@article{Mossad_Batut_Yilmaz-Gut_micro_drive-2022,
author = {Mossad, Omar and Batut, Bérénice and Yilmaz, Bahtiyar and 
          Dokalis, Nikolaos and Mezo, Charlotte and Nent, Elisa and 
          Nabavi, Lara Susann and Mayer, Melanie and Maron, Feres Jose 
          Mocayar and Buescher, Joerg M. and de Aguero, Mercedes Gomez 
          and Szalay, Antal and Lammermann, Tim and Macpherson, Andrew 
          J. and Ganal-Vonarburg, Stephanie C. and Backofen, Rolf and 
          Erny, Daniel and Prinz, Marco and Blank, Thomas},
title = {Gut microbiota drives age-related oxidative stress and 
         mitochondrial damage in microglia via the metabolite 
         {N}(6)-carboxymethyllysine},
journal = {Nat Neurosci},
year = {2022},
doi = {10.1038/s41593-022-01027-3},
volume = {25},
user = {backofen},
pmid = {35241804},
pages = {295-305},
number = {3},
issn = {1097-6256},
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.}
}