Changes in microglial morphologies during brain aging in common marmosets.

Microglia are critical modulators of neuronal activity, regulating brain function through removal of dying neurons, pruning non-functional synapses, and producing ligands that support neuronal survival. Microglial morphologies change with aging, shifting from a homeostatic, surveillant state (ramified morphology) to a more reactive state (intermediate, amoeboid, and dystrophic morphology). Common marmosets (Callithrix jacchus) are a valuable translational nonhuman primate model for aging, and studies of neuroinflammation and neurodegenerative disease. These small, genetically diverse platyrrhine primates are considered aged at 7 years, have a maximum potential lifespan of 12+ years, and display age-related changes in motor, sensorimotor, and cognitive function. Here we quantified microglial morphologies in 24 aged marmosets (7–18 years) in the dorsolateral prefrontal cortex (dlPFC, Brodmann’s area 9), hippocampal regions CA1 and CA3, and the entorhinal cortex (ENT) via immunohistochemistry against Iba1. The proportion of ramified microglia showed a significant negative correlation with age in dlPFC, CA1, and CA3, and the proportion of dystrophic microglia showed a significant positive correlation with age in all four regions examined. Males displayed a significantly higher proportion of dystrophic microglia than females in CA1. Sex did not significantly affect the proportion of microglia morphologies in any other brain region. A significant interaction between age and sex was found for the proportion of intermediate microglia in ENT. Overall, these data suggest brain aging in marmosets from middle-age to older adulthood is characterized by an increase in dystrophic microglia, and age-related changes in microglial morphology manifest differently in male and female marmosets in hippocampal regions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00429-026-03082-z.