Mechanisms linking circadian clocks, sleep, and neurodegeneration

Science, Journal Year: 2016, Volume and Issue: 354(6315), P. 1004 - 1008

Published: Nov. 24, 2016

Disruptions of normal circadian rhythms and sleep cycles are consequences aging can profoundly affect health. Accumulating evidence indicates that disturbances, which have long been considered symptoms many neurodegenerative conditions, may actually drive pathogenesis early in the course these diseases. In this Review, we explore potential cellular molecular mechanisms linking dysfunction loss to diseases, with a focus on Alzheimer’s disease. We examine interplay between central peripheral rhythms, clock gene function, maintaining brain homeostasis, discuss therapeutic implications. The influence number key processes involved neurodegeneration, suggesting systems might be manipulated promote healthy aging.

Language: Английский

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Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures

Endocrine Reviews, Journal Year: 2016, Volume and Issue: 37(6), P. 584 - 608

Published: Oct. 20, 2016

Abstract Circadian (∼24-hour) timing systems pervade all kingdoms of life and temporally optimize behavior physiology in humans. Relatively recent changes to our environments, such as the introduction artificial lighting, can disorganize circadian system, from level molecular clocks that regulate cellular activities synchronization between daily cycles solar day. Sleep/wake are intertwined with global trends indicate these, too, increasingly subject disruption. A large proportion world's population is at increased risk environmentally driven rhythm sleep disruption, a minority individuals also genetically predisposed misalignment disorders. The consequences disruption system profound include myriad metabolic ramifications, some which may be compounded by adverse effects on dietary choices. If not addressed, deleterious will continue cause widespread health problems; therefore, implementation numerous behavioral pharmaceutical interventions help restore alignment enhance important.

Language: Английский

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Melatonin as a Hormone: New Physiological and Clinical Insights

Endocrine Reviews, Journal Year: 2018, Volume and Issue: 39(6), P. 990 - 1028

Published: Sept. 12, 2018

Melatonin is a ubiquitous molecule present in almost every live being from bacteria to humans. In vertebrates, besides produced peripheral tissues and acting as an autocrine paracrine signal, melatonin centrally synthetized by neuroendocrine organ, the pineal gland. Independently of considered species, hormone always during night its production secretory episode duration are directly dependent on length night. As tightly linked light/dark cycle, main hormonal systemic integrative action coordinate behavioral physiological adaptations environmental geophysical day season. The circadian signal daily regularity, contrast between concentrations, specially developed ways action. During episode, coordinates adaptive physiology through immediate effects primes responses prospective that will only appear at daytime, when absent. Similarly, annual history central nervous/endocrine system seasons come. Remarkably, maternal programs fetuses' behavior cope with cycle season after birth. These unique turn into biological time-domain–acting molecule. review focuses above considerations, proposes putative classification clinical dysfunctions, discusses general guidelines therapeutic use melatonin.

Language: Английский

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Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals

Molecular Metabolism, Journal Year: 2016, Volume and Issue: 5(12), P. 1175 - 1186

Published: Oct. 25, 2016

Changes to the microbial community in human gut have been proposed promote metabolic disturbances that also occur after short periods of sleep loss (including insulin resistance). However, whether affects microbiota remains unknown.In a randomized within-subject crossover study utilizing standardized in-lab protocol (with fixed meal times and exercise schedules), we studied nine normal-weight men at two occasions: nights partial deprivation (PSD; opportunity 02:45-07:00 h), normal (NS; 22:30-07:00 h). Fecal samples were collected within 24 h before, nights, either NS or PSD. In addition, participants underwent an oral glucose tolerance test following each intervention.Microbiota composition analysis (V4 16S rRNA gene sequencing) revealed days PSD vs. NS, individuals exhibited increased Firmicutes:Bacteroidetes ratio, higher abundances families Coriobacteriaceae Erysipelotrichaceae, lower abundance Tenericutes (all P < 0.05) - previously all associated with perturbations animal models. no effect on beta diversity fecal short-chain fatty acid concentrations was found. Fasting postprandial sensitivity decreased 0.05).Our findings demonstrate short-term induces subtle effects microbiota. To what extent observed changes contribute consequences warrants further investigations larger more prolonged studies, assess how impacts who already are metabolically compromised.

Language: Английский

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Sleep deprivation and stress: a reciprocal relationship

Interface Focus, Journal Year: 2020, Volume and Issue: 10(3), P. 20190092 - 20190092

Published: April 17, 2020

Sleep is highly conserved across evolution, suggesting vital biological functions that are yet to be fully understood. Animals and humans experiencing partial sleep restriction usually exhibit detrimental physiological responses, while total prolonged loss could lead death. The perturbation of homeostasis accompanied by an increase in hypothalamic–pituitary–adrenal (HPA) axis activity, leading a rise circulating levels stress hormones (e.g. cortisol humans, corticosterone rodents). Such follow circadian release pattern under undisturbed conditions participate the regulation sleep. investigation consequences deprivation, from molecular changes behavioural alterations, has been used study fundamental However, reciprocal relationship between activity HPA problematic when investigating using traditional sleep-deprivation protocols can induce per se . This especially true studies rodents which deprivation achieved exogenous, potentially stressful, sensory–motor stimulations undoubtedly confuse their conclusions. While more research needed explore mechanisms underlying health, avoiding as confounding factor therefore crucial. review examines evidence intricate links context experimental proposes sophisticated framework for procedures benefit recent progress biotechnological tools precise neuromodulation, such chemogenetics optogenetics, well improved automated real-time sleep-scoring algorithms.

