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Methionine restriction slows down senescence in human diploid fibroblasts
Summary Methionine restriction (MetR) extends lifespan in animal models including rodents. Using human diploid fibroblasts (HDF), we report here that MetR significantly extends their replicative lifespan, thereby postponing cellular senescence. MetR significantly decreased activity of mitochondrial...
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Published in: | Aging cell 2014-12, Vol.13 (6), p.1038-1048 |
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container_title | Aging cell |
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creator | Kozieł, Rafał Ruckenstuhl, Christoph Albertini, Eva Neuhaus, Michael Netzberger, Christine Bust, Maria Madeo, Frank Wiesner, Rudolf J. Jansen‐Dürr, Pidder |
description | Summary
Methionine restriction (MetR) extends lifespan in animal models including rodents. Using human diploid fibroblasts (HDF), we report here that MetR significantly extends their replicative lifespan, thereby postponing cellular senescence. MetR significantly decreased activity of mitochondrial complex IV and diminished the accumulation of reactive oxygen species. Lifespan extension was accompanied by a significant decrease in the levels of subunits of mitochondrial complex IV, but also complex I, which was due to a decreased translation rate of several mtDNA‐encoded subunits. Together, these findings indicate that MetR slows down aging in human cells by modulating mitochondrial protein synthesis and respiratory chain assembly. |
doi_str_mv | 10.1111/acel.12266 |
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Methionine restriction (MetR) extends lifespan in animal models including rodents. Using human diploid fibroblasts (HDF), we report here that MetR significantly extends their replicative lifespan, thereby postponing cellular senescence. MetR significantly decreased activity of mitochondrial complex IV and diminished the accumulation of reactive oxygen species. Lifespan extension was accompanied by a significant decrease in the levels of subunits of mitochondrial complex IV, but also complex I, which was due to a decreased translation rate of several mtDNA‐encoded subunits. Together, these findings indicate that MetR slows down aging in human cells by modulating mitochondrial protein synthesis and respiratory chain assembly.</description><identifier>ISSN: 1474-9718</identifier><identifier>EISSN: 1474-9726</identifier><identifier>DOI: 10.1111/acel.12266</identifier><identifier>PMID: 25273919</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Age Factors ; Amino acids ; Animals ; B cells ; cellular senescence ; Diploidy ; Disease Models, Animal ; fibroblast ; Fibroblasts - cytology ; Fibroblasts - drug effects ; Fibroblasts - metabolism ; Humans ; Medical research ; methionine ; Methionine - administration & dosage ; Methionine - deficiency ; Methionine - metabolism ; mitochondria ; Mitochondria - metabolism ; Original ; oxidative stress ; Oxidative Stress - physiology ; Protein biosynthesis ; Rodents ; Senescence</subject><ispartof>Aging cell, 2014-12, Vol.13 (6), p.1038-1048</ispartof><rights>2014 The Authors. published by the Anatomical Society and John Wiley & Sons Ltd.</rights><rights>2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.</rights><rights>COPYRIGHT 2014 John Wiley & Sons, Inc.</rights><rights>Copyright © 2014 The Anatomical Society and John Wiley & Sons Ltd</rights><rights>2014 The Authors. published by the Anatomical Society and John Wiley & Sons Ltd. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5856-2f9a6895cbd6d0fd51f271ebd46565e5c9fdecb2b94733faf43200b36705c3963</citedby><cites>FETCH-LOGICAL-c5856-2f9a6895cbd6d0fd51f271ebd46565e5c9fdecb2b94733faf43200b36705c3963</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326930/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1627002993?