CIRCADIAN RHYTHMS IN HEALTHY AGING—EFFECTS DOWNSTREAM FROM THE PACEMAKER

Using both previously published findings and entirely new data, we present evidence in support of the argument that the circadian dysfunction of advancing age in the healthy human is primarily one of failing to transduce the circadian signal from the circadian timing system (CTS) to rhythms “downstream” from the pacemaker rather than one of failing to generate the circadian signal itself. Two downstream rhythms are considered: subjective alertness and objective performance. For subjective alertness, we show that in both normal nychthemeral (24h routine, sleeping at night) and unmasking (36h of constant wakeful bed rest) conditions, advancing age, especially in men, leads to flattening of subjective alertness rhythms, even when circadian temperature rhythms are relatively robust. For objective performance, an unmasking experiment involving manual dexterity, visual search, and visual vigilance tasks was used to demonstrate that the relationship between temperature and performance is strong in the young, but not in older subjects (and especially not in older men). (Chronobiology International, 17(3), 355–368, 2000)     

Circadian rhythms of performance: new trends

This brief review is concerned with how human performance efficiency changes as a function of time of day. It presents an overview of some of the research paradigms and conceptual models that have been used to investigate circadian performance rhythms. The influence of homeostatic and circadian processes on performance regulation is discussed. The review also briefly presents recent mathematical models of alertness that have been used to predict cognitive performance. Related topics such as interindividual differences and the postlunch dip are presented. (Chronobiology International, 17(6), 719-732, 2000)     

Circadian rhythms and sleep in human aging

This issue of Chronobiology International is dedicated to the age-related changes in circadian rhythms as they occur in humans. It seems timely to give an overview of the knowledge and hypotheses on these changes now that we enter a century in which the number and percentage of elderly in the population will be unprecedented. Although we should take care not to follow the current tendency to think of old age as a disease—ignoring the fine aspects of being old—there is definitely an age-related increase in the risk of a number of conditions that are at least uncomfortable.

Circadian rhythms have been attributed adaptive values that usually go unnoticed, but can surface painfully clear when derangements occur. Alterations in the regulation of circadian rhythms are thought to contribute to the symptoms of a number of conditions for which the risk is increased in old age (e.g., sleep disturbances, dementia, and depression). A multidisciplinary approach to investigate the mechanisms of age-related changes in circadian regulation eventually may result in treatment strategies that will improve the quality of life of the growing number of elderly.

Although diverse topics are addressed in this issue, the possible mechanisms by which a deranged circadian timing system may be involved in sleep disturbances receives the most attention. This seems appropriate in view of the numerous studies that have addressed this relation in the last decade and also because of the high frequency and strong impact of sleep disturbances in the elderly. This introduction to the special issue first briefly addresses the impact of disturbed sleep in the elderly to show that the development of therapeutic methods other than the currently available pharmacological treatments should be given high priority. I believe that chronobiological insights may play an important role in the development of rational therapeutical methods.(Chronobiology International, 17(3), 233-243, 2000)     

Circadian rhythms and the evolution of photoperiodic timing in insects

This review discusses possible evolutionary trends in insect photoperiodism, mainly from a chronobiological perspective. A crucial step was the forging of a link between the hormones regulating diapause and the systems of biological rhythms, circadian or circannual, which have independently evolved in eukaryotes to synchronize physiology and behaviour to the daily cycles of light and darkness. In many of these responses a central feature is that the circadian system resets to a constant phase at the beginning of the subjective night, and then ‘measures’ the duration of the next scotophase. In ‘external coincidence’, one version of such a clock, light now has a dual role. First, it serves to entrain the circadian system to the stream of pulses making up the light/dark cycle and, second, it regulates the nondiapause/diapause switch in development by illuminating/not illuminating a specific light sensitive phase falling at the end of the critical night length. Important work by A. D. Lees on the aphid Megoura viciae using so‐called ‘night interruption experiments' demonstrates that pulses falling early in the night lead to long‐day effects that are reversible by a subsequent dark period longer than the critical night length and also show maximal sensitivity in the blue–green range of the spectrum. Pulses falling in the latter half of the night, however, produce long‐day effects that are irreversible by a subsequent long‐night and show a spectral sensitivity extending into the red. With movement to higher latitudes, insects develop genetic clines in various parameters, including critical night length, the number of long‐night cycles needed for diapause induction, the strength of the response, and the ‘depth’ or intensity of the diapause thus induced. Evidence for these and other types of photoperiodic response suggests that they provided strong selective advantages for insect survival.     

Circadian locomotor rhythms in individual honeybees

ABSTRACT. The circadian locomotor (walking) rhythms of individual forager honeybees ( Apis mellifera ligustica L.) were measured under a variety of conditions. In constant dark the rhythms exhibited endogenous periodicities that were less than 24 h, whereas under constant light the periods tended to be greater than 24 h. Individual honeybees readily entrained to photoperiods, displaying a diurnal pattern of entrainment with most of the activity occurring in late photophase. Evidence is presented which suggests that foraging behaviour and general locomotor behaviour may be governed by two different circadian clock systems.     

