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Summary There is emerging evidence that circadian misalignment may alter energy expenditure, leading to obesity risk among those with irregular schedules [ 1 , 2 , 3 , 4 , 5 ]. It has been reported that energy expenditure is affected by the timing of sleep, exercise, and meals [ 6 ]. However, it is unclear whether the circadian system also modulates energy expenditure, independent of behavioral state and food intake. Here, we used a forced desynchrony protocol to examine whether fasted resting energy expenditure (REE) varies with circadian phase in seven participants. This protocol allowed us to uncouple sleep-wake and activity-related effects from the endogenous circadian rhythm, demonstrating that REE varies by circadian phase. REE is lowest at circadian phase ∼0°, corresponding to the endogenous core body temperature (CBT) nadir in the late biological night, and highest at circadian phase ∼180° in the biological afternoon and evening. Furthermore, we found that respiratory quotient (RQ), reflecting macronutrient utilization, also varies by circadian phase. RQ is lowest at circadian phase ∼240° and highest at circadian phase ∼60°, which corresponds to biological morning. This is the first characterization of a circadian profile in fasted resting energy expenditure and fasted respiratory quotient (with rhythmic profiles in both carbohydrate and lipid oxidation), decoupled from effects of activity, sleep-wake cycle, and diet in humans. The rhythm in energy expenditure and macronutrient metabolism may contribute to greater weight gain in shift workers and others with irregular schedules.

OBJECTIVES: Exposure to light can have acute alerting and circadian phase-shifting effects. This study investigated the effects of evening exposure to blue-enriched polychromatic white (BEL) vs. polychromatic white light (WL) on sleep inertia dissipation the following morning in older adults. METHODS: Ten healthy older adults (average age = 63.3 yrs; 6F) participated in a 13-day study comprising three baseline days, an initial circadian phase assessment, four days with 2-h evening light exposures, a post light exposure circadian phase assessment and three recovery days. Participants were randomized to either BEL or WL of the same irradiance for the four evening light exposures. On the next mornings at 2, 12, 22 and 32 minutes after each wake time, the participants completed a 90-s digit-symbol substitution test (DSST) to assess working memory, and objective alertness was assessed using a wake EEG recording. DSST and power density from the wake EEG recordings were compared between the two groups. RESULTS: DSST performance improved with time awake (p< 0.0001) and across study days in both light exposure groups (p< 0.0001). There was no main effect of group, although we observed a significant day × group interaction (p=0.0004), whereby participants exposed to BEL performed significantly better on the first two mornings after light exposures than participants in WL (post-hoc, p< 0.05). On those days, the BEL group showed higher EEG activity in some of the frequency bins in the sigma and beta range (p

Aging is associated with a marked increase in sleep complaints, and one factor causing sleep disruption is waking to void (nocturia). Urological surveys have found that few young adults report nocturia symptoms, but about half of those in their 60's and nearly 80% of older age groups are affected. Sleep surveys have found nocturia is a major cause of sleep disruption, with a majority of older adults with sleep disruption citing the need to void as the cause of their awakening. While much of the urological literature implies that nocturia causes sleep disruption, age-related changes in sleep depth and continuity may make it more likely that an older adult will wake in response to a filling bladder, or that an older adult will wake for another reason and then decide to void. There is also evidence that age-related changes in the amplitude of circadian rhythms contribute to nocturia. There is a well-described circadian rhythm in urine output, and evidence of circadian rhythmicity in some diuretic and anti-diuretic hormones. In this article, we describe how age-related changes in sleep depth and continuity and age-related changes in circadian rhythm amplitude may contribute to nocturia, and how nocturia in turn leads to sleep disruption. Better understanding of how changes in sleep and circadian rhythmicity impact nocturia may lead to improved treatments and better quality of life for older adults.

Aging is associated with numerous changes, including changes in sleep timing, duration, and quality. The circadian timing system interacts with a sleep-wake homeostatic system to regulate human sleep, including sleep timing and structure. This article reviews key features of the human circadian timing system, age-related changes in the circadian timing system, and how those changes may contribute to the observed alterations in sleep.

Access to electric light might have shifted the ancestral timing and duration of human sleep. To test this hypothesis, we studied two communities of the historically hunter-gatherer indigenous Toba/Qom in the Argentinean Chaco. These communities share the same ethnic and sociocultural background, but one has free access to electricity while the other relies exclusively on natural light. We fitted participants in each community with wrist activity data loggers to assess their sleep-wake cycles during one week in the summer and one week in the winter. During the summer, participants with access to electricity had a tendency to a shorter daily sleep bout (43 ± 21 min) than those living under natural light conditions. This difference was due to a later daily bedtime and sleep onset in the community with electricity, but a similar sleep offset and rise time in both communities. In the winter, participants without access to electricity slept longer (56 ± 17 min) than those with access to electricity, and this was also related to earlier bedtimes and sleep onsets than participants in the community with electricity. In both communities, daily sleep duration was longer during the winter than during the summer. Our field study supports the notion that access to inexpensive sources of artificial light and the ability to create artificially lit environments must have been key factors in reducing sleep in industrialized human societies. Fil: De La Iglesia, Horacio O.. University of Washington; Estados Unidos Fil: Fernandez Duque, Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Centro de Ecología Aplicada del Litoral. Universidad Nacional del Nordeste. Centro de Ecología Aplicada del Litoral; Argentina. Universidad Nacional de Formosa. Facultad de Recursos Naturales; Argentina. University of Yale; Estados Unidos Fil: Golombek, Diego Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina Fil: Lanza, Norberto Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Investigaciones Geohistóricas. Universidad Nacional del Nordeste. Instituto de Investigaciones Geohistóricas; Argentina Fil: Duffy, Jeanne F.. Harvard Medical School; Estados Unidos Fil: Czeisler, Charles A.. Harvard Medical School; Estados Unidos Fil: Valeggia, Claudia Rita. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Yale; Estados Unidos

The timing, duration, and consolidation of sleep result from the interaction of the circadian timing system with a sleep-wake homeostatic process. When aligned and functioning optimally, this allows wakefulness throughout the day and a long consolidated sleep episode at night. Mismatch between the desired timing of sleep and the ability to fall and remain asleep is a hallmark of the circadian rhythm sleep-wake disorders. This article discusses changes in circadian regulation of sleep with aging; how age influences the prevalence, diagnosis, and treatment of circadian rhythm sleep-wake disorders; and how neurologic diseases in older patients affect circadian rhythms and sleep.

