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Biological clock ticks for men, too: genetic defects linked to sperm of older fathers.
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Circadian rhythms in the neonate and in old age: what do they tell us about the development and decay of the body clock in humans?
This overview describes changes in human circadian rhythms in the neonate and in aged subjects. Since a measured circadian rhythm is derived from an endogenous (clock-driven) component and an exogenous component (due to rhythms in the environment and lifestyle), this account attempts to separate these possibilities in any particular case. Experimental methods for distinguishing between these components are described, and it is concluded that the data are rarely clear enough for such distinctions in mechanism to be made with confidence. Nevertheless, the evidence to date suggests that changes to the endogenous and exogenous components during both the development and decay of circadian rhythms are involved. This being the case, and accepting that poorly developed circadian rhythms are often associated with poor general health and development, methods to strengthen circadian rhythms are described.
Age-specific problems in rhythmic timing.
The authors investigated performance in 2 rhythm tasks in young (M = 23.8 years) and older (M = 71.4 years) amateur pianists to test whether slowing of a central clock can explain age-related changes in timing variability. Successive keystrokes in the rhythm tasks were separated by either identical (isochronous) time intervals or varying (anisochronous) intervals. Variability was comparable for young and older adults in the isochronous task; pronounced age effects were found for the anisochronous rhythm. Analyses of covariances between intervals rule out slowing of a central clock as an explanation of the findings, which instead support the distinction between target specification, timekeeper execution, and motor implementation proposed by the rhythm program hypothesis (D. Vorberg & A. M. Wing, 1996). Age stability was found at the level of motor implementation, but there were age-related deficits for processes related to target-duration specification.
Sleep, biological rhythms and aging.
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Age-related changes in the circadian and homeostatic regulation of human sleep.
The reduction of electroencephalographic (EEG) slow-wave activity (SWA) (EEG power density between 0.75-4.5 Hz) and spindle frequency activity, together with an increase in involuntary awakenings during sleep, represent the hallmarks of human sleep alterations with age. It has been assumed that this decrease in non-rapid eye movement (NREM) sleep consolidation reflects an age-related attenuation of the sleep homeostatic drive. To test this hypothesis, we measured sleep EEG characteristics (i.e., SWA, sleep spindles) in healthy older volunteers in response to high (sleep deprivation protocol) and low sleep pressure (nap protocol) conditions. Despite the fact that the older volunteers had impaired sleep consolidation and reduced SWA levels, their relative SWA response to both high and low sleep pressure conditions was similar to that of younger persons. Only in frontal brain regions did we find an age-related diminished SWA response to high sleep pressure. On the other hand, we have clear evidence that the circadian regulation of sleep during the 40 h nap protocol was changed such that the circadian arousal signal in the evening was weaker in the older study participants. More sleep occurred during the wake maintenance zone, and subjective sleepiness ratings in the late afternoon and evening were higher than in younger participants. In addition, we found a diminished melatonin secretion and a reduced circadian modulation of REM sleep and spindle frequency-the latter was phase-advanced relative to the circadian melatonin profile. Therefore, we favor the hypothesis that age-related changes in sleep are due to weaker circadian regulation of sleep and wakefulness. Our data suggest that manipulations of the circadian timing system, rather than the sleep homeostat, may offer a potential strategy to alleviate age-related decrements in sleep and daytime alertness levels.
The influence of administration time on chemotherapy-induced nausea and vomiting.
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An empiric approach to level of care determinations: the importance of executive measures.
