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Selective anticancer agents suppress aging in Drosophila

2013; Impact Journals LLC; Volume: 4; Issue: 9 Linguagem: Inglês

10.18632/oncotarget.1272

1949-2553

Anton Danilov, Mikhail Shaposhnikov, Ekaterina Plyusnina, V. R. Kogan, П. О. Федичев, Alexey Moskalev,

Neurobiology and Insect Physiology Research

// Anton Danilov 1 , Mikhail Shaposhnikov 1,2 , Ekaterina Plyusnina 1,2 , Valeria Kogan 3,4 , Peter Fedichev 3,4 and Alexey Moskalev 1,2,3 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.