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Ning G, Li BN, Wu H, Shi RB, Peng AJ, Wang HY, Zhou X. Regulation of testosterone synthesis by circadian clock genes and its research progress in male diseases. Asian J Androl 2025:00129336-990000000-00298. [PMID: 40101130 DOI: 10.4103/aja20258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Accepted: 01/20/2025] [Indexed: 03/20/2025] Open
Abstract
ABSTRACT The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms. Testosterone, as one of the most critical sex hormones, is essential for the development of the reproductive system, maintenance of reproductive function, and the overall health of males. The secretion of testosterone in mammals is characterized by distinct circadian rhythms and is closely associated with the regulation of circadian clock genes. Here we review the central and peripheral regulatory mechanisms underlying the influence of circadian clock genes upon testosterone synthesis. We also examined the specific effects of these genes on the occurrence, development, and treatment of common male diseases, including late-onset hypogonadism, erectile dysfunction, male infertility, and prostate cancer.
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Affiliation(s)
- Gang Ning
- The First Clinical College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China
- Department of Andrology, The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China
| | - Bo-Nan Li
- Affiliated Changsha Hospital of Hunan Normal University, Changsha 410023, China
| | - Hui Wu
- The First Clinical College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China
| | - Ruo-Bing Shi
- The First Clinical College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China
| | - A-Jian Peng
- The First Clinical College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China
| | - Hao-Yu Wang
- The First Clinical College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China
| | - Xing Zhou
- Department of Andrology, The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China
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Holmes TL, Chabronova A, Denning C, James V, Peffers MJ, Smith JGW. Footprints in the Sno: investigating the cellular and molecular mechanisms of SNORD116. Open Biol 2025; 15:240371. [PMID: 40101781 PMCID: PMC11919532 DOI: 10.1098/rsob.240371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Revised: 01/11/2025] [Accepted: 02/04/2025] [Indexed: 03/20/2025] Open
Abstract
The small nucleolar RNA (snoRNA) SNORD116 is a small non-coding RNA of interest across multiple biomedical fields of research. Much of the investigation into SNORD116 has been undertaken in the context of the congenital disease Prader-Willi syndrome, wherein SNORD116 expression is lost. However, emerging evidence indicates wider roles in various disease and tissue contexts such as cellular growth, metabolism and signalling. Nevertheless, a conclusive mechanism of action for SNORD116 remains to be established. Here, we review the key findings from these investigations, with the aim of identifying common elements from which to elucidate potential targets and mechanisms of SNORD116. A key recurring element identified is disruption to the insulin/IGF-1 and PI3K/mTOR signalling pathways, contributing to many of the phenotypes associated with SNORD116 modulation explored in this review.
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Affiliation(s)
- Terri L Holmes
- Centre for Metabolic Health, Norwich Medical School, University of East Anglia, Norwich, Norfolk NR4 7UQ, UK
| | - Alzbeta Chabronova
- Department of Musculoskeletal Ageing Science, University of Liverpool, Liverpool, UK
| | - Chris Denning
- Department of Stem Cell Biology, University of Nottingham, Nottingham, UK
| | - Victoria James
- School of Veterinary Medicine and Science, University of Nottingham, Nottingham, UK
| | - Mandy J Peffers
- Department of Musculoskeletal Ageing Science, University of Liverpool, Liverpool, UK
| | - James G W Smith
- Centre for Metabolic Health, Norwich Medical School, University of East Anglia, Norwich, Norfolk NR4 7UQ, UK
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Sun Q, Zhu J, Zhao X, Huang X, Qu W, Tang X, Ma D, Shu Q, Li X. Mettl3-m 6A-NPY axis governing neuron-microglia interaction regulates sleep amount of mice. Cell Discov 2025; 11:10. [PMID: 39905012 PMCID: PMC11794856 DOI: 10.1038/s41421-024-00756-y] [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: 05/14/2024] [Accepted: 11/13/2024] [Indexed: 02/06/2025] Open
Abstract
Sleep behavior is regulated by diverse mechanisms including genetics, neuromodulation and environmental signals. However, it remains completely unknown regarding the roles of epitranscriptomics in regulating sleep behavior. In the present study, we showed that the deficiency of RNA m6A methyltransferase Mettl3 in excitatory neurons specifically induces microglia activation, neuroinflammation and neuronal loss in thalamus of mice. Mettl3 deficiency remarkably disrupts sleep rhythm and reduces the amount of non-rapid eye movement sleep. We also showed that Mettl3 regulates neuropeptide Y (NPY) via m6A modification and Mettl3 conditional knockout (cKO) mice displayed significantly decreased expression of NPY in thalamus. In addition, the dynamic distribution pattern of NPY is observed during wake-sleep cycle in cKO mice. Ectopic expression of Mettl3 and NPY significantly inhibits microglia activation and neuronal loss in thalamus, and restores the disrupted sleep behavior of cKO mice. Collectively, our study has revealed the critical function of Mettl3-m6A-NPY axis in regulating sleep behavior.
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Affiliation(s)
- Qihang Sun
- Children's Hospital, School of Medicine, Zhejiang University, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China
- The Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Jinpiao Zhu
- Children's Hospital, School of Medicine, Zhejiang University, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China.
- Department of Rehabilitation, Perioperative and Systems Medicine Laboratory, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China.
| | - Xingsen Zhao
- Institute of Biotechnology, Xianghu Laboratory, Hangzhou, Zhejiang, China
| | - Xiaoli Huang
- Children's Hospital, School of Medicine, Zhejiang University, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China
| | - Wenzheng Qu
- Children's Hospital, School of Medicine, Zhejiang University, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China
| | - Xia Tang
- Children's Hospital, School of Medicine, Zhejiang University, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China
| | - Daqing Ma
- Department of Rehabilitation, Perioperative and Systems Medicine Laboratory, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China.
- Division of Anesthetics, Pain Medicine & Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK.
| | - Qiang Shu
- Children's Hospital, School of Medicine, Zhejiang University, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China.
| | - Xuekun Li
- Children's Hospital, School of Medicine, Zhejiang University, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China.
- The Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
- Binjiang Institute of Zhejiang University, Hangzhou, Zhejiang, China.
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4
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Nôga DA, Meth EMS, Pacheco AP, Cedernaes J, Xue P, Benedict C. Habitual sleep duration, healthy eating, and digestive system cancer mortality. BMC Med 2025; 23:44. [PMID: 39865237 PMCID: PMC11770963 DOI: 10.1186/s12916-025-03882-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 01/16/2025] [Indexed: 01/28/2025] Open
Abstract
BACKGROUND Lifestyle choices, such as dietary patterns and sleep duration, significantly impact the health of the digestive system and may influence the risk of mortality from digestive system cancer. METHODS This study aimed to examine the associations between sleep duration, dietary habits, and mortality from digestive system cancers. The analysis included 406,584 participants from the UK Biobank cohort (54.1% women; age range: 38-73 years), with sleep duration classified as short (≤ 6 h, 24.2%), normal (7-8 h, 68.4%), and long (≥ 9 h, 7.4%). Healthy eating habits were defined as a daily intake of at least 25 g of fibre, seven portions of fruits and vegetables, and fewer than four servings of meat per week. These dietary factors were combined into a score ranging from 0 (least healthy) to 3 (healthiest). Cox proportional hazards regression analyses were conducted, with a median follow-up period of 12.6 years, ending on September 30, 2021. RESULTS 3949 participants died from cancer of the digestive system. Both short and long sleep duration were associated with an increased risk of mortality from cancer of the digestive system (1.09 (1.01-1.18) and 1.14 (1.03-1.27), respectively). Additionally, a diet score ≥ 1 was linked to a lower cancer risk (0.72-0.91 (0.59-0.96)). Adjusting for smoking, type 2 diabetes, and body mass index (BMI) status eliminated the association between sleep duration and digestive cancer mortality. The association between healthy dietary patterns and the risk of digestive system cancer mortality did not vary by sleep duration. CONCLUSIONS Aberrant sleep durations may increase the risk of mortality from digestive system cancer, potentially through smoking, higher BMI, and type 2 diabetes. However, aberrant sleep durations do not seem to reduce the protective effects of a healthy dietary pattern.
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Affiliation(s)
- Diana A Nôga
- Department of Pharmaceutical Biosciences, Uppsala University, Box 593, Husargatan 3, Uppsala, 751 24, Sweden.
| | - Elisa M S Meth
- Department of Pharmaceutical Biosciences, Uppsala University, Box 593, Husargatan 3, Uppsala, 751 24, Sweden
| | - André P Pacheco
- Department of Pharmaceutical Biosciences, Uppsala University, Box 593, Husargatan 3, Uppsala, 751 24, Sweden
- Department of Research and Innovation, Division of Mental Health and Addiction, Oslo University Hospital, Sognsvannsveien 21, Oslo, 0372, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Postboks 1039 Blindern, 0315, Oslo, Norway
| | - Jonathan Cedernaes
- Department of Medical Sciences, Uppsala University, Akademiska Sjukhuset, Ing. 40, 5 Tr, Uppsala, 751 85, Sweden
- Department of Medical Cell Biology, Uppsala University, Box 571, Husargatan 3, Uppsala, 751 24, Sweden
| | - Pei Xue
- Department of Pharmaceutical Biosciences, Uppsala University, Box 593, Husargatan 3, Uppsala, 751 24, Sweden
| | - Christian Benedict
- Department of Pharmaceutical Biosciences, Uppsala University, Box 593, Husargatan 3, Uppsala, 751 24, Sweden
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Skinner CM, Conboy MJ, Conboy IM. DNA methylation clocks struggle to distinguish inflammaging from healthy aging, but feature rectification improves coherence and enhances detection of inflammaging. GeroScience 2025:10.1007/s11357-024-01460-1. [PMID: 39825170 DOI: 10.1007/s11357-024-01460-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 11/26/2024] [Indexed: 01/20/2025] Open
Abstract
Biological age estimation from DNA methylation and determination of relevant biomarkers is an active research problem which has predominantly been tackled with black-box penalized regression. Machine learning is used to select a small subset of features from hundreds of thousands of CpG probes and to increase generalizability typically lacking with ordinary least-squares regression. Here, we show that such feature selection lacks biological interpretability and relevance in the clocks of the first and next generations and clarify the logic by which these clocks systematically exclude biomarkers of aging and age-related disease. Moreover, in contrast to the assumption that regularized linear regression is needed to prevent overfitting, we demonstrate that hypothesis-driven selection of biologically relevant features in conjunction with ordinary least squares regression yields accurate, well-calibrated, generalizable clocks with high interpretability. We further demonstrate that the interplay of inflammaging-related shifts of predictor values and their corresponding weights, which we term feature shifts, contributes to the lack of resolution between health and inflammaging in conventional linear models. Lastly, we introduce a method of feature rectification, which aligns these shifts to improve the distinction of age predictions for healthy people vs. patients with various chronic inflammation diseases.
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Affiliation(s)
- Colin M Skinner
- Department of Bioengineering and QB3, University of California, Berkeley, Berkeley, CA, 94720, USA
| | - Michael J Conboy
- Department of Bioengineering and QB3, University of California, Berkeley, Berkeley, CA, 94720, USA
| | - Irina M Conboy
- Department of Bioengineering and QB3, University of California, Berkeley, Berkeley, CA, 94720, USA.
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Hong S, Lee DB, Yoon DW, Yoo SL, Kim J. The Effect of Sleep Disruption on Cardiometabolic Health. Life (Basel) 2025; 15:60. [PMID: 39860000 PMCID: PMC11766988 DOI: 10.3390/life15010060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/03/2025] [Accepted: 01/04/2025] [Indexed: 01/27/2025] Open
Abstract
Sleep disruption has emerged as a significant public health concern with profound implications for metabolic health. This review synthesizes current evidence demonstrating the intricate relationships between sleep disturbances and cardiometabolic dysfunction. Epidemiological studies have consistently demonstrated that insufficient sleep duration (<7 h) and poor sleep quality are associated with increased risks of obesity, type 2 diabetes, and cardiovascular disease. The underlying mechanisms are multifaceted, involving the disruption of circadian clock genes, alterations in glucose and lipid metabolism, the activation of inflammatory pathways, and the modulation of the gut microbiome. Sleep loss affects key metabolic regulators, including AMPK signaling and disrupts the secretion of metabolic hormones such as leptin and ghrelin. The latest evidence points to the role of sleep-induced changes in the composition and function of gut microbiota, which may contribute to metabolic dysfunction through modifications in the intestinal barrier and inflammatory responses. The NLRP3 inflammasome and NF-κB signaling pathways have been identified as crucial mediators linking sleep disruption to metabolic inflammation. An understanding of these mechanisms has significant implications for public health and clinical practice, suggesting that improving sleep quality could be an effective strategy for preventing and treating cardiometabolic disorders in modern society.
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Affiliation(s)
- SeokHyun Hong
- Sleep Medicine Institute, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea; (S.H.); (D.-B.L.); (S.-L.Y.)
- Department of Biomedical Laboratory Science, College of Health Science, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea
| | - Da-Been Lee
- Sleep Medicine Institute, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea; (S.H.); (D.-B.L.); (S.-L.Y.)
| | - Dae-Wui Yoon
- Sleep Medicine Institute, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea; (S.H.); (D.-B.L.); (S.-L.Y.)
- Department of Biomedical Laboratory Science, College of Health Science, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea
| | - Seung-Lim Yoo
- Sleep Medicine Institute, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea; (S.H.); (D.-B.L.); (S.-L.Y.)
