Circadian and circannual rhythms of hormonal variables in elderly men and women

A group of fourteen men (73 ± 5 yr of age), and eighteen women (77 ± 7 yr of age) institutionalized at the Berceni Clinical Hospital, Bucharest, Romania, were studied over a 24-hr span once during each season (winter, spring, summer and fall). All subjects followed a diurnal activity pattern with rest at night and ate three meals per day with breakfast at about 0830, lunch at about 1300 and dinner at about 1830. The meals were similar, although not identical for all subjects during all seasons. On each day of sampling blood was collected at 4-hr intervals over a 24-hr span. Seventeen hormonal variables were determined by radioimmunoassay. Statistically significant circadian rhythms were detected and quantitated by population mean cosinor analysis in pooled data from all four seasons in both sexes for ACTH, aldosterone, Cortisol, C-peptide, dehydroepiandrosterone-sulfate (DHEA-S), immunoreactive insulin, prolactin, 17-OH progesterone, testosterone, total T₄ and TSH. In women, estradiol and progesterone also were determined and showed a circadian rhythm during all seasons. Total T, and FSH showed circadian rhythm detection by cosinor analysis in the men only; LH showed no consistent circadian rhythm as group phenomenon in men or women.

A circannual rhythm was detected using the circadian means of each subject at each season as input for the population mean cosinor in the women for ACTH, C-peptide, DHEA-S, FSH, LH, progesterone, 17-OH progesterone and TSH. In the men, a circannual rhythm was detected for ACTH, FSH, insulin, LH, testosterone and T₃. There were phase differences between men and women in ACTH, FSH and LH. In those functions in which both the circadian and circannual rhythms were statistically significant, a comparison of the amplitudes showed in the women a higher circannual rather than circadian amplitude for DHEA-S. In 17-OH progesterone, TSH and C-peptide, the circadian amplitude in women was larger. In men, the circannual amplitude of T₃ was larger than the circadian amplitude and in insulin the circadian amplitude was larger than the circannual amplitude. There was no statistically significant difference between the circadian and circannual amplitudes in the women in ACTH and progesterone and in the men in ACTH and testosterone.     

Internal desynchronization of circadian rhythms and tolerance to shift work

Intolerance to shift work may result from individual susceptibility to an internal desynchronization. Some shift workers (SW) who show desynchronization of their circadian rhythms (e.g., sleep-wake, body temperature, and grip strength of both hands) exhibit symptoms of SW intolerance, such as sleep alteration, persistent fatigue, sleep medication dependence, and mood disturbances, including depression. Existing time series data previously collected from 48 male Caucasian French SW were reanalyzed specifically to test the hypothesis that internal synchronization of circadian rhythms is associated with SW intolerance and symptoms. The entry of the subjects into the study was randomized. Three groups were formed thereafter: SW with good tolerance (n=14); SW with poor tolerance, as evident by medical complaints for at least one year (n=19); and former SW (n=15) with very poor tolerance and who had been discharged from night work for at 1.5 yr span but who were symptom-free at the time of the study. Individual and longitudinal time series of selected variables (self-recorded sleep-wake data using a sleep log, self-measured grip strength of both hands using a Colin Gentile dynamometer, and oral temperature using a clinical thermometer) were gathered for at least 15 days, including during one or two night shifts. Measurements were performed 4-5 times/24 h. Power spectra used to quantify the prominent period (tau) and t-test, chi square, and correlation coefficient were used as statistical tools. The mean (+/-SEM) age of SW with good tolerance was greater than that of SW with poor tolerance (44.9+/-2.1 yrs vs. 40.1+/-2.6 yrs, p<.001) and of former SW discharged from night work (very poor tolerance; 33.4+/-1.7, p<.001). The shift-work duration (yrs) was longer in SW with good than poor tolerance (19.9+/-2.2 yrs vs. 15.7+/-2.2; p<0.002) and former SW (10.7+/-1.2; p<.0001). The correlation between subject age and shift-work duration was stronger in tolerant SW (r=0.97, p<.0001) than in non-tolerant SW (r=0.80, p<0.001) and greater than that of former SW (r=0.72, p<.01). The mean sleep-wake rhythm tau was 24 h for all 48 subjects. The number of desynchronized circadian rhythms (tau differing from 24 h) was greater in non-tolerant than in tolerant SW (chi square=38.9, p<.0001). In Former SW (i.e., 15 individuals assessed in follow-up studies done 1.5 to 20 yrs after return to day work), both symptoms of intolerance and internal desynchronization were reduced or absent. The results suggest that non-tolerant SW are particularly sensitive to the internal desynchronization of their circadian time organization.     

