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Related Experiment Video

Updated: Jan 20, 2026

Manual Muscle Testing: A Method of Measuring Extremity Muscle Strength Applied to Critically Ill Patients
09:44

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Association Between Abnormal DNA Methylation and Altered Transcriptome in Muscle Five Years After Critical Illness.

Ceren Uzun Ayar1, Fabian Güiza1,2, Inge Derese1

  • 1Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.

Journal of Cachexia, Sarcopenia and Muscle
|January 19, 2026
PubMed
Summary

Persistent muscle weakness after intensive care unit (ICU) admission is linked to abnormal DNA methylation. This epigenetic change in muscle tissue correlates with altered RNA expression, potentially explaining long-term muscle strength loss in former ICU patients.

Keywords:
DNA methylationcritical illnessepigeneticsmuscle weaknesspost‐intensive care syndrometranscriptome

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Area of Science:

  • Epigenetics
  • Genomics
  • Critical Care Medicine

Background:

  • Critically ill patients often experience persistent muscle weakness years after intensive care unit (ICU) admission.
  • Previous studies noted altered RNA expression in muscles of former ICU patients, indicating disrupted mitochondrial function, lipid metabolism, and fibrosis, linked to muscle strength loss.

Purpose of the Study:

  • To investigate if abnormal DNA methylation in skeletal muscle years after critical illness is associated with altered RNA expression patterns.
  • To explore the potential epigenetic basis for long-term muscle weakness following critical illness.

Main Methods:

  • Genome-wide DNA methylation analysis using Illumina EPIC arrays on skeletal muscle biopsies from 118 former ICU patients and 30 controls.
  • Identification of differentially methylated positions (DMPs) and pathway enrichment analysis.
  • Correlation analysis between DMPs and differentially expressed RNAs (DERNAs), and identification of risk factors for abnormal DNA methylation.

Main Results:

  • Former ICU patients exhibited 7379 DMPs compared to controls, associated with 1334 genes enriched in muscle contraction and vascular development pathways.
  • DMPs showed stronger correlations with DERNAs, particularly those linked to reduced muscle strength and previously identified disrupted pathways (mitochondrial function, lipid metabolism, fibrosis).
  • Older age, female sex, and specific ICU treatments (glucocorticoids, benzodiazepines) and follow-up medications (opioids, antipsychotics) were associated with increased DNA methylation abnormalities.

Conclusions:

  • Abnormal DNA methylation in muscle tissue 5 years post-critical illness is associated with long-term altered RNA expression and reduced muscle strength.
  • These findings suggest a potential epigenetic mechanism underlying persistent muscle weakness after critical illness.
  • Abnormal DNA methylation correlated with potentially modifiable risk factors, offering avenues for prevention and treatment strategies.