Age-Associated Changes In Basal Nf-Kappa B Function In Human Cd4(+) T Lymphocytes Via Dysregulation Of Pi3 Kinase

Immune impairment and high circulating level of pro-inflammatory cytokines are landmarks of human aging. However, the molecular basis of immune dys-regulation and the source of inflammatory markers remain unclear. Here we demonstrate that in the absence of overt cell stimulation gene expression mediated by the transcription factor NF-kappa B is higher in purified and rested human CD4(+) T lymphocytes from older compared to younger individuals. This increase of NF-kappa B -associated transcription includes transcripts for pro-inflammatory cytokines such as IL-1 and chemokines such as CCL2 and CXCL10. We demonstrate that NF-kappa B up-regulation is cell-intrinsic and mediated in part by phosphatidylinositol 3-kinase (PI3K) activity induced in response to metabolic activity, which can be moderated by rapamycin treatment. Our observations provide direct evidence that dys-regulated basal NF-kappa B activity may contribute to the mild pro-inflammatory state of aging.