Loss of Mir146b with aging contributes to inflammation and mitochondrial dysfunction in thioglycollate-elicited peritoneal macrophages
- Washington University School of Medicine, United States
- 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
Funding
National Institutes of Health (R01 EY019287-08)
- Rajendra S Apte
Glenn Foundation for Medical Research
- Rajendra S Apte
American Federation for Aging Research
- Rajendra S Apte
Carl Marshall Reeves and Mildred Almen Reeves Foundation
- Rajendra S Apte
Jeffery T. Fort Innovation Fund
- Rajendra S Apte
Starr Foundation
- Rajendra S Apte
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Bérénice A Benayoun, University of Southern California, United States
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).
Version history
- Received: January 20, 2021
- Accepted: August 20, 2021
- Accepted Manuscript published: August 23, 2021 (version 1)
- Accepted Manuscript updated: August 25, 2021 (version 2)
- Accepted Manuscript updated: August 26, 2021 (version 3)
- 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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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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