Chronic circadian disturbance by a shortened light-dark cycle increases mortality.

Chronic circadian disturbance, a condition of desynchronization between endogenous clock and environmental light-dark (LD) cycle, is known to cause adverse physiological changes including mortality. However, it is yet unclear whether these consequences result from disturbance of endogenous clock or condition of the LD cycle per se. To address this issue, we imposed 3 different periods of LD cycle (T) on wild type and functional clock-defective (Per1(-/-)Per2(-/-)) mice. We found that the disturbed rhythms of locomotor activity and body temperature resulted from interaction of endogenous clock and T cycle and the chronic state of the disturbance suppressed the endogenous circadian rhythm. Interestingly, the endogenous clock and the T cycles affected body weight and food intake independently, while their interaction affected the life span resulting increased mortality of wild type mice in a shortened T cycle. These results strongly indicate the presence of both separate and combined effects of the endogenous clock and T cycle on different physiological variables implying that shift work scheduling can be an important influence on health parameters.