Does reduced IGF-1R signaling in Igf1r+/- mice alter aging?
Mutations in insulin/IGF-1 signaling pathway have been shown to lead to increased longevity in various invertebrate models. Therefore, the effect of the haplo-insufficiency of the IGF-1 receptor (Igf1r(+/-)) on longevity/aging was evaluated in C57Bl/6 mice using rigorous criteria where lifespan and...
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| Veröffentlicht in: | PloS one 2011-11, Vol.6 (11), p.e26891 |
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| creator | Bokov, Alex F Garg, Neha Ikeno, Yuji Thakur, Sachin Musi, Nicolas DeFronzo, Ralph A Zhang, Ning Erickson, Rebecca C Gelfond, Jon Hubbard, Gene B Adamo, Martin L Richardson, Arlan |
| description | Mutations in insulin/IGF-1 signaling pathway have been shown to lead to increased longevity in various invertebrate models. Therefore, the effect of the haplo-insufficiency of the IGF-1 receptor (Igf1r(+/-)) on longevity/aging was evaluated in C57Bl/6 mice using rigorous criteria where lifespan and end-of-life pathology were measured under optimal husbandry conditions using large sample sizes. Igf1r(+/-) mice exhibited reductions in IGF-1 receptor levels and the activation of Akt by IGF-1, with no compensatory increases in serum IGF-1 or tissue IGF-1 mRNA levels, indicating that the Igf1r(+/-) mice show reduced IGF-1 signaling. Aged male, but not female Igf1r(+/-) mice were glucose intolerant, and both genders developed insulin resistance as they aged. Female, but not male Igf1r(+/-) mice survived longer than wild type mice after lethal paraquat and diquat exposure, and female Igf1r(+/-) mice also exhibited less diquat-induced liver damage. However, no significant difference between the lifespans of the male Igf1r(+/-) and wild type mice was observed; and the mean lifespan of the Igf1r(+/-) females was increased only slightly (less than 5%) compared to wild type mice. A comprehensive pathological analysis showed no significant difference in end-of-life pathological lesions between the Igf1r(+/-) and wild type mice. These data show that the Igf1r(+/-) mouse is not a model of increased longevity and delayed aging as predicted by invertebrate models with mutations in the insulin/IGF-1 signaling pathway. |
| doi_str_mv | 10.1371/journal.pone.0026891 |
| format | Article |
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Therefore, the effect of the haplo-insufficiency of the IGF-1 receptor (Igf1r(+/-)) on longevity/aging was evaluated in C57Bl/6 mice using rigorous criteria where lifespan and end-of-life pathology were measured under optimal husbandry conditions using large sample sizes. Igf1r(+/-) mice exhibited reductions in IGF-1 receptor levels and the activation of Akt by IGF-1, with no compensatory increases in serum IGF-1 or tissue IGF-1 mRNA levels, indicating that the Igf1r(+/-) mice show reduced IGF-1 signaling. Aged male, but not female Igf1r(+/-) mice were glucose intolerant, and both genders developed insulin resistance as they aged. Female, but not male Igf1r(+/-) mice survived longer than wild type mice after lethal paraquat and diquat exposure, and female Igf1r(+/-) mice also exhibited less diquat-induced liver damage. However, no significant difference between the lifespans of the male Igf1r(+/-) and wild type mice was observed; and the mean lifespan of the Igf1r(+/-) females was increased only slightly (less than 5%) compared to wild type mice. A comprehensive pathological analysis showed no significant difference in end-of-life pathological lesions between the Igf1r(+/-) and wild type mice. These data show that the Igf1r(+/-) mouse is not a model of increased longevity and delayed aging as predicted by invertebrate models with mutations in the insulin/IGF-1 signaling pathway.