The effects of exogenous antioxidants on lifespan and oxidative stress resistance in Drosophila melanogaster.
We used the fruit fly Drosophila melanogaster to test the effects of feeding the superoxide dismutase (SOD) mimetic drugs Euk-8 and -134 and the mitochondria-targeted mitoquinone (MitoQ) on lifespan and oxidative stress resistance of wild type and SOD-deficient flies. Our results reaffirm the findings by other workers that exogenous antioxidant can rescue pathology associated with compromised defences to oxidative stress, but fail to extend the lifespan of normal, wild type animals. All three drugs showed a dose-dependent increase in toxicity in wild type flies, an effect that was exacerbated in the presence of the redox-cycling drug paraquat. However, important findings from this study were that in SOD-deficient flies, where the antioxidant drugs increased lifespan, the effects were sex-specific and, for either sex, the effects were also variable depending on (1) the stage of development from which the drugs were given, and (2) the magnitude of the dose. These findings place significant constraints on the role of oxidative stress in normal ageing.
Magwere
Tapiwanashe
T
Centre for Research on Ageing, University College London, Department of Biology, Darwin Building, Gower Street, London WC1E 6BT, United Kingdom.
West
Melanie
M
Riyahi
Kumars
K
Murphy
Michael P
MP
Smith
Robin A J
RA
Partridge
Linda
L
D000375:Aging; D000818:Animals; D030801:Animals, Genetically Modified; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster; D005260:Female; D005609:Free Radicals; D017344:Genes, Insect; D006720:Homozygote; D008136:Longevity; D008297:Male; D015233:Models, Statistical; D009861:Onium Compounds / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D018384:Oxidative Stress; D010269:Paraquat / Q000494:pharmacology; D034622:RNA Interference; D012737:Sex Factors; D013482:Superoxide Dismutase / Q000378:metabolism; D013696:Temperature; D013997:Time Factors; D014320:Triphenylmethyl Compounds / Q000494:pharmacology; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000494:pharmacology
D000975:Antioxidants; D005609:Free Radicals; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D014320:Triphenylmethyl Compounds; D014451:Ubiquinone; C011561:triphenylmethylphosphonium; C429014:mitoquinone; D013482:Superoxide Dismutase; D010269:Paraquat