- Department of Biomedical Laboratory Science, College of Health Science, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea
| | - Jinkwan Kim
- Sleep Medicine Institute, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea; (S.H.); (D.-B.L.); (S.-L.Y.)
- Department of Biomedical Laboratory Science, College of Health Science, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea
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Sun WT, Du JY, Wang J, Wang YL, Dong ED. Potential preservative mechanisms of cardiac rehabilitation pathways on endothelial function in coronary heart disease. SCIENCE CHINA. LIFE SCIENCES 2025; 68:158-175. [PMID: 39395086 DOI: 10.1007/s11427-024-2656-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 06/17/2024] [Indexed: 10/14/2024]
Abstract
Cardiac rehabilitation, a comprehensive exercise-based lifestyle and medical management, is effective in decreasing morbidity and improving life quality in patients with coronary heart disease. Endothelial function, an irreplaceable indicator in coronary heart disease progression, is measured by various methods in traditional cardiac rehabilitation pathways, including medicinal treatment, aerobic training, and smoking cessation. Nevertheless, studies on the effect of some emerging cardiac rehabilitation programs on endothelial function are limited. This article briefly reviewed the endothelium-beneficial effects of different cardiac rehabilitation pathways, including exercise training, lifestyle modification and psychological intervention in patients with coronary heart disease, and related experimental models, and summarized both uncovered and potential cellular and molecular mechanisms of the beneficial roles of various cardiac rehabilitation pathways on endothelial function. In exercise training and some lifestyle interventions, the enhanced bioavailability of nitric oxide, increased circulating endothelial progenitor cells (EPCs), and decreased oxidative stress are major contributors to preventing endothelial dysfunction in coronary heart disease. Moreover, the preservation of endothelial-dependent hyperpolarizing factors and inflammatory suppression play roles. On the one hand, to develop more endothelium-protective rehabilitation methods in coronary heart disease, adequately designed and sized randomized multicenter clinical trials should be advanced using standardized cardiac rehabilitation programs and existing assessment methods. On the other hand, additional studies using suitable experimental models are warranted to elucidate the relationship between some new interventions and endothelial protection in both macro- and microvasculature.
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Affiliation(s)
- Wen-Tao Sun
- Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital), School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, 266071, China.
| | - Jian-Yong Du
- Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital), School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, 266071, China
| | - Jia Wang
- Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital), School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, 266071, China
| | - Yi-Long Wang
- Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital), School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, 266071, China
| | - Er-Dan Dong
- Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital), School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, 266071, China.
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, 100191, China.
- The Institute of Cardiovascular Sciences, Peking University, Beijing, 100191, China.
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, 100191, China.
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Thacher JD, Snigireva A, Dauter UM, Delaval MN, Oudin A, Mattisson K, Sørensen M, Borgquist S, Albin M, Broberg K. Road traffic noise and breast cancer: DNA methylation in four core circadian genes. Clin Epigenetics 2024; 16:168. [PMID: 39587706 PMCID: PMC11590349 DOI: 10.1186/s13148-024-01774-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Accepted: 11/05/2024] [Indexed: 11/27/2024] Open
Abstract
BACKGROUND Transportation noise has been linked with breast cancer, but existing literature is conflicting. One proposed mechanism is that transportation noise disrupts sleep and the circadian rhythm. We investigated the relationships between road traffic noise, DNA methylation in circadian rhythm genes, and breast cancer. We selected 610 female participants (318 breast cancer cases and 292 controls) enrolled into the Malmö, Diet, and Cancer cohort. DNA methylation of CpGs (N = 29) in regulatory regions of circadian rhythm genes (CRY1, BMAL1, CLOCK, and PER1) was assessed by pyrosequencing of DNA from lymphocytes collected at enrollment. To assess associations between modeled 5-year mean residential road traffic noise and differentially methylated CpG positions, we used linear regression models adjusting for potential confounders, including sociodemographics, shiftwork, and air pollution. Linear mixed effects models were used to evaluate road traffic noise and differentially methylated regions. Unconditional logistic regression was used to investigate CpG methylation and breast cancer. RESULTS We found that higher mean road traffic noise was associated with lower DNA methylation of three CRY1 CpGs (CpG1, CpG2, and CpG12) and three BMAL1 CpGs (CpG2, CpG6, and CpG7). Road traffic noise was also associated with differential methylation of CRY1 and BMAL1 promoters. In CRY1 CpG2 and CpG5 and in CLOCK CpG1, increasing levels of methylation tended to be associated with lower odds of breast cancer, with odds ratios (OR) of 0.88 (95% confidence interval (CI) 0.76-1.02), 0.84 (95% CI 0.74-0.96), and 0.80 (95% CI 0.68-0.94), respectively. CONCLUSIONS In summary, our data suggest that DNA hypomethylation in CRY1 and BMAL1 could be part of a causal chain from road traffic noise to breast cancer. This is consistent with the hypothesis that disruption of the circadian rhythm, e.g., from road traffic noise exposure, increases the risk of breast cancer. Since no prior studies have explored this association, it is essential to replicate our results.
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Affiliation(s)
- Jesse D Thacher
- Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
| | | | - Ulrike Maria Dauter
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Mathilde N Delaval
- Joint Mass Spectrometry Centre (JMSC), Cooperation Group Comprehensive Molecular Analytics, Helmholtz Munich, Neuherberg, Germany
| | - Anna Oudin
- Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden
| | - Kristoffer Mattisson
- Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden
| | - Mette Sørensen
- Work, Environment and Cancer, Danish Cancer Institute, Copenhagen, Denmark
- Department of Natural Science and Environment, Roskilde University, Roskilde, Denmark
| | - Signe Borgquist
- Department of Oncology, Aarhus University Hospital, Aarhus University, Aarhus, Denmark
- Department of Clinical Sciences Lund, Oncology, Lund University and Skåne University Hospital, Lund, Sweden
| | - Maria Albin
- Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Karin Broberg
- Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
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Latha Laxmi IP, Tamizhselvi R. Epigenetic events influencing the biological clock: Panacea for neurodegeneration. Heliyon 2024; 10:e38836. [PMID: 39430507 PMCID: PMC11489350 DOI: 10.1016/j.heliyon.2024.e38836] [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: 01/24/2024] [Revised: 09/28/2024] [Accepted: 10/01/2024] [Indexed: 10/22/2024] Open
Abstract
The human biological clock is the 24-h internal molecular network of circadian genes in synchronization with other cells in response to external stimuli. The rhythmicity of the clock genes is maintained by positive and negative transcriptional feedback loops coordinating the 24-h oscillation in different tissues. The superchiasmatic nucleus, the central pacemaker of the biological clock diminishes with aging causing alterations in the clock rhythmicity leading to the onset of neurodegenerative diseases mainly Alzheimer's disease, Parkinson's disease, and Huntington's disease. Studies have shown that brain and muscle Arnt -like 1 (Bmal1) and Circadian Locomotor Output Cycles Kaput (Clock) gene expression is altered in the onset of neurodegeneration. One of the major symptoms of neurodegeneration is changes in the sleep/wake cycle. Moreover, variations in circadian clock oscillations can happen due to lifestyle changes, addiction to alcohol, cocaine, drugs, smoking, food habits and most importantly eating and sleep/awake cycle patterns which can significantly impact the expression of circadian genes. Recent studies have focused on the molecular function of clock genes affected due to environmental cues. Epigenetic modifications are influenced by the external environmental factors. This review aims to focus on the principal mechanism of epigenetics influencing circadian rhythm disruption leading to neurodegeneration and as well as targeting the epigenetic modulators could be a novel therapeutic approach to combat neurodegenerative disorders.
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Affiliation(s)
| | - Ramasamy Tamizhselvi
- School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, India
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10
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Skinner CM, Conboy MJ, Conboy IM. DNA methylation clocks struggle to distinguish inflammaging from healthy aging, but feature rectification improves coherence and enhances detection of inflammaging. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.10.09.617512. [PMID: 39416129 PMCID: PMC11482923 DOI: 10.1101/2024.10.09.617512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2024]
Abstract
Biological age estimation from DNA methylation and determination of relevant biomarkers is an active research problem which has predominantly been tackled with black-box penalized regression. Machine learning is used to select a small subset of features from hundreds of thousands CpG probes and to increase generalizability typically lacking with ordinary least-squares regression. Here, we show that such feature selection lacks biological interpretability and relevance in the clocks of the first- and next-generations, and clarify the logic by which these clocks systematically exclude biomarkers of aging and disease. Moreover, in contrast to the assumption that regularized linear regression is needed to prevent overfitting, we demonstrate that hypothesis-driven selection of biologically relevant features in conjunction with ordinary least squares regression yields accurate, well-calibrated, generalizable clocks with high interpretability. We further demonstrate that the interplay of disease-related shifts of predictor values and their corresponding weights, which we term feature shifts, contributes to the lack of resolution between health and disease in conventional linear models. Lastly, we introduce a method of feature rectification, which aligns these shifts to improve the distinction of age predictions for healthy people vs. patients with various diseases. Key Findings There is no apparent biological significance of the CpGs selected by first- and next-generation clocksThe range of residuals for first- and next-generation clock predications on healthy samples is very large; for all models tested, a prediction error of +/-10-20 years is within the 95% range of variation for healthy controls and does not signify age accelerationThere is no significant shift in the mean of residuals for patient populations relative to healthy populations for most studied first- and next-generation clocks. For those with significance, the effect size is very small.Hypothesis-driven feature pre-selection, coupled with modified forward step-wise selection yields age predictors on par with first and next-generation clocks. EN/ML is not needed.Disease-related shifts at different CpG probes, along with learned model weights, can be either positive or negative; their combination leads to de-coherence effect in linear models.Model coherence can be induced by rectifying features to have only positive shifts in patient samples; this provides a better resolution between health and disease in DNAm age models, and expectedly, introduces more non-linearity to the input data.
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11
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Sochal M, Ditmer M, Tarasiuk-Zawadzka A, Binienda A, Turkiewicz S, Wysokiński A, Karuga FF, Białasiewicz P, Fichna J, Gabryelska A. Circadian Rhythm Genes and Their Association with Sleep and Sleep Restriction. Int J Mol Sci 2024; 25:10445. [PMID: 39408776 PMCID: PMC11476465 DOI: 10.3390/ijms251910445] [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] [Received: 08/07/2024] [Revised: 09/23/2024] [Accepted: 09/27/2024] [Indexed: 10/20/2024] Open
Abstract
Deprivation of sleep (DS) and its effects on circadian rhythm gene expression are not well understood despite their influence on various physiological and psychological processes. This study aimed to elucidate the changes in the expression of circadian rhythm genes following a night of sleep and DS. Their correlation with sleep architecture and physical activity was also examined. The study included 81 participants who underwent polysomnography (PSG) and DS with actigraphy. Blood samples were collected after PSG and DS. Expression levels of brain and muscle ARNT-like 1 (BMAL1), circadian locomotor output cycles kaput (CLOCK), neuronal PAS domain protein 2 (NPAS2), period 1 (PER1), cryptochrome 1 (CRY1) and nuclear receptor subfamily 1 group D member 1 (NR1D1) were analyzed using qRT-PCR. DS decreased the expression of CLOCK and BMAL1 while increasing PER1. PER1 expression correlated positively with total sleep time and non-rapid-eye-movement (NREM) sleep duration and negatively with sleep latency, alpha, beta and delta waves in the O1A2 lead. Physical activity during DS showed positive correlations with CLOCK, BMAL1, and CRY1. The findings highlight the role of PER1 in modulating sleep patterns, suggesting potential targets for managing sleep-related disorders. Further research is essential to deepen the understanding of these relationships and their implications.
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Affiliation(s)
- Marcin Sochal
- Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland; (M.D.); (S.T.); (F.F.K.); (P.B.); (A.G.)
| | - Marta Ditmer
- Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland; (M.D.); (S.T.); (F.F.K.); (P.B.); (A.G.)
| | | | - Agata Binienda
- Department of Biochemistry, Medical University of Lodz, 90-419 Lodz, Poland; (A.T.-Z.); (A.B.); (J.F.)
| | - Szymon Turkiewicz
- Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland; (M.D.); (S.T.); (F.F.K.); (P.B.); (A.G.)
| | - Adam Wysokiński
- Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Lodz, 90-419 Lodz, Poland;
| | - Filip Franciszek Karuga
- Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland; (M.D.); (S.T.); (F.F.K.); (P.B.); (A.G.)
| | - Piotr Białasiewicz
- Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland; (M.D.); (S.T.); (F.F.K.); (P.B.); (A.G.)
| | - Jakub Fichna
- Department of Biochemistry, Medical University of Lodz, 90-419 Lodz, Poland; (A.T.-Z.); (A.B.); (J.F.)
| | - Agata Gabryelska
- Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland; (M.D.); (S.T.); (F.F.K.); (P.B.); (A.G.)
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12
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Yang T, Wang HR, Mou YK, Liu WC, Wang Y, Song XY, Ren C, Song XC. Mutual Influence Between Allergic Rhinitis and Sleep: Factors, Mechanisms, and interventions-A Narrative Review. Nat Sci Sleep 2024; 16:1451-1467. [PMID: 39318396 PMCID: PMC11420902 DOI: 10.2147/nss.s482258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 09/11/2024] [Indexed: 09/26/2024] Open
Abstract
Patients with allergic rhinitis (AR) have a high incidence of sleep disorders, such as insomnia, which can easily exacerbate nasal symptoms. The aggravation of nasal symptoms further promotes the deterioration of sleep disorders, forming a vicious cycle. Severe cases may even trigger psychological and neurological issues, such as anxiety, depression, and cognitive impairment, causing significant distress to patients, making clinical diagnosis and treatment difficult, and increasing costs. Furthermore, satisfactory therapeutics remain lacking. As the pathogenesis of AR-associated sleep disorders is not clear and research is still insufficient, paying attention to and understanding AR-related sleep disorders is crucial in clinical practice. Multiple studies have shown that the most crucial issues in current research on AR and sleep are analyzing the relationship between AR and sleep disorders, searching for the influencing factors, and investigating potential targets for diagnosis and treatment. This review aimed to identify and summarize the results of relevant studies using "AR" and "sleep disorders" as search terms. In addition, we evaluated the correlation between AR and sleep disorders and examined their interaction and potential mechanisms, offering a foundation for additional screening of potential diagnostic biomarkers and therapeutic targets.
