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P13-kinase inhibition induces dauer formation, thermotolerance and longevity in C. elegans
P Babar1, C Adamson, G A Walker
1The School of Biological Sciences, The University of Manchester, UK.
Abstract:
The effects of 2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), an inhibitor of mammalian phosphatidylinositol 3-OH kinase, was tested on an insulin signaling-like pathway in the nematode Caenorhabditis elegans. Populations of C. elegans were treated with LY294002 at different stages of the life cycle, and its effects on development, thermotolerance and longevity were assessed. At concentrations of 160 microM and above, LY294002 significantly induced both dauer formation and thermotolerance. Treatment of adult worms also resulted in a small, but significant, increase in life span. The results presented are consistent with the view that a neuroendocrine signaling pathway functions in adult worms to determine stress resistance and longevity.
Insights
The compound LY294002, a phosphatidylinositol 3-OH kinase inhibitor, promotes dauer formation and enhances thermotolerance in Caenorhabditis elegans. It also slightly increases lifespan, suggesting a role in stress resistance and longevity pathways.
Area of Science:
- * Molecular Biology
- * Genetics
- * Gerontology
Background:
- * The phosphatidylinositol 3-OH kinase (PI3K) pathway is crucial for cellular functions including growth, proliferation, and survival.
- * Understanding PI3K signaling in model organisms like Caenorhabditis elegans can provide insights into conserved biological processes.
- * Insulin signaling pathways are implicated in regulating development, metabolism, and lifespan across species.
Purpose of the Study:
- * To investigate the effects of the PI3K inhibitor LY294002 on an insulin signaling-like pathway in Caenorhabditis elegans.
- * To assess the impact of LY294002 on key life-history traits, including development, stress resistance, and longevity.
- * To explore the potential role of neuroendocrine signaling in mediating stress resistance and lifespan in C. elegans.
Main Methods:
- * Treatment of C. elegans populations with varying concentrations of LY294002 at different life stages.
- * Assessment of dauer formation, a developmental arrest stage triggered by environmental stress.
- * Measurement of thermotolerance through exposure to elevated temperatures.
- * Quantification of lifespan in adult worms following LY294002 treatment.
Main Results:
- * LY294002 significantly induced dauer formation at concentrations of 160 microM and higher.
- * Enhanced thermotolerance was observed in C. elegans treated with LY294002.
- * A modest but statistically significant increase in lifespan was noted in adult worms exposed to LY294002.
- * These findings suggest a conserved role for PI3K signaling in stress response.
Conclusions:
- * The PI3K inhibitor LY294002 modulates developmental pathways and stress resistance in C. elegans.
- * The results support the hypothesis that a neuroendocrine signaling pathway influences stress resistance and longevity in adult worms.
- * This study highlights the utility of C. elegans as a model for dissecting conserved signaling pathways affecting aging and stress resilience.