Effects of insufficient sleep on circadian rhythmicity and expression amplitude of the human blood transcriptome
Open accessAbstract
Significance: Insufficient sleep and circadian rhythm disruption are associated with negative health outcomes, but the mechanisms involved remain largely unexplored. We show that one wk of insufficient sleep alters gene expression in human blood cells, reduces the amplitude of circadian rhythms in gene expression, and intensifies the effects of subsequent acute total sleep loss on gene expression. The affected genes are involved in chromatin remodeling, regulation of gene expression, and immune and stress responses. The data imply molecular mechanisms mediating the effects of sleep loss on health and highlight the interrelationships between sleep homeostasis, circadian rhythmicity, and metabolism.
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Moller-Levet et al. reported reduced amplitude of circadian expression of core clock genes following seven nights of sleep restriction (6 h TIB each night) in human white blood cells.
“Previously, Moller-Levet et al. [65] reported reduced amplitude of circadian expression of core clock genes following seven nights of sleep restriction (6 h TIB each night), in human white blood cells.”
From Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms (2021) · cites this paper as [65]
Experimental restriction of sleep to 4-5 h per night for 1-2 weeks down-regulates gene pathways for macromolecular biosynthesis and metabolic processes.
“down-regulates gene pathways for macromolecular biosynthesis and metabolic processes8”
From Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses (2016) · cites this paper as [8]
Gene-expression profiling has established a complex but defined interaction between the circadian system and sleep homeostasis in humans.
“Gene-expression profiling has established that there is a complex, but defined, interaction between the circadian system and sleep homeostasis (8) in humans.”
From Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt (2015) · cites this paper as [8]
One week of a 5.70-hour-per-night sleep restriction protocol affects rhythms of the human blood transcriptome.
“1 wk of 5.70 h per night SR protocol was shown to affect rhythms of the human blood transcriptome (8).”
From Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt (2015) · cites this paper as [8]
Transcript studies show that oxidative stress and reactive oxygen species pathways are significantly induced in blood after sleep loss.
“Although plasmalogens were not significantly changed in the human study, transcript studies have shown that pathways involved in oxidative stress and reactive oxygen species are significantly induced in blood upon sleep loss (8).”
From Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt (2015) · cites this paper as [8]
Mounting evidence indicates that sleep loss induces an oxidative metabolic state.
“Mounting evidence points to sleep loss inducing an oxidative metabolic state (8,48).”
From Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt (2015) · cites this paper as [8]
The dampening of the cortisol rhythm after 2 nights of sleep loss is consistent with recent studies that have shown that lack of sleep alters the phase and the amplitude of circadian-driven rhythms.
“The dampening of the cortisol rhythm after 2 nights of sleep loss is consistent with recent studies that have shown that lack of sleep alters the phase and the amplitude of circadian-driven rhythms (40, 41).”
From Adverse effects of two nights of sleep restriction on the hypothalamic-pituitary-adrenal axis in healthy men (2014) · cites this paper as [41]
During the night of and the morning after total sleep deprivation or restriction, NK-cell activity is reduced in healthy humans.
“During both the night of and the morning after total sleep deprivation or restriction, NK-cell activity was reduced in healthy humans (253, 254, 386)”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [386]
Partial sleep restriction for 4 hours in bed per night for 5-7 days activated several gene pathways, notably those involved in the stress response and apoptosis, as measured by gene microarray.
“Partial sleep restriction for 4 hours in bed per night for 5–7 days activated several gene pathways, notably those that were involved in the stress response and apoptosis, as measured by gene microarray [94, 95].”
From Association between sleep deficiency and cardiometabolic disease: implications for health disparities (2016) · cites this paper as [95]
Sleep restriction can lead to a disproportionate increase in food intake.
“While sleep restriction increases energy expenditure due to increased wakefulness, it can lead to a disproportionate increase in food intake, decrease in physical activity, and weight gain.”
