A multi ‐level assessment of the bidirectional relationship between aging and the circadian clock

AbstractThe daily temporal order of physiological processes and behavior contribute to the wellbeing of many organisms including humans. The central circadian clock, which coordinates the timing within our body, is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Like other parts of the brain, aging impairs the SCN function, which in turn promotes the development and progress of aging related diseases. We here review the impact of aging on the different levels of the circadian clock machinery ‐ from molecules to organs – with a focus on the role of the SCN. We find that the molecular clock is less effected by aging compared to other cellular components of the clock. Proper rhythmic regulation of intracellular signaling, ion channels and neuronal excitability of SCN neurons are greatl y disturbed in aging. This suggests a disconnect between the molecular clock and the electrophysiology of these cells. The neuronal network of the SCN is able to compensate for some of these cellular deficits. However, it still results in a clear reduction in the amplitude of the SCN electrical rhyt hm, suggesting a weakening of the output timing signal. Consequently, other brain areas and organs not only show aging‐related deficits in their own local clocks, but also receive a weaker systemic timing signal. The negative spiral completes with the weakening of positive feed‐back from the per iphery to the SCN. Consequently, chronotherapeutic interventions should aim at str...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: REVIEW Source Type: research