Circadian system is considered as an important adaptive mechanism to deal with the periodical light/dark (LD) alternation induced by Earth rotation. Most circadian rhythms are under the control of a major pacemaker located in the suprachiasmatic nucleus (SCN). In addition, this clock is thought to synchronize multiple peripheral oscillators ensuring temporal coordination of metabolism and behaviour, allowing anticipation to periodical daily changes caused by light, food availability and exercise. At molecular level, circadian clocks are composed by a set of proteins that generate self-sustained circadian oscillations through positive and negative transcriptional/translational feedback loops.

Age-related changes in the circadian system, including phase advance and instability, amplitude reduction, period shortening, internal desynchronization and rhythmicity loss, are well documented, and seemingly contribute to various aging pathologies. Thus, the measurement of circadian marker rhythms such as locomotor activity or body temperature can be used as biomarkers for aging.

However, what is less known is that a primary alteration of circadian system (chronodisruption) plays a direct role in the aging process. Epidemiological studies show that shift work and bright light exposure during the night are associated with metabolic syndrome, sleep disorders, and breast, colorrectal and prostate cancer. Similarly, animal studies show a premature aging in SCN lesioned arrhythmic animals or in those subjected to light-dark shifts, ahemeral LD cycles or continuous light.

Recent findings demonstrate that circadian proteins play, in addition, non-circadian activities related with many physiological processes, including those associated with aging. Clock protein BMAL1 seems to participate in metabolism regulation, genotoxic stress response, reactive oxygen species homeostasis and premature aging, as it has been described in BMAL1 deficient mice.

This project was funded by Seneca Foundation (PI/05700/07), by Instituto de Salud Carlos III (RETICEF, RD06/0013/0019), and by the Ministry of Education and Science (BFU2007-60658/BFI).