Molecular mechanisms of TNF-alpha-induced apoptosis in aging human T cell subsets.

TNF-alpha, a pro-inflammatory cytokine, exerts its biological activity by signaling via its two receptors, TNFR-1 and TNFR-2 and by activating NF-kappaB. NF-kappaB is essential for survival of many cell types; however, TNF-alpha also induces cell death. During human aging TNF-alpha production and TNF-alpha-induced apoptosis are increased. In this brief review, we will discuss the TNF-alpha-mediated signaling and various molecular mechanisms underlying increased apoptosis in T cell subsets in aged humans with a special reference to alterations in transcription factor NF-kappaB and Fas-associated death domain (FADD).