N-acetyl-L-cysteine mimics the effect of dietary restriction on lifespan and reduces amyloid beta-induced toxicity in Caenorhabditis elegans

The effects of antioxidants on lifespan have been widely studied. Our previous study showed supplementation with N-acetyl-l-cysteine (NAC) extends the lifespan of Caenorhabditis elegans. Here we aimed to determine the lifespan-extending mechanism involved with NAC and the effect of NAC on Alzheimer's disease (AD). NAC further increased the lifespan of age-1 and clk-1 mutants, which have increased lifespan owing to reduced insulin/IGF-1-like signaling and mitochondrial function, respectively. There was no additional lifespan extension in eat-2 background, a genetic model of dietary restriction (DR), by NAC. Gene knockdown experiments revealed that the effect of NAC is not dependent on SKN-1, a protein-sensing DR status, whereas DAF-16, a transcription factor regulating stress-responsive genes, is required for lifespan extension by NAC. NAC delayed paralysis caused by amyloid beta. Our results show that NAC mimics the effect of DR on lifespan, possibly through the induction of DAF-16 nuclear localization and may retard the incidence of AD.