Circadian rhythms of proliferation events in two mouse carcinomas

We studied the index of DNA synthesis (DNAs) of two cellular carcinomas: the hepatocellular ES12a and the mammary TN60 of mice, throughout one circadian cycle. In the results, we observed that both tumors have circadian rhythms (CRs), but the peaks of DNAs vary. Besides, the mean of DNAs along 24 h shows significative differences, the TN60 has higher values than the ES12a. These observed CR in the DNAs index in both carcinomas mean that, at least in partly, the proliferation of cancer cells can be regulated by endocrine factor as it normally occurs in ordinary cells. The big problem we can find for the chronopharmacology is that it is impossible to know in advance the rate of proliferation of each tumor.     

Circadian rhythms of demand-feeding and locomotor activity in rainbow trout

Under free-running conditions, most rainbow trout displayed circadian feeding rhythms, although the expression of circadian rhythmicity depended on the experimental condition: 16·7% of fish under constant dim light (LL dim), 66·1% under a 45 :45 min light-dark cycle (LD pulses), and 83·8% under constant light (LL). Under LD pulses, the period length of the free-running rhythms for feeding was significantly shorter (21·9 ± 0·7 h, n =8) than under LL (26·2 ± 0·3 h, n =10). Period length for locomotor activity under LL was 25·8 ± 0·6 h ( n =4). Under LD conditions, the daily demand-feeding profile was always confined to the light phase and chiefly composed of two main episodes, directly after lights on (light elicited) and in anticipation to lights off (endogenous). Contrasting to feeding, the diel locomotor activity profile varied remarkably: a diurnal activity pattern at the bottom, while a clearly nocturnal pattern at the surface. These results contribute to a better understanding of feeding and locomotor rhythms of rainbow trout, providing evidence for the existence of a biological clock involved in their circadian control. This finding contrasts with the previously recorded lack of an endogenous oscillator in the pineal organ driving the rhythmic secretion of melatonin, which suggests different locations from the pineal for the circadian pacemakers in this species.     

The daily rhythms of mitochondrial gene expression and oxidative stress regulation are altered by aging in the mouse liver

The circadian clock regulates many cellular processes, notably including the cell cycle, metabolism and aging. Mitochondria play essential roles in metabolism and are the major sites of reactive oxygen species (ROS) production in the cell. The clock regulates mitochondrial functions by driving daily changes in NAD⁺ levels and Sirt3 activity. In addition to this central route, in the present study, we find that the expression of some mitochondrial genes is also rhythmic in the liver, and that there rhythms are disrupted by the Clock^Δ19 mutation in young mice, suggesting that they are regulated by the core circadian oscillator. Related to this observation, we also find that the regulation of oxidative stress is rhythmic in the liver. Since mitochondria and ROS play important roles in aging, and mitochondrial functions are also disturbed by aging, these related observations prompt the compelling hypothesis that circadian oscillators influence aging by regulating ROS in mitochondria. During aging, the expression rhythms of some mitochondrial genes were altered in the liver and the temporal regulation over the dynamics of mitochondrial oxidative stress was disrupted. However, the expression of clock genes was not affected. Our results suggested that mitochondrial functions are combinatorially regulated by the clock and other age-dependent mechanism(s), and that aging disrupts mitochondrial rhythms through mechanisms downstream of the clock.     

Circadian self-feeding rhythms in greater amberjack Seriola dumerili (Risso)

In the present study, 10 greater amberjack Seriola dumerili held individually were given free access to self-feeder, and trigger actuations were continuously monitored. Most (80%) of greater amberjack developed stable self-feeding activity within 1 week. The fish was a rigidly diurnal feeder under a 12L:12D cycle, with a feeding peak of 1–3 h occurring just after the onset of lights. Under constant conditions, all 10 individual fish exhibited free-running self-feeding rhythms, which persisted for 43 days without a sign of damping out. As far as is known, this seems to be the longest record of free-running behavioural rhythms in fishes. Except one fish free-ran at a period length (τ) of 25·2 h, τ of free-running self-feeding rhythms in the other nine fish was shorter than 24 h, ranging from 20·0 h to 21·5 h. In addition, phase transients of feeding activity were observed in response to the advancement of lights on. It is concluded that feeding activity in greater amberjack is mediated by endogenous circadian oscillators.     

