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1
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Zhang Y, Zhang Q, Liu R, Zhang D, Hu G, Chen X. Circadian disruption in cancer and regulation of cancer stem cells by circadian clock genes: An updated review. Cancer Lett 2024; 611:217391. [PMID: 39672457 DOI: 10.1016/j.canlet.2024.217391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 11/13/2024] [Accepted: 12/10/2024] [Indexed: 12/15/2024]
Abstract
Circadian rhythm, regulated by a time keeping system termed as the circadian clock, is important for many biological processes in eukaryotes. Disordered circadian rhythm is implicated in different human diseases, including cardiovascular disease, neurologic disease, metabolic disorders, and cancer. The stem like-cancer cells (or cancer stem cells, CSCs) are proposed to stand at the top of the heterogeneous hierarchy in different solid tumors, which are responsible for tumor initiation, development, therapy resistance and metastasis. Emerging evidence has shown that circadian clock genes potentially regulate the stemness and features of CSCs in several malignant systems, including leukemia, glioblastoma, breast cancer, colorectal cancer and prostate cancer. The chronotherapies targeting CSCs are therefore of therapeutic potentials in treating malignancies. In this review, we have summarized our current knowledge of circadian clock gene regulation in normal stem/progenitor cells. Moreover, we have provided evidence linking dysregulations of circadian clock genes and cancer development. Importantly, we have listed the potential mechanisms underlying circadian clock gene regulation of CSCs. Finally, we have offered the current attempts of chronotherapy targeting CSCs. Elucidating the molecular regulation of circadian clock gene in CSCs will provide us a novel direction for the development of therapeutics to target CSCs.
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Affiliation(s)
- Yiling Zhang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qiang Zhang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Rundong Liu
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Dingxiao Zhang
- Provincial Key Laboratory of Animal Models and Molecular Medicine, School of Biomedical Sciences, Hunan University, Changsha, Hunan, 410082, China
| | - Guangyuan Hu
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Xin Chen
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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2
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Rajan PK, Udoh UAS, Finley R, Pierre SV, Sanabria J. The Biological Clock of Liver Metabolism in Metabolic Dysfunction-Associated Steatohepatitis Progression to Hepatocellular Carcinoma. Biomedicines 2024; 12:1961. [PMID: 39335475 PMCID: PMC11428469 DOI: 10.3390/biomedicines12091961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 08/12/2024] [Accepted: 08/19/2024] [Indexed: 09/30/2024] Open
Abstract
Circadian rhythms are endogenous behavioral or physiological cycles that are driven by a daily biological clock that persists in the absence of geophysical or environmental temporal cues. Circadian rhythm-related genes code for clock proteins that rise and fall in rhythmic patterns driving biochemical signals of biological processes from metabolism to physiology and behavior. Clock proteins have a pivotal role in liver metabolism and homeostasis, and their disturbances are implicated in various liver disease processes. Encoded genes play critical roles in the initiation and progression of metabolic dysfunction-associated steatohepatitis (MASH) to hepatocellular carcinoma (HCC) and their proteins may become diagnostic markers as well as therapeutic targets. Understanding molecular and metabolic mechanisms underlying circadian rhythms will aid in therapeutic interventions and may have broader clinical applications. The present review provides an overview of the role of the liver's circadian rhythm in metabolic processes in health and disease, emphasizing MASH progression and the oncogenic associations that lead to HCC.
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Affiliation(s)
- Pradeep Kumar Rajan
- Marshall Institute for Interdisciplinary Research, Huntington, WV 25703, USA
- Department of Surgery, School of Medicine, Marshall University, Huntington, WV 25701, USA
| | - Utibe-Abasi S Udoh
- Marshall Institute for Interdisciplinary Research, Huntington, WV 25703, USA
- Department of Surgery, School of Medicine, Marshall University, Huntington, WV 25701, USA
| | - Robert Finley
- Department of Surgery, School of Medicine, Marshall University, Huntington, WV 25701, USA
| | - Sandrine V Pierre
- Marshall Institute for Interdisciplinary Research, Huntington, WV 25703, USA
| | - Juan Sanabria
- Marshall Institute for Interdisciplinary Research, Huntington, WV 25703, USA
- Department of Surgery, School of Medicine, Marshall University, Huntington, WV 25701, USA
- Department of Nutrition and Metabolomic Core Facility, School of Medicine, Case Western Reserve University, Cleveland, OH 44100, USA
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3
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Streng AA, Van Dycke KCG, van Oostrom CTM, Salvatori DCF, Hulsegge G, Chaves I, Roenneberg T, Zander SAL, van Steeg H, van der Horst GTJ, van Kerkhof LWM. Impact of Simulated Rotating Shift Work on Mammary Tumor Development in the p53R270H©/+WAPCre Mouse Model for Breast Cancer. J Biol Rhythms 2023; 38:476-491. [PMID: 37357746 DOI: 10.1177/07487304231178340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/27/2023]
Abstract
Epidemiological studies associate night shift work with increased breast cancer risk. However, the underlying mechanisms are not clearly understood. To better understand these mechanisms, animal models that mimic the human situation of different aspects of shift work are needed. In this study, we used "timed sleep restriction" (TSR) cages to simulate clockwise and counterclockwise rotating shift work schedules and investigated predicted sleep patterns and mammary tumor development in breast tumor-prone female p53R270H©/+WAPCre mice. We show that TSR cages are effective in disturbing normal activity and estimated sleep patterns. Although circadian rhythms were not shifted, we observed effects of the rotating schedules on sleep timing and sleep duration. Sleep loss during a simulated shift was partly compensated after the shift and also partly during the free days. No effects were observed on body weight gain and latency time of breast cancer development. In summary, our study shows that the TSR cages can be used to model shift work in mice and affect patterns of activity and sleep. The effect of disturbing sleep patterns on carcinogenesis needs to be further investigated.
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Affiliation(s)
- Astrid A Streng
- Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands
- Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
| | - Kirsten C G Van Dycke
- Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands
- Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
| | - Conny T M van Oostrom
- Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
| | - Daniela C F Salvatori
- Experimental Pathology Services Lab, Central Laboratory Animal Facility, Leiden University Medical Center, Leiden, The Netherlands
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - Gerben Hulsegge
- Sustainable Productivity and Employability, Netherlands Organization for Applied Scientific Research (TNO), Leiden, The Netherlands
| | - Inês Chaves
- Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Till Roenneberg
- Institute of Medical Psychology, Ludwig-Maximilians-University, Munich, Germany
| | - Serge A L Zander
- Experimental Pathology Services Lab, Central Laboratory Animal Facility, Leiden University Medical Center, Leiden, The Netherlands
| | - Harry van Steeg
- Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
| | - Gijsbertus T J van der Horst
- Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Linda W M van Kerkhof
- Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
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4
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Shafaati M, Sadeghniiat K, Priyanka, Najafia A, Zandi M, Akbarpour S, Choudhary OP. The relevance of the circadian timing system role in patients with HIV/AIDS: a quick glance. Int J Surg 2023; 109:2831-2834. [PMID: 36928027 PMCID: PMC10498842 DOI: 10.1097/js9.0000000000000103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 11/16/2022] [Indexed: 03/18/2023]
Affiliation(s)
- Maryam Shafaati
- Occupational Sleep Research Center, Baharloo Hospital, Tehran University of Medical Sciences, Tehran, Iran
- Department of Microbiology, Faculty Science, Jahrom Branch, Islamic Azad University, Jahrom, Iran
| | - Khosro Sadeghniiat
- Occupational Sleep Research Center, Baharloo Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Priyanka
- Department of Veterinary Microbiology, College of Veterinary Science, Guru Angad Dev Veterinary and Animal Sciences University (GADVASU), Rampura Phul, Bathinda, Punjab, India
| | - Arezu Najafia
- Occupational Sleep Research Center, Baharloo Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Milad Zandi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Samaneh Akbarpour
- Occupational Sleep Research Center, Baharloo Hospital, Tehran University of Medical Sciences, Tehran, Iran
- Sleep Breathing Disorders Research Center (SBDRC), Tehran University of Medical Sciences, Tehran, Iran
| | - Om Prakash Choudhary
- Department of Veterinary Anatomy and Histology, College of Veterinary Sciences and Animal Husbandry, Central Agricultural University (I), Selesih, Aizawl, Mizoram, India
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5
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Cazarin J, DeRollo RE, Ahmad Shahidan SNAB, Burchett JB, Mwangi D, Krishnaiah S, Hsieh AL, Walton ZE, Brooks R, Mello SS, Weljie AM, Dang CV, Altman BJ. MYC disrupts transcriptional and metabolic circadian oscillations in cancer and promotes enhanced biosynthesis. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.01.03.522637. [PMID: 36711638 PMCID: PMC9881876 DOI: 10.1101/2023.01.03.522637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
The molecular circadian clock, which controls rhythmic 24-hour oscillation of genes, proteins, and metabolites in healthy tissues, is disrupted across many human cancers. Deregulated expression of the MYC oncoprotein has been shown to alter expression of molecular clock genes, leading to a disruption of molecular clock oscillation across cancer types. It remains unclear what benefit cancer cells gain from suppressing clock oscillation, and how this loss of molecular clock oscillation impacts global gene expression and metabolism in cancer. We hypothesized that MYC or its paralog N-MYC (collectively termed MYC herein) suppress oscillation of gene expression and metabolism to upregulate pathways involved in biosynthesis in a static, non-oscillatory fashion. To test this, cells from distinct cancer types with inducible MYC were examined, using time-series RNA-sequencing and metabolomics, to determine the extent to which MYC activation disrupts global oscillation of genes, gene expression pathways, and metabolites. We focused our analyses on genes, pathways, and metabolites that changed in common across multiple cancer cell line models. We report here that MYC disrupted over 85% of oscillating genes, while instead promoting enhanced ribosomal and mitochondrial biogenesis and suppressed cell attachment pathways. Notably, when MYC is activated, biosynthetic programs that were formerly circadian flipped to being upregulated in an oscillation-free manner. Further, activation of MYC ablates the oscillation of nutrient transporter proteins while greatly upregulating transporter expression, cell surface localization, and intracellular amino acid pools. Finally, we report that MYC disrupts metabolite oscillations and the temporal segregation of amino acid metabolism from nucleotide metabolism. Our results demonstrate that MYC disruption of the molecular circadian clock releases metabolic and biosynthetic processes from circadian control, which may provide a distinct advantage to cancer cells.
