The role of O-GlcNAc modification in aging-related deterioration of Toll-like receptor signaling in macrophages

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In the present study, to clarify the molecular mechanism of age-related deterioration of macrophage inflammatory responses, lipopolysaccharide (LPS) responsiveness of peritoneal macrophages were compared between 2-month-old and 12-month-old mice. In middle age, the production of pro-inflammatory cytokine in response to LPS was reduced at the protein level but not at the mRNA level. In addition, Toll-like receptor signaling was not affected in middle age. In contrast, the phosphorylation level of eukaryotic initiation factor (eIF)-2alpha was increased in middle age. These results suggest that macrophage inflammatory responses were deteriorated at the post-transcriptional level in middle age, and that the age-related phenomena are associated with the reduction of mRNA translation mediated by increased phosphorylation of eIF-2alpha.