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The rising tide of obesity is strongly associated with daily calorie intake and sedentary lifestyle-promoting transportation refs. These rhythms have evolved and permit organisms to effectively respond to the predictable daily change in the light: These rhythmic transcripts encode key rate-determining steps in neuroendocrine, signaling, and metabolic pathways.
Such regulation temporally separates incompatible cellular processes and optimizes cellular and organismal fitness.
Although the circadian clock is cell-autonomous and is present in the majority of tissue types, the circadian system is organized in a hierarchical manner in which the hypothalamic suprachiasmatic nucleus SCN functions as the master circadian clock that uses both diffusible and synaptic mechanisms to orchestrate circadian rhythms in the peripheral organs at appropriate phase.
Photoreceptive retinal ganglion cells send ambient light information to the SCN through monosynaptic connection to ensure that the circadian system is entrained to the daily light: Whereas light is the dominant timing cue for the SCN oscillator, time of food intake affects the phase of the clocks in peripheral tissues 15including liver, muscle, and adipose tissues.
For many of our ancestors, food was probably scarce and primarily consumed during daylight hours, leaving long hours of overnight fasting.
With the advent of affordable artificial lighting and industrialization, modern humans began to experience prolonged hours of illumination every day and resultant extended consumption of food.
The modern lifestyle perturbed the human circadian system in three primary ways: Although it is difficult to separate the consequence of each of these perturbations on metabolism and physiology, animal models and recent experimental human studies have begun to elucidate the mechanisms and consequence of these circadian disruptions.
During night-shift work the individuals are subject to both prolonged hours of artificial lighting and an abnormal eating schedule.
Furthermore, during the weekend the tendency to maintain a day-active social life imposes a jet-lag—type paradigm in which both central and peripheral clocks attempt to adjust to a weekend lifestyle. Although such internal desynchrony has never been demonstrated directly in humans, based on animal experimental work this is presumed to result in chronic disruption of circadian rhythms, which may help explain the known association between night work and several diseases, including cardiovascular disease, diabetes, obesity, certain types of cancer, and neurodegenerative diseases 16 In addition to shift work, modern human societies experience prolonged illumination 18 and erratic eating patterns, both of which are known to perturb the circadian system.
In nocturnal rodent models, extended illumination has been shown to increase predisposition to metabolic diseases. Conversely, in diurnal flies a shift to nighttime feeding compromises fat metabolism and fecundity These studies highlight the importance of temporal organization of sleep and feeding relative to the circadian system.
Both nutrient quality and genetic factors appear to affect meal timing in rodents. Mutation in the circadian clock gene Per1 affecting a conserved phosphorylation site causes mice to consume more food during the daytime and predisposes them to metabolic diseases The widely used diet-induced obesity model in mice also perturbs feeding; mice fed a high-fat diet ad libitum consume small meals throughout day and night Both diet-induced obesity and obesity in Per1 mutant mice can be prevented by restricting access to high-fat diet only during the nighttime The surprising effectiveness of TRF without altering caloric intake or source of calories suggests a potentially effective meal-timing intervention for humans.
Indeed, recent human studies suggest that earlier meal timing associates with improved effectiveness of weight-loss therapy in overweight and obese patients 24 The mechanism underlying the beneficial effect of TRF is likely complex and acts on multiple pathways.
The daily fasting and feeding episodes trigger alternative activation of fasting-responsive cAMP response element binding protein CREB and AMP kinase, and feeding responsive insulin-dependent mammalian target of rapamycin mTOR pathways implicated in metabolic homeostasis.
In addition, these pathways also impinge on the circadian clock and improve robustness of oscillation of clock components and downstream targets Accordingly, gene-expression studies indicate that TRF supports circadian rhythmicity of thousands of hepatic transcripts The confluence of genomics and genetics in mice is unraveling the pathways from the core clock components to specific nutrient metabolism.
The nuclear hormone receptors REV-ERBs are integral to the circadian clock and directly regulate transcription of several key rate-determining enzymes for fatty acid and cholesterol metabolism Although cryptochrome proteins are strong transcriptional suppressors, they also inhibit cAMP signaling and thereby tune CREB-mediated gluconeogenesis These and other modes of regulation 31 provide a mechanistic framework by which meal-timing affects the circadian clock and, in turn, affects metabolic homeostasis in mammals.
Cellular and Molecular Mechanisms: Data collected from individuals practicing severe dietary restriction indicate that humans undergo many of the same molecular, metabolic, and physiologic adaptations typical of long-lived CR rodents Here we briefly highlight four general mechanisms by which IER protects cells against injury and disease.
Compared with their usual ad libitum feeding conditions, laboratory animals maintained on IER exhibit numerous changes, suggesting heightened adaptive stress responses at the molecular, cellular, and organ system levels.The authors theorized that rotating shifts made it more difficult for workers to maintain a regular sleep-wake cycle, negatively affecting sleep quality and potentially weakening insulin.
A circadian clock, or circadian oscillator, is a biochemical oscillator that cycles with a stable phase and is synchronized with solar time.. Such a clock's in vivo period, is necessarily almost exactly 24 hours (the earth's current solar day).In most living things, internally synchronized circadian clocks make it possible for the organism to anticipate daily environmental changes.
The use of light-emitting electronic devices for reading, communication, and entertainment has greatly increased recently. We found that the use of these devices before bedtime prolongs the time it takes to fall asleep, delays the circadian clock, suppresses levels of the sleep-promoting hormone melatonin, reduces the amount and delays the timing of REM sleep, and reduces alertness the.
Congratulations Michael, Jeffrey and Michael for your unveiling of the molecular mechanisms that control the circadian rhythm. Yes, our three science heroes have figured out that while we sleep our “protein batteries” get recharged and during the day our “protein batteries” get depleted. Corrigendum to “Interrelationship between Sleep and Exercise: A Systematic Review”, Brett A.
Dolezal, Eric V.
Neufeld, David M. Boland, Jennifer L. Martin, and Christopher B. Cooper Advances in Preventive Medicine Corrigendum (1 page), Article ID , Volume (). The authors theorized that rotating shifts made it more difficult for workers to maintain a regular sleep-wake cycle, negatively affecting sleep quality and potentially weakening insulin.