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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 QNZ (0.03 μM) on locomotor activity Drosophila melanogaster(A, B) spontaneous activity. (C, D) negative geotaksis test. * p< 0.001, ** p< 0.05 (x2 test).
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Figure 6: Effect of QNZ (0.03 μM) on locomotor activity Drosophila melanogaster(A, B) spontaneous activity. (C, D) negative geotaksis test. * p< 0.001, ** p< 0.05 (x2 test).

Mentions: Application of QNZ did not affect the lifespan of males in all studied concentrations (3, 0.3, 0.03 μM). In females QNZ induced decreasing of lifespan (Table 1, Fig. S9). QNZ in concentrations of 3, 0.3, 0.03 μM increased female fecundity (Table 1, Fig. 5). QNZ in concentration of 0.03 μM increased the locomotor activity of females (Fig. 6) and in the concentration of 3 μM activity of the males (Fig. 7). Treatnent with QNZ in concentration of 0.3 μM did not affect activity of males or females (Fig. S10)


Selective anticancer agents suppress aging in Drosophila.

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

Effect of QNZ (0.03 μM) on locomotor activity Drosophila melanogaster(A, B) spontaneous activity. (C, D) negative geotaksis test. * 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 6: Effect of QNZ (0.03 μM) on locomotor activity Drosophila melanogaster(A, B) spontaneous activity. (C, D) negative geotaksis test. * p< 0.001, ** p< 0.05 (x2 test).
Mentions: Application of QNZ did not affect the lifespan of males in all studied concentrations (3, 0.3, 0.03 μM). In females QNZ induced decreasing of lifespan (Table 1, Fig. S9). QNZ in concentrations of 3, 0.3, 0.03 μM increased female fecundity (Table 1, Fig. 5). QNZ in concentration of 0.03 μM increased the locomotor activity of females (Fig. 6) and in the concentration of 3 μM activity of the males (Fig. 7). Treatnent with QNZ in concentration of 0.3 μM did not affect activity of males or females (Fig. S10)

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