Characterization of Aging-Associated Up-Regulation of Constitutive Nuclear Factor-κB Binding Activity

Changes occur in gene expression during aging in vivo and in replicative senescence in vitro, suggesting that aging can affect gene regulation. We have recently observed age-related changes in ubiquitously expressed, oxidative stress-responsive nuclear factor-κB (NF-κB) pathway during aging. Here we report a significant age-related increase in nuclear NF-κB binding activity together with increased protein levels of p52 and p65 components in rat liver. An additional, higher molecular weight protein band seen in their western blots suggests that their post-translational modification (but not phosphorylation) occurs in liver, which might affect their nuclear localization and binding activity during aging. However, aging did not affect the protein levels of the main IκB inhibitors (IκBα and IκBβ) or IκB kinase (IKK)-complex subunits (IKKα, -β, and -γ) involved in NF-κB activation. In addition, the level of Ser32-phosphorylated IκBα was unaffected by age, suggesting that neither the IKK complex nor altered lev...