The NAD+/Sirtuin Pathway May Influence Lifespan by Activating Mitochondrial Stress Response and FOXO Signaling

NAD(+) levels are reduced in aged mice and Caenorhabditis elegans.

• Decreasing NAD(+) levels is associated with further reduction in worm lifespan.
• Restoration of NAD(+) through genetic or pharmacological means may prevent age-related metabolic decline.
• The effects of NAD(+) restoration rely on the protein deacetylase sir-2.1.
• Induction of mitonuclear protein imbalance and activation of stress signaling are involved in the observed longevity effects.
• Activation of the mitochondrial unfolded protein response and nuclear translocation of the FOXO transcription factor DAF-16 are linked to NAD(+) modulation.

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