Effect of Obstructive Sleep Apnea and CPAP on Telomere Length and Its Associated Mechanisms: A Pilot Study

Abstract

The present study aimed to investigate the effect of obstructive sleep apnea (OSA) and its treatment with continuous positive airway pressure (CPAP), the gold standard treatment for OSA on changes of telomere length and its associated mechanisms. In this mechanistic pilot study of a selective patient population (middle-aged men, BMI < 35 kg/m², moderate–severe OSA), a 6-month randomized, double-blind, and sham-controlled clinical trial was conducted (Clinical Trials: NCT04872816, April 29, 2021 retrospectively registered). Participants were randomized to CPAP or sham-CPAP (randomization schema 2:1) and attended 7 visits, undergoing clinical assessments and blood collection to determine mean leukocyte telomere length (LTL) and assess metabolic and inflammatory markers. Among 127 individuals contacted, 46 met the inclusion criteria (n = 30 in the CPAP group and n = 16 in the sham-CPAP group). At baseline, individuals in both groups were homogeneous with respect to LTL (p = 0.106). Adherence during the intervention was measured in hours per night, recorded as 5.29 ± 1.09 hours/night for the sham-CPAP group and 5.71 ± 0.19 hours/night for the CPAP group, representing the last 30 days prior to the final visit. Three measurements of LTL were taken at baseline, 3 months, and 6 months. After 6 months of intervention, a statistically significant effect of treatment was observed (p = 0.001) on LTL, with the sham-CPAP group showing a greater reduction (1.0117 ± 0.1552, 0.9457 ± 0.0747, 0.8482 ± 0.2163) compared with the CPAP group (1.0960 ± 0.1122, 1.0521 ± 0.1094, 1.0675 ± 0.1225). Furthermore, a negative correlation between delta LTL and delta TNF-α at Visit 7 and Visit 1 was found (ρ = −0.216, p = 0.003), primarily attributed to the sham-CPAP intervention (ρ = −0.383, p = 0.009) compared with CPAP use (ρ = 0.021, p = 0.800). We conclude that CPAP, compared with sham-CPAP placebo, was associated with stabilization in LTL, potentially through modulation of TNF-α.

Keywords

obstructive sleep apnea continuous positive airway pressure telomere length aging TNF-α

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References

1. Lavie

. Oxidative stress in obstructive sleep apnea and intermittent hypoxia—revisited—the bad ugly and good: Implications to the heart and brain. Sleep Med Rev 2015;20:27–45.

2. Kregel

, Zhang

. An integrated view of oxidative stress in aging: Basic mechanisms, functional effects, and pathological considerations. Am J Physiol Regul Integr Comp Physiol 2007;292(1):R18–R36.

3. Rubtsova

, Vasilkova

, Malyavko

, et al. Telomere lengthening and other functions of telomerase. Acta Naturae 2012;4(2):44–61.

4. Blackburn

, Epel

, Lin

. Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection. Science 2015;350(6265):1193–1198.

5. von Zglinicki

. Role of oxidative stress in telomere length regulation and replicative senescence. Ann N Y Acad Sci 2000;908:99–110.

6. Huang

, Zhou

, Chen

, et al. The association between obstructive sleep apnea and shortened telomere length: A systematic review and meta-analysis. Sleep Med 2018;48:107–112.

7. Cherif

, Tarry

, Ozanne

, et al. Ageing and telomeres: A study into organ- and gender-specific telomere shortening. Nucleic Acids Res 2003;31(5):1576–1583.

8. Bertolazi

, Fagondes

, Hoff

, et al. Validation of the Brazilian Portuguese version of the Pittsburgh Sleep Quality Index. Sleep Med 2011;12(1):70–75.

9. Bertolazi

, Fagondes

, Hoff

, et al. Portuguese-language version of the Epworth Sleepiness Scale: Validation for use in Brazil. J Bras Pneumol 2009;35(9):877–883.

10.

10. Benedito-Silva

, et al. A self-assessment questionnaire for the determination of morningness–eveningness types in Brazil. Prog Clin Biol Res 1990;341B:89–98.

11.

11.CCEB. Critério de Classificação Econômica Brasil (CCEB). 2003.

12.

12. Bittencourt

, Silva

, Conway

. Laboratório do sono—Estrutura física e pessoal, técnica polissonográfica, questionário de sono e banco de dados. São Paulo: Associação Fundo de Incentivo à Pesquisa; 2005.

13.

13. Craig

, Marshall

, Sjöström

, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 2003;35(8):1381–1395.

14.

14. Cunha

. Manual da versão em português das escalas Beck. Casa do Psicologo, São Paulo; 2001.

15.

15. Gorsuch

. The general factor in the test anxiety questionnaire. Psychol Rep 1966;19(1):308.

16.

16. Berry

, Brooks

, Gamaldo

, et al. AASM Scoring Manual Updates for 2017 (Version 2.4). J Clin Sleep Med 2017;13(5):665–666.

17.

17. Farré

, Hernández

, Montserrat

, Rotger

, Ballester

, Navajas

. Sham continuous positive airway pressure for placebo-controlled studies in sleep apnoea. Lancet 1999;353(9159):1154.

18.

18. Cawthon

. Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Res 2009;37(3):e21.

19.

19. Almendros

, Wang

, Gozal

. The polymorphic and contradictory aspects of intermittent hypoxia. Am J Physiol Lung Cell Mol Physiol 2014;307(2):L129–L40.

20.

20. Zhang

SXL

, Khalyfa

, Wang

, et al. Sleep fragmentation promotes NADPH oxidase 2-mediated adipose tissue inflammation leading to insulin resistance in mice. Int J Obes (Lond) 2014;38(4):619–624.

21.

21. Carreras

, Zhang

, Peris

, et al. Chronic sleep fragmentation induces endothelial dysfunction and structural vascular changes in mice. Sleep 2014;37(11):1817–1824.

22.

22. Barceló

, Piérola

, López-Escribano

, et al. Telomere shortening in sleep apnea syndrome. Respir Med 2010;104(8):1225–1229.

23.

23. Tempaku

, Mazzotti

, Hirotsu

, et al. The effect of the severity of obstructive sleep apnea syndrome on telomere length. Oncotarget 2016;7(43):69216–69224.

24.

24. Choi

K-M

, Thomas

, Yoon

, et al. Interaction between obstructive sleep apnea and shortened telomere length on brain white matter abnormality. Sleep 2016;39(9):1639–1645.

25.

25. Riestra

, Gebreab

, Xu

, et al. Obstructive sleep apnea risk and leukocyte telomere length in African Americans from the MH-GRID study. Sleep Breath 2017;21(3):751–757.

26.

26. Kim

, Lee

, Bhattacharjee

, et al. Leukocyte telomere length and plasma catestatin and myeloid-related protein 8/14 concentrations in children with obstructive sleep apnea. Chest 2010;138(1):91–99.

27.

27. Polonis

, Somers

, Becari

, et al. Moderate-to-severe obstructive sleep apnea is associated with telomere lengthening. Am J Physiol Heart Circ Physiol 2017;313(5):H1022–H1030.

28.

28. Lin

C-C

, Wang

H-Y

, Liaw

S-F

, et al. Effect of oral appliance on circulating leukocyte telomere length and SIRT1 in obstructive sleep apnea. Clin Oral Investig 2019;23(3):1397–1405.

29.

29. Khan

, Chuturgoon

, Naidoo

. Telomeres and atherosclerosis. Cardiovasc J Afr 2012;23(10):563–571.

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