Soluble IL-13 receptor-α1, or sIL13rα1, is a soluble protein that binds to interleukin-13 (IL-13) that has been previously described in mice. The function of sIL13rα1 remains unclear, but it has been hypothesized to act as a decoy receptor for IL-13. Recent studies have identified a role for IL-13 in glucose metabolism, suggesting that a decoy receptor for IL-13 might increase circulating glucose levels. Here, we report that delivery of sIL13rα1 to mice by either gene transfer or recombinant protein decreases blood glucose levels. Surprisingly, the glucose-lowering effect of sIL13rα1 was preserved in mice lacking IL-13, demonstrating that IL-13 was not required for the effect. In contrast, deletion of IL-4 in mice eliminated the hypoglycemic effect of sIL13rα1. In humans, endogenous blood levels of IL13rα1 varied substantially, although there were no differences between diabetic and nondiabetic patients. There was no circadian variation of sIL13rα1 in normal human volunteers. Delivery of sIL13rα1 fused to a fragment crystallizable (Fc) domain provided sustained glucose lowering in mice on a high-fat diet, suggesting a potential therapeutic strategy. These data reveal sIL13rα1 as a circulating human protein with an unexpected role in glucose metabolism.

Work-related musculoskeletal disorders (WMSDs) persist as the leading occupational injury, accounting for nearly half of nurses’ total occupational injuries. Musculoskeletal pain is a known cause of sleep disruption, and individuals with WMSDs that interfere with sleep often report more pain. Evening chronotype has been associated with poor sleep among nurses. However, the associations among chronotype, sleep, and WMSDs are still unclear, and were explored in the present study. A cross-sectional survey was administered to 397 nurses, with 47.4% reporting WMSDs. Robust Poisson regression modeling suggested that evening type (PR = 1.32, p < .05), prolonged sleep onset latency (PR = 1.37, p < .05), and using sleep-promoting substances (PR = 1.35, p < .01) were associated with increased risk of WMSDs among nurses, after adjusting for shift work, regular exercise, body mass index, and other covariates. This study suggests that well-designed evidence-based nonpharmacological interventions to improve sleep may reduce the risk of WMSDs among nurses.

In the past 50 y, there has been a decline in average sleep duration and quality, with adverse consequences on general health. A representative survey of 1,508 American adults recently revealed that 90% of Americans used some type of electronics at least a few nights per week within 1 h before bedtime. Mounting evidence from countries around the world shows the negative impact of such technology use on sleep. This negative impact on sleep may be due to the short-wavelength-enriched light emitted by these electronic devices, given that artificial-light exposure has been shown experimentally to produce alerting effects, suppress melatonin, and phase-shift the biological clock. A few reports have shown that these devices suppress melatonin levels, but little is known about the effects on circadian phase or the following sleep episode, exposing a substantial gap in our knowledge of how this increasingly popular technology affects sleep. Here we compare the biological effects of reading an electronic book on a light-emitting device (LE-eBook) with reading a printed book in the hours before bedtime. Participants reading an LE-eBook took longer to fall asleep and had reduced evening sleepiness, reduced melatonin secretion, later timing of their circadian clock, and reduced next-morning alertness than when reading a printed book. These results demonstrate that evening exposure to an LE-eBook phase-delays the circadian clock, acutely suppresses melatonin, and has important implications for understanding the impact of such technologies on sleep, performance, health, and safety.

Treatment of circadian rhythm sleep disorders (CRSD) may include light therapy, chronotherapy and melatonin. Exogenous melatonin is increasingly being used in patients with insomnia or CRSD. Although pharmacopoeias and the European food safety authority (EFSA) recommend administering melatonin 1 -2 h before desired bedtime, several studies have shown that melatonin is not always effective if administered according to that recommendation. Crucial for optimal treatment of CRSD, melatonin and other treatments should be administered at a time related to individual circadian timing (typically assessed using the dim light melatonin onset (DLMO)). If not administered according to the individual patient's circadian timing, melatonin and other treatments may not only be ineffective, they may even result in contrary effects. Endogenous melatonin levels can be measured reliably in saliva collected at the patient's home. A clinically reliably DLMO can be calculated using a fixed threshold. Diary and polysomnographic sleep-onset time do not reliably predict DLMO or circadian timing in patients with CRSD. Knowing the patient's individual circadian timing by assessing DLMO can improve diagnosis and treatment of CRSD with melatonin as well as other therapies such as light or chronotherapy, and optimizing treatment timing will shorten the time required to achieve results.

Objectives: To evaluate associations between sleep duration at midlife and later life and change in sleep duration over time and cognition in older women. Design: Participants reported sleep duration in 1986 and 2000, and a subgroup of older participants began cognitive testing in 1995 to 2001; follow-up testing was conducted three times, at 2-year intervals. Setting: Prospective Nurses' Health Study cohort. Participants: Female nurses aged 70 and older free of stroke and depression at the initial cognitive assessment (N = 15,385). Measurements: Validated, telephone-based cognitive battery to measure cognitive function; four repeated assessments over 6 years were averaged to estimate overall cognition at older ages, and trajectories of cognitive change were evaluated over follow up. Results: Extreme sleep durations in later life were associated with worse average cognition (P < .001 for the quadratic term for a global score averaging all six cognitive tests). For example, women sleeping 5 h/d or less had worse global cognition than those sleeping 7 h/d, as did women sleeping 9 h/d or more; differences were equivalent to nearly 2 additional years of age. Associations were similar, although slightly attenuated, for sleep duration in midlife. Women whose sleep duration changed by 2 h/d or more over time had worse cognition than women with no change in sleep duration (e.g., for the global score, P < .001 for the quadratic term). Sleep duration was not associated with trajectories of cognitive function over 6 years, which might be attributable to short follow-up for detecting cognitive decline. Conclusion: Extreme sleep durations at midlife and later life and extreme changes in sleep duration over time appear to be associated with poor cognition in older women.

