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  Gut microbiota drives age-related oxidative stress and mitochondrial damage in microglia via the metabolite N6-carboxymethyllysine

Mossad, O., Batut, B., Yilmaz, B., Dokalis, N., Mezö, C., Nent, E., et al. (2022). Gut microbiota drives age-related oxidative stress and mitochondrial damage in microglia via the metabolite N6-carboxymethyllysine. Nature Neuroscience, 25, 295-305. doi:10.1038/s41593-022-01027-3.

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 Creators:
Mossad, Omar1, Author
Batut, Bérénice1, Author
Yilmaz, Bahtiyar1, Author
Dokalis, Nikolaos1, Author
Mezö, Charlotte1, Author
Nent, Elisa2, Author
Nabavi, Lara Susann1, Author
Mayer, Melanie1, Author
Maron, Feres José Mocayar1, Author
Büscher, Jörg Martin2, Author              
de Agüero, Mercedes Gomez1, Author
Szalay, Antal1, Author
Lämmermann, Tim2, Author              
Macpherson, Andrew J1, Author
Ganal-Vonarburg, Stephanie C1, Author
Backofen, Rolf1, Author
Erny, Daniel1, Author
Prinz, Marco1, Author
Blank, Thomas1, Author
Affiliations:
1Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243648              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_1565141              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2022-03-03
 Publication Status: Published online
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41593-022-01027-3
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Title: Nature Neuroscience
  Other : Nat. Neurosci.
Source Genre: Journal
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Publ. Info: New York, NY : Nature America Inc.
Pages: - Volume / Issue: 25 Sequence Number: - Start / End Page: 295 - 305 Identifier: ISSN: 1097-6256
CoNE: https://pure.mpg.de/cone/journals/resource/954925610931