mTOR regulates the expression of DNA damage response enzymes in long‐lived Snell dwarf, GHRKO, and PAPPA‐KO mice
Summary Studies of the mTOR pathway have prompted speculation that diminished mTOR complex‐1 (mTORC1) function may be involved in controlling the aging process. Our previous studies have shown diminished mTORC1 activity in tissues of three long‐lived mutant mice: Snell dwarf mice, growth hormone rec...
Gespeichert in:
Veröffentlicht in: | Aging cell 2017-02, Vol.16 (1), p.52-60 |
---|---|
Hauptverfasser: | , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 60 |
---|---|
container_issue | 1 |
container_start_page | 52 |
container_title | Aging cell |
container_volume | 16 |
creator | Dominick, Graham Bowman, Jacqueline Li, Xinna Miller, Richard A. Garcia, Gonzalo G. |
description | Summary
Studies of the mTOR pathway have prompted speculation that diminished mTOR complex‐1 (mTORC1) function may be involved in controlling the aging process. Our previous studies have shown diminished mTORC1 activity in tissues of three long‐lived mutant mice: Snell dwarf mice, growth hormone receptor gene disrupted mice (GHRKO), and in this article, mice deficient in the pregnancy‐associated protein‐A (PAPPA‐KO). The ways in which lower mTOR signals slow aging and age‐related diseases are, however, not well characterized. Here, we show that Snell, GHKRO, and PAPPA‐KO mice express high levels of two proteins involved in DNA repair, O‐6‐methylguanine‐DNA methyltransferase (MGMT) and N‐myc downstream‐regulated gene 1 (NDRG1). Furthermore, we report that lowering mTOR enhances MGMT and NDRG1 protein expression via post‐transcriptional mechanisms. We show that the CCR4‐NOT complex, a post‐transcriptional regulator of gene expression, is downstream of the mTORC1 pathway and may be responsible for the upregulation of MGMT and NDRG1 in all three varieties of long‐lived mice. Our data thus suggest a novel link between DNA repair and mTOR signaling via post‐transcriptional regulation involving specific alteration in the CCR4‐NOT complex, whose modulation could control multiple aspects of the aging process. |
doi_str_mv | 10.1111/acel.12525 |
format | Article |
fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5242303</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A707845779</galeid><sourcerecordid>A707845779</sourcerecordid><originalsourceid>FETCH-LOGICAL-c6145-5d896144281fd4b05396a52a35fcae5ed224dc22d2644bbdc7a3773dd2f6f07e3</originalsourceid><addsrcrecordid>eNqNktFu0zAUhiMEYmNwwwMgS9wgtBbbsePkZlJUxoZW0WqMa8uNT7pMjl3iZKNc8Qg8I0_CKR2FIYSwL3xkf-e39ftPkqeMjhmOV6YCN2Zccnkv2WdCiVGheHZ_V7N8L3kU4xWlTBU0fZjscZWxXOViP-nbi9k56WA5ONNDJP0lEPi06iDGJngSavL6XUmsac0SEIur4CMS_vO6RbrxxAW__Pblq2uuwZL3Hpwj9sZ09SE5OT0_mx0S4y2Zl_N5idTZjLRNBY-TB7VxEZ7crgfJhzfHF5PT0XR28nZSTkdVxoQcSZsXWAies9qKBZVpkRnJTSrryoAEy7mwFeeWZ0IsFrZSJlUqtZbXWU0VpAfJ0VZ3NSxasBX4vjNOr7qmNd1aB9Pouye-udTLcK0lFzylKQq8uBXowscBYq_bJqLbzngIQ9RoIj4uzwv5H2gqJRUZKxB9_gd6FYbOoxNIyVxmion8F7U0DnTj64BPrDaiulQUP08qtdEa_4XCaQGdDh7qBvfvNLzcNlRdiLGDemcHo3oTJ72Jk_4RJ4Sf_W7gDv2ZHwTYFrjBa9b_kNLl5Hi6Ff0OSOnUJw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1858567148</pqid></control><display><type>article</type><title>mTOR regulates the expression of DNA damage response enzymes in long‐lived Snell dwarf, GHRKO, and PAPPA‐KO mice</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Access via Wiley Online Library</source><source>Wiley Online Library Open Access</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Dominick, Graham ; Bowman, Jacqueline ; Li, Xinna ; Miller, Richard A. ; Garcia, Gonzalo G.</creator><creatorcontrib>Dominick, Graham ; Bowman, Jacqueline ; Li, Xinna ; Miller, Richard A. ; Garcia, Gonzalo G.</creatorcontrib><description>Summary
Studies of the mTOR pathway have prompted speculation that diminished mTOR complex‐1 (mTORC1) function may be involved in controlling the aging process. Our previous studies have shown diminished mTORC1 activity in tissues of three long‐lived mutant mice: Snell dwarf mice, growth hormone receptor gene disrupted mice (GHRKO), and in this article, mice deficient in the pregnancy‐associated protein‐A (PAPPA‐KO). The ways in which lower mTOR signals slow aging and age‐related diseases are, however, not well characterized. Here, we show that Snell, GHKRO, and PAPPA‐KO mice express high levels of two proteins involved in DNA repair, O‐6‐methylguanine‐DNA methyltransferase (MGMT) and N‐myc downstream‐regulated gene 1 (NDRG1). Furthermore, we report that lowering mTOR enhances MGMT and NDRG1 protein expression via post‐transcriptional mechanisms. We show that the CCR4‐NOT complex, a post‐transcriptional regulator of gene expression, is downstream of the mTORC1 pathway and may be responsible for the upregulation of MGMT and NDRG1 in all three varieties of long‐lived mice. Our data thus suggest a novel link between DNA repair and mTOR signaling via post‐transcriptional regulation involving specific alteration in the CCR4‐NOT complex, whose modulation could control multiple aspects of the aging process.