The Mitochondria-Targeted Plastoquinone-Derivative SkQ1 Promotes Health and Increases Drosophila melanogaster Longevity in Various Environments.

Mitochondria play an important role in aging. Strongly reduced function of the mitochondria shortens life span, whereas moderate reduction prolongs life span, with reactive oxygen species production being the major factor contributing to life span changes. Previously, picomolar concentrations of the mitochondria-targeted antioxidant SkQ1 were shown to increase the life span of Drosophila by approximately 10%.

Reproducible effects of the mitochondria-targeted plastoquinone derivative SkQ1 on Drosophila melanogaster lifespan under different experimental scenarios.

Previously, extremely low, nanomolar concentrations of the mitochondria-targeted plastoquinone derivative SkQ1 (10-(6'-plastoquinonyl) decyltriphenylphosphonium) were shown to prolong the lifespan of male and female Drosophila melanogaster by about 10 % (Anisimov et al., Biochemistry (Moscow) 73:1329-1342, 2008). Using long-term monitoring of SkQ1 effects on the Drosophila lifespan, we analyzed different integral parameters of Drosophila survival and mortality under SkQ1 treatment.

Mitochondria-targeted plastoquinone derivative SkQ1 increases early reproduction of Drosophila melanogaster at the cost of early survival.

It was previously found that 20 pM SkQ1 (10-(6'-plastoquinonyl) decyltriphenylphosphonium) solution increased lifespan of virgin females and males of the fruit fly Drosophila melanogaster with maximal and highly reproducible effect on early survival of females. In this paper we demonstrate that SkQ1 solution of the same concentration does not increase lifespan of mated females and males, early effect on female survival being absent, whereas early fertility and the total number of progeny are elevated in treated flies. Increase in fertility observed in young mated females instead of increase of survival typical for young virgin females might illustrate the trade-off between the fly's lifespan and reproduction.

[Regularory elements of the copia retrotransposon determine different levels of expression in different organs of males and females of Drosophila melanogaster].

Using a model system in which the expression of the reporter gene lacZ is under the control of five deleted variants of the copia retrotransposon regulatory region, which includes the 5'-long terminal repeat (LTR) and the 5'-untranslated region (5'-UTR), their contribution to the control of retrotransposon activity in different organs of males and females of Drosophila melanogaster was analyzed. The whole regulatory region provides expression of the reporter gene at the embryonic stage, and in larvae and adult flies only in generative organs. The 5'-end of LTR harbors a positive regulator that determines expression of the retrotransposon in organs of all types.

Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 5. SkQ1 prolongs lifespan and prevents development of traits of senescence.

Very low (nano- and subnanomolar) concentrations of 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) were found to prolong lifespan of a fungus (Podospora anserina), a crustacean (Ceriodaphnia affinis), an insect (Drosophila melanogaster), and a mammal (mouse). In the latter case, median lifespan is doubled if animals live in a non-sterile vivarium. The lifespan increase is accompanied by rectangularization of the survival curves (an increase in survival is much larger at early than at late ages) and disappearance of typical traits of senescence or retardation of their development.