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0026891</identifier><identifier>PMID: 22132081</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aging ; Aging - drug effects ; Aging - physiology ; AKT protein ; Animal husbandry ; Animal models ; Animals ; Apoptosis ; Biology ; Diquat ; Drosophila ; Female ; Females ; Gene Expression Regulation - drug effects ; Glucose Tolerance Test ; Glycogen Synthase Kinase 3 - metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Insulin ; Insulin - pharmacology ; Insulin resistance ; Insulin-Like Growth Factor Binding Protein 5 - genetics ; Insulin-Like Growth Factor Binding Protein 5 - metabolism ; Insulin-like growth factor I ; Insulin-Like Growth Factor I - pharmacology ; Insulin-like growth factors ; Invertebrates ; Lesions ; Life span ; Liver ; Longevity ; Male ; Medicine ; Mice ; Mice, Inbred C57BL ; mRNA ; Mutation ; Oxidative stress ; Oxidative Stress - drug effects ; Paraquat ; Phosphorylation - drug effects ; Proto-Oncogene Proteins c-akt - metabolism ; Receptor, IGF Type 1 - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Rodents ; Science ; Signal transduction ; Signal Transduction - drug effects ; Signaling ; Trauma centers</subject><ispartof>PloS one, 2011-11, Vol.6 (11), p.e26891</ispartof><rights>2011 Bokov et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Bokov et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c576t-dd4afdf31122bce457ac887c38518e152b219e9f36a2d461e015d6f5a88001ab3</citedby><cites>FETCH-LOGICAL-c576t-dd4afdf31122bce457ac887c38518e152b219e9f36a2d461e015d6f5a88001ab3</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/PMC3223158/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223158/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22132081$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bokov, Alex F</creatorcontrib><creatorcontrib>Garg, Neha</creatorcontrib><creatorcontrib>Ikeno, Yuji</creatorcontrib><creatorcontrib>Thakur, Sachin</creatorcontrib><creatorcontrib>Musi, Nicolas</creatorcontrib><creatorcontrib>DeFronzo, Ralph A</creatorcontrib><creatorcontrib>Zhang, Ning</creatorcontrib><creatorcontrib>Erickson, Rebecca C</creatorcontrib><creatorcontrib>Gelfond, Jon</creatorcontrib><creatorcontrib>Hubbard, Gene B</creatorcontrib><creatorcontrib>Adamo, Martin L</creatorcontrib><creatorcontrib>Richardson, Arlan</creatorcontrib><title>Does reduced IGF-1R signaling in Igf1r+/- mice alter aging?</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Mutations in insulin/IGF-1 signaling pathway have been shown to lead to increased longevity in various invertebrate models. Therefore, the effect of the haplo-insufficiency of the IGF-1 receptor (Igf1r(+/-)) on longevity/aging was evaluated in C57Bl/6 mice using rigorous criteria where lifespan and end-of-life pathology were measured under optimal husbandry conditions using large sample sizes. Igf1r(+/-) mice exhibited reductions in IGF-1 receptor levels and the activation of Akt by IGF-1, with no compensatory increases in serum IGF-1 or tissue IGF-1 mRNA levels, indicating that the Igf1r(+/-) mice show reduced IGF-1 signaling. Aged male, but not female Igf1r(+/-) mice were glucose intolerant, and both genders developed insulin resistance as they aged. Female, but not male Igf1r(+/-) mice survived longer than wild type mice after lethal paraquat and diquat exposure, and female Igf1r(+/-) mice also exhibited less diquat-induced liver damage. 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metabolism</subject><subject>Insulin-like growth factor I</subject><subject>Insulin-Like Growth Factor I - pharmacology</subject><subject>Insulin-like growth factors</subject><subject>Invertebrates</subject><subject>Lesions</subject><subject>Life span</subject><subject>Liver</subject><subject>Longevity</subject><subject>Male</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>mRNA</subject><subject>Mutation</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Paraquat</subject><subject>Phosphorylation - drug effects</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Receptor, IGF Type 1 - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Rodents</subject><subject>Science</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Signaling</subject><subject>Trauma centers</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNp1kVtLxDAQhYMo3v-BaMFH6ZpJmjRFUMTrgiCIPodsMq1dus2adAX_vV23ij74lJA555uZHEIOgI6A53A69YvQmmY09y2OKGVSFbBGtqHgLJWM8vVf9y2yE-OUUsGVlJtkizHgjCrYJmfXHmMS0C0sumR8d5vCUxLrqifXbZXUbTKuSggnp2kyqy0mpukwJKbqixd7ZKM0TcT94dwlL7c3z1f36cPj3fjq8iG1Ipdd6lxmSldyAMYmFjORG6tUbrkSoBAEmzAosCi5NMxlEpCCcLIURilKwUz4LjlaceeNj3rYO2rgQBkrIOO9YrxSOG-meh7qmQkf2ptafz34UGkTuto2qK2lBdCCCsizDCwvkCkhpO2_LxcOl6zzodtiMkNnse2Caf5A_1ba-lVX_l1zxjgI1QOOB0DwbwuM3T8jZyuVDT7GgOVPB6B6GfC3Sy8D1kPAve3w93Q_pu9E-Sc896Ar</recordid><startdate>20111123</startdate><enddate>20111123</enddate><creator>Bokov, Alex F</creator><creator>Garg, Neha</creator><creator>Ikeno, Yuji</creator><creator>Thakur, Sachin</creator><creator>Musi, Nicolas</creator><creator>DeFronzo, Ralph A</creator><creator>Zhang, Ning</creator><creator>Erickson, Rebecca C</creator><creator>Gelfond, Jon</creator><creator>Hubbard, Gene B</creator><creator>Adamo, Martin L</creator><creator>Richardson, Arlan</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20111123</creationdate><title>Does reduced IGF-1R signaling in Igf1r+/- mice alter aging?