-
Journal of Hematology & Oncology Mar 2022The circadian rhythm is an evolutionarily conserved time-keeping system that comprises a wide variety of processes including sleep-wake cycles, eating-fasting cycles,... (Review)
Review
The circadian rhythm is an evolutionarily conserved time-keeping system that comprises a wide variety of processes including sleep-wake cycles, eating-fasting cycles, and activity-rest cycles, coordinating the behavior and physiology of all organs for whole-body homeostasis. Acute disruption of circadian rhythm may lead to transient discomfort, whereas long-term irregular circadian rhythm will result in the dysfunction of the organism, therefore increasing the risks of numerous diseases especially cancers. Indeed, both epidemiological and experimental evidence has demonstrated the intrinsic link between dysregulated circadian rhythm and cancer. Accordingly, a rapidly increasing understanding of the molecular mechanisms of circadian rhythms is opening new options for cancer therapy, possibly by modulating the circadian clock. In this review, we first describe the general regulators of circadian rhythms and their functions on cancer. In addition, we provide insights into the mechanisms underlying how several types of disruption of the circadian rhythm (including sleep-wake, eating-fasting, and activity-rest) can drive cancer progression, which may expand our understanding of cancer development from the clock perspective. Moreover, we also summarize the potential applications of modulating circadian rhythms for cancer treatment, which may provide an optional therapeutic strategy for cancer patients.
Topics: Circadian Clocks; Circadian Rhythm; Homeostasis; Humans; Neoplasms; Sleep
PubMed: 35246220
DOI: 10.1186/s13045-022-01238-y -
Alcohol Research & Health : the Journal... 2001The daily light-dark cycle governs rhythmic changes in the behavior and/or physiology of most species. Studies have found that these changes are governed by a biological... (Review)
Review
The daily light-dark cycle governs rhythmic changes in the behavior and/or physiology of most species. Studies have found that these changes are governed by a biological clock, which in mammals is located in two brain areas called the suprachiasmatic nuclei. The circadian cycles established by this clock occur throughout nature and have a period of approximately 24 hours. In addition, these circadian cycles can be synchronized to external time signals but also can persist in the absence of such signals. Studies have found that the internal clock consists of an array of genes and the protein products they encode, which regulate various physiological processes throughout the body. Disruptions of the biological rhythms can impair the health and well-being of the organism.
Topics: Alcoholism; Animals; Biological Clocks; Circadian Rhythm; Gene Expression; Humans; Sleep Disorders, Circadian Rhythm; Sleep Stages; Suprachiasmatic Nucleus
PubMed: 11584554
DOI: No ID Found -
Nature Oct 2021Time-restricted feeding (TRF) has recently gained interest as a potential anti-ageing treatment for organisms from Drosophila to humans. TRF restricts food intake to...
Time-restricted feeding (TRF) has recently gained interest as a potential anti-ageing treatment for organisms from Drosophila to humans. TRF restricts food intake to specific hours of the day. Because TRF controls the timing of feeding, rather than nutrient or caloric content, TRF has been hypothesized to depend on circadian-regulated functions; the underlying molecular mechanisms of its effects remain unclear. Here, to exploit the genetic tools and well-characterized ageing markers of Drosophila, we developed an intermittent TRF (iTRF) dietary regimen that robustly extended fly lifespan and delayed the onset of ageing markers in the muscles and gut. We found that iTRF enhanced circadian-regulated transcription and that iTRF-mediated lifespan extension required both circadian regulation and autophagy, a conserved longevity pathway. Night-specific induction of autophagy was both necessary and sufficient to extend lifespan on an ad libitum diet and also prevented further iTRF-mediated lifespan extension. By contrast, day-specific induction of autophagy did not extend lifespan. Thus, these results identify circadian-regulated autophagy as a critical contributor to iTRF-mediated health benefits in Drosophila. Because both circadian regulation and autophagy are highly conserved processes in human ageing, this work highlights the possibility that behavioural or pharmaceutical interventions that stimulate circadian-regulated autophagy might provide people with similar health benefits, such as delayed ageing and lifespan extension.
Topics: Aging; Animals; Autophagy; Biomarkers; Circadian Clocks; Circadian Rhythm; Darkness; Drosophila melanogaster; Feeding Behavior; Female; Longevity; Male; Time Factors
PubMed: 34588695
DOI: 10.1038/s41586-021-03934-0 -
Immunity Feb 2014Immune parameters change with time of day and disruption of circadian rhythms has been linked to inflammatory pathologies. A circadian-clock-controlled immune system... (Review)
Review
Immune parameters change with time of day and disruption of circadian rhythms has been linked to inflammatory pathologies. A circadian-clock-controlled immune system might allow an organism to anticipate daily changes in activity and feeding and the associated risk of infection or tissue damage to the host. Responses to bacteria have been shown to vary depending on time of infection, with mice being more at risk of sepsis when challenged ahead of their activity phase. Studies highlight the extent to which the molecular clock, most notably the core clock proteins BMAL1, CLOCK, and REV-ERBα, control fundamental aspects of the immune response. Examples include the BMAL1:CLOCK heterodimer regulating toll-like receptor 9 (TLR9) expression and repressing expression of the inflammatory monocyte chemokine ligand (CCL2) as well as REV-ERBα suppressing the induction of interleukin-6. Understanding the daily rhythm of the immune system could have implications for vaccinations and how we manage infectious and inflammatory diseases.
Topics: Animals; Circadian Rhythm; Gene Expression Regulation; Humans; Immunity; Nuclear Receptor Subfamily 1, Group D, Member 1
PubMed: 24560196
DOI: 10.1016/j.immuni.2014.02.002 -
Autophagy Mar 2022Macroautophagy/autophagy plays crucial roles in aging and the pathogenesis of age-related diseases. Studies in various animal models demonstrate the conserved...
