Behavioral deficits, organ weight changes, and altered gut microbiota in single-housed middle-aged mice

In this study, we uncovered novel and intriguing effects of aging on mouse behavior, brain neurotransmitter levels, and gut microbiota, with a particular focus on the transition from young adulthood to middle age. Using C57BL/6 J male mice of different ages (young adults at 12 weeks, middle-aged at 30 weeks, and older middle-aged mice at 45 weeks), we observed notable changes. Middle- and older middle-aged mice exhibited reduced spontaneous activity and shorter central stay times in the open field test compared to young adult mice. Nesting behavior was also delayed in older middle-aged mice. In the novel object recognition test, long-term memory was impaired in middle-aged and older middle-aged mice. However, the concentrations of brain neurotransmitters (such as γ-aminobutyric acid and serotonin) and their precursor amino acids in the prefrontal cortex did not vary significantly with age. Analysis of the cecal microbiota revealed age-related changes in bacterial composition. Specifically, Deferribacterota was significantly more abundant in the middle-aged mice than in the young adult mice, and Pseudomonadota was more abundant in older middle-aged mice than in young adult mice. In conclusion, our study provides an integrative descriptive dataset highlighting age-related differences in behavior and gut microbiota among adult mice, contributing to a better characterization of normal aging processes.