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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

Arsun Bektas1, Yongqing Zhang3, Elin Lehmann3, William H. Wood III3, Kevin G. Becker3, Karen Madara4, Luigi Ferrucci1, Ranjan Sen2
  • 1Translational Gerontology Branch, National Institute on Aging, Baltimore, MD 21224, USA
  • 2Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD 21224, USA
  • 3Laboratory of Genetics, National Institute on Aging, Baltimore, MD 21224, USA
  • 4Clinical Research Branch, National Institute on Aging, Baltimore, MD 21224, USA
Received: October 15, 2014Accepted: December 4, 2014Published: December 6, 2014
https://doi.org/10.18632/aging.100705

Copyright: © 2014 Bektas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.