This study conducted an investigation into the impact of different dosages of vitamin E supplementation on histopathological alterations, cognitive behaviors, and the expression of age-associated genes in the heart and hippocampus of aged mice. Mice at 12 months of age received varying doses of vitamin E (100 mg/kg, 200 mg/kg, and 400 mg/kg) orally through gavage for 28 days. The results indicated that vitamin E supplementation improved working memory and spatial learning, reduced oxidative stress in the heart and brain tissues, and positively influenced the expression of SIRT1, Nrf2, and Calstabin2 genes. Interestingly, the efficacy of vitamin E was dose-dependent, with higher doses demonstrating more beneficial effects. The study also examined the influence of vitamin E on the activities of antioxidant enzymes, such as SOD and GPX, as well as the levels of MDA, a marker of oxidative stress, and found that vitamin E supplementation resulted in dose-related changes in these parameters. The findings also indicate that higher doses of vitamin E, particularly at 400 mg/kg, demonstrated more beneficial effects. However, the study emphasizes the need for further research to confirm these findings and to explore the potential clinical applications of vitamin E supplementation in addressing age-related conditions.