Language: Английский

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Role of sleep quality in the metabolic syndrome

Diabetes Metabolic Syndrome and Obesity, Journal Year: 2016, Volume and Issue: Volume 9, P. 281 - 310

Published: Aug. 1, 2016

Abstract: Emerging evidence has assigned an important role to sleep as a modulator of metabolic homeostasis. The impact variations in duration, sleep-disordered breathing, and chronotype cardiometabolic function encompasses wide array perturbations spanning from obesity, insulin resistance, type 2 diabetes, the syndrome, cardiovascular disease risk mortality both adults children. Here, we critically extensively review published literature on such issues provide comprehensive overview most salient pathophysiologic pathways underlying links between sleep, disorders, functioning. Keywords: apnea, circadian clock,

Language: Английский

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The importance of gene–environment interactions in human obesity

Clinical Science, Journal Year: 2016, Volume and Issue: 130(18), P. 1571 - 1597

Published: Aug. 8, 2016

The worldwide obesity epidemic has been mainly attributed to lifestyle changes. However, who becomes obese in an obesity-prone environment is largely determined by genetic factors. In the last 20 years, important progress made elucidation of architecture obesity. parallel with successful gene identifications, number gene–environment interaction (GEI) studies grown rapidly. This paper reviews growing body evidence supporting interactions field Heritability, monogenic and polygenic provide converging that obesity-predisposing genes interact a variety environmental, treatment exposures. some skepticism remains regarding validity these based on several issues, which include statistical modelling, confounding, low replication rate, underpowered analyses, biological assumptions measurement precision. What follows this review includes (1) introduction study GEI, (2) GEI obesity, (3) outline mechanisms may explain effects, (4) methodological challenges associated potential solutions, (5) future directions research. Thus far, provided deeper understanding influencing have tremendous applications emerging personalized medicine individualized recommendations.

Language: Английский

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Clock Genes and Altered Sleep–Wake Rhythms: Their Role in the Development of Psychiatric Disorders

International Journal of Molecular Sciences, Journal Year: 2017, Volume and Issue: 18(5), P. 938 - 938

Published: April 29, 2017

In mammals, the circadian clocks network (central and peripheral oscillators) controls rhythms orchestrates expression of a range downstream genes, allowing organism to anticipate adapt environmental changes. Beyond their role in rhythms, several studies have highlighted that clock genes may more widespread physiological effect on cognition, mood, reward-related behaviors. Furthermore, single nucleotide polymorphisms core been associated with psychiatric disorders (such as autism spectrum disorder, schizophrenia, anxiety disorders, major depressive bipolar attention deficit hyperactivity disorder). However, underlying mechanisms these associations remain be ascertained cause-effect relationships are not clearly established. The objective this article is clarify altered sleep-wake development (sleep problems often observed at early onset disorders). First, molecular described. Then, between disrupted including discussed. Further research open interesting perspectives promising avenues for detection therapeutic intervention disorders.

Language: Английский

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Ad libitum Weekend Recovery Sleep Fails to Prevent Metabolic Dysregulation during a Repeating Pattern of Insufficient Sleep and Weekend Recovery Sleep

Current Biology, Journal Year: 2019, Volume and Issue: 29(6), P. 957 - 967.e4

Published: Feb. 28, 2019

Language: Английский

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An Overview of Epigenetics in Obesity: The Role of Lifestyle and Therapeutic Interventions

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1341 - 1341

Published: Jan. 25, 2022

Obesity has become a global epidemic that negative impact on population health and the economy of nations. Genetic predispositions have been demonstrated to substantial role in unbalanced energy metabolism seen obesity. However, these genetic variations cannot entirely explain massive growth obesity over last few decades. Accumulating evidence suggests modern lifestyle characteristics such as intake energy-dense foods, adopting sedentary behavior, or exposure environmental factors industrial endocrine disruptors all contribute rising epidemic. Recent advances study DNA its alterations considerably increased our understanding function epigenetics regulating expenditure metabolic diseases. These epigenetic modifications influence how is transcribed without altering sequence. They are dynamic, reflecting interplay between body surroundings. Notably, changes reversible, making them appealing targets for therapeutic corrective interventions. In this review, I discuss disordered what degree weight reduction strategies pharmacological drugs can restore balance by restoring normal profiles.

Language: Английский

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