Age-associated changes in basal NF-κB function in human CD4<sup>+</sup> T lymphocytes via dysregulation of PI3 kinase

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

doi:doi:10.18632/aging.100705

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 Bektas^1,, Yongqing Zhang^3,, Elin Lehmann^3,, William H. Wood III^3,, Kevin G. Becker^3,, Karen Madara^4,, Luigi Ferrucci^1,, Ranjan Sen^2,,

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

https://doi.org/10.18632/aging.100705
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Bektas A, Zhang Y, Lehmann E, Wood WH, Becker KG, Madara K, Ferrucci L, Sen R, . Age-associated changes in basal NF-κB function in human CD4⁺ T lymphocytes via dysregulation of PI3 kinase. Aging (Albany NY). 2014; 6:957-969. https://doi.org/10.18632/aging.100705

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Provider: 
        TY  - JOUR
        AU  - Bektas, Arsun 
        AU  - Zhang, Yongqing 
        AU  - Lehmann, Elin 
        AU  - Wood, William H. 
        AU  - Becker, Kevin G. 
        AU  - Madara, Karen 
        AU  - Ferrucci, Luigi 
        AU  - Sen, Ranjan 
        TI  - Age-associated changes in basal NF-κB function in human CD4<sup>+</sup> T lymphocytes via dysregulation of PI3 kinase
        JO  - 
        JA  - Aging (Albany NY)
        VL  - 6
        IS  - 11
        PB  - 
        SN  - 
        UR  - https://doi.org/10.18632/aging.100705
        DO  - 10.18632/aging.100705
        SP  - 957
        EP  - 969
        PY  - 
        AB  - 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.
        ER  -

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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.