Mitochondrial Antioxidants Fail in Flies

Mitochondrially targeted antioxidants - such as gene engineering of increased amounts of catalase - are shown to extend life in mice, but here researchers find no such effect (or a negative effect) in flies: "The simultaneous overexpression of multiple copies of Mn superoxide dismutase (SOD) and ectopic catalase (mtCat) transgenes in the mitochondria of the fruit fly, Drosophila melanogaster, was shown previously to diminish the life span. The hypothesis tested in the present study was that this effect was due primarily to the presence of one or the other transgene. An alternative hypothesis was that both transgenes have additive, negative effects. Crosses were performed between five pairs of transgenic lines containing single-copy insertions of either mtCat, Mn SOD, or P element vector control transgenes at unique loci, and the life spans of progeny containing two mtCat, Mn SOD or vector insertions were determined. Increasing amounts of mitochondrial catalase activity tended to be associated with decreases in mean life span. Overexpression of two copies of the genomic Mn SOD transgene had no effect on life span. The results do not support the hypothesis that enhanced mitochondrial SOD or catalase activity promotes longevity in flies." This suggests that it's possible to set up a situation in mammals wherein mitochondrially targeted antioxidants are harmful to life span, but I'm not aware of any examples.



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