| Summary: | Reduction of insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) promotes longevity across species. In the nematode <i>Caenorhabditis elegans</i>, ablation of germline stem cells (GSCs) and activity changes of the conserved signaling mediators <i>unc-43/CaMKII</i> (calcium/calmodulin-dependent kinase type II) and <i>egl-8/PLCβ</i> (phospholipase Cβ) also increase lifespan. Like IIS, these pathways depend on the conserved transcription factor <i>daf-16/FOXO</i> for lifespan extension, but how they functionally interact is unknown. Here, we show that altered <i>unc-43/egl-8</i> activity further increases the lifespan of long-lived GSC-deficient worms, but not of worms that are long-lived due to a strong reduction-of-function mutation in the insulin/IGF1-like receptor <i>daf-2</i>. Additionally, we provide evidence for <i>unc-43</i> and, to a lesser extent, <i>egl-8</i> modulating the expression of certain collagen genes, which were reported to be dispensable for longevity of these particular <i>daf-2</i> mutant worms, but not for other forms of longevity. Together, these results provide new insights into the conditions and potential mechanisms by which CaMKII- and PLCβ-signals modulate <i>C. elegans</i> lifespan.
|
|---|