Dietary thiols accelerate aging of C. elegans

Ivan Gusarov, Ilya Shamovsky, Bibhusita Pani, Laurent Gautier, Svetlana Eremina, Olga Katkova-Zhukotskaya, Alexander Mironov, Alexander А. Makarov and Evgeny Nudler ()
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Ivan Gusarov: New York University School of Medicine
Ilya Shamovsky: New York University School of Medicine
Bibhusita Pani: New York University School of Medicine
Laurent Gautier: New York University School of Medicine
Svetlana Eremina: Engelhardt Institute of Molecular Biology, Russian Academy of Science
Olga Katkova-Zhukotskaya: Engelhardt Institute of Molecular Biology, Russian Academy of Science
Alexander Mironov: Engelhardt Institute of Molecular Biology, Russian Academy of Science
Alexander А. Makarov: Engelhardt Institute of Molecular Biology, Russian Academy of Science
Evgeny Nudler: New York University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-24634-3

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