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Circadian rhythms play an influential role in nearly all aspects of physiology and behavior in the vast majority of species on Earth. The biological clockwork that regulates these rhythms is dynamic over the lifespan: rhythmic activities such as sleep/wake patterns change markedly as we age, and in many cases they become increasingly fragmented. Given that prolonged disruptions of normal rhythms are highly detrimental to health, deeper knowledge of how our biological clocks change with age may create valuable opportunities to improve health and longevity for an aging global population. In this Review, we synthesize key findings from the study of circadian rhythms in later life, identify patterns of change documented to date, and review potential physiological mechanisms that may underlie these changes.

The endogenous circadian system provides an adaptive means of aligning cellular activity, physiological processes, and behaviors with the predictable 24 hour solar cycle. Circadian rhythms play a crucial role in the regulation of sleep by influencing not only the time of day at which sleep occurs but also a variety of other characteristics of sleep including sleep propensity, architecture, and the consolidation of nightly sleep episodes and daily waking in humans. Circadian rhythms exhibit marked plasticity across the life span, with older adulthood being no exception, and developmental changes in a variety of physiological rhythms are implicated in the characteristics of sleep observed in healthy older adulthood. In this chapter, we summarize the role of the circadian system in sleep, describe age-related changes in circadian rhythms, examine how these changes are implicated in the characteristics of sleep in later life, and consider how circadian-oriented interventions may help to address sleep disturbances among otherwise healthy older adults.

The body’s internal timekeeping system is an under-recognized but highly influential force in behaviors and emotions including anger and reactive aggression. Predictable cycles or rhythms in behavior are expressed on several different time scales such as circadian (circa diem, or approximately 24-h rhythms) and infradian (exceeding 24 h, such as monthly or seasonal cycles). The circadian timekeeping system underlying rhythmic behaviors in mammals is constituted by a network of clocks distributed throughout the brain and body, the activity of which synchronizes to a central pacemaker, or master clock. Our daily experiences with the external environment including social activity strongly influence the exact timing of this network. In the present review, we examine evidence from a number of species and propose that anger and reactive aggression interact in multiple ways with circadian clocks. Specifically, we argue that: (i) there are predictable rhythms in the expression of aggression and anger; (ii) disruptions of the normal functioning of the circadian system increase the likelihood of aggressive behaviors; and (iii) conversely, chronic expression of anger can disrupt normal rhythmic cycles of physiological activities and create conditions for pathologies such as cardiovascular disease to develop. Taken together, these observations suggest that a comprehensive perspective on anger and reactive aggression must incorporate an understanding of the role of the circadian timing system in these intense affective states.

Despite varied etiologies and symptoms, several neurodegenerative diseases – specifically, Alzheimer’s, Parkinson’s, and Huntington’s diseases – share the common feature of abnormal circadian rhythms, such as those in behavior (e.g., disrupted sleep/wake cycles), physiological processes (e.g., diminished hormone release), and biochemical activities (e.g., antioxidant production). Circadian disturbances are among the earliest symptoms of these diseases, and the molecular mechanisms of the circadian system are suspected to play a pivotal, and possibly causal, role in their natural histories. Here, we review the common circadian abnormalities observed in Alzheimer’s, Parkinson’s, and Huntington’s diseases, and summarize the evidence that the molecular circadian clockwork directly influences the course of these disease states. On the basis of this research, we explore several circadian-oriented interventions proposed as treatments for these neurological disorders.

Food anticipatory activity (FAA) refers to a daily rhythm of locomotor activity that emerges under conditions of food restriction, whereby animals develop an intense, predictable period of activity in the few hours leading up to a predictable, daily delivery of food. The neural mechanisms by which FAA is regulated are not yet fully understood. Although a number of brain regions appear to be involved in regulating the development and expression of FAA, there is little evidence to date concerning the role of the anterior agranular insular cortex (AICa). The AICa plays a critical role in integrating the perception of visceral states with motivational behaviour such as feeding. We assessed the effect of bilateral electrolytic or ibotenic acid lesions of the AICa on FAA in male Wistar rats receiving food for varying lengths of time (2 h, 3 h, or 5 h) during the middle of the light phase (starting at either ZT4 or ZT6). Contrary to our initial expectations, we found that both electrolytic and ibotenic acid lesions significantly increased, rather than decreased, the amount of FAA expressed in lesioned rats. Despite increased FAA, lesioned rats did not eat significantly more during restricted feeding (RF) periods than control rats. Similar to controls, AlCa-lesioned rats showed negligible anticipatory activity to a restricted treat suggesting that the increased anticipatory activity in lesioned rats is associated with food restriction, rather than the appetitive value of the meal. Monitoring behaviour in an open field indicated that increased FAA in AlCa-lesioned rats was not explained by a general increase in locomotor activity. Together, these findings suggest that the AICa contributes to the network of brain regions involved in FAA.

Normal circadian rhythms of behavior are disrupted in disorders involving the dopamine (DA) system, such as Parkinson's disease. We have reported previously using unilateral injections of the catecholamine toxin, 6-hydroxydopamine (6-OHDA), into the medial forebrain bundle that DA signaling regulates daily expression of the clock protein, PERIOD2 (PER2), in the dorsal striatum of the rat. In the present study, we made widespread lesions of DA fibers using large injections of 6-OHDA into the third ventricle to determine the involvement of DA in normal daily rhythms of wheel-running activity and PER2 patterns in the suprachiasmatic nucleus (SCN) and several regions of the limbic forebrain. Rats injected with 6-OHDA and housed in constant darkness were less active in the wheel and showed a disorganized pattern of activity in which wheel running was not confined to a specific phase over 24 h. The 6-OHDA injection had no effect on the daily PER2 pattern in the SCN, but blunted the normal rise in PER2 in the dorsal striatum. 6-OHDA also blunted PER2 expression in the periventricular nucleus of the hypothalamus, a region in which a daily PER2 pattern has not been previously reported in male rats, and in the oval nucleus of the bed nucleus of the stria terminalis, but not in the central nucleus of the amygdala. These results indicate that DA plays a prominent role in regulating circadian activity at both behavioral and molecular levels.

Circadian rhythms in rodents respond to arousing, nonphotic stimuli that contribute to daily patterns of entrainment. To examine whether the motivational significance of a stimulus is important for eliciting nonphotic circadian phase shirts in Syrian hamsters (Mesocricetus auratus), the authors compared responses to a highly rewarding stimulus (lateral hypothalamic brain stimulation reward [BSR]) and a highly aversive stimulus (footshock). Animals were housed on a 14:10-hr light-dark cycle until test day, when they were given a 1-hr BSR session (trained animals) or a 1-mA electric footshock at 1 of 8 circadian times, and were maintained in constant dark thereafter. Both BSR pulses and footshock produced nonphotic phase response curves. These results support the hypothesis that arousal resulting from the motivational significance of a stimulus is a major factor in nonphotic phase shifts.