Macroautophagy/autophagy plays crucial roles in aging and the pathogenesis of age-related diseases. Studies in various animal models demonstrate the conserved requirement for autophagy-related genes in multiple anti-aging interventions. A recent study from the Shirasu-Hiza lab showed that a newly designed intermittent time-restricted feeding (iTRF) dietary regimen can robustly extend fly healthspan and lifespan through circadian rhythm-dependent activation of autophagy. The night-specific induction of autophagy is both necessary and sufficient for iTRF-mediated health benefits. The study provides the intriguing possibility that novel behavioral or pharmaceutical interventions that promote night-specific autophagy can be used to promote healthy aging.
Topics: Aging; Animals; Autophagy; Circadian Rhythm; Fasting; Longevity
PubMed: 35220894
DOI: 10.1080/15548627.2022.2039524 -
Current Psychiatry Reports Mar 2019Disruptions in circadian rhythms are believed to underlie the illness course of bipolar disorder (BD). This review evaluates recent studies on the treatment of circadian... (Review)
Review
PURPOSE OF REVIEW
Disruptions in circadian rhythms are believed to underlie the illness course of bipolar disorder (BD). This review evaluates recent studies on the treatment of circadian dysfunction in BD.
RECENT FINDINGS
Targeted social rhythm therapy may be useful for bipolar depression though some studies suggest that a non-targeted psychosocial or pharmacological intervention may be just as efficacious. Lithium holds potential for addressing circadian dysfunction in BD. Blue-blocking therapy may be useful for mania and midday bright light therapy may relieve depression.
CONCLUSIONS
Psychosocial, pharmacological, and light-based approaches are promising avenues for treating circadian dysfunction in BD.
Topics: Bipolar Disorder; Circadian Rhythm; Depression; Depressive Disorder; Humans; Lithium Compounds; Phototherapy
PubMed: 30826893
DOI: 10.1007/s11920-019-1001-8 -
Human Molecular Genetics Oct 2017Circadian rhythms are 24-h rhythms in physiology and behaviour generated by molecular clocks, which serve to coordinate internal time with the external world. The... (Review)
Review
Circadian rhythms are 24-h rhythms in physiology and behaviour generated by molecular clocks, which serve to coordinate internal time with the external world. The circadian system is a master regulator of nearly all physiology and its disruption has major consequences on health. Sleep and circadian rhythm disruption (SCRD) is a ubiquitous feature in today's 24/7 society, and studies on shift-workers have shown that SCRD can lead not only to cognitive impairment, but also metabolic syndrome and psychiatric illness including depression (1,2). Mouse models of clock mutants recapitulate these deficits, implicating mechanistic and causal links between SCRD and disease pathophysiology (3-5). Importantly, treating clock disruption reverses and attenuates these adverse health states in animal models (6,7), thus establishing the circadian system as a novel therapeutic target. Significantly, circadian and clock-controlled gene mutations have recently been identified by Genome-Wide Association Studies (GWAS) in the aetiology of sleep, mental health and metabolic disorders. This review will focus upon the genetics of circadian rhythms in sleep and health.
Topics: Animals; Circadian Clocks; Circadian Rhythm; Depression; Humans; Mental Disorders; Mice; Models, Animal; Sleep
PubMed: 28977444
DOI: 10.1093/hmg/ddx240 -
Nature Oct 2019Group 3 innate lymphoid cells (ILC3s) are major regulators of inflammation, infection, microbiota composition and metabolism. ILC3s and neuronal cells have been shown to...
Group 3 innate lymphoid cells (ILC3s) are major regulators of inflammation, infection, microbiota composition and metabolism. ILC3s and neuronal cells have been shown to interact at discrete mucosal locations to steer mucosal defence. Nevertheless, it is unclear whether neuroimmune circuits operate at an organismal level, integrating extrinsic environmental signals to orchestrate ILC3 responses. Here we show that light-entrained and brain-tuned circadian circuits regulate enteric ILC3s, intestinal homeostasis, gut defence and host lipid metabolism in mice. We found that enteric ILC3s display circadian expression of clock genes and ILC3-related transcription factors. ILC3-autonomous ablation of the circadian regulator Arntl led to disrupted gut ILC3 homeostasis, impaired epithelial reactivity, a deregulated microbiome, increased susceptibility to bowel infection and disrupted lipid metabolism. Loss of ILC3-intrinsic Arntl shaped the gut 'postcode receptors' of ILC3s. Strikingly, light-dark cycles, feeding rhythms and microbial cues differentially regulated ILC3 clocks, with light signals being the major entraining cues of ILC3s. Accordingly, surgically or genetically induced deregulation of brain rhythmicity led to disrupted circadian ILC3 oscillations, a deregulated microbiome and altered lipid metabolism. Our work reveals a circadian circuitry that translates environmental light cues into enteric ILC3s, shaping intestinal health, metabolism and organismal homeostasis.
Topics: ARNTL Transcription Factors; Animals; Biological Clocks; Brain; Circadian Rhythm; Cues; Feeding Behavior; Female; Gastrointestinal Microbiome; Homeostasis; Immunity, Innate; Intestines; Light; Lipid Metabolism; Lymphocytes; Male; Mice; Photoperiod
PubMed: 31534216
DOI: 10.1038/s41586-019-1579-3 -
Frontiers in Endocrinology 2020
Topics: Chronobiology Disorders; Circadian Clocks; Circadian Rhythm; Humans
PubMed: 33013708
DOI: 10.3389/fendo.2020.00637 -
Frontiers in Cellular and Infection... 2020
Topics: Circadian Rhythm; Host-Parasite Interactions
PubMed: 33224903
DOI: 10.3389/fcimb.2020.613181