Fig. 2.

Gene signatures of aged microglia subsets. Different single-cell RNAseq studies have analyzed aged microglia. Their findings show the majority of cells to have a homeostatic gene signature, characterized by housekeeping genes that support healthy microglia function (in blue). The morphology of homeostatic microglia is highly ramified with extended and arborized processes [8]. In addition, aged mice show an enrichment of two subpopulations of microglia (in light pink, red). Although the signatures described in different studies are not completely overlapping, they share common features such as the upregulation of IFN-regulated genes (IRM, OA3) or genes related to inflammation, phagocytosis and lipid metabolism (ARM, OA2, WAM) [50, 58, 65, 67]. Aged microglia display shorter and thickened processes, with inclusions that arise from either phagocytosis or lipid accumulations [17, 134]; however, it remains to be clarified if the two subtypes have similar or distinctive morphological characteristics