Genes That Act Downstream of Sensory Neurons to Influence Longevity, Dauer Formation, and Pathogen Responses in Caenorhabditis elegans

Abstract

The sensory systems of multicellular organisms are designed to provide information about the environment and thus elicit appropriate changes in physiology and behavior. In the nematode Caenorhabditis elegans, sensory neurons affect the decision to arrest during development in a diapause state, the dauer larva, and modulate the lifespan of the animals in adulthood. However, the mechanisms underlying these effects are incompletely understood. Using whole-genome microarray analysis, we identified transcripts whose levels are altered by mutations in the intraflagellar transport protein daf-10, which result in impaired development and function of many sensory neurons in C. elegans. In agreement with existing genetic data, the expression of genes regulated by the transcription factor DAF-16/FOXO was affected by daf-10 mutations. In addition, we found altered expression of transcriptional targets of the DAF-12/nuclear hormone receptor in the daf-10 mutants and showed that this pathway influences specifically the dauer formation phenotype of these animals. Unexpectedly, pathogen-responsive genes were repressed in daf-10 mutant animals, and these sensory mutants exhibited altered susceptibility to and behavioral avoidance of bacterial pathogens. Moreover, we found that a solute transporter gene mct-1/2, which was induced by daf-10 mutations, was necessary and sufficient for longevity. Thus, sensory input seems to influence an extensive transcriptional network that modulates basic biological processes in C. elegans. This situation is reminiscent of the complex regulation of physiology by the mammalian hypothalamus, which also receives innervations from sensory systems, most notably the visual and olfactory systems.

Inhibition of elongin C promotes longevity and protein homeostasis via HIF‐1 in C. elegans

“…elc‐1p::elc‐1::gfp transgenic animals were generated as described previously with some modifications (Gaglia et al ., 2012). The elc‐1p::elc‐1::gfp construct (25 ng μL −1 ) was injected into the gonad of day 1 adult hermaphrodites with a co‐injection marker, odr‐1p::rfp (75 ng μL −1 ).…”

SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat

“…Fluorescence imaging was performed as described previously with modifications (Gaglia et al 2012). For glucose-rich diet feeding experiments, transgenic worms were fed with specific RNAi bacteria with or without 2% glucose from eggs to day 1 adults unless otherwise mentioned.…”

Food-derived sensory cues modulate longevity via distinct neuroendocrine insulin-like peptides

“…Dye filling assay was performed as previously described (Gaglia et al 2012). Well-fed worms were washed three times with M9 buffer and centrifuged at 2000 rpm to spin down the worms.…”