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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 combined use of rapamycin (5 μM) and wortmannin (5 μM) on lifespan Drosophila melanogaster* p< 0.001, ** p< 0.05 (Kolmogorov-Smirnov test).
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Figure 10: Effect of combined use of rapamycin (5 μM) and wortmannin (5 μM) on lifespan Drosophila melanogaster* p< 0.001, ** p< 0.05 (Kolmogorov-Smirnov test).

Mentions: As a result of combined application of wortmannin (5 μM) and rapamycin (5 μM) we observed the increase in the median lifespan by 14.6%, and the age of 90% mortality by 23.4% in females. The median lifespan of males increased by 2.4% (Table 1, Fig. 10).


Selective anticancer agents suppress aging in Drosophila.

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

Effect of combined use of rapamycin (5 μM) and wortmannin (5 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 10: Effect of combined use of rapamycin (5 μM) and wortmannin (5 μM) on lifespan Drosophila melanogaster* p< 0.001, ** p< 0.05 (Kolmogorov-Smirnov test).
Mentions: As a result of combined application of wortmannin (5 μM) and rapamycin (5 μM) we observed the increase in the median lifespan by 14.6%, and the age of 90% mortality by 23.4% in females. The median lifespan of males increased by 2.4% (Table 1, Fig. 10).

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