Accelerated Biological Aging and a Nonlinear Risk Threshold for Sleep Apnea: Evidence from NHANES and Mediation by Oxidative-Metabolic Dysregulation
By: Jia Guo, Xiaona Wang and Ranran Zhao
References
- THEORELL-HAGLÖW J., MILLER CB., BARTLETT DJ., YEE BJ., OPENSHAW HD., GRUNSTEIN RR. Gender differences in obstructive sleep apnoea, insomnia and restless legs syndrome in adults - What do we know? A clinical update. Sleep Med Rev. 2018;38:28–38.
- FRANKLIN KA., LINDBERG E. Obstructive sleep apnea is a common disorder in the population-a review on the epidemiology of sleep apnea. J Thorac Dis. 2015;7(8):1311–1322.
- LOPEZ-JIMENEZ F., SERT KUNIYOSHI FH., GAMI A., SOMERS VK. Obstructive sleep apnea: implications for cardiac and vascular disease. Chest 2008;133(3):793–804.
- YAGGI HK., CONCATO J., KERNAN WN., LICHTMAN JH., BRASS LM., MOHSENIN V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med. 2005;353(19):2034–2041.
- DRAGER LF., LOPES HF., MAKI-NUNES C., TROMBETTA IC., TOSCHI-DIAS E., ALVES MJNN., et al. The impact of obstructive sleep apnea on metabolic and inflammatory markers in consecutive patients with metabolic syndrome. PLoS One 2010;5(8):e12065.
- DOUGLAS N., YOUNG A., ROEBUCK T., HO S., MILLER BR., KEE K., et al. Prevalence of depression in patients referred with snoring and obstructive sleep apnoea. Intern Med J. 2013;43(6):630–634.
- REDLINE S., AZARBARZIN A., PEKER Y. Obstructive sleep apnoea heterogeneity and cardiovascular disease. Nat Rev Cardiol. 2023;20(8):560–573.
- LV R., LIU X., ZHANG Y., DONG N., WANG X., HE Y., et al. Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome. Signal Transduct Target Ther. 2023;8(1):218.
- HAO M., ZHANG H., WU J., HUANG Y., LI X., WANG M., et al. Gompertz Law-Based Biological Age (GOLD BioAge): A Simple and Practical Measurement of Biological Ageing to Capture Morbidity and Mortality Risks. Adv Sci. 2025;12(32):e01765.
- LEVINE ME., LU AT., QUACH A., CHEN BH., ASSIMES TL., BANDINELLI S., et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany. NY). 2018;10(4):573–591.
- GASPAR LS., ÁLVARO AR., MOITA J., CAVADAS C. Obstructive Sleep Apnea and Hallmarks of Aging. Trends Mol Med. 2017;23(8):675–692.
- BORGONI S., KUDRYASHOVA KS., BURKA K., DE MAGALHÃES JP. Targeting immune dysfunction in aging. Ageing Res Rev. 2021;70:101410.
- DOMÍNGUEZ F., FUSTER V., FERNÁNDEZ-ALVIRA JM., FERNÁNDEZ-FRIERA L., LÓPEZ-MELGAR B., BLANCO-ROJO R., et al. Association of Sleep Duration and Quality With Subclinical Atherosclerosis. J Am Coll Cardiol. 2019;73(2):134–144.
- WANG H., ZHANG J., NING J., CUI Y., HOU H., LIU M., et al. Oxidative stress and inflammation mediate the association between Life’s Crucial 9 and biological ageing: A secondary analysis of two observational studies. J Nutr Health Aging. 2025;29(7):100575.
- STARR ME., HU Y., STROMBERG AJ., CARMICAL JR., WOOD TG., EVERS BM., et al. Gene expression profile of mouse white adipose tissue during inflammatory stress: age-dependent upregulation of major procoagulant factors. Aging Cell. 2013;12(2):194–206.
- MENG X-H., CHEN B., ZHANG JP. Intracellular Insulin and Impaired Autophagy in a Zebrafish model and a Cell Model of Type 2 diabetes. Int J Biol Sci. 2017;13(8):985–995.
- FOSTER GD., SANDERS MH., MILLMAN R., ZAMMIT G., BORRADAILE KE., NEWMAN AB., et al. Obstructive sleep apnea among obese patients with type 2 diabetes. Diabetes Care. 2009;32(6):1017–1019.
- CHEN L., CAO Z., HAN F., GAO Z., HE Q. Chronic intermittent hypoxia from pedostage decreases glucose transporter 4 expression in adipose tissue and causes insulin resistance. Chin Med