Opinion Obstructive Sleep Apnea and Hallmarks of Aging Laetitia S. Gaspar, 1,y Ana Rita Álvaro, 1,y Joaquim Moita, 2 and Cláudia Cavadas 1,3, * Obstructive sleep apnea (OSA) is one of the most common sleep disorders. Since aging is a risk factor for OSA development, it is expected that its preva- lence will increase with the current increase in life span. In recent years, several studies have shown that OSA potentially contributes to functional decline, mainly prompted by chronic intermittent hypoxia and sleep fragmentation. Here, we propose that OSA might anticipate/aggravate aging by inducing cellular and molecular impairments that characterize the aging process, such as stem cell exhaustion, telomere attrition and epigenetic changes. We suggest that further knowledge on the impact of OSA on aging mechanisms might contribute to a better understanding of how OSA might putatively accelerate aging and aging-related diseases. Obstructive Sleep Apnea According to the International Classification of Sleep Disorders, OSA is a sleep-related breath- ing disorder characterized by recurrent episodes of complete (apnea) or partial (hypoapnea) obstruction of the upper airway during sleep while respiratory efforts continue, frequently inducing arousals (Box 1) [1]. Successive airflow interruptions or reductions during sleep culminate in intermittent hypoxia (IH) (see Glossary) and repetitive arousals result in sleep fragmentation (SF), inducing sympathetic neural activity (SNA), with increases and swings in both systemic blood and arterial pulmonary pressures [2,3]. OSA has been recognized as one of the most common sleep disorders. Indeed, according to World Health Organization, 100 million individuals worldwide exhibit some degree of OSA, a prevalence that has substantially increased over the past two decades, and which is expected to increase in the near future ([4,5], reviewed in [6]). The expected increase in OSA has been related to an increased prevalence of obesity and to aging (Box 2), two important risk factors for OSA [1]. Despite the high prevalence of OSA, it is estimated that 80–90% of total OSA cases remain undiagnosed [4]. The gold standard of OSA diagnosis is polysomnography (PSG), performed overnight in a sleep laboratory (Box 3). Unfortunately, PSG is labor intensive and expensive, which results in unnecessary delays in OSA diagnosis and treatment [7]. In addition, OSA has been recognized as a multifactorial and heterogeneous disease, showing variability in its symptoms, etiology, comorbid conditions, and outcomes, which are only poorly predicted based on the severity of disease as determined from PSG [2,3,8]. In this context, efforts should be made to determine the specific pathophysiology of each patient, paving the way for personalized OSA medicine. Application of continuous positive airway pressure (CPAP) via a mask, which alleviates upper airway obstruction, constitutes the first line in OSA treatment. However, the CPAP mask is not effective in some patients, while others are unable to tolerate its use (Box 4). In this context, OSA may have a high economic impact on healthcare systems, mainly due to Trends Obstructive sleep apnea (OSA) preva- lence has substantially increased over the past two decades and, in indus- trialized countries, it is estimated to become one of the most common chronic diseases. OSA has recently been associated with earlier cognitive decline; thus, OSA treatment might delay aging- associated functional decline. OSA-associated epigenetic changes may underlie disease-associated het- erogeneity in terms of symptoms, out- comes, and even treatment response. Telomere length is reduced in leuko- cytes from patients with OSA, sug- gesting accelerated cellular aging and inducing a higher risk for age- related diseases. Blood-circulating endothelial progeni- tor cells may be reduced in patients with OSA, compromising the endothe- lial repair capacity and contributing to endothelial apoptosis. 1 CNC – Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal 2 Sleep Medicine Unit, Coimbra Hospital and University Center (CHUC), Coimbra, Portugal 3 Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal y These authors contributed equally. *Correspondence: ccavadas@ci.uc.pt (C. Cavadas). Trends in Molecular Medicine, August 2017, Vol. 23, No. 8 http://dx.doi.org/10.1016/j.molmed.2017.06.006 675 © 2017 Elsevier Ltd. All rights reserved.