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Affiliation(s)
- Juliana Cazarin
- Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
| | - Rachel E. DeRollo
- Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
| | | | - Jamison B. Burchett
- Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
| | - Daniel Mwangi
- Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
| | - Saikumari Krishnaiah
- Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Institute of Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA
- Chronobiology and Sleep Institute, University of Pennsylvania, Philadelphia, PA, USA
| | | | | | | | - Stephano S. Mello
- Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
- Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA
| | - Aalim M. Weljie
- Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Institute of Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA
- Chronobiology and Sleep Institute, University of Pennsylvania, Philadelphia, PA, USA
| | - Chi V. Dang
- Ludwig Institute for Cancer Research, New York, NY, USA
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, MD, USA
| | - Brian J. Altman
- Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
- Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA
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6
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Cazarin J, DeRollo RE, Shahidan SNABA, Burchett JB, Mwangi D, Krishnaiah S, Hsieh AL, Walton ZE, Brooks R, Mello SS, Weljie AM, Dang CV, Altman BJ. MYC disrupts transcriptional and metabolic circadian oscillations in cancer and promotes enhanced biosynthesis. PLoS Genet 2023; 19:e1010904. [PMID: 37639465 PMCID: PMC10491404 DOI: 10.1371/journal.pgen.1010904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 09/08/2023] [Accepted: 08/07/2023] [Indexed: 08/31/2023] Open
Abstract
The molecular circadian clock, which controls rhythmic 24-hour oscillation of genes, proteins, and metabolites in healthy tissues, is disrupted across many human cancers. Deregulated expression of the MYC oncoprotein has been shown to alter expression of molecular clock genes, leading to a disruption of molecular clock oscillation across cancer types. It remains unclear what benefit cancer cells gain from suppressing clock oscillation, and how this loss of molecular clock oscillation impacts global gene expression and metabolism in cancer. We hypothesized that MYC or its paralog N-MYC (collectively termed MYC herein) suppress oscillation of gene expression and metabolism to upregulate pathways involved in biosynthesis in a static, non-oscillatory fashion. To test this, cells from distinct cancer types with inducible MYC were examined, using time-series RNA-sequencing and metabolomics, to determine the extent to which MYC activation disrupts global oscillation of genes, gene expression pathways, and metabolites. We focused our analyses on genes, pathways, and metabolites that changed in common across multiple cancer cell line models. We report here that MYC disrupted over 85% of oscillating genes, while instead promoting enhanced ribosomal and mitochondrial biogenesis and suppressed cell attachment pathways. Notably, when MYC is activated, biosynthetic programs that were formerly circadian flipped to being upregulated in an oscillation-free manner. Further, activation of MYC ablates the oscillation of nutrient transporter proteins while greatly upregulating transporter expression, cell surface localization, and intracellular amino acid pools. Finally, we report that MYC disrupts metabolite oscillations and the temporal segregation of amino acid metabolism from nucleotide metabolism. Our results demonstrate that MYC disruption of the molecular circadian clock releases metabolic and biosynthetic processes from circadian control, which may provide a distinct advantage to cancer cells.
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Affiliation(s)
- Juliana Cazarin
- Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America
| | - Rachel E. DeRollo
- Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America
| | - Siti Noor Ain Binti Ahmad Shahidan
- Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America
| | - Jamison B. Burchett
- Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America
| | - Daniel Mwangi
- Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America
| | - Saikumari Krishnaiah
- Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Institute of Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Chronobiology and Sleep Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Annie L. Hsieh
- The Wistar Institute, Philadelphia, Pennsylvania, United States of America
| | - Zandra E. Walton
- The Wistar Institute, Philadelphia, Pennsylvania, United States of America
| | - Rebekah Brooks
- The Wistar Institute, Philadelphia, Pennsylvania, United States of America
| | - Stephano S. Mello
- Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America
- Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, United States of America
| | - Aalim M. Weljie
- Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Institute of Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Chronobiology and Sleep Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Chi V. Dang
- Ludwig Institute for Cancer Research, New York, New York, United States of America
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
- Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Maryland, United States of America
| | - Brian J. Altman
- Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America
- Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, United States of America
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Wang Y, Guo H, He F. Circadian disruption: from mouse models to molecular mechanisms and cancer therapeutic targets. Cancer Metastasis Rev 2023; 42:297-322. [PMID: 36513953 DOI: 10.1007/s10555-022-10072-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 11/25/2022] [Indexed: 12/15/2022]
Abstract
The circadian clock is a timekeeping system for numerous biological rhythms that contribute to the regulation of numerous homeostatic processes in humans. Disruption of circadian rhythms influences physiology and behavior and is associated with adverse health outcomes, especially cancer. However, the underlying molecular mechanisms of circadian disruption-associated cancer initiation and development remain unclear. It is essential to construct good circadian disruption models to uncover and validate the detailed molecular clock framework of circadian disruption in cancer development and progression. Mouse models are the most widely used in circadian studies due to their relatively small size, fast reproduction cycle, easy genome manipulation, and economic practicality. Here, we reviewed the current mouse models of circadian disruption, including suprachiasmatic nuclei destruction, genetic engineering, light disruption, sleep deprivation, and other lifestyle factors in our understanding of the crosstalk between circadian rhythms and oncogenic signaling, as well as the molecular mechanisms of circadian disruption that promotes cancer growth. We focused on the discoveries made with the nocturnal mouse, diurnal human being, and cell culture and provided several circadian rhythm-based cancer therapeutic strategies.
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Affiliation(s)
- Yu Wang
- Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Haidong Guo
- Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
- Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Feng He
- Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
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Stenger S, Grasshoff H, Hundt JE, Lange T. Potential effects of shift work on skin autoimmune diseases. Front Immunol 2023; 13:1000951. [PMID: 36865523 PMCID: PMC9972893 DOI: 10.3389/fimmu.2022.1000951] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 11/29/2022] [Indexed: 02/16/2023] Open
Abstract
Shift work is associated with systemic chronic inflammation, impaired host and tumor defense and dysregulated immune responses to harmless antigens such as allergens or auto-antigens. Thus, shift workers are at higher risk to develop a systemic autoimmune disease and circadian disruption with sleep impairment seem to be the key underlying mechanisms. Presumably, disturbances of the sleep-wake cycle also drive skin-specific autoimmune diseases, but epidemiological and experimental evidence so far is scarce. This review summarizes the effects of shift work, circadian misalignment, poor sleep, and the effect of potential hormonal mediators such as stress mediators or melatonin on skin barrier functions and on innate and adaptive skin immunity. Human studies as well as animal models were considered. We will also address advantages and potential pitfalls in animal models of shift work, and possible confounders that could drive skin autoimmune diseases in shift workers such as adverse lifestyle habits and psychosocial influences. Finally, we will outline feasible countermeasures that may reduce the risk of systemic and skin autoimmunity in shift workers, as well as treatment options and highlight outstanding questions that should be addressed in future studies.
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Affiliation(s)
- Sarah Stenger
- Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany
| | - Hanna Grasshoff
- Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany
| | - Jennifer Elisabeth Hundt
- Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany
- Center for Research on Inflammation of the Skin, University of Lübeck, Lübeck, Germany
| | - Tanja Lange
- Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany
- Center for Research on Inflammation of the Skin, University of Lübeck, Lübeck, Germany
- Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany
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Xian H, Li Y, Zou B, Chen Y, Yin H, Li X, Pan Y. Identification of TIMELESS and RORA as key clock molecules of non-small cell lung cancer and the comprehensive analysis. BMC Cancer 2022; 22:107. [PMID: 35078435 PMCID: PMC8788117 DOI: 10.1186/s12885-022-09203-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 01/13/2022] [Indexed: 12/21/2022] Open
Abstract
Background The incidence rate of non-small cell lung cancer (NSCLC) has been increasing worldwide, and the correlation of circadian rhythm disruption with a raised risk of cancer and worse prognosis has been shown by accumulating evidences recently. On the other hand, drug resistance and the impact of tumor heterogeneity have been inevitable in NSCLC therapy. These both lead to an urgent need to identify more useful prognostic and predictive markers for NSCLC diagnosis and treatment, especially on the aspect of circadian clock genes. Methods The expression of the main clock genes in cancer was probed with TIMER and Oncomine databases. The prognostic value of key clock genes was probed systematically with the Kaplan–Meier estimate and Cox regression on samples from TCGA database. RT-qPCR was performed on patient tissue samples to further validate the results from databases. The functional enrichment analysis was performed using the “ClusterProfiler” R package, and the correlation of key clock genes with tumor mutation burden, immune checkpoint, and immune infiltration levels were also assessed using multiple algorithms including TIDE, TIMER2.0, and XCELL. Results TIMELESS was significantly upregulated in lung tissue of clinical lung cancer patients as well as TCGA and Oncomine databases, while RORA was downregulated. Multivariate Cox regression analysis indicated that TIMELESS (P = 0.004, HR = 1.21 [1.06, 1.38]) and RORA (P = 0.047, HR = 0.868 [0.755, 0.998]) has a significant correlation with overall survival in NSCLC. Genes related to TIMELESS were enriched in the cell cycle and immune system, and the function of RORA was mainly focused on oncogenic signaling pathways or glycosylation and protein activation. Also, TIMELESS was positively correlated with tumor mutation burden while RORA was negatively correlated with it. TIMELESS and RORA were also significantly correlated with immune checkpoint and immune infiltration levels in NSCLC. Additionally, TIMELESS showed a significant positive relationship with lipid metabolism. Conclusions TIMELESS and RORA were identified as key clock genes in NSCLC, and were independent prognostic factors for overall survival in NSCLC. The function of them were assessed in many aspects, indicating the strong potential of the two genes to serve as biomarkers for NSCLC progression and prognosis. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09203-1.
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10
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Borniger JC. Cancer as a tool for preclinical psychoneuroimmunology. Brain Behav Immun Health 2021; 18:100351. [PMID: 34988496 PMCID: PMC8710415 DOI: 10.1016/j.bbih.2021.100351] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 09/03/2021] [Accepted: 09/17/2021] [Indexed: 12/20/2022] Open
Abstract
Cancer represents a novel homeostatic challenge to the host system. How the brain senses and responds to changes in peripheral physiology elicited by tumor growth is a largely untapped area of research. This is especially relevant given the widespread prevalence of systemic problems that people with various types of cancer experience. These include disruptions in sleep/wake cycles, cognitive function, depression, and changes in appetite/food intake, among others. Critically, many of these problems are evident prior to diagnosis, indicating that their etiology is potentially distinct from the effects of cancer treatment or the stress of a cancer diagnosis. Psychoneuroimmunology (PNI) is well equipped to tackle these types of problems, as it uses approaches from multiple disciplines to understand how specific stimuli (endogenous and environmental) are transduced into neural, endocrine, and immune signals that ultimately regulate health and behavior. In this article, I first provide a brief historical perspective of cancer and PNI, introduce the idea of cancer as a systemic homeostatic challenge, and provide examples from preclinical literature supporting this hypothesis. Given the rise of advanced tools in neuroscience (e.g., calcium imaging), we can now monitor and manipulate genetically defined neural circuits over the extended time scales necessary to disentangle distal communication between peripheral tumors and the brain.
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11
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Adams KL, Sun EF, Alaidrous W, de Roode JC. Constant Light and Frequent Schedule Changes Do Not Impact Resistance to Parasites in Monarch Butterflies. J Biol Rhythms 2021; 36:286-296. [PMID: 33445989 DOI: 10.1177/0748730420985312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Organisms have evolved internal biological clocks to regulate their activities based on external environmental cues, such as light, temperature, and food. Environmental disruption of these rhythms, such as caused by constant light or frequent light schedule changes, has been shown to impair development, reduce survival, and increase infection susceptibility and disease progression in numerous organisms. However, the precise role of the biological clock in host-parasite interactions is understudied and has focused on unnatural host-parasite combinations in lab-adapted inbred models. Here, we use the natural interaction between monarch butterflies (Danaus plexippus) and their virulent protozoan parasite, Ophryocystis elektroscirrha, to investigate the effects of constant light and frequent light schedule changes on development, survival, and parasite susceptibility. We show that constant light exposure slows the monarchs' rate of development but does not increase susceptibility to parasitic infection. Furthermore, frequent schedule changes decrease parasite growth, but have no effect on egg-to-adult survival of infected monarchs. Interestingly, these conditions are usually disruptive to the biological clock, but do not significantly impact the clock of monarch larvae. These unexpected findings show that constant light and frequent schedule changes can uncouple host and parasite performance and highlight how natural relationships are needed to expand our understanding of clocks in host-parasite interactions.