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Affiliation(s)
- Ting Yang
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China
- Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China
- Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China
| | - Han-Rui Wang
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China
- Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China
- Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China
| | - Ya-Kui Mou
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China
- Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China
- Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China
| | - Wan-Chen Liu
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China
- Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China
- Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China
| | - Yao Wang
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China
- Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China
- Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China
| | - Xiao-Yu Song
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China
- Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China
- Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China
| | - Chao Ren
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China
- Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China
- Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China
- Department of Neurology, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China
| | - Xi-Cheng Song
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China
- Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China
- Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China
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13
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Cherubini JM, Cheng JL, Armstrong CM, Kamal MJ, Parise G, MacDonald MJ. Acute partial sleep restriction does not impact arterial function in young and healthy humans. Exp Physiol 2024; 109:1492-1504. [PMID: 38900696 PMCID: PMC11363128 DOI: 10.1113/ep091699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Accepted: 05/30/2024] [Indexed: 06/22/2024]
Abstract
Habitual short sleep durations are associated with several cardiovascular diseases. Experimental research generally supports these findings as metrics of arterial function are impaired after complete deprivation of sleep and after longer periods of partial sleep restriction. The acute influence of a single instance of partial sleep restriction (PSR), however, has not been defined. We evaluated arterial structure and function among 32 university-aged participants on two occasions: once after normal habitual sleep (NS), and again the morning after an acute partial sleep restriction (PSR) intervention involving only 3 h of sleep for a single night. Endothelial function was measured using ultrasonography at the brachial artery via flow-mediated dilatation (FMD), and a ramp peak oxygen uptake test was used to evaluate cardiorespiratory fitness. Blood samples were collected from a subset of participants to investigate the influence of circulatory factors on cellular mechanisms implicated in endothelial function. Sleep duration was lower after a night of PSR compared to NS (P < 0.001); however, there were no appreciable differences in any haemodynamic outcome between conditions. FMD was not different between NS and PSR (NS: 6.5 ± 2.9%; PSR: 6.3 ± 2.9%; P = 0.668), and cardiorespiratory fitness did not moderate the haemodynamic response to PSR (all P > 0.05). Ex vivo cell culture results aligned with in vivo data, showing that acute PSR does not alter intracellular processes involved in endothelial function. No differences in arterial structure or function were observed between NS and acute PSR in healthy and young participants, and cardiorespiratory fitness does not modulate the arterial response to acute sleep restriction.
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Affiliation(s)
| | - Jem L. Cheng
- Department of KinesiologyMcMaster UniversityHamiltonOntarioCanada
| | | | - Michael J. Kamal
- Department of KinesiologyMcMaster UniversityHamiltonOntarioCanada
| | - Gianni Parise
- Department of KinesiologyMcMaster UniversityHamiltonOntarioCanada
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14
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Chen Y, Xu W, Chen Y, Gong J, Wu Y, Chen S, He Y, Yu H, Xie L. The effect of acute sleep deprivation on cortisol level: a systematic review and meta-analysis. Endocr J 2024; 71:753-765. [PMID: 38777757 DOI: 10.1507/endocrj.ej23-0714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/25/2024] Open
Abstract
Acute sleep deprivation has aroused widespread concern and the relationship between acute sleep deprivation and cortisol levels is inconsistent. This study aimed to explore additional evidence and details. The PubMed, Web of Science, EMBASE, CLINAHL and Cochrane databases were searched for eligible studies published up to June 7, 2023. All analyses were performed using Review Manager 5.4 and Stata/SE 14.0. A total of 24 studies contributed to this meta-analysis. There was no significant difference in cortisol levels between participants with acute sleep deprivation and normal sleep in 21 crossover-designed studies (SMD = 0.18; 95% CI: -0.11, 0.45; p = 0.208) or 3 RCTs (SMD = 0.26; 95% CI: -0.22, 0.73; p = 0.286). Subgroup analysis revealed that the pooled effects were significant for studies using serum as the sample (SMD = 0.46; 95%CI: 0.11, 0.81; p = 0.011). Studies reporting cortisol levels in the morning, in the afternoon and in the evening did not show significant difference (p > 0.05). The pooled effects were statistically significant for studies with multiple measurements (SMD = 0.28; 95%CI: 0.03, 0.53; p = 0.027) but not for studies with single cortisol assessments (p = 0.777). When the serum was used as the test sample, the cortisol levels of individuals after acute sleep deprivation were higher than those with normal sleep.
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Affiliation(s)
- Yifei Chen
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun 130021, China
| | - Wenhui Xu
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun 130021, China
| | - Yiru Chen
- Clinical Nutrition Department, Third Hospital of Jilin University, Changchun 130032, China
| | - Jiayu Gong
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun 130021, China
| | - Yanyan Wu
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun 130021, China
| | - Shutong Chen
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun 130021, China
| | - Yuan He
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun 130021, China
| | - Haitao Yu
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun 130021, China
| | - Lin Xie
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun 130021, China
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15
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Schrader LA, Ronnekleiv-Kelly SM, Hogenesch JB, Bradfield CA, Malecki KM. Circadian disruption, clock genes, and metabolic health. J Clin Invest 2024; 134:e170998. [PMID: 39007272 PMCID: PMC11245155 DOI: 10.1172/jci170998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/16/2024] Open
Abstract
A growing body of research has identified circadian-rhythm disruption as a risk factor for metabolic health. However, the underlying biological basis remains complex, and complete molecular mechanisms are unknown. There is emerging evidence from animal and human research to suggest that the expression of core circadian genes, such as circadian locomotor output cycles kaput gene (CLOCK), brain and muscle ARNT-Like 1 gene (BMAL1), period (PER), and cyptochrome (CRY), and the consequent expression of hundreds of circadian output genes are integral to the regulation of cellular metabolism. These circadian mechanisms represent potential pathophysiological pathways linking circadian disruption to adverse metabolic health outcomes, including obesity, metabolic syndrome, and type 2 diabetes. Here, we aim to summarize select evidence from in vivo animal models and compare these results with epidemiologic research findings to advance understanding of existing foundational evidence and potential mechanistic links between circadian disruption and altered clock gene expression contributions to metabolic health-related pathologies. Findings have important implications for the treatment, prevention, and control of metabolic pathologies underlying leading causes of death and disability, including diabetes, cardiovascular disease, and cancer.
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Affiliation(s)
| | - Sean M Ronnekleiv-Kelly
- Molecular and Environmental Toxicology Center and
- Department of Surgery, Division of Surgical Oncology, School of Medicine and Public Health, University of Wisconsin, Madison Wisconsin, USA
| | - John B Hogenesch
- Divisions of Human Genetics and Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | | | - Kristen Mc Malecki
- Molecular and Environmental Toxicology Center and
- Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA
- Division of Environmental and Occupational Health Sciences, University of Illinois Chicago, Chicago, Illinois, USA
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16
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Knowles OE, Soria M, Saner NJ, Trewin AJ, Alexander SE, Roberts SSH, Hiam D, Garnham AP, Drinkwater EJ, Aisbett B, Lamon S. The interactive effect of sustained sleep restriction and resistance exercise on skeletal muscle transcriptomics in young females. Physiol Genomics 2024; 56:506-518. [PMID: 38766755 DOI: 10.1152/physiolgenomics.00010.2024] [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] [Received: 01/30/2024] [Revised: 05/03/2024] [Accepted: 05/09/2024] [Indexed: 05/22/2024] Open
Abstract
Both sleep loss and exercise regulate gene expression in skeletal muscle, yet little is known about how the interaction of these stressors affects the transcriptome. The aim of this study was to investigate the effect of nine nights of sleep restriction (SR), with repeated resistance exercise (REx) sessions, on the skeletal muscle transcriptome of young, trained females. Ten healthy females aged 18-35 yr old undertook a randomized cross-over study of nine nights of SR (5 h time in bed) and normal sleep (NS; ≥7 h time in bed) with a minimum 6-wk washout. Participants completed four REx sessions per condition (days 3, 5, 7, and 9). Muscle biopsies were collected both pre- and post-REx on days 3 and 9. Gene and protein expression were assessed by RNA sequencing and Western blot, respectively. Three or nine nights of SR had no effect on the muscle transcriptome independently of exercise. However, close to 3,000 transcripts were differentially regulated (false discovery rate < 0.05) 48 h after the completion of three resistance exercise sessions in both NS and SR conditions. Only 39% of downregulated genes and 18% of upregulated genes were common between both conditions, indicating a moderating effect of SR on the response to exercise. SR and REx interacted to alter the enrichment of skeletal muscle transcriptomic pathways in young, resistance-trained females. Performing exercise when sleep restricted may not provide the same adaptive response for individuals as if they were fully rested.NEW & NOTEWORTHY This study investigated the effect of nine nights of sleep restriction, with repeated resistance exercise sessions, on the skeletal muscle transcriptome of young, trained females. Sleep restriction and resistance exercise interacted to alter the enrichment of skeletal muscle transcriptomic pathways in young, resistance-trained females. Performing exercise when sleep restricted may not provide the same adaptive response for individuals as if they were fully rested.
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Affiliation(s)
- Olivia E Knowles
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - Megan Soria
- School of Life and Environmental Sciences, Deakin University, Geelong, Victoria, Australia
| | - Nicholas J Saner
- Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia
| | - Adam J Trewin
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - Sarah E Alexander
- Cardiometabolic Health and Exercise Physiology, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
| | - Spencer S H Roberts
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - Danielle Hiam
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - Andrew P Garnham
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - Eric J Drinkwater
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - Brad Aisbett
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - Séverine Lamon
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
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17
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Richter E, Patel P, Babu JR, Wang X, Geetha T. The Importance of Sleep in Overcoming Childhood Obesity and Reshaping Epigenetics. Biomedicines 2024; 12:1334. [PMID: 38927541 PMCID: PMC11201669 DOI: 10.3390/biomedicines12061334] [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: 05/14/2024] [Revised: 06/10/2024] [Accepted: 06/12/2024] [Indexed: 06/28/2024] Open
Abstract
The development of childhood obesity is a complex process influenced by a combination of genetic predisposition and environmental factors, such as sleep, diet, physical activity, and socioeconomic status. Long-term solutions for decreasing the risk of childhood obesity remain elusive, despite significant advancements in promoting health and well-being in school and at home. Challenges persist in areas such as adherence to interventions, addressing underlying social determinants, and individual differences in response to treatment. Over the last decade, there has been significant progress in epigenetics, along with increased curiosity in gaining insights into how sleep and lifestyle decisions impact an individual's health. Epigenetic modifications affect the expression of genes without causing changes to the fundamental DNA sequence. In recent years, numerous research studies have explored the correlation between sleep and the epigenome, giving a better understanding of DNA methylation, histone modification, and non-coding RNAs. Although significant findings have been made about the influence of sleep on epigenetics, a notable gap exists in the literature concerning sleep-related genes specifically associated with childhood obesity. Consequently, it is crucial to delve deeper into this area to enhance our understanding. Therefore, this review primarily focuses on the connection between sleep patterns and epigenetic modifications in genes related to childhood obesity. Exploring the interplay between sleep, epigenetics, and childhood obesity can potentially contribute to improved overall health outcomes. This comprehensive review encompasses studies focusing on sleep-related genes linked to obesity.
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Affiliation(s)
- Erika Richter
- Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA
| | - Priyadarshni Patel
- Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA
| | - Jeganathan Ramesh Babu
- Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA
- Boshell Metabolic Diseases and Diabetes Program, Auburn University, Auburn, AL 36849, USA
- Alabama Agricultural Experiment Station, Auburn University, Auburn, AL 36849, USA
| | - Xu Wang
- Alabama Agricultural Experiment Station, Auburn University, Auburn, AL 36849, USA
- Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
- HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA
| | - Thangiah Geetha
- Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA
- Boshell Metabolic Diseases and Diabetes Program, Auburn University, Auburn, AL 36849, USA
- Alabama Agricultural Experiment Station, Auburn University, Auburn, AL 36849, USA
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18
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Li T, Cao Y, Zhou P, Xie Y, Tao S, Zou L, Yang Y, Tao F, Wu X. Prospective study of the association between chronotypes and depressive symptoms in Chinese university students: Moderating effects of PER1 gene DNA methylation. Chronobiol Int 2024; 41:621-631. [PMID: 38568246 DOI: 10.1080/07420528.2024.2337891] [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] [Received: 12/07/2023] [Accepted: 03/27/2024] [Indexed: 05/22/2024]
Abstract
Most studies have shown a link between chronotypes and mental health and have identified evening chronotypes (E-types) as a potential risk for depressive symptoms. However, the mechanisms behind this association remain unknown. Abnormal expression of the PER1 gene was not only associated with circadian rhythm disturbance, but also closely related to mental illness. Therefore, this study aimed to examine the association of chronotype with depressive symptoms, and further explore the moderating effects of the PER1 gene DNA methylation on chronotypes and depressive symptoms in Chinese university students. In a stratified cluster sampling design, chronotype and depressive symptoms were assessed in 1 042 university students from 2 universities in a two-year prospective survey from April 2019 to October 2020. The survey was conducted once every 6 months, corresponding to the time points in April 2019 (T0), October 2019 (T1), April 2020 (T2), and October 2020 (T3). At T0, the Morning and Evening Questionnaire 5 (MEQ-5) was adopted to assess chronotype. At T0-T3, the Patient Health Questionnaire 9 (PHQ-9) was adopted to investigate depressive symptoms. Meanwhile, at T0, participants were subjected to a health check-up trip in the hospital, and blood samples were taken from the students to measure the PER1 gene DNA methylation levels. Binary logistic regression was used to analyze the association of chronotypes with depressive symptoms. The depression/total depression group was coded as 1, while the remaining participants was defined as one group, and was coded as 0. The PROCESS plug-in of SPSS software was used to analyze the moderating effects of PER1 gene DNA methylation on the association of chronotype with depressive symptoms. After adjusting for covariates, the results indicated that T0 E-types were positively correlated with T0-T3 depression/total depression in female university students. Furthermore, the PER1 gene DNA methylation has negative moderating effects between T0 chronotype and T3 depressive symptoms and has a sex difference. This study can provide more favorable scientific value for the prevention and control of depression in university students.
