Role of NF-κB signaling pathway in increased tumor necrosis factor-α-induced apoptosis of lymphocytes in aged humans

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Abstract
In human aging, lymphocytes display increased sensitivity to tumor necrosis factor- (TNF-)-induced apoptosis. TNF- induces both survival and apoptotic signals. The survival signal is mediated by the activation of NF-B. Although a role of certain proapoptotic molecules in aging has been reported, a role of altered NF-B signaling pathway has not been explored in detail. In this study, we have compared TNF--induced activation of NF-B, phosphorylation of IB, and the expression of IKK between lymphocytes from young and aged humans. Furthermore, we have explored a role of IKK in increased susceptibility of lymphocytes from aged humans to TNF--induced apoptosis. Lymphocytes from aged humans displayed decreased activation of NF-B, reduced phosphorylation of IB, and decreased expression of IKK. In addition, overexpression of IKK in lymphocytes from aged humans normalized TNF--induced apoptosis to the level of young subjects. These data suggest a deficiency of NF-B signaling pathway and a role of IKK, at least in part, for increased sensitivity of lymphocytes from aged humans to TNF--induced apoptosis.