</description><identifier>ISSN: 1474-9718</identifier><identifier>EISSN: 1474-9726</identifier><identifier>DOI: 10.1111/acel.12525</identifier><identifier>PMID: 27618784</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Aging ; Animals ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; Deoxyribonucleic acid ; DNA ; DNA Damage ; DNA Modification Methylases - genetics ; DNA Modification Methylases - metabolism ; DNA repair ; DNA Repair Enzymes - genetics ; DNA Repair Enzymes - metabolism ; Down-Regulation - drug effects ; Dwarfism - metabolism ; Enzymes ; Female ; Gene expression ; Genes ; Genetic transcription ; IGF ; Intracellular Signaling Peptides and Proteins - genetics ; Intracellular Signaling Peptides and Proteins - metabolism ; Liver - drug effects ; Liver - metabolism ; Longevity ; Male ; Mice ; Mice, Knockout ; Models, Biological ; molecular biology of aging ; Original ; Pregnancy-Associated Plasma Protein-A - deficiency ; Pregnancy-Associated Plasma Protein-A - metabolism ; Receptors, CCR4 - metabolism ; Receptors, Somatotropin - deficiency ; Receptors, Somatotropin - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Rodents ; signal transduction ; Sirolimus - pharmacology ; Somatotropin ; TOR Serine-Threonine Kinases - metabolism ; Transcription Factors - metabolism ; Tumor Suppressor Proteins - genetics ; Tumor Suppressor Proteins - metabolism</subject><ispartof>Aging cell, 2017-02, Vol.16 (1), p.52-60</ispartof><rights>2016 The Authors. published by the Anatomical Society and John Wiley & Sons Ltd.</rights><rights>2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.</rights><rights>COPYRIGHT 2016 John Wiley & Sons, Inc.</rights><rights>Copyright © 2017 The Anatomical Society and John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6145-5d896144281fd4b05396a52a35fcae5ed224dc22d2644bbdc7a3773dd2f6f07e3</citedby><cites>FETCH-LOGICAL-c6145-5d896144281fd4b05396a52a35fcae5ed224dc22d2644bbdc7a3773dd2f6f07e3</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/PMC5242303/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242303/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1417,11562,27924,27925,45574,45575,46052,46476,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27618784$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dominick, Graham</creatorcontrib><creatorcontrib>Bowman, Jacqueline</creatorcontrib><creatorcontrib>Li, Xinna</creatorcontrib><creatorcontrib>Miller, Richard A.</creatorcontrib><creatorcontrib>Garcia, Gonzalo G.</creatorcontrib><title>mTOR regulates the expression of DNA damage response enzymes in long‐lived Snell dwarf, GHRKO, and PAPPA‐KO mice</title><title>Aging cell</title><addtitle>Aging Cell</addtitle><description>Summary
Studies of the mTOR pathway have prompted speculation that diminished mTOR complex‐1 (mTORC1) function may be involved in controlling the aging process. Our previous studies have shown diminished mTORC1 activity in tissues of three long‐lived mutant mice: Snell dwarf mice, growth hormone receptor gene disrupted mice (GHRKO), and in this article, mice deficient in the pregnancy‐associated protein‐A (PAPPA‐KO). The ways in which lower mTOR signals slow aging and age‐related diseases are, however, not well characterized. Here, we show that Snell, GHKRO, and PAPPA‐KO mice express high levels of two proteins involved in DNA repair, O‐6‐methylguanine‐DNA methyltransferase (MGMT) and N‐myc downstream‐regulated gene 1 (NDRG1). Furthermore, we report that lowering mTOR enhances MGMT and NDRG1 protein expression via post‐transcriptional mechanisms. We show that the CCR4‐NOT complex, a post‐transcriptional regulator of gene expression, is downstream of the mTORC1 pathway and may be responsible for the upregulation of MGMT and NDRG1 in all three varieties of long‐lived mice. Our data thus suggest a novel link between DNA repair and mTOR signaling via post‐transcriptional regulation involving specific alteration in the CCR4‐NOT complex, whose modulation could control multiple aspects of the aging process.