Social interaction mitigates cognitive impairments and tau pathology in socially isolated aged mice.

Background: Social isolation significantly heightens the risk of dementia among the elderly. Maintaining social engagement has been proposed as a potential strategy to attenuate age-related cognitive decline. Objective: This study investigates whether social interaction with young conspecifics could improve cognitive function in aged mice with chronic social isolation. Methods: Twenty-month-old male C57BL/6 mice with long-term social isolation were randomly assigned to either cohousing with 3-month-old young mice or continued isolation for two months. Cognitive function was assessed using Y-maze spontaneous alternation and fear conditioning tests. Synaptic integrity and pathological markers were evaluated through western blotting and immunofluorescence. Results: Cohoused mice exhibited significantly enhanced novel arm exploration in the Y-maze and improved contextual fear memory compared to isolated controls. Molecular analyses revealed increased synapsin-1 expression and decreased tau phosphorylation at Ser214 in the cohousing group. Immunofluorescence demonstrated greater astrocyte density in the dentate gyrus of cohoused mice. Conclusions: Our findings demonstrate that social interaction with young counterparts can rescue isolation-induced cognitive deficits in aged mice, potentially through mechanisms involving tau phosphorylation regulation and synaptic protein restoration. These results provide preclinical evidence supporting social intervention strategies for preventing cognitive decline in socially isolated elderly individuals.