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A bile acid-like steroid modulates Caenorhabditis elegans lifespan through nuclear receptor signaling

MPG-Autoren
http://pubman.mpdl.mpg.de/cone/persons/resource/persons50166

Gerisch,  Birgit
Ribosomes, Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50409

Lehrach,  Hans
Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50070

Antebi,  Adam
Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Zitation

Gerisch, B., Rottiers, V., Li, D., Motola, D. L., Cummins, C. L., Lehrach, H., et al. (2007). A bile acid-like steroid modulates Caenorhabditis elegans lifespan through nuclear receptor signaling. Proceedings of the National Academy of Sciences of the United States of America, 104(12), 5014-5019. doi:10.1073/pnas.0700847104.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0010-8217-9
Zusammenfassung
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.