Research Progress on the Role of SIRT1 in Obstructive Sleep Apnea
DOI:
https://doi.org/10.54097/w1fxej06Keywords:
SIRT1, Obstructive Sleep Apnea, Biomarkers, Genetic PolymorphismAbstract
Obstructive Sleep Apnea (OSA) is a common sleep disorder. OSA is closely related to a variety of serious complications such as cardiovascular diseases, metabolic disorders, diabetes, cognitive impairment, and tumors. Silent information regulator 2 homolog 1(SIRT1), a class III histone deacetylase, regulates key biological processes such as anti-oxidation, anti-inflammation, metabolic homeostasis and apoptosis. It plays a core protective role in a variety of pathophysiological mechanisms of OSA. This review systematically summarized the association of SIRT1 and its gene polymorphisms with the occurrence and development of OSA and its complications, elaborated the changes in the expression level of SIRT1 in OSA animal models and patients, and commented on the clinical research progress of targeted activation of SIRT1 as a potential treatment strategy for OSA. These findings provide an important theoretical basis and new ideas for the development of new strategies for clinical prevention, diagnosis and treatment of OSA based on SIRT1.
Downloads
References
[1] Lv, R. et al. Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome. Signal Transduct Target Ther 8, 218 (2023). https://doi.org:10.1038/ s41392-023-01496-3.
[2] Benjafield, A. V. et al. Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. Lancet Respir Med 7, 687-698 (2019). https://doi.org:10.1016/ s2213-2600(19)30198-5.
[3] Yeghiazarians, Y. et al. Obstructive Sleep Apnea and Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation 144, e56-e67 (2021). https://doi.org:10.1161/cir.0000000000000988.
[4] Maniaci, A. et al. Anxiety, depression and sleepiness in OSA patients treated with barbed reposition pharyngoplasty: a prospective study. Eur Arch Otorhinolaryngol 279, 4189-4198 (2022). https://doi.org:10.1007/s00405-022-07369-9.
[5] Dharmakulaseelan, L. & Boulos, M. I. Sleep Apnea and Stroke: A Narrative Review. Chest 166, 857-866 (2024). https://doi. org: 10. 1016/j.chest.2024.04.028.
[6] Huang, Q. et al. A SIRT1 Activator, Ginsenoside Rc, Promotes Energy Metabolism in Cardiomyocytes and Neurons. J Am Chem Soc 143, 1416-1427 (2021). https://doi.org:10. 1021/jacs. 0c 10836.
[7] Yang, Y. et al. Regulation of SIRT1 and Its Roles in Inflammation. Front Immunol 13, 831168 (2022). https://doi. org: 10. 3389/fimmu.2022.831168.
[8] Chen, C., Zhou, M., Ge, Y. & Wang, X. SIRT1 and aging related signaling pathways. Mech Ageing Dev 187, 111215 (2020). https://doi.org:10.1016/j.mad.2020.111215.
[9] Tian, C., Huang, R. & Xiang, M. SIRT1: Harnessing multiple pathways to hinder NAFLD. Pharmacol Res 203, 107155 (2024). https://doi.org:10.1016/j.phrs.2024.107155.
[10] Chung, J. Y. & Knutson, B. A. Bypassing the guardian: regulated cell death pathways in p53-mutant cancers. Cell Mol Biol Lett 30, 68 (2025). https://doi.org:10.1186/s11658-025-00751-5.
[11] Gupta, S. et al. Harnessing the FOXO-SIRT1 axis: insights into cellular stress, metabolism, and aging. Biogerontology 26, 65 (2025). https://doi.org:10.1007/s10522-025-10207-0.
[12] Zhao, X. et al. Sirt1 inhibits macrophage polarization and inflammation in gouty arthritis by inhibiting the MAPK/NF-κB/AP-1 pathway and activating the Nrf2/HO-1 pathway. Inflamm Res 73, 1173-1184 (2024). https://doi.org: 10.1007/ s00011-024-01890-9.
[13] He, Y. et al. SIRT6 inhibits TNF-α-induced inflammation of vascular adventitial fibroblasts through ROS and Akt signaling pathway. Exp Cell Res 357, 88-97 (2017). https://doi.org: 10.1016/ j.yexcr.2017.05.001.
[14] Zhang, Y. et al. SIRT1 alleviates isoniazid-induced hepatocyte injury by reducing histone acetylation in the IL-6 promoter region. Int Immunopharmacol 67, 348-355 (2019). https://doi. org: 10.1016/j.intimp.2018.11.054.
[15] Bai, M. et al. SIRT1 relieves Necrotizing Enterocolitis through inactivation of Hypoxia-inducible factor (HIF)-1a. Cell Cycle 19, 2018-2027 (2020). https://doi.org:10.1080/ 15384101. 2020. 1788251.
[16] Ministrini, S. et al. Sirtuin 1 in Endothelial Dysfunction and Cardiovascular Aging. Front Physiol 12, 733696 (2021). https://doi.org:10.3389/fphys.2021.733696.
[17] Kheirandish-Gozal, L. & Gozal, D. Obstructive Sleep Apnea and Inflammation: Proof of Concept Based on Two Illustrative Cytokines. Int J Mol Sci 20 (2019). https://doi.org:10. 3390/ ijms 20030459.