From Metabolic effects of sleep disruption, links to obesity and diabetes (2014) · cites this paper as [39]
Sleep restriction can lead to weight gain.
“While sleep restriction increases energy expenditure due to increased wakefulness, it can lead to a disproportionate increase in food intake, decrease in physical activity, and weight gain.”
From Metabolic effects of sleep disruption, links to obesity and diabetes (2014) · cites this paper as [39]
Sleep restriction increases energy expenditure due to increased wakefulness.
“While sleep restriction increases energy expenditure due to increased wakefulness, it can lead to a disproportionate increase in food intake, decrease in physical activity, and weight gain.”
From Metabolic effects of sleep disruption, links to obesity and diabetes (2014) · cites this paper as [39]
In the second study, food intake was 6% greater in sleep restricted compared to control condition, and increase in energy intake was larger than increase in energy expenditure, resulting in larger increase in body weight.
“In the second study, food intake was 6% greater in the sleep restricted compared to control condition, i.e., the increase in energy intake was larger than the increase in EE, resulting in a larger increase in body weight [39]**.”
From Metabolic effects of sleep disruption, links to obesity and diabetes (2014) · cites this paper as [39]
Partial sleep restriction to 5 h TIB vs 9 h TIB for 5 nights increases daily energy expenditure by 5% as measured by whole room calorimetry.
“In a different study, partial sleep restriction to 5 h TIB as compared to 9 h TIB for 5 nights increased daily EE by 5% as measured by whole room calorimetry [39]**.”
From Metabolic effects of sleep disruption, links to obesity and diabetes (2014) · cites this paper as [39]
Discrepancies in findings on energy expenditure may be explained by higher sensitivity of whole room calorimetry (0.5-2%) compared to doubly labeled water (6-8%).
“The discrepancies in the findings of whether or not there is an effect of sleep restriction on EE may be explained by the higher sensitivity of whole room calorimetry used to estimate EE (0.5-2%) as compared to that of doubly labeled water method (6-8%) [39]**).”
From Metabolic effects of sleep disruption, links to obesity and diabetes (2014) · cites this paper as [39]
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- Authors
- Möller-Levet, C. S., Archer, S. N., Bucca, G., Laing, E. E., Slak, A., Kabiljo, R., Lo, J. C. Y., Santhi, N., von Schantz, M., Smith, C. P., & Dijk, D.-J.
- Affiliations
- Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
- University of Surrey (GB)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-02-25
- Volume
- 110
- Issue
- 12
- Pages
- E1132-41
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3607048
- OpenAlex
- W2117375244
- Cited by
- 576
- References
- 68
- Citations by year
- 2026: 33 · 2025: 39 · 2024: 38 · 2023: 41 · 2022: 47 · 2021: 41 · 2020: 57 · 2019: 36 · 2018: 44 · 2017: 38 · 2016: 38 · 2015: 53 · 2014: 50 · 2013: 21
- FWCI
- 29.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Brighton Repository (University of Brighton) (publishedVersion, other-oa)
- Northumbria Research Link (Northumbria University) (acceptedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Biotechnology and Biological Sciences Research Council (BB/F022883/1, BB/F022883)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- insufficient sleep, circadian rhythm disruption, circadian rhythmicity, blood transcriptome, total sleep deprivation, sleep homeostasis, oxidative stress, metabolism, inflammation, clock genes, Per1, Per2, Per3, CRY2, clocks, NR1D1, NR1D2, RORA, DEC1, CK1ε, interleukin-6, STAT3, KCNV2, CAMK2D, peroxiredoxin 2, peroxiredoxin 5, GLUT3, SLC2A5, ghrelin, ABCA1, chromatin modification, gene expression regulation
- MeSH terms
- Adult, Circadian Rhythm, Female, Gene Expression Regulation, Homeostasis, Humans, Male, Sleep Deprivation, Transcriptome
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