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However, in Drosophila , increased ETC complex I activity extended lifespan apparently through an oxidation of both the mitochondrial and cytoplasmic [NAD + ]/[NADH] to increase cytoplasmic NAD + levels to activate nucleocytoplasmic sirtuins to override the potential pro-aging effects of oxidation of the mitochondrial [NAD + ]/[NADH] on longevity (Mookerjee et al., 2010), may also slow aging by oxidizing the cytoplasmic [NAD + ]/[NADH], even though the mitochondrial [NAD + ]/[NADH] is also oxidized

doi:10.1016/j.mito.2012.11.005