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Reducing the metabolic burden of rRNA synthesis promotes healthy longevity in Caenorhabditis elegans

Author

Listed:
  • Samim Sharifi

    (Friedrich Schiller University Jena
    Leibniz Institute on Aging – Fritz Lipmann Institute
    Matter Bio, Inc.)

  • Prerana Chaudhari

    (Leibniz Institute on Aging – Fritz Lipmann Institute)

  • Asya Martirosyan

    (Leibniz Institute on Aging – Fritz Lipmann Institute
    University of Cologne)

  • Alexander Otto Eberhardt

    (Friedrich Schiller University Jena)

  • Finja Witt

    (University of Innsbruck)

  • André Gollowitzer

    (University of Innsbruck)

  • Lisa Lange

    (Friedrich Schiller University Jena
    Leibniz Institute on Aging – Fritz Lipmann Institute)

  • Yvonne Woitzat

    (Leibniz Institute on Aging – Fritz Lipmann Institute)

  • Eberechukwu Maryann Okoli

    (Leibniz Institute on Aging – Fritz Lipmann Institute)

  • Huahui Li

    (Leibniz Institute on Aging – Fritz Lipmann Institute
    Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology)

  • Norman Rahnis

    (Leibniz Institute on Aging – Fritz Lipmann Institute)

  • Joanna Kirkpatrick

    (Leibniz Institute on Aging – Fritz Lipmann Institute)

  • Oliver Werz

    (Friedrich Schiller University Jena)

  • Alessandro Ori

    (Leibniz Institute on Aging – Fritz Lipmann Institute
    Genentech)

  • Andreas Koeberle

    (University of Innsbruck)

  • Holger Bierhoff

    (Friedrich Schiller University Jena
    Leibniz Institute on Aging – Fritz Lipmann Institute)

  • Maria Ermolaeva

    (Leibniz Institute on Aging – Fritz Lipmann Institute
    Friedrich Schiller University Jena)

Abstract

Ribosome biogenesis is initiated by RNA polymerase I (Pol I)-mediated synthesis of pre-ribosomal RNA (pre-rRNA). Pol I activity was previously linked to longevity, but the underlying mechanisms were not studied beyond effects on nucleolar structure and protein translation. Here we use multi-omics and functional tests to show that curtailment of Pol I activity remodels the lipidome and preserves mitochondrial function to promote longevity in Caenorhabditis elegans. Reduced pre-rRNA synthesis improves energy homeostasis and metabolic plasticity also in human primary cells. Conversely, the enhancement of pre-rRNA synthesis boosts growth and neuromuscular performance of young nematodes at the cost of accelerated metabolic decline, mitochondrial stress and premature aging. Moreover, restriction of Pol I activity extends lifespan more potently than direct repression of protein synthesis, and confers geroprotection even when initiated late in life, showcasing this intervention as an effective longevity and metabolic health treatment not limited by aging.

Suggested Citation

  • Samim Sharifi & Prerana Chaudhari & Asya Martirosyan & Alexander Otto Eberhardt & Finja Witt & André Gollowitzer & Lisa Lange & Yvonne Woitzat & Eberechukwu Maryann Okoli & Huahui Li & Norman Rahnis &, 2024. "Reducing the metabolic burden of rRNA synthesis promotes healthy longevity in Caenorhabditis elegans," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46037-w
    DOI: 10.1038/s41467-024-46037-w
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