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Macrosialin increases during normal brain aging are attenuated by caloric restriction

Angela M Wong1, Nilay V Patel, Nimesh K Patel

  • 1Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-0191, USA. angelawo@usc.edu

Neuroscience Letters
|September 15, 2005
PubMed

Insights

Aging increases macrosialin (CD68) expression in mouse brains, particularly in the corpus callosum and striatum. Caloric restriction mitigated this increase, suggesting a role for oxidative stress and inflammation in microglial activation.

Area of Science:

  • Neuroscience
  • Immunology
  • Aging Research

Background:

  • Microglia, the brain's immune cells, exhibit an activated phenotype during normal aging.
  • This activation involves morphological changes and the upregulation of inflammatory markers like CD11b and MHC II.

Purpose of the Study:

  • To investigate the age-related changes in macrosialin (CD68) expression in specific brain regions of mice.
  • To determine the effect of caloric restriction (CR) on these age-related changes.
  • To explore the role of oxidized lipoproteins and inflammatory stimuli in regulating macrosialin expression in microglial cells.

Main Methods:

  • Quantitative analysis of macrosialin mRNA and protein levels in different brain regions (corpus callosum, striatum, hippocampus, cerebellum) of young (4 months) and aged (24 months) male C57BL/6NNia mice.
  • Assessment of macrosialin expression in mice subjected to caloric restriction.
  • In vitro experiments using murine BV-2 microglial cells treated with oxidized low-density lipoproteins (oxLDL) and inflammatory activators (lipopolysaccharide plus interferon-gamma).

Main Results:

  • Macrosialin mRNA and protein levels significantly increased (≥50%) in the corpus callosum and striatum of aged mice compared to young mice.
  • Caloric restriction attenuated the age-related increase in macrosialin expression.
  • Oxidized low-density lipoproteins (oxLDL) induced macrosialin protein expression by 50% in BV-2 microglial cells.
  • Inflammatory stimuli (LPS + IFN-γ) also upregulated macrosialin in BV-2 cells.

Conclusions:

  • The age-related increase in macrosialin expression in specific brain regions is influenced by factors associated with aging, such as oxidized lipoproteins and inflammation.
  • Caloric restriction may counteract age-related microglial activation by modulating macrosialin expression.
  • Macrosialin serves as a potential biomarker for age-related microglial activation and inflammation in the brain.

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