The functional changes of the circadian system organization in aging.

The circadian clock drives periodic oscillations at different levels of an organism from genes to behavior. This timing system is highly conserved across species from insects to mammals and human beings. The question of how the circadian clock is involved in the aging process continues to attract more attention. We aim to characterize the detrimental impact of aging on the circadian clock organization. We review studies on different components of the circadian clock at the central and periperal levels, and their changes in aged rodents and humans, and the fruit fly Drosophila. Intracellular signaling, cellular activity and intercellular coupling in the central pacemaker have been found to decline with advancing age. Evidence of degradation of the molecular clockwork reflected by clock gene expression in both central and peripheral oscillators due to aging is inadequate. The findings on age-associated molecular and functional changes of peripheral clocks are mixed. We conclude that aging can affect the circadian clock organization at various levels, and the impairment of the central network may be a fundamental mechanism of circadian disruption seen in aged species.