Epigenetic regulators and biological age modulation in Obstructive Sleep Apnea, pre and post Continuous Positive Airway Pressure treatment

Obstructive Sleep Apnea (OSA), a prevalent sleep disorder linked to cardiovascular morbidity and accelerated aging, was investigated for molecular and epigenetic changes before and after Continuous Positive Airway Pressure (C-PAP) therapy. This study aimed to first assess expression levels of non-coding RNAs (lncRNAs MALAT1, BACE1-AS; miRNAs miR-210-3p, miR-485-5p, miR-139-3p) and secondly evaluate DNA methylation age (DNAmAge) using the Bekaert algorithm in OSA patients pre- and post-C-PAP versus healthy controls. Expression analysis revealed elevated MALAT1 and BACE1-AS in OSA patients, normalizing post-C-PAP. miR-210-3p and miR-485-5p levels were significantly higher pre-treatment, decreasing post-therapy, while suppressed miR-139-3p increased toward control levels. These findings underscore non-coding RNAs as dynamic biomarkers of OSA pathophysiology and therapeutic response. DNAmAge analysis demonstrated accelerated biological aging (delta age) in OSA patients (p < 0.0001) compared to controls. Unexpectedly, delta age increased further post-C-PAP (p < 0.0001), suggesting residual epigenetic aging despite clinical improvement. These highlights potential irreversible cellular damage from chronic hypoxia and inflammation, emphasizing the need for early intervention. In conclusion, C-PAP partially reverses OSA-related dysregulation of non-coding RNAs but does not mitigate accelerated biological aging, implicating lasting epigenetic impacts. These insights advocate for biomarker-driven monitoring and further research into strategies addressing both molecular and aging-related consequences of OSA.