Skip to main content
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian
  • Log in
  • My Cart

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses

New Research In

Physical Sciences

Featured Portals

  • Physics
  • Chemistry
  • Sustainability Science

Articles by Topic

  • Applied Mathematics
  • Applied Physical Sciences
  • Astronomy
  • Computer Sciences
  • Earth, Atmospheric, and Planetary Sciences
  • Engineering
  • Environmental Sciences
  • Mathematics
  • Statistics

Social Sciences

Featured Portals

  • Anthropology
  • Sustainability Science

Articles by Topic

  • Economic Sciences
  • Environmental Sciences
  • Political Sciences
  • Psychological and Cognitive Sciences
  • Social Sciences

Biological Sciences

Featured Portals

  • Sustainability Science

Articles by Topic

  • Agricultural Sciences
  • Anthropology
  • Applied Biological Sciences
  • Biochemistry
  • Biophysics and Computational Biology
  • Cell Biology
  • Developmental Biology
  • Ecology
  • Environmental Sciences
  • Evolution
  • Genetics
  • Immunology and Inflammation
  • Medical Sciences
  • Microbiology
  • Neuroscience
  • Pharmacology
  • Physiology
  • Plant Biology
  • Population Biology
  • Psychological and Cognitive Sciences
  • Sustainability Science
  • Systems Biology
Research Article

Effects of insufficient sleep on circadian rhythmicity and expression amplitude of the human blood transcriptome

Carla S. Möller-Levet, Simon N. Archer, Giselda Bucca, Emma E. Laing, Ana Slak, Renata Kabiljo, June C. Y. Lo, Nayantara Santhi, Malcolm von Schantz, Colin P. Smith, and Derk-Jan Dijk
PNAS first published February 25, 2013; https://doi.org/10.1073/pnas.1217154110
Carla S. Möller-Levet
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Simon N. Archer
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Giselda Bucca
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Emma E. Laing
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ana Slak
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Renata Kabiljo
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
June C. Y. Lo
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nayantara Santhi
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Malcolm von Schantz
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Colin P. Smith
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Derk-Jan Dijk
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: d.j.dijk@surrey.ac.uk
  1. Edited by Joseph S. Takahashi, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, and approved January 23, 2013 (received for review October 3, 2012)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

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.

Abstract

Insufficient sleep and circadian rhythm disruption are associated with negative health outcomes, including obesity, cardiovascular disease, and cognitive impairment, but the mechanisms involved remain largely unexplored. Twenty-six participants were exposed to 1 wk of insufficient sleep (sleep-restriction condition 5.70 h, SEM = 0.03 sleep per 24 h) and 1 wk of sufficient sleep (control condition 8.50 h sleep, SEM = 0.11). Immediately following each condition, 10 whole-blood RNA samples were collected from each participant, while controlling for the effects of light, activity, and food, during a period of total sleep deprivation. Transcriptome analysis revealed that 711 genes were up- or down-regulated by insufficient sleep. Insufficient sleep also reduced the number of genes with a circadian expression profile from 1,855 to 1,481, reduced the circadian amplitude of these genes, and led to an increase in the number of genes that responded to subsequent total sleep deprivation from 122 to 856. Genes affected by insufficient sleep were associated with circadian rhythms (PER1, PER2, PER3, CRY2, CLOCK, NR1D1, NR1D2, RORA, DEC1, CSNK1E), sleep homeostasis (IL6, STAT3, KCNV2, CAMK2D), oxidative stress (PRDX2, PRDX5), and metabolism (SLC2A3, SLC2A5, GHRL, ABCA1). Biological processes affected included chromatin modification, gene-expression regulation, macromolecular metabolism, and inflammatory, immune and stress responses. Thus, insufficient sleep affects the human blood transcriptome, disrupts its circadian regulation, and intensifies the effects of acute total sleep deprivation. The identified biological processes may be involved with the negative effects of sleep loss on health, and highlight the interrelatedness of sleep homeostasis, circadian rhythmicity, and metabolism.

  • bloodomics
  • chronobiology
  • leukocyte
  • genomics

Footnotes

  • ↵1C.S.M.-L., S.N.A., G.B., C.P.S., and D.-J.D. contributed equally to this work.

  • ↵2To whom correspondence should be addressed. E-mail: d.j.dijk{at}surrey.ac.uk.
  • Author contributions: S.N.A., E.E.L., M.v.S., C.P.S., and D.-J.D. designed research; C.S.M.-L., G.B., E.E.L., A.S., R.K., J.C.Y.L., and N.S. performed research; C.S.M.-L., G.B., E.E.L., A.S., and R.K. analyzed data; and C.S.M.-L., S.N.A., E.E.L., M.v.S., C.P.S., and D.-J.D. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE39445). Custom microarray design deposited at GEO (accession no. GPL15331).

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1217154110/-/DCSupplemental.

Freely available online through the PNAS open access option.

Next
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Effects of insufficient sleep on circadian rhythmicity and expression amplitude of the human blood transcriptome
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Sleep loss and the human blood transcriptome
Carla S. Möller-Levet, Simon N. Archer, Giselda Bucca, Emma E. Laing, Ana Slak, Renata Kabiljo, June C. Y. Lo, Nayantara Santhi, Malcolm von Schantz, Colin P. Smith, Derk-Jan Dijk
Proceedings of the National Academy of Sciences Feb 2013, 201217154; DOI: 10.1073/pnas.1217154110

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Sleep loss and the human blood transcriptome
Carla S. Möller-Levet, Simon N. Archer, Giselda Bucca, Emma E. Laing, Ana Slak, Renata Kabiljo, June C. Y. Lo, Nayantara Santhi, Malcolm von Schantz, Colin P. Smith, Derk-Jan Dijk
Proceedings of the National Academy of Sciences Feb 2013, 201217154; DOI: 10.1073/pnas.1217154110
Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley
Proceedings of the National Academy of Sciences: 118 (3)
Current Issue

Submit

Sign up for Article Alerts

Jump to section

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Abstract depiction of a guitar and musical note
Science & Culture: At the nexus of music and medicine, some see disease treatments
Although the evidence is still limited, a growing body of research suggests music may have beneficial effects for diseases such as Parkinson’s.
Image credit: Shutterstock/agsandrew.
Large piece of gold
News Feature: Tracing gold's cosmic origins
Astronomers thought they’d finally figured out where gold and other heavy elements in the universe came from. In light of recent results, they’re not so sure.
Image credit: Science Source/Tom McHugh.
Dancers in red dresses
Journal Club: Friends appear to share patterns of brain activity
Researchers are still trying to understand what causes this strong correlation between neural and social networks.
Image credit: Shutterstock/Yeongsik Im.
White and blue bird
Hazards of ozone pollution to birds
Amanda Rodewald, Ivan Rudik, and Catherine Kling talk about the hazards of ozone pollution to birds.
Listen
Past PodcastsSubscribe
Goats standing in a pin
Transplantation of sperm-producing stem cells
CRISPR-Cas9 gene editing can improve the effectiveness of spermatogonial stem cell transplantation in mice and livestock, a study finds.
Image credit: Jon M. Oatley.

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Special Feature Articles – Most Recent
  • List of Issues

PNAS Portals

  • Anthropology
  • Chemistry
  • Classics
  • Front Matter
  • Physics
  • Sustainability Science
  • Teaching Resources

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Librarians
  • Press
  • Site Map
  • PNAS Updates

Feedback    Privacy/Legal

Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490