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,11560,25751,27922,27923,37010,37011,44588,46050,46474,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25273919$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kozieł, Rafał</creatorcontrib><creatorcontrib>Ruckenstuhl, Christoph</creatorcontrib><creatorcontrib>Albertini, Eva</creatorcontrib><creatorcontrib>Neuhaus, Michael</creatorcontrib><creatorcontrib>Netzberger, Christine</creatorcontrib><creatorcontrib>Bust, Maria</creatorcontrib><creatorcontrib>Madeo, Frank</creatorcontrib><creatorcontrib>Wiesner, Rudolf J.</creatorcontrib><creatorcontrib>Jansen‐Dürr, Pidder</creatorcontrib><title>Methionine restriction slows down senescence in human diploid fibroblasts</title><title>Aging cell</title><addtitle>Aging Cell</addtitle><description>Summary
Methionine restriction (MetR) extends lifespan in animal models including rodents. Using human diploid fibroblasts (HDF), we report here that MetR significantly extends their replicative lifespan, thereby postponing cellular senescence. MetR significantly decreased activity of mitochondrial complex IV and diminished the accumulation of reactive oxygen species. Lifespan extension was accompanied by a significant decrease in the levels of subunits of mitochondrial complex IV, but also complex I, which was due to a decreased translation rate of several mtDNA‐encoded subunits. Together, these findings indicate that MetR slows down aging in human cells by modulating mitochondrial protein synthesis and respiratory chain assembly.</description><subject>Age Factors</subject><subject>Amino acids</subject><subject>Animals</subject><subject>B cells</subject><subject>cellular senescence</subject><subject>Diploidy</subject><subject>Disease Models, Animal</subject><subject>fibroblast</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - metabolism</subject><subject>Humans</subject><subject>Medical research</subject><subject>methionine</subject><subject>Methionine - administration & dosage</subject><subject>Methionine - deficiency</subject><subject>Methionine - metabolism</subject><subject>mitochondria</subject><subject>Mitochondria - metabolism</subject><subject>Original</subject><subject>oxidative stress</subject><subject>Oxidative Stress - physiology</subject><subject>Protein biosynthesis</subject><subject>Rodents</subject><subject>Senescence</subject><issn>1474-9718</issn><issn>1474-9726</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>PIMPY</sourceid><recordid>eNp9kVtrFDEUxwdRbK2--AFkwBcRds1lkkxehGWpWljxRZ9DJpduSiZZkxmXfnvPduvSipg85CT5nf-5Nc1rjJYY1gdtXFxiQjh_0pzjTnQLKQh_erJxf9a8qPUGISwkos-bM8KIoBLL8-bqq5u2IaeQXFtcnUowE1zbGvO-tjbvwXTJVeOScW1I7XYedWpt2MUcbOvDUPIQdZ3qy-aZ17G6V_fnRfPj0-X39ZfF5tvnq_VqszCsZ3xBvNS8l8wMllvkLcOeCOwG23HGmWNGeuvMQAbZCUq99h0lCA2UC8QMlZxeNB-Purt5GJ2FxKaio9qVMOpyq7IO6vFPClt1nX8pEOKSIhB4dy9Q8s8ZalZjgPpi1MnluSrMiZA9ET0F9O1f6E2eS4Ly7iiEiJQPqGsdnQrJZ4hrDqJqBVmLHrrdAbX8BwXbujGYnJwP8P7I4f3RwZRca3H-VCNG6jB4dRi8uhs8wG8eduWE_pk0APgI7CHM7X-k1Gp9uTmK_gYq7Lf8</recordid><startdate>201412</startdate><enddate>201412</enddate><creator>Kozieł, Rafał</creator><creator>Ruckenstuhl, Christoph</creator><creator>Albertini, Eva</creator><creator>Neuhaus, Michael</creator><creator>Netzberger, Christine</creator><creator>Bust, Maria</creator><creator>Madeo, Frank</creator><creator>Wiesner, Rudolf J.