<p>Objective(s): The purpose of this study was to evaluate the effect of moderate-intensity swimmingexercise on learning and memory by the Morris water maze test. Changes in the expressions ofcyclic AMP-response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF)proteins alternative pathway which were activated by sirtuin-1 (SIRT-1) were investigated.Materials and Methods: The study included thirty-two male Sprague-Dawley rats (350-500 g, 11-12 and 15–16 months old). The rats were randomly divided into four groups with 8 rats in eachgroup. The groups were designed as follows: Control-1 (11-12 months), Exercise-1 (11-12 months),Control-2 (15-16 months), Exercise-2 (15-16 months). Moderate-intensity exercise was assigned for30 min/day, 5 days/week, for the whole training period of 8 weeks.Results: There were statistically significant differences between the groups on the third day (P=0.005)when swim speeds increased in the exercise groups. There was a statistically significant differencebetween Exercise 1 and Exercise 2 groups, the entries in the platform zone decreased in Exercise 2group (P=0.026). While there were no histopathological findings observed in any group, increasedSIRT-1, BNDF, and CREB expressions were seen in exercise groups compared with control groups.Conclusion: In aged rats exercising at moderate intensity, increased expression of CREB and BDNF,and SIRT-1 could improve hippocampal-dependent memory<br></p>