Age-associated Changes in Basal NF-B Function in Human CD4+ T Lymphocytes via Dysregulation of PI3 Kinase (dataset 2)

Immune impairment and high circulating level of pro-inflammatory cytokines are landmarks of human aging. However, the molecular basis of immune dysregulation 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-B is higher in purified and rested human CD4+ T lymphocytes from older compared to younger individuals. This increase of NF-B -associated transcription includes transcripts for pro-inflammatory cytokines such as IL-1 and chemokines such as CCL2 and CXCL10. We demonstrate that NF-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 dysregulated basal NF-B activity may contribute to the mild pro-inflammatory state of aging.

23

Bektas A, Zhang Y, Lehmann E, Wood WH 3rd, Becker KG, Madara K, Ferrucci L, Sen R