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Affiliation(s)
- Tingting Li
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Yuxuan Cao
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Panfeng Zhou
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Yang Xie
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Shuman Tao
- MOE Key Laboratory of Population Health Across Life Cycle, Hefei, Anhui, China
- Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course, Anhui Medical University, Hefei, Anhui, China
| | - Liwei Zou
- MOE Key Laboratory of Population Health Across Life Cycle, Hefei, Anhui, China
- Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course, Anhui Medical University, Hefei, Anhui, China
| | - Yajuan Yang
- School of Nursing, Anhui Medical University, Hefei, Anhui, China
| | - Fangbiao Tao
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- MOE Key Laboratory of Population Health Across Life Cycle, Hefei, Anhui, China
- Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course, Anhui Medical University, Hefei, Anhui, China
- NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei, Anhui, China
| | - Xiaoyan Wu
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- MOE Key Laboratory of Population Health Across Life Cycle, Hefei, Anhui, China
- Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course, Anhui Medical University, Hefei, Anhui, China
- NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei, Anhui, China
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19
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You Y, Chen Y, Liu R, Zhang Y, Wang M, Yang Z, Liu J, Ma X. Inverted U-shaped relationship between sleep duration and phenotypic age in US adults: a population-based study. Sci Rep 2024; 14:6247. [PMID: 38486063 PMCID: PMC10940593 DOI: 10.1038/s41598-024-56316-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Accepted: 03/05/2024] [Indexed: 03/18/2024] Open
Abstract
Sleep is a modifiable behavior that can be targeted in interventions aimed at promoting healthy aging. This study aims to (i) identify the sleep duration trend in US adults; (ii) investigate the relationship between sleep duration and phenotypic age; and (iii) explore the role of exercise in this relationship. Phenotypic age as a novel index was calculated according to biomarkers collected from US adults based on the National Health and Nutrition Examination Survey (NHANES). Sleep information was self-reported by participants and discerned through individual interviews. The principal analytical method employed was weighted multivariable linear regression modeling, which accommodated for the complex multi-stage sampling design. The potential non-linear relationship was explored using a restricted cubic spline (RCS) model. Furthermore, subgroup analyses evaluated the potential effects of sociodemographic and lifestyle factors on the primary study outcomes. A total of 13,569 participants were finally included in, thereby resulting in a weighted population of 78,880,615. An examination of the temporal trends in sleep duration revealed a declining proportion of individuals with insufficient and markedly deficient sleep time since the 2015-2016 cycle. Taken normal sleep group as a reference, participants with extreme short sleep [β (95% CI) 0.582 (0.018, 1.146), p = 0.044] and long sleep [β (95% CI) 0.694 (0.186, 1.203), p = 0.010] were both positively associated with phenotypic age using the fully adjusted model. According to the dose-response relationship between sleep duration and phenotypic age, long sleep duration can benefit from regular exercise activity, whereas short sleep duration with more exercise tended to have higher phenotypic age. There is an inverted U-shaped relationship between short and long sleep durations and phenotypic age. This study represents an important step forward in our understanding of the complex relationship between sleep and healthy aging. By shedding light on this topic and providing practical exercise recommendations for promoting healthy sleep habits, researchers can help individuals live longer, healthier, and more fulfilling lives.
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Affiliation(s)
- Yanwei You
- Division of Sports Science and Physical Education, Tsinghua University, Beijing, 100084, China
- School of Social Sciences, Tsinghua University, Beijing, 100084, China
- IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China
| | - Yuquan Chen
- School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing & Health Sciences, Monash University, Melbourne, VIC, 3004, Australia
| | - Ruidong Liu
- Division of Sports Science and Physical Education, Tsinghua University, Beijing, 100084, China
- Sports Coaching College, Beijing Sport University, Beijing, 100091, China
| | - Yangchang Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Capital Medical University, Beijing, 100169, China
| | - Meiqing Wang
- Division of Sports Science and Physical Education, Tsinghua University, Beijing, 100084, China
- School of Social Sciences, Tsinghua University, Beijing, 100084, China
- IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China
| | - Zihao Yang
- Division of Sports Science and Physical Education, Tsinghua University, Beijing, 100084, China
- School of Social Sciences, Tsinghua University, Beijing, 100084, China
- IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China
| | - Jianxiu Liu
- Division of Sports Science and Physical Education, Tsinghua University, Beijing, 100084, China.
- Vanke School of Public Health, Tsinghua University, Beijing, 100084, China.
- IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China.
| | - Xindong Ma
- Division of Sports Science and Physical Education, Tsinghua University, Beijing, 100084, China.
- IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China.
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20
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Hong SH, Lee DB, Yoon DW, Kim J. Melatonin Improves Glucose Homeostasis and Insulin Sensitivity by Mitigating Inflammation and Activating AMPK Signaling in a Mouse Model of Sleep Fragmentation. Cells 2024; 13:470. [PMID: 38534314 PMCID: PMC10969771 DOI: 10.3390/cells13060470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 03/03/2024] [Accepted: 03/05/2024] [Indexed: 03/28/2024] Open
Abstract
Sleep fragmentation (SF) can increase inflammation and production of reactive oxygen species (ROS), leading to metabolic dysfunction. SF is associated with inflammation of adipose tissue and insulin resistance. Several studies have suggested that melatonin may have beneficial metabolic effects due to activating AMP-activated protein kinase (AMPK). However, it is unclear whether melatonin affects the AMPK signaling pathway in SF-induced metabolic dysfunction. Therefore, we hypothesize that SF induces metabolic impairment and inflammation in white adipose tissue (WAT), as well as altered intracellular homeostasis. We further hypothesize that these conditions could be improved by melatonin treatment. We conducted an experiment using adult male C57BL/6 mice, which were divided into three groups: control, SF, and SF with melatonin treatment (SF+Mel). The SF mice were housed in SF chambers, while the SF+Mel mice received daily oral melatonin. After 12 weeks, glucose tolerance tests, insulin tolerance tests, adipose tissue inflammation tests, and AMPK assessments were performed. The SF mice showed increased weight gain, impaired glucose regulation, inflammation, and decreased AMPK in WAT compared to the controls. Melatonin significantly improved these outcomes by mitigating SF-induced metabolic dysfunction, inflammation, and AMPK downregulation in adipose tissue. The therapeutic efficacy of melatonin against cardiometabolic impairments in SF may be due to its ability to restore adipose tissue homeostatic pathways.
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Affiliation(s)
- Seok Hyun Hong
- Sleep Medicine Institute, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea; (S.H.H.); (D.-B.L.)
- Department of Biomedical Laboratory Science, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea
| | - Da-Been Lee
- Sleep Medicine Institute, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea; (S.H.H.); (D.-B.L.)
- Department of Health and Safety Convergence Science, Graduate School, Korea University, Seoul 02841, Republic of Korea
| | - Dae-Wui Yoon
- Sleep Medicine Institute, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea; (S.H.H.); (D.-B.L.)
- Department of Biomedical Laboratory Science, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea
| | - Jinkwan Kim
- Sleep Medicine Institute, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea; (S.H.H.); (D.-B.L.)
- Department of Biomedical Laboratory Science, Jungwon University, Goesan-gun 28204, Chungcheongbuk-do, Republic of Korea
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21
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Reisert H, Miner B, Farhadian S. Sleep deficiency among people living with human immunodeficiency virus: A growing challenge. HIV Med 2024; 25:5-15. [PMID: 37485570 PMCID: PMC10803648 DOI: 10.1111/hiv.13526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 07/04/2023] [Indexed: 07/25/2023]
Abstract
PURPOSE OF REVIEW The purpose of this narrative review is to consolidate and summarize the existing literature on sleep deficiency among people living with human immunodeficiency virus (HIV; PLWH), to discuss the potential impact of antiretroviral therapy on sleep deficiency and to identify priorities for future research in this area. RECENT FINDINGS Three important domains of sleep deficiency include alterations in sleep quality (including sleep disorders), duration and timing. The existing HIV and sleep deficiency literature, which is robust for sleep quality but sparser for sleep duration or sleep timing, has identified epidemiological correlates and outcomes associated with sleep deficiency including sociodemographic factors, HIV-specific factors, aspects of physical and mental health and cognition. SUMMARY Sleep deficiency is a common problem among PLWH and is likely underdiagnosed, although more high-quality research is needed in this area. Sleep quality has received the most attention in the literature via methodologies that assess subjective/self-reported sleep quality, objective sleep quality or both. There is significantly less research on sleep duration and minimal research on sleep timing. Use of certain antiretroviral therapy drugs may be associated with sleep deficiency for some individuals. Future research should utilize larger, longitudinal studies with consistent, comprehensive and validated methods to assess both subjective and objective measures of sleep deficiency to better understand the prevalence, correlates and clinical implications of sleep deficiency in PLWH.
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Affiliation(s)
- Hailey Reisert
- Yale School of Medicine, Section of Infectious Diseases, New Haven, CT, USA
| | - Brienne Miner
- Yale School of Medicine, Section of Geriatrics, New Haven, CT, USA
| | - Shelli Farhadian
- Yale School of Medicine, Section of Infectious Diseases, New Haven, CT, USA
- Yale School of Medicine, Department of Neurology, New Haven, CT, USA
- Yale School of Public Health, Department of Epidemiology of Microbial Diseases, New Haven, CT, USA
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22
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Vaquer-Alicea A, Yu J, Liu H, Lucey BP. Plasma and cerebrospinal fluid proteomic signatures of acutely sleep-deprived humans: an exploratory study. SLEEP ADVANCES : A JOURNAL OF THE SLEEP RESEARCH SOCIETY 2023; 4:zpad047. [PMID: 38046221 PMCID: PMC10691441 DOI: 10.1093/sleepadvances/zpad047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 11/06/2023] [Indexed: 12/05/2023]
Abstract
Study Objectives Acute sleep deprivation affects both central and peripheral biological processes. Prior research has mainly focused on specific proteins or biological pathways that are dysregulated in the setting of sustained wakefulness. This exploratory study aimed to provide a comprehensive view of the biological processes and proteins impacted by acute sleep deprivation in both plasma and cerebrospinal fluid (CSF). Methods We collected plasma and CSF from human participants during one night of sleep deprivation and controlled normal sleep conditions. One thousand and three hundred proteins were measured at hour 0 and hour 24 using a high-scale aptamer-based proteomics platform (SOMAscan) and a systematic biological database tool (Metascape) was used to reveal altered biological pathways. Results Acute sleep deprivation decreased the number of upregulated and downregulated biological pathways and proteins in plasma but increased upregulated and downregulated biological pathways and proteins in CSF. Predominantly affected proteins and pathways were associated with immune response, inflammation, phosphorylation, membrane signaling, cell-cell adhesion, and extracellular matrix organization. Conclusions The identified modifications across biofluids add to evidence that acute sleep deprivation has important impacts on biological pathways and proteins that can negatively affect human health. As a hypothesis-driving study, these findings may help with the exploration of novel mechanisms that mediate sleep loss and associated conditions, drive the discovery of new sleep loss biomarkers, and ultimately aid in the identification of new targets for intervention to human diseases.
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Affiliation(s)
- Ana Vaquer-Alicea
- Department of Neurology, Washington University School of Medicine, St Louis, MO, USA
| | - Jinsheng Yu
- Department of Genetics, Washington University School of Medicine, St Louis, MO, USA
| | - Haiyan Liu
- Department of Neurology, Washington University School of Medicine, St Louis, MO, USA
| | - Brendan P Lucey
- Department of Neurology, Washington University School of Medicine, St Louis, MO, USA
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23
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Liu J, Huang B, Ding F, Li Y. Environment factors, DNA methylation, and cancer. ENVIRONMENTAL GEOCHEMISTRY AND HEALTH 2023; 45:7543-7568. [PMID: 37715840 DOI: 10.1007/s10653-023-01749-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Accepted: 08/30/2023] [Indexed: 09/18/2023]
Abstract
Today, the rapid development of science and technology and the rapid change in economy and society are changing the way of life of human beings and affecting the natural, living, working, and internal environment on which human beings depend. At the same time, the global incidence of cancer has increased significantly yearly, and cancer has become the number one killer that threatens human health. Studies have shown that diet, living habits, residential environment, mental and psychological factors, intestinal flora, genetics, social factors, and viral and non-viral infections are closely related to human cancer. However, the molecular mechanisms of the environment and cancer development remain to be further explored. In recent years, DNA methylation has become a key hub and bridge for environmental and cancer research. Some environmental factors can alter the hyper/hypomethylation of human cancer suppressor gene promoters, proto-oncogene promoters, and the whole genome, causing low/high expression or gene mutation of related genes, thereby exerting oncogenic or anticancer effects. It is expected to develop early warning markers of cancer environment based on DNA methylation, thereby providing new methods for early detection of cancers, diagnosis, and targeted therapy. This review systematically expounds on the internal mechanism of environmental factors affecting cancer by changing DNA methylation, aiming to help establish the concept of cancer prevention and improve people's health.