Circadian rhythms and feeding time in fishes

Synopsis Although several studies have described effects of meal frequency and timing of meals on growth performance and body composition of different species of fishes, the mechanisms by which such variables influence the energy partitioning processes is not known. They may interact with the natural feeding rhythm of the fish, or with various behavioural and physiological parameters that exhibit circadian-like patterns; however, in most cases, the endogenous character of such rhythms is not clear. The time of feeding, perse, can act as a Zeitgeber and override the effect of the light/dark alternation. Fish that are fed always at the same time of day show typical pre-feeding activity. Blood levels of some nutrients and hormones also show peaks or troughs at the time of feeding, but whether these are pre-feeding or post-prandial events is not clear. These results from fish are compared with similar studies with mammals. The existence and location of an endogenous multi-oscillator system is also discussed.     

Circadian Determinants of the Postlunch Dip in Performance

This study compared rectal temperature rhythms in groups of subjects who either did (n = 5) or did not (n - 7) show a clear postlunch dip in performance at a monotonous (25-30 min) vigilance task. Performance was tested every 2h in a standardized routine with lunch replaced by hourly liquid food supplements. Those showing the postlunch performance dip had a higher amplitude and later peaking 12h component to their rectal temperature rhythm that those who did not, resulting in flat, rather than rising, temperatures over the 10:00-15:00 time interval. The effect could not be explained by intergroup differences in prior sleep, morningness, or gender, although there was a trend (p = 0.09) for the “dip” group to be slightly younger (21.8y vs. 24.2y). The postlunch dip appears to be an endogenous phenomenon individually determined, but related to the strength of the (12h) harmonic of the circadian system.     

Circadian rhythms measured by actigraphy during oncological treatments: a systematic review

During oncological treatment patients often suffer from fatigue, insomnia, and daytime inactivity. This cluster of symptoms and overall survival are linked with circadian rhythm disruptions in rest-activity, which can be objectively characterized using actigraphy. We systematically reviewed the body of literature using actigraphy to characterize the circadian rhythm disruption in patients during oncological treatments and studies that introduced interventions to deal with this disruption. Thirteen observational and two interventional studies were included in this review. These mainly described patients with breast cancer undergoing chemotherapy, and the disruptions were persistent among these patients, and the disruptions peaked at the start of chemotherapy cycles and decreased during the periods in between. Light and behavioral therapy showed some alleviating effects in patients with breast cancer. We also found that circadian rhythm disruptions were prevalent in patients during other cancer therapies. Effective cancer therapy controls cancer growth and improves circadian organization. Cancer therapy itself, however, also contributes to cancer associated circadian dys-synchrony. Interrupting this vicious cycle represents an important opportunity for diminishing cancer patients’ suffering and improving or even prolonging their useful and enjoyable lives.     

Circadian rhythms and the induction of flowering in the long-day grass Lolium temulentum L.

Plants of Lolium temulentum L. strain Ceres were grown in 8-h short day (SD) for 45 d before being exposed either to a single long day (LD) or to a single 8-h SD given during an extended dark period. For LD induction, the critical photoperiod was between 12 and 14 h, and more than 16 h were needed for a maximal flowering response. During exposure to a single 24-h LD, the translocation of the floral stimulus began between the fourteenth and the sixteenth hours after the start of the light period, and was completed by the twenty-fourth hour. Full flowering was also induced by one 8-h SD beginning 4 or 28 h after the start of a 40-h dark period, i.e. by shifting 12 h forward or beyond the usual SD. The effectiveness of a so-called ‘displaced short day’ (DSD) was not affected by light quality and light intensity. With a mixture of incandescent and fluorescent lights at a total photosynthetic photon flux density of 400 μmol m⁻² s⁻¹, a 4-h light exposure beginning 4 h after the start of a 40-h dark period was sufficient to induce 100% flowering. The flower-inducing effect of a single 8-h DSD was also assessed during a 64-h dark period. Results revealed two maxima at a 20-h interval. This fluctuation in light sensitivity suggests that a circadian rhythm is involved in the control of flowering of L. temulentum.     

Circadian rhythms in human erythrocytes in vitro not confirmed

Abstract

Human erythrocytes, white and resealed erythrocyte ghosts, and hemolysates were analysed for the occurrence of circadian and ultradian rhythms in vitro. Although the experimental conditions were extensively varied, we did not find any indication for the existence of rhythmicity. These results are at variance with the reports by others.     

Circadian rhythms in honeybees: entrainment by feeding cycles

ABSTRACT. Colonies of the South African honeybee race Apis mellifera capensis (Escholtz) were maintained under constant conditions of illumination (200 lux), temperature (25±lC) and relative humidity (65±3%). Activity was measured at the hive entrance. After ad libitum feeding for at least 5 days, food was presented for only 2 h/day either for 1 week (series 1) or for 2 weeks (series 2). In the last part of each experiment, food was again available all the time. Colonies which showed free-running circadian activity rhythms (with periods ranging from 22.6 to 24.8 h) during ad libitum feeding were submitted to feeding cycles with inter-feeding intervals (T) of 22, 23, 24 and 25 h. In most of these experiments the rhythms were synchronized by the feeding schedule, resulting in a stable phase-angle difference between onset of activity and onset of food availability. The duration of this anticipatory activity was positively correlated with T. When ad libitum feeding was resumed, the period of the rhythm induced by the feeding schedule persisted for a few days. Thereafter, the rhythm was free-running again with a period close to that observed in the first part of the experiment. The conclusion is drawn that, under the influence of periodic feeding, the activity of honeybee colonies has the characteristics of an entrained circadian system.     

