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.
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.
['Li|Tie-Mei|TM|', 'Liu|Weilong|W|', 'Lu|Shan|S|', 'Zhang|Yan-Ping|YP|', 'Jia|Le-Mei|LM|', 'Chen|Jie|J|', 'Li|Xiangke|X|', 'Lei|Xiaoguang|X|', 'Dong|Meng-Qiu|MQ|http://orcid.org/0000-0002-6094-1182']
D000818:Animals D030801:Animals, Genetically Modified D017173:Caenorhabditis elegans D029742:Caenorhabditis elegans Proteins D002782:Cholestenes D002851:Chromatography, High Pressure Liquid D005854:Germ Cells D007814:Larva D008136:Longevity D013058:Mass Spectrometry D009154:Mutation D060888:Real-Time Polymerase Chain Reaction D051880:Receptors, Notch D015398:Signal Transduction D013696:Temperature
glp-1 steroid hormone dafachronic acid daf-12 C. elegans dauer