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Affiliation(s)
- Kandis L Adams
- Department of Biology, Emory University, Atlanta, GA, USA
| | | | - Wajd Alaidrous
- Department of Biology, Emory University, Atlanta, GA, USA
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Abstract
Circadian rhythms govern a large array of physiological and metabolic functions. Perturbations of the daily cycle have been linked to elevated risk of developing cancer as well as poor prognosis in patients with cancer. Also, expression of core clock genes or proteins is remarkably attenuated particularly in tumours of a higher stage or that are more aggressive, possibly linking the circadian clock to cellular differentiation. Emerging evidence indicates that metabolic control by the circadian clock underpins specific hallmarks of cancer metabolism. Indeed, to support cell proliferation and biomass production, the clock may direct metabolic processes of cancer cells in concert with non-clock transcription factors to control how nutrients and metabolites are utilized in a time-specific manner. We hypothesize that the metabolic switch between differentiation or stemness of cancer may be coupled to the molecular clockwork. Moreover, circadian rhythms of host organisms appear to dictate tumour growth and proliferation. This Review outlines recent discoveries of the interplay between circadian rhythms, proliferative metabolism and cancer, highlighting potential opportunities in the development of future therapeutic strategies.
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Affiliation(s)
- Kenichiro Kinouchi
- Center for Epigenetics and Metabolism, U1233 INSERM, Department of Biological Chemistry, University of California, Irvine, CA, USA.
- Department of Endocrinology, Metabolism, and Nephrology, School of Medicine, Keio University, Tokyo, Japan.
| | - Paolo Sassone-Corsi
- Center for Epigenetics and Metabolism, U1233 INSERM, Department of Biological Chemistry, University of California, Irvine, CA, USA.
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13
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Halim MA, Tan FHP, Azlan A, Rasyid II, Rosli N, Shamsuddin S, Azzam G. Ageing, Drosophila melanogaster and Epigenetics. Malays J Med Sci 2020; 27:7-19. [PMID: 32684802 PMCID: PMC7337951 DOI: 10.21315/mjms2020.27.3.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Accepted: 01/31/2020] [Indexed: 11/03/2022] Open
Abstract
Ageing is a phenomenon where the accumulation of all the stresses that alter the functions of living organisms, halter them from maintaining their physiological balance and eventually lead to death. The emergence of epigenetic tremendously contributed to the knowledge of ageing. Epigenetic changes in cells or tissues like deoxyribonucleic acid (DNA) methylation, modification of histone proteins, transcriptional modification and also the involvement of non-coding DNA has been documented to be associated with ageing. In order to study ageing, scientists have taken advantage of several potential organisms to aid them in their study. Drosophila melanogaster has been an essential model in establishing current understanding of the mechanism of ageing as they possess several advantages over other competitors like having homologues to more than 75% of human disease genes, having 50% of Drosophila genes are homologues to human genes and most importantly they are genetically amenable. Here, we would like to summarise the extant knowledge about ageing and epigenetic process and the role of Drosophila as an ideal model to study epigenetics in association with ageing process.
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Affiliation(s)
- Mardani Abdul Halim
- USM-RIKEN International Centre for Ageing Science (URICAS), Universiti Sains Malaysia, Pulau Pinang, Malaysia.,School of Biological Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia
| | - Florence Hui Ping Tan
- USM-RIKEN International Centre for Ageing Science (URICAS), Universiti Sains Malaysia, Pulau Pinang, Malaysia.,School of Biological Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia
| | - Azali Azlan
- USM-RIKEN International Centre for Ageing Science (URICAS), Universiti Sains Malaysia, Pulau Pinang, Malaysia.,School of Biological Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia
| | - Ian Ilham Rasyid
- School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - Nurlina Rosli
- School of Biological Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia
| | - Shaharum Shamsuddin
- USM-RIKEN International Centre for Ageing Science (URICAS), Universiti Sains Malaysia, Pulau Pinang, Malaysia.,School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - Ghows Azzam
- USM-RIKEN International Centre for Ageing Science (URICAS), Universiti Sains Malaysia, Pulau Pinang, Malaysia.,School of Biological Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia
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14
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Benitah SA, Welz PS. Circadian Regulation of Adult Stem Cell Homeostasis and Aging. Cell Stem Cell 2020; 26:817-831. [DOI: 10.1016/j.stem.2020.05.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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15
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Alam H, Tang M, Maitituoheti M, Dhar SS, Kumar M, Han CY, Ambati CR, Amin SB, Gu B, Chen TY, Lin YH, Chen J, Muller FL, Putluri N, Flores ER, DeMayo FJ, Baseler L, Rai K, Lee MG. KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer. Cancer Cell 2020; 37:599-617.e7. [PMID: 32243837 PMCID: PMC7178078 DOI: 10.1016/j.ccell.2020.03.005] [Citation(s) in RCA: 142] [Impact Index Per Article: 28.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 11/08/2019] [Accepted: 03/04/2020] [Indexed: 12/19/2022]
Abstract
Epigenetic modifiers frequently harbor loss-of-function mutations in lung cancer, but their tumor-suppressive roles are poorly characterized. Histone methyltransferase KMT2D (a COMPASS-like enzyme, also called MLL4) is among the most highly inactivated epigenetic modifiers in lung cancer. Here, we show that lung-specific loss of Kmt2d promotes lung tumorigenesis in mice and upregulates pro-tumorigenic programs, including glycolysis. Pharmacological inhibition of glycolysis preferentially impedes tumorigenicity of human lung cancer cells bearing KMT2D-inactivating mutations. Mechanistically, Kmt2d loss widely impairs epigenomic signals for super-enhancers/enhancers, including the super-enhancer for the circadian rhythm repressor Per2. Loss of Kmt2d decreases expression of PER2, which regulates multiple glycolytic genes. These findings indicate that KMT2D is a lung tumor suppressor and that KMT2D deficiency confers a therapeutic vulnerability to glycolytic inhibitors.
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Affiliation(s)
- Hunain Alam
- Department of Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
| | - Ming Tang
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1901 East Road, Houston, TX 77054, USA
| | - Mayinuer Maitituoheti
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1901 East Road, Houston, TX 77054, USA
| | - Shilpa S Dhar
- Department of Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
| | - Manish Kumar
- Department of Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
| | - Chae Young Han
- Department of Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
| | - Chandrashekar R Ambati
- Advanced Technology Core and Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Samir B Amin
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1901 East Road, Houston, TX 77054, USA
| | - Bingnan Gu
- Department of Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
| | - Tsai-Yu Chen
- Department of Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
| | - Yu-Hsi Lin
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, 1881 East Road, Houston, TX 77054, USA
| | - Jichao Chen
- Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Florian L Muller
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, 1881 East Road, Houston, TX 77054, USA
| | - Nagireddy Putluri
- Advanced Technology Core and Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Elsa R Flores
- Department of Molecular Oncology and Cancer Biology and Evolution Program, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA
| | - Francesco J DeMayo
- Reproductive and Developmental Biology Laboratory, The National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA
| | - Laura Baseler
- Department of Veterinary Medicine & Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
| | - Kunal Rai
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1901 East Road, Houston, TX 77054, USA.
| | - Min Gyu Lee
- Department of Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
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16
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Emotional distress, brain functioning, and biobehavioral processes in cancer patients: a neuroimaging review and future directions. CNS Spectr 2020; 25:79-100. [PMID: 31010446 DOI: 10.1017/s1092852918001621] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Despite emerging evidence that distress and adversity can contribute to negative health outcomes in cancer, little is known about the brain networks, regions, or circuits that can contribute to individual differences in affect/distress states and health outcomes in treated cancer patients. To understand the state-of-the-science in this regard, we reviewed neuroimaging studies with cancer patients that examined the associations between negative affect (distress) and changes in the metabolism or structure of brain regions. Cancer patients showed changes in function and/or structure of key brain regions such as the prefrontal cortex, thalamus, amygdala, hippocampus, cingulate cortex (mainly subgenual area), hypothalamus, basal ganglia (striatum and caudate), and insula, which are associated with greater anxiety, depression, posttraumatic stress disorder (PTSD) symptoms, and distress. These results provide insights for understanding the effects of these psychological and emotional factors on peripheral stress-related biobehavioral pathways known to contribute to cancer progression and long-term health outcomes. This line of work provides leads for understanding the brain-mediated mechanisms that may explain the health effects of psychosocial interventions in cancer patients and survivors. A multilevel and integrated model for distress management intervention effects on psychological adaptation, biobehavioral processes, cancer pathogenesis, and clinical outcomes is proposed for future research.
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17
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García-Costela M, Escudero-Feliú J, Puentes-Pardo JD, San Juán SM, Morales-Santana S, Ríos-Arrabal S, Carazo Á, León J. Circadian Genes as Therapeutic Targets in Pancreatic Cancer. Front Endocrinol (Lausanne) 2020; 11:638. [PMID: 33042011 PMCID: PMC7516350 DOI: 10.3389/fendo.2020.00638] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 08/06/2020] [Indexed: 12/24/2022] Open
Abstract
Pancreatic cancer is one of the most lethal cancers worldwide due to its symptoms, early metastasis, and chemoresistance. Thus, the mechanisms contributing to pancreatic cancer progression require further exploration. Circadian rhythms are the daily oscillations of multiple biological processes regulated by an endogenous clock. Several evidences suggest that the circadian clock may play an important role in the cell cycle, cell proliferation and apoptosis. In addition, timing of chemotherapy or radiation treatment can influence the efficacy and toxicity treatment. Here, we revisit the studies on circadian clock as an emerging target for therapy in pancreatic cancer. We highlight those potential circadian genes regulators that are commonly affected in pancreatic cancer according to most recent reports.
