Loss of Mir146b with aging contributes to inflammation and mitochondrial dysfunction in thioglycollate-elicited peritoneal macrophages

  1. Andrea Santeford
  2. Aaron Y Lee
  3. Abdoulaye Sene
  4. Lynn M Hassman
  5. Alexey A Sergushichev
  6. Ekaterina Loginicheva
  7. Maxim N Artyomov
  8. Philip A Ruzycki
  9. Rajendra Apte  Is a corresponding author
  1. Washington University School of Medicine, United States
  2. Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, United States

Abstract

Macrophages undergo programmatic changes with age leading to altered cytokine polarization and immune dysfunction, shifting these critical immune cells from protective sentinels to disease promoters. The molecular mechanisms underlying macrophage inflammaging are poorly understood. Using an unbiased RNA-seq approach, we identified Mir146b as a microRNA whose expression progressively and unidirectionally declined with age in thioglycollate-elicited murine macrophages. Mir146b deficiency led to altered macrophage cytokine expression and reduced mitochondrial metabolic activity, two hallmarks of cellular aging. Single cell RNA sequencing identified patterns of altered inflammation and interferon gamma signaling in Mir146b deficient macrophages. Identification of Mir146b as a potential regulator of macrophage aging provides novel insights into immune dysfunction associated with aging.

Data availability

Sequencing data have been deposited in GEO under accession code GSE164476.

Article and author information

Author details

  1. Andrea Santeford

    Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7691-6213
  2. Aaron Y Lee

    Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Abdoulaye Sene

    Ophthalmology and Visual Sciences, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St.Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Lynn M Hassman

    Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Alexey A Sergushichev

    Pathology, Washington University School of Medicine, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Ekaterina Loginicheva

    Pathology, Washington University School of Medicine, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Maxim N Artyomov

    Pathology, Washington University School of Medicine, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Philip A Ruzycki

    Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Rajendra Apte

    Pathology, Washington University School of Medicine, Saint Louis, United States
    For correspondence
    apte@wustl.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2281-2336

Funding

National Institutes of Health (R01 EY019287-08)

  • Rajendra Apte

Glenn Foundation for Medical Research

  • Rajendra Apte

American Federation for Aging Research

  • Rajendra Apte

Carl Marshall Reeves and Mildred Almen Reeves Foundation

  • Rajendra Apte

Jeffery T. Fort Innovation Fund

  • Rajendra Apte

Starr Foundation

  • Rajendra Apte

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

Ethics

Animal experimentation: All animal use and experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of Washington University in Saint Louis and performed according to the Washington University Animal Care and Use Guidelines (protocol numbers 2018-0160 and 20-0003).

Reviewing Editor

  1. Bérénice A Benayoun, University of Southern California, United States

Publication history

  1. Received: January 20, 2021
  2. Accepted: August 20, 2021
  3. Accepted Manuscript published: August 23, 2021 (version 1)
  4. Accepted Manuscript updated: August 25, 2021 (version 2)
  5. Accepted Manuscript updated: August 26, 2021 (version 3)
  6. Version of Record published: September 2, 2021 (version 4)

Copyright

© 2021, Santeford 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. Andrea Santeford
  2. Aaron Y Lee
  3. Abdoulaye Sene
  4. Lynn M Hassman
  5. Alexey A Sergushichev
  6. Ekaterina Loginicheva
  7. Maxim N Artyomov
  8. Philip A Ruzycki
  9. Rajendra Apte
(2021)
Loss of Mir146b with aging contributes to inflammation and mitochondrial dysfunction in thioglycollate-elicited peritoneal macrophages
eLife 10:e66703.
https://doi.org/10.7554/eLife.66703

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