A novel 3-hydroxysteroid dehydrogenase that regulates reproductive development and longevity.
Endogenous small molecule metabolites that regulate animal longevity are emerging as a novel means to influence health and life span. In C. elegans, bile acid-like steroids called the dafachronic acids (DAs) regulate developmental timing and longevity through the conserved nuclear hormone receptor D...
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Public Library of Science (PLoS)
2012
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oai:doaj.org-article:1fbb10ee35964a4ea240eed92e3507212021-11-18T05:36:41ZA novel 3-hydroxysteroid dehydrogenase that regulates reproductive development and longevity.1544-91731545-788510.1371/journal.pbio.1001305https://doaj.org/article/1fbb10ee35964a4ea240eed92e3507212012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22505847/pdf/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Endogenous small molecule metabolites that regulate animal longevity are emerging as a novel means to influence health and life span. In C. elegans, bile acid-like steroids called the dafachronic acids (DAs) regulate developmental timing and longevity through the conserved nuclear hormone receptor DAF-12, a homolog of mammalian sterol-regulated receptors LXR and FXR. Using metabolic genetics, mass spectrometry, and biochemical approaches, we identify new activities in DA biosynthesis and characterize an evolutionarily conserved short chain dehydrogenase, DHS-16, as a novel 3-hydroxysteroid dehydrogenase. Through regulation of DA production, DHS-16 controls DAF-12 activity governing longevity in response to signals from the gonad. Our elucidation of C. elegans bile acid biosynthetic pathways reveals the possibility of novel ligands as well as striking biochemical conservation to other animals, which could illuminate new targets for manipulating longevity in metazoans.Joshua WollamDaniel B MagnerLilia MagomedovaElisabeth RassYidong ShenVeerle RottiersBianca HabermannCarolyn L CumminsAdam AntebiPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 10, Iss 4, p e1001305 (2012) |
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DOAJ |
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DOAJ |
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EN |
| topic |
Biology (General) QH301-705.5 |
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Biology (General) QH301-705.5 Joshua Wollam Daniel B Magner Lilia Magomedova Elisabeth Rass Yidong Shen Veerle Rottiers Bianca Habermann Carolyn L Cummins Adam Antebi A novel 3-hydroxysteroid dehydrogenase that regulates reproductive development and longevity. |
| description |
Endogenous small molecule metabolites that regulate animal longevity are emerging as a novel means to influence health and life span. In C. elegans, bile acid-like steroids called the dafachronic acids (DAs) regulate developmental timing and longevity through the conserved nuclear hormone receptor DAF-12, a homolog of mammalian sterol-regulated receptors LXR and FXR. Using metabolic genetics, mass spectrometry, and biochemical approaches, we identify new activities in DA biosynthesis and characterize an evolutionarily conserved short chain dehydrogenase, DHS-16, as a novel 3-hydroxysteroid dehydrogenase. Through regulation of DA production, DHS-16 controls DAF-12 activity governing longevity in response to signals from the gonad. Our elucidation of C. elegans bile acid biosynthetic pathways reveals the possibility of novel ligands as well as striking biochemical conservation to other animals, which could illuminate new targets for manipulating longevity in metazoans. |
| format |
article |
| author |
Joshua Wollam Daniel B Magner Lilia Magomedova Elisabeth Rass Yidong Shen Veerle Rottiers Bianca Habermann Carolyn L Cummins Adam Antebi |
| author_facet |
Joshua Wollam Daniel B Magner Lilia Magomedova Elisabeth Rass Yidong Shen Veerle Rottiers Bianca Habermann Carolyn L Cummins Adam Antebi |
| author_sort |
Joshua Wollam |
| title |
A novel 3-hydroxysteroid dehydrogenase that regulates reproductive development and longevity. |
| title_short |
A novel 3-hydroxysteroid dehydrogenase that regulates reproductive development and longevity. |
| title_full |
A novel 3-hydroxysteroid dehydrogenase that regulates reproductive development and longevity. |
| title_fullStr |
A novel 3-hydroxysteroid dehydrogenase that regulates reproductive development and longevity. |
| title_full_unstemmed |
A novel 3-hydroxysteroid dehydrogenase that regulates reproductive development and longevity. |
| title_sort |
novel 3-hydroxysteroid dehydrogenase that regulates reproductive development and longevity. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/1fbb10ee35964a4ea240eed92e350721 |
| work_keys_str_mv |
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1718424897699446784 |