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Affiliation(s)
- María García-Costela
- Research Unit, Biosanitary Research Institute of Granada, ibs.GRANADA, Granada, Spain
| | - Julia Escudero-Feliú
- Research Unit, Biosanitary Research Institute of Granada, ibs.GRANADA, Granada, Spain
| | - Jose D. Puentes-Pardo
- Research Unit, Biosanitary Research Institute of Granada, ibs.GRANADA, Granada, Spain
- Jose D. Puentes-Pardo
| | - Sara Moreno San Juán
- Cytometry and Michroscopy Research Service, Biosanitary Research Institute of Granada, ibs.GRANADA, Granada, Spain
| | - Sonia Morales-Santana
- Proteomic Research Service, Biosanitary Research Institute of Granada, ibs.GRANADA, Granada, Spain
- Endocrinology Unit, Endocrinology Division, CIBER of Fragility and Healthy Aging (CIBERFES), San Cecilio University Hospital, Granada, Spain
| | - Sandra Ríos-Arrabal
- Research Unit, Biosanitary Research Institute of Granada, ibs.GRANADA, Granada, Spain
- *Correspondence: Sandra Ríos-Arrabal
| | - Ángel Carazo
- Genomic Research Service, Biosanitary Research Institute of Granada, ibs.GRANADA, Granada, Spain
| | - Josefa León
- Research Unit, Biosanitary Research Institute of Granada, ibs.GRANADA, Granada, Spain
- Clinical Management Unit of Digestive Disease, San Cecilio University Hospital, Granada, Spain
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18
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Abstract
Cancer is a systemic disease. In order to fully understand it, we must take a holistic view on how cancer interacts with its host. The brain monitors and responds to natural and aberrant signals arriving from the periphery, particularly those of metabolic or immune origin. As has been well described, a hallmark of cancer is marked disruption of metabolic and inflammatory processes. Depending on the salience and timing of these inputs, the brain responds via neural and humoral routes to alter whole-body physiology. These responses have consequences for tumor growth and metastasis, directly influencing patient quality of life and subsequent mortality. Additionally, environmental inputs such as light, diet, and stress, can promote inappropriate neural activity that benefits cancer. Here, I discuss evidence for brain-tumor interactions, with special emphasis on subcortical neuromodulator neural populations, and potential ways of harnessing this cross-talk as a novel approach for cancer treatment.
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Affiliation(s)
- Jeremy C Borniger
- Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, P154 MSLS Building, 1201 Welch Rd., Stanford, CA 94305, USA
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19
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Association of Time-Varying Rest-Activity Rhythm With Survival in Older Adults With Lung Cancer. Cancer Nurs 2018; 43:45-51. [PMID: 30299421 DOI: 10.1097/ncc.0000000000000647] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
BACKGROUND To the best of our knowledge, this is the first study to examine the relationship of rest-activity rhythm with survival in older adults with lung cancer and to consider variations in rest-activity rhythm over time. OBJECTIVE The aim of this study was to explore the relationship between rest-activity rhythm variations and survival in 33 older adults with lung cancer by considering rest-activity rhythm as a time-dependent covariate over time. METHODS In this prospective study with 5 repeated measurements, patients' rest-activity rhythm over 3 days was measured using actigraphy. The rest-activity rhythm was represented using the dichotomy index I (in-bed activity) < O (out-of-bed activity). The median I < O was used as the cutoff point, with an I < O of greater than or equal to 85.59% and less than 85.59% indicating robust and disrupted rest-activity rhythms, respectively. Data were analyzed using the Cox regression model with time-dependent repeated measurements of a covariate. RESULTS In the time-dependent multivariate Cox model, a disrupted rest-activity rhythm was independently associated with a higher risk of death than was a robust rest-activity rhythm (hazard ratio, 16.05; P = .009). CONCLUSION A time-varying rest-activity rhythm is incrementally associated with mortality in older adults with lung cancer and represents a rigorous and independent prognostic factor for their survival. IMPLICATIONS FOR PRACTICE Clinicians may need to pay more attention to the rest-activity rhythms of older adults with lung cancer during disease progression. Future studies should account for the variation in rest-activity rhythm over time.
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20
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Froy O, Garaulet M. The Circadian Clock in White and Brown Adipose Tissue: Mechanistic, Endocrine, and Clinical Aspects. Endocr Rev 2018; 39:261-273. [PMID: 29490014 PMCID: PMC6456924 DOI: 10.1210/er.2017-00193] [Citation(s) in RCA: 111] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2017] [Accepted: 02/22/2018] [Indexed: 12/19/2022]
Abstract
Obesity is a major risk factor for the development of illnesses, such as insulin resistance and hypertension, and has become a serious public health problem. Mammals have developed a circadian clock located in the hypothalamic suprachiasmatic nuclei (SCN) that responds to the environmental light-dark cycle. Clocks similar to the one located in the SCN are found in peripheral tissues, such as the kidney, liver, and adipose tissue. The circadian clock regulates metabolism and energy homeostasis in peripheral tissues by mediating activity and/or expression of key metabolic enzymes and transport systems. Knockouts or mutations in clock genes that lead to disruption of cellular rhythmicity have provided evidence to the tight link between the circadian clock and metabolism. In addition, key proteins play a dual role in regulating the core clock mechanism, as well as adipose tissue metabolism, and link circadian rhythms with lipogenesis and lipolysis. Adipose tissues are distinguished as white, brown, and beige (or brite), each with unique metabolic characteristics. Recently, the role of the circadian clock in regulating the differentiation into the different adipose tissues has been investigated. In this review, the role of clock proteins and the downstream signaling pathways in white, brown, and brite adipose tissue function and differentiation will be reviewed. In addition, chronodisruption and metabolic disorders and clinical aspects of circadian adiposity will be addressed.
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Affiliation(s)
- Oren Froy
- Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel
| | - Marta Garaulet
- Department of Physiology, University of Murcia, Murcia, Spain.,Instituto Murciano de Investigación Biosanitaria (IMIB), Campus de Ciencias de la Salud, Murcia, Spain
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21
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Walton ZE, Altman BJ, Brooks RC, Dang CV. Circadian Clock's Cancer Connections. ANNUAL REVIEW OF CANCER BIOLOGY-SERIES 2018. [DOI: 10.1146/annurev-cancerbio-030617-050216] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Zandra E. Walton
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
| | - Brian J. Altman
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
| | - Rebekah C. Brooks
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
| | - Chi V. Dang
- Ludwig Institute for Cancer Research, New York, NY 10017, USA
- The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
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22
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Zhao S, Wang Y, Guo T, Yu W, Li J, Tang Z, Yu Z, Zhao L, Zhang Y, Wang Z, Wang P, Li Y, Li F, Sun Z, Xuan Y, Tang R, Deng WG, Guo W, Gu C. YBX1 regulates tumor growth via CDC25a pathway in human lung adenocarcinoma. Oncotarget 2018; 7:82139-82157. [PMID: 27384875 PMCID: PMC5347681 DOI: 10.18632/oncotarget.10080] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2015] [Accepted: 05/28/2016] [Indexed: 12/21/2022] Open
Abstract
Y-box binding protein 1 (YBX1) is involved in the multi-tumor occurrence and development. However, the regulation of YBX1 in lung tumorigenesis and the underlying mechanisms, especially its relationship with CDC25a, was remains unclear. In this study, we analyzed the expression and clinical significance of YBX1 and CDC25a in lung adenocarcinoma and identified their roles in the regulation of lung cancer growth. The retrospective analysis of 116 patients with lung adenocarcinoma indicated that YBX1 was positively correlated with CDC25a expression. The Cox-regression analysis showed only high-ranking TNM stage and low CDC25a expression were an independent risk factor of prognosis in enrolled patients. High expression of YBX1 or CDC25a protein was also observed in lung adenocarcinoma cells compared with HLF cells. ChIP assay demonstrated the binding of endogenous YBX1 to the CDC25a promoter region. Overexpression of exogenous YBX1 up-regulated the expression of the CDC25a promoter-driven luciferase. By contrast, inhibition of YBX1 by siRNA markedly decreased the capability of YBX1 binding to CDC25a promoter in A549 and H322 cells. Inhibition of YBX1 expression also blocked cell cycle progression, suppressed cell proliferation and induced apoptosis via the CDC25a pathway in vitro. Moreover, inhibition of YBX1 by siRNA suppressed tumorigenesis in a xenograft mouse model and down-regulated the expression of YBX1, CDC25a, Ki67 and cleaved caspase 3 in the tumor tissues of mice. Collectively, these results demonstrate inhibition of YBX1 suppressed lung cancer growth partly via the CDC25a pathway and high expression of YBX1/CDC25a predicts poor prognosis in human lung adenocarcinoma.
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Affiliation(s)
- Shilei Zhao
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.,Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
| | - Yan Wang
- Department of Respiratory Medicine, The People's Hospital of Liaoning Province, Shenyang, China
| | - Tao Guo
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.,Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
| | - Wendan Yu
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
| | - Jinxiu Li
- Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
| | - Zhipeng Tang
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
| | - Zhenlong Yu
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
| | - Lei Zhao
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.,Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
| | - Yixiang Zhang
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.,Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
| | - Ziyi Wang
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.,Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
| | - Peng Wang
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.,Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
| | - Yechi Li
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.,Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
| | - Fengzhou Li
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
| | - Zhe Sun
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.,Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
| | - Yang Xuan
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
| | - Ranran Tang
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
| | - Wu-Guo Deng
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.,State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China
| | - Wei Guo
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
| | - Chundong Gu
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.,Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
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23
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Lunn RM, Blask DE, Coogan AN, Figueiro MG, Gorman MR, Hall JE, Hansen J, Nelson RJ, Panda S, Smolensky MH, Stevens RG, Turek FW, Vermeulen R, Carreón T, Caruso CC, Lawson CC, Thayer KA, Twery MJ, Ewens AD, Garner SC, Schwingl PJ, Boyd WA. Health consequences of electric lighting practices in the modern world: A report on the National Toxicology Program's workshop on shift work at night, artificial light at night, and circadian disruption. THE SCIENCE OF THE TOTAL ENVIRONMENT 2017; 607-608:1073-1084. [PMID: 28724246 PMCID: PMC5587396 DOI: 10.1016/j.scitotenv.2017.07.056] [Citation(s) in RCA: 230] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Revised: 07/07/2017] [Accepted: 07/07/2017] [Indexed: 05/24/2023]
Abstract
The invention of electric light has facilitated a society in which people work, sleep, eat, and play at all hours of the 24-hour day. Although electric light clearly has benefited humankind, exposures to electric light, especially light at night (LAN), may disrupt sleep and biological processes controlled by endogenous circadian clocks, potentially resulting in adverse health outcomes. Many of the studies evaluating adverse health effects have been conducted among night- and rotating-shift workers, because this scenario gives rise to significant exposure to LAN. Because of the complexity of this topic, the National Toxicology Program convened an expert panel at a public workshop entitled "Shift Work at Night, Artificial Light at Night, and Circadian Disruption" to obtain input on conducting literature-based health hazard assessments and to identify data gaps and research needs. The Panel suggested describing light both as a direct effector of endogenous circadian clocks and rhythms and as an enabler of additional activities or behaviors that may lead to circadian disruption, such as night-shift work and atypical and inconsistent sleep-wake patterns that can lead to social jet lag. Future studies should more comprehensively characterize and measure the relevant light-related exposures and link these exposures to both time-independent biomarkers of circadian disruption and biomarkers of adverse health outcomes. This information should lead to improvements in human epidemiological and animal or in vitro models, more rigorous health hazard assessments, and intervention strategies to minimize the occurrence of adverse health outcomes due to these exposures.
