PRJNA571347
Atlas of Microglia-Microbiota in Aging (AMMA)
Microglia, the resident brain macrophages, display high plasticity in response to their environment. Aging of the central nervous system (CNS), when microglial physiology is especially disrupted, is a major risk factor for a myriad of neurodegenerative diseases. Therefore, it is crucial to decipher the intrinsic and extrinsic factors, like sex and the microbiota, that potentially modulate this process. Transcriptomic profiling of microglia showed a distinct aging dynamic in females and males. In the absence of the gut microbiota, we found less priming, a lowered rate of lysosomal dysfunction and oxidative stress as well as reduced mitochondrial dysfunction in microglia of the aging brain. In addition, we demonstrated intriguing sex- and age-dependent changes in the gut microbiota's composition and function. This study highlights the sexually dimorphic communication between gut microbiota and microglia throughout aging and illustrates that certain aspects of microglial aging are majorly instigated by the gut microbiota.