Circadian rhythms and glial cells of the central nervous system

Glial cells are the most abundant cells in the central nervous system and play crucial roles in neural development, homeostasis, immunity, and conductivity. Over the past few decades, glial cell activity in mammals has been linked to circadian rhythms, the 24-h chronobiological clocks that regulate many physiological processes. Indeed, glial cells rhythmically express clock genes that cell-autonomously regulate glial function. In addition, recent findings in rodents have revealed that disruption of the glial molecular clock could impact the entire organism. In this review, we discuss the impact of circadian rhythms on the function of the three major glial cell types – astrocytes, microglia, and oligodendrocytes – across different locations within the central nervous system. We also review recent evidence uncovering the impact of glial cells on the body's circadian rhythm. Together, this sheds new light on the involvement of glial clock machinery in various diseases.     

Circadian rhythms and dynamic dietary calcium feeding affect laying performance,calcium and phosphorus levels in laying hens

This study was conducted to determine the effects of dynamic feeding low and high Ca in layer diets on laying performance, calcium, and phosphate concentration in both serum and tibia. 180 Brown Hy-line, 41 weeks old of laying hens were randomly distributed into 3 groups with 6 replicates and each replicate was 10 birds. During the 10-week experiment period, control group (CON group) received control diet (contained 3.4% Ca) at both 0730 and 1530 h, low–high group (LH group) received low Ca diet (contained 3.2% Ca) at 0730 h and high Ca diet (contained 3.6% Ca) at 1530 h, while high–low group (HL group) received the contrary to the LH group. Blood and tibia samples were collected at 4 h intervals. The dynamic Ca feeding schedule exerted significant effects on Ca intake in the morning and afternoon, also on feed conversion ratio (FCR) of the HL group comparing to the LH group (p<0.05). Serum Ca in the LH group were lower at 0000, 0400 and 1600 h comparing with the CON group (p < 0.05), and serum Ca: P ratio values in the LH group were lower at 0000, 0800, and 2000 h comparing with the CON group (p<0.05). These results indicated that dynamic feeding Ca improved FCR and affected the circadian variation of serum Ca concentration in laying hens.     

生物钟在卵巢生理和病理中的作用

哺乳动物的昼夜节律是基因编码的分子钟在体内产生的一种以大约24 h为周期的生理现象,使机体的生理过程与外界环境的变化相协调,是对环境适应的一种表现.在哺乳动物中,繁殖生理功能受生物钟系统的调节.在下丘脑-垂体-卵巢(hypothalamic-pituitary-ovarian,HPO)轴的各组织中均已观察到生物钟基因的...     

Circadian Hematologic Time Structure in the Elderly

Twenty-three clinically healthy, diurnally active elderly subjects, 71 ± 5 years of age were studied over a 24-hr span (six samples). Complete blood counts and differential counts were done (Ortho ELT-8, Wright stained smears). The circadian rhythm parameters of the hematologic variables in the elderly subjects were compared with reference values obtained from a larger group of clinically healthy young adult and adult subjects studied independently. The data were analyzed by cosinor and the Bingham test. Circadian rhythms in the number of circulating formed elements in the peripheral blood persist in the aged. In comparison with the young adult, the elderly subjects show differences in the timing (phase advance) of the circadian rhythms in circulating neutrophil leukocytes and lymphocytes, a decrease in the circadian amplitude of circulating platelets, a decrease in circadian rhythm adjusted mean (mesor) in the red cell count, and in the neutrophil band forms.     

Circadian rhythms in biologically closed electrical circuits of plants

The circadian clock regulates a wide range of electrophysiological and developmental processes in plants. Here, we discuss the direct influence of a circadian clock on biologically closed electrochemical circuits in vivo. The biologically closed electrochemical circuits in the leaves of C. miniata (Kaffir lily), Aloe vera and Mimosa pudica, which regulate their physiology, were analyzed using the charge stimulation method. Plants are able to memorize daytime and nighttime. Even at continuous light or darkness, plants recognize nighttime or daytime and change the input resistance. The circadian clock can be maintained endogenously and has electrochemical oscillators, which can activate ion channels in biologically closed electrochemical circuits. The activation of voltage gated channels depends on the applied voltage, electrical charge, and the speed of transmission of electrical energy from the electrostimulator to plants.