</title><author>Bokov, Alex F ; Garg, Neha ; Ikeno, Yuji ; Thakur, Sachin ; Musi, Nicolas ; DeFronzo, Ralph A ; Zhang, Ning ; Erickson, Rebecca C ; Gelfond, Jon ; Hubbard, Gene B ; Adamo, Martin L ; Richardson, Arlan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c576t-dd4afdf31122bce457ac887c38518e152b219e9f36a2d461e015d6f5a88001ab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Aging</topic><topic>Aging - 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Therefore, the effect of the haplo-insufficiency of the IGF-1 receptor (Igf1r(+/-)) on longevity/aging was evaluated in C57Bl/6 mice using rigorous criteria where lifespan and end-of-life pathology were measured under optimal husbandry conditions using large sample sizes. Igf1r(+/-) mice exhibited reductions in IGF-1 receptor levels and the activation of Akt by IGF-1, with no compensatory increases in serum IGF-1 or tissue IGF-1 mRNA levels, indicating that the Igf1r(+/-) mice show reduced IGF-1 signaling. Aged male, but not female Igf1r(+/-) mice were glucose intolerant, and both genders developed insulin resistance as they aged. Female, but not male Igf1r(+/-) mice survived longer than wild type mice after lethal paraquat and diquat exposure, and female Igf1r(+/-) mice also exhibited less diquat-induced liver damage. However, no significant difference between the lifespans of the male Igf1r(+/-) and wild type mice was observed; and the mean lifespan of the Igf1r(+/-) females was increased only slightly (less than 5%) compared to wild type mice. A comprehensive pathological analysis showed no significant difference in end-of-life pathological lesions between the Igf1r(+/-) and wild type mice. These data show that the Igf1r(+/-) mouse is not a model of increased longevity and delayed aging as predicted by invertebrate models with mutations in the insulin/IGF-1 signaling pathway.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22132081</pmid><doi>10.1371/journal.pone.0026891</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2011-11, Vol.6 (11), p.e26891 |
| issn | 1932-6203 1932-6203 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Aging Aging - drug effects Aging - physiology AKT protein Animal husbandry Animal models Animals Apoptosis Biology Diquat Drosophila Female Females Gene Expression Regulation - drug effects Glucose Tolerance Test Glycogen Synthase Kinase 3 - metabolism Glycogen Synthase Kinase 3 beta Humans Insulin Insulin - pharmacology Insulin resistance Insulin-Like Growth Factor Binding Protein 5 - genetics Insulin-Like Growth Factor Binding Protein 5 - metabolism Insulin-like growth factor I Insulin-Like Growth Factor I - pharmacology Insulin-like growth factors Invertebrates Lesions Life span Liver Longevity Male Medicine Mice Mice, Inbred C57BL mRNA Mutation Oxidative stress Oxidative Stress - drug effects Paraquat Phosphorylation - drug effects Proto-Oncogene Proteins c-akt - metabolism Receptor, IGF Type 1 - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Rodents Science Signal transduction Signal Transduction - drug effects Signaling Trauma centers |
| title | Does reduced IGF-1R signaling in Igf1r+/- mice alter aging? |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T06%3A11%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Does%20reduced%20IGF-1R%20signaling%20in%20Igf1r+/-%20mice%20alter%20aging?&rft.jtitle=PloS%20one&rft.au=Bokov,%20Alex%20F&rft.date=2011-11-23&rft.volume=6&rft.issue=11&rft.spage=e26891&rft.pages=e26891-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0026891&rft_dat=%3Cproquest_plos_%3E2900287251%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1310229143&rft_id=info:pmid/22132081&rft_doaj_id=oai_doaj_org_article_cc091090517441c39e28556c68975de3&rfr_iscdi=true |