bile acid-like steroid modulates Caenorhabditis elegans lifespan through nuclear receptor signaling
Broad aspects of Caenorhabditis elegans life history, including larval developmental timing, arrest at the dauer diapause, and longevity, are regulated by the nuclear receptor DAF-12. Endogenous DAF-12 ligands are 3-keto bile acid-like steroids, called dafachronic acids, which rescue larval defects...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2007-03, Vol.104 (12), p.5014-5019 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Gerisch, Birgit Rottiers, Veerle Li, Dongling Motola, Daniel L Cummins, Carolyn L Lehrach, Hans Mangelsdorf, David J Antebi, Adam |
| description | Broad aspects of Caenorhabditis elegans life history, including larval developmental timing, arrest at the dauer diapause, and longevity, are regulated by the nuclear receptor DAF-12. Endogenous DAF-12 ligands are 3-keto bile acid-like steroids, called dafachronic acids, which rescue larval defects of hormone-deficient mutants, such as daf-9/cytochrome P450 and daf-36/Rieske oxygenase, and activate DAF-12. Here we examined the effect of dafachronic acid on pathways controlling lifespan. Dafachronic acid supplementation shortened the lifespan of long-lived daf-9 mutants and abolished their stress resistance, indicating that the ligand is "proaging" in response to signals from the dauer pathways. However, the ligand extended the lifespan of germ-line ablated daf-9 and daf-36 mutants, showing that it is "antiaging" in the germ-line longevity pathway. Thus, dafachronic acid regulates C. elegans lifespan according to signaling state. These studies provide key evidence that bile acid-like steroids modulate aging in animals. |
| doi_str_mv | 10.1073/pnas.0700847104 |
| format | Article |
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Endogenous DAF-12 ligands are 3-keto bile acid-like steroids, called dafachronic acids, which rescue larval defects of hormone-deficient mutants, such as daf-9/cytochrome P450 and daf-36/Rieske oxygenase, and activate DAF-12. Here we examined the effect of dafachronic acid on pathways controlling lifespan. Dafachronic acid supplementation shortened the lifespan of long-lived daf-9 mutants and abolished their stress resistance, indicating that the ligand is "proaging" in response to signals from the dauer pathways. However, the ligand extended the lifespan of germ-line ablated daf-9 and daf-36 mutants, showing that it is "antiaging" in the germ-line longevity pathway. Thus, dafachronic acid regulates C. elegans lifespan according to signaling state. These studies provide key evidence that bile acid-like steroids modulate aging in animals.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0700847104</identifier><identifier>PMID: 17360327</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Adaptation, Physiological - drug effects ; Aging ; Animals ; Bile ; Bile acids ; Bile Acids and Salts - pharmacology ; Biological Sciences ; Caenorhabditis elegans ; Caenorhabditis elegans - drug effects ; Caenorhabditis elegans - physiology ; Caenorhabditis elegans Proteins - metabolism ; Cell Nucleus - drug effects ; Cytochrome P-450 Enzyme System - metabolism ; Genetics ; Germ Cells - drug effects ; Heat tolerance ; Hormonal regulation ; Hormones ; Intestines - drug effects ; Invertebrate Hormones - pharmacology ; Larva - drug effects ; Larval development ; Ligands ; Longevity ; Longevity - drug effects ; Molecular biology ; Nematode larvae ; Oxidative stress ; Receptors, Cytoplasmic and Nuclear - metabolism ; Recombinant Fusion Proteins - metabolism ; Signal Transduction - drug effects ; Steroids ; Stress tolerance ; Temperature</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2007-03, Vol.104 (12), p.5014-5019</ispartof><rights>Copyright 2007 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Mar 20, 2007</rights><rights>2007 by The National Academy of Sciences of the USA 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c552t-aa35d0727b5005948ee66b9c99e14da1ab9997dbd1da0df01b7c777dcd1fdd913</citedby><cites>FETCH-LOGICAL-c552t-aa35d0727b5005948ee66b9c99e14da1ab9997dbd1da0df01b7c777dcd1fdd913</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/104/12.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25427136$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25427136$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17360327$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gerisch, Birgit</creatorcontrib><creatorcontrib>Rottiers, Veerle</creatorcontrib><creatorcontrib>Li, Dongling</creatorcontrib><creatorcontrib>Motola, Daniel L</creatorcontrib><creatorcontrib>Cummins, Carolyn L</creatorcontrib><creatorcontrib>Lehrach, Hans</creatorcontrib><creatorcontrib>Mangelsdorf, David J</creatorcontrib><creatorcontrib>Antebi, Adam</creatorcontrib><title>bile acid-like steroid modulates Caenorhabditis elegans lifespan through nuclear receptor signaling</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Broad aspects of Caenorhabditis elegans life history, including larval developmental timing, arrest at the dauer diapause, and longevity, are regulated by the nuclear receptor DAF-12. Endogenous DAF-12 ligands are 3-keto bile acid-like steroids, called dafachronic acids, which rescue larval defects of hormone-deficient mutants, such as daf-9/cytochrome P450 and daf-36/Rieske oxygenase, and activate DAF-12. Here we examined the effect of dafachronic acid on pathways controlling lifespan. Dafachronic acid supplementation shortened the lifespan of long-lived daf-9 mutants and abolished their stress resistance, indicating that the ligand is "proaging" in response to signals from the dauer pathways. However, the ligand extended the lifespan of germ-line ablated daf-9 and daf-36 mutants, showing that it is "antiaging" in the germ-line longevity pathway. Thus, dafachronic acid regulates C. elegans lifespan according to signaling state. These studies provide key evidence that bile acid-like steroids modulate aging in animals.