Studies using self-report and physiological markers of circadian rhythmicity have demonstrated sex differences in a number of circadian attributes including morningness-eveningness, entrained phase, and intrinsic period. However, these sex differences have not been examined at the level of the molecular clock and not in human cerebral cortex. The authors tested the hypothesis that there are detectable daily rhythms of clock gene expression in human cerebral cortex and that there are significant sex differences in the timing of these rhythms. The expression levels of 3 clock genes— PER2, PER3, and ARNTL1—were quantified in samples of dorsolateral prefrontal cortex from 490 deceased individuals in 2 cohort studies of older individuals, the Religious Orders Study and the Rush Memory and Aging Project, using mRNA microarray data. Clock gene expression at death was parameterized as a function of time of death using cosine curves and was examined for sex differences in the phase of these curves. Significant daily variation was seen in the expression of PER2 ( p = 0.004), PER3 ( p = 0.003), and ARNTL1 ( p = 0.0005). PER2/3 expression peaked at 10:38 (95% confidence interval [CI], 09:20-11:56) and 10:44 (95% CI, 09:29-11:59), respectively, and ARNTL1 expression peaked in antiphase to this at 21:23 (95% CI, 20:16-22:30). The timing of the expression of all 3 genes was significantly earlier in women than in men ( PER2 6.8 h, p = 0.002; PER3 5.5 h, p = 0.001; ARNTL1 4.7 h, p = 0.007). Daily rhythms of clock gene expression are present in human cerebral cortex and can be inferred from postmortem samples. Moreover, these rhythms are relatively delayed in men compared with women.

A common complaint of older persons is disturbed sleep, typically characterized as an inability to return to sleep after waking. As every sleep episode (i.e., time in bed) includes multiple transitions between wakefulness and sleep (which can be subdivided into rapid eye movement [REM] sleep and non-REM [NREM] sleep), we applied survival analysis to sleep data to determine whether changes in the "hazard" (duration-dependent probability) of awakening from sleep and/or returning to sleep underlie age-related sleep disturbances. The hazard of awakening from sleep-specifically NREM sleep-was much greater in older than in young adults. We found, however, that when an individual had spontaneously awakened, the probability of falling back asleep was not greater in young persons. Independent of bout length, the number of transitions between NREM and REM sleep stages relative to number of transitions to wake was approximately 6 times higher in young than older persons, highlighting the difficulty in maintaining sleep in older persons. Interventions to improve age-related sleep complaints should thus target this change in awakenings. © 2013 Elsevier Inc.

The sleep electroencephalogram (EEG) is highly heritable in humans and yet little is known about the genetic basis of inter-individual differences in sleep architecture. The aim of this study was to identify associations between candidate circadian gene variants and the polysomnogram, recorded under highly controlled laboratory conditions during a baseline, overnight, 8 h sleep opportunity. A candidate gene approach was employed to analyze single-nucleotide polymorphisms from five circadian-related genes in a two-phase analysis of 84 healthy young adults (28 F; 23.21 ± 2.97 years) of European ancestry. A common variant in Period2 (PER2) was associated with 20 min less slow-wave sleep (SWS) in carriers of the minor allele than in noncarriers, representing a 22% reduction in SWS duration. Moreover, spectral analysis in a subset of participants (n = 37) showed the same PER2 polymorphism was associated with reduced EEG power density in the low delta range (0.25-1.0 Hz) during non-REM sleep and lower slow-wave activity (0.75-4.5 Hz) in the early part of the sleep episode. These results indicate the involvement of PER2 in the homeostatic process of sleep. Additionally, a rare variant in Melatonin Receptor 1B was associated with longer REM sleep latency, with minor allele carriers exhibiting an average of 65 min (87%) longer latency from sleep onset to REM sleep, compared to noncarriers. These findings suggest that circadian-related genes can modulate sleep architecture and the sleep EEG, including specific parameters previously implicated in the homeostatic regulation of sleep.

Background and Objective Previous studies in adults have focused on differences in sleep timing with respect to morning and evening (ME) types, or gender difference in the distribution of ME types. We aimed to examine sleep habits and behaviors (daytime sleepiness and caffeine consumption) of adult ME types, and to examine whether the factors associated with ME type differed between men and women. Methods Among 1,086 subjects to whom we administered the Korean version of Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ-K), the Korean version of the Epworth Sleepiness Scale (KESS), the Pittsburgh Sleep Quality Index (PSQI) and asked questions about their sleep-wake timing and caffeine use, the data from 911 subjects (age: 38.4 ± 10.9 years, range: 18–88; F : M = 565 : 346) were analyzed. Standard scores of the MEQ were used to categorize the subjects as morning type (MT), evening type (ET) and neither type (NT). Results In the overall group, results from the PSQI indicated a significantly shorter sleep duration and greater caffeine consumption in ET when compared to those of MT or NT (p < 0.05). This was also found in the subgroup of women (p < 0.01), but not in the subgroup of men. Daytime sleepiness as reported on the KESS was significantly greater in the ET than the NT or MT overall (p < 0.05) and among the women (p < 0.01), but did not reach significance among men. Conclusions Our study found that ET subjects perceived their sleep quality as poorer than that of MT or NT subjects regardless of gender. We also found that ET women had significantly shorter sleep duration, greater daytime sleepiness, and larger caffeine consumption than MT or NT women, but we did not find the same findings in the men.

Objective: Circadian rhythms influence the timing of behavior, neurological diseases, and even death. Rare mutations in homologs of evolutionarily conserved clock genes are found in select pedigrees with extreme sleep timing, and there is suggestive evidence that certain common polymorphisms may be associated with self-reported day/night preference. However, no common polymorphism has been associated with the timing of directly observed human behavioral rhythms or other physiological markers of circadian timing at the population level. Methods: We performed a candidate gene association study with replication, evaluating associations between polymorphisms in homologs of evolutionarily conserved clock genes and the timing of behavioral rhythms measured by actigraphy. For validated polymorphisms, we evaluated associations with transcript expression and time of death in additional cohorts. Results: rs7221412, a common polymorphism near period homolog 1 (PER1), was associated with the timing of activity rhythms in both the discovery and replication cohorts (joint p ¼ 2.1 � 10 � 7 ). Mean activity timing was delayed by 67 minutes in rs7221412 GG versus rs7221412 AA homozygotes. rs7221412 also showed a suggestive time-dependent relationship with both cerebral cortex (p ¼ 0.05) and CD14 þ CD16 � monocyte (p ¼ 0.02) PER1 expression and an interesting association with time of death (p ¼ 0.015) in which rs7221412 GG individuals had a mean time of death nearly 7 hours later than rs7221412 AA/AG . Interpretation: A common polymorphism near PER1 is associated with the timing of human behavioral rhythms, and shows evidence of association with time of death. This may be mediated by differential PER1 expression. These results may facilitate individualized scheduling of shift work, medical treatments, or monitoring of vulnerable patient populations. ANN NEUROL 2012;72:324–334

