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In addition, knockdown of mitochondrial NADH-generating citric acid cycle enzyme MDH2 in mice extended lifespan (Mao et al., 2025), which may have been due to an oxidizing shift in both the mitochondrial and cytoplasmic [NAD + ]/[NADH], although the potential mechanism driving the oxidation of the cytoplasmic [NAD + ]/[NADH] is unclear

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