|Citation||McElwee JJ, Schuster E, Blanc E, Thomas JH, Gems D. Shared transcriptional signature in Caenorhabditis elegans Dauer larvae and long-lived daf-2 mutants implicates detoxification system in longevity assurance. J Biol Chem, 2004.|
|Short Description||Shared transcriptional signature in Caenorhabditis elegans Dauer larvae and long-lived daf-2 mutants implicates detoxification system in longevity assurance. |
GEO Record: GSE1762 Platform: GPL200
Download gene-centric, log2 transformed data: WBPaper00024278.ce.mr.csv
|# of Conditions||20|
|Full Description||In the nematode Caenorhabditis elegans, formation of the long-lived dauer larva, and adult aging are both controlled by insulin/IGF-1 signaling (IIS). Potentially, increased adult lifespan in daf-2 insulin/IGF-1 receptor mutants results from mis-expression in the adult of a dauer larva longevity program. Using oligonucleotide microarray analysis we identify a dauer transcriptional signature in daf-2 mutant adults. By means of a non-biased statistical approach we identify gene classes whose expression is altered similarly in dauers and daf-2 mutants, which represent potential determinants of lifespan. These include known determinants of longevity: the small heat shock protein (smHSP)/a-crystallins are up-regulated in both milieus. The cytochrome P450, short-chain dehydrogenase/reductase, UDP-glucuronosyltransferase and (in daf-2 mutants) glutathione S-transferase gene classes were also up-regulated. These four gene classes act together in metabolism and excretion of toxic endobiotic and xenobiotic metabolites. This suggests that diverse toxic lipophilic and electrophilic metabolites, disposed of by phase 1 and phase 2 drug metabolism, may be major determinants of the molecular damage that causes aging. In addition, we observed down-regulation of genes linked to nutrient uptake, including nhx-2 and pep-2. These work together in uptake of dipeptides in the intestine, implying dietary restriction in daf-2 mutants. Some gene groups up-regulated in dauers and/or daf-2 were enriched for certain promoter elements: the daf-16-binding element, the heat shock response element, the heat shock-associated sequence or the hif-1 response element. By contrast, the daf-16-associated element was enriched in genes down-regulated in dauers and daf-2 mutants. Thus, particular promoter elements appear longevity or aging associated.