BACKGROUND: The ability to predict the level of care received by elderly retirees was compared in a discriminant model and using a classification tree derived from cognitive and noncognitive variables. Methods. Participants were 193 residents (mean age, 79.1+/-5.1 years) of a single, 1,500-bed, continuing care retirement community. They were given a battery of cognitive measures that included tests of general cognition, memory, and executive control function. A multivariate discriminant model of level of care was compared with a classification tree. RESULTS: Residents in congregate high-rises (n=115) differed significantly from those in apartment settings (n=78) with respect to age, Executive Interview (EXIT 25), and the Executive Clock-Drawing Task (CLOX). Only age and executive control function measures (CLOX1, EXIT 25, and Trail Making Test Part B [Trails B]) contributed independently to a discriminant model of level of care (Wilke's lambda=0.92; F [df 4,170]=3.48; p <.01). Sixty-three percent of participants were correctly classified. A classification tree derived from the same variable set was more accurate (75% correctly classified). Age, CLOX1, and EXIT 25 made the most important contributions to the model. The EXIT 25 and CLOX1 thresholds empirically derived from this model coincide with the fifth percentiles for these instruments in a young adult sample. CONCLUSIONS: Executive control function appears to be most responsible for the effect of cognition on level of care. Young adult norms may be most relevant when the effects of cognitive impairment on functional status are assessed.
Biotechnology--updates and new developments.
Areas of priority for intensive discovery would be the agbiotechnology and biomedical sectors using gene technology as a platform. The use of genetic manipulation in farming and the use of plants as 'pharma' factories to manufacture therapeutics would be on the rise. The human genome will continue to have a powerful impact on research and development of human diseases and healthcare. Discovery of genetics and pharmacogenomics will have great impact on drug development and will allow the prediction of the patient' s response to various drugs as well as the onset of individualised or 'designer drugs'. Human stem cells could have their cellular clocks reset by the cloning process, enhancing opportunities to grow young cells, tissues and organs for an aging population. The cellular clock could also be reset by therapeutic cloning. Bioinformatics would be a technology which would be synonymous with biotechnology. The analyses of biotechnology research would be conducted in silico and would involve the exchange of information among sophisticated computer databases. Applications of biotechnology would be even more evident in environmental technology, food development and food processing. In electronics, the use of the specificity of proteins in biochips is underway. In tandem with the explosions in research, regulatory issues, legislation and intellectual property rights will evolve to enhance the climate of discovery and innovation. Public education will have to be continually enhanced as awareness could negate any fear resulting from novel and innovative improvements from biotechnology.
Rethinking the biological clock: eleventh-hour moms, miracle moms and meanings of age-related infertility.
Over the past generation, aging and female reproduction have been lodged within the gendered and gendering debates regarding women's involvement in the workforce and demographic shifts toward delayed parenting that culminate in discourses on the "biological clock". Technological solutions to the biological clock, specifically in vitro fertilization, have led to clinical attempts to assess "ovarian reserve", or qualitative and quantitative changes in the ovary that correlate with aging and with successful infertility treatment. Rupturing the longstanding historical connections between menstruation and female reproductive capacity by specifically focusing on the aging of a woman's eggs, the clinical designation of "diminished ovarian reserve" has come to imply that a woman has "old eggs". This is associated in practitioners' and patients' minds with the eclipse of a woman's reproductive potential and with hidden harbingers of menopause. In an ethnographic interview study of 79 couples in the US who conceived after using donor oocytes, we found that women voiced two different narratives that described their experience and attitudes when confronted with an apparent age-related decline in their fertility. The "eleventh-hour mom" narrative was voiced by women who initially tried to become pregnant with their own eggs and turned to donated oocytes as a second-choice option, whereas the "miracle mom" narrative was expressed by women who were generally older, some of whom had entered infertility treatment hoping to conceive with their own eggs, but some who knew from the outset that it was not going to be possible. Through their narratives women not only embodied and made meaningful "diminished ovarian reserve" in varying ways that connect with cultural, social, structural/organizational, symbolic and physical aspects of aging, they reproduced the socio-biological project of the biological clock, but rooted this social project in the metaphor of "old eggs" rather than menopause.
The circadian rhythm of core temperature: effects of physical activity and aging.
