Aging and circadian disruption: causes and effects

Abstract

The relationship between aging and daily "circadian" behavior in humans is bidirectional: on the one hand, dysfunction of circadian clocks promotes age-related maladies; on the other, aging per se leads to changes and disruption in circadian behavior and physiology. For the latter case, recent research suggests that changes to both homeostatic and circadian sleep regulatory mechanisms may play a role. Could hormonal changes be in part responsible?

Figure 1. Top panel

In vivo, a central clock in the suprachiasmatic nucleus (SCN) determines the timing of daily behavior, and communicates this timing to peripheral clocks in other tissues and brain loci that control sleep. The timing of sleep influences clock phase by controlling when the eyes receive environmental light. Inset graph, This light phase-shifts the clock differently at different times of day (Data reproduced from [11]). Black stars, Feedback loops affecting sleep in the elderly. 1. A shorter period in the SCN would shift sleep earlier, but this has not been observed experimentally in humans. 2. Changes to sleep-wake structure, either by affecting homeostatic sleep or by affecting the circadian drive to sleep at night, 3. could feed back to affect light availability and therefore clock phase because of natural time-dependent differences in phase shifting. 4. Hormones could directly affect peripheral clocks at sleep-wake centers to affect sleep timing without altering the central clock in the SCN. Bottom panel.In vitro, treatment of primary human fibroblasts with serum from older subjects (OS) results in a shorter period and an earlier phase of cellular circadian rhythms than that obtained with serum from younger subjects (YS). Heat treatment (OSHI) abolished this effect. (Data reproduced from [5].)