Further Extension of Lifespan by IUnc-43/CaMKII/I and IEgl-8/PLCβ/I Mutations in Germline-Deficient ICaenorhabditis elegans/I

• Published in: Cells (Basel, Switzerland) Switzerland), 2022-11, Vol.11 (22)
• Main Authors: Mack, Hildegard I. D, Buck, Laura G, Skalet, Sonja, Kremer, Jennifer, Li, Hao, Mack, Elisabeth K. M
• Format: Article
• Language: English
• Subjects: Caenorhabditis elegans; Cellular signal transduction; Gene mutations; Genetic aspects; Life spans (Biology); Microbiological research; Physiological aspects; Protein kinases
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11223527

Reduction of insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) promotes longevity across species. In the nematode Caenorhabditis elegans, ablation of germline stem cells (GSCs) and activity changes of the conserved signaling mediators unc-43/CaMKII (calcium/calmodulin-dependent kinase type II) and egl-8/PLCβ (phospholipase Cβ) also increase lifespan. Like IIS, these pathways depend on the conserved transcription factor daf-16/FOXO for lifespan extension, but how they functionally interact is unknown. Here, we show that altered unc-43/egl-8 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 daf-2. Additionally, we provide evidence for unc-43 and, to a lesser extent, egl-8 modulating the expression of certain collagen genes, which were reported to be dispensable for longevity of these particular daf-2 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 C. elegans lifespan.