The circadian rhythm of core temperature depends upon several interacting rhythms, of both endogenous and exogenous origin, but an understanding of the process requires these two components to be separated. Constant routines remove the exogenous (masking) component at source, but they are severely limited in their application. By contrast, several purification methods have successfully reduced the masking component of overt circadian rhythms measured in field circumstances. One important, but incidental, outcome from these methods is that they enable a quantitative estimate of masking effects to be obtained. It has been shown that these effects of activity upon the temperature rhythm show circadian rhythmicity, and more detailed investigations of this have aided our understanding of thermoregulation and the genesis of the circadian rhythm of core temperature itself. The observed circadian rhythm of body temperature varies with age; in comparison with adults, it is poorly developed in the neonate and deteriorates in the aged subject. Comparing masked and purified data enables the reasons for these differences--whether due to the body clock, the effector pathways or organs, or irregularities due to the individual's lifestyle--to begin to be understood. Such investigations stress the immaturity of the circadian rhythm in the human neonate and its deterioration in elderly compared with younger subjects, but they also indicate the robustness of the body clock itself into advanced age, at least in mice.
Comparison of the Munich Chronotype Questionnaire with the Horne-Ostberg's Morningness-Eveningness Score.
We report on results from an Internet survey of sleeping habits in a Dutch population using the Munich Chronotype Questionnaire (MCTQ), supplemented with the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ). The MCTQ was completed by 5,055 responders, of which 2,481 also completed the MEQ. MEQ score correlated well with the MCTQ assessment of time of mid-sleep on free days (MSF; r = - 0.73) and on workdays (MSW; r = - 0.61). MEQ was more strongly correlated with MSF (50% of sleep time) than with sleep onset (0%), rise time (100%), or with any other percentile (10 to 40, 60% to 90%) of sleep on free days. The study shows that chronotype (based on MSF as measured by the MCTQ) strongly correlates with morningness-eveningness (as measured by the MEQ). However, the MCTQ collects additional detailed information on sleep-wake behavior under natural conditions.
Dependence of subthalamic nucleus oscillations on movement and dopamine in Parkinson's disease.
Local field potentials and pairs of neurones in the subthalamic nucleus (STN) of patients with Parkinson's disease show high-frequency oscillations (HFOs) at 15-30 Hz. This study explores how these HFOs are modulated by voluntary movements and by dopaminergic medication. We examined 15 patients undergoing implantation of bilateral deep brain stimulating electrodes using microelectrode recordings of pairs of STN neurones (eight patients) and macroelectrode recordings of local field potentials from the STN (14 patients). Synchronized HFOs between STN neurones were observed in 28 out of 37 pairs in five patients who had tremor in the operating room and none of 45 pairs in three patients who did not. In two of the three non-tremulous patients, HFOs in the frequency spectra of local field potentials were detected but were weaker than in those patients with tremor. Active movement suppressed synchronized HFOs in three out of five pairs of neurones, independent of changes in firing rate. HFOs observed in the local field potentials in nine out of 14 patients were reduced with voluntary movement in six of the eight patients tested. Dopaminergic medication decreased the incidence of synchronized HFOs in STN neurone pairs, reduced HFO synchrony in a pair of tremor cells concurrent with a reduction in firing rate and limb tremor, and decreased HFOs of local field potentials in the STN. These results demonstrate that HFO synchronization in the STN is reduced by voluntary movements and by exogenous dopaminergic medication. A mechanism for neuronal oscillatory synchronization in basal ganglia is proposed. It is suggested that the firing of STN neurones can be synchronized by 15-30 Hz cortical beta oscillatory activity, particularly when dopamine deficiency results in a higher background firing rate of STN neurones, and that this synchronization contributes to parkinsonian pathophysiology.
Spontaneous low-frequency oscillations decline in the aging brain.
