Diapause-associated metabolic traits reiterated in long-lived daf-2 mutants in the nematode Caenorhabditis elegans.
The longevity of the Caenorhabditis elegans diapausal dauer larva greatly exceeds that of the adult. Dauer formation and adult ageing are both regulated by insulin/IGF-1 signaling (IIS). Reduced IIS, e.g. by mutation of the daf-2 insulin/IGF-1 receptor gene, increases adult lifespan. This may reflect mis-expression in the adult of dauer longevity-assurance processes. Since IIS plays a central role in the regulation of metabolism, metabolic alterations shared by dauer larvae and daf-2 adults represent candidate mechanisms for lifespan determination. We have conducted a detailed comparison of transcript profile data from dauers and daf-2 mutant adults, focusing on expression of metabolic pathway genes. Our results imply up-regulation in both dauers and daf-2 mutant adults of gluconeogenesis, glyoxylate pathway activity, and trehalose biosynthesis. Down-regulation of the citric acid cycle and mitochondrial respiratory chain occurs in dauers, but not daf-2 adults. However, the F(1) ATPase inhibitor was up-regulated in both, implying enhanced homeostasis in conditions where mitochondria are stressed. Overall, the data implies increased conversion of fat to carbohydrate, and conservation of ATP stocks in daf-2 mutant adults, suggesting a state of increased energy availability. We postulate that this fuels increased somatic maintenance activity, as suggested by the disposable soma theory.
McElwee
Joshua J
JJ
Department of Biology, University College London, UK.
Schuster
Eugene
E
Blanc
Eric
E
Thornton
Janet
J
Gems
David
D
D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism / Q000502:physiology*; D019343:Citric Acid / Q000378:metabolism; D002952:Citric Acid Cycle; D004579:Electron Transport; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D005943:Gluconeogenesis; D006019:Glycolysis; D008954:Models, Biological; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D006180:Proton-Translocating ATPases / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors; D014199:Trehalose / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D015854:Up-Regulation
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; D014280:Triglycerides; C108831:daf-16 protein, C elegans; D019343:Citric Acid; D014199:Trehalose; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; D006180:Proton-Translocating ATPases