PROLONGED SOCIAL ISOLATION INDUCES AGE-DEPENDENT COGNITIVE IMPAIRMENTS IN MICE

Social isolation (SI) is increasingly recognized as an environmental stressor associated with adverse cognitive outcomes, with evidence suggesting that susceptibility is particularly heightened during aging. We investigated the effects of 8 weeks of SI on cognitive performance in young (5 months) and aged (22 months) male C57BL/6J/Ukj mice. Cognitive function was assessed during the final two weeksof SI using the Barnes maze.
Following SI, both young and aged mice exhibited impaired learning during the 6-day acquisition, reflected by increased latency to reach the escape box. Short-term memory was assessed with the escape box removed and was impaired in SI mice of both ages, as indicated by reduced time at the former target location, with increased latency observed only in aged SI mice. Long-term memory was assessed by retention of the escape box at its original position, and cognitive flexibility by relocation of the target to the opposite position. Both long-term memory and cognitive flexibility were selectively impaired in aged SI mice, reflected by prolonged latencies, with impaired search strategy observed specifically in the long-term memory task.
Together, these findings demonstrate that prolonged SI induces age-dependent cognitive impairments. While both young and aged mice exhibited increased latency during learning and the short-term memory task, aging markedly exacerbated deficits in long-term memory and cognitive flexibility. Our results highlight that SI impairs cognition across ages while age remains a critical modifier of susceptibility, indicating that older individuals are particularly vulnerable to its detrimental effects.