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Dietary thiols accelerate aging of C. elegans

Author

Listed:
  • 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
    Howard Hughes Medical Institute, New York University School of Medicine)

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.

Suggested Citation

  • Ivan Gusarov & Ilya Shamovsky & Bibhusita Pani & Laurent Gautier & Svetlana Eremina & Olga Katkova-Zhukotskaya & Alexander Mironov & Alexander А. Makarov & Evgeny Nudler, 2021. "Dietary thiols accelerate aging of C. elegans," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24634-3
    DOI: 10.1038/s41467-021-24634-3
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    References listed on IDEAS

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    1. Nicholas A. Bishop & Leonard Guarente, 2007. "Two neurons mediate diet-restriction-induced longevity in C. elegans," Nature, Nature, vol. 447(7144), pages 545-549, May.
    2. Javier Apfeld & Cynthia Kenyon, 1999. "Regulation of lifespan by sensory perception in Caenorhabditis elegans," Nature, Nature, vol. 402(6763), pages 804-809, December.
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    Cited by:

    1. Shengjie Fan & Yingxuan Yan & Ying Xia & Zhenyu Zhou & Lingling Luo & Mengnan Zhu & Yongli Han & Deqiang Yao & Lijun Zhang & Minglv Fang & Lina Peng & Jing Yu & Ying Liu & Xiaoyan Gao & Huida Guan & H, 2023. "Pregnane X receptor agonist nomilin extends lifespan and healthspan in preclinical models through detoxification functions," Nature Communications, Nature, vol. 14(1), pages 1-23, December.

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