Biological Mechanisms Underlying the Adverse Health Consequences of Human Circadian Misalignment from Night Shift Work.
10 affiliations
- 1Department of Translational Medicine and Physiology, Washington State University, Spokane, WA USA.
- 2Sleep and Performance Research Center, Washington State University, Spokane, WA USA.
- 3Behaviour-Brain-Body Research Centre, Adelaide University, Adelaide, SA Australia.
- 4Division of Endocrinology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA USA.
- 5Genomics Center, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA USA.
- 6Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA USA.
- 7Department of Anatomy, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
- 8Department of Biological Sciences, North Carolina State University, Raleigh, NC USA.
- 9Department of Pharmaceutical Sciences, Washington State University, Spokane, WA USA.
- 10Center for Human Health and the Environment, North Carolina State University, Raleigh, NC USA.
Abstract
Purpose of review
The waking and working times of night shift workers are displaced relative to the natural light/dark cycle, putting behavioral patterns in misalignment with the circadian regulation of biological processes. This state of circadian misalignment constitutes a circadian health problem, with widespread negative consequences for metabolic, cardiovascular, and mental health, as well as elevated risk of cancer. Scientific advances over the past decade have shed light on key aspects of the underlying biological mechanisms. With a focus on recent human studies, this paper reviews novel insights into what drives the adverse health consequences of circadian misalignment due to night shift work.Recent findings
Misalignment between the central circadian pacemaker and externally driven behavioral patterns during night shift work produces a rapid uncoupling of peripheral rhythms, reflected in the cargo of exosomes and other signaling mechanisms, and causes conflict between central and peripheral regulatory mechanisms. This endogenous internal desynchrony has been shown to be linked to shifted meal timing and, in part, may be mediated by the gut microbiome. Endogenous internal desynchrony leads to insulin resistance - a manifestation of metabolic dysfunction. It perturbs the cardiometabolic and immune systems, and also erodes mental health. At the cellular level, mistimed DNA repair mechanisms leave residual DNA damage after exposure to a night shift schedule - which, over time, may result in genomic instability and ultimately carcinogenesis.Summary
A systems biology perspective serves to elucidate how the effects of endogenous circadian disruption from night shift work increase the risk of acute and chronic illnesses. Internal desynchrony, endogenous in nature, is a common underlying cause. Time-restricted eating may help to address metabolic dysfunction due to night shift work; countermeasures for other negative health outcomes, including cancer and mental health disorders, remain to be developed.
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BibTeX
@article{lundholm2026biological,
title = {{Biological Mechanisms Underlying the Adverse Health Consequences of Human Circadian Misalignment from Night Shift Work.}},
author = {Kirsie R Lundholm and Brieann C Satterfield and Siobhan Banks and Peter Y Liu and Chathuri J Kombala and Gabriela Hurtado-Alvarado and Adam J Greer and Rachael A Muck and Matthew A Layton and Dan Du and Shobhan Gaddameedhi and Hans P A Van Dongen},
journal = {Current sleep medicine reports},
year = {2026},
month = oct,
doi = {10.1007/s40675-026-00404-9},
url = {https://europepmc.org/article/MED/42927053},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Biological Mechanisms Underlying the Adverse Health Consequences of Human Circadian Misalignment from Night Shift Work.
AU - Kirsie R Lundholm
AU - Brieann C Satterfield
AU - Siobhan Banks
AU - Peter Y Liu
AU - Chathuri J Kombala
AU - Gabriela Hurtado-Alvarado
AU - Adam J Greer
AU - Rachael A Muck
AU - Matthew A Layton
AU - Dan Du
AU - Shobhan Gaddameedhi
AU - Hans P A Van Dongen
PY - 2026
DA - 2026/10/23
JO - Current sleep medicine reports
DO - 10.1007/s40675-026-00404-9
UR - https://europepmc.org/article/MED/42927053
AB - Purpose of review The waking and working times of night shift workers are displaced relative to the natural light/dark cycle, putting behavioral patterns in misalignment with the circadian regulation of biological processes. This state of circadian misalignment constitutes a circadian health problem, with widespread negative consequences for metabolic, cardiovascular, and mental health, as well as elevated risk of cancer. Scientific advances over the past decade have shed light on key aspects of the underlying biological mechanisms. With a focus on recent human studies, this paper reviews novel insights into what drives the adverse health consequences of circadian misalignment due to night shift work.Recent findings Misalignment between the central circadian pacemaker and externally driven behavioral patterns during night shift work produces a rapid uncoupling of peripheral rhythms, reflected in the cargo of exosomes and other signaling mechanisms, and causes conflict between central and peripheral regulatory mechanisms. This endogenous internal desynchrony has been shown to be linked to shifted meal timing and, in part, may be mediated by the gut microbiome. Endogenous internal desynchrony leads to insulin resistance - a manifestation of metabolic dysfunction. It perturbs the cardiometabolic and immune systems, and also erodes mental health. At the cellular level, mistimed DNA repair mechanisms leave residual DNA damage after exposure to a night shift schedule - which, over time, may result in genomic instability and ultimately carcinogenesis.Summary A systems biology perspective serves to elucidate how the effects of endogenous circadian disruption from night shift work increase the risk of acute and chronic illnesses. Internal desynchrony, endogenous in nature, is a common underlying cause. Time-restricted eating may help to address metabolic dysfunction due to night shift work; countermeasures for other negative health outcomes, including cancer and mental health disorders, remain to be developed.
SN - 2198-6401
ER -