@Article{Mossad_Batut_Yilmaz-Gut_micro_drive-2022,
  author =	 {Mossad, Omar and Batut, Berenice 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},
  volume =	 {25},
  number =	 {3},
  pages =	 {295-305},
  user =	 {backofen},
  pmid =	 {35241804},
  doi = 	 {10.1038/s41593-022-01027-3},
  issn = 	 {1097-6256},
  issn = 	 {1546-1726},
  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.}
}