomarkers
Cardiomyocytes
Colleges & universities
Deoxyribonucleic acid
DNA
DNA methylation
Epigenetics
Gene expression
Genomes
Health aspects
Heart attacks
Laboratories
Mammals
Methylation
Mitochondrial DNA
Oxidative stress
Science
Senescence
Stem cells
title Mitochondrial DNA Hypomethylation Is a Biomarker Associated with Induced Senescence in Human Fetal Heart Mesenchymal Stem Cells
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T10%3A10%3A10IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mitochondrial%20DNA%20Hypomethylation%20Is%20a%20Biomarker%20Associated%20with%20Induced%20Senescence%20in%20Human%20Fetal%20Heart%20Mesenchymal%20Stem%20Cells&rft.jtitle=Stem%20Cells%20International&rft.au=Cui,%20Jiuwei&rft.date=2017-01-01&rft.volume=2017&rft.issue=2017&rft.spage=277&rft.epage=288-022&rft.pages=277-288-022&rft.issn=1687-966X&rft.eissn=1687-9678&rft_id=info:doi/10.1155/2017/1764549&rft_dat=%3Cgale_doaj_%3EA555409672%3C/gale_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-a741t-21065c145b6c71af9b2bc76022459e73caaa7a933b858cae3c92a548f1766aa93%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1889364420&rft_id=info:pmid/28484495&rft_galeid=A555409672&rft_airiti_id=P20150730003_201712_201801170015_201801170015_277_288_022&rfr_iscdi=true