Circadian rhythms: biological clocks work in phospho-time

The 24 hour molecular oscillator requires precisely calibrated degradation of core clock proteins, like PERIOD. New studies shed light on a sequential series of PERIOD phosphorylation events that first inhibits, then accelerates PERIOD degradation.     

Circadian temperature rhythms in clockwise and counter-clockwise rapidly rotating shift schedules

The purpose of this study was to examine the circadian temperature rhythm in clockwise (CW) and counter-clockwise (CCW) rapidly rotating shift schedules. Arguments against the CCW rotation of shifts are that they result in shortened sleep and promote greater disruption of circadian rhythms. The 3-week study included a week of day shifts (0800-1600) and 2 weeks of shiftwork. The CW 2-2-1 schedule rotated from two early mornings (0600-1400) to two evenings (1400-2200) to one midnight shift (2200-0600) allowing 24 hours off at each shift rotation and a 48-hour weekend. The CCW schedule rotated from two evenings to two early mornings to one midnight shifts allowing only 8 hours off at each shift rotation and an 80-hour weekend. Analysis of the 72-hr periods at the end of each workweek, including the midnight shifts and recovery periods during weeks 2 and 3 were compared to the same 72-hour period at the end of week 1 (baseline). A cosine function that fit the temperature curves by minimizing the sums of squares produced parameters that underwent analysis of covariance procedures. Significant differences were found between rotation conditions for amplitude and acrophase. An attenuation of amplitude and a delay in the acrophase was the found for the counter-clockwise condition. Features inherent in this schedule might explain these effects, particularly, the increased opportunity for "sleeping in" at the beginning of the week and an expanded (2-shift) workday at the end of the week.     

Internal desynchronization of circadian rhythms and tolerance of shift work

Fifteen male subjects including 12 shift workers (oil refinery operators) volunteered to document circadian rhythms in sleep-wake, grip strength of both hands, peak expiratory flow, heart rate, self-rated drowsiness, fatigue and attention. Each of these variables was measured 4 to 6 times/day for 2 to 3 weeks. In addition, both axillary temperature (with a shielded probe) and wrist activity were almost continuously recorded at 15 min intervals during the same time span. Individual time series were analyzed according to several statistical methods (power spectrum, cosinor, chi 2, etc.), in order to estimate the prominent circadian period tau and to evaluate both individual and subgroup differences with regard to tolerance of shift work, age, duration of shift work. The present study confirms for continuously recorded temperature and wrist activity, grip strength of both hands, heart rate and peak expiratory flow that intolerance of shift work is frequently associated with an internal desynchronization. However, this conclusion cannot be extended to circadian rhythms in self-rated drowsiness, fatigue and attention. The internal desynchronization among several circadian rhythms supports the hypothesis that these latter are driven by several oscillators, with presumable differences between right and left hemispheres as suggested by unequal values of tau in rhythms of both hand grip strength. Since an internal desynchronization can be observed in tolerant shift workers having no complaint, it is likely that symptoms of intolerance are related to the subject's sensitivity to internal desynchronization rather than to the desynchronization itself.     

Circadian changes in salivary constituents and conductivity in women and men.