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Affiliation(s)
- Jie Liu
- Department of General Surgery, Second Hospital of Lanzhou University, Lan Zhou, China
- Key Laboratory of the Digestive System Tumors of Gansu Province, Second Hospital of Lanzhou University, Lan Zhou, China
| | - Binjie Huang
- Department of General Surgery, Second Hospital of Lanzhou University, Lan Zhou, China
- Key Laboratory of the Digestive System Tumors of Gansu Province, Second Hospital of Lanzhou University, Lan Zhou, China
| | - Feifei Ding
- Department of General Surgery, Second Hospital of Lanzhou University, Lan Zhou, China
- Key Laboratory of the Digestive System Tumors of Gansu Province, Second Hospital of Lanzhou University, Lan Zhou, China
| | - Yumin Li
- Department of General Surgery, Second Hospital of Lanzhou University, Lan Zhou, China.
- Key Laboratory of the Digestive System Tumors of Gansu Province, Second Hospital of Lanzhou University, Lan Zhou, China.
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24
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Jansen EC, Zhang KP, Dolinoy DC, Burgess HJ, O'Brien LM, Langen E, Unwala N, Ehlinger J, Mulcahy MC, Goodrich JM. Early-to-mid pregnancy sleep and circadian markers in relation to birth outcomes: An epigenetics pilot study. Chronobiol Int 2023; 40:1224-1234. [PMID: 37722702 PMCID: PMC10626590 DOI: 10.1080/07420528.2023.2256854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 09/03/2023] [Indexed: 09/20/2023]
Abstract
Maternal sleep and circadian health during pregnancy are emerging as important predictors of pregnancy outcomes, but examination of potential epigenetic mechanisms is rare. We investigated links between maternal leukocyte DNA methylation of circadian genes and birth outcomes within a pregnancy cohort. Women (n = 96) completed a questionnaire and provided a blood sample at least once during early-to-mid pregnancy (average gestation weeks = 14.2). Leukocyte DNA was isolated and DNA methylation (average percent of methylation) at multiple CpG sites within BMAL1, PER1, and MTNR1B genes were quantified by pyrosequencing. Birth outcomes including gestational age at delivery, birthweight, and head circumference were abstracted from medical charts. Linear regression analyses were run between each CpG site with birth outcomes, adjusting for important confounders. Sleep duration and timing were assessed as secondary exposures. Higher methylation of a CpG site in PER1 was associated with smaller log-transformed head circumference (β=-0.02 with 95% CI -0.02 to 0.01; P, trend = 0.04). Higher methylation of MTNR1B (averaged across sites) was associated with lower log-transformed birthweight (-0.08 with 95% CI -0.16 to -0.01; P, trend = 0.0495). In addition, longer sleep duration was associated with higher birthweight (0.10 with 95% CI 0.02 to 0.18 comparing > 9 h to < 8 h; P, trend = 0.04). This pilot investigation revealed that higher methylation of PER1 and MTNR1B genes, and sleep duration measured in early-to-mid pregnancy were related to birth outcomes.
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Affiliation(s)
- Erica C Jansen
- Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - Kelvin Pengyuan Zhang
- Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - Dana C Dolinoy
- Environmental Health Sciences and Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | | | | | - Elizabeth Langen
- Obstetrics and Gynecology, Michigan Medicine, Ann Arbor, Michigan, USA
| | - Naquia Unwala
- Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - Jessa Ehlinger
- Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - Molly C Mulcahy
- Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - Jaclyn M Goodrich
- Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
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25
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Lyons LC, Vanrobaeys Y, Abel T. Sleep and memory: The impact of sleep deprivation on transcription, translational control, and protein synthesis in the brain. J Neurochem 2023; 166:24-46. [PMID: 36802068 PMCID: PMC10919414 DOI: 10.1111/jnc.15787] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 01/31/2023] [Accepted: 02/07/2023] [Indexed: 02/20/2023]
Abstract
In countries around the world, sleep deprivation represents a widespread problem affecting school-age children, teenagers, and adults. Acute sleep deprivation and more chronic sleep restriction adversely affect individual health, impairing memory and cognitive performance as well as increasing the risk and progression of numerous diseases. In mammals, the hippocampus and hippocampus-dependent memory are vulnerable to the effects of acute sleep deprivation. Sleep deprivation induces changes in molecular signaling, gene expression and may cause changes in dendritic structure in neurons. Genome wide studies have shown that acute sleep deprivation alters gene transcription, although the pool of genes affected varies between brain regions. More recently, advances in research have drawn attention to differences in gene regulation between the level of the transcriptome compared with the pool of mRNA associated with ribosomes for protein translation following sleep deprivation. Thus, in addition to transcriptional changes, sleep deprivation also affects downstream processes to alter protein translation. In this review, we focus on the multiple levels through which acute sleep deprivation impacts gene regulation, highlighting potential post-transcriptional and translational processes that may be affected by sleep deprivation. Understanding the multiple levels of gene regulation impacted by sleep deprivation is essential for future development of therapeutics that may mitigate the effects of sleep loss.
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Affiliation(s)
- Lisa C Lyons
- Program in Neuroscience, Department of Biological Science, Florida State University, Tallahassee, Florida, USA
| | - Yann Vanrobaeys
- Department of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
- Iowa Neuroscience Institute, Iowa City, Iowa, USA
- Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, Iowa, USA
| | - Ted Abel
- Department of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
- Iowa Neuroscience Institute, Iowa City, Iowa, USA
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26
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Wendrich KS, Azimi H, Ripperger JA, Ravussin Y, Rainer G, Albrecht U. Deletion of the Circadian Clock Gene Per2 in the Whole Body, but Not in Neurons or Astroglia, Affects Sleep in Response to Sleep Deprivation. Clocks Sleep 2023; 5:204-225. [PMID: 37092429 PMCID: PMC10123656 DOI: 10.3390/clockssleep5020017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 04/11/2023] [Accepted: 04/11/2023] [Indexed: 04/25/2023] Open
Abstract
The sleep-wake cycle is a highly regulated behavior in which a circadian clock times sleep and waking, whereas a homeostatic process controls sleep need. Both the clock and the sleep homeostat interact, but to what extent they influence each other is not understood. There is evidence that clock genes, in particular Period2 (Per2), might be implicated in the sleep homeostatic process. Sleep regulation depends also on the proper functioning of neurons and astroglial cells, two cell-types in the brain that are metabolically dependent on each other. In order to investigate clock-driven contributions to sleep regulation we non-invasively measured sleep of mice that lack the Per2 gene either in astroglia, neurons, or all body cells. We observed that mice lacking Per2 in all body cells (Per2Brdm and TPer2 animals) display earlier onset of sleep after sleep deprivation (SD), whereas neuronal and astroglial Per2 knock-out animals (NPer2 and GPer2, respectively) were normal in that respect. It appears that systemic (whole body) Per2 expression is important for physiological sleep architecture expressed by number and length of sleep bouts, whereas neuronal and astroglial Per2 weakly impacts night-time sleep amount. Our results suggest that Per2 contributes to the timing of the regulatory homeostatic sleep response by delaying sleep onset after SD and attenuating the early night rebound response.
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Affiliation(s)
- Katrin S Wendrich
- Department of Biology, University of Fribourg, 1700 Fribourg, Switzerland
| | - Hamid Azimi
- Section of Medicine, Department of Neuroscience, University of Fribourg, 1700 Fribourg, Switzerland
| | - Jürgen A Ripperger
- Department of Biology, University of Fribourg, 1700 Fribourg, Switzerland
| | - Yann Ravussin
- Section of Medicine, Department of Endocrinology, Metabolism and Cardiovascular System, University of Fribourg, 1700 Fribourg, Switzerland
| | - Gregor Rainer
- Section of Medicine, Department of Neuroscience, University of Fribourg, 1700 Fribourg, Switzerland
| | - Urs Albrecht
- Department of Biology, University of Fribourg, 1700 Fribourg, Switzerland
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27
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Ou Y, Zong D, Ouyang R. Role of epigenetic abnormalities and intervention in obstructive sleep apnea target organs. Chin Med J (Engl) 2023; 136:631-644. [PMID: 35245923 PMCID: PMC10129098 DOI: 10.1097/cm9.0000000000002080] [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] [Received: 08/03/2022] [Indexed: 11/26/2022] Open
Abstract
ABSTRACT Obstructive sleep apnea (OSA) is a common condition that has considerable impacts on human health. Epigenetics has become a rapidly developing and exciting area in biology, and it is defined as heritable alterations in gene expression and has regulatory effects on disease progression. However, the published literature that is integrating both of them is not sufficient. The purpose of this article is to explore the relationship between OSA and epigenetics and to offer better diagnostic methods and treatment options. Epigenetic modifications mainly manifest as post-translational modifications in DNA and histone proteins and regulation of non-coding RNAs. Chronic intermittent hypoxia-mediated epigenetic alterations are involved in the progression of OSA and diverse multiorgan injuries, including cardiovascular disease, metabolic disorders, pulmonary hypertension, neural dysfunction, and even tumors. This article provides deeper insights into the disease mechanism of OSA and potential applications of targeted diagnosis, treatment, and prognosis in OSA complications.
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Affiliation(s)
- Yanru Ou
- Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
| | - Dandan Zong
- Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
| | - Ruoyun Ouyang
- Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
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28
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Moderating effects of PER3 gene DNA methylation on the association of sleep quality with mental health in Chinese young adults. J Affect Disord 2023; 323:716-722. [PMID: 36528137 DOI: 10.1016/j.jad.2022.12.048] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 10/02/2022] [Accepted: 12/12/2022] [Indexed: 12/23/2022]
Abstract
BACKGROUND Poor sleepers have a higher prevalence of mental health problems, and vice versa. However, the mechanisms underlying this association remain unknown. We aimed to examine the bidirectional association between sleep quality and mental health, and further explore the moderating effects of PER3 gene DNA methylation on the association. METHODS This prospective longitudinal study was conducted from April 2019 to May 2021, integrated questionnaire and blood sample data from 2 universities in Anhui and Jiangxi Provinces. The current study recruited 1179 young adults at baseline and conducted the follow-up survey among 1135 half a year later. The sleep quality and depressive symptoms, anxiety symptoms, and stress symptoms were assessed using a questionnaire at baseline and follow-up. Blood samples were collected at baseline, and MethyTarget™ was used to detect the PER3 gene DNA methylation level. A cross-lag model was used to examine the bidirectional association between sleep quality and mental health. The PROCESS plug-in of SPSS software was used to analyse the moderating effects of PER3 gene DNA methylation. RESULTS Cross-lagged analyses suggested a significant bidirectional relationship between poor sleep quality and depressive symptoms, anxiety symptoms, and stress symptoms. Sleep quality at baseline was a significant predictor of depressive symptoms (β = 0.344, P < 0.001), anxiety symptoms (β = 0.348, P < 0.001), and stress symptoms (β = 0.324, P < 0.001) half a year later. Depressive symptoms (β = 0.049, P < 0.001), anxiety symptoms (β = 0.055, P < 0.001), and stress symptoms (β = 0.063, P < 0.001) at baseline were also significant predictors of poor sleep quality half a year later. Furthermore, PER3 gene DNA methylation has negative moderating effects between sleep quality at baseline and depressive symptoms (β = -11.706, P = 0.012), anxiety symptoms (β = -10.289, P = 0.019), and stress symptoms (β = -10.799, P = 0.024) half a year later and a sex difference. Among boys, PER3 gene DNA methylation has positive moderating effects between anxiety symptoms at baseline and sleep quality (β = 3.337, P = 0.018) half a year later. However, there was no association between mental health at baseline and sleep quality half a year later among girls. CONCLUSION Bidirectional relationships were identified between sleep quality and mental health among Chinese young adults during the study period. DNA methylation evidence supports a negative moderating effect of PER3 gene DNA methylation on the relationship between sleep quality at baseline and mental health half a year later and had sex differences. Among boys, PER3 gene DNA methylation had positive moderating effects between anxiety symptoms at baseline and sleep quality half a year later. These findings point to the importance of circadian clock gene DNA methylation in the relationship between sleep quality and mental health.
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29
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Liu S, Wang X, Zheng Q, Gao L, Sun Q. Sleep Deprivation and Central Appetite Regulation. Nutrients 2022; 14:nu14245196. [PMID: 36558355 PMCID: PMC9783730 DOI: 10.3390/nu14245196] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 11/29/2022] [Accepted: 12/01/2022] [Indexed: 12/12/2022] Open
Abstract
Research shows that reduced sleep duration is related to an increased risk of obesity. The relationship between sleep deprivation and obesity, type 2 diabetes, and other chronic diseases may be related to the imbalance of appetite regulation. To comprehensively illustrate the specific relationship between sleep deprivation and appetite regulation, this review introduces the pathophysiology of sleep deprivation, the research cutting edge of animal models, and the central regulatory mechanism of appetite under sleep deprivation. This paper summarizes the changes in appetite-related hormones orexin, ghrelin, leptin, and insulin secretion caused by long-term sleep deprivation based on the epidemiology data and animal studies that have established sleep deprivation models. Moreover, this review analyzes the potential mechanism of associations between appetite regulation and sleep deprivation, providing more clues on further studies and new strategies to access obesity and metabolic disease.