Light exposure in the early night induces phase delays of the circadian rhythm in melatonin in humans. Previous studies have investigated the effect of timing, intensity, wavelength, history and pattern of light stimuli on the human circadian timing system. We present results from a study of the duration–response relationship to phase-delaying bright light. Thirty-nine young healthy participants (16 female; 22.18±3.62 years) completed a 9-day inpatient study. Following three baseline days, participants underwent an initial circadian phase assessment procedure in dim light (

Evening bright light exposure is reported to ameliorate daytime sleepiness and age-related sleep complaints, and also delays the timing of circadian rhythms. We tested whether evening light exposure given to older adults with sleep-wake complaints would delay the timing of their circadian rhythms with respect to their sleep timing, thereby reducing evening sleepiness and improving subsequent sleep quality. We examined the impact of evening light exposure from two different light sources on subjective alertness, EEG activity during wakefulness, and sleep stages. Ten healthy older adults with sleep complaints (mean age=63.3 years; 6F) participated in a 13-day study. After three baseline days, circadian phase was assessed. On the evening of days 5-8 the subjects were exposed for 2h to either polychromatic blue-enriched white light or standard white fluorescent light, and on the following day circadian phase was re-assessed. Subjects were allowed to leave the laboratory during all but the two days when the circadian phase assessment took place. Evening assessments of subjective alertness, and wake and sleep EEG data were analyzed. Subjective alertness and wake EEG activity in the alpha range (9.75-11.25 Hz) were significantly higher during light exposures when compared to the pre-light exposure evening (p

Background and Objective Sleep disturbances resulting from a mismatch between the sleep-wake schedule and an individual’s chronotype can influence work or school performance and numerous health outcomes. Individual chronotype can be determined by genetic factors, and is influenced by environmental factors which could change throughout life. We aimed to examine self-reported changes in chronotype during three different periods of life (childhood, teenage years, and adulthood). Methods Three hundred forty-three (age: 37.8 ± 11.6 years, range: 18–82; F: M = 214: 129) adult visitors to a National Museum in Korea were recruited for this study. The Korean version of the Horne-Östberg Morningness-Eveningness Questionnaire (MEQ-K) was administered and standard MEQ-K scores were used to categorize subjects as morning type (MT), evening type (ET), or neither type (NT). Binary logistic regression analyses were applied to examine the relationships of gender, current age, and childhood/teenager ME type with change in chronotype between childhood, teenage years, and adulthood. Results The ages, gender distribution, and years of education were different between the chronotype groups (p < 0.01). Individuals who reported childhood MT or ET had a lower probability of changing their chronotype between childhood and their teenage years compared with individuals reporting childhood NT (p < 0.0001), whereas individuals reporting teenage MT or ET had a higher probability (p < 0.0001). Furthermore, older individuals had a lower probability of reporting a chronotype change between childhood or teenage years and adulthood (p < 0.01). Conclusions Most individuals reported the same chronotype from childhood to their teenage years but a different chronotype between the teenage years and adulthood. Older age was associated with a lower probability of reporting a different chronotype during childhood or teenage years.

The Stroop color-naming task is one of the most widely studied tasks involving the inhibition of a prepotent response, regarded as an executive function. Several studies have examined performance on versions of the Stroop task under conditions of acute sleep deprivation. Though these studies revealed effects on Stroop performance, the results often do not differentiate between general effects of sleep deprivation on performance and effects specifically on interference in the Stroop task. To examine the effect of prolonged wakefulness on performance on the Stroop task, we studied participants in a 40-hour “constant routine” protocol during which they remained awake in constant conditions and performed a Stroop color-naming task every two hours. We found that reaction time was slowest when the color and word did not match (incongruent), fastest when the color and word did match (congruent), and intermediate when participants named the color of the non-word stimulus (neutral). Performance on all three trial types degraded significantly as a function of time awake. Extended wakefulness did not significantly change the additional time needed respond when the color and word did not match (Stroop interference), nor did it change the amount of facilitation when color and word matched. These results indicate that one night of sleep deprivation influences performance on the Stroop task by an overall increase in response time, but does not appear to impact the underlying processes of interference or facilitation. The results suggest that the degree to which an “executive function” is affected by sleep deprivation may depend on the particular executive function studied and the degree to which it is subserved by the prefrontal cortex.

Genetic association studies of the CLOCK 3111C/T polymorphism and diurnal preference have yielded conflicting results since the first report that the 3111C allele was associated with eveningness. The goal of the present study was to investigate the association of this polymorphism with diurnal preference and circadian physiology in a group of 179 individuals, by comparing the frequency of the 3111C allele to diurnal preference, habitual sleep timing, circadian phase markers, and circadian period. We did not find a significant association between this allele and morningness/eveningness or any circadian marker.

