Skip to main content

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • 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
  • 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
  • Log in
  • My Cart

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • 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
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
  1. Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom

See allHide authors and affiliations

PNAS March 19, 2013 110 (12) E1132-E1141; 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.

View Full Text
PreviousNext
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 Mar 2013, 110 (12) E1132-E1141; 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 Mar 2013, 110 (12) E1132-E1141; DOI: 10.1073/pnas.1217154110
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley

Article Classifications

  • Biological Sciences
  • Medical Sciences
Proceedings of the National Academy of Sciences: 110 (12)
Table of Contents

Submit

Sign up for Article Alerts

Jump to section

  • Article
    • Abstract
    • Results
    • Discussion
    • Methods
    • Acknowledgments
    • Footnotes
    • References
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Water from a faucet fills a glass.
News Feature: How “forever chemicals” might impair the immune system
Researchers are exploring whether these ubiquitous fluorinated molecules might worsen infections or hamper vaccine effectiveness.
Image credit: Shutterstock/Dmitry Naumov.
Reflection of clouds in the still waters of Mono Lake in California.
Inner Workings: Making headway with the mysteries of life’s origins
Recent experiments and simulations are starting to answer some fundamental questions about how life came to be.
Image credit: Shutterstock/Radoslaw Lecyk.
Cave in coastal Kenya with tree growing in the middle.
Journal Club: Small, sharp blades mark shift from Middle to Later Stone Age in coastal Kenya
Archaeologists have long tried to define the transition between the two time periods.
Image credit: Ceri Shipton.
Mouse fibroblast cells. Electron bifurcation reactions keep mammalian cells alive.
Exploring electron bifurcation
Jonathon Yuly, David Beratan, and Peng Zhang investigate how electron bifurcation reactions work.
Listen
Past PodcastsSubscribe
Panda bear hanging in a tree
How horse manure helps giant pandas tolerate cold
A study finds that giant pandas roll in horse manure to increase their cold tolerance.
Image credit: Fuwen Wei.

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
  • Subscribers
  • Librarians
  • Press
  • Cozzarelli Prize
  • Site Map
  • PNAS Updates
  • FAQs
  • Accessibility Statement
  • Rights & Permissions
  • About
  • Contact

Feedback    Privacy/Legal

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