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Selective anticancer agents suppress aging in Drosophila.

Danilov A, Shaposhnikov M, Plyusnina E, Kogan V, Fedichev P, Moskalev A - Oncotarget (2013)

Bottom Line: Mutations of the PI3K, TOR, iNOS, and NF-κB genes increase lifespan of model organisms and reduce the risk of some aging-associated diseases.The greatest lifespan expanding effect was achieved by a combination of rapamycin (5 μM) and wortmannin (5 μM) (by 23.4%).The bioinformatic analysis (KEGG, REACTOME.PATH, DOLite, and GO.BP) showed the greatest aging-suppressor activity of rapamycin, consistent with experimental data.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biology, Komi Science Center, Russian Academy of Sciences, Syktyvkar, 167982, Russia.

ABSTRACT
Mutations of the PI3K, TOR, iNOS, and NF-κB genes increase lifespan of model organisms and reduce the risk of some aging-associated diseases. We studied the effects of inhibitors of PI3K (wortmannin), TOR (rapamycin), iNOS (1400W), NF-κB (pyrrolidin dithiocarbamate and QNZ), and the combined effects of inhibitors: PI3K (wortmannin) and TOR (rapamycin), NF-κB (pyrrolidin dithiocarbamates) and PI3K (wortmannin), NF-κB (pyrrolidine dithiocarbamates) and TOR (rapamycin) on Drosophila melanogaster lifespan and quality of life (locomotor activity and fertility). Our data demonstrate that pharmacological inhibition of PI3K, TOR, NF-κB, and iNOS increases lifespan of Drosophila without decreasing quality of life. The greatest lifespan expanding effect was achieved by a combination of rapamycin (5 μM) and wortmannin (5 μM) (by 23.4%). The bioinformatic analysis (KEGG, REACTOME.PATH, DOLite, and GO.BP) showed the greatest aging-suppressor activity of rapamycin, consistent with experimental data.

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Effect of 1400W (0.03, 0.3, 3 μM) on fertility of females Drosophila melanogaster* p< 0.001, ** p< 0.05 (x2 test).
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Figure 9: Effect of 1400W (0.03, 0.3, 3 μM) on fertility of females Drosophila melanogaster* p< 0.001, ** p< 0.05 (x2 test).

Mentions: In males 1400W in concentrations of 0.03 and 3 μM and significantly increased the median lifespan (by 3 and 7%, respectively) and the age of 90% mortality (by 13 and 5%, respectively). In females we observed a decrease in median lifespan (by 2-5%) and the age of 90% mortality (by 4-5%) when exposed to 1400W at different concentrations (Table 1, Fig. S11). In concentrations of 0.3 and 3 0.03 μM 1400W increased the locomotor activity of the males (Fig. 8, S12 and S13). In females locomotor activity increased only when exposed to 1400W in concentration of 0.3 μM (Fig. 8, S12 and S13). 1400W in concentration of 0.3 μM increased female fertility during the first half of life, and in concentration of 0.03 μM increased fertility throughout life (Table 1, Fig. 9).


Selective anticancer agents suppress aging in Drosophila.

Danilov A, Shaposhnikov M, Plyusnina E, Kogan V, Fedichev P, Moskalev A - Oncotarget (2013)

Effect of 1400W (0.03, 0.3, 3 μM) on fertility of females Drosophila melanogaster* p< 0.001, ** p< 0.05 (x2 test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3824538&req=5

Figure 9: Effect of 1400W (0.03, 0.3, 3 μM) on fertility of females Drosophila melanogaster* p< 0.001, ** p< 0.05 (x2 test).
Mentions: In males 1400W in concentrations of 0.03 and 3 μM and significantly increased the median lifespan (by 3 and 7%, respectively) and the age of 90% mortality (by 13 and 5%, respectively). In females we observed a decrease in median lifespan (by 2-5%) and the age of 90% mortality (by 4-5%) when exposed to 1400W at different concentrations (Table 1, Fig. S11). In concentrations of 0.3 and 3 0.03 μM 1400W increased the locomotor activity of the males (Fig. 8, S12 and S13). In females locomotor activity increased only when exposed to 1400W in concentration of 0.3 μM (Fig. 8, S12 and S13). 1400W in concentration of 0.3 μM increased female fertility during the first half of life, and in concentration of 0.03 μM increased fertility throughout life (Table 1, Fig. 9).

Bottom Line: Mutations of the PI3K, TOR, iNOS, and NF-κB genes increase lifespan of model organisms and reduce the risk of some aging-associated diseases.The greatest lifespan expanding effect was achieved by a combination of rapamycin (5 μM) and wortmannin (5 μM) (by 23.4%).The bioinformatic analysis (KEGG, REACTOME.PATH, DOLite, and GO.BP) showed the greatest aging-suppressor activity of rapamycin, consistent with experimental data.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biology, Komi Science Center, Russian Academy of Sciences, Syktyvkar, 167982, Russia.

ABSTRACT
Mutations of the PI3K, TOR, iNOS, and NF-κB genes increase lifespan of model organisms and reduce the risk of some aging-associated diseases. We studied the effects of inhibitors of PI3K (wortmannin), TOR (rapamycin), iNOS (1400W), NF-κB (pyrrolidin dithiocarbamate and QNZ), and the combined effects of inhibitors: PI3K (wortmannin) and TOR (rapamycin), NF-κB (pyrrolidin dithiocarbamates) and PI3K (wortmannin), NF-κB (pyrrolidine dithiocarbamates) and TOR (rapamycin) on Drosophila melanogaster lifespan and quality of life (locomotor activity and fertility). Our data demonstrate that pharmacological inhibition of PI3K, TOR, NF-κB, and iNOS increases lifespan of Drosophila without decreasing quality of life. The greatest lifespan expanding effect was achieved by a combination of rapamycin (5 μM) and wortmannin (5 μM) (by 23.4%). The bioinformatic analysis (KEGG, REACTOME.PATH, DOLite, and GO.BP) showed the greatest aging-suppressor activity of rapamycin, consistent with experimental data.

Show MeSH
Related in: MedlinePlus