title: Macrosialin increases during normal brain aging are attenuated by caloric restriction.
abstract: 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 >or=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-gamma (IFN-gamma) 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.
authors.affiliation: Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-0191, USA. angelawo@usc.edu
authors.forename: Angela M
authors.initials: AM
authors.lastname: Wong
authors.forename: Nilay V
authors.initials: NV
authors.lastname: Patel
authors.forename: Nimesh K
authors.initials: NK
authors.lastname: Patel
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Todd E
authors.initials: TE
authors.lastname: Morgan
authors.forename: Maria C
authors.initials: MC
authors.lastname: de Beer
authors.forename: Willem J S
authors.initials: WJ
authors.lastname: de Villiers
authors.forename: Caleb E
authors.initials: CE
authors.lastname: Finch
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D031204:Caloric Restriction; D002460:Cell Line; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D007371:Interferon-gamma; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C099252:oxidized low density lipoprotein