Loss of Mir146b with aging contributes to inflammation and mitochondrial dysfunction in thioglycollate-elicited peritoneal macrophages
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 unbiase...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2021-08-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/66703 |
| _version_ | 1811200299761664000 |
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| author | Andrea Santeford Aaron Y Lee Abdoulaye Sene Lynn M Hassman Alexey A Sergushichev Ekaterina Loginicheva Maxim N Artyomov Philip A Ruzycki Rajendra S Apte |
| author_facet | Andrea Santeford Aaron Y Lee Abdoulaye Sene Lynn M Hassman Alexey A Sergushichev Ekaterina Loginicheva Maxim N Artyomov Philip A Ruzycki Rajendra S Apte |
| author_sort | Andrea Santeford |
| collection | DOAJ |
| description | 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 sequencing (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-seq 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. |
| first_indexed | 2024-04-12T02:02:28Z |
| format | Article |
| id | doaj.art-6fb8d853a91b4d1da48547761a3b3cc2 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:02:28Z |
| publishDate | 2021-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-6fb8d853a91b4d1da48547761a3b3cc22022-12-22T03:52:38ZengeLife Sciences Publications LtdeLife2050-084X2021-08-011010.7554/eLife.66703Loss of Mir146b with aging contributes to inflammation and mitochondrial dysfunction in thioglycollate-elicited peritoneal macrophagesAndrea Santeford0https://orcid.org/0000-0002-7691-6213Aaron Y Lee1Abdoulaye Sene2Lynn M Hassman3Alexey A Sergushichev4Ekaterina Loginicheva5Maxim N Artyomov6Philip A Ruzycki7Rajendra S Apte8https://orcid.org/0000-0003-2281-2336Department of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine, St. Louis, United StatesDepartment of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine, St. Louis, United StatesDepartment of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine, St. Louis, United StatesDepartment of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine, St. Louis, United StatesDepartment of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, United StatesDepartment of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, United StatesDepartment of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, United StatesDepartment of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine, St. Louis, United StatesDepartment of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine, St. Louis, United States; Department of Medicine, Washington University in St. Louis School of Medicine, St. Louis, United States; Department of Developmental Biology, Washington University in St. Louis School of Medicine, St. Louis, United StatesMacrophages 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 sequencing (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-seq 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.https://elifesciences.org/articles/66703macrophageagingmitochondrial metabolism |
| spellingShingle | Andrea Santeford Aaron Y Lee Abdoulaye Sene Lynn M Hassman Alexey A Sergushichev Ekaterina Loginicheva Maxim N Artyomov Philip A Ruzycki Rajendra S Apte Loss of Mir146b with aging contributes to inflammation and mitochondrial dysfunction in thioglycollate-elicited peritoneal macrophages eLife macrophage aging mitochondrial metabolism |
| title | Loss of Mir146b with aging contributes to inflammation and mitochondrial dysfunction in thioglycollate-elicited peritoneal macrophages |
| title_full | Loss of Mir146b with aging contributes to inflammation and mitochondrial dysfunction in thioglycollate-elicited peritoneal macrophages |
| title_fullStr | Loss of Mir146b with aging contributes to inflammation and mitochondrial dysfunction in thioglycollate-elicited peritoneal macrophages |
| title_full_unstemmed | Loss of Mir146b with aging contributes to inflammation and mitochondrial dysfunction in thioglycollate-elicited peritoneal macrophages |
| title_short | Loss of Mir146b with aging contributes to inflammation and mitochondrial dysfunction in thioglycollate-elicited peritoneal macrophages |
| title_sort | loss of mir146b with aging contributes to inflammation and mitochondrial dysfunction in thioglycollate elicited peritoneal macrophages |
| topic | macrophage aging mitochondrial metabolism |
| url | https://elifesciences.org/articles/66703 |
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