Changes In Circadian Regulation Research Articles

Circadian sleep regulation and brain tissue microstructure in cognitively unimpaired older adults

AbstractBackgroundCircadian dysfunction increases with age, leading to changes in the circadian regulation of physiological and biological rhythms, including sleep. Actigraphy studies demonstrated that altered 24‐h rest‐activity patterns, an estimate of circadian sleep‐wake regulation, is related to cognitive decline and tightly linked to Alzheimer’s disease progression. Here, we assessed whether circadian sleep regulation, measured during a multiple naps protocol, is related to brain microstructural integrity in a group of cognitively unimpaired older adults.MethodEighty‐six retired older individuals (mean age [SD] = 69.9 ± 5.2 y.o., 32 females, Table 1) with no major sleep disorders or medical condition, underwent an in‐lab 40‐h multiple naps protocol and brain structural magnetic resonance imaging. As rapid eye movement (REM) sleep is under strong circadian control, circadian REM sleep amplitude was computed by fitting a Gaussian curve on REM sleep duration (% of total sleep time) measured for each nap opportunity. The multiparametric mapping protocol was used to derive indices of brain tissue microstructure using magnetization transfer saturation (MTsat), R1 and R2* maps (hMRI toolbox v0.2.2). Statistical models were adjusted for age, sex, education, and for additional covariates related to sleep architecture and its circadian modulation, including mean REM% and sleep efficiency (SE), the accumulation of REM sleep and sleep need (slope of a fitted first‐order polynomial curve), and circadian SE amplitude.ResultsWhole‐brain voxel‐based quantification analysis revealed that low circadian REM amplitude was related to low MTsat, R1 and R2* values in several white matter regions mostly located around the lateral ventricles (Figure 1A). In addition, a significant association was observed between low circadian REM amplitude and low R1 values in two grey matter clusters encompassing the hippocampus, entorhinal cortex, thalamus and hypothalamus (Figure 1B).ConclusionOur findings provide first evidence that changes in circadian sleep regulation is associated with microstructural changes in key brain regions sensitive to the aging process and involved in sleep‐wake regulation. These results further emphasize the relevance of monitoring circadian sleep regulation for the early detection of individuals at risk for neurodegeneration and cognitive decline.

Age-related changes in circadian regulation of the human plasma lipidome

Aging alters the amplitude and phase of centrally regulated circadian rhythms. Here we evaluate whether peripheral circadian rhythmicity in the plasma lipidome is altered by aging through retrospective lipidomics analysis on plasma samples collected in 24 healthy individuals (9 females; mean ± SD age: 40.9 ± 18.2 years) including 12 younger (4 females, 23.5 ± 3.9 years) and 12 middle-aged older, (5 females, 58.3 ± 4.2 years) individuals every 3 h throughout a 27-h constant routine (CR) protocol, which allows separating evoked changes from endogenously generated oscillations in physiology. Cosinor regression shows circadian rhythmicity in 25% of lipids in both groups. On average, the older group has a ~14% lower amplitude and a ~2.1 h earlier acrophase of the lipid circadian rhythms (both, p ≤ 0.001). Additionally, more rhythmic circadian lipids have a significant linear component in addition to the sinusoidal across the 27-h CR in the older group (44/56) compared to the younger group (18/58, p < 0.0001). Results from individual-level data are consistent with group-average results. Results indicate that prevalence of endogenous circadian rhythms of the human plasma lipidome is preserved with healthy aging into middle-age, but significant changes in rhythmicity include a reduction in amplitude, earlier acrophase, and an altered temporal relationship between central and lipid rhythms.

Molecular Response of the Brain to Cross-Generational Warming in a Coral Reef Fish

Ocean warming is a threat to marine biodiversity, as it can push marine species beyond their physiological limits. Detrimental effects can occur when marine poikilotherms are exposed to conditions beyond their thermal optima. However, acclamatory mechanisms, such as plasticity, may enable compensation of detrimental effects if warming is experienced during development or across generations. Studies evaluating the molecular responses of fishes to warming have mostly focused on liver, muscle, and gonads, and little is known about the effects on other vital organs, including the brain. This study evaluated the transcriptional program of the brain in the coral reef fish Acanthochromis polyacanthus, exposed to two different warming scenarios: +1.5°C and +3.0°C, across successive generations. Fish were exposed to these conditions in both developmental (F1 and F2) and transgenerational settings (F2 only), as well as a treatment with step-wise warming between generations. The largest differences in gene expression were between individuals of the first and second generation, a pattern that was corroborated by pairwise comparisons between Control F1 and Control F2 (7,500 DEGs) fish. This large difference could be associated with parental effects, as parents of the F1 generation were collected from the wild, whereas parents of the F2 generation were reared in captivity. A general response to warming was observed at both temperatures and in developmental and transgenerational treatments included protein folding, oxygen transport (i.e., myoglobin), apoptosis and cell death, modification of cellular structure, mitochondrial activity, immunity and changes in circadian regulation. Treatments at the highest temperature showed a reduction in synaptic activity and neurotransmission, which matches previous behavioral observations in coral reef fishes. The Transgenerational +3.0°C treatment showed significant activation of the gene pls3, which is known for the development of neuro-muscular junctions under heat-stress. F2 samples exposed to step-wise warming showed an intermediate response, with few differentially expressed genes compared to developmental and transgenerational groups (except for Transgenerational +1.5°C). In combination with previous studies on liver gene expression, this study indicates that warming produces a molecular signature of stress response in A. polyacanthus that is influenced both by the intensity of warming as well as the duration of exposure.

Circadian Rhythm Sleep-Wake Disorders in Older Adults.

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.

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)