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Metabotropic GABA signalling modulates longevity in C. elegans

Author

Listed:
  • Lei Chun

    (College of Life Science and Technology, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology
    Life Sciences Institute, University of Michigan)

  • Jianke Gong

    (College of Life Science and Technology, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology
    Life Sciences Institute, University of Michigan)

  • Fengling Yuan

    (College of Life Science and Technology, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology)

  • Bi Zhang

    (College of Life Science and Technology, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology
    Life Sciences Institute, University of Michigan)

  • Hongkang Liu

    (College of Life Science and Technology, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology)

  • Tianlin Zheng

    (College of Life Science and Technology, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology)

  • Teng Yu

    (College of Life Science and Technology, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology)

  • X. Z. Shawn Xu

    (Life Sciences Institute, University of Michigan)

  • Jianfeng Liu

    (College of Life Science and Technology, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology)

Abstract

The nervous system plays an important but poorly understood role in modulating longevity. GABA, a prominent inhibitory neurotransmitter, is best known to regulate nervous system function and behaviour in diverse organisms. Whether GABA signalling affects aging, however, has not been explored. Here we examined mutants lacking each of the major neurotransmitters in C. elegans, and find that deficiency in GABA signalling extends lifespan. This pro-longevity effect is mediated by the metabotropic GABAB receptor GBB-1, but not ionotropic GABAA receptors. GBB-1 regulates lifespan through G protein-PLCβ signalling, which transmits longevity signals to the transcription factor DAF-16/FOXO, a key regulator of lifespan. Mammalian GABAB receptors can functionally substitute for GBB-1 in lifespan control in C. elegans. Our results uncover a new role of GABA signalling in lifespan regulation in C. elegans, raising the possibility that a similar process may occur in other organisms.

Suggested Citation

  • Lei Chun & Jianke Gong & Fengling Yuan & Bi Zhang & Hongkang Liu & Tianlin Zheng & Teng Yu & X. Z. Shawn Xu & Jianfeng Liu, 2015. "Metabotropic GABA signalling modulates longevity in C. elegans," Nature Communications, Nature, vol. 6(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9828
    DOI: 10.1038/ncomms9828
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    Cited by:

    1. Luis Filipe Costa-Machado & Esther Garcia-Dominguez & Rebecca L. McIntyre & Jose Luis Lopez-Aceituno & Álvaro Ballesteros-Gonzalez & Andrea Tapia-Gonzalez & David Fabregat-Safont & Tobias Eisenberg & , 2023. "Peripheral modulation of antidepressant targets MAO-B and GABAAR by harmol induces mitohormesis and delays aging in preclinical models," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

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