Fig. 8. The proposed mechanism of the C. elegans response to exogenous thiols.

An excessive amount of GSH supplied by an E. coli diet leads to accumulation of a higher level of endogenous thiols (including GSH and Cys), which perturbs global gene expression, including the inhibition of SKN-1-mediated transcription, and accelerates aging. Acivicin restricts dietary GSH intake, favors an increased ROS production in mitochondria, which triggers the UPR-like response, enhances proteotoxic stress resistance, ultimately leading to an extended lifespan.