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Affiliation(s)
- Ruth M Lunn
- Office of the Report on Carcinogens, Division of the National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, United States
| | - David E Blask
- Department of Structural and Cellular Biology, Laboratory of Chrono-Neuroendocrine Oncology, Tulane University School of Medicine, New Orleans, LA, United States
| | - Andrew N Coogan
- Maynooth University Department of Psychology, National University of Ireland, Maynooth, County Kildare, Ireland
| | - Mariana G Figueiro
- Light and Health Program, Lighting Research Center, Rensselaer Polytechnic Institute, Troy, NY, United States
| | - Michael R Gorman
- Department of Psychology and Center for Circadian Biology, University of California, San Diego, CA, United States
| | - Janet E Hall
- Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States
| | - Johnni Hansen
- Danish Cancer Society Research Centre, Copenhagen, Denmark
| | - Randy J Nelson
- Department of Neuroscience, Neuroscience Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | | | - Michael H Smolensky
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, United States; Sleep Medicine, The University of Texas-Houston McGovern School of Medicine, Houston, TX, United States
| | - Richard G Stevens
- School of Medicine, University of Connecticut, Farmington, CT, United States
| | - Fred W Turek
- Center for Sleep & Circadian Biology, Northwestern University, Evanston, IL, United States
| | - Roel Vermeulen
- Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands
| | - Tania Carreón
- National Institute for Occupational Safety and Health (NIOSH), Centers for Disease Control and Prevention, Cincinnati, OH, United States
| | - Claire C Caruso
- National Institute for Occupational Safety and Health (NIOSH), Centers for Disease Control and Prevention, Cincinnati, OH, United States
| | - Christina C Lawson
- National Institute for Occupational Safety and Health (NIOSH), Centers for Disease Control and Prevention, Cincinnati, OH, United States
| | - Kristina A Thayer
- Office of Health Assessment and Translation, Division of the National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, United States
| | - Michael J Twery
- National Center on Sleep Disorders Research, Division of Lung Diseases, National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD, United States
| | - Andrew D Ewens
- Contractor in support of the NIEHS Report on Carcinogens, Integrated Laboratory Systems (ILS), Durham, NC, United States
| | - Sanford C Garner
- Contractor in support of the NIEHS Report on Carcinogens, Integrated Laboratory Systems (ILS), Durham, NC, United States
| | - Pamela J Schwingl
- Contractor in support of the NIEHS Report on Carcinogens, Integrated Laboratory Systems (ILS), Durham, NC, United States
| | - Windy A Boyd
- Office of Health Assessment and Translation, Division of the National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, United States.
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Chang WP, Smith R, Lin CC. Age and rest–activity rhythm as predictors of survival in patients with newly diagnosed lung cancer. Chronobiol Int 2017; 35:188-197. [DOI: 10.1080/07420528.2017.1391278] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Affiliation(s)
- Wen-Pei Chang
- Department of Nursing, Taipei Medical University-Shuang Ho Hospital, Ministry of Health and Welfare, New Taipei City, Taiwan
- School of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan
| | - Robert Smith
- School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Chia-Chin Lin
- School of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan
- School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
- FAAN, Alice Ho Miu Ling Nethersole Charity Foundation Professor in Nursing, Pokfulam, Hong Kong
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Hunter CM, Figueiro MG. Measuring Light at Night and Melatonin Levels in Shift Workers: A Review of the Literature. Biol Res Nurs 2017; 19:365-374. [PMID: 28627309 PMCID: PMC5862149 DOI: 10.1177/1099800417714069] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Shift work, especially that involving rotating and night shifts, is associated with an increased risk of diseases, including cancer. Attempts to explain the association between shift work and cancer in particular have focused on the processes of melatonin production and suppression. One hypothesis postulates that exposure to light at night (LAN) suppresses melatonin, whose production is known to slow the development of cancerous cells, while another proposes that circadian disruption associated with shift work, and not just LAN, increases health risks. This review focuses on six studies that employed quantitative measurement of LAN and melatonin levels to assess cancer risks in shift workers. These studies were identified via searching the PubMed database for peer-reviewed, English-language articles examining the links between shift work, LAN, and disease using the terms light at night, circadian disruption, health, risk, cancer, shift work, or rotating shift. While the results indicate a growing consensus on the relationship between disease risks (particularly cancer) and circadian disruption associated with shift work, the establishment of a direct link between LAN and disease has been impeded by contradictory studies and a lack of consistent, quantitative methods for measuring LAN in the research to date. Better protocols for assessing personal LAN exposure are required, particularly those employing calibrated devices that measure and sample exposure to workplace light conditions, to accurately assess LAN's effects on the circadian system and disease. Other methodologies, such as measuring circadian disruption and melatonin levels in the field, may also help to resolve discrepancies in the findings.
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Affiliation(s)
- Claudia M. Hunter
- Lighting Research Center, Rensselaer Polytechnic Institute, Troy, NY, USA
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Abstract
PURPOSE OF REVIEW This study aims to discuss possible reasons why research to date has not forged direct links between light at night, acute melatonin suppression or circadian disruption, and risks for disease. RECENT FINDINGS Data suggest that irregular light-dark patterns or light exposures at the wrong circadian time can lead to circadian disruption and disease risks. However, there remains an urgent need to: (1) specify light stimulus in terms of circadian rather than visual response; (2) when translating research from animals to humans, consider species-specific spectral and absolute sensitivities to light; (3) relate the characteristics of photometric measurement of light at night to the operational characteristics of the circadian system; and (4) examine how humans may be experiencing too little daytime light, not just too much light at night. SUMMARY To understand the health effects of light-induced circadian disruption, we need to measure and control light stimulus during the day and at night.
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Affiliation(s)
- Mariana G Figueiro
- Lighting Research Center, Rensselaer Polytechnic Institute, Troy, NY, 12180,
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Abstract
Sleep plays a vital role in brain function and systemic physiology across many body systems. Problems with sleep are widely prevalent and include deficits in quantity and quality of sleep; sleep problems that impact the continuity of sleep are collectively referred to as sleep disruptions. Numerous factors contribute to sleep disruption, ranging from lifestyle and environmental factors to sleep disorders and other medical conditions. Sleep disruptions have substantial adverse short- and long-term health consequences. A literature search was conducted to provide a nonsystematic review of these health consequences (this review was designed to be nonsystematic to better focus on the topics of interest due to the myriad parameters affected by sleep). Sleep disruption is associated with increased activity of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, metabolic effects, changes in circadian rhythms, and proinflammatory responses. In otherwise healthy adults, short-term consequences of sleep disruption include increased stress responsivity, somatic pain, reduced quality of life, emotional distress and mood disorders, and cognitive, memory, and performance deficits. For adolescents, psychosocial health, school performance, and risk-taking behaviors are impacted by sleep disruption. Behavioral problems and cognitive functioning are associated with sleep disruption in children. Long-term consequences of sleep disruption in otherwise healthy individuals include hypertension, dyslipidemia, cardiovascular disease, weight-related issues, metabolic syndrome, type 2 diabetes mellitus, and colorectal cancer. All-cause mortality is also increased in men with sleep disturbances. For those with underlying medical conditions, sleep disruption may diminish the health-related quality of life of children and adolescents and may worsen the severity of common gastrointestinal disorders. As a result of the potential consequences of sleep disruption, health care professionals should be cognizant of how managing underlying medical conditions may help to optimize sleep continuity and consider prescribing interventions that minimize sleep disruption.
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Affiliation(s)
- Goran Medic
- Market Access, Horizon Pharma B.V., Utrecht
- Unit of Pharmacoepidemiology & Pharmacoeconomics, Department of Pharmacy, University of Groningen, Groningen, The Netherlands
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Kiehn JT, Tsang AH, Heyde I, Leinweber B, Kolbe I, Leliavski A, Oster H. Circadian Rhythms in Adipose Tissue Physiology. Compr Physiol 2017; 7:383-427. [PMID: 28333377 DOI: 10.1002/cphy.c160017] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The different types of adipose tissues fulfill a wide range of biological functions-from energy storage to hormone secretion and thermogenesis-many of which show pronounced variations over the course of the day. Such 24-h rhythms in physiology and behavior are coordinated by endogenous circadian clocks found in all tissues and cells, including adipocytes. At the molecular level, these clocks are based on interlocked transcriptional-translational feedback loops comprised of a set of clock genes/proteins. Tissue-specific clock-controlled transcriptional programs translate time-of-day information into physiologically relevant signals. In adipose tissues, clock gene control has been documented for adipocyte proliferation and differentiation, lipid metabolism as well as endocrine function and other adipose oscillations are under control of systemic signals tied to endocrine, neuronal, or behavioral rhythms. Circadian rhythm disruption, for example, by night shift work or through genetic alterations, is associated with changes in adipocyte metabolism and hormone secretion. At the same time, adipose metabolic state feeds back to central and peripheral clocks, adjusting behavioral and physiological rhythms. In this overview article, we summarize our current knowledge about the crosstalk between circadian clocks and energy metabolism with a focus on adipose physiology. © 2017 American Physiological Society. Compr Physiol 7:383-427, 2017.
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Affiliation(s)
- Jana-Thabea Kiehn
- Chronophysiology Group, Medical Department I, University of Lübeck, Lübeck, Germany
| | - Anthony H Tsang
- Chronophysiology Group, Medical Department I, University of Lübeck, Lübeck, Germany
| | - Isabel Heyde
- Chronophysiology Group, Medical Department I, University of Lübeck, Lübeck, Germany
| | - Brinja Leinweber
- Chronophysiology Group, Medical Department I, University of Lübeck, Lübeck, Germany
| | - Isa Kolbe
- Chronophysiology Group, Medical Department I, University of Lübeck, Lübeck, Germany
| | - Alexei Leliavski
- Institute of Systemic Inflammation Research, University of Lübeck, Lübeck, Germany
| | - Henrik Oster
- Chronophysiology Group, Medical Department I, University of Lübeck, Lübeck, Germany
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Liu F, Chang HC. Physiological links of circadian clock and biological clock of aging. Protein Cell 2017; 8:477-488. [PMID: 28108951 PMCID: PMC5498335 DOI: 10.1007/s13238-016-0366-2] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Accepted: 12/20/2016] [Indexed: 12/20/2022] Open
Abstract
Circadian rhythms orchestrate biochemical and physiological processes in living organisms to respond the day/night cycle. In mammals, nearly all cells hold self-sustained circadian clocks meanwhile couple the intrinsic rhythms to systemic changes in a hierarchical manner. The suprachiasmatic nucleus (SCN) of the hypothalamus functions as the master pacemaker to initiate daily synchronization according to the photoperiod, in turn determines the phase of peripheral cellular clocks through a variety of signaling relays, including endocrine rhythms and metabolic cycles. With aging, circadian desynchrony occurs at the expense of peripheral metabolic pathologies and central neurodegenerative disorders with sleep symptoms, and genetic ablation of circadian genes in model organisms resembled the aging-related features. Notably, a number of studies have linked longevity nutrient sensing pathways in modulating circadian clocks. Therapeutic strategies that bridge the nutrient sensing pathways and circadian clock might be rational designs to defy aging.