Recent studies have demonstrated that use of light‐emitting (LE) electronic devices in the evening close to bedtime negatively affects physiology and behavior, especially that of sleep and circadian rhythms (Bonnefond et al. 2006; Van den Bulck 2007; Cajochen et al. 2011; Munezawa et al. 2011; Arora et al. 2013, 2014; Czeisler 2013; Foley et al. 2013; Wood et al. 2013; Gamble et al. 2014; Heath et al. 2014; Chang et al. 2015; Carter et al. 2016; Czeisler and Shanahan 2016). Rapid technological advances and market pressures have led to near ubiquitous use of LE‐devices (e.g., desktop, laptop, and tablet computers, cell/smart phones, televisions, and video games) in the modern home and workplace; and such devices are now integral to many daily functions including communication, commerce, recreation, and access to news and information. Greater utility, availability, and portability of LE‐devices have additionally led to widespread LE‐device use in the evening and incorporation into the bedtime routine. A recent National Sleep Foundation survey found that 90% of Americans reported use of LE‐devices within an hour of their bedtimes, and greater use was associated with worse sleep outcomes at all ages (Gradisar et al. 2013). That and other studies have shown that adolescents and young adults are particularly likely to use LE‐devices before bedtime, often multiple LE‐devices at the same time, and the amount of LE‐device use in the evening is associated with multiple negative outcomes including delayed bedtimes, longer sleep latencies, sleep interruption from the LE‐devices during the night, shorter sleep durations, increased daytime sleepiness, and even obesity (Van den Bulck 2007; Munezawa et al. 2011; Arora et al. 2013, 2014; Foley et al. 2013; Gradisar et al. 2013; Gamble et al. 2014; Pourzanjani et al. 2015; Carter et al. 2016; Czeisler and Shanahan 2016). Light exposure per se is thought to cause many of the negative effects from evening use of LE‐devices. Retinal photoreceptors transmit light information to the master circadian clock in the hypothalamus, the suprachiasmatic nucleus (SCN), which regulates secretion of the pineal hormone melatonin together with rhythms in physiology and behavior including sleep, metabolism, immunity, alertness, and performance (Goel et al. 2013; Scheiermann et al. 2013; Qian and Scheer 2016). In the evening hours around bedtime, light exposure suppresses melatonin secretion and causes a phase delay shift in circadian rhythm timing such that melatonin secretion is reset to begin at a later time on subsequent nights (an effect similar to jet lag from extending daylight exposure later due to westward travel) (Khalsa et al. 2003; St Hilaire et al. 2012). This in turn can induce misalignment between the timing of the circadian rhythm of sleep propensity and the timing of sleep, reducing the duration, and quality of sleep (Czeisler et al. 1980; Dijk and Czeisler 1994). Misalignment can also cause delays in bedtime which, especially in children and adolescents, are associated with worse outcomes including behavioral risk factors and mental health problems such as depression (Gangwisch et al. 2010; Lemola et al. 2015; McGlinchey and Harvey 2015). There are also acute effects of light exposure that increase physiological and subjective levels of alertness (Lockley et al. 2006; Cajochen 2007; Rahman et al. 2014), which may impact when an individual feels tired and chooses to go to sleep when they are exposed to light in the evening. Furthermore, the effects of light on sleep, alertness, and circadian physiology are even greater from light exposures that are brighter, longer in duration, timed later in the evening, and contain short‐wavelength light (Lewy et al. 1980; Zeitzer et al. 2000; Brainard et al. 2001; Thapan et al. 2001; Khalsa et al. 2003; Lockley et al. 2006; Cajochen 2007; Santhi et al. 2012; St Hilaire et al. 2012; Lucas et al. 2014; Rahman et al. 2014). Because LE‐devices are often used for extended periods close to bedtime and their screens are typically illuminated by light‐emitting diodes (LED) that are rich in short‐wavelength light (Chang et al. 2015; Gringras et al. 2015) to which the human circadian system is particularly sensitive (Brainard et al. 2001; Thapan et al. 2001; Lockley et al. 2003; Ruger et al. 2013), their use is likely to increase alertness and impact sleep. Our group reported findings from a laboratory‐controlled, within‐subject, counter‐balanced, and randomized study in which the effects of light exposure from five consecutive evenings of reading on a LE‐tablet computer were compared to five consecutive evenings reading from printed books prior to a strictly imposed 10 pm bedtime, followed by an 8‐h scheduled sleep episode in total darkness (Chang et al. 2015). Compared to the evenings with printed books, the LE‐tablet reading condition caused significant melatonin suppression, circadian phase delay shifts, longer sleep latencies, reduced rapid eye movement (REM) sleep, increased alertness prior to bedtime, and lower next‐morning alertness. Those findings provided direct evidence that the light exposure from a tablet computer negatively affected sleep, circadian rhythms, and alertness under controlled laboratory conditions. In that study, the duration of evening reading sessions was set to four hours, bedtimes were fixed at 22:00, and in the LE‐tablet condition the device was placed at a fixed distance from participants and activities were restricted to reading electronic books (eBooks). Other studies that tested the effects of LE‐devices have similarly controlled aspects of the duration, timing, illuminance, and screen content of light exposures (Cajochen et al. 2011; Wood et al. 2013; Heath et al. 2014; van der Lely et al. 2015; Gronli et al. 2016). Now that the effects of LE‐devices on sleep, circadian rhythms, and alertness have been established even when bedtimes are held at a fixed time under controlled laboratory conditions, it is critical to evaluate the impact of LE‐devices on self‐selected bedtimes, sleep, alertness, and circadian rhythms in a randomized trial under controlled laboratory conditions. Increased evening alertness, melatonin suppression, and delayed circadian rhythm timing are likely key factors contributing to epidemiological findings showing associations between evening LE‐device use and later bedtimes (Foley et al. 2013; Gamble et al. 2014; Hysing et al. 2015). Additionally, such devices have numerous capabilities (e.g., internet, email, social media, games, videos, calendar, live streaming). Personal engagement with the diverse available activities may contribute to the selection of later bedtimes, thereby further prolonging evening light exposure from the device, and potentially leading to similar or even greater effects on sleep and circadian rhythms as those already observed under conditions with fixed bedtimes and light exposures. Therefore, in a follow‐up investigation to Chang et al. (Chang et al. 2015) we utilized a similar study design under controlled laboratory conditions, while allowing participants to self‐select their nightly bedtimes and LE‐tablet activities. We aimed to test whether under these unrestricted conditions, evening use of LE‐tablets compared to reading printed materials would affect self‐selection of bedtimes, and influence melatonin secretion, sleep, circadian timing, and alertness.

Aging is associated with an earlier timing of circadian rhythms and a shorter phase angle between wake time and the timing of melatonin secretion or the core body temperature nadir. Light has a phase-dependent effect on the circadian pacemaker, and modifications of habitual light exposure in older people could contribute to a change in the timing of circadian rhythms or in the phase angle of entrainment. In this study, we compare natural light exposure of community-dwelling older and young subjects studied at the same time of year, focusing on the pattern of light exposure across the waking day. We recorded light exposure data for 3 to 8 days from 22 older (aged 66.01 ± 5.83) and 22 young subjects (aged 23.41 ± 4.57), living at home on self-selected sleepwake schedules, and matched for time of year. All subjects were from New England (latitude 42.3° N to 43° N). We compared the percentage of the waking day spent by older and young subjects at 4 different light levels (from very dim to very bright). We compared hourly averaged light exposure data in each group according to clock time and with respect to each subject’s daily sleepwake times. Although both age groups spent more than half of their waking hours in dim or moderate room light intensity (

Healthy aging is associated with changes in sleep-wake regulation, and those changes often lead to problems sleeping, both during the night and during daytime. We aimed to examine the electroencephalographic (EEG) sleep spectra during non-rapid eye movement (NREM) sleep when sleep was scheduled at all times of day.After three 24-h baseline (BL) days, participants were scheduled to live on 20-hour "days" consisting of 6.7 hours of bed rest and 13.3 hours of wakefulness for 12 consecutive days (forced desynchrony, FD). The EEG was recorded from a central derivation during all scheduled sleep episodes, with subsequent visual scoring and spectral analysis.Intensive Physiological Monitoring Unit of the BrighamWomen's Hospital General Clinical Research Center.Twenty-four healthy older subjects (64.2 +/- 6.3 yr; 13 women, 11 men)Compared with BL nights, EEG activity in the slow wave (0.5 to 5.25 Hz), theta (6 to 6.25 and 7 Hz), alpha (10 to 11.25 Hz), and high spindle range (14.5 to 15.5 Hz) was significantly greater during FD, when subjects slept across many times of day and night. During FD, there was a significant interaction between homeostatic and circadian factors, such that EEG delta activity (0.5 to 1.5 Hz) was higher in the biological morning/early afternoon than at other times. EEG activity was significantly increased in almost all frequency ranges (0.5 to 21 Hz) during the biological day, as compared with the biological night, except for the lower EEG spindle range (12.25 to 14 Hz). Overall, EEG beta activity was positively correlated with wakefulness and negatively correlated with total sleep time.Our findings provide some new evidence for the underlying mechanisms that contribute to age-related difficulties in sleep consolidation, especially when sleep occurs during the daytime.

