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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 PDTC (125 μM) and wortmannin (0.005 μM) on lifespan Drosophila melanogaster* p< 0.001, ** p< 0.05 (Kolmogorov-Smirnov test).
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Figure 12: Effect of combined use of PDTC (125 μM) and wortmannin (0.005 μM) on lifespan Drosophila melanogaster* p< 0.001, ** p< 0.05 (Kolmogorov-Smirnov test).

Mentions: A mixture of PDTC (125 μM) with wortmannin (0.005 μM), and PDTC (125 μM) with rapamycin (0.005 μM) increased the median lifespan in males (by 10%) and females (by 10 and 12%, respectively). We also observed an increase in the age of 90% mortality in females by 11.3% and 8.1% respectively (Table 1, Fig. 11 and 12). The study of age-related dynamics of female fertility revealed no adverse effects of mixtures of PDTC (125 μM) with rapamycin (5 μM) and PDTC (125 μM) with wortmannin (5 μM) (Table 1, Fig. S14). When flies were exposed to mixtures of PDTC (125 μM) with wortmannin (5 μM) and PDTC (125 μM) with rapamycin (5 μM) we observed a significant increase in locomotor activity of males and females in the test on negative geotaxis and increasing of spontaneous activity in females (Table 1, Fig. 13 and 14).


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 PDTC (125 μM) and wortmannin (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 12: Effect of combined use of PDTC (125 μM) and wortmannin (0.005 μM) on lifespan Drosophila melanogaster* p< 0.001, ** p< 0.05 (Kolmogorov-Smirnov test).
Mentions: A mixture of PDTC (125 μM) with wortmannin (0.005 μM), and PDTC (125 μM) with rapamycin (0.005 μM) increased the median lifespan in males (by 10%) and females (by 10 and 12%, respectively). We also observed an increase in the age of 90% mortality in females by 11.3% and 8.1% respectively (Table 1, Fig. 11 and 12). The study of age-related dynamics of female fertility revealed no adverse effects of mixtures of PDTC (125 μM) with rapamycin (5 μM) and PDTC (125 μM) with wortmannin (5 μM) (Table 1, Fig. S14). When flies were exposed to mixtures of PDTC (125 μM) with wortmannin (5 μM) and PDTC (125 μM) with rapamycin (5 μM) we observed a significant increase in locomotor activity of males and females in the test on negative geotaxis and increasing of spontaneous activity in females (Table 1, Fig. 13 and 14).

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