Circadian rhythms are present in various species, and circadian rhythm disorder (CRD) affects people of all ages, especially those with age-related neurodegenerative diseases. Gut microbiota, which changes with age, also exhibits circadian rhythms. Disruption of gut microbial balance can trigger neurodegenerative diseases. This study explored the link between aging, CRD, and gut microbes by modeling CRD through light/dark cycle control. We found that aging worsened cognitive and mood disorders, along with gut microbial imbalance, intestinal barrier damage, and systemic inflammation in aged mice with CRD. Abnormal circadian gene expression increased oxidative stress. However, time-restricted feeding (TRF) improved CRD effects in aged mice by boosting Akkermansia muciniphila and inhibiting the NOD-like signaling pathway. This study shows that older mice exhibit increased behavioral and functional issues under CRD-related stress due to complex causes like systemic inflammation from a proinflammatory gut microbiome and oxidative stress from disrupted circadian genes. Maintaining a regular eating schedule significantly alleviates these CRD-induced issues in aged mice.
