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Review
. 2025 Nov 25;26(23):11392.
doi: 10.3390/ijms262311392.

Exercise and Epigenetic Regulation in COPD: Current Evidence and Potential Mechanistic Pathways

Yuanming Zhong  1 , Jianhua Xu  1 , Xia Chen  1 , Yi Lv  2 , Xi Zheng  1   2
Affiliations
Review

Exercise and Epigenetic Regulation in COPD: Current Evidence and Potential Mechanistic Pathways

Yuanming Zhong et al. Int J Mol Sci. .

Abstract

Chronic obstructive pulmonary disease (COPD) remains a major global health burden, characterized by persistent airflow limitation, progressive lung tissue destruction, and systemic comorbidities. Conventional pharmacological therapies alleviate symptoms but have limited efficacy in halting disease progression. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, are increasingly recognized as important regulators of the inflammatory and oxidative pathways involved in COPD pathogenesis. Exercise is a cornerstone of pulmonary rehabilitation and consistently improves exercise capacity, symptoms, and systemic inflammatory markers in COPD. Emerging studies suggest that exercise is associated with changes in epigenetic regulators. This review summarizes current clinical and preclinical findings on how aerobic training, resistance exercise, and high-intensity interval training are linked to alterations in DNA methylation, histone marks, and non-coding RNA expression, and discusses the biological plausibility that these changes could influence COPD-related pathways such as antioxidant responses, protease and antiprotease balance, and inflammatory signaling. Critical gaps remain regarding tissue specificity, temporal dynamics, and causal mechanisms. Future research should prioritize longitudinal and mechanistic studies to clarify whether epigenetic responses contribute to the benefits of exercise in COPD and to assess their potential as biomarkers or therapeutic targets.

Keywords: DNA methylation; chronic obstructive pulmonary disease; epigenetics; exercise; histone modifications; non-coding RNAs; pulmonary rehabilitation.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Epigenetic regulation in the pathogenesis of COPD. Created with BioRender.com, der, b. (2025) https://BioRender.com/oikyxt2 (accessed on 4 November 2025).
Figure 2
Figure 2
Exercise modalities in COPD rehabilitation: outcomes and mechanisms.
Figure 3
Figure 3
Exercise-induced epigenetic modulation in COPD. Created with BioRender.com, der, b. (2025) https://BioRender.com/my4a89c (accessed on 4 November 2025).
See this image and copyright information in PMC

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