Induction and regulation of NFkappaB during aging: role of protein kinases.

Aging is accompanied by significant declines in immune function. To understand the basis for this age-related decline we have investigated the induction and regulation of transcription factor NFkappaB in murine T cells. We report that anti-CD3 treatment of T lymphocytes from old mice resulted in significantly lower levels of NFkappaB than those observed in similarly treated T cells from young mice. Pretreatment of T cells with staurosporine reduced the induction of NFkappaB in anti-CD3-activated cells from young mice but had no effect in similarly treated T cells from old mice. However, pretreatment with H-89 had little or no effect on the induction of NFkappaB in T cells from young mice, but significantly enhanced the induction of NFkappaB in T cells from old mice. These results suggest that the impairment in the generation of NFkappaB during aging may reflect age-associated differences in the regulation of protein kinase A.