Dietary restriction in Caenorhabditis elegans
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.
Sensory ray genes
These experiments were undertaken with the goal of identifying genes whose expression is enriched in or restricted to the sensory rays of the C. elegans male tail. We constructed two mutant strains in which ray development is either compromised (EM672) or enhanced (EM673), and harvested mRNA from adult males. Labeled cDNAs were compared on seven arrays (representing three different sets of mRNA preps). In all experiments, Channel 1 (green) represents the EM672 expression profile and Channel 2 (Red) corresponds to EM673. Ray-enriched genes would therefore generally be expected to have higher intensities in Channel 2 than in Channel 1. Experimental details and results from these studies are available in D.S. Portman and S.W. Emmons (2004) Identification of C. elegans sensory ray genes using whole-genome expression profiling. Groups of assays that are related as part of a time series. Keywords: time_series_design