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Circadian rhythm disorganization produces profound cardiovascular and renal disease in hamsters
Abstract
Sleep deprivation, shift work, and jet lag all disrupt normal biological rhythms and have major impacts on health; however, circadian disorganization has never been shown as a causal risk factor in organ disease. We now demonstrate devastating effects of rhythm disorganization on cardiovascular and renal integrity and that interventions based on circadian principles prevent disease pathology caused by a short-period mutation ( tau) of the circadian system in hamsters. The point mutation in the circadian regulatory gene, casein kinase-1ε, produces early onset circadian entrainment with fragmented patterns of behavior in +/ tau heterozygotes. Animals die at a younger age with cardiomyopathy, extensive fibrosis, and severely impaired contractility; they also have severe renal disease with proteinuria, tubular dilation, and cellular apoptosis. On light cycles appropriate for their genotype (22 h), cyclic behavioral patterns are normalized, cardiorenal phenotype is reversed, and hearts and kidneys show normal structure and function. Moreover, hypertrophy does not develop in animals whose suprachiasmatic nucleus was ablated as young adults. Circadian organization therefore is critical for normal health and longevity, whereas chronic global asynchrony is implicated in the etiology of cardiac and renal disease.
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In the citing paper
“Disruptions of the molecular clock in animals cause significant CV disease (61), exemplifying the importance of these rhythms.”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [61]
In the citing paper
“Cardiomyopathy was observed in hamsters whose internal circadian clock period did not match the external 24-hour light cycle (i.e., 20-hour period due to the tau mutation) (61,144).”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [61]
In the citing paper
“Tau mutant hamsters have a shorter life span and have cardiomyopathy, fibrosis, and impaired heart contractility when they live on a 24-h light/dark cycle which is beyond their circadian timing system’s range of entrainment and thus causes the animal’s behavioral cycle and biological timing system to be out of phase (i.e., desynchronized; Martino et al., 2008).”
From The impact of the circadian timing system on cardiovascular and metabolic function (2012) · cites this paper as Martino et al., 2008
In the citing paper
“Tau mutant hamsters have a shorter life span and have cardiomyopathy, fibrosis, and impaired heart contractility when they live on a 24-h light/dark cycle which is beyond their circadian timing system’s range of entrainment and thus causes the animal’s behavioral cycle and biological timing system to be out of phase (i.e., desynchronized; Martino et al., 2008).”
From The impact of the circadian timing system on cardiovascular and metabolic function (2012) · cites this paper as Martino et al., 2008
In the citing paper
“Remarkably, when Tau mutant hamsters are placed in 22-h light/dark cycles, similar to their endogenous circadian period, these pathological changes are largely reversed.”
From The impact of the circadian timing system on cardiovascular and metabolic function (2012) · cites this paper as Martino et al., 2008
In the citing paper
“for example, in hamsters living in a light:dark cycle 2 hours different from the period of their normal clock, cardiac hypertrophy and renal failure are observed.57”
From Sleep Deprivation and Circadian Disruption (2015) · cites this paper as [57]
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Crnko, S. (2022) · Utrecht University Repository (Utrecht University) · doi:10.33540/919
Metadata
- Authors
- Martino, T. A., Oudit, G. Y., Herzenberg, A. M., Tata, N., Koletar, M. M., Kabir, G. M., Belsham, D. D., Backx, P. H., Ralph, M. R., & Sole, M. J.
- Affiliations
- University Health Network (CA)
- ORCID
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2008-05
- Volume
- 294
- Issue
- 5
- Pages
- R1675-R1683
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2117583882
- Cited by
- 317
- References
- 28
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 27 · 2023: 15 · 2022: 17 · 2021: 18 · 2020: 16 · 2019: 20 · 2018: 11 · 2017: 18 · 2016: 14 · 2015: 20 · 2014: 20 · 2013: 21 · 2012: 15
- FWCI
- 9.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- CK1ε, tau mutations, circadian entrainment, cardiomyopathy, myocardial fibrosis, kidney disease, proteinuria, apoptosis, light cycle, aging, longevity, sleep deprivation, shift work, jet lag, hamster
- MeSH terms
- Animals, Blood Pressure, Body Temperature, Cardiovascular Diseases, Circadian Rhythm, Echocardiography, Electrophoresis, Polyacrylamide Gel, Cricetinae, Heart Rate, Immunohistochemistry, Kidney, Kidney Diseases, Kidney Function Tests, Kidney Glomerulus, Microscopy, Electron, Motor Activity, Myocardium, Mass Spectrometry, Suprachiasmatic Nucleus, Ventricular Function, Left, tau Proteins, In Situ Nick-End Labeling, Proteomics
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