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Affiliation(s)
- Fang Liu
- Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.,University of Chinese Academy of Sciences, Shanghai, 200031, China
| | - Hung-Chun Chang
- Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
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Ball LJ, Palesh O, Kriegsfeld LJ. The Pathophysiologic Role of Disrupted Circadian and Neuroendocrine Rhythms in Breast Carcinogenesis. Endocr Rev 2016; 37:450-466. [PMID: 27712099 PMCID: PMC5045494 DOI: 10.1210/er.2015-1133] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Most physiological processes in the brain and body exhibit daily (circadian) rhythms coordinated by an endogenous master clock located in the suprachiasmatic nucleus of the hypothalamus that are essential for normal health and functioning. Exposure to sunlight during the day and darkness at night optimally entrains biological rhythms to promote homeostasis and human health. Unfortunately, a major consequence of the modern lifestyle is increased exposure to sun-free environments during the day and artificial lighting at night. Additionally, behavioral disruptions to circadian rhythms (ie, repeated transmeridian flights, night or rotating shift work, or sleep disturbances) have a profound influence on health and have been linked to a number of pathological conditions, including endocrine-dependent cancers. Specifically, night shift work has been identified as a significant risk factor for breast cancer in industrialized countries. Several mechanisms have been proposed by which shift work-induced circadian disruptions promote cancer. In this review, we examine the importance of the brain-body link through which circadian disruptions contribute to endocrine-dependent diseases, including breast carcinogenesis, by negatively impacting neuroendocrine and neuroimmune cells, and we consider preventive measures directed at maximizing circadian health.
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Affiliation(s)
- Lonnele J Ball
- Department of Psychology (L.J.B., L.J.K.) and The Helen Wills Neuroscience Institute (L.J.K.), University of California, Berkeley, California 94720; and Department of Psychiatry and Behavioral Sciences (O.P.), Stanford University School of Medicine, Stanford, California 94305
| | - Oxana Palesh
- Department of Psychology (L.J.B., L.J.K.) and The Helen Wills Neuroscience Institute (L.J.K.), University of California, Berkeley, California 94720; and Department of Psychiatry and Behavioral Sciences (O.P.), Stanford University School of Medicine, Stanford, California 94305
| | - Lance J Kriegsfeld
- Department of Psychology (L.J.B., L.J.K.) and The Helen Wills Neuroscience Institute (L.J.K.), University of California, Berkeley, California 94720; and Department of Psychiatry and Behavioral Sciences (O.P.), Stanford University School of Medicine, Stanford, California 94305
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Prendergast BJ, Cable EJ, Stevenson TJ, Onishi KG, Zucker I, Kay LM. Circadian Disruption Alters the Effects of Lipopolysaccharide Treatment on Circadian and Ultradian Locomotor Activity and Body Temperature Rhythms of Female Siberian Hamsters. J Biol Rhythms 2016; 30:543-56. [PMID: 26566981 DOI: 10.1177/0748730415609450] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The effect of circadian rhythm (CR) disruption on immune function depends on the method by which CRs are disrupted. Behavioral and thermoregulatory responses induced by lipopolysaccharide (LPS) treatment were assessed in female Siberian hamsters in which circadian locomotor activity (LMA) rhythms were eliminated by exposure to a disruptive phase-shifting protocol (DPS) that sustains arrhythmicity even when hamsters are housed in a light-dark cycle. This noninvasive treatment avoids genome manipulations and neurological damage associated with other models of CR disruption. Circadian rhythmic (RHYTH) and arrhythmic (ARR) hamsters housed in a 16L:8D photocycle were injected with bacterial LPS near the onset of the light (zeitgeber time 1; ZT1) or dark (ZT16) phase. LPS injections at ZT16 and ZT1 elicited febrile responses in both RHYTH and ARR hamsters, but the effect was attenuated in the arrhythmic females. In ZT16, LPS inhibited LMA in the dark phase immediately after injection but not on subsequent nights in both chronotypes; in contrast, LPS at ZT1 elicited more enduring (~4 day) locomotor hypoactivity in ARR than in RHYTH hamsters. Power and period of dark-phase ultradian rhythms (URs) in LMA and Tb were markedly altered by LPS treatment, as was the power in the circadian waveform. Disrupted circadian rhythms in this model system attenuated responses to LPS in a trait- and ZT-specific manner; changes in UR period and power are novel components of the acute-phase response to infection that may affect energy conservation.
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Affiliation(s)
- Brian J Prendergast
- Department of Psychology, University of Chicago, Chicago, Illinois Committee on Neurobiology, University of Chicago, Chicago, Illinois
| | - Erin J Cable
- Department of Psychology, University of Chicago, Chicago, Illinois
| | | | - Kenneth G Onishi
- Department of Psychology, University of Chicago, Chicago, Illinois
| | - Irving Zucker
- Department of Psychology, University of California, Berkeley, California Department of Integrative Biology, University of California, Berkeley, California
| | - Leslie M Kay
- Department of Psychology, University of Chicago, Chicago, Illinois Committee on Neurobiology, University of Chicago, Chicago, Illinois
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A systematic review and meta-analysis of randomized controlled trials of cognitive behavior therapy for insomnia (CBT-I) in cancer survivors. Sleep Med Rev 2016; 27:20-8. [DOI: 10.1016/j.smrv.2015.07.001] [Citation(s) in RCA: 197] [Impact Index Per Article: 21.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2015] [Revised: 06/30/2015] [Accepted: 07/13/2015] [Indexed: 11/20/2022]
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Pérez S, Murias L, Fernández-Plaza C, Díaz I, González C, Otero J, Díaz E. Evidence for clock genes circadian rhythms in human full-term placenta. Syst Biol Reprod Med 2015; 61:360-6. [PMID: 26247999 DOI: 10.3109/19396368.2015.1069420] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Biological rhythms are driven by endogenous biological clocks; in mammals, the master clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. This master pacemaker can synchronize other peripheral oscillators in several tissues such as some involved in endocrine or reproductive functions. The presence of an endogenous placental clock has received little attention. In fact, there are no studies in human full-term placentas. To test the existence of an endogenous pacemaker in this tissue we have studied the expression of circadian locomoter output cycles kaput (Clock), brain and muscle arnt-like (Bmal)1, period (Per)2, and cryptochrome (Cry)1 mRNAs at 00, 04, 08, 12, 16, and 20 hours by qPCR. The four clock genes studied are expressed in full-term human placenta. The results obtained allow us to suggest that a peripheral oscillator exists in human placenta. Data were analyzed using Fourier series where only the Clock and Bmal1 expression shows a circadian rhythm.
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Affiliation(s)
- Silvia Pérez
- a Transplants, Cell Therapy and Regenerative Medicine Unit, Central University Hospital of Asturias (HUCA) , Oviedo , Spain
| | - Lucía Murias
- b Area of Physiology, Department of Functional Biology, University of Oviedo , Oviedo , Spain
| | | | - Irene Díaz
- d Area of Computation Science and Artificial Intelligence, Department of Computer Science, University of Oviedo , Oviedo , Spain
| | - Celestino González
- b Area of Physiology, Department of Functional Biology, University of Oviedo , Oviedo , Spain
| | - Jesús Otero
- a Transplants, Cell Therapy and Regenerative Medicine Unit, Central University Hospital of Asturias (HUCA) , Oviedo , Spain
| | - Elena Díaz
- b Area of Physiology, Department of Functional Biology, University of Oviedo , Oviedo , Spain
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Guerrero-Vargas NN, Guzmán-Ruiz M, Fuentes R, García J, Salgado-Delgado R, Basualdo MDC, Escobar C, Markus RP, Buijs RM. Shift Work in Rats Results in Increased Inflammatory Response after Lipopolysaccharide Administration: A Role for Food Consumption. J Biol Rhythms 2015; 30:318-30. [PMID: 26017928 DOI: 10.1177/0748730415586482] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
The suprachiasmatic nucleus (SCN) drives circadian rhythms in behavioral and physiological variables, including the inflammatory response. Shift work is known to disturb circadian rhythms and is associated with increased susceptibility to develop disease. In rodents, circadian disruption due to shifted light schedules (jet lag) induced increased innate immune responses. To gain more insight into the influence of circadian disruption on the immune response, we characterized the inflammatory response in a model of rodent shift work and demonstrated that circadian disruption affected the inflammatory response to lipopolysaccharide (LPS) both in vivo and in vitro. Since food consumption is a main disturbing element in the shift work schedule, we also evaluated the inflammatory response to LPS in a group of rats that had no access to food during their working hours. Our results demonstrated that the shift work schedule decreased basal TNF-α levels in the liver but not in the circulation. Despite this, we observed that shift work induced increased cytokine response after LPS stimulation in comparison to control rats. Also, Kupffer cells (liver macrophages) isolated from shift work rats produced more TNF-α in response to in vitro LPS stimulation, suggesting important effects of circadian desynchronization on the functionality of this cell type. Importantly, the effects of shift work on the inflammatory response to LPS were prevented when food was not available during the working schedule. Together, these results show that dissociating behavior and food intake from the synchronizing drive of the SCN severely disturbs the immune response.
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Affiliation(s)
- Natalí N Guerrero-Vargas
- Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México
| | - Mara Guzmán-Ruiz
- Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México
| | - Rebeca Fuentes
- Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México
| | - Joselyn García
- Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México
| | | | - María del Carmen Basualdo
- Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México
| | - Carolina Escobar
- Departamento de Anatomía, Facultad de Medicina, Universidad Nacional Autónoma de México, México
| | - Regina P Markus
- Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo (USP), São Paulo, Brazil
| | - Ruud M Buijs
- Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México
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Sallam H, El-Serafi AT, Filipski E, Terelius Y, Lévi F, Hassan M. The effect of circadian rhythm on pharmacokinetics and metabolism of the Cdk inhibitor, roscovitine, in tumor mice model. Chronobiol Int 2015; 32:608-14. [PMID: 25938685 DOI: 10.3109/07420528.2015.1022782] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Roscovitine is a selective Cdk-inhibitor that is under investigation in phase II clinical trials under several conditions, including chemotherapy. Tumor growth inhibition has been previously shown to be affected by the dosing time of roscovitine in a Glasgow osteosarcoma xenograft mouse model. In the current study, we examined the effect of dose timing on the pharmacokinetics, biodistribution and metabolism of this drug in different organs in B6D2F1 mice. The drug was orally administered at resting (ZT3) or activity time of the mice (ZT19) at a dose of 300 mg/kg. Plasma and organs were removed at serial time points (10, 20 and 30 min; 1, 2, 4, 6, 8, 12 and 24 h) after the administration. Roscovitine and its carboxylic metabolite concentrations were analyzed using HPLC-UV, and pharmacokinetic parameters were calculated in different organs. We found that systemic exposure to roscovitine was 38% higher when dosing at ZT3, and elimination half-life was double compared to when dosing at ZT19. Higher organ concentrations expressed as (organ/plasma) ratio were observed when dosing at ZT3 in the kidney (180%), adipose tissue (188%), testis (132%) and lungs (112%), while the liver exposure to roscovitine was 120% higher after dosing at ZT19. The metabolic ratio was approximately 23% higher at ZT19, while the intrinsic clearance (CLint) was approximately 67% higher at ZT19, indicating faster and more efficient metabolism. These differences may be caused by circadian differences in the absorption, distribution, metabolism and excretion processes governing roscovitine disposition in the mice. In this article, we describe for the first time the chronobiodistribution of roscovitine in the mouse and the contribution of the dosing time to the variability of its metabolism. Our results may help in designing better dosing schedules of roscovitine in clinical trials.