It is well known that aging leads to a degeneration of the vascular system. Hence, one may hypothesize that spontaneous oscillations decrease in the cerebral microvasculature with aging. Accordingly, the authors investigated the age dependency of spontaneous oscillations in the visual cortex during rest and functional activation. Functional near-infrared spectroscopy was used because it is particularly sensitive to the microvasculature. Visual stimulation led to an increase of oxyhemoglobin, total hemoglobin, and a decrease of deoxyhemoglobin, without any influence of age. Peaks of normalized power spectral density were detected for spontaneous low-frequency (0.07 to 0.11 Hz) and very-low-frequency (0.01 to 0.05 Hz) oscillations, with a higher amplitude for oxyhemoglobin than for deoxyhemoglobin. Spontaneous low-frequency oscillations of oxyhemoglobin and deoxyhemoglobin declined strongly with aging during both rest and visual stimulation. Reduction of spontaneous low-frequency oscillations might indicate a declining spontaneous activity in microvascular smooth muscle cells, in conjunction with an increased vessel stiffness with aging.
[Corticosteroid fractions of human periosteum with special reference to age and seasonal changes].
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Aging, rhythms of physical performance, and adjustment to changes in the sleep-activity cycle.
OBJECTIVES: Shiftwork causes disturbances of the normal sleep-wake cycle and circadian rhythm. There is concern that aging workers have more problems than younger counterparts when the human body clock is disrupted. This review considers issues relating to aging, the circadian body clock, and adjustment to altered sleep-wake schedules. METHODS: Reports on effects of aging on the human body clock were reviewed. Research concerned with adjustment to circadian phase shifts (as occurs in night work) was considered. RESULTS: With aging there is an increased tendency towards morningness which is linked with difficulties in sleeping. The peak time and amplitude of normal circadian rhythms are altered. Tolerance of shiftwork can be linked with social factors as well as adaptation of the body clock. CONCLUSIONS: People habituated to night work seem to have developed mechanisms which allow them to cope with disruptions to lifestyle and the endogenous body clock. Elderly people are more suited to phase advances, as occur in morning workshifts, than to phase delays such as nocturnal work.
The relationship between local field potential and neuronal discharge in the subthalamic nucleus of patients with Parkinson's disease.
Depth recordings in patients with Parkinson's disease (PD) have demonstrated prominent oscillatory activity in the beta frequency (13-35 Hz) band in local field potentials (LFPs) recorded from the region of the subthalamic nucleus (STN). Although this activity has been hypothesized to contribute to bradykinesia, it is unclear to what extent the LFP oscillations arise in the STN and are synchronous with local neuronal discharge. We therefore recorded both LFPs and multi-neuronal activity from microelectrodes inserted into STN in six PD patients (8 sides) during functional neurosurgery. As microelectrodes passed from above STN into STN, there was a pronounced increase in beta frequency band LFP activity. Furthermore, spike-triggered averages of LFP activity suggested that the discharges of neurons in STN were locked to beta oscillations in the LFP. The LFP is therefore likely to represent synchronous activity in populations of neurons in the STN of patients with PD.
Sexual dimorphism in the complexity of cardiac pacemaker activity.
This study explored the effects of gender and aging on the complexity of cardiac pacemaker activity. Electrocardiogram signals were studied in normal women (n = 240) and men (n = 240) ranging in age from 40 to 79 yr. Nonlinear analysis of short-term resting R-R intervals was performed using the correlation dimension (CD), approximate entropy (ApEn), and largest Lyapunov exponent (LLE). Evidence of nonlinear structure was obtained by the surrogate data test. CD, ApEn, and LLE were negatively correlated with age. Despite similar means and SDs of the R-R intervals, women had a significantly higher CD, ApEn, and LLE compared with men in the age strata of 40-44 and 45-49 yr. CD and ApEn were strongly (r > 0.71) correlated with low- and high-frequency components. We conclude that the resting cardiac pacemaker activity of women is more complex than that of men in middle age, and the gender-related difference diminishes after the age of 50 yr. The higher complexity implies a more comprehensive neural modulation.