No one can escape from memory decay with advancing age. Understanding molecular mechanisms underlying age-related memory impairment (AMI) is important not only from the scientific viewpoint but also for elucidating novel targets that may eventually lead to developing therapeutics for combating memory loss. AMI had been generally considered to be an overall or nonspecific decay of memory processes that results from dysfunction of neural networks. However, behavioral genetic tests of this hypothesis have not been carried out. Using Drosophila, we have demonstrated the first extensive behavioral-genetic characterization of AMI. We discovered that AMI results from the specific decay of only one memory component, amnesiac-dependent middle-term memory, and not other components. In support of this finding, we show that memory in aged flies is identical to that of amnesiac mutants, and while other memory mutants show a further decrease in memory upon aging, amnesiac flies do not. These results provide the first identification of a specific gene pathway underlying AMI.