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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 rapamycin (0.005 μM) on lifespan Drosophila melanogaster* p< 0.001, ** p< 0.05 (Kolmogorov-Smirnov test).
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Figure 1: Effect of rapamycin (0.005 μM) on lifespan Drosophila melanogaster* p< 0.001, ** p< 0.05 (Kolmogorov-Smirnov test).

Mentions: Exposure to rapamycin (0.005 μM) caused a statistically significant (p <0.01) increase in median lifespan in males (by 14%) and females (by 12%) (Table 1, Fig. 1). Rapamycin in concentration of 0.005 μM increased activity in negative geotaxis test in males, and significantly increased fertility of females (Table 1, Fig. 2 and S1).


Selective anticancer agents suppress aging in Drosophila.

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

Effect of rapamycin (0.005 μM) on lifespan Drosophila melanogaster* p< 0.001, ** p< 0.05 (Kolmogorov-Smirnov test).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Effect of rapamycin (0.005 μM) on lifespan Drosophila melanogaster* p< 0.001, ** p< 0.05 (Kolmogorov-Smirnov test).
Mentions: Exposure to rapamycin (0.005 μM) caused a statistically significant (p <0.01) increase in median lifespan in males (by 14%) and females (by 12%) (Table 1, Fig. 1). Rapamycin in concentration of 0.005 μM increased activity in negative geotaxis test in males, and significantly increased fertility of females (Table 1, Fig. 2 and S1).

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