IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-18280-4.html
   My bibliography  Save this article

The precursor of PI(3,4,5)P3 alleviates aging by activating daf-18(Pten) and independent of daf-16

Author

Listed:
  • Dawei Shi

    (Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS)
    Center for Quantitative Biology (CQB), Peking University
    University of Chinese Academy of Sciences)

  • Xian Xia

    (Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS)
    Center for Quantitative Biology (CQB), Peking University
    University of Chinese Academy of Sciences)

  • Aoyuan Cui

    (University of Chinese Academy of Sciences
    CAS Key Laboratory of Nutrition, Metabolism and Food Safety, SINH, SIBS, CAS)

  • Zhongxiang Xiong

    (Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS)
    ShanghaiTech University)

  • Yizhen Yan

    (Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS)
    University of Chinese Academy of Sciences)

  • Jing Luo

    (Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS)
    Beijing Forestry University)

  • Guoyu Chen

    (Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS)
    University of Chinese Academy of Sciences)

  • Yingying Zeng

    (Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS)
    ShanghaiTech University)

  • Donghong Cai

    (Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS)
    University of Chinese Academy of Sciences)

  • Lei Hou

    (Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS)
    University of Chinese Academy of Sciences)

  • Joseph McDermott

    (Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS))

  • Yu Li

    (CAS Key Laboratory of Nutrition, Metabolism and Food Safety, SINH, SIBS, CAS)

  • Hong Zhang

    (University of Chinese Academy of Sciences
    CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, CAS)

  • Jing-Dong J. Han

    (Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS)
    Center for Quantitative Biology (CQB), Peking University)

Abstract

Aging is characterized by the loss of homeostasis and the general decline of physiological functions, accompanied by various degenerative diseases and increased rates of mortality. Aging targeting small molecule screens have been performed many times, however, few have focused on endogenous metabolic intermediates—metabolites. Here, using C. elegans lifespan assays, we conducted a worm metabolite screen and identified an eukaryotes conserved metabolite, myo-inositol (MI), to extend lifespan, increase mobility and reduce fat content. Genetic analysis of enzymes in MI metabolic pathway suggest that MI alleviates aging through its derivative PI(4,5)P2. MI and PI(4,5)P2 are precursors of PI(3,4,5)P3, which is negatively related to longevity. The longevity effect of MI is dependent on the tumor suppressor gene, daf-18 (homologous to mouse Pten), independent of its classical pathway downstream genes, akt or daf-16. Furthermore, we found MI effects on aging and lifespan act through mitophagy regulator PTEN induced kinase-1 (pink-1) and mitophagy. MI’s anti-aging effect is also conserved in mouse, indicating a conserved mechanism in mammals.

Suggested Citation

  • Dawei Shi & Xian Xia & Aoyuan Cui & Zhongxiang Xiong & Yizhen Yan & Jing Luo & Guoyu Chen & Yingying Zeng & Donghong Cai & Lei Hou & Joseph McDermott & Yu Li & Hong Zhang & Jing-Dong J. Han, 2020. "The precursor of PI(3,4,5)P3 alleviates aging by activating daf-18(Pten) and independent of daf-16," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18280-4
    DOI: 10.1038/s41467-020-18280-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-18280-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-18280-4?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
    ---><---

    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:11:y:2020:i:1:d:10.1038_s41467-020-18280-4. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.