miR-125-chinmo pathway regulates dietary restriction dependent enhancement of lifespan in Drosophila

  1. Manish Pandey
  2. Sakshi Bansal
  3. Sudipta Bar
  4. Amit Kumar Yadav
  5. Nicholas S Sokol
  6. Jason M Tennessen
  7. Pankaj Kapahi  Is a corresponding author
  8. Geetanjali Chawla  Is a corresponding author
  1. Regional Centre for Biotechnology, India
  2. Buck Institute for Research on Aging, United States
  3. Translational Health Science and Technology Institute, India
  4. Indiana University, United States

Abstract

Dietary restriction (DR) extends healthy lifespan in diverse species. Age and nutrient-related changes in the abundance of microRNAs (miRNAs) and their processing factors have been linked to organismal longevity. However, the mechanisms by which they modulate lifespan and the tissue-specific role of miRNA-mediated networks in DR-dependent enhancement of lifespan remains largely unexplored. We show that two neuronally enriched and highly conserved microRNAs, miR-125 and let-7 mediate the DR response in Drosophila melanogaster. Functional characterization of miR-125 demonstrates its role in neurons while its target chinmo acts both in neurons and the fat body to modulate fat metabolism and longevity. Proteomic analysis revealed that Chinmo exerts its DR effects by regulating the expression of FATP, CG2017, CG9577, CG17554, CG5009, CG8778, CG9527, and FASN1. Our findings identify miR-125 as a conserved effector of the DR pathway and open the avenue for this small RNA molecule and its downstream effectors to be considered as potential drug candidates for the treatment of late-onset diseases and biomarkers for healthy aging in humans.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2, 3, 4, 5, 6, 7, 8.Proteomics analysis data done in Figure 7 is also provided in Supplementary files 3 and 4 (Upregulated and downregulated processes).

Article and author information

Author details

  1. Manish Pandey

    RNA Biology Laboratory, Regional Centre for Biotechnology, Faridabad, India
    Competing interests
    The authors declare that no competing interests exist.
  2. Sakshi Bansal

    RNA Biology Laboratory, Regional Centre for Biotechnology, Faridabad, India
    Competing interests
    The authors declare that no competing interests exist.
  3. Sudipta Bar

    Larry L. Hillblom Center for Integrative Studies of Aging, Buck Institute for Research on Aging, Novato, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Amit Kumar Yadav

    NCD, Translational Health Science and Technology Institute, Faridabad, India
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9445-8156
  5. Nicholas S Sokol

    Department of Biology, Indiana University, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jason M Tennessen

    Department of Biology, Indiana University, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3527-5683
  7. Pankaj Kapahi

    Larry L. Hillblom Center for Integrative Studies of Aging, Buck Institute for Research on Aging, Novato, United States
    For correspondence
    Pkapahi@buckinstitute.org
    Competing interests
    The authors declare that no competing interests exist.
  8. Geetanjali Chawla

    RNA Biology Laboratory, Regional Centre for Biotechnology, Faridabad, India
    For correspondence
    gchawla@rcb.res.in
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0354-3716

Funding

DBT-Wellcome Trust India Alliance (IA/I(S)/17/1/503085)

  • Geetanjali Chawla

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Dario Riccardo Valenzano, Max Planck Institute for Biology of Ageing, Germany

Version history

  1. Received: September 1, 2020
  2. Accepted: June 7, 2021
  3. Accepted Manuscript published: June 8, 2021 (version 1)
  4. Version of Record published: June 25, 2021 (version 2)

Copyright

© 2021, Pandey et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Manish Pandey
  2. Sakshi Bansal
  3. Sudipta Bar
  4. Amit Kumar Yadav
  5. Nicholas S Sokol
  6. Jason M Tennessen
  7. Pankaj Kapahi
  8. Geetanjali Chawla
(2021)
miR-125-chinmo pathway regulates dietary restriction dependent enhancement of lifespan in Drosophila
eLife 10:e62621.
https://doi.org/10.7554/eLife.62621

Share this article

https://doi.org/10.7554/eLife.62621

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