IN MAMMALS, THE SUPRACHIASMATIC NUCLEUS IS A CENTRAL NEURAL PACEMAKER THAT GENERATES CIRCADIAN RHYTHMS IN PHYSIOLOGIC AND BEHAV-IORAL measures, including the timing of sleep, hormone production, body temperature, and waking neurobehavioral performance.1–4 Studies of humans isolated from daily changes in the environment have led to the realization that the timing and organization of sleep, alertness, and performance vary with the circadian phase of the underlying, near 24-hour oscillation.5–7 Neurobehavioral performance in many sleep-deprivation studies has also been reported to be closely linked to homeostatic factors influenced by the duration of prior wakefulness.8 Previous studies have suggested that it is the precise balance between sleep-wake homeostatic factors and the circadian rhythm of alertness and sleep propensity that allow for stable alertness and performance throughout the waking day during entrainment.9–11 A recent study in which chronic misalignment between internal biologic time and the imposed sleep-wake schedule was imposed across 4 weeks showed that cognitive performance (i.e., learning) was significantly impaired, whereas subjects in the same study who remained entrained improved their performance.12 Using forced desynchrony (FD) studies, the circadian modulation of performance and alertness has been revealed.9,13–15 A 28-hour FD protocol has shown that, even within the range of 0 to 18 hours of wakefulness, the contribution of the circadian system to variations of alertness and performance is approximately equal to the contribution of the sleep-wake homeostat in young subjects.10 A study using a 20-hour FD protocol (with a 13.7-hour wake episode) also found circadian modulation of alertness and several aspects of cognitive performance.14 Previous 28-hour FD studies have found that, when scheduled to sleep at an adverse circadian phase, healthy young adults cannot take advantage of the 9.33-hour sleep opportunity on every night.16,17 In fact, when the end of the scheduled sleep episode is at an adverse circadian phase (beginning in the biological daytime between about 110° and 290°), the latter quarter of the scheduled sleep episode is severely disrupted, with sleep efficiency averaging below 70%.17 However, how that lost sleep then impacts subsequent sleep and wake episodes and daytime performance was not explored in those studies. A widely used performance test in studies of circadian rhythms or sleep deprivation is the Psychomotor Vigilance Task (PVT).18 This task has been reported to show no long-lasting training effects.8,18 In contrast, many other performance tests do have learning or practice effects, whereby, with repeated practice, performance on the task gradually improves.12,19,20 Therefore, consideration of those learning or practice effects should be made in analyzing data from long-duration studies. In a preliminary report, we found that a calculation performance task, a test of throughput, showed learning effects across a 4-week FD study, in which a saturating exponential function provided the best fit to the data for all subjects.21 Most prior studies in which both circadian and wake-dependent influences on performance have been assessed were of a 1- to 4-week duration. In the study we report here, subjects participated in a 6-week 28-hour FD study designed to assess circadian period estimates. Several performance measures were given to the subjects throughout the protocol. To examine the practice effects on a calculation performance test, we included a similar addition task that had been used in our prior preliminary report.21 We also included the PVT, given the prior reports suggesting that it has no such practice effects. We aimed to examine whether performance on the addition and PVT would show significant changes across the 6-week FD study, as well as to analyze the circadian and wake-dependent homeostatic modulation on both types of performance, taking into account interindividual differences.

OBJECTIVES: To determine whether healthy aging is associated with increased sleepiness and whether healthy older adults experience more sleepiness when acutely sleep deprived. DESIGN: A 5-day inpatient circadian rhythm–sleep study consisting of 3 baseline nights followed by an extended 26-hour wake episode under constant conditions. SETTING: Intensive Physiological Monitoring Unit, General Clinical Research Center, Brigham and Women's Hospital. PARTICIPANTS: Thirty-seven healthy participants without medical, psychological, or sleep disorders: 26 young (7 women, 19 men; mean age 21.9±3.3, range 18–29) and 11 “young-old” adults (3 women, 8 men; mean age 68.1±3.6, range 65–76). INTERVENTION: An extended 26-hour wake episode under constant conditions. MEASUREMENTS: Electroencephalographic-verified wakefulness, slow eye movements, sustained attention, subjective sleepiness. RESULTS: During the first 16 hours corresponding to the usual waking day, both groups rated themselves as alert and had similar levels of vigilance and little evidence of sleepiness. As the wake episode continued, the older subjects were less impaired, showing faster reaction times, fewer performance lapses and attentional failures, and less frequent unintentional sleep episodes than the younger subjects. CONCLUSION: This small study suggests that excessive sleepiness is not normal in healthy older adults. Symptoms of excessive sleepiness in this population, including reliance on caffeine to maintain alertness, should be evaluated and treated. Further study is needed to determine whether daytime sleepiness in middle-old (75–84 years) and old-old (≥85) adults is normal or is instead associated with sleep restriction, undiagnosed sleep disorders, medication side effects, mood disorders, or other medical disorders that disrupt sleep.

The circadian system in animals and humans, being near but not exactly 24-hours in cycle length, must be reset on a daily basis in order to remain in synchrony with external environmental time. This process of entrainment is achieved in most mammals through regular exposure to light and darkness. In this chapter, we review the results of studies conducted in our laboratory and others over the past 25 years in which the effects of light on the human circadian timing system were investigated. These studies have revealed, how the timing, intensity, duration, and wavelength of light affect the human biological clock. Our most recent studies also demonstrate that there is much yet to learn about the effects of light on the human circadian timing system.

