Effects of ageing on the fine distribution of the circadian CLOCK protein in reticular formation neurons

Many biochemical, physiological and behavioural processes, from bacteria to human, exhibit roughly 24 h cyclic oscillations deWned as circadian rhythms. However, during ageing, numerous aspects of the circadian biology undergo alterations; in particular, the sleep pattern changes, with more frequent awakenings and shorter sleep time. The basic mechanism of the circadian clock relies on intracellular molecular pathways involving interlocking transcriptional/translational feedback loops, and CLOCK protein, a transcription factor, is essential for normal circadian rhythms. In this study, the Wne distribution of CLOCK protein has been analysed, in adult and old rats, at diVerent phases of the daily cycle in the neurons of the medullary reticular formation, involved in the control of the sleep– wake cycle. The results demonstrate quali–quantitative modiWcations of CLOCK protein in the neurons of old animals, suggesting that such a deregulation of the intracellular clock mechanism may play some role in the degeneration of the sleep–wake circadian cycle.