Activation of the Tor/Myc signaling axis in intestinal stem and progenitor cells affects longevity, stress resistance and metabolism in drosophila

Strilbytska, Olha; Semaniuk, Uliana; Storey, Kenneth B.; Edgar, Bruce A.; Lushchak, Oleh

doi:10.1016/j.cbpb.2016.09.008

Cited by 18 publications

(21 citation statements)

References 49 publications

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“…Intestinal stem cell proliferation increases during aging, which causes an accumulation of ISC progenitor cells that have impaired terminal differentiation pathways [34]. Our previous study showed that the lifespan of Drosophila was decreased when Rheb was overexpressed in ISCs and lifespan was even shorter when Myc was coexpressed [16]. Present results propose a critical role for TOR/Myc signaling pathway in progenitor stem cells, EBs, which in turn can have a strong impact on Drosophila stress resistance and lifespan.…”

Section: Discussionmentioning

confidence: 57%

“…Flies that expressed Rheb and Myc-Rheb in EBs were less resistant to starvation and malnutrition. But our previous results showed that low carbohydrate or low protein diets increase lifespan of Rheb and Myc-Rheb-expressing flies [16]. Choi and colleagues [35] demonstrated that starvation caused a delay in EC growth and a prolonged contact between ISCs and their progenitors.…”

Section: Discussionmentioning

confidence: 89%

“…In EBs TOR signaling and Myc have a strong impact on cell differentiaion into either EC or EE, which in turn influences metabolic processes, stress resistance, gut integrity, and fly survival. Our previous study had already demonstrated that both Myc and Rheb expression in stem and progenitor cells have a great impact on Drosophila lifespan, stress resistance and metabolism [16]. The present study aims to show an important role of TOR/Myc signaling axis in EB cells in fruit fly.…”

Section: Introductionmentioning

confidence: 78%

“…Our previous results showed significant impact of TOR/Myc activation in Drosophila EB on fly survival [16]. Mean lifespan of control flies (SuH/+) was about 34 days at 29°C.…”

Section: Lifespan and Stress Resistancementioning

confidence: 89%

“…0.5% sucrose was used for starvation assays [16]. Flies involved in oxidative stress resistance experiments were given a 5% sucrose medium supplemented with 20 mM menadione, a polycyclic aromatic ketone that generates intracellular reactive oxygen species (ROS).…”

Section: Malnutrition Starvation and Oxidative Stressmentioning

confidence: 99%

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Longevity and stress resistance are affected by activation of TOR/Myc in progenitor cells of Drosophila gut

et al. 2017

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Diverse physiological pathways have been shown to regulate longevity, stress resistance, fecundity and feeding rates, and metabolism in Drosophila. Here we tesed physiological traits in flies with Rheb and MycRheb overexpressed in gut progenitor cells, known as enteroblasts (EBs). We found that activation of TOR signaling by overexpression of Rheb in EBs decreases survival and stress resistance. Additionall, we showed that Myc co-expression in EBs reduces fly fecundity and feeding rate. Rheb overexpression enhanced the level of whole body glucose. Higher relative expression of the metabolic genes dilps, akh, tobi and pepck was, however, observed. The role of TOR/Myc in the regulation of genes involved in lipid metabolism and protein synthesis was established. We showed a significant role of TOR/ Myc in EBs in the regulation of the JAK/STAT, EGFR and insulin signaling pathways in Drosophila gut. These results highlight the importance of the balance between all different types of cells and confirm previous studies demonstrating that promotion of homeostasis in the intestine of Drosophila may function as a mechanism for the extension of organismal lifespan. Overall, the results demonstrate a role of TOR signaling and its downstream target Myc in EB cells in the regulation of Drosophila physiological processes.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 78%

“…Our previous results showed significant impact of TOR/Myc activation in Drosophila EB on fly survival [16]. Mean lifespan of control flies (SuH/+) was about 34 days at 29°C.…”

Section: Lifespan and Stress Resistancementioning

confidence: 89%

Section: Malnutrition Starvation and Oxidative Stressmentioning

confidence: 99%

See 3 more Smart Citations