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Summary The goal of this study is to test the role of mitochondria and of mitochondrial metabolism in determining the processes that influence aging of female and male Drosophila. We observe that Drosophila simulans females tended to have shorter lifespan, higher levels of hydrogen peroxide production and significantly lower levels of catalase but not superoxide dismutase compared to males. In contrast, mammalian females tend to be longer lived, have lower rates of reactive oxygen species production and higher antioxidant activity. In both Drosophila and mammals, mitochondria extracted from females consume a higher quantity of oxygen when provided with adenosine diphosphate and have a greater mtDNA copy number than males. Combined, these data illustrate important similarities between the parameters that influence aging and mitochondrial metabolism in Drosophila and in mammals but also show surprising differences.

Summary Lifespans of organisms vary greatly even among individuals of the same species. Under the framework of the free oxygen radical theory of aging, it is predicted that variation in individual lifespan within a species will correlate with variation in the accumulation of oxidative damage to cell components from reactive oxygen species. In this study we test the hypothesis that variation in survival of three wild-caught Drosophila simulans fly lines (HW09, NC48 and MD106) correlates with three key aspects of mitochondrial bioenergetics. The rank order of median survival was HW09 > MD106 > NC48. Young HW09 flies (11–18 days) had (i) highest ADP:O (quantity of oxygen consumed by mitochondria when provided with a quantity of ADP) when metabolizing both electron transport chain complex I and complex III substrates; (ii) lowest rate of mitochondrial hydrogen peroxide production from complex III; and (iii) highest cytochrome c oxidase activity from complex IV. Rate of hydrogen peroxide production increased and cytochrome c oxidase activity decreased in all lines in the age range 11–25 days. This is the first study to correlate natural variation in organism survival with natural variation in mitochondrial bioenergetics.