Characterization of the behavioral correlates of early functional decline in mice

Conventional aging research often focuses on late-life frailty, even though human studies have shown that some cognitive trajectories begin to decline decades earlier. This thesis sought to identify early behavioral signatures of functional decline in mice, focusing on the transition from young adulthood to middle age. Standardized assays and a naturalistic, goal-directed predation task were applied across cross-sectional and longitudinal cohorts spanning 2 to 10/11 months of age. Cross-sectionally, some behavior followed a non-linear trajectory: predatory drive and open field exploration peaked at 6 months and declined by 11 months, whereas motor outputs such as voluntary wheel engagement and running cadence showed a progressive decline from 2 to 6 to 11 months. Multivariate analyses indicated a coordinated reconfiguration of behavioral profiles from 2 to 11 months. Longitudinally, repeated testing preserved high predatory drive, consistent with experience-dependent maintenance of task competence, but did not prevent age-related reductions in voluntary wheel engagement and running cadence. Overall, the data define an inflection window between 6 and 10/11 months, providing a tractable period for molecular profiling and geroprotective intervention testing before late-life decline.