IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-46037-w.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-46037-w
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-46037-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Andrew G. Fraser & Ravi S. Kamath & Peder Zipperlen & Maruxa Martinez-Campos & Marc Sohrmann & Julie Ahringer, 2000. "Functional genomic analysis of C. elegans chromosome I by systematic RNA interference," Nature, Nature, vol. 408(6810), pages 325-330, November.
    2. Varnesh Tiku & Chirag Jain & Yotam Raz & Shuhei Nakamura & Bree Heestand & Wei Liu & Martin Späth & H. Eka. D. Suchiman & Roman-Ulrich Müller & P. Eline Slagboom & Linda Partridge & Adam Antebi, 2017. "Small nucleoli are a cellular hallmark of longevity," Nature Communications, Nature, vol. 8(1), pages 1-9, December.
    3. Emilien Nicolas & Pascaline Parisot & Celina Pinto-Monteiro & Roxane de Walque & Christophe De Vleeschouwer & Denis L. J. Lafontaine, 2016. "Involvement of human ribosomal proteins in nucleolar structure and p53-dependent nucleolar stress," Nature Communications, Nature, vol. 7(1), pages 1-12, September.
    4. Abigail Buchwalter & Martin W. Hetzer, 2017. "Nucleolar expansion and elevated protein translation in premature aging," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    5. Coleen T. Murphy & Steven A. McCarroll & Cornelia I. Bargmann & Andrew Fraser & Ravi S. Kamath & Julie Ahringer & Hao Li & Cynthia Kenyon, 2003. "Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans," Nature, Nature, vol. 424(6946), pages 277-283, July.
    6. Marta Artal-Sanz & Nektarios Tavernarakis, 2009. "Prohibitin couples diapause signalling to mitochondrial metabolism during ageing in C. elegans," Nature, Nature, vol. 461(7265), pages 793-797, October.
    7. Popi Syntichaki & Kostoula Troulinaki & Nektarios Tavernarakis, 2007. "eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans," Nature, Nature, vol. 445(7130), pages 922-926, February.
    8. Danny Filer & Maximillian A. Thompson & Vakil Takhaveev & Adam J. Dobson & Ilektra Kotronaki & James W. M. Green & Matthias Heinemann & Jennifer M. A. Tullet & Nazif Alic, 2017. "RNA polymerase III limits longevity downstream of TORC1," Nature, Nature, vol. 552(7684), pages 263-267, December.
    9. Patrick Narbonne & Richard Roy, 2009. "Caenorhabditis elegans dauers need LKB1/AMPK to ration lipid reserves and ensure long-term survival," Nature, Nature, vol. 457(7226), pages 210-214, January.
    10. Nick Lane & William Martin, 2010. "The energetics of genome complexity," Nature, Nature, vol. 467(7318), pages 929-934, October.
    11. Maria Thürmer & André Gollowitzer & Helmut Pein & Konstantin Neukirch & Elif Gelmez & Lorenz Waltl & Natalie Wielsch & René Winkler & Konstantin Löser & Julia Grander & Madlen Hotze & Sönke Harder & A, 2022. "PI(18:1/18:1) is a SCD1-derived lipokine that limits stress signaling," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Guocheng Fang & Zhen Qiao & Luqi Huang & Hui Zhu & Jun Xie & Tian Zhou & Zhongshu Xiong & I-Hsin Su & Dayong Jin & Yu-Cheng Chen, 2024. "Single-cell laser emitting cytometry for label-free nucleolus fingerprinting," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Yan-Ping Zhang & Wen-Hong Zhang & Pan Zhang & Qi Li & Yue Sun & Jia-Wen Wang & Shaobing O. Zhang & Tao Cai & Cheng Zhan & Meng-Qiu Dong, 2022. "Intestine-specific removal of DAF-2 nearly doubles lifespan in Caenorhabditis elegans with little fitness cost," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Aqilah Amran & Lara Pigatto & Johanna Farley & Rasoul Godini & Roger Pocock & Sandeep Gopal, 2024. "The matrisome landscape controlling in vivo germ cell fates," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. 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.
    5. Christos Karelakis & Zacharias Papanikolaou & Christina Keramopoulou & George Theodossiou, 2024. "Green Growth, Green Development and Climate Change Perceptions: Evidence from a Greek Region," Agriculture, MDPI, vol. 14(8), pages 1-17, July.
