Oncotarget

Research Papers:

Selective anticancer agents suppress aging in Drosophila

Anton Danilov, Mikhail Shaposhnikov, Ekaterina Plyusnina, Valeria Kogan, Peter Fedichev and Alexey Moskalev _

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Oncotarget. 2013; 4:1507-1526. https://doi.org/10.18632/oncotarget.1272

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Abstract

Anton Danilov1, Mikhail Shaposhnikov1,2, Ekaterina Plyusnina1,2, Valeria Kogan3,4, Peter Fedichev3,4 and Alexey Moskalev1,2,3

1 Institute of Biology, Komi Science Center, Russian Academy of Sciences, Syktyvkar, 167982, Russia

2 Syktyvkar State University, Syktyvkar, 167001, Russia

3 Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, 141700, Russia

4 Quantum Pharmaceuticals, Ul. Kosmonavta Volkova 6A-1205, Moscow, 125171, Russia

Correspondence:

Alexey Moskalev, email:

Keywords: longevity, quality of life, aging-suppressive substances, anticancer agents, PI3K, TOR, iNOS, NF-κB, Drosophila melanogaster

Received: August 10, 2013 Accepted: September 6, 2013 Published: September 7, 2013

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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