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Investigating the role of the myeloid circadian clock in aging

The circadian clock regulates daily rhythms across the entire organism, ranging from rhythmic gene transcription to daily cycles in mood. The intrinsic cellular clock consists of a transcription-translation feedback loop between the heterodimers Bmal/Clock and Per/Cry. In healthy immune cells, this clock drives circadian rhythms in cell trafficking, phagocytosis, and cytokine release among many other homeostatic activities. Animals lacking innate immune cell rhythms experience higher rates of sepsis and mortality during an infection. Since aging is often characterized by a loss of homeostatic immune functions, we hypothesized that dysfunction of the cellular circadian clock with aging contributes dysfunction in the immune system and an increased risk for disease. In this study, we used transcriptomic approaches to identify rhythmically expressed genes and pathways and observed that the core cellular clock remains rhythmic with aging. While aged animals still expressed a high number of rhythmic genes, the coordination of these rhythms became impaired. We also used genetic approaches to disrupt the intrinsic cellular clock and observed mild cognitive impairment in middle aged animals. These results suggest that the circadian clock may contribute to age-associated dysfunction in systemic inflammation.