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Affiliation(s)
- Shuailing Liu
- Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang 110122, China
| | - Xiya Wang
- Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang 110122, China
| | - Qian Zheng
- Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang 110122, China
| | - Lanyue Gao
- Experimental Center for School of Public Health, China Medical University, Shenyang 110122, China
| | - Qi Sun
- Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang 110122, China
- Correspondence: ; Tel./Fax: +86-15840312720
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Teo P, Henry BA, Moran LJ, Cowan S, Bennett C. The role of sleep in PCOS: what we know and what to consider in the future. Expert Rev Endocrinol Metab 2022; 17:305-318. [PMID: 35815469 DOI: 10.1080/17446651.2022.2082941] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 05/24/2022] [Indexed: 10/18/2022]
Abstract
INTRODUCTION Sleep disturbance and clinical sleep conditions disrupt endocrine signals, energy expenditure and nutritional intake. Women with polycystic ovary syndrome (PCOS) are at higher risk of sleep disturbances and clinical conditions. It is possible that sleep may contribute to the exacerbation of PCOS. This review aims to explore the relationship between sleep and chronic disease, particularly in women with PCOS. AREAS COVERED This review narratively explores what sleep is, how to measure sleep and the possible mechanisms that support the link between sleep in adipose tissue deposition, insulin resistance and the presentation of PCOS. EXPERT OPINION Research shows that disturbed sleep and clinical sleep conditions disrupt energy expenditure. This may increase adipose tissue deposition and exacerbate insulin resistance which are known to worsen the presentation of PCOS. Further, sleep disturbance in women with PCOS may ameliorate any positive lifestyle changes made after diagnosis. Cognitive behavioural therapy interventions for sleep are a successful strategy for the management of sleep disturbances in the general population. However, such interventions are yet to be trialled in women with PCOS. Given the proposed implications, interventions to improve sleep could provide additional support for women with PCOS to successfully implement lifestyle strategies and should be further investigated.
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Affiliation(s)
- Peiseah Teo
- Department of Physiology, Monash University, Melbourne, VIC, Australia
| | - Belinda A Henry
- Department of Physiology, Monash University, Melbourne, VIC, Australia
- Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia
| | - Lisa J Moran
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia
| | | | - Christie Bennett
- Department of Nutrition, Dietetics and Food, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia
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31
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Abstract
Sleep loss has negative impacts on quality of life, mood, cognitive function and heath. Insomnia or difficulty sleeping is also a prevalent issue, affecting up to 35% of the population at some point in their lives. Insomnia is linked to poor mood, increased use of health care resources, and decreased quality of life as well as possible links to cardiovascular risk factors and disease. Studies have shown an increase in cortisol levels, decreased immunity, and increased markers of sympathetic activity in sleep-deprived healthy subjects and those with chronic insomnia. The literature also shows that subjective complaints consistent with chronic insomnia and shortened sleep time, both independently and in combination, can be associated with the development of diabetes, hypertension, and cardiovascular disease. In this article, we will explore the relationship and strength of association between insufficient sleep and insomnia with these health conditions.
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Affiliation(s)
- Meena S Khan
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA; Department of Neurology, The Ohio State University, Columbus, OH, USA.
| | - Rita Aouad
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
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Meng M, Jiang Y, Lin J, Zhang J, Wang G, Zhu Q, Lin Q, Jiang F. The mediating effect of DNA methylation in the association between maternal sleep during pregnancy and offspring adiposity status: a prospective cohort study. Clin Epigenetics 2022; 14:66. [PMID: 35596190 PMCID: PMC9123687 DOI: 10.1186/s13148-022-01284-w] [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: 02/21/2022] [Accepted: 04/23/2022] [Indexed: 11/23/2022] Open
Abstract
Background Childhood overweight/obesity is a global public health concern. It is important to identify its early-life risk factors. Maternal poor sleep is common in late pregnancy, and previous studies indicated that poor sleep may influence the offspring’s adiposity status. However, very few studies in humans investigated the effect of the different sleep parameters (sleep quantity, quality, and timing) on the offspring’s adiposity indicators, and long-term studies are even more scarce. In addition, the underlying mechanism remains unclear. The present study therefore aimed to examine the association between the three maternal sleep dimensions in the late pregnancy and the offspring adiposity indicators and to explore the potential mediating effect of the cord blood DNA methylation in the above association. Methods Included participants in the current study were 2211 healthy pregnant women with singleton gestation from the Shanghai Birth Cohort (SBC) and Shanghai Sleep Birth Cohort (SSBC). Maternal nighttime sleep duration, quality, and midpoint (an indicator of circadian rhythm) were assessed by the same instrument in both cohorts during late pregnancy, and the offspring’s body mass index (BMI) and subcutaneous fat (SF) were measured at 2 years old. Additionally, in 231 SSBC samples, the genome-wide DNA methylation levels were measured using the Illumina Infinium Methylation EPIC BeadChip. The multivariate linear regression was used to determine the associations between the maternal sleep parameters and the offspring adiposity indicators. The epigenome-wide association study was conducted to identify the maternal sleep-related CpG sites. The mediation analysis was performed to evaluate the potential intermediate role of DNA methylation in the association between maternal sleep and offspring adiposity indicators. Results The mean maternal nighttime sleep duration and the sleep midpoint for combined cohorts were 9.24 ± 1.13 h and 3.02 ± 0.82, respectively, and 24.5% of pregnant women experienced poor sleep quality in late pregnancy. After adjusting for the covariates, the maternal later sleep midpoint was associated with the increased SF in offspring (Coef. = 0.62, 95% CI 0.37–0.87, p < 0.001) at 2 years old. However, no significant associations of the nighttime sleep duration or sleep quality with the offspring adiposity indicators were found. In the SSBC sample, 45 differential methylated probes (DMPs) were associated with the maternal sleep midpoint, and then, we observed 10 and 3 DMPs that were also associated with the offspring’s SF and BMI at 2 years, of which cg04351668 (MARCH9) and cg12232388 significantly mediated the relationship of sleep midpoint and SF and cg12232388 and cg12225226 mediated the sleep midpoint–BMI association, respectively. Conclusions Maternal later sleep timing in late pregnancy was associated with higher childhood adiposity in the offspring. Cord blood DNA methylation may play a mediation role in that relationship. Supplementary Information The online version contains supplementary material available at 10.1186/s13148-022-01284-w.
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Affiliation(s)
- Min Meng
- Department of Developmental and Behavioral Pediatrics, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, China.,Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China
| | - Yanrui Jiang
- Department of Developmental and Behavioral Pediatrics, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, China.,Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China
| | - Jianfei Lin
- Department of Developmental and Behavioral Pediatrics, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, China.,Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China
| | - Jun Zhang
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China.,School of Public Health, Shanghai Jiao Tong University, Shanghai, 200025, China
| | - Guanghai Wang
- Department of Developmental and Behavioral Pediatrics, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, China.,Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China.,Shanghai Center for Brain Science and Brain-Inspired Technology, Shanghai, 201602, China
| | - Qi Zhu
- Department of Developmental and Behavioral Pediatrics, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, China.,Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China
| | - Qingmin Lin
- School of Life Science and Biotechnology, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, 200240, China.
| | - Fan Jiang
- Department of Developmental and Behavioral Pediatrics, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, China. .,Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China. .,Shanghai Center for Brain Science and Brain-Inspired Technology, Shanghai, 201602, China.
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Ritchie HK, Broussard JL. CrossTalk proposal: Insufficient sleep is responsible for increased risk of metabolic disease in shift workers. J Physiol 2022; 600:1599-1602. [PMID: 35218007 PMCID: PMC8976737 DOI: 10.1113/jp282189] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 01/11/2022] [Indexed: 12/29/2022] Open
Affiliation(s)
- Hannah K Ritchie
- Publications Center of Excellence, OPEN Health Communications, Evergreen, CO, USA
| | - Josiane L Broussard
- Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.,Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA
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Effects of sleep manipulation on markers of insulin sensitivity: a systematic review and meta-analysis of randomized controlled trials. Sleep Med Rev 2022; 62:101594. [DOI: 10.1016/j.smrv.2022.101594] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 12/30/2021] [Accepted: 01/18/2022] [Indexed: 01/03/2023]
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35
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Galow AM, Peleg S. How to Slow down the Ticking Clock: Age-Associated Epigenetic Alterations and Related Interventions to Extend Life Span. Cells 2022; 11:468. [PMID: 35159278 PMCID: PMC8915189 DOI: 10.3390/cells11030468] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 01/26/2022] [Indexed: 02/04/2023] Open
Abstract
Epigenetic alterations pose one major hallmark of organismal aging. Here, we provide an overview on recent findings describing the epigenetic changes that arise during aging and in related maladies such as neurodegeneration and cancer. Specifically, we focus on alterations of histone modifications and DNA methylation and illustrate the link with metabolic pathways. Age-related epigenetic, transcriptional and metabolic deregulations are highly interconnected, which renders dissociating cause and effect complicated. However, growing amounts of evidence support the notion that aging is not only accompanied by epigenetic alterations, but also at least in part induced by those. DNA methylation clocks emerged as a tool to objectively determine biological aging and turned out as a valuable source in search of factors positively and negatively impacting human life span. Moreover, specific epigenetic signatures can be used as biomarkers for age-associated disorders or even as targets for therapeutic approaches, as will be covered in this review. Finally, we summarize recent potential intervention strategies that target epigenetic mechanisms to extend healthy life span and provide an outlook on future developments in the field of longevity research.
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Affiliation(s)
- Anne-Marie Galow
- Institute for Genome Biology, Research Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, Germany
| | - Shahaf Peleg
- Research Group Epigenetics, Metabolism and Longevity, Research Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, Germany
- Institute of Neuroregeneration and Neurorehabilitation of Qingdao University, Qingdao 266071, China
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Mahmoud AM. An Overview of Epigenetics in Obesity: The Role of Lifestyle and Therapeutic Interventions. Int J Mol Sci 2022; 23:ijms23031341. [PMID: 35163268 PMCID: PMC8836029 DOI: 10.3390/ijms23031341] [Citation(s) in RCA: 66] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 01/22/2022] [Accepted: 01/24/2022] [Indexed: 02/06/2023] Open
Abstract
Obesity has become a global epidemic that has a negative impact on population health and the economy of nations. Genetic predispositions have been demonstrated to have a substantial role in the unbalanced energy metabolism seen in obesity. However, these genetic variations cannot entirely explain the massive growth in obesity over the last few decades. Accumulating evidence suggests that modern lifestyle characteristics such as the intake of energy-dense foods, adopting sedentary behavior, or exposure to environmental factors such as industrial endocrine disruptors all contribute to the rising obesity epidemic. Recent advances in the study of DNA and its alterations have considerably increased our understanding of the function of epigenetics in regulating energy metabolism and expenditure in obesity and metabolic diseases. These epigenetic modifications influence how DNA is transcribed without altering its sequence. They are dynamic, reflecting the interplay between the body and its surroundings. Notably, these epigenetic changes are reversible, making them appealing targets for therapeutic and corrective interventions. In this review, I discuss how these epigenetic modifications contribute to the disordered energy metabolism in obesity and to what degree lifestyle and weight reduction strategies and pharmacological drugs can restore energy balance by restoring normal epigenetic profiles.
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Affiliation(s)
- Abeer M Mahmoud
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
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37
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Role of Sleep Restriction in Daily Rhythms of Expression of Hypothalamic Core Clock Genes in Mice. Curr Issues Mol Biol 2022; 44:609-625. [PMID: 35723328 PMCID: PMC8929085 DOI: 10.3390/cimb44020042] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/17/2022] [Accepted: 01/19/2022] [Indexed: 12/12/2022] Open
Abstract
Lack of sleep time is a menace to modern people, and it leads to chronic diseases and mental illnesses. Circadian processes control sleep, but little is known about how sleep affects the circadian system. Therefore, we performed a 28-day sleep restriction (SR) treatment in mice. Sleep restriction disrupted the clock genes’ circadian rhythm. The circadian rhythms of the Cry1 and Per1/2/3 genes disappeared. The acrophase of the clock genes (Bmal1, Clock, Rev-erbα, and Rorβ) that still had a circadian rhythm was advanced, while the acrophase of negative clock gene Cry2 was delayed. Clock genes’ upstream signals ERK and EIFs also had circadian rhythm disorders. Accompanied by changes in the central oscillator, the plasma output signal (melatonin, corticosterone, IL-6, and TNF-α) had an advanced acrophase. While the melatonin mesor was decreased, the corticosterone, IL-6, and TNF-α mesor was increased. Our results indicated that chronic sleep loss could disrupt the circadian rhythm of the central clock through ERK and EIFs and affect the output signal downstream of the core biological clock.
