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Series GSE9682 Query DataSets for GSE9682
Status Public on Dec 15, 2008
Title Dietary restriction in Caenorhabditis elegans
Organism Caenorhabditis elegans
Experiment type Expression profiling by array
Summary Dietary restriction (DR) is the most effective and reproducible intervention to extend lifespan in divergent species1. In mammals, two regimens of DR, intermittent fasting (IF) and caloric restriction (CR), have proven to extend lifespan and reduce the incidence of age-related disorders2. An important characteristic of IF is that it can increase lifespan, even when there is little or no overall decrease in calorie intake2. The molecular mechanisms underlying IF-induced longevity, however, remain largely unknown. Here we establish an IF regimen that effectively extends the lifespan of Caenorhabditis elegans, and show that a nutrient-related signalling molecule, the low molecular weight GTPase Cel-Rheb, has a dual role in lifespan regulation; Cel-Rheb is required for the IF-induced longevity, whereas inhibition of Cel-Rheb mimics the CR effects. We also show that Cel-Rheb exerts its effects in part via the insulin/IGF-like signalling effector DAF-16 in IF, and that Cel-Rheb is required for fasting-induced nuclear translocation of DAF-16. We find that HSP-12.6, a DAF-16 target, functions to mediate the IF-induced longevity. Furthermore, our analyses demonstrate that most of fasting-induced upregulated genes require Cel-Rheb function for their induction, and that Cel-Rheb/Cel-TOR signalling is required for the fasting-induced downregulation of an insulin-like peptide, INS-7. These findings identify the essential role of signalling via Cel-Rheb in IF-induced longevity and gene expression changes, and suggest a molecular link between the IF-induced longevity and the insulin/IGF-like signalling pathway.
Overall design We examined fasting-induced changes of the gene expression profiles in Caenorhabditis elegans. We performed the genome-wide analysis by using Affymetrix GeneChip oligonucleotide microarrays, and examined the effect of downregulation of Cel-Rheb and Cel-TOR by RNAi on the expression profiles. Five independent experiments were performed with wild type N2. Synchronized worms under six conditions (control-fed, control-fasting, Rheb RNAi-fed, Rheb RNAi-fasting, TOR RNAi-fed, and TOR RNAi-fasting) were collected and frozen with liquid nitrogen at day 4 of adulthood. Total RNA was extracted with Sepasol(R)-RNA ⅠSuper (Nacalai tesque), and purified with RNeasy Mini Kit (Qiagen), according to manufacture’s instructions. Synthesis of cDNA, in vitro transcription and biotin labelling cRNA, and hybridization to the C. elegans Genome Array (Affymetrix) were performed according to Affymetrix protocols. Hybridized arrays were scanned using an Affymetrix GeneChip Scanner. Scanned chip images were analyzed with GeneSpring GX 7.3.1 (Agilent Technologies).
Contributor(s) Honjoh S, Yamamoto T, Nishida E
Citation(s) 19079239
Submission date Nov 26, 2007
Last update date Jul 06, 2016
Contact name Eisuke Nishida
Phone +81-75-753-4230
Organization name Graduate School of Biostudies, Kyoto University
Department Department of Cell and Developmental Biology
Street address Kitashirakawa, Sakyo-ku
City Kyoto
ZIP/Postal code 606-8502
Country Japan
Platforms (1)
GPL200 [Celegans] Affymetrix C. elegans Genome Array
Samples (24)
GSM311471 N2-controlRNAi-fed-biological rep1
GSM311472 N2-controlRNAi-fed-biological rep2
GSM311473 N2-controlRNAi-fed-biological rep3
BioProject PRJNA103573

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Supplementary file Size Download File type/resource
GSE9682_RAW.tar 51.8 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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