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Affiliation(s)
- Hatem Sallam
- Experimental Cancer Medicine, Department of Laboratory Medicine, Karolinska Institutet , Stockholm , Sweden
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Huang C, Madsen MT, Gögenur I. Circadian rhythms measured by actigraphy during oncological treatments: a systematic review. BIOL RHYTHM RES 2015. [DOI: 10.1080/09291016.2015.1004840] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Koutras A, Sakellakis M, Makatsoris T, Psachoulia C, Kardari M, Nikolakopoulos A, Gogos C, Kalofonos HP. Seasonal variability in the incidence of carcinomatous meningitis. J Neurosurg 2015; 122:543-6. [PMID: 25574572 DOI: 10.3171/2014.11.jns14174] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECT The aim of the study was to investigate whether there are seasonal differences in the occurrence of carcinomatous meningitis (CM), with a greater prevalence of the disease in months with higher temperatures. METHODS The authors searched the records of all patients with a diagnosis of CM from 1998 until 2013 at the University Hospital of Patras, Greece. The date of hospitalization was extracted for each patient. The cases were divided into 2 categories depending on the time of CM diagnosis. Based on the official data regarding the annual temperature distribution in this region, the authors divided the patients into 2 groups. The first group consisted of cases diagnosed with CM from October 15 to April 15 (cold climate and shorter daytime duration), whereas the second group comprised patients diagnosed between April 15 and October 15 (warm climate and longer daytime duration). RESULTS Overall, 44 confirmed cases of CM were found. The most common type of malignancy associated with the development of CM was breast cancer (27 patients), while the second most common tumor was lung carcinoma (11 patients). The median interval between the time of initial cancer diagnosis and CM was 4.5 years. Thirty-one patients were diagnosed with CM during the period between April 15 and October 15, while the remaining 13 patients developed CM between October 15 and April 15, a significant difference (p = 0.01). CONCLUSIONS Significantly more patients developed CM during the warm season of the year. To the authors' knowledge, this is the first study to provide evidence for the potential seasonal variability in CM incidence. However, these results should be validated prospectively in larger cohorts.
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Magnone MC, Langmesser S, Bezdek AC, Tallone T, Rusconi S, Albrecht U. The Mammalian circadian clock gene per2 modulates cell death in response to oxidative stress. Front Neurol 2015; 5:289. [PMID: 25628599 PMCID: PMC4292776 DOI: 10.3389/fneur.2014.00289] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Accepted: 12/19/2014] [Indexed: 11/23/2022] Open
Abstract
Living in the earth’s oxygenated environment forced organisms to develop strategies to cope with the damaging effects of molecular oxygen known as reactive oxygen species (ROS). Here, we show that Per2, a molecular component of the mammalian circadian clock, is involved in regulating a cell’s response to oxidative stress. Mouse embryonic fibroblasts (MEFs) containing a mutation in the Per2 gene are more resistant to cytotoxic effects mediated by ROS than wild-type cells, which is paralleled by an altered regulation of bcl-2 expression in Per2 mutant MEFs. The elevated survival rate and alteration of NADH/NAD+ ratio in the mutant cells is reversed by introduction of the wild-type Per2 gene. Interestingly, clock synchronized cells display a time dependent sensitivity to paraquat, a ROS inducing agent. Our observations indicate that the circadian clock is involved in regulating the fate of a cell to survive or to die in response to oxidative stress, which could have implications for cancer development and the aging process.
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Affiliation(s)
- Maria Chiara Magnone
- Department of Biology, Division of Biochemistry, University of Fribourg , Fribourg , Switzerland
| | - Sonja Langmesser
- Department of Biology, Division of Biochemistry, University of Fribourg , Fribourg , Switzerland
| | - April Candice Bezdek
- Department of Biology, Division of Biochemistry, University of Fribourg , Fribourg , Switzerland
| | - Tiziano Tallone
- Department of Biology, Division of Biochemistry, University of Fribourg , Fribourg , Switzerland
| | - Sandro Rusconi
- Department of Biology, Division of Biochemistry, University of Fribourg , Fribourg , Switzerland
| | - Urs Albrecht
- Department of Biology, Division of Biochemistry, University of Fribourg , Fribourg , Switzerland
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Matthews EE, Berger AM, Schmiege SJ, Cook PF, McCarthy MS, Moore CM, Aloia MS. Cognitive behavioral therapy for insomnia outcomes in women after primary breast cancer treatment: a randomized, controlled trial. Oncol Nurs Forum 2014; 41:241-53. [PMID: 24650832 DOI: 10.1188/14.onf.41-03ap] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
PURPOSE/OBJECTIVES To examine the effect of cognitive-behavioral therapy for insomnia (CBTI) on sleep improvement, daytime symptoms, and quality of life (QOL) in breast cancer survivors (BCSs) after cancer treatment. DESIGN A prospective, longitudinal, randomized, controlled trial. SETTING Oncology clinics, breast cancer support groups, and communities in Colorado. SAMPLE 56 middle-aged BCSs with chronic insomnia. METHODS Women were randomly assigned to CBTI or behavioral placebo treatment (BPT) and completed measures of sleep, QOL, functioning, fatigue, and mood at baseline, postintervention, and at three- and six-month follow-ups. MAIN RESEARCH VARIABLES Sleep outcomes (e.g., sleep efficiency, sleep latency, total sleep time, wake after sleep onset, number of nightly awakenings); secondary variables included sleep medication use, insomnia severity, QOL, physical function, cognitive function, fatigue, depression, anxiety, and sleep attitudes or knowledge. FINDINGS Sleep efficiency and latency improved more in the CBTI group than the BPT group; this difference was maintained during follow-up. Women in the CBTI group had less subjective insomnia, greater improvements in physical and cognitive functioning, positive sleep attitudes, and increased sleep hygiene knowledge. No group differences in improvement were noted relative to QOL, fatigue, or mood. CONCLUSIONS Nurse-delivered CBTI appears to be beneficial for BCSs' sleep latency/efficiency, insomnia severity, functioning, sleep knowledge, and attitudes more than active placebo, with sustained benefit over time. IMPLICATIONS FOR NURSING Oncology nurses are in a unique position to identify insomnia in cancer survivors. When sleep disturbances become chronic, nurses need to make recommendations and referrals.
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Affiliation(s)
| | - Ann M Berger
- College of Nursing, Omaha Division, University of Nebraska Medical Center
| | - Sarah J Schmiege
- Department of Biostatistics and Informatics, School of Public Health
| | - Paul F Cook
- College of Nursing, University of Colorado in Denver
| | | | - Camille M Moore
- Department of Biostatistics and Informatics in the School of Public Health, University of Colorado in Denver
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40
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Baumann A, Feilhauer K, Bischoff SC, Froy O, Lorentz A. IgE-dependent activation of human mast cells and fMLP-mediated activation of human eosinophils is controlled by the circadian clock. Mol Immunol 2014; 64:76-81. [PMID: 25466613 DOI: 10.1016/j.molimm.2014.10.026] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2014] [Revised: 09/29/2014] [Accepted: 10/29/2014] [Indexed: 12/20/2022]
Abstract
Symptoms of allergic attacks frequently exhibit diurnal variations. Accordingly, we could recently demonstrate that mast cells and eosinophils - known as major effector cells of allergic diseases - showed an intact circadian clock. Here, we analyzed the role of the circadian clock in the functionality of mast cells and eosinophils. Human intestinal mast cells (hiMC) were isolated from intestinal mucosa; human eosinophils were isolated from peripheral blood. HiMC and eosinophils were synchronized by dexamethasone before stimulation every 4h around the circadian cycle by FcɛRI crosslinking or fMLP, respectively. Signaling molecule activation was examined using Western blot, mRNA expression by real-time RT-PCR, and mediator release by multiplex analysis. CXCL8 and CCL2 were expressed and released in a circadian manner by both hiMC and eosinophils in response to activation. Moreover, phosphorylation of ERK1/2, known to be involved in activation of hiMC and eosinophils, showed circadian rhythms in both cell types. Interestingly, all clock genes hPer1, hPer2, hCry1, hBmal1, and hClock were expressed in a similar circadian pattern in activated and unstimulated cells indicating that the local clock controls hiMC and eosinophils and subsequently allergic reactions but not vice versa.
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Affiliation(s)
- Anja Baumann
- Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany
| | | | - Stephan C Bischoff
- Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany
| | - Oren Froy
- Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel
| | - Axel Lorentz
- Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
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41
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Kent BA. Synchronizing an aging brain: can entraining circadian clocks by food slow Alzheimer's disease? Front Aging Neurosci 2014; 6:234. [PMID: 25225484 PMCID: PMC4150207 DOI: 10.3389/fnagi.2014.00234] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2014] [Accepted: 08/15/2014] [Indexed: 01/21/2023] Open
Abstract
Alzheimer's disease (AD) is a global epidemic. Unfortunately, we are still without effective treatments or a cure for this disease, which is having devastating consequences for patients, their families, and societies around the world. Until effective treatments are developed, promoting overall health may hold potential for delaying the onset or preventing neurodegenerative diseases such as AD. In particular, chronobiological concepts may provide a useful framework for identifying the earliest signs of age-related disease as well as inexpensive and noninvasive methods for promoting health. It is well reported that AD is associated with disrupted circadian functioning to a greater extent than normal aging. However, it is unclear if the central circadian clock (i.e., the suprachiasmatic nucleus) is dysfunctioning, or whether the synchrony between the central and peripheral clocks that control behavior and metabolic processes are becoming uncoupled. Desynchrony of rhythms can negatively affect health, increasing morbidity and mortality in both animal models and humans. If the uncoupling of rhythms is contributing to AD progression or exacerbating symptoms, then it may be possible to draw from the food-entrainment literature to identify mechanisms for re-synchronizing rhythms to improve overall health and reduce the severity of symptoms. The following review will briefly summarize the circadian system, its potential role in AD, and propose using a feeding-related neuropeptide, such as ghrelin, to synchronize uncoupled rhythms. Synchronizing rhythms may be an inexpensive way to promote healthy aging and delay the onset of neurodegenerative disease such as AD.