Older adults have reduced sleep quality compared to younger adults when sleeping at habitual times, and greater sleep disruption when their sleep is at adverse times. The purpose of this analysis was to investigate how subjective measures of sleep relate to objectively-recorded sleep in older subjects scheduled to sleep at all times of day. We analyzed data from 24 healthy older (55–74 years) subjects who took part in a 32-day inpatient study where polysomnography (PSG) was recorded each night and subjective sleep was assessed after each scheduled wake time. The study included baseline nights and a forced desynchrony (FD) protocol when the subjects lived on a 20-hr rest-activity schedule. Our post-sleep questionnaire both included quantitative and qualitative questions about the prior sleep. Under baseline and FD conditions, objective and subjective sleep latency were correlated, subjective sleep duration was related to slow wave sleep and wake after sleep onset, subjective sleep quality was related to Stage 1 and 2 sleep, and sleepiness and refreshment at wake time were related to duration of premature awakening. During FD, most measures of objective and subjective sleep varied with circadian phase, and many additional correlations between objective and subjective sleep were present. Our findings show that when sleeping at habitual times, these healthy older subjects did not perceive their generally poor sleep quality, but under FD conditions where sleep quality changed from day-to-day their subjective sleep ratings were more associated with their objective sleep.

In this chapter, we present a series of four articles derived from a Introductory Workshop on Biological Rhythms presented at the 72nd Annual Cold Spring Harbor Symposium on Quantitative Biology: Clocks and Rhythms. A diverse range of species, from cyanobacteria to humans, evolved endogenous biological clocks that allow for the anticipation of daily variations in light and temperature. The ability to anticipate environmental variation promotes optimal performance and survival. In the first article, Introduction to Chronobiology, we present a brief historical timeline of how circadian concepts and terminology have emerged since the early observation of daily leaf movement in plants made by an astronomer in the 1700s. Workshop Part IA provides an overview of the molecular basis for rhythms generation in several key model organisms, Workshop Part IB focuses on how biology built a brain clock capable of coordinating the daily timing of essential brain and physiological processes, and Workshop Part IC gives key insight into how researchers study sleep and rhythms in humans.

Rhythms of sleep and wakefulness (typically measured as rest/activity rhythms) are among the most prominent of biological rhythms and therefore were among the first to be recorded in early chronobiological studies. These rhythms can provide useful information about the central biological clock, although an appreciation of the problems associated with using rest/activity to infer central clock function is important in the design and interpretation of chronobiological experiments in both animals and humans. Here, we review the anatomical and neurophysiologic bases of sleep regulation in mammals as well as similarities and differences between the sleep of humans and that of other organisms. We outline how human sleep is measured, the role of the circadian system in models of human sleep regulation, and human circadian rhythm sleep disorders. Although the function of sleep is still not completely understood, sleep has a critical role for human health, and we have attempted to outline the role that the circadian timing system has in regulating human sleep and in contributing to sleep disorders.

Sleep deficiency, which can be caused by acute sleep deprivation, chronic insufficient sleep, untreated sleep disorders, disruption of circadian timing, and other factors, is endemic in the United States, including among professional and nonprofessional drivers and operators. Vigilance and attention are critical for safe transportation operations, but fatigue and sleepiness compromise vigilance and attention by slowing reaction times and impairing judgment and decision-making abilities. Research studies, polls, and accident investigations indicate that many Americans drive a motor vehicle or operate an aircraft, train, or marine vessel while drowsy, putting themselves and others at risk for error and accident. In this chapter, we will outline some of the factors that contribute to sleepiness, present evidence from laboratory and field studies demonstrating how sleepiness impacts transportation safety, review how sleepiness is measured in laboratory and field settings, describe what is known about interventions for sleepiness in transportation settings, and summarize what we believe are important gaps in our knowledge of sleepiness and transportation safety.

The light-dark cycle is the primary synchronizing factor that keeps the internal circadian pacemaker appropriately aligned with the environmental 24-h day. Although it is known that ocular light exposure can effectively shift the human circadian pacemaker and do so in an intensity-dependent manner, the curve that describes the relationship between light intensity and pacemaker response has not been fully characterized for light exposure in the late biological night. We exposed subjects to 3 consecutive days of 5 h of experimental light, centered 1.5 h after the timing of the fitted minimum of core body temperature, and show that such light can phase advance shift the human circadian pacemaker in an intensity-dependent manner, with a logistic model best describing the relationship between light intensity and phase shift. A similar sigmoidal relationship is also observed between light intensity and the suppression of plasma melatonin concentrations that occurs during the experimental light exposure. As with a simpler, 1-day light exposure during the early biological night, our data indicate that the human circadian pacemaker is highly sensitive even to typical room light intensities during the late biological night, with ∼100 lux evoking half of the effects observed with light 10 times as bright.

Shift work results in a misalignment between circadian timing and the sleep/wake schedule, leading to irregular and poor quality sleep. Inconsistent input from the daily light cycle further interferes with circadian entrainment. It has been hypothesized that scheduling the sleep/dark cycle on the night shift could aid in promoting adaptation to night shift work by facilitating appropriate phase shifts. In a simulated shift-work study, we compared the ability of two sleep/dark schedules to shift circadian phase. Our results indicate that scheduled sleep/darkness can aid in adaptation to night shift work by inducing both advance and delay phase shifts, depending on the timing of the sleep schedule, although the size of the phase shifts are not sufficient to produce complete adaptation to the night shift. These results have applications to night shift workers, particularly in occupations in which alterations in the timing of light exposure cannot be achieved during working hours.

While we do not yet understand all the functions of sleep, its critical role for normal physiology and behaviour is evident. Its amount and temporal pattern depend on species and condition. Humans sleep about a third of the day with the longest, consolidated episode during the night. The change in lifestyle from hunter-gatherers via agricultural communities to densely populated industrialized centres has certainly affected sleep, and a major concern in the medical community is the impact of insufficient sleep on health [1,2]. One of the causal mechanisms leading to insufficient sleep is altered exposure to the natural light-dark cycle. This includes the wide availability of electric light, attenuated exposure to daylight within buildings, and evening use of light-emitting devices, all of which decrease the strength of natural light-dark signals that entrain circadian systems [3]. Fil: de la Iglesia, Daniel Horacio. University of Washington; Estados Unidos Fil: Moreno, Claudia. Stockholms Universitet; Suecia. Universidade de Sao Paulo; Brasil. Stockholms Universitet; Suecia Fil: Lowden, Arne. Stockholms Universitet; Suecia Fil: Louzada, Fernando. Universidade Federal do Paraná; Brasil Fil: Marqueze, Elaine. Universidade de Sao Paulo; Brasil. Universidade Católica de Santos; Brasil Fil: Levandovski, Rosa. Universidade Federal do Rio Grande do Sul; Brasil Fil: Pilz, Luisa K.. Universidade Federal do Rio Grande do Sul; Brasil. Ludwig Maximilians Universitat; Alemania Fil: Valeggia, Claudia Rita. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Yale; Estados Unidos Fil: Fernandez Duque, Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Yale; Estados Unidos Fil: Golombek, Diego Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina Fil: Czeisler, Charles A.. Brigham and Women’s Hospital; Estados Unidos. Harvard Medical School; Estados Unidos Fil: Skene, Debra J.. University of Surrey. Faculty of Health & Medical Sciences; Reino Unido Fil: Duffy, Jeanne F.. Brigham and Women’s Hospital; Estados Unidos. Harvard Medical School; Estados Unidos Fil: Roenneberg, Till. Ludwig Maximilians Universitat; Alemania