Circadian rhythms in salivary [glucose], [Na+], [K+] and conductivity were measured in 2 age groups of men (men A, 20-45 years and men B, 46-60 years) and 8 different states of fertility in women (normally menstruating, taking oral contraceptives, pregnant, lactational amenorrhea, lactational amenorrhea and taking oral contraceptives, lactating and menstruating, menopausal, and post-menopausal). Unstimulated whole saliva (2-3 ml) was collected every 3 h over a 48 h span. Analysis of Spearman Rank Correlations indicated significant circadian rhythms (significant positive coefficients) for all groups of [Na+] (mean = 0.577 +/- 0.040) and conductivity (mean = 0.410 +/- 0.050). There was no evidence of differences in prominence of rhythm across groups for [Na+] and conductivity. [K+] showed less evidence of rhythms and much greater variability between groups (mean correlation coefficient = 0.198 +/- 0.055). Rhythms in [glucose] (mean correlation coefficient = 0.409 +/- 0.051) were evident in all groups except men B (0.016), menopausal women (0.151) and post-menopausal women (0.310). Model analysis of the data showed no discernible rhythmic trend with age for either conductivity, [Na+] or [K+], where any differences were explainable by the group characteristics. The rhythm in [glucose] showed a significant weakening with age over all groups (F-ratio = 7.46**), and was different between men A and men B (F-ratio = 6.95**). It was concluded that circadian rhythms were present in whole unstimulated saliva for conductivity and [Na+] and that these rhythms were independent of reproductive state, whereas circadian rhythms in [K+] were dependent on reproductive state. Circadian rhythms for [glucose] were dependent on age. The loss of a rhythm in [glucose] with age indicates that glucose, Na+ and K+ are not linked in their entry into saliva. The influence of entry and reabsorption on the final concentrations of glucose, Na+ and K+ in saliva is discussed.     

Recovery after shift work: Relation to coronary risk factors in women

Shift work increases the risk for developing cardiovascular disease. There is, however, little knowledge of what aspects of shift scheduling that are detrimental and what characteristics promote good health. The aim of the present study was to evaluate whether coronary risk factors deteriorate after a hard work period and whether recovery, in the form of a week off, was sufficient to improve them. A total of 19 women worked an extremely rapidly rotating and clockwise shift schedule at a paper and pulp factory. They underwent two health examinations, one at the end of the work period and one after the week off. In addition, the women were divided into a tolerant and a vulnerable group, depending on their satisfaction with their work hours. Most risk factors did not change, but total cholesterol and low-density lipoprotein (LDL)-cholesterol were lower after the working period than after the week-off. In addition, vulnerable women had higher levels of total cholesterol and a higher ratio of total cholesterol/high-density lipoprotein (HDL) than tolerant ones. In conclusion, the finding that a week-off worsens cholesterol levels was against our hypothesis and suggests further studies on how activities/responsibilities outside the workplace affect shift-working women. It was also shown that susceptible shift workers had worse lipid profiles.     

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 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)     

The relation of age to the adjustment of the circadian rhythms of oral temperature and sleepiness to shift work

The relation of age to the adjustment of the circadian rhythms of oral temperature (T0) and sleepiness (S) in shift work was studied. 145 healthy female nurses underwent detailed laboratory and field measurements. Self-rated sleepiness, and oral temperature measured with a special extended-scale mercury thermometer, were recorded at 2 hr intervals during a morning (M) and 2 consecutive night (N) shifts. Sleeping times were registered during the same days. The results were analyzed separately in the age-groups of 22-29, 30-39 and 40-49-year-old subjects. From the morning shift to the second night shift day, the oral temperature and sleepiness acrophases shifted significantly (p less than 0.001) forward in all age groups. The amplitude decreased in the youngest and in the 30-39-year old age groups but not in the oldest age group. During the second night shift day, the acrophases and amplitudes of oral temperature rhythms were significantly different (P less than 0.05) between the groups, but there were no significant differences by age in the change of the circadian rhythms from morning to the second night shift days. The results thus fail to corroborate that physiological adjustment to night work would be influenced by age.     

Circadian rhythms and memory: not so simple as cogs and gears

The influence of circadian rhythms on memory has long been studied; however, the molecular prerequisites for their interaction remain elusive. The hippocampus, which is a region of the brain important for long‐term memory formation and temporary maintenance, shows circadian rhythmicity in pathways central to the memory‐consolidation process. As neuronal plasticity is the translation of numerous inputs, illuminating the direct molecular links between circadian rhythms and memory consolidation remains a daunting task. However, the elucidation of how clock genes contribute to synaptic plasticity could provide such a link. Furthermore, the idea that memory training could actually function as a zeitgeber for hippocampal neurons is worth consideration, based on our knowledge of the entrainment of the circadian clock system. The integration of many inputs in the hippocampus affects memory consolidation at both the cellular and the systems level, leaving the molecular connections between circadian rhythmicity and memory relatively obscure but ripe for investigation.