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

Arsun Bektas, Yongqing Zhang, William H. Wood, Kevin G. Becker, Karen Madara, Luigi Ferrucci, Ranjan Sen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)18-36
Number of pages19
JournalAging
Volume5
Issue number1
StatePublished - Jan 2013
Externally publishedYes

Keywords

  • Aene expression
  • Aging
  • CD4 T cell
  • Human
  • NF-κB

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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