</description><subject>Aging</subject><subject>Animals</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Damage</subject><subject>DNA Modification Methylases - genetics</subject><subject>DNA Modification Methylases - metabolism</subject><subject>DNA repair</subject><subject>DNA Repair Enzymes - genetics</subject><subject>DNA Repair Enzymes - metabolism</subject><subject>Down-Regulation - drug effects</subject><subject>Dwarfism - metabolism</subject><subject>Enzymes</subject><subject>Female</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic transcription</subject><subject>IGF</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Longevity</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Models, Biological</subject><subject>molecular biology of aging</subject><subject>Original</subject><subject>Pregnancy-Associated Plasma Protein-A - deficiency</subject><subject>Pregnancy-Associated Plasma Protein-A - metabolism</subject><subject>Receptors, CCR4 - metabolism</subject><subject>Receptors, Somatotropin - deficiency</subject><subject>Receptors, Somatotropin - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Rodents</subject><subject>signal transduction</subject><subject>Sirolimus - pharmacology</subject><subject>Somatotropin</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><subject>Transcription Factors - metabolism</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Tumor Suppressor Proteins - metabolism</subject><issn>1474-9718</issn><issn>1474-9726</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNktFu0zAUhiMEYmNwwwMgS9wgtBbbsePkZlJUxoZW0WqMa8uNT7pMjl3iZKNc8Qg8I0_CKR2FIYSwL3xkf-e39ftPkqeMjhmOV6YCN2Zccnkv2WdCiVGheHZ_V7N8L3kU4xWlTBU0fZjscZWxXOViP-nbi9k56WA5ONNDJP0lEPi06iDGJngSavL6XUmsac0SEIur4CMS_vO6RbrxxAW__Pblq2uuwZL3Hpwj9sZ09SE5OT0_mx0S4y2Zl_N5idTZjLRNBY-TB7VxEZ7crgfJhzfHF5PT0XR28nZSTkdVxoQcSZsXWAies9qKBZVpkRnJTSrryoAEy7mwFeeWZ0IsFrZSJlUqtZbXWU0VpAfJ0VZ3NSxasBX4vjNOr7qmNd1aB9Pouye-udTLcK0lFzylKQq8uBXowscBYq_bJqLbzngIQ9RoIj4uzwv5H2gqJRUZKxB9_gd6FYbOoxNIyVxmion8F7U0DnTj64BPrDaiulQUP08qtdEa_4XCaQGdDh7qBvfvNLzcNlRdiLGDemcHo3oTJ72Jk_4RJ4Sf_W7gDv2ZHwTYFrjBa9b_kNLl5Hi6Ff0OSOnUJw</recordid><startdate>201702</startdate><enddate>201702</enddate><creator>Dominick, Graham</creator><creator>Bowman, Jacqueline</creator><creator>Li, Xinna</creator><creator>Miller, Richard A.</creator><creator>Garcia, Gonzalo G.</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</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>7TM</scope><scope>5PM</scope></search><sort><creationdate>201702</creationdate><title>mTOR regulates the expression of DNA damage response enzymes in long‐lived Snell dwarf, GHRKO, and PAPPA‐KO mice</title><author>Dominick, Graham ; Bowman, Jacqueline ; Li, Xinna ; Miller, Richard A. ; Garcia, Gonzalo G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6145-5d896144281fd4b05396a52a35fcae5ed224dc22d2644bbdc7a3773dd2f6f07e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aging</topic><topic>Animals</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Damage</topic><topic>DNA Modification Methylases - genetics</topic><topic>DNA Modification Methylases - metabolism</topic><topic>DNA repair</topic><topic>DNA Repair Enzymes - genetics</topic><topic>DNA Repair Enzymes - metabolism</topic><topic>Down-Regulation - drug effects</topic><topic>Dwarfism - metabolism</topic><topic>Enzymes</topic><topic>Female</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic transcription</topic><topic>IGF</topic><topic>Intracellular Signaling Peptides and Proteins - genetics</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Longevity</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Models, Biological</topic><topic>molecular biology of aging</topic><topic>Original</topic><topic>Pregnancy-Associated Plasma Protein-A - deficiency</topic><topic>Pregnancy-Associated Plasma Protein-A - metabolism</topic><topic>Receptors, CCR4 - metabolism</topic><topic>Receptors, Somatotropin - deficiency</topic><topic>Receptors, Somatotropin - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Rodents</topic><topic>signal transduction</topic><topic>Sirolimus - pharmacology</topic><topic>Somatotropin</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><topic>Transcription Factors - metabolism</topic><topic>Tumor Suppressor Proteins - genetics</topic><topic>Tumor Suppressor Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dominick, Graham</creatorcontrib><creatorcontrib>Bowman, Jacqueline</creatorcontrib><creatorcontrib>Li, Xinna</creatorcontrib><creatorcontrib>Miller, Richard A.