Epigenetic age acceleration in obstructive sleep apnea is reversible with adherent treatment

Author(s): Rene Cortese, David Sanz-Rubio, Leila Kheirandish-Gozal, José Maria Marin, David Gozal

Epigenetic age acceleration in obstructive sleep apnea is reversible with adherent treatment - article image

Eur Respir J Published online April 21, 2022 | https://erj.ersjournals.com/content/59/4/2103042

Digest author(s): Manuel Sánchez-de-la-Torre | 10 November, 2022

Obstructive sleep apnoea (OSA) is a chronic and prevalent disease that affects more than 20% of the adult population. This pathology has been related to loss of quality of life, neurodegenerative diseases, cardiovascular diseases, and cancer. The pathophysiological consequences of OSA mainly include repetitive episodes of hypoxia-reoxygenation, sleep arousals and intrathoracic pressure changes, promote oxidative stress, inflammation, and endothelial dysfunction.

The progressive population aging (by 2030, 1 in 6 people in the world will be aged 60 years or over) points to the priority need to increase knowledge and improve the management of chronic and frequent pathologies closely linked to the aging process, as is the case of OSA. OSA has been traditionally considered a sleep disorder related to age, as its prevalence is two to three times higher in older adults than in younger adults.  In the last years the relationship between OSA and aging has been widely studied suggesting that the physiologic changes induced by OSA resemble those induced by aging. It has been reported that OSA is associated with specific hallmarks of aging, being this relationship more evident in younger adults. However, it is still necessary to evaluate the impact of OSA treatment in the reversibility of the pathophysiological mechanisms that induce an acceleration of the aging process.

In this interesting study, Cortese et al explored specific molecular mechanisms related to the aging process that constitute useful tool for predicting biological age. Specifically, these authors studied the role of epigenetic characterization in the aging process in patients with OSA. The Epigenetic Clocks or DNA Methylation Clocks inform about a pathological process or exposure factors that induce biological aging. The authors explored the epigenetic clocks from the DNA methylation profiles of peripheral blood mononuclear cells and assessed the epigenetic age variation from the chronological age. The authors of this study identified that patients with OSA present a systemic epigenetic age acceleration compared to subjects without OSA (matched non-snoring controls). Furthermore, the authors reported that 12 months of adherent treatment with continuous positive airway pressure (CPAP) (>4 hours per night) was associated with deceleration of the epigenetically based biological aging. Interestingly, the authors described that deceleration in epigenetic aging observed in OSA patients receiving CPAP treatment is attenuated in those patients with increased inflammation (higher C-reactive protein plasma levels). In the context studied, this fact would indicate that the effect of CPAP treatment would be dependent on the patient profile, identifying a potential diminished effect of CPAP treatment in patients with a high comorbid burden.

This study concluded that the pathophysiological consequences of OSA promote the acceleration of biological age. This acceleration would be partially reversible by adherent treatment of OSA with CPAP. This seminal study leaves important open questions such as the dependent effect of the profile of the patient treated based on cardio-metabolic comorbidity, or the age of the subject, among other variables. Likewise, it will be interesting to know if this effect is observed in patients treated with other treatments than CPAP and the maintenance of the deceleration process over time.

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