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Prolonged Mild Sleep Restriction Changes Epigenome-Wide DNA Methylation in Peripheral Blood Cells: A Randomized
Rocio Barragán1,2,3,4, Christian K Dye5,6, Brooke Aggarwal3,7
1Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, Valencia, Spain.
Aging and Disease
|March 30, 2026
Summary
Prolonged mild sleep restriction (SR) alters DNA methylation (DNAm) patterns in core circadian genes and other genes across the epigenome. These changes may indicate a plastic epigenetic mechanism influencing aging-related disease susceptibility.
Area of Science:
- Epigenetics and Chronobiology
- Molecular Biology and Genetics
Background:
- DNA methylation (DNAm) is linked to age-related disease susceptibility.
- Previous studies suggest sleep deprivation may alter DNAm, but long-term effects remain unclear.
Purpose of the Study:
- To investigate if prolonged mild sleep restriction (SR) causes differentially methylated loci (DML) in circadian genes.
- To explore epigenome-wide changes in DML following SR.
Main Methods:
- Pooled analysis of two randomized crossover trials involving 60 healthy adults.
- Participants underwent periods of adequate sleep (AS) and SR (-1.5h/night) over 6 weeks.
- DNA methylation levels were measured using the EPICv.2 array, with analysis of sleep condition x week interactions.
Main Results:
- Significant sleep condition x week interactions for DNAm in core circadian genes ARNTL, CLOCK, and NPAS2.
- Suggestive top DML identified in SNHG3-RCC1, FAF1, and MMP12, with most showing hypermethylation after SR.
- Associated pathways included aging-related genes in TGF-beta signaling, glucagon signaling, and fatty acid degradation.
Conclusions:
- Prolonged mild SR is associated with DNAm changes in core clock genes and other genes epigenome-wide.
- These findings suggest a potentially plastic epigenetic mechanism influenced by sleep restriction.
- Further studies are needed to replicate these preliminary results.
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