Dataset for Gut microbiota drives age-related oxidative stress and mitochondrial damage in microglia via the metabolite N(6)-Carboxymethyllysine

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 aged brains. Unbiased metabolomic analyses of serum and brain tissue revealed the accumulation of N(6)-carboxymethyllysine (CML) in microglia of the aging brain. CML mediated a burst of reactive oxygen species (ROS) and impeded mitochondrial activity and ATP reservoirs in microglia. We validated the age-dependent rise in CML levels in sera and brains of human subjects. 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 gut microbiota.