We investigated the influence of age and a 20% or 52% reduction in dietary calories (caloric restriction) on expression of mRNA for a number of transcription factors and signal-transducing proteins using 4, 16, and 30-month-old female mice of the long-lived C3B10RF1 strain. In all age groups, 52% caloric restriction, which extends maximum life span by approximately 33%, increased insulin receptor mRNA by 15% to 25% over the levels in animals fed ad libitum. Aging increased insulin receptor mRNA and glucocorticoid-receptor mRNA in all dietary groups. A similar increase in glucocorticoid receptor mRNA was not observed for male mice of three other strains, suggesting the change is sex- or strain-specific and not a general feature of aging. These changes appear to be specific. Neither caloric restriction nor age had an effect on the level of mRNA for insulin-like growth factor-I, RNA polymerase II elongation-factor S-II, or transcription factors Sp1, CCAAT and enhancer binding protein, or proto-oncogene c-jun.