</creator><creator>Jansen‐Dürr, Pidder</creator><general>John Wiley & Sons, Inc</general><general>BlackWell Publishing Ltd</general><scope>24P</scope><scope>WIN</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>7QP</scope><scope>7TK</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201412</creationdate><title>Methionine restriction slows down senescence in human diploid fibroblasts</title><author>Kozieł, Rafał ; Ruckenstuhl, Christoph ; Albertini, Eva ; Neuhaus, Michael ; Netzberger, Christine ; Bust, Maria ; Madeo, Frank ; Wiesner, Rudolf J. ; Jansen‐Dürr, Pidder</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5856-2f9a6895cbd6d0fd51f271ebd46565e5c9fdecb2b94733faf43200b36705c3963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Age Factors</topic><topic>Amino acids</topic><topic>Animals</topic><topic>B cells</topic><topic>cellular senescence</topic><topic>Diploidy</topic><topic>Disease Models, Animal</topic><topic>fibroblast</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - drug effects</topic><topic>Fibroblasts - metabolism</topic><topic>Humans</topic><topic>Medical research</topic><topic>methionine</topic><topic>Methionine - administration & dosage</topic><topic>Methionine - deficiency</topic><topic>Methionine - metabolism</topic><topic>mitochondria</topic><topic>Mitochondria - metabolism</topic><topic>Original</topic><topic>oxidative stress</topic><topic>Oxidative Stress - physiology</topic><topic>Protein biosynthesis</topic><topic>Rodents</topic><topic>Senescence</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kozieł, Rafał</creatorcontrib><creatorcontrib>Ruckenstuhl, Christoph</creatorcontrib><creatorcontrib>Albertini, Eva</creatorcontrib><creatorcontrib>Neuhaus, Michael</creatorcontrib><creatorcontrib>Netzberger, Christine</creatorcontrib><creatorcontrib>Bust, Maria</creatorcontrib><creatorcontrib>Madeo, Frank</creatorcontrib><creatorcontrib>Wiesner, Rudolf J.</creatorcontrib><creatorcontrib>Jansen‐Dürr, Pidder</creatorcontrib><collection>Wiley Open Access</collection><collection>Wiley Free Archive</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>Biological Sciences</collection><collection>Biological Science Database</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 China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Aging cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kozieł, Rafał</au><au>Ruckenstuhl, Christoph</au><au>Albertini, Eva</au><au>Neuhaus, Michael</au><au>Netzberger, Christine</au><au>Bust, Maria</au><au>Madeo, Frank</au><au>Wiesner, Rudolf J.</au><au>Jansen‐Dürr, Pidder</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Methionine restriction slows down senescence in human diploid fibroblasts</atitle><jtitle>Aging cell</jtitle><addtitle>Aging Cell</addtitle><date>2014-12</date><risdate>2014</risdate><volume>13</volume><issue>6</issue><spage>1038</spage><epage>1048</epage><pages>1038-1048</pages><issn>1474-9718</issn><eissn>1474-9726</eissn><abstract>Summary
Methionine restriction (MetR) extends lifespan in animal models including rodents. Using human diploid fibroblasts (HDF), we report here that MetR significantly extends their replicative lifespan, thereby postponing cellular senescence. MetR significantly decreased activity of mitochondrial complex IV and diminished the accumulation of reactive oxygen species. Lifespan extension was accompanied by a significant decrease in the levels of subunits of mitochondrial complex IV, but also complex I, which was due to a decreased translation rate of several mtDNA‐encoded subunits. Together, these findings indicate that MetR slows down aging in human cells by modulating mitochondrial protein synthesis and respiratory chain assembly.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>25273919</pmid><doi>10.1111/acel.12266</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Age Factors Amino acids Animals B cells cellular senescence Diploidy Disease Models, Animal fibroblast Fibroblasts - cytology Fibroblasts - drug effects Fibroblasts - metabolism Humans Medical research methionine Methionine - administration & dosage Methionine - deficiency Methionine - metabolism mitochondria Mitochondria - metabolism Original oxidative stress Oxidative Stress - physiology Protein biosynthesis Rodents Senescence |
title | Methionine restriction slows down senescence in human diploid fibroblasts |
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