Mossad, Omar; Batut, Bérénice; Yilmaz, Bahtiyar; Dokalis, Nikolaos; Mezö, Charlotte; Nent, Elisa; Nabavi, Lara Susann; Mayer, Melanie; Maron, Feres José Mocayar; Buescher, Joerg M; Gomez de Agüero, Mercedes; Szalay, Antal; Lämmermann, Tim; Macpherson, Andrew J; Ganal-Vonarburg, Stephanie C; Backofen, Rolf; Erny, Daniel; Prinz, Marco; Blank, Thomas (2022). Gut microbiota drives age-related oxidative stress and mitochondrial damage in microglia via the metabolite N6-carboxymethyllysine. Nature neuroscience, 25(3), pp. 295-305. Nature America 10.1038/s41593-022-01027-3
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Microglial function declines during aging. The interaction of microglia with the gut microbiota has been well characterized during development and adulthood but not in aging. Here, we compared microglial transcriptomes from young-adult and aged mice housed under germ-free and specific pathogen-free conditions and found that the microbiota influenced aging associated-changes in microglial gene expression. The absence of gut microbiota diminished oxidative stress and ameliorated mitochondrial dysfunction in microglia from the brains of aged mice. Unbiased metabolomic analyses of serum and brain tissue revealed the accumulation of N6-carboxymethyllysine (CML) in the microglia of the aging brain. CML mediated a burst of reactive oxygen species and impeded mitochondrial activity and ATP reservoirs in microglia. We validated the age-dependent rise in CML levels in the sera and brains of humans. Finally, a microbiota-dependent increase in intestinal permeability in aged mice mediated the elevated levels of CML. This study adds insight into how specific features of microglia from aged mice are regulated by the gut microbiota.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie |
UniBE Contributor: |
Yilmaz, Bahtiyar (A), Gomez de Agüero Tamargo, Maria de la Mercedes, Macpherson, Andrew, Ganal-Vonarburg, Stephanie Christine |
ISSN: |
1097-6256 |
Publisher: |
Nature America |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
07 Mar 2022 09:43 |
Last Modified: |
05 Dec 2022 16:12 |
Publisher DOI: |
10.1038/s41593-022-01027-3 |
PubMed ID: |
35241804 |
BORIS DOI: |
10.48350/166595 |
URI: |
https://boris.unibe.ch/id/eprint/166595 |
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