</creatorcontrib><creatorcontrib>Garcia, Gonzalo G.</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library (Open Access Collection)</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Access via ProQuest (Open Access)</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>Nucleic Acids Abstracts</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>Dominick, Graham</au><au>Bowman, Jacqueline</au><au>Li, Xinna</au><au>Miller, Richard A.</au><au>Garcia, Gonzalo G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>mTOR regulates the expression of DNA damage response enzymes in long‐lived Snell dwarf, GHRKO, and PAPPA‐KO mice</atitle><jtitle>Aging cell</jtitle><addtitle>Aging Cell</addtitle><date>2017-02</date><risdate>2017</risdate><volume>16</volume><issue>1</issue><spage>52</spage><epage>60</epage><pages>52-60</pages><issn>1474-9718</issn><eissn>1474-9726</eissn><abstract>Summary
Studies of the mTOR pathway have prompted speculation that diminished mTOR complex‐1 (mTORC1) function may be involved in controlling the aging process. Our previous studies have shown diminished mTORC1 activity in tissues of three long‐lived mutant mice: Snell dwarf mice, growth hormone receptor gene disrupted mice (GHRKO), and in this article, mice deficient in the pregnancy‐associated protein‐A (PAPPA‐KO). The ways in which lower mTOR signals slow aging and age‐related diseases are, however, not well characterized. Here, we show that Snell, GHKRO, and PAPPA‐KO mice express high levels of two proteins involved in DNA repair, O‐6‐methylguanine‐DNA methyltransferase (MGMT) and N‐myc downstream‐regulated gene 1 (NDRG1). Furthermore, we report that lowering mTOR enhances MGMT and NDRG1 protein expression via post‐transcriptional mechanisms. We show that the CCR4‐NOT complex, a post‐transcriptional regulator of gene expression, is downstream of the mTORC1 pathway and may be responsible for the upregulation of MGMT and NDRG1 in all three varieties of long‐lived mice. Our data thus suggest a novel link between DNA repair and mTOR signaling via post‐transcriptional regulation involving specific alteration in the CCR4‐NOT complex, whose modulation could control multiple aspects of the aging process.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>27618784</pmid><doi>10.1111/acel.12525</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1474-9718 |
ispartof | Aging cell, 2017-02, Vol.16 (1), p.52-60 |
issn | 1474-9718 1474-9726 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5242303 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Access via Wiley Online Library; Wiley Online Library Open Access; PubMed Central; Alma/SFX Local Collection |
subjects | Aging Animals Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Deoxyribonucleic acid DNA DNA Damage DNA Modification Methylases - genetics DNA Modification Methylases - metabolism DNA repair DNA Repair Enzymes - genetics DNA Repair Enzymes - metabolism Down-Regulation - drug effects Dwarfism - metabolism Enzymes Female Gene expression Genes Genetic transcription IGF Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism Liver - drug effects Liver - metabolism Longevity Male Mice Mice, Knockout Models, Biological molecular biology of aging Original Pregnancy-Associated Plasma Protein-A - deficiency Pregnancy-Associated Plasma Protein-A - metabolism Receptors, CCR4 - metabolism Receptors, Somatotropin - deficiency Receptors, Somatotropin - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Rodents signal transduction Sirolimus - pharmacology Somatotropin TOR Serine-Threonine Kinases - metabolism Transcription Factors - metabolism Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism |
title | mTOR regulates the expression of DNA damage response enzymes in long‐lived Snell dwarf, GHRKO, and PAPPA‐KO mice |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T08%3A26%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=mTOR%20regulates%20the%20expression%20of%20DNA%20damage%20response%20enzymes%20in%20long%E2%80%90lived%20Snell%20dwarf,%20GHRKO,%20and%20PAPPA%E2%80%90KO%20mice&rft.jtitle=Aging%20cell&rft.au=Dominick,%20Graham&rft.date=2017-02&rft.volume=16&rft.issue=1&rft.spage=52&rft.epage=60&rft.pages=52-60&rft.issn=1474-9718&rft.eissn=1474-9726&rft_id=info:doi/10.1111/acel.12525&rft_dat=%3Cgale_pubme%3EA707845779%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1858567148&rft_id=info:pmid/27618784&rft_galeid=A707845779&rfr_iscdi=true |