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Lin W, Saner NJ, Weng X, Caruana NJ, Botella J, Kuang J, Lee MJC, Jamnick NA, Pitchford NW, Garnham A, Bartlett JD, Chen H, Bishop DJ. The Effect of Sleep Restriction, With or Without Exercise, on Skeletal Muscle Transcriptomic Profiles in Healthy Young Males. Front Endocrinol (Lausanne) 2022; 13:863224. [PMID: 35937838 PMCID: PMC9355502 DOI: 10.3389/fendo.2022.863224] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 06/22/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Inadequate sleep is associated with many detrimental health effects, including increased risk of developing insulin resistance and type 2 diabetes. These effects have been associated with changes to the skeletal muscle transcriptome, although this has not been characterised in response to a period of sleep restriction. Exercise induces a beneficial transcriptional response within skeletal muscle that may counteract some of the negative effects associated with sleep restriction. We hypothesised that sleep restriction would down-regulate transcriptional pathways associated with glucose metabolism, but that performing exercise would mitigate these effects. METHODS 20 healthy young males were allocated to one of three experimental groups: a Normal Sleep (NS) group (8 h time in bed per night (TIB), for five nights (11 pm - 7 am)), a Sleep Restriction (SR) group (4 h TIB, for five nights (3 am - 7 am)), and a Sleep Restriction and Exercise group (SR+EX) (4 h TIB, for five nights (3 am - 7 am) and three high-intensity interval exercise (HIIE) sessions (performed at 10 am)). RNA sequencing was performed on muscle samples collected pre- and post-intervention. Our data was then compared to skeletal muscle transcriptomic data previously reported following sleep deprivation (24 h without sleep). RESULTS Gene set enrichment analysis (GSEA) indicated there was an increased enrichment of inflammatory and immune response related pathways in the SR group post-intervention. However, in the SR+EX group the direction of enrichment in these same pathways occurred in the opposite directions. Despite this, there were no significant changes at the individual gene level from pre- to post-intervention. A set of genes previously shown to be decreased with sleep deprivation was also decreased in the SR group, but increased in the SR+EX group. CONCLUSION The alterations to inflammatory and immune related pathways in skeletal muscle, following five nights of sleep restriction, provide insight regarding the transcriptional changes that underpin the detrimental effects associated with sleep loss. Performing three sessions of HIIE during sleep restriction attenuated some of these transcriptional changes. Overall, the transcriptional alterations observed with a moderate period of sleep restriction were less evident than previously reported changes following a period of sleep deprivation.
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Affiliation(s)
- Wentao Lin
- College of Exercise and Health, Guangzhou Sport University, Guangzhou, China
| | - Nicholas J. Saner
- Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia
- Human Integrative Physiology, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
| | - Xiquan Weng
- College of Exercise and Health, Guangzhou Sport University, Guangzhou, China
| | - Nikeisha J. Caruana
- Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia
- Department of Biochemistry and Pharmacology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia
| | - Javier Botella
- Department of Biochemistry and Pharmacology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia
| | - Jujiao Kuang
- Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia
| | - Matthew J-C. Lee
- Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia
| | - Nicholas A. Jamnick
- Metabolic Research Unit, Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, VIC, Australia
| | - Nathan W. Pitchford
- School of Health Sciences, University of Tasmania, Launceston, TAS, Australia
| | - Andrew Garnham
- Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia
| | | | - Hao Chen
- College of Exercise and Health, Guangzhou Sport University, Guangzhou, China
- *Correspondence: Hao Chen, ; David J. Bishop,
| | - David J. Bishop
- Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia
- *Correspondence: Hao Chen, ; David J. Bishop,
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Carpena MX, Bonilla C, Matijasevich A, Martins-Silva T, Genro JP, Hutz MH, Rohde LA, Tovo-Rodrigues L. Sleep-related traits and attention-deficit/hyperactivity disorder comorbidity: Shared genetic risk factors, molecular mechanisms, and causal effects. World J Biol Psychiatry 2021; 22:778-791. [PMID: 33821771 DOI: 10.1080/15622975.2021.1907719] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
OBJECTIVES To evaluate the shared genetic components, common pathways and causal relationship between ADHD and sleep-related phenotypes. METHODS We used the largest genome-wide association summary statistics available for attention-deficit/hyperactivity disorder (ADHD) and various sleep-related phenotypes (insomnia, napping, daytime dozing, snoring, ease getting up, daytime sleepiness, sleep duration and chronotype). We estimated the genomic correlation using cross-trait linkage disequilibrium score regression (LDSR) and investigated the potential common mechanisms using gene-based cross-trait metanalyses and functional enrichment analyses. The causal effect was estimated using two-sample Mendelian randomisation (TSMR), using the inverse variance weighted method as the main estimator. RESULTS A positive genomic correlation between insomnia, daytime napping, daytime dozing, snoring, daytime sleepiness, short and long sleep duration, and ADHD was observed. Insomnia, daytime sleepiness, and snoring shared genes with ADHD, that are involved in neurobiological functions and regulatory signalling pathways. The TSMR supported a causal effect of insomnia, daytime napping, and short sleep duration on ADHD, and of ADHD on long sleep duration and chronotype. CONCLUSION Comorbidity between sleep phenotypes and ADHD may be mediated by common genetic factors that play an important role in neuronal signalling pathways. A causal effect of sleep disturbances and short sleep duration on ADHD reinforced their role as predictors of ADHD.
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Affiliation(s)
- Marina Xavier Carpena
- Post-Graduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil
| | - Carolina Bonilla
- Departamento de Medicina Preventiva, Faculdade de Medicina FMUSP, Universidade de São Paulo, SP, Brasil.,Population Health Sciences, University of Bristol, Bristol, UK
| | - Alicia Matijasevich
- Post-Graduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.,Departamento de Medicina Preventiva, Faculdade de Medicina FMUSP, Universidade de São Paulo, SP, Brasil
| | - Thais Martins-Silva
- Post-Graduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil
| | - Julia P Genro
- Graduate Program in Biosciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
| | - Mara Helena Hutz
- Department of Genetics, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Luis Augusto Rohde
- Federal University of Rio Grande do Sul, Department of Psychiatry, Child & Adolescent Psychiatry Unit, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil
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Aghagoli G, Del Re A, Yano N, Zhang Z, Gheit AA, Phillips RK, Sellke FW, Fedulov AV. Methylome of skeletal muscle tissue in patients with hypertension and diabetes undergoing cardiopulmonary bypass. Epigenomics 2021; 13:1853-1866. [PMID: 34802257 PMCID: PMC8619827 DOI: 10.2217/epi-2021-0388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 11/08/2021] [Indexed: 11/21/2022] Open
Abstract
Background: Epigenomic changes occurring during surgery have been neglected in research; diabetes and hypertension can affect the epigenome but little is known about the epigenetics of skeletal muscle (SKM). Methods: DNA methylation was profiled via Illumina MethylationEPIC arrays in SKM samples obtained at the beginning and end of heart surgery with cardiopulmonary bypass. Results: Methylation in patients with hypertension and diabetes was significantly different, more so for uncontrolled diabetes; hypertension alone produced minimal effect. The affected pathways involved IL-1, IL-12, IL-18, TNF-α, IFN-γ, VEGF, NF-κB and Wnt signaling, apoptosis and DNA damage response. Significant changes occurred during surgery and included loci in the Hippo-YAP/TAZ pathway. Conclusion: Cardiopulmonary bypass surgery affects the SKM methylome, and the combination of hypertension and diabetes induces changes in the SKM epigenome in contrast to hypertension alone.
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Affiliation(s)
- Ghazal Aghagoli
- Alpert Medical School of Brown University, Department of Surgery, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA
| | - Andrew Del Re
- Alpert Medical School of Brown University, Department of Surgery, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA
| | - Naohiro Yano
- Alpert Medical School of Brown University, Department of Surgery, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA
| | - Zhiqi Zhang
- Alpert Medical School of Brown University, Department of Surgery, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA
| | - Ahmad Aboul Gheit
- Alpert Medical School of Brown University, Department of Surgery, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA
| | - Ronald K Phillips
- Alpert Medical School of Brown University, Department of Surgery, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA
| | - Frank W Sellke
- Alpert Medical School of Brown University, Department of Surgery, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA
| | - Alexey V Fedulov
- Alpert Medical School of Brown University, Department of Surgery, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA
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Applying deductive reasoning and the principles of particle physics to aging research. Aging (Albany NY) 2021; 13:22611-22622. [PMID: 34543232 PMCID: PMC8507302 DOI: 10.18632/aging.203555] [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: 07/28/2021] [Accepted: 09/11/2021] [Indexed: 11/25/2022]
Abstract
Aging is debatably one of the biggest mysteries for humanity, a process consisting of myriads of genetic, molecular, environmental, and stochastic deleterious events, leading to a progressive loss of organism functionality. Aging research currently lacks a common conceptual framework, and one challenge in establishing it is the fact that aging is a highly complex process. To help develop a framework of standard aging rules, we suggest the use of deductive reasoning based on particle physics' principles. Specifically, the principles that we suggest applying to study aging are discreteness of processes, transformation as a result of interaction, and understanding of threshold. Using this framework, biological aging may be described as a sequence of highly discrete molecular transformations caused by a combination of various specific internal and external factors. Internal organismal function and interaction of an organism with the environment result in chronic accumulation of molecular damage and other deleterious consequences of metabolism and the consequent loss of system's functionality. The loss of functionality occurs as a series of thresholds the organism reaches before it turns into an utterly non-functional state. We discuss how having a common ground may benefit aging research, introduce the logic of new principles and analyze specific examples of how this framework could be used to study aging and design longevity interventions.
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Mateus Brandão LE, Espes D, Westholm JO, Martikainen T, Westerlund N, Lampola L, Popa A, Vogel H, Schürmann A, Dickson SL, Benedict C, Cedernaes J. Acute sleep loss alters circulating fibroblast growth factor 21 levels in humans: A randomised crossover trial. J Sleep Res 2021; 31:e13472. [PMID: 34476847 DOI: 10.1111/jsr.13472] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 07/14/2021] [Accepted: 08/12/2021] [Indexed: 12/11/2022]
Abstract
The hormone fibroblast growth factor 21 (FGF21) modulates tissue metabolism and circulates at higher levels in metabolic conditions associated with chronic sleep-wake disruption, such as type 2 diabetes and obesity. In the present study, we investigated whether acute sleep loss impacts circulating levels of FGF21 and tissue-specific production, and response pathways linked to FGF21. A total of 15 healthy normal-weight young men participated in a randomised crossover study with two conditions, sleep loss versus an 8.5-hr sleep window. The evening before each intervention, fasting blood was collected. Fasting, post-intervention morning skeletal muscle and adipose tissue samples underwent quantitative polymerase chain reaction and DNA methylation analyses, and serum FGF21 levels were measured before and after an oral glucose tolerance test. Serum levels of FGF21 were higher after sleep loss compared with sleep, both under fasting conditions and following glucose intake (~27%-30%, p = 0.023). Fasting circulating levels of fibroblast activation protein, a protein which can degrade circulating FGF21, were not altered by sleep loss, whereas DNA methylation in the FGF21 promoter region increased only in adipose tissue. However, even though specifically the muscle exhibited transcriptional changes indicating adverse alterations to redox and metabolic homeostasis, no tissue-based changes were observed in expression of FGF21, its receptors, or selected signalling targets, in response to sleep loss. In summary, we found that acute sleep loss resulted in increased circulating levels of FGF21 in healthy young men, which may occur independent of a tissue-based stress response in metabolic peripheral tissues. Further studies may decipher whether changes in FGF21 signalling after sleep loss modulate metabolic outcomes associated with sleep or circadian disruption.
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Affiliation(s)
| | - Daniel Espes
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden.,Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
| | - Jakub Orzechowski Westholm
- Department of Biochemistry and Biophysics, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Stockholm University, Stockholm, Sweden
| | | | | | - Lauri Lampola
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Alexandru Popa
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Heike Vogel
- Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.,German Center for Diabetes Research, Neuherberg, Germany.,Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology Cottbus - Senftenberg, , The Brandenburg Medical School Theodor Fontane and the University of Potsdam, Potsdam, Germany
| | - Annette Schürmann
- Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.,German Center for Diabetes Research, Neuherberg, Germany
| | - Suzanne L Dickson
- Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | | | - Jonathan Cedernaes
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden.,Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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The role of clock genes in sleep, stress and memory. Biochem Pharmacol 2021; 191:114493. [DOI: 10.1016/j.bcp.2021.114493] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 02/22/2021] [Accepted: 02/23/2021] [Indexed: 12/23/2022]
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Gene expression correlates of advanced epigenetic age and psychopathology in postmortem cortical tissue. Neurobiol Stress 2021; 15:100371. [PMID: 34458511 PMCID: PMC8377489 DOI: 10.1016/j.ynstr.2021.100371] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 07/02/2021] [Accepted: 07/23/2021] [Indexed: 11/22/2022] Open
Abstract
Psychiatric stress has been associated with accelerated epigenetic aging (i.e., when estimates of cellular age based on DNA methylation exceed chronological age) in both blood and brain tissue. Little is known about the downstream biological effects of accelerated epigenetic age on gene expression. In this study we examined associations between DNA methylation-derived estimates of cellular age that range from decelerated to accelerated relative to chronological age (“DNAm age residuals”) and transcriptome-wide gene expression. This was examined using tissue from three post-mortem cortical regions (ventromedial and dorsolateral prefrontal cortex and motor cortex, n = 97) from the VA National PTSD Brain Bank. In addition, we examined how posttraumatic stress disorder (PTSD) and alcohol-use disorders (AUD) moderated the association between DNAm age residuals and gene expression. Transcriptome-wide results across brain regions, psychiatric diagnoses, and cohorts (full sample and male and female subsets) revealed experiment-wide differential expression of 11 genes in association with PTSD or AUD in interaction with DNAm age residuals. This included the inflammation-related genes IL1B, RCOR2, and GCNT1. Candidate gene class analyses and gene network enrichment analyses further supported differential expression of inflammation/immune gene networks as well as glucocorticoid, circadian, and oxidative stress-related genes. Gene co-expression network modules suggested enrichment of myelination related processes and oligodendrocyte enrichment in association with DNAm age residuals in the presence of psychopathology. Collectively, results suggest that psychiatric stress accentuates the association between advanced epigenetic age and expression of inflammation genes in the brain. This highlights the role of inflammatory processes in the pathophysiology of accelerated cellular aging and suggests that inflammatory pathways may link accelerated cellular aging to premature disease onset and neurodegeneration, particularly in stressed populations. This suggests that anti-inflammatory interventions may be an important direction to pursue in evaluating ways to prevent or delay cellular aging and increase resilience to diseases of aging.
