Mild sleep restriction and DNA methylation: randomized crossover trial in 60 adults
In a pooled analysis of two randomized crossover trials, 60 healthy adults sleeping 7–9 h per night spent two 6-week periods with adequate sleep or 1.5 h less sleep per night. Prolonged mild sleep restriction was associated with methylation differences in core clock genes and, exploratorily, elsewhere in the epigenome. [1]
Automatic summary · not editorially reviewed
The key findings
Sixty healthy adults who habitually slept 7–9 h per night completed two 6-week periods: adequate sleep versus 1.5 h less sleep per night, in a pooled analysis of two randomized crossover trials. [1]
Sleep condition by week interactions were significant at methylation sites in the core circadian genes ARNTL, CLOCK and NPAS2. [1]
In the exploratory epigenome-wide analysis, all but one of the top suggestive sites showed hypermethylation after sleep restriction versus adequate sleep, and the authors call for replication. [1]
The source at a glance
- Study type / format
- Pooled analysis of two randomized crossover trials (abstract only).
- Population / context
- 60 healthy adults aged 20 years or older (65% women) who habitually slept 7–9 h per night.
- Summary based on
- Study abstract
- Original publication
- March 21, 2026
Two crossover trials in habitual 7–9 h sleepers
The abstract reports a pooled analysis of two randomized crossover trials of sleep restriction. Participants were 60 healthy adults (65% women, age 20 years or older) who habitually slept 7–9 h per night. Each person completed two 6-week intervention periods: maintaining habitual adequate sleep (at least 7 h per night) and sleep restriction of 1.5 h less per night, separated by a washout interval. DNA methylation was measured in morning fasting blood samples taken at baseline and at the endpoint of each period, using an EPICv.2 array.
Supporting source [1]
Clock-gene and exploratory methylation differences after restriction
In the candidate approach for core circadian genes, the interaction between sleep condition and week was significant at sites in ARNTL (p<0.001), CLOCK (p=0.001) and NPAS2 (both p=0.009). In the exploratory epigenome-wide analysis, the most suggestive sites were in SNHG3-RCC1 (p=1.34E-06), FAF1 (p=2.25E-05) and MMP12 (p=2.78E-05). All but one of these sites showed hypermethylation after sleep restriction compared with adequate sleep. The most significant pathways involved aging-related genes in TGF-beta signaling, glucagon signaling and fatty acid degradation.
Supporting source [1]
Preliminary associations, not proven causes or health effects
The authors describe the findings as showing that prolonged mild sleep restriction is associated with DNA methylation in core clock candidate genes and suggest differences in other genes across the epigenome, pointing to a potentially plastic epigenetic mechanism. They call the results preliminary and state that studies are needed to replicate them. The abstract does not report whether these methylation differences translate into changes in disease risk or biological age, and it does not describe the size of the methylation changes.
Supporting source [1]
How to interpret this
This explainer is based only on the abstract; the full text was not reviewed. The epigenome-wide findings are exploratory, the authors call the results preliminary and ask for replication, and the abstract reports no health or biological-age outcomes.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Barragán R, Dye CK, Aggarwal B, Jelic S, Coltell O, Corella D, St-Onge MP. · europepmc.org · March 21, 2026