Long-lived Ames dwarf mice share many phenotypic characteristics with animals subjected to caloric restriction (CR) but they are not CR mimetics. CR prolongs longevity in both normal and Ames dwarf mice. Using real-time polymerase chain reaction and western blot, we have examined the expression of genes related to insulin signaling in the liver of normal and dwarf mice subjected to 30% CR. The results revealed divergent responses of dwarf and normal animals to CR raising an interesting possibility that CR may affect longevity of normal and dwarf mice by different mechanisms. Moreover, effects of dwarfism on the expression of the examined genes differed from the effects of CR, thus adding to the evidence that these long-lived mutants are not CR mimetics.