Pharmacological inhibition of phosphoinositide 3 and TOR kinases improves survival of Drosophila melanogaster.
Recent progress in our understanding of genetic mechanisms of aging and longevity provides an opportunity to select some enzymes as targets for pharmacological correction. The phosphoinositide 3-kinase (PI3K) and TOR-kinase cascades are affected in some long-lived mutants of different animals, such as nematodes and mice. The purpose of this study was to investigate the geroprotector efficiency of the inhibitors of enzymes that are known to be affected in long-lived mutants. Experimental animals were exposed to low dozes of LY-294002 (5 microM), wortmannin (0.5 microM), and rapamycin (0.5 microM) separately during their lifetimes. We have shown that the specific PI3K inhibitors (LY-294002 and wortmannin) and the TOR-kinase inhibitor rapamycin slightly increase the median and maximal lifespan of the fruit fly, Drosophila melanogaster.
Moskalev
A A
AA
Institute of Biology of Komi Science Center of the Ural Division of the Russian Academy of Sciences, Syktyvkar, Russia. amoskalev@list.ru
Shaposhnikov
M V
MV
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors*; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D005260:Female; D008136:Longevity / Q000187:drug effects / Q000502:physiology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011494:Protein Kinases; D020123:Sirolimus / Q000494:pharmacology; D013534:Survival; D058570:TOR Serine-Threonine Kinases; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D029721:Drosophila Proteins; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D011494:Protein Kinases; C416303:target of rapamycin protein, Drosophila; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus; D000077191:Wortmannin