</description><subject>Adaptation, Physiological - drug effects</subject><subject>Aging</subject><subject>Animals</subject><subject>Bile</subject><subject>Bile acids</subject><subject>Bile Acids and Salts - pharmacology</subject><subject>Biological Sciences</subject><subject>Caenorhabditis elegans</subject><subject>Caenorhabditis elegans - drug effects</subject><subject>Caenorhabditis elegans - physiology</subject><subject>Caenorhabditis elegans Proteins - metabolism</subject><subject>Cell Nucleus - drug effects</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>Genetics</subject><subject>Germ Cells - drug effects</subject><subject>Heat tolerance</subject><subject>Hormonal regulation</subject><subject>Hormones</subject><subject>Intestines - drug effects</subject><subject>Invertebrate Hormones - pharmacology</subject><subject>Larva - drug effects</subject><subject>Larval development</subject><subject>Ligands</subject><subject>Longevity</subject><subject>Longevity - drug effects</subject><subject>Molecular biology</subject><subject>Nematode larvae</subject><subject>Oxidative stress</subject><subject>Receptors, Cytoplasmic and Nuclear - metabolism</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Steroids</subject><subject>Stress tolerance</subject><subject>Temperature</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0b9v1DAUB_AIgehRmJkAiwGxpH12fjheKqETBaRKDNDZerFfcj588WEnqPz3JLpTDxhg8uCPv_bzN8uec7jgIIvL_YDpAiRAU0oO5YNsxUHxvC4VPMxWAELmTSnKs-xJSlsAUFUDj7MzLosaCiFXmWmdJ4bG2dy7b8TSSDE4y3bBTh5HSmyNNIS4wda60SVGnnocEvOuo7THgY2bGKZ-w4bJeMLIIhnajyGy5PoBvRv6p9mjDn2iZ8f1PLu9fv91_TG_-fzh0_rdTW6qSow5YlFZkEK2FUClyoaorltllCJeWuTYKqWkbS23CLYD3kojpbTG8s5axYvz7OqQu5_aHVlDwxjR6310O4w_dUCn_9wZ3Eb34YfmjeBcyDngzTEghu8TpVHvXDLkPQ4UpqQlCNVAXf8XCqiaSig1w9d_wW2Y4vwti-FFA6oQM7o8IBNDSpG6-ydz0EvNeqlZn2qeT7z8fdKTP_Y6g1dHsJw8xZWaC10BXyLe_lvobvJ-pLtxpi8OdJvmXu-tqEoheVGfLuswaOyjS_r2yzIegJyf04jiF5wk0Po</recordid><startdate>20070320</startdate><enddate>20070320</enddate><creator>Gerisch, Birgit</creator><creator>Rottiers, Veerle</creator><creator>Li, Dongling</creator><creator>Motola, Daniel L</creator><creator>Cummins, Carolyn L</creator><creator>Lehrach, Hans</creator><creator>Mangelsdorf, David J</creator><creator>Antebi, Adam</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7ST</scope><scope>7U6</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20070320</creationdate><title>bile acid-like steroid modulates Caenorhabditis elegans lifespan through nuclear receptor signaling</title><author>Gerisch, Birgit ; 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Endogenous DAF-12 ligands are 3-keto bile acid-like steroids, called dafachronic acids, which rescue larval defects of hormone-deficient mutants, such as daf-9/cytochrome P450 and daf-36/Rieske oxygenase, and activate DAF-12. Here we examined the effect of dafachronic acid on pathways controlling lifespan. Dafachronic acid supplementation shortened the lifespan of long-lived daf-9 mutants and abolished their stress resistance, indicating that the ligand is "proaging" in response to signals from the dauer pathways. However, the ligand extended the lifespan of germ-line ablated daf-9 and daf-36 mutants, showing that it is "antiaging" in the germ-line longevity pathway. Thus, dafachronic acid regulates C. elegans lifespan according to signaling state. These studies provide key evidence that bile acid-like steroids modulate aging in animals.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>17360327</pmid><doi>10.1073/pnas.0700847104</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2007-03, Vol.104 (12), p.5014-5019 |
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| subjects | Adaptation, Physiological - drug effects Aging Animals Bile Bile acids Bile Acids and Salts - pharmacology Biological Sciences Caenorhabditis elegans Caenorhabditis elegans - drug effects Caenorhabditis elegans - physiology Caenorhabditis elegans Proteins - metabolism Cell Nucleus - drug effects Cytochrome P-450 Enzyme System - metabolism Genetics Germ Cells - drug effects Heat tolerance Hormonal regulation Hormones Intestines - drug effects Invertebrate Hormones - pharmacology Larva - drug effects Larval development Ligands Longevity Longevity - drug effects Molecular biology Nematode larvae Oxidative stress Receptors, Cytoplasmic and Nuclear - metabolism Recombinant Fusion Proteins - metabolism Signal Transduction - drug effects Steroids Stress tolerance Temperature |
| title | bile acid-like steroid modulates Caenorhabditis elegans lifespan through nuclear receptor signaling |
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