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Mitochondrial MDH2 knockdown could have extended mouse lifespan by activating a prolongevity mitochondrial unfolded protein response (UPR mt ) gene expression program that enhances the cellular redox state downstream of initial detrimental redox changes, possibly by inducing the expression of LDH or G3PS enzymes to compensate for the oxidation of the mitochondrial [NAD + ]/[NADH]