Fig 1: (a–d): (a) A homogenous distribution of hippocampal microglial cells is lost in the aged brain. Histological sections were taken from adult WT (3 months), adult Per1−/−-mice (3 months), aged WT (24 months) and aged Per1−/−-mice (24 months). Representative Iba-1 immunostained sections are shown for each age group. The comparison of clustered microglia across age groups revealed significant differences in their clustering pattern, with an increased number of microglia in close proximity to each other in aged mice. Scale bars 100 µm. (b) Histological sections were taken from aged WT (24 months) and aged Per1−/−-mice (24 months). The comparison of clustered microglia in the corpus callosum revealed similar differences in their clustering pattern, with an increased number of microglia in close proximity to each other in aged Per1−/−-mice. Scale bar 100 µm. (c) Densitometric analysis of Iba1 immunoreactivity in the hippocampus of WT (white scale) and Per1−/−-mice (grey scale). *** p < 0.001 and ### p < 0.001. (d) Aged Per1−/−-mice show significant alterations of microglia morphology, including soma volume increase and shortening of processes. Significant differences between means were statistically assessed by ANOVA. ** p < 0.01 and ## p < 0.01 were considered statistically significant. * Difference between the age groups; # differences between genotypes.