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However, various cellular insults compromise GPX4 activity by reducing its key cofactor (reduced GSH) and essential cellular reducing equivalent (NAD(P)H) for the recycling of GSH, inhibiting its protein synthesis, or through enhanced degradation (Figure 3)

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The interest stems from indirect, mechanistic reasoning: NAD+ activates sirtuins and supports mitochondrial function, and animal studies have linked NAD+ restoration to improved metabolic markers and, in some rodent models, reduced fat accumulation