The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
Gut microbiota drives age-related oxidative stress and mitochondrial damage in microglia via the metabolite N6-carboxymethyllysine
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 N 6-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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“Microbiome-mediated disruption of the intestinal barrier during aging facilitates excessive translocation of N6-carboxymethyllysine across the intestinal mucosal barrier into the bloodstream.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [404]
In the citing paper
“This increased translocation results in the accumulation of N6-carboxymethyllysine in the brain, which in turn contributes to microglial dysfunction by inducing oxidative stress and mitochondrial dysfunction.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [404]
In the citing paper
“N6-carboxymethyllysine may promote mitochondrial impairment and oxidative stress in microglia [69]”
From Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity via AMPK/SOD2 Pathway (2023) · cites this paper as [69]
In the citing paper
“Reduced oxidative stress and improved mitochondrial dysfunction were recently reported in the brain microglia of old GF mice compared to their SPF counterparts46.”
From Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype (2023) · cites this paper as [46]
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Metadata
- Authors
- Mossad, O., Batut, B., Yilmaz, B., Dokalis, N., Mezö, C., Nent, E., Nabavi, L. S., Mayer, M., Maron, F. J. M., Buescher, J. M., de Agüero, M. G., Szalay, A., Lämmermann, T., Macpherson, A. J., Ganal-Vonarburg, S. C., Backofen, R., Erny, D., Prinz, M., & Blank, T.
- Affiliations
- University of Freiburg (DE)
- Max Planck Institute of Immunobiology and Epigenetics (DE)
- University of Bern (CH)
- Corresponding author
- Blank, Thomas
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2022-03
- Volume
- 25
- Issue
- 3
- Pages
- 295-305
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W4214818594
- Cited by
- 241
- References
- 63
- Citations by year
- 2026: 41 · 2025: 64 · 2024: 64 · 2023: 45 · 2022: 27
- FWCI
- 17.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- gut microbiota, microglia, aging, oxidative stress, mitochondrial dysfunction, advanced glycation end products, germ-free mice, intestinal permeability, reactive oxygen species, ATP metabolism, brain aging, metabolomics
- MeSH terms
- Gastrointestinal Microbiome, Animals, Lysine, Microglia, Oxidative Stress, Mice
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