Circadian clock genes Per1/Per2 deficiency induces premature age-related motor function decline in mice

The circadian clock genes Per1 and Per2 play a crucial role in regulating circadian rhythms. However, the consequences of their deficiency on motor function and age-related behavioral changes remain poorly understood. This study aimed to investigate the age-dependent effects of Per1/Per2 double knockout (DKO) on motor function in mice. Using wheel-running assays under a 12-hour light/12-hour dark cycle, we compared circadian entrainment between 2-month-old and 9-month-old DKO and wild-type (WT) mice. Motor function was assessed via the pole test and rotarod test, while exploratory behavior was evaluated using the open field test. We further analyzed the main and interaction effects of genotype and age on both circadian and motor parameters. Results showed that Per1/Per2 DKO markedly disrupted light-entrained behavioral rhythms in both age groups. While DKO mice aged from showing no motor deficits at 2 months to pronounced declines in balance and exploration by 9 months. Interaction analysis revealed a significant main effect of Per1/Per2 deficiency on balance and coordination, whereas age alone had no significant effect. Both factors affected exploration, with the genetic effect worsening with age. Notably, severe circadian disruption was present in young mice before motor deficits appeared. In conclusion, Per1/Per2 deficiency exacerbates age-related motor decline. Our finding that circadian disruption precedes motor deficits demonstrates that these clock genes are indispensable for preserving motor function and behavioral organization during aging.