Dietary thiols accelerate aging of C. elegans

• Published in: Nature communications Vol. 12; no. 1; pp. 4336 - 14
• Main Authors: Gusarov, Ivan, Shamovsky, Ilya, Pani, Bibhusita, Gautier, Laurent, Eremina, Svetlana, Katkova-Zhukotskaya, Olga, Mironov, Alexander, Makarov, Alexander А., Nudler, Evgeny
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15-07-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 14/34; 14/35; 38; 38/91; 631/443/7; 631/45; 64; 64/11; 96; 96/2; Acetylcysteine; Acetylcysteine - pharmacology; Age related diseases; Aging; Aging - drug effects; Aging - genetics; Aging - physiology; Animals; Animals, Genetically Modified; Antioxidants; Biosynthesis; Caenorhabditis elegans - drug effects; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - genetics; Constraining; Consumption; Diet; Dietary Supplements; DNA-Binding Proteins - genetics; Escherichia coli; Female; Fibroblasts - metabolism; Gene expression; Gene Expression Regulation - drug effects; Glutathione; Glutathione - metabolism; Glutathione - pharmacology; Humanities and Social Sciences; Humans; Life span; Male; Microbiota; multidisciplinary; Paraquat - pharmacology; Protein folding; Reactive oxygen species; Reactive Oxygen Species - metabolism; Science; Science (multidisciplinary); Sulfhydryl Compounds - metabolism; Thiols; Transcription; Transcription Factors - genetics; Unfolded Protein Response - physiology
• ISSN: 2041-1723; 2041-1723
• 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.
Reactive oxygen species are required for the long lifespan, and glutathione is an antioxidant. Here the authors show that limiting the consumption of dietary thiols, including those naturally derived from the microbiota, increases proteotoxic stress resistance in worms and human cells, and extends C. elegans lifespan.