Background: Healthy non-pharmacological lifestyle factors, such as regular physical exercise and dietary supplementation, have been shown to significantly improve cognitive outcomes over time compared to a more sedentary lifestyle and poor diet. Furthermore, exercise may serve as a potential protective factor in attenuating the effects associated with cognitive decline that are characteristic of neurodegenerative disorders, such as Alzheimer's disease (AD). Evidence indicates that certain dietary interventions can also attenuate the effects of neurodegeneration and positively impact longevity. Supplementation with polyphenols such as ellagic acid (EA), which is abundant in pomegranate juice, may help provide neuroprotective and longevity benefits.
Methods: This study examined the potential protective potential of EA and exercise and provides insight into the combined use of a polyphenol-rich diet and exercise to enhance behavioral outcomes and lifespan in a transgenic Drosophila melanogaster (fruit fly) model of AD with the Aβ42 gene.
Results: Fruit flies subjected to a 120-minute exercise regimen performed better on a climbing assay than flies that did not exercise. Conversely, flies that exercised for 30 min passed marginally more trials on a learning and memory assay using an aversive stimulus than flies that did not exercise, whereas both groups performed better than flies subjected to the more intense exercise condition.
Conclusion: These results suggest a hormetic effect of exercise regarding memory performance. Finally, flies fed a low dose of dietary EA (0.24 mg/mL) lived significantly longer than flies fed the control diet or higher concentrations of EA, again suggesting a hormetic effect of EA on longevity.
Keywords: animal models; human disease genetics; neuroinflammation; neuroscience.
© 2026 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.