Tyrosine phosphorylation-dependent activation of NFκB is compromised in T cells from the elderly

• Published in: Experimental gerontology 2004-04, Vol.39 (4), p.559-566
• Main Authors: Ponnappan, Subramaniam, Uken-Trebilcock, Gina, Lindquist, Michael, Ponnappan, Usha
• Format: Article
• Language: English
• Subjects: Aging; Immune-senescence; IκB; Kinase; NFκB; p56lck; Pervanadate; Pro-oxidants; T lymphocytes; Tyrosine phosphorylation
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/j.exger.2003.12.012

NFκB induction and gene regulation are compromised in T lymphocytes during aging. This has been attributed to altered proteasomal function resulting in decreased ubiquitin-mediated degradation of IκBα. However, little is known about the impact of aging on the mechanisms that lead to the release of active NFκB employing pro-oxidant pathways. Oxidant-mediated activation of NFκB has been previously shown to involve proteasome independent mechanisms and hence may be an important alternate conduit to the induction of this central transcription factor in aging. Employing H 2O 2 and pervanadate we not only demonstrate lowered tyrosine phosphorylation of IκBα, but also compromised induction of nuclear NFκB in T cells from the elderly. Lowered tyrosine phosphorylation of IκBα may be due to a decrease in activity of p56 lck and ZAP-70, since treatment with piceatannol, an inhibitor of syk and src family kinases, mimics age associated decline in tyrosine phosphorylation of IκBα in T cells from young donors. Thus, alternate pathways of NFκB induction are also impaired in T cells from the elderly and may underlie immune-deficit accompanying aging.