Chronic inflammation in mice exposed to the long-term un-entrainable light–dark cycles

Abstract

Shift work is indispensable in our modern society; therefore, measures for maintaining the health of shift workers are urgently required. In this prospective study observing the effects of different types of scheduled light–dark shift conditions in wild-type mice, we reared mice for 630 days under two chronic jet lag conditions with distinct programs of light and darkness: an 8-h phase delay every 7 days (delay, n = 14) or an 8-h phase advance every 4 days (advance, n = 34). “Delay” represents a mild condition in which mice are entrained, whereas “Advance” represents a condition of circadian rhythm disorder in which mice are not entrained. Our results showed that the 26.5% (9/34) mice reared under the “Advance” shift condition died or were sacrificed by humane endpoint throughout the experiment, whereas the first death under “Delay” condition occurred on day 611. The mortality rate of the mice reared under “Advance” condition was higher than the mice under “Delay” condition [HR (95% CI) 4.26 (0.54–33.6)]. In “Advance” mice of shorter lifespan, which showed splenomegaly and increased myeloid cells in bone marrow, which indicates that chronic inflammation existed in those mice. Although this study is still preliminary, these findings suggest that prolonged severe circadian rhythm disorder may result in the induction of chronic inflammation and tend to result in a shorter lifespan. Further studies are needed to understand why and how circadian rhythm disorder increases the risk of various dysfunction of physiology and diseases.