Macrosialin increases during normal brain aging are attenuated by caloric restriction

During normal aging, microglia develop an activated phenotype characterized by morphologic changes and induction of CD11b, MHC II, and other inflammatory markers. We show that macrosialin (CD68), a macrophage-specific protein, is increased by aging in selected brain regions of male C57BL/6NNia mice. In corpus callosum and striatum, macrosialin mRNA and protein increased ≥50% (24 months versus 4 months); hippocampus and cerebellum were unchanged. Caloric restriction (CR) attenuated these age-related increases. Since CR attenuates age-related increases in oxidative damage and inflammation, we examined whether oxidized lipoproteins and inflammatory processes regulate macrosialin using murine BV-2 microglial cells as a model. Oxidized low-density lipoproteins (oxLDL) induced macrosialin protein by 50%. Moreover, macrosialin was induced in response to lipopolysaccharide (LPS) plus interferon-γ (IFN-γ) which activates inflammatory pathways in BV-2 cells. Thus, the previously documented increase in oxidized lipoproteins, inflammation, and microglial activation during normal aging may contribute to the age-related increase in macrosialin expression.