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Actigraphy-derived rest-activity rhythms are associated with nocturnal blood pressure in young women. J Hypertens 2021; 39:2413-2421. [PMID: 34387571 DOI: 10.1097/hjh.0000000000002966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
INTRODUCTION Misalignment between lifestyle behaviors and endogenous circadian rhythms is associated with elevated nocturnal blood pressure (BP) in experimental studies; however, less is known about free-living (i.e. nonlaboratory) circadian disruption and nocturnal BP. Additionally, sex-specific cardiovascular implications of circadian disruption are unclear. OBJECTIVE To examine the associations between rest--activity rhythms (RAR), a field-based estimate of circadian disruption, and nocturnal BP characteristics in male and female young adults. METHODS Fifty participants (20 ± 1 years; 20 men/30 women) underwent 24-h ambulatory BP monitoring following 14 days of wrist actigraphy. RAR variables of interdaily stability (day-to-day consistency in RAR), intradaily variability (within-day fragmentation of RAR), and relative amplitude (difference between peak vs. trough activity) were derived from actigraphy. Multivariable regression models of mean nocturnal SBP, DBP, and SBP dipping were generated to test main associations with RAR variables, and sex × RAR interactions. Daytime BP, race, BMI, physical activity, sleep duration, alcohol, caffeine, and sodium intake were considered as covariates. RESULTS In the full sample, no main associations between RAR and nocturnal BP characteristics were found. Sex interacted with RAR such that in women, higher interdaily stability (β = -5.39, 95% CI = -10.04 to -0.73, P = 0.024) and relative amplitude (β = -4.78, 95% CI = -9.22 to -0.34, P = 0.036) were both associated with lower nocturnal SBP. Sex-stratified multivariable models of nocturnal BP also revealed associations between interdaily stability and relative amplitude with SBP dipping in women (all P ≤ 0.01). No associations were apparent in men. CONCLUSION Consistent and high-amplitude RAR are favorably associated with nocturnal BP characteristics in young female adults.
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Gaine ME, Bahl E, Chatterjee S, Michaelson JJ, Abel T, Lyons LC. Altered hippocampal transcriptome dynamics following sleep deprivation. Mol Brain 2021; 14:125. [PMID: 34384474 PMCID: PMC8361790 DOI: 10.1186/s13041-021-00835-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 07/27/2021] [Indexed: 12/13/2022] Open
Abstract
Widespread sleep deprivation is a continuing public health problem in the United States and worldwide affecting adolescents and adults. Acute sleep deprivation results in decrements in spatial memory and cognitive impairments. The hippocampus is vulnerable to acute sleep deprivation with changes in gene expression, cell signaling, and protein synthesis. Sleep deprivation also has long lasting effects on memory and performance that persist after recovery sleep, as seen in behavioral studies from invertebrates to humans. Although previous research has shown that acute sleep deprivation impacts gene expression, the extent to which sleep deprivation affects gene regulation remains unknown. Using an unbiased deep RNA sequencing approach, we investigated the effects of acute sleep deprivation on gene expression in the hippocampus. We identified 1,146 genes that were significantly dysregulated following sleep deprivation with 507 genes upregulated and 639 genes downregulated, including protein coding genes and long non-coding RNAs not previously identified as impacted by sleep deprivation. Notably, genes significantly upregulated after sleep deprivation were associated with RNA splicing and the nucleus. In contrast, downregulated genes were associated with cell adhesion, dendritic localization, the synapse, and postsynaptic membrane. Furthermore, we found through independent experiments analyzing a subset of genes that three hours of recovery sleep following acute sleep deprivation was sufficient to normalize mRNA abundance for most genes, although exceptions occurred for some genes that may affect RNA splicing or transcription. These results clearly demonstrate that sleep deprivation differentially regulates gene expression on multiple transcriptomic levels to impact hippocampal function.
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Affiliation(s)
- Marie E Gaine
- Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
- Department of Pharmaceutical Sciences and Experimental Therapeutics (PSET), College of Pharmacy, University of Iowa, Iowa City, IA, USA
| | - Ethan Bahl
- Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
- Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA, USA
| | - Snehajyoti Chatterjee
- Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
| | - Jacob J Michaelson
- Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
- Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA, USA
- Department of Communication Sciences and Disorders, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA, USA
- Iowa Institute of Human Genetics, University of Iowa, Iowa City, IA, USA
| | - Ted Abel
- Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
| | - Lisa C Lyons
- Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
- Department of Biological Science, Program in Neuroscience, Florida State University, Tallahassee, FL, USA.
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Abstract
The original rationale for the adoption of daylight saving time (DST) was to conserve energy; however, the effects of DST on energy consumption are questionable or negligible. Conversely, there is substantial evidence that DST transitions have the cumulative effect on sleep deprivation with its adverse health effects. In light of current evidence, the European Commission in 2018 decided that biannual clock change in Europe would be abolished. Current indirect evidence supports the adoption of perennial standard time, which aligns best with the human circadian system and has the potential to produce benefits for public health and safety.
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Dashti HS, Ordovás JM. Genetics of Sleep and Insights into Its Relationship with Obesity. Annu Rev Nutr 2021; 41:223-252. [PMID: 34102077 DOI: 10.1146/annurev-nutr-082018-124258] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Considerable recent advancements in elucidating the genetic architecture of sleep traits and sleep disorders may provide insight into the relationship between sleep and obesity. Despite the considerable involvement of the circadian clock in sleep and metabolism, few shared genes, including FTO, were implicated in genome-wide association studies (GWASs) of sleep and obesity. Polygenic scores composed of signals from GWASs of sleep traits show largely null associations with obesity, suggesting lead variants are unique to sleep. Modest genome-wide genetic correlations are observed between many sleep traits and obesity and are largest for snoring.Notably, U-shaped positive genetic correlations with body mass index (BMI) exist for both short and long sleep durations. Findings from Mendelian randomization suggest robust causal effects of insomnia on higher BMI and, conversely, of higher BMI on snoring and daytime sleepiness. Bidirectional effects between sleep duration and daytime napping with obesity may also exist. Limited gene-sleep interaction studies suggest that achieving favorable sleep, as part of a healthy lifestyle, may attenuate genetic predisposition to obesity, but whether these improvements produce clinically meaningful reductions in obesity risk remains unclear. Investigations of the genetic link between sleep and obesity for sleep disorders other than insomnia and in populations of non-European ancestry are currently limited. Expected final online publication date for the Annual Review of Nutrition, Volume 41 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Affiliation(s)
- Hassan S Dashti
- Center for Genomic Medicine and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA; .,Broad Institute, Cambridge, Massachusetts 02142, USA
| | - José M Ordovás
- Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111, USA.,Precision Nutrition and Obesity Program, IMDEA Alimentación, 28049 Madrid, Spain
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Abdul F, Sreenivas N, Kommu JVS, Banerjee M, Berk M, Maes M, Leboyer M, Debnath M. Disruption of circadian rhythm and risk of autism spectrum disorder: role of immune-inflammatory, oxidative stress, metabolic and neurotransmitter pathways. Rev Neurosci 2021; 33:93-109. [PMID: 34047147 DOI: 10.1515/revneuro-2021-0022] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 05/01/2021] [Indexed: 12/27/2022]
Abstract
Circadian rhythms in most living organisms are regulated by light and synchronized to an endogenous biological clock. The circadian clock machinery is also critically involved in regulating and fine-tuning neurodevelopmental processes. Circadian disruption during embryonic development can impair crucial phases of neurodevelopment. This can contribute to neurodevelopmental disorders like autism spectrum disorder (ASD) in the offspring. Increasing evidence from studies showing abnormalities in sleep and melatonin as well as genetic and epigenetic changes in the core elements of the circadian pathway indicate a pivotal role of circadian disruption in ASD. However, the underlying mechanistic basis through which the circadian pathways influence the risk and progression of ASD are yet to be fully discerned. Well-recognized mechanistic pathways in ASD include altered immune-inflammatory, nitro oxidative stress, neurotransmission and synaptic plasticity, and metabolic pathways. Notably, all these pathways are under the control of the circadian clock. It is thus likely that a disrupted circadian clock will affect the functioning of these pathways. Herein, we highlight the possible mechanisms through which aberrations in the circadian clock might affect immune-inflammatory, nitro-oxidative, metabolic pathways, and neurotransmission, thereby driving the neurobiological sequelae leading to ASD.
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Affiliation(s)
- Fazal Abdul
- Department of Human Genetics, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore, 560029, Karnataka, India
| | - Nikhitha Sreenivas
- Department of Human Genetics, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore, 560029, Karnataka, India
| | - John Vijay Sagar Kommu
- Department of Child and Adolescent Psychiatry, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore, 560029, Karnataka, India
| | - Moinak Banerjee
- Human Molecular Genetics Division, Rajiv Gandhi Centre for Biotechnology, Thycaud Post, Poojappura, Trivandrum, 695014, Kerala, India
| | - Michael Berk
- School of Medicine, IMPACT Strategic Research Centre, Deakin University, Barwon Health, PO Box 281, Geelong, Victoria, 3220, Australia.,Orygen, The Centre of Excellence in Youth Mental Health, The Department of Psychiatry, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, Victoria, 3052, Australia
| | - Michael Maes
- School of Medicine, IMPACT Strategic Research Centre, Deakin University, Barwon Health, PO Box 281, Geelong, Victoria, 3220, Australia.,Department of Psychiatry, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Pathum Wan, Pathum Wan District, Bangkok, 10330, Thailand.,Department of Psychiatry, Medical University of Plovdiv, bul. "Vasil Aprilov" 15A, 4002 Tsetar, Plovdiv, Bulgaria
| | - Marion Leboyer
- Université Paris Est Creteil (UPEC), AP-HP, Hôpitaux Universitaires "H. Mondor", DMU IMPACT, INSERM, IMRB, Translational Neuropsychiatry, Fondation FondaMental, 8, rue du Général Sarrail, 94010, Creteil, France
| | - Monojit Debnath
- Department of Human Genetics, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore, 560029, Karnataka, India
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Wang Y, Zeng Y, Zhang X, Meng Q, Mi F, Wang S, Xu F, Sun Y, Feng Y, Yin J. Daytime Napping Duration Is Positively Associated With Risk of Hyperuricemia in a Chinese Population. J Clin Endocrinol Metab 2021; 106:e2096-e2105. [PMID: 33507274 DOI: 10.1210/clinem/dgab043] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Indexed: 11/19/2022]
Abstract
CONTEXT Loss of sleep or disturbance of sleep-wake cycles has been related to metabolic impairments. However, few studies have investigated the association between daily sleep duration and hyperuricemia. OBJECTIVE We investigated daily sleep duration (daytime napping and nocturnal sleep) with hyperuricemia risk. METHODS We cross-sectionally analyzed data from the China Multi-Ethnic Cohort (CMEC), Yunnan region. A total of 22 038 participants aged 30 to 79 years were recruited in 2018. Hyperuricemia was defined as serum uric acid (SUA) above 7.0 mg/dL in men and above 6.0 mg/dL in women. Outcomes were associations between daily sleep duration and hyperuricemia. RESULTS We found that the longest daytime napping duration was associated with a higher risk of hyperuricemia in the crude model (odds ratio [OR] [95% CI], 2.22 [1.88-2.61], P < .001) and in a multivariable adjustment model (OR, 1.69; 95% CI, 1.41-2.01, P < .001) after adjusting for demographic, sleep habits, and metabolic risk factors. The association was moderately attenuated with additionally adjusted for serum creatinine (OR, 1.54; 95% CI, 1.28-1.86, P < .001). Longer daytime napping duration was also related to higher risk of hyperuricemia combined with metabolic syndrome (MetS). Respondents in the group with daytime napping duration greater than or equal to 90 minutes presented with a higher risk of hyperuricemia combined with MetS (OR, 1.39; 95% CI, 1.06-1.79; P < .001) in the fully adjusted model. We did not observe any relation between nocturnal sleep duration and risk of hyperuricemia in the study. CONCLUSION Longer daytime napping duration (but not nocturnal sleep duration) was independently associated with risk of hyperuricemia in a Chinese population.
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Affiliation(s)
- Yanjiao Wang
- School of Public Health, Kunming Medical University, Chenggong District, Kunming, China
| | - Yongli Zeng
- School of Public Health, Kunming Medical University, Chenggong District, Kunming, China
| | - Xuehui Zhang
- School of Public Health, Kunming Medical University, Chenggong District, Kunming, China
| | - Qiong Meng
- School of Public Health, Kunming Medical University, Chenggong District, Kunming, China
| | - Fei Mi
- School of Public Health, Kunming Medical University, Chenggong District, Kunming, China
| | - Songmei Wang
- School of Public Health, Kunming Medical University, Chenggong District, Kunming, China
| | - Fang Xu
- School of Public Health, Kunming Medical University, Chenggong District, Kunming, China
| | - Yan Sun
- Department of Ultrasound, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yuemei Feng
- School of Public Health, Kunming Medical University, Chenggong District, Kunming, China
| | - Jianzhong Yin
- School of Public Health, Kunming Medical University, Chenggong District, Kunming, China
- Baoshan College of Traditional Chinese Medicine, Baoshan, China
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