[18] Badran, M., Bender, S. B. & Gozal, D. Cardiovascular Disease in Obstructive Sleep Apnea: Putative Contributions of Mineralocorticoid Receptors. Int J Mol Sci 24 (2023). https://doi.org:10.3390/ijms24032245.
[19] Zhou, R., Wang, Q., Zhang, C., Ma, J. & Wang, G. [The expression of SIRT1 in brainstem of rats in different types of hypoxia and its significance]. Zhonghua Jie He He Hu Xi Za Zhi 37, 352-355 (2014).
[20] Zhang, K. et al. The Protective Role of Leptin in Neurological Damage Induced by Chronic Intermittent Hypoxia. Mol Neurobiol (2025). https://doi.org:10.1007/s12035-025-05018-w.
[21] Yaman, M. et al. Evaluation of SIRT1 Protein Levels and SIRT1/rs7895833 Distributions in Turkish Patients With Obstructive Sleep Apnea. J Clin Lab Anal 39, e70014 (2025). https://doi.org:10.1002/jcla.70014.
[22] Chen, W. J. et al. Effect of Nasal CPAP on SIRT1 and Endothelial Function in Obstructive Sleep Apnea Syndrome. Lung 193, 1037-1045 (2015). https://doi.org:10.1007/s00408-015-9790-y.
[23] Khalyfa, A. et al. Plasma exosomes in OSA patients promote endothelial senescence: effect of long-term adherent continuous positive airway pressure. Sleep 43 (2020). https:// doi. org: 10.1093/sleep/zsz217.
[24] Lin, C. C., Wang, H. Y., Liaw, S. F., Chiu, C. H. & Lin, M. W. Effect of oral appliance on circulating leukocyte telomere length and SIRT1 in obstructive sleep apnea. Clin Oral Investig 23, 1397-1405 (2019). https://doi.org:10.1007/s00784-018-2560-5.
[25] Wang, Q. et al. Resveratrol attenuates intermittent hypoxia-induced insulin resistance in rats: involvement of Sirtuin 1 and the phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT pathway. Mol Med Rep 11, 151-158 (2015). https://doi.org: 10.3892/ mmr.2014.2762.
[26] Zhang, L. et al. Nicotinamide Phosphoribosyltransferase Acetylation Mediating Muscle Dysfunction Contributes to Sleep Apnoea in Obesity. J Cachexia Sarcopenia Muscle 16, e13693 (2025). https://doi.org:10.1002/jcsm.13693.
[27] Sun, L. et al. Metoprolol prevents chronic obstructive sleep apnea-induced atrial fibrillation by inhibiting structural, sympathetic nervous and metabolic remodeling of the atria. Sci Rep 7, 14941 (2017). https://doi.org:10.1038/s41598-017-14960-2.
[28] Pai, P. Y. et al. Angiotensin II receptor blocker irbesartan attenuates sleep apnea-induced cardiac apoptosis and enhances cardiac survival and Sirtuin 1 upregulation. Sleep Breath 26, 1161-1172 (2022). https://doi.org:10.1007/s11325-021-02499-6.
[29] Wei, Q. et al. Effects of chronic intermittent hypoxia on left cardiac function in young and aged mice. Am J Physiol Regul Integr Comp Physiol 322, R241-r252 (2022). https://doi.org: 10. 1152/ajpregu.00256.2021.
[30] Zhang, K., Ma, D., Wu, Y. & Xu, Z. Impact of Chronic Intermittent Hypoxia on Cognitive Function and Hippocampal Neurons in Mice: A Study of Inflammatory and Oxidative Stress Pathways. Nat Sci Sleep 16, 2029-2043 (2024). https:// doi.org: 10.2147/nss.S489232.
[31] Zhang, C. et al. The HMGB1-RAGE/TLR-TNF-α signaling pathway may contribute to kidney injury induced by hypoxia. Exp Ther Med 17, 17-26 (2019). https://doi.org: 10.3892/ etm. 2018. 6932.
[32] Javaheri, S. et al. Treatment of OSA and its Impact on Cardiovascular Disease, Part 2: JACC State-of-the-Art Review. J Am Coll Cardiol 84, 1224-1240 (2024). https://doi.org: 10.1016/ j.jacc.2024.07.024.
[33] He, X. et al. Resveratrol Alleviates the Prenatally Intermittent Hypoxia-Induced Cognitive Impairment in Male Offspring Mice Through Modulating the SIRT1/HIF-1α Pathway. Brain Behav 15, e70413 (2025). https://doi.org:10.1002/brb3.70413.
[34] Zhao, F. et al. Protective effect of Astragaloside IV on chronic intermittent hypoxia-induced vascular endothelial dysfunction through the calpain-1/SIRT1/AMPK signaling pathway. Front Pharmacol 13, 920977 (2022). https://doi.org:10.3389/ fphar. 2022. 920977.
[35] Li, D. et al. Danggui-Buxue decoction alleviated vascular senescence in mice exposed to chronic intermittent hypoxia through activating the Nrf2/HO-1 pathway. Pharm Biol 61, 1041-1053 (2023). https://doi.org:10.1080/ 13880209. 2023. 2230753.
[36] Zhang, J. et al. Downregulation of miR-34c-5p alleviates chronic intermittent hypoxia-induced myocardial damage by targeting sirtuin 1. J Biochem Mol Toxicol 36, e23164 (2022). https://doi.org:10.1002/jbt.23164.
Downloads
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
