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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 wortmannin (0.005 μM) on locomotor activity Drosophila melanogaster(A, B) spontaneous activity. (C, D) negative geotaksis test. * p< 0.001, ** p< 0.05 (χ2 test).
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Figure 3: Effect of wortmannin (0.005 μM) on locomotor activity Drosophila melanogaster(A, B) spontaneous activity. (C, D) negative geotaksis test. * p< 0.001, ** p< 0.05 (χ2 test).

Mentions: Wortmannin in concentration of 5 μM increased the median lifespan of males by 5% (p <0.05), but decreased in females by 8.2% (p <0.05). In concentration of 0.005 μM wortmannin had no statistically significant effect on lifespan (Table 1, Fig. S2). Treatment with wortmannin in a concentration of 5 μM decreased spontaneous locomotor activity in females during the second half of life, however, however the end of life activity in treated females was higher than in the control. Wortmannin in concentrations of 0.005 and 5 μM increased the reproductive period in females (Table 1, Fig. S3). Wortmannin in concentration of 0.005 μM and 5 μM in males and 5 μM in females significantly increased activity in the test on negative geotaxis (Table 1, Fig. 3 and S4).


Selective anticancer agents suppress aging in Drosophila.

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

Effect of wortmannin (0.005 μM) on locomotor activity Drosophila melanogaster(A, B) spontaneous activity. (C, D) negative geotaksis test. * p< 0.001, ** p< 0.05 (χ2 test).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Effect of wortmannin (0.005 μM) on locomotor activity Drosophila melanogaster(A, B) spontaneous activity. (C, D) negative geotaksis test. * p< 0.001, ** p< 0.05 (χ2 test).
Mentions: Wortmannin in concentration of 5 μM increased the median lifespan of males by 5% (p <0.05), but decreased in females by 8.2% (p <0.05). In concentration of 0.005 μM wortmannin had no statistically significant effect on lifespan (Table 1, Fig. S2). Treatment with wortmannin in a concentration of 5 μM decreased spontaneous locomotor activity in females during the second half of life, however, however the end of life activity in treated females was higher than in the control. Wortmannin in concentrations of 0.005 and 5 μM increased the reproductive period in females (Table 1, Fig. S3). Wortmannin in concentration of 0.005 μM and 5 μM in males and 5 μM in females significantly increased activity in the test on negative geotaxis (Table 1, Fig. 3 and S4).

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