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Age-related dysfunction of p53-regulated phagocytic activity in macrophages

Yohko Yamaguchi1, Kohei Kaida1, Yusuke Suenaga2

  • 1Division of Molecular Medicine, Department of Biomolecular Science, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba, 274-8510, Japan.

Biochemical and Biophysical Research Communications
|July 25, 2020
PubMed

Insights

Aging impairs macrophage phagocytosis due to p53 pathway dysregulation. In young mice, p53 suppresses phagocytosis and c-Myc, affecting M2 genes, but this link is lost in old mice, revealing a key aging mechanism.

Area of Science:

  • Immunology
  • Cellular Aging
  • Molecular Biology

Background:

  • Aging is associated with reduced macrophage phagocytic capacity and a shift from M2-like to M1-like phenotypes.
  • The precise molecular underpinnings of these age-related macrophage functional declines are not fully elucidated.

Purpose of the Study:

  • To investigate the role of p53 in regulating macrophage phagocytic activity and M2-like gene expression during aging.
  • To determine if p53's influence on phagocytosis and c-Myc is preserved in aged macrophages.

Main Methods:

  • Comparative analysis of p53 activity, phagocytosis, c-Myc levels, and M2-related gene expression in macrophages from young and old mice.
  • Chemical induction of p53 in macrophages to assess its functional impact.
  • Assessment of c-Myc suppression effects on M2-related genes in aged macrophages.

Main Results:

  • Functional p53, capable of inducing target genes like p21 and Mdm2, was present in macrophages from both young and old mice.
  • In young mouse macrophages, induced p53 decreased phagocytic activity and c-Myc levels, subsequently reducing M2-related gene expression.
  • In old mouse macrophages, phagocytic activity and c-Myc expression were independent of p53 activity, and c-Myc suppression did not alter M2-related genes.

Conclusions:

  • Dysregulation of p53 function in aged macrophages contributes to their diminished phagocytic activity.
  • The p53-c-Myc-M2 gene axis regulating phagocytosis in young macrophages is impaired during aging.
Keywords:
AgingImmune functionMacrophagesPhagocytic activityc-Mycp53

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