Aging is associated with specific sleep complaints, including earlier awakening and decreased sleep consolidation at the end of the night. The circadian pacemaker influences sleep timing and consolidation, and it has been hypothesized that a change in the circadian timing system may contribute to age-related changes in sleep. Here, we examined the relationship between circadian period and wake time, circadian phase, and diurnal preference (morningness–eveningness) in older subjects, and found no significant correlation between those measures, in contrast to our findings from young subjects. These results provide further evidence that the interaction between the circadian system and sleep–wake timing is altered in aging, and suggest that a shortening of circadian period with age cannot account for the advanced circadian phase and earlier wake times of older subjects.

A diverse range of species, from cyanobacteria to humans, evolved endogenous biological clocks that allow for the anticipation of daily variations in light and temperature. The ability to anticipate regular environmental rhythms promotes optimal performance and survival. Herein we present a brief historical timeline of how circadian concepts and terminology have emerged since the early observation of daily leaf movement in plants made by an astronomer in the 1700s.

To review circadian rhythm sleep disorders, including underlying causes, diagnostic considerations, and typical treatments.Literature review and discussion of specific cases.Survey studiesCircadian rhythm sleep disorders are a distinct class of sleep disorders characterized by a mismatch between the desired timing of sleep and the ability to fall asleep and remain asleep. If untreated, CRSD can lead to insomnia and excessive daytime sleepiness, with negative medical, psychological, and social consequences. It is important for physicians to recognize potential circadian rhythm sleep disorders so that appropriate diagnosis, treatment, and referral can be made.

The daily rhythm of melatonin influences multiple physiological measures, including sleep tendency, circadian rhythms, and reproductive function in seasonally breeding mammals. The biological signal for photoperiodic changes in seasonally breeding mammals is a change in the duration of melatonin secretion, which in a natural environment reflects the different durations of daylight across the year, with longer nights leading to a longer duration of melatonin secretion. These seasonal changes in the duration of melatonin secretion do not simply reflect the known acute suppression of melatonin secretion by ocular light exposure, but also represent long-term changes in the endogenous nocturnal melatonin episode that persist in constant conditions. As the eyes of totally blind individuals do not transmit ocular light information, we hypothesized that the duration of the melatonin secretory episode in blind subjects would be longer than those in sighted individuals, who are exposed to light for all their waking hours in an urban environment. We assessed the melatonin secretory profile during constant posture, dim light conditions in 17 blind and 157 sighted adults, all of whom were healthy and using no prescription or nonprescription medications. The duration of melatonin secretion was not significantly different between blind and sighted individuals. Healthy blind individuals after years without ocular light exposure do not have a longer duration of melatonin secretion than healthy sighted individuals.

In humans, experimental studies of circadian resetting typically have been limited to lengthy episodes of exposure to continuous bright light. To evaluate the time course of the human endogenous circadian pacemaker's resetting response to brief episodes of intermittent bright light, we studied 16 subjects assigned to one of two intermittent lighting conditions in which the subjects were presented with intermittent episodes of bright-light exposure at 25- or 90-min intervals. The effective duration of bright-light exposure was 31% or 63% compared with a continuous 5-h bright-light stimulus. Exposure to intermittent bright light elicited almost as great a resetting response compared with 5 h of continuous bright light. We conclude that exposure to intermittent bright light produces robust phase shifts of the endogenous circadian pacemaker. Furthermore, these results demonstrate that humans, like other species, exhibit an enhanced sensitivity to the initial minutes of bright-light exposure.

The circadian pacemaker and sleep homeostasis play pivotal roles in vigilance state control. It has been hypothesized that age-related changes in the human circadian pacemaker, as well as sleep homeostatic mechanisms, contribute to the hallmarks of age-related changes in sleep, that is, earlier wake time and reduced sleep consolidation. Assessments of circadian parameters in healthy young (approximately 20-30 years old) and older people (approximately 65-75 years old)--in the absence of the confounding effects of sleep, changes in posture, and light exposure--have demonstrated that an earlier wake time in older people is accompanied by about a 1 h advance of the rhythms of core body temperature and melatonin. In addition, older people wake up at an earlier circadian phase of the body temperature and plasma melatonin rhythm. The amplitude of the endogenous circadian component of the core body temperature rhythm assessed during constant routine and forced desynchrony protocols is reduced by 20-30% in older people. Recent assessments of the intrinsic period of the human circadian pacemaker in the absence of the confounding effects of light revealed no age-related reduction of this parameter in both sighted and blind individuals. Wake maintenance and sleep initiation are not markedly affected by age except that sleep latencies are longer in older people when sleep initiation is attempted in the early morning. In contrast, major age-related reductions in the consolidation and duration of sleep occur at all circadian phases. Sleep of older people is particularly disrupted when scheduled on the rising limb of the temperature rhythm, indicating that the sleep of older people is more susceptible to arousal signals generated by the circadian pacemaker. Sleep-homeostatic mechanisms, as assayed by the sleep-deprivation-induced increase of EEG slow-wave activity (SWA), are operative in older people, although during both baseline sleep and recovery sleep SWA in older people remains at lower levels. The internal circadian phase advance of awakening, as well as the age-related reduction in sleep consolidation, appears related to an age-related reduction in the promotion of sleep by the circadian pacemaker during the biological night in combination with a reduced homeostatic pressure for sleep. Early morning light exposure associated with this advance of awakening in older people could reinforce the advanced circadian phase. Quantification of the interaction between sleep homeostasis and circadian rhythmicity contributes to understanding age-related changes in sleep timing and quality.