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Affiliation(s)
- Brianne A. Kent
- Department of Psychology, University of CambridgeCambridge, UK
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42
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Chang WP, Lin CC. Correlation between rest-activity rhythm and survival in cancer patients experiencing pain. Chronobiol Int 2014; 31:926-34. [PMID: 24984030 DOI: 10.3109/07420528.2014.931412] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
The purpose of this study was to investigate the influence of rest-activity rhythm on the survival of cancer patients. This study collected data related to cancer patients experiencing pain who had been hospitalized for treatment between August 2006 and October 2007. Data included the Karnofsky Performance Status Index as a representation of functional condition as well as the Brief Pain Inventory and the Pittsburgh Sleep Quality Index. Actigraphic methods were used to record the dichotomy index (I < O) of patients' rest-activity rhythms over periods of three consecutive days. Patients were closely followed until 31 July 2013. Results were analyzed using Kaplan-Meier survival analysis, log-rank testing and Cox proportional hazards regression analysis to evaluate whether alterations in the rest-activity rhythm affected the survival rate of the patients. Of the 68 hospitalized cancer patients experiencing pain at the time of admission, 51 subsequently died within the study period. A significant difference was observed in the survival curves between the regular I < O group and the disrupted I < O group (log rank = 7.942, p = 0.005). A multivariable proportional hazard model was used for analysis of overall survival, revealing that the risk of death within the study period among patients with disrupted I < O was 4.59 times higher than that of patients with regular I < O (95% CI: 1.92-10.96, p = 0.001). Among patients with poor performance status, the risk of death among patients with disrupted I < O was 8.68 times higher than that of patients with regular I < O (95% CI: 2.50-30.09, p = 0.001). Disruptions in rest-activity rhythm were negatively correlated with the survival of hospitalized cancer patients experiencing pain. Effects were particularly pronounced in cancer patients with poor performance status.
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Affiliation(s)
- Wen-Pei Chang
- School of Nursing, College of Nursing, Graduate Institute of Nursing, Taipei Medical University , Taipei , Taiwan and
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Pluquet O, Dejeans N, Chevet E. Watching the clock: endoplasmic reticulum-mediated control of circadian rhythms in cancer. Ann Med 2014; 46:233-43. [PMID: 24491143 DOI: 10.3109/07853890.2013.874664] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
In the past 20 years both the circadian clock and endoplasmic reticulum (ER) stress signaling have emerged as major players in oncogenesis and cancer development. Although several lines of evidence have established functional links between these two molecular pathways, their interconnection and the subsequent functional implications in cancer development remain to be fully characterized. Herein, we provide an extensive review of the literature depicting the molecular connectivity linking ER stress signaling and the circadian clock and elaborate on the potential use of these functional interactions in cancer therapeutics.
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Affiliation(s)
- Olivier Pluquet
- Institut de Biologie de Lille, CNRS UMR8161/Universités Lille 1 et Lille 2/Institut Pasteur de Lille , 1, rue du Pr. Calmette, BP 447, 59021 Lille , France
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Ali T, Choe J, Awab A, Wagener TL, Orr WC. Sleep, immunity and inflammation in gastrointestinal disorders. World J Gastroenterol 2013; 19:9231-9239. [PMID: 24409051 PMCID: PMC3882397 DOI: 10.3748/wjg.v19.i48.9231] [Citation(s) in RCA: 108] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2013] [Revised: 09/11/2013] [Accepted: 09/29/2013] [Indexed: 02/06/2023] Open
Abstract
Sleep disorders have become a global issue, and discovering their causes and consequences are the focus of many research endeavors. An estimated 70 million Americans suffer from some form of sleep disorder. Certain sleep disorders have been shown to cause neurocognitive impairment such as decreased cognitive ability, slower response times and performance detriments. Recent research suggests that individuals with sleep abnormalities are also at greater risk of serious adverse health, economic consequences, and most importantly increased all-cause mortality. Several research studies support the associations among sleep, immune function and inflammation. Here, we review the current research linking sleep, immune function, and gastrointestinal diseases and discuss the interdependent relationship between sleep and these gastrointestinal disorders. Different physiologic processes including immune system and inflammatory cytokines help regulate the sleep. The inflammatory cytokines such as tumor necrosis factor, interleukin-1 (IL-1), and IL-6 have been shown to be a significant contributor of sleep disturbances. On the other hand, sleep disturbances such as sleep deprivation have been shown to up regulate these inflammatory cytokines. Alterations in these cytokine levels have been demonstrated in certain gastrointestinal diseases such as inflammatory bowel disease, gastro-esophageal reflux, liver disorders and colorectal cancer. In turn, abnormal sleep brought on by these diseases is shown to contribute to the severity of these same gastrointestinal diseases. Knowledge of these relationships will allow gastroenterologists a great opportunity to enhance the care of their patients.
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45
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Circadian aspects of energy metabolism and aging. Ageing Res Rev 2013; 12:931-40. [PMID: 24075855 DOI: 10.1016/j.arr.2013.09.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2013] [Revised: 09/10/2013] [Accepted: 09/17/2013] [Indexed: 11/24/2022]
Abstract
Life span extension has been a goal of research for several decades. Resetting circadian rhythms leads to well being and increased life span, while clock disruption is associated with increased morbidity accelerated aging. Increased longevity and improved health can be achieved by different feeding regimens that reset circadian rhythms and may lead to better synchrony in metabolism and physiology. This review focuses on the circadian aspects of energy metabolism and their relationship with aging in mammals.
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46
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Prendergast BJ, Cable EJ, Patel PN, Pyter LM, Onishi KG, Stevenson TJ, Ruby NF, Bradley SP. Impaired leukocyte trafficking and skin inflammatory responses in hamsters lacking a functional circadian system. Brain Behav Immun 2013; 32:94-104. [PMID: 23474187 PMCID: PMC3686870 DOI: 10.1016/j.bbi.2013.02.007] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2013] [Revised: 02/20/2013] [Accepted: 02/27/2013] [Indexed: 01/19/2023] Open
Abstract
The immune system is under strong circadian control, and circadian desynchrony is a risk factor for metabolic disorders, inflammatory responses and cancer. Signaling pathways that maintain circadian rhythms (CRs) in immune function in vivo, and the mechanisms by which circadian desynchrony impairs immune function, remain to be fully identified. These experiments tested the hypothesis that the hypothalamic circadian pacemaker in the suprachiasmatic nucleus (SCN) drives CRs in the immune system, using a non-invasive model of SCN circadian arrhythmia. Robust CRs in blood leukocyte trafficking, with a peak during the early light phase (ZT4) and nadir in the early dark phase (ZT18), were absent in arrhythmic hamsters, as were CRs in spleen clock gene (per1, bmal1) expression, indicating that a functional pacemaker in the SCN is required for the generation of CRs in leukocyte trafficking and for driving peripheral clocks in secondary lymphoid organs. Pinealectomy was without effect on CRs in leukocyte trafficking, but abolished CRs in spleen clock gene expression, indicating that nocturnal melatonin secretion is necessary for communicating circadian time information to the spleen. CRs in trafficking of antigen presenting cells (CD11c(+) dendritic cells) in the skin were abolished, and antigen-specific delayed-type hypersensitivity skin inflammatory responses were markedly impaired in arrhythmic hamsters. The SCN drives robust CRs in leukocyte trafficking and lymphoid clock gene expression; the latter of which is not expressed in the absence of melatonin. Robust entrainment of the circadian pacemaker provides a signal critical to diurnal rhythms in immunosurveilliance and optimal memory T-cell dependent immune responses.
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Affiliation(s)
- Brian J. Prendergast
- Department of Psychology, University of Chicago, Chicago, IL 60637,Committee on Neurobiology, University of Chicago, Chicago, IL 60637
| | - Erin J. Cable
- Department of Psychology, University of Chicago, Chicago, IL 60637
| | - Priyesh N. Patel
- Department of Psychology, University of Chicago, Chicago, IL 60637
| | - Leah M. Pyter
- Department of Psychology, University of Chicago, Chicago, IL 60637
| | | | | | - Norman F. Ruby
- Department of Biological Sciences, Stanford University, Palo Alto, CA 94305
| | - Sean P. Bradley
- Department of Psychology, University of Chicago, Chicago, IL 60637
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Abstract
The objective of the study was to perform a literature review on the health consequences of working rotating shifts and implications for structural design. A literature search was performed in June 2012 and a selection of the most relevant peer-review articles was included in the present review. Shift workers are more likely to suffer from a circadian sleep disorder characterized by sleepiness and insomnia. Shift work is associated with decreased productivity, impaired safety, diminished quality of life and adverse effects on health. Circadian disruption resulting from rotating shift work has also been associated with increased risk for metabolic syndrome, diabetes, cardiovascular disease and cancer. This article summarizes the known health effects of shift work and discusses how light can be used as a countermeasure to minimize circadian disruption at night while maintaining alertness. In the context of the lighted environment, implications for the design of newborn intensive care units are also discussed.
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Affiliation(s)
- M G Figueiro
- Lighting Research Center, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
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Golombek DA, Casiraghi LP, Agostino PV, Paladino N, Duhart JM, Plano SA, Chiesa JJ. The times they're a-changing: effects of circadian desynchronization on physiology and disease. ACTA ACUST UNITED AC 2013; 107:310-22. [PMID: 23545147 DOI: 10.1016/j.jphysparis.2013.03.007] [Citation(s) in RCA: 76] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Circadian rhythms are endogenous and need to be continuously entrained (synchronized) with the environment. Entrainment includes both coupling internal oscillators to external periodic changes as well as synchrony between the central clock and peripheral oscillators, which have been shown to exhibit different phases and resynchronization speed. Temporal desynchronization induces diverse physiological alterations that ultimately decrease quality of life and induces pathological situations. Indeed, there is a considerable amount of evidence regarding the deleterious effect of circadian dysfunction on overall health or on disease onset and progression, both in human studies and in animal models. In this review we discuss the general features of circadian entrainment and introduce diverse experimental models of desynchronization. In addition, we focus on metabolic, immune and cognitive alterations under situations of acute or chronic circadian desynchronization, as exemplified by jet-lag and shiftwork schedules. Moreover, such situations might lead to an enhanced susceptibility to diverse cancer types. Possible interventions (including light exposure, scheduled timing for meals and use of chronobiotics) are also discussed.
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Affiliation(s)
- Diego A Golombek
- Laboratory of Chronobiology, National University of Quilmes/CONICET, Buenos Aires, Argentina.
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49
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Liu Z, Chu G. Chronobiology in mammalian health. Mol Biol Rep 2012; 40:2491-501. [DOI: 10.1007/s11033-012-2330-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2012] [Accepted: 11/19/2012] [Indexed: 11/30/2022]
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50
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Froy O. Circadian rhythms and obesity in mammals. ISRN OBESITY 2012; 2012:437198. [PMID: 24527263 PMCID: PMC3914271 DOI: 10.5402/2012/437198] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/16/2012] [Accepted: 11/11/2012] [Indexed: 02/02/2023]
Abstract
Obesity has become a serious public health problem and a major risk factor for the development of illnesses, such as insulin resistance and hypertension. Attempts to understand the causes of obesity and develop new therapeutic strategies have mostly focused on caloric intake and energy expenditure. Recent studies have shown that the circadian clock controls energy homeostasis by regulating the circadian expression and/or activity of enzymes, hormones, and transport systems involved in metabolism. Moreover, disruption of circadian rhythms leads to obesity and metabolic disorders. Therefore, it is plausible that resetting of the circadian clock can be used as a new approach to attenuate obesity. Feeding regimens, such as restricted feeding (RF), calorie restriction (CR), and intermittent fasting (IF), provide a time cue and reset the circadian clock and lead to better health. In contrast, high-fat (HF) diet leads to disrupted circadian expression of metabolic factors and obesity. This paper focuses on circadian rhythms and their link to obesity.
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Affiliation(s)
- Oren Froy
- Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, P.O. Box 12, 76100 Rehovot, Israel
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