Introduction: The disabling effects of dementia, an incurable disease with little effect on mortality, affect society far more than many other conditions. Objective: The aim of this study was to stop or delay the onset of dementia using low-cost methods such as physical exercise. Methods: Senescence-accelerated model-prone (SAMP) 10 mice were made to perform a user-friendly shaking exercise for 25 weeks. The motor function and hippocampal functions (learning, spatial cognition) of the mice were evaluated using behavioral experiments. The degree of hippocampal aging was evaluated based on brain morphology. The association between behavioral performance of the mice and the degree of hippocampal aging was then evaluated. Results: The behavioral test results showed that the shaking group had higher motor coordination (p < 0.01) and motor learning (p < 0.05). Significantly higher performances in the learning ability were observed in the shaking group at a middle-period experiment (p < 0.05); the spatial cognitive functions also improved (p < 0.05). The shaking group showed delayed ageing of cells in the dentate gyrus (DG; area: p < 0.01) and cornu Ammonis (CA; area: p < 0.01) regions of the hippocampus. Conclusions: The shaking exercise enhances the activity of mice and reduces age-associated decreases in learning and spatial cognitive functions. Regarding hippocampal morphology, shaking exercise can prevent non-functional protein accumulation, cell atrophy, and cell loss. Specifically, shaking exercise protects cell growth and regeneration in the DG area and enhances the learning function of the hippocampus. Furthermore, shaking exercise maintained the spatial cognitive function of cells in the CA3 and CA1 regions, and prevented the chronic loss of CA2 transmission that decreased the spatial memory decline in mice.

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