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

作者：Gerisch Birgit; Rottiers Veerle; Li Dongling; Motola Daniel L; Cummins Carolyn L; Lehrach Hans; Mangelsdorf David J; Antebi Adam^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2007, 104(12): 5014-5019.

DOI：10.1073/pnas.0700847104

• aging
• DAF-12
• hormone
• dafachronic acid
• germ-line longevity

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.

• 出版日期2007-3-20