Journal
AGING-US
Volume 5, Issue 1, Pages 18-36Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/aging.100522
Keywords
human; CD4(+) T cell; NF-kappa B; aging; aene expression
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Funding
- Intramural Research Program of the National Institute on Aging (Baltimore, MD)
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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-kappa B. Most NF-kappa B target genes are not induced in a sustained manner in cells derived from older compared to younger individuals. However, a subset of NF-kappa B 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-kappa B 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.
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