Dietary thiols accelerate aging of C. elegans

Nat Commun. 2021 Jul 15;12(1):4336. doi: 10.1038/s41467-021-24634-3.


Glutathione (GSH) is the most abundant cellular antioxidant. As reactive oxygen species (ROS) are widely believed to promote aging and age-related diseases, and antioxidants can neutralize ROS, it follows that GSH and its precursor, N-acetyl cysteine (NAC), are among the most popular dietary supplements. However, the long- term effects of GSH or NAC on healthy animals have not been thoroughly investigated. We employed C. elegans to demonstrate that chronic administration of GSH or NAC to young or aged animals perturbs global gene expression, inhibits skn-1-mediated transcription, and accelerates aging. In contrast, limiting the consumption of dietary thiols, including those naturally derived from the microbiota, extended lifespan. Pharmacological GSH restriction activates the unfolded protein response and increases proteotoxic stress resistance in worms and human cells. It is thus advantageous for healthy individuals to avoid excessive dietary antioxidants and, instead, rely on intrinsic GSH biosynthesis, which is fine-tuned to match the cellular redox status and to promote homeostatic ROS signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Aging / drug effects*
  • Aging / genetics
  • Aging / physiology
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • DNA-Binding Proteins / genetics
  • Dietary Supplements
  • Escherichia coli
  • Female
  • Fibroblasts / metabolism
  • Gene Expression Regulation / drug effects
  • Glutathione / metabolism
  • Glutathione / pharmacology*
  • Humans
  • Male
  • Paraquat / pharmacology
  • Reactive Oxygen Species / metabolism
  • Sulfhydryl Compounds / metabolism
  • Transcription Factors / genetics
  • Unfolded Protein Response / physiology


  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Reactive Oxygen Species
  • Sulfhydryl Compounds
  • Transcription Factors
  • skn-1 protein, C elegans
  • Glutathione
  • Paraquat
  • Acetylcysteine