Circadian disruption and human health

Journal of Clinical Investigation, Год журнала: 2021, Номер 131(19)

Опубликована: Сен. 30, 2021

Circadian disruption is pervasive and can occur at multiple organizational levels, contributing to poor health outcomes individual population levels. Evidence points a bidirectional relationship, in that circadian increases disease severity many diseases disrupt rhythms. Importantly, increase the risk for expression development of neurologic, psychiatric, cardiometabolic, immune disorders. Thus, harnessing rich findings from preclinical translational research biology enhance via circadian-based approaches represents unique opportunity personalized/precision medicine overall societal well-being. In this Review, we discuss implications human using bench-to-bedside approach. science applied clinical population-based Given broad regulation health, Review focuses its discussion on selected examples metabolic, cardiovascular, allergic, immunologic disorders highlight interrelatedness between potential interventions, such as bright light therapy exogenous melatonin, well chronotherapy improve and/or modify outcomes.

Язык: Английский

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Communicating clocks shape circadian homeostasis

Science, Год журнала: 2021, Номер 371(6530)

Опубликована: Фев. 11, 2021

Regulating multiple body clocks Circadian rhythms that affect tissues and organ systems are aligned with the dark-light cycle other external inputs such as feeding. But how is time keeping modulated throughout complex anatomical regions? Koronowski Sassone-Corsi reviewed central regulators in brain peripheral organs can behave cooperatively or independently to modulate circadian rhythms. This systemic view of rhythm modulation important understand behavior disease, because dysregulated associated metabolic syndrome cancer. Science , this issue p. eabd0951

Язык: Английский

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Training the Circadian Clock, Clocking the Drugs, and Drugging the Clock to Prevent, Manage, and Treat Chronic Diseases

Trends in Pharmacological Sciences, Год журнала: 2018, Номер 39(9), С. 812 - 827

Опубликована: Июль 27, 2018

Язык: Английский

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Molecular regulations of circadian rhythm and implications for physiology and diseases

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Фев. 8, 2022

The term "circadian rhythms" describes endogenous oscillations with ca. 24-h period associated the earth's daily rotation and light/dark cycle. Such rhythms reflect existence of an intrinsic circadian clock that temporally orchestrates physiological processes to adapt internal environment external cues. At molecular level, consists multiple sets transcription factors resulting in autoregulatory transcription-translation feedback loops. Notably, addition their primary role as generator rhythm, biological plays a key controlling functions almost all tissues organs. It regulates several intracellular signaling pathways, ranging from cell proliferation, DNA damage repair response, angiogenesis, metabolic redox homeostasis, inflammatory immune response. In this review, we summarize findings showing crosstalk between some describing scenario wherein reciprocal regulation impinges upon aspects mammalian physiology. Moreover, based on evidence indicating can be challenged by environmental factors, social behaviors, well pre-existing pathological conditions, discuss implications misalignment human pathologies, such cancer diseases. Accordingly, disruption rhythm has been reported affect are relevant Expanding our understanding field represents intriguing transversal medicine challenge order establish precision medicine.

Язык: Английский

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Allostasis: A Brain-Centered, Predictive Mode of Physiological Regulation

Trends in Neurosciences, Год журнала: 2019, Номер 42(10), С. 740 - 752

Опубликована: Сен. 2, 2019

Язык: Английский

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Circadian Expression of Migratory Factors Establishes Lineage-Specific Signatures that Guide the Homing of Leukocyte Subsets to Tissues

Immunity, Год журнала: 2018, Номер 49(6), С. 1175 - 1190.e7

Опубликована: Дек. 1, 2018

The number of leukocytes present in circulation varies throughout the day, reflecting bone marrow output and emigration from blood into tissues. Using an organism-wide circadian screening approach, we detected oscillations pro-migratory factors that were distinct for specific vascular beds individual leukocyte subsets. This rhythmic molecular signature governed time-of-day-dependent homing behavior subsets to organs. Ablation BMAL1, a transcription factor central clock function, endothelial cells or demonstrated recruitment is dependent on both microenvironmental cell-autonomous oscillations. These oscillatory patterns defined trafficking homeostasis inflammation determined detectable tumor burden cancer models. Rhythms expression migration capacities preserved human primary leukocytes. definition spatial temporal profiles guiding organs provides resource further study impact rhythms immunity.

Язык: Английский

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Nuclear Receptor Subfamily 1 Group D Member 1 Regulates Circadian Activity of NLRP3 Inflammasome to Reduce the Severity of Fulminant Hepatitis in Mice

Gastroenterology, Год журнала: 2017, Номер 154(5), С. 1449 - 1464.e20

Опубликована: Дек. 24, 2017

Язык: Английский

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Circadian clock component REV-ERBα controls homeostatic regulation of pulmonary inflammation

Journal of Clinical Investigation, Год журнала: 2018, Номер 128(6), С. 2281 - 2296

Опубликована: Март 20, 2018

Recent studies reveal that airway epithelial cells are critical pulmonary circadian pacemaker cells, mediating rhythmic inflammatory responses. Using mouse models, we now identify the repressor REV-ERBα as essential to mechanism coupling clock innate immunity, involving both myeloid and bronchial in temporal gating determining amplitude of response inhaled endotoxin. Dual mutation its paralog REV-ERBβ epithelia further augmented responses chemokine activation, but also initiated a basal state, revealing homeostatic role for REV-ERB proteins suppression endogenous proinflammatory unchallenged cells. However, plays dominant role, deletion alone had no impact on In turn, challenges cause striking changes stability degradation protein, driven by SUMOylation ubiquitination. We developed novel selective oxazole-based inverse agonist REV-ERB, which protects protein from degradation, used this how cytokines trigger rapid elaboration an response. Thus, dynamic couple core immunity.

Язык: Английский

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Dendritic cells direct circadian anti-tumour immune responses

Nature, Год журнала: 2022, Номер 614(7946), С. 136 - 143

Опубликована: Дек. 5, 2022

Abstract The process of cancer immunosurveillance is a mechanism tumour suppression that can protect the host from development throughout its lifetime 1,2 . However, it unknown whether effectiveness fluctuates over single day. Here we demonstrate initial time day engraftment dictates ensuing size across mouse models. Using immunodeficient mice as well lacking lineage-specific circadian functions, show dendritic cells (DCs) and CD8 + T exert anti-tumour functions control melanoma volume. Specifically, find rhythmic trafficking DCs to draining lymph node governs response tumour-antigen-specific dependent on expression co-stimulatory molecule CD80. As consequence, immunotherapy more effective when synchronized with DC shows outcomes in suggests similar effects humans. These data rhythms immune components are not only critical for controlling but also be therapeutic relevance.

Язык: Английский

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Circadian tumor infiltration and function of CD8+ T cells dictate immunotherapy efficacy

Cell, Год журнала: 2024, Номер 187(11), С. 2690 - 2702.e17

Опубликована: Май 1, 2024

The quality and quantity of tumor-infiltrating lymphocytes, particularly CD8+ T cells, are important parameters for the control tumor growth response to immunotherapy. Here, we show in murine human cancers that these exhibit circadian oscillations, driven by both endogenous clock leukocytes rhythmic leukocyte infiltration, which depends on endothelial cells microenvironment. To harness rhythms therapeutically, demonstrate efficacy chimeric antigen receptor cell therapy immune checkpoint blockade can be improved adjusting time treatment during day. Furthermore, time-of-day-dependent signatures models predict overall survival patients with melanoma correlate anti-PD-1 therapy. Our data functional significance dynamics microenvironment suggest importance leveraging features improving future clinical trial design patient care.

Язык: Английский

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