title: No Significant Increase in the Δ4- and Δ7-Dafachronic Acid Concentration in the Long-Lived glp-1 Mutant, nor in the Mutants Defective in Dauer Formation.
abstract: The steroid hormone dafachronic acid (DA) regulates dauer formation and lifespan in Caenorhabditis elegans by binding to the nuclear receptor DAF-12. However, little is known about how DA concentrations change under various physiologic conditions and about how DA/DAF-12 signaling interacts with other signaling pathways that also regulate dauer formation and lifespan. Using a sensitive bioanalytical method, we quantified the endogenous DA concentrations in a long-lived germline-less glp-1 mutant and in the Dauer formation-defective (Daf-d) mutants daf-12, daf-16, daf-5, and daf-3. We found that the DA concentration in the glp-1 mutant was similar to that in the wild type (WT). This result is contrary to the long-held belief that germline loss-induced longevity involves increased DA production and suggests instead that this type of longevity involves an enhanced response to DA. We also found evidence suggesting that increased DA sensitivity underlies lifespan extension triggered by exogenous DA. At the L2/L3 stage, the DA concentration in a daf-12 null mutant decreased to 22% of the WT level. This finding is consistent with the previously proposed positive feedback regulation between DAF-12 and DA production. Surprisingly, the DA concentrations in the daf-16, daf-5, and daf-3 mutants were only 19-34% of the WT level at the L2/L3 stage, slightly greater than those in the Dauer formation-constitutive (Daf-c) mutants at the pre-dauer stage (4-15% of the WT L2 control). Our experimental evidence suggested that the positive feedback between DA and DAF-12 was partially induced in the three Daf-d mutants.
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing 102206, China.
authors.forename: Tie-Mei
authors.initials: TM
authors.lastname: Li
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing 102206, China.
authors.forename: Weilong
authors.initials: W
authors.lastname: Liu
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing 102206, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing 102206, China.
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Zhang
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing 102206, China.
authors.forename: Le-Mei
authors.initials: LM
authors.lastname: Jia
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing 102206, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing 102206, China.
authors.forename: Xiangke
authors.initials: X
authors.lastname: Li
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing 102206, China Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Lei
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing 102206, China dongmengqiu@nibs.ac.cn.
authors.forename: Meng-Qiu
authors.identifier: http://orcid.org/0000-0002-6094-1182
authors.initials: MQ
authors.lastname: Dong
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002782:Cholestenes / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D005854:Germ Cells / Q000378:metabolism; D007814:Larva / Q000378:metabolism; D008136:Longevity; D013058:Mass Spectrometry; D009154:Mutation; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013696:Temperature
chemical_list: D029742:Caenorhabditis elegans Proteins; D002782:Cholestenes; C060620:Glp-1 protein, C elegans; D051880:Receptors, Notch; C533799:delta4-dafachronic acid; C533798:delta7-dafachronic acid
keywords: C. elegans dauer; daf-12; dafachronic acid; glp-1; steroid hormone