    6. Jin-Hyuck Jeong & Jun-Seok Han & Youngae Jung & Seung-Min Lee & So-Hyun Park & Mooncheol Park & Min-Gi Shin & Nami Kim & Mi Sun Kang & Seokho Kim & Kwang-Pyo Lee & Ki-Sun Kwon & Chun-A. Kim & Yong Ryo, 2023. "A new AMPK isoform mediates glucose-restriction induced longevity non-cell autonomously by promoting membrane fluidity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Hope Dang & Raul Castro-Portuguez & Luis Espejo & Grant Backer & Samuel Freitas & Erica Spence & Jeremy Meyers & Karissa Shuck & Emily A. Gardea & Leah M. Chang & Jonah Balsa & Niall Thorns & Caroline, 2023. "On the benefits of the tryptophan metabolite 3-hydroxyanthranilic acid in Caenorhabditis elegans and mouse aging," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    8. Cristiana Bersaglieri & Jelena Kresoja-Rakic & Shivani Gupta & Dominik Bär & Rostyslav Kuzyakiv & Martina Panatta & Raffaella Santoro, 2022. "Genome-wide maps of nucleolus interactions reveal distinct layers of repressive chromatin domains," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    9. Arles Urrutia & Víctor A García-Angulo & Andrés Fuentes & Mauricio Caneo & Marcela Legüe & Sebastián Urquiza & Scarlett E Delgado & Juan Ugalde & Paula Burdisso & Andrea Calixto, 2020. "Bacterially produced metabolites protect C. elegans neurons from degeneration," PLOS Biology, Public Library of Science, vol. 18(3), pages 1-31, March.
    10. Fix, Blair, 2020. "Economic Development and the Death of the Free Market," SocArXiv g86am, Center for Open Science.
    11. Melvin Pan & Christiane Zorbas & Maki Sugaya & Kensuke Ishiguro & Miki Kato & Miyuki Nishida & Hai-Feng Zhang & Marco M. Candeias & Akimitsu Okamoto & Takamasa Ishikawa & Tomoyoshi Soga & Hiroyuki Abu, 2022. "Glutamine deficiency in solid tumor cells confers resistance to ribosomal RNA synthesis inhibitors," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    12. Emily L. Spaulding & Alexis M. Feidler & Lio A. Cook & Dustin L. Updike, 2022. "RG/RGG repeats in the C. elegans homologs of Nucleolin and GAR1 contribute to sub-nucleolar phase separation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    13. Fix, Blair, 2016. "Energy and Institution Size," Working Papers on Capital as Power 2016/04, Capital As Power - Toward a New Cosmology of Capitalism.
    14. 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.
    15. James C. Murphy & Elena M. Harrington & Sophie Schumann & Elton J. R. Vasconcelos & Timothy J. Mottram & Katherine L. Harper & Julie L. Aspden & Adrian Whitehouse, 2023. "Kaposi’s sarcoma-associated herpesvirus induces specialised ribosomes to efficiently translate viral lytic mRNAs," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    16. Cyril Statzer & Jin Meng & Richard Venz & Monet Bland & Stacey Robida-Stubbs & Krina Patel & Dunja Petrovic & Raffaella Emsley & Pengpeng Liu & Ianessa Morantte & Cole Haynes & William B. Mair & Alban, 2022. "ATF-4 and hydrogen sulfide signalling mediate longevity in response to inhibition of translation or mTORC1," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    17. Carolien Bastiaanssen & Pilar Bobadilla Ugarte & Kijun Kim & Giada Finocchio & Yanlei Feng & Todd A. Anzelon & Stephan Köstlbacher & Daniel Tamarit & Thijs J. G. Ettema & Martin Jinek & Ian J. MacRae , 2024. "RNA-guided RNA silencing by an Asgard archaeal Argonaute," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    18. Sihai Yang & Xian-Hua Han & Yen-Wei Chen, 2023. "GND-PCA Method for Identification of Gene Functions Involved in Asymmetric Division of C. elegans," Mathematics, MDPI, vol. 11(9), pages 1-15, April.
    19. Changnan Wang & Bingying Wang & Taruna Pandey & Yong Long & Jianxiu Zhang & Fiona Oh & Jessica Sima & Ruyin Guo & Yun Liu & Chao Zhang & Shaeri Mukherjee & Michael Bassik & Weichun Lin & Huichao Deng , 2022. "A conserved megaprotein-based molecular bridge critical for lipid trafficking and cold resilience," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    20. Mitchell P Levesque & Teva Vernoux & Wolfgang Busch & Hongchang Cui & Jean Y Wang & Ikram Blilou & Hala Hassan & Keiji Nakajima & Noritaka Matsumoto & Jan U Lohmann & Ben Scheres & Philip N Benfey, 2006. "Whole-Genome Analysis of the SHORT-ROOT Developmental Pathway in Arabidopsis," PLOS Biology, Public Library of Science, vol. 4(5), pages 1-1, May.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46037-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.