Aging
Navigate
Submit an Article
Research Paper|Volume 5, Issue 1|pp 18—36

Age-associated alterations in inducible gene transcription in human CD4+ T lymphocytes

Arsun Bektas2, Yongqing Zhang3, William H. Wood III.3, Kevin G. Becker3, Karen Madara4, Luigi Ferrucci2, Ranjan Sen1
  • 1Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
  • 2Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
  • 3Research Resources Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
  • 4Clinical Research Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
Received: October 15, 2012Accepted: January 25, 2013Published: January 30, 2013
https://doi.org/10.18632/aging.100522

Copyright: © 2013 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

Age associated immune dysregulation results in a pro-inflammatory state and increased susceptibility to infections and autoimmune diseases. Studies show that signaling initiated at the T cell antigen receptor (TCR) is impaired in CD4+ T cells from old compared to young mice. Here we examined TCR-inducible gene expression changes in CD4+ T cells during human aging. We reveal a dichotomy in gene expression mediated by the inducible transcription factor NF-κB. Most NF-κB target genes are not induced in a sustained manner in cells derived from older compared to younger individuals. However, a subset of NF-κB target genes including genes associated with chronic pro-inflammatory state in the elderly, such as interleukin 1 and 6, continue to be up-regulated even in the absence of NF-κB induction. In addition, we identify other widespread changes in gene expression between cells derived from older and younger individuals. Surprisingly, many of the most noteworthy age-associated changes in human CD4+ T cells differ from those seen in murine models. Our studies provide the first view of age-associated alteration of TCR-inducible gene expression in human CD4+ T cells.