Age-associated alterations in pro-inflammatory gene expression in humans

National Institute On Aging

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Abstract

During the current fiscal (2008) year we carried out the following studies:[unreadable] [unreadable] (1) We completed analysis of 18 donor samples with regard to NF-κB induction and gene expression in CD4+ cells. We found elevated constitutive levels of NF-κB pathway in cells from donors above the age of 65, suggesting a possible source of age-associated chronic inflammation. p65/Rel A and NF-κB-dependent gene expression was reduced in the same cohort, indicative of immune attenuation in the elderly.[unreadable] [unreadable] (2) We analyzed NF-κB induction and NF-κB-dependent gene expression in highly purified nave (CD45RA+) and memory (CD45RO+) CD4+ T cells from peripheral blood. Kinetic analysis of NF-κB induction showed no differences in NF-κB induction in response to TCR and co-receptor stimulation between the two cell populations. In contrast, NF-κB-dependent gene expression was much enhanced in memory cells. We infer that NF-κB is more "effectively" utilized in memory cells; the molecular basis for this difference is under investigation.[unreadable] [unreadable] (3) We purified monocytes from human peripheral blood and investigated NF-κB induction in response to lipopolysaccharide (LPS). We found rapid IκBα degradation but relatively low levels of nuclear p65/Rel A induction in these cells. RNA analysis is underway.