Obstructive Sleep Apnea as an Acceleration Trigger of Cellular Senescence Processes through Telomere Shortening

Abstract

Obstructive sleep apnea (OSA) is chronic disorder which is characterized by recurrent pauses of breathing during sleep which leads to hypoxia and its two main pathological sequelae: oxidative stress and chronic inflammation. Both are also associated with cellular senescence. As OSA patients present with higher prevalence of age-related disorders, such as atrial hypertension or diabetes mellitus type 2, a relationship between OSA and accelerated aging is observable. Furthermore, it has been established that these OSA are associated with telomere shortening. This process in OSA is likely caused by increased oxidative DNA damage due to increased reactive oxygen species levels, DNA repair disruptions, hypoxia, chronic inflammation, and circadian clock disturbances. The aim of the review is to summarize study outcomes on changes in leukocyte telomere length (LTL) in OSA patients and describe possible molecular mechanisms which connect cellular senescence and the pathophysiology of OSA. The majority of OSA patients are characterized by LTL attrition due to oxidative stress, hypoxia and inflammation, which make a kind of positive feedback loop, and circadian clock disturbance.

Disruption of Circadian Rhythm Genes in Obstructive Sleep Apnea Patients—Possible Mechanisms Involved and Clinical Implication

“…The cause of HIF-1 α overexpression in patients suffering from the aforementioned diseases is not clear. One of the postulated factors is oxidative stress caused by an imbalance between the increased production of reactive oxygen species and a relative shortage of antioxidant defense and increased HIF-1 α expression in the protective response to oxidative stress [ 110 , 111 , 112 , 113 ], which is similar to the cellular senescence process in OSA patients [ 114 ]. Furthermore, increased HIF-1 levels in the brain may improve creatinine metabolism and correlate with a better treatment response to antidepressants [ 115 ].…”

“Leaky Gut” as a Keystone of the Connection between Depression and Obstructive Sleep Apnea Syndrome? A Rationale and Study Design

“…Its prevalence is increasing worldwide [3,4]. Metabolic disorders are in particular closely associated with OSA syndrome (OSAS) which is a chronic disorder characterized by intermittent hypoxia during sleep with re-oxygenation injury [5,6]. In fact, more than two thirds of people with OSA is at least overweight and weight loss helps reduce OSA severity or attenuate other symptoms (reviewed in [7]).…”

“…Moreover, OSA is currently -regarded as an additional factor contributing to the pathogenesis of obesityrelated comorbidities [8]. Multiple comorbid conditions such as metabolic complications (e.g., obesity, cardiovascular risk factors, ischemic heart disease and atrial fibrillation, impaired lipid levels, insulin resistance or type 2 diabetes mellitus and non-alcoholic fatty liver disease (NAFLD)), insomnia, depression (up to 35% [9]) or accelerated aging are particularly prevalent in individuals with OSA [3,5,[10][11][12][13]. Among OSA patients there are those with extremely high prescription of antidepressants, anxiolytics, hypnotics and sedatives [3].…”

“…However, the high co-occurrence rate suggests a possible partly pathophysiological overlap between depressive and sleep apnoea syndromes. The chronic low-grade inflammation (CLGI), oxidative stress, or microbiota dysfunction are all interplaying biological mechanisms that have been suggested [1,5,[18][19][20].…”

“…Most civilization diseases, including depression and OSA, have been shown to be associated with CLGI. OSA symptoms lead to hypoxia and its severe pathological aftereffect [5]. The cross-sectional epidemiological research found that oxygen saturation is a predictor of inflammation in the course of OSA [21].…”