Circadian clock communication during homeostasis and ageing

Nature Reviews Molecular Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Language: Английский

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Circadian rhythm disruption in critically ill patients

Acta Physiologica, Journal Year: 2023, Volume and Issue: 238(1)

Published: March 14, 2023

Abstract Patients admitted to the intensive care unit (ICU) are in need of continuous organ replacement strategies and specialized care, for example because neurological dysfunction, cardio‐pulmonary instability, liver or kidney failure, trauma, hemorrhagic septic shock even preterm birth. The 24‐h nursing interventions provided critically ill patients significantly limit resting and/or recovery phases. Consecutively, patient's endogenous circadian rhythms misaligned disrupted, which turn may interfere with their critical condition. A more thorough understanding complex interactions effectors tissue‐specific molecular clocks could therefore serve as potential means enhancing personalized treatment patients, conceivably restoring network thus accelerating physical neurocognitive recovery. This review addresses overarching issue how affected disturbed newborns adults ICU, whether conflicting external environmental cues ICU environment further promote disruption severity illness. We direct special attention influence cell‐type specific on dysfunctions such brain pneumonia‐ ventilator‐associated lung inflammation, cardiovascular shock. Finally, we address rhythm stabilization enhance accelerate clinical

Language: Английский

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Circadian Synchrony: Sleep, Nutrition, and Physical Activity

Frontiers in Network Physiology, Journal Year: 2021, Volume and Issue: 1

Published: Oct. 12, 2021

The circadian clock in mammals regulates the sleep/wake cycle and many associated behavioral physiological processes. cellular mechanism involves a transcriptional negative feedback loop that gives rise to rhythms gene expression with an approximately 24-h periodicity. To maintain system robustness, clocks throughout body must be synchronized their functions coordinated. In mammals, master is located suprachiasmatic nucleus (SCN) of hypothalamus. SCN entrained light/dark through photic signal transduction subsequent induction core expression. turn relays time-of-day information peripheral tissues. While highly responsive cues, are more sensitive non-photic resetting cues such as nutrients, temperature, neuroendocrine hormones. For example, feeding/fasting physical activity can entrain signaling pathways regulation genes proteins. As such, timing food intake matters. ideal world, cycles cycle. However, asynchronous environmental those experienced by shift workers frequent travelers, often lead misalignment between clocks. Emerging evidence suggests resulting disruption various diseases chronic conditions cause further desynchrony accelerate disease progression. this review, we discuss how sleep, nutrition, synchronize chronomedicine may offer novel strategies for intervention.

Language: Английский

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Circadian rhythm disruption in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for the post-acute sequelae of COVID-19

Brain Behavior & Immunity - Health, Journal Year: 2022, Volume and Issue: 20, P. 100412 - 100412

Published: Jan. 10, 2022

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a common and disabling disorder primarily characterized by persistent fatigue exercise intolerance, with associated sleep disturbances, autonomic dysfunction, cognitive problems. The causes of ME/CFS are not well understood but may coincide immune inflammatory responses following viral infections. During the current SARS-CoV2 coronavirus pandemic, has been increasingly reported to overlap "long COVID" symptoms, also called post-acute sequelae COVID-19 (PASC). Given prominence activity problems in ME/CFS, circadian rhythm disruption examined as contributing factor ME/CFS. While these studies rhythms have pursued for decades, evidence linking remains inconclusive. A major limitation older chronobiology was unavailability modern molecular methods study incomplete understanding outside brain peripheral organ systems. Major methodological conceptual advancements since made. Over same time, biomarker research progressed. Together, new developments justify renewed interest Presently, we review from perspective rhythms, covering both newer that make use methods. We focus on transforming growth beta (TGFB), cytokine previously an important role especially cells. propose disrupted TGFB signaling play disrupting physiological sleep, activity, cognition, leading insomnia, energy cognition problems, depression, dysfunction Since SARS-like infections cause changes previous outbreaks caused ME/CFS-like syndromes, chronobiological considerations immediate implications context pandemic possibly suggest avenues therapeutic interventions.

Language: Английский

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Immunotherapeutic approach to reduce senescent cells and alleviate senescence‐associated secretory phenotype in mice

Aging Cell, Journal Year: 2023, Volume and Issue: 22(5)

Published: March 26, 2023

Abstract Accumulation of senescent cells (SNCs) with a senescence‐associated secretory phenotype (SASP) has been implicated as major source chronic sterile inflammation leading to many age‐related pathologies. Herein, we provide evidence that bifunctional immunotherapeutic, HCW9218, capabilities neutralizing TGF‐β and stimulating immune cells, can be safely administered systemically reduce SNCs alleviate SASP in mice. In the diabetic db/db mouse model, subcutaneous administration HCW9218 reduced islet β resulting improved glucose tolerance, insulin resistance, aging index. naturally aged mice, durably level SASP, lower expression pro‐inflammatory genes peripheral organs. treatment also reverted pattern key regulatory circadian gene mice levels observed young impacted associated metabolism fibrosis liver. Single‐nucleus RNA Sequencing analysis further revealed differentially changed transcriptomic landscape hepatocyte subtypes involving metabolic, signaling, cell‐cycle, pathways Long‐term survival studies showed physical performance without compromising health span Thus, represents novel immunotherapeutic approach clinically promising new class senotherapeutic agents targeting cellular diseases.

Language: Английский

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Circadian immunity from bench to bedside: a practical guide

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(3)

Published: Feb. 1, 2024

The immune system is built to counteract unpredictable threats, yet it relies on predictable cycles of activity function properly. Daily rhythms in are an expanding area study, and many originate from a genetically based timekeeping mechanism known as the circadian clock. challenge how harness these biological improve medical interventions. Here, we review recent literature documenting clocks organize fundamental innate adaptive activities, immunologic consequences rhythm sleep disruption, persisting knowledge gaps field. We then consider evidence linking vaccination, important clinical realization function. Finally, discuss practical steps translate immunity patient's bedside.

Language: Английский

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Time-of-day effects of cancer drugs revealed by high-throughput deep phenotyping

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 22, 2024

Abstract The circadian clock, a fundamental biological regulator, governs essential cellular processes in health and disease. Circadian-based therapeutic strategies are increasingly gaining recognition as promising avenues. Aligning drug administration with the rhythm can enhance treatment efficacy minimize side effects. Yet, uncovering optimal timings remains challenging, limiting their widespread adoption. In this work, we introduce high-throughput approach integrating live-imaging data analysis techniques to deep-phenotype cancer cell models, evaluating rhythms, growth, responses. We devise streamlined process for profiling sensitivities across different times of day, identifying windows responsive types combinations. Finally, implement multiple computational tools uncover genetic factors shaping time-of-day sensitivity. Our versatile is adaptable various facilitating its broad application relevance. Ultimately, research leverages rhythms optimize anti-cancer treatments, improved outcomes transformative strategies.

Language: Английский

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The circadian clock and extracellular matrix homeostasis in aging and age-related diseases

AJP Cell Physiology, Journal Year: 2023, Volume and Issue: 325(1), P. C52 - C59

Published: May 29, 2023

The extracellular matrix (ECM) is the noncellular scaffolding component present within all tissues and organs. It provides crucial biochemical biomechanical cues to instruct cellular behavior has been shown be under circadian clock regulation, a highly conserved cell-intrinsic timekeeping mechanism that evolved with 24-hour rhythmic environment. Aging major risk factor for many diseases, including cancer, fibrosis, neurodegenerative disorders. Both aging our modern 24/7 society disrupt rhythms, which could contribute altered ECM homeostasis. Understanding daily dynamics of how this changes age will have profound impact on tissue health, disease prevention, improving treatments. Maintaining oscillations proposed as hallmark health. On other hand, hallmarks turn out key regulators mechanisms. In review, we summarize new work linking clocks aging. We discuss in properties during may dysregulation. also consider dampening compromise dynamic regulation homeostasis matrix-rich tissues. This review aims encourage concepts testable hypotheses about two-way interactions between context

Language: Английский

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Mechanical control of the mammalian circadian clock via YAP/TAZ and TEAD

The Journal of Cell Biology, Journal Year: 2023, Volume and Issue: 222(9)

Published: June 28, 2023

Autonomous circadian clocks exist in nearly every mammalian cell type. These cellular are subjected to a multilayered regulation sensitive the mechanochemical microenvironment. Whereas biochemical signaling that controls clock is increasingly well understood, mechanisms underlying by mechanical cues largely unknown. Here we show fibroblast mechanically regulated through YAP/TAZ nuclear levels. We use high-throughput analysis of single-cell rhythms and apply controlled mechanical, biochemical, genetic perturbations study expression gene Rev-erbα. observe Rev-erbα oscillations disrupted with translocation. By targeted mutations overexpression YAP/TAZ, this mechanobiological regulation, which also impacts core components such as Bmal1 Cry1, depends on binding transcriptional effector TEAD. This mechanism could explain impairment observed when activity upregulated, cancer aging.

Language: Английский

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The circadian clock gene, BMAL1, promotes radiosensitization in nasopharyngeal carcinoma by inhibiting the epithelial-to-mesenchymal transition via the TGF-β1/Smads/Snail1 axis

Oral Oncology, Journal Year: 2024, Volume and Issue: 152, P. 106798 - 106798

Published: April 13, 2024

Acquired radio-resistance is thought to be one of the main causes recurrent metastasis after failure nasopharyngeal carcinoma (NPC) radiotherapy, which may related X-ray-induced epithelial–mesenchymal transition (EMT) activation. The circadian clock gene, BMAL1, has been shown correlate with sensitivity NPCs but specific mechanism not reported. NPC cells were irradiated by conventional fractionation generate radiotherapy-resistant cells. BMAL1 gene stabilization/overexpression and interference obtained lentiviral transfection. Western blotting, colony formation analysis, cell counting kit-8 assays, wound-healing tests, Transwell flow cytometry, EDU method, nuclear plasma separation experiments, HE staining, immunohistochemical staining TUNEL performed explore influence molecular on NPC-acquired EMT through in vitro vivo experiments. results indicated that there was a gradual downregulation protein expression during routine dose induction activation present radiation-resistant line 5-8FR, accompanied significant enhancement proliferation, migration invasion. significantly increased radiosensitivity 5-8FR reversed acquired NPCs, accomplished inhibiting TGF-β1/Smads/Snail1 axis-mediated EMT.

Language: Английский

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