Research Paper Volume 6, Issue 11 pp 957—969
Age-associated changes in basal NF-κB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase
- 1 Translational Gerontology Branch, National Institute on Aging, Baltimore, MD 21224, USA
- 2 Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD 21224, USA
- 3 Laboratory of Genetics, National Institute on Aging, Baltimore, MD 21224, USA
- 4 Clinical Research Branch, National Institute on Aging, Baltimore, MD 21224, USA
Received: October 15, 2014 Accepted: December 4, 2014 Published: December 6, 2014
https://doi.org/10.18632/aging.100705How to Cite
Abstract
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-κB is higher in purified and rested human CD4+ T lymphocytes from older compared to younger individuals. This increase of NF-κB-associated transcription includes transcripts for pro-inflammatory cytokines such as IL-1 and chemokines such as CCL2 and CXCL10. We demonstrate that NF-κB 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-κB activity may contribute to the mild pro-inflammatory state of aging.