Telomere Shortening in Middle-Aged Men with Sleep-disordered Breathing.

RATIONALE Sleep disorders may lead to stress-induced premature aging and telomere shortening. OBJECTIVES To determine whether obstructive sleep apnea syndrome causing intermittent hypoxemic episodes was associated with telomere shortening independently from the comorbidities associated with this syndrome. METHODS We conducted a cross-sectional study in 161prospectivelly enrolled, untreated, middle-aged men free of known comorbidities related or unrelated to sleep apnea. Each participant underwent full standard overnight polysomnography. Patients with apnea sleep syndrome were naive to treatment. MEASUREMENTS AND MAIN RESULTS In univariate analysis, we found that telomere shortening was associated with older age, apnea-hypopnea index, oxygen desaturation index, waist circumference, and fat mass. After adjustment for age, only apnea-hypopnea index and oxygen desaturation index were significantly related to telomere shortening. The mean telomere length ratio was 0.70 ± 0.37 in the participants without sleep apnea, compared with 0.61 ± 0.22 and 0.53 ± 0.16 in those with mild to moderate and severe sleep apnea, respectively (P = 0.01). In multivariate analysis, we found that oxygen desaturation index was the only factor independently associated with telomere length. Arterial stiffness assessed by carotid-femoral pulse wave velocity correlated negatively with telomere length. CONCLUSIONS Intermittent hypoxemia due to obstructive sleep apnea syndrome is a major contributor to telomere shortening in middle-aged men. Oxidative stress may explain this finding.

[1]  A. Houssaini,et al.  Telomere Dysfunction and Cell Senescence in Chronic Lung Diseases: Therapeutic Potential. , 2015, Pharmacology & therapeutics.

[2]  S. Nakajima,et al.  Targeted DNA damage at individual telomeres disrupts their integrity and triggers cell death , 2015, Nucleic acids research.

[3]  S. Tufik,et al.  Telomere length as a marker of sleep loss and sleep disturbances: a potential link between sleep and cellular senescence. , 2015, Sleep medicine.

[4]  B. Housset,et al.  Aging-Related Systemic Manifestations in COPD Patients and Cigarette Smokers , 2015, PloS one.

[5]  O. Wolkowitz,et al.  Major depressive disorder and accelerated cellular aging: results from a large psychiatric cohort study , 2014, Molecular Psychiatry.

[6]  Geoff Der,et al.  Gender and telomere length: Systematic review and meta-analysis , 2014, Experimental Gerontology.

[7]  J. Eriksson,et al.  The history of sleep apnea is associated with shorter leukocyte telomere length: the Helsinki Birth Cohort Study. , 2014, Sleep medicine.

[8]  P. Lévy,et al.  Visceral white fat remodelling contributes to intermittent hypoxia-induced atherogenesis , 2013, European Respiratory Journal.

[9]  Manuel Serrano,et al.  The Hallmarks of Aging , 2013, Cell.

[10]  M. Armanios Telomeres and age-related disease: how telomere biology informs clinical paradigms. , 2013, The Journal of clinical investigation.

[11]  A. Steptoe,et al.  Short Sleep Duration Is Associated with Shorter Telomere Length in Healthy Men: Findings from the Whitehall II Cohort Study , 2012, PloS one.

[12]  A. Benetos,et al.  “Is obesity linked to aging?” Adipose tissue and the role of telomeres , 2012, Ageing Research Reviews.

[13]  David L. Ergun,et al.  Dual-Energy X-Ray Absorptiometry for Quantification of Visceral Fat , 2012, Obesity.

[14]  P. Validire,et al.  Telomere dysfunction causes sustained inflammation in chronic obstructive pulmonary disease. , 2011, American journal of respiratory and critical care medicine.

[15]  Jiali Han,et al.  Associations between Rotating Night Shifts, Sleep Duration, and Telomere Length in Women , 2011, PloS one.

[16]  J. Soriano,et al.  Telomere shortening in sleep apnea syndrome. , 2010, Respiratory medicine.

[17]  B. Housset,et al.  Shortened telomeres in circulating leukocytes of patients with chronic obstructive pulmonary disease. , 2009, American journal of respiratory and critical care medicine.

[18]  O. Melander,et al.  Telomere Length Is Associated With Obesity Parameters but With a Gender Difference , 2008, Obesity.

[19]  J. Stradling,et al.  Endothelial function and arterial stiffness in minimally symptomatic obstructive sleep apnea. , 2008, American journal of respiratory and critical care medicine.

[20]  S. Stevens,et al.  Blood leucocyte telomere DNA content predicts vascular telomere DNA content in humans with and without vascular disease. , 2008, European heart journal.

[21]  P. Factor,et al.  Inflammation, Oxidative Stress, and Repair Capacity of the Vascular Endothelium in Obstructive Sleep Apnea , 2008, Circulation.

[22]  M. Adachi,et al.  Association between lipid peroxidation and inflammation in obstructive sleep apnoea , 2006, European Respiratory Journal.

[23]  L. Bortolotto,et al.  Early signs of atherosclerosis in obstructive sleep apnea. , 2005, American journal of respiratory and critical care medicine.

[24]  A. Aviv,et al.  Obesity, cigarette smoking, and telomere length in women , 2005, The Lancet.

[25]  A. Aviv,et al.  Short Telomeres Are Associated With Increased Carotid Atherosclerosis in Hypertensive Subjects , 2004, Hypertension.

[26]  T. Zglinicki Oxidative stress shortens telomeres , 2002 .

[27]  J. Skurnick,et al.  Telomere Length as an Indicator of Biological Aging: The Gender Effect and Relation With Pulse Pressure and Pulse Wave Velocity , 2001, Hypertension.

[28]  E. van Cauter,et al.  Age-related changes in slow wave sleep and REM sleep and relationship with growth hormone and cortisol levels in healthy men. , 2000, JAMA.

[29]  W. Seeger,et al.  Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea. Impact of continuous positive airway pressure therapy. , 2000, American journal of respiratory and critical care medicine.

[30]  V. Somers,et al.  Intermittent hypoxemia and OSA: implications for comorbidities. , 2015, Chest.

[31]  Kathryn A. Lee,et al.  Telomere length is associated with sleep duration but not sleep quality in adults with human immunodeficiency virus. , 2014, Sleep.

[32]  Paula G. Williams,et al.  Cellular aging and restorative processes: subjective sleep quality and duration moderate the association between age and telomere length in a sample of middle-aged and older adults. , 2014, Sleep.