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Glycogen controls Caenorhabditis elegans lifespan and resistance to oxidative stress

Author

Listed:
  • Ivan Gusarov

    (New York University School of Medicine)

  • Bibhusita Pani

    (New York University School of Medicine)

  • Laurent Gautier

    (New York University School of Medicine)

  • Olga Smolentseva

    (New York University School of Medicine)

  • Svetlana Eremina

    (Engelhardt Institute of Molecular Biology, Russian Academy of Science)

  • Ilya Shamovsky

    (New York University School of Medicine)

  • Olga Katkova-Zhukotskaya

    (Engelhardt Institute of Molecular Biology, Russian Academy of Science)

  • Alexander Mironov

    (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

A high-sugar diet has been associated with reduced lifespan in organisms ranging from worms to mammals. However, the mechanisms underlying the harmful effects of glucose are poorly understood. Here we establish a causative relationship between endogenous glucose storage in the form of glycogen, resistance to oxidative stress and organismal aging in Caenorhabditis elegans. We find that glycogen accumulated on high dietary glucose limits C. elegans longevity. Glucose released from glycogen and used for NADPH/glutathione reduction renders nematodes and human hepatocytes more resistant against oxidative stress. Exposure to low levels of oxidants or genetic inhibition of glycogen synthase depletes glycogen stores and extends the lifespan of animals fed a high glucose diet in an AMPK-dependent manner. Moreover, glycogen interferes with low insulin signalling and accelerates aging of long-lived daf-2 worms fed a high glucose diet. Considering its extensive evolutionary conservation, our results suggest that glycogen metabolism might also have a role in mammalian aging.

Suggested Citation

  • Ivan Gusarov & Bibhusita Pani & Laurent Gautier & Olga Smolentseva & Svetlana Eremina & Ilya Shamovsky & Olga Katkova-Zhukotskaya & Alexander Mironov & Evgeny Nudler, 2017. "Glycogen controls Caenorhabditis elegans lifespan and resistance to oxidative stress," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15868
    DOI: 10.1038/ncomms15868
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    Cited by:

    1. Guohong, 2020. "Effects of Five Kinds of Drinking Water on the Lifespan of Daphnia Pulex," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 27(4), pages 20899-20903, May.
    2. Elite Possik & Laura-Lee Klein & Perla Sanjab & Ruyuan Zhu & Laurence Côté & Ying Bai & Dongwei Zhang & Howard Sun & Anfal Al-Mass & Abel Oppong & Rasheed Ahmad & Alex Parker & S.R. Murthy Madiraju & , 2023. "Glycerol 3-phosphate phosphatase/PGPH-2 counters metabolic stress and promotes healthy aging via a glycogen sensing-AMPK-HLH-30-autophagy axis in C. elegans," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Eirini Lionaki & Ilias Gkikas & Ioanna Daskalaki & Maria-Konstantina Ioannidi & Maria I. Klapa & Nektarios Tavernarakis, 2022. "Mitochondrial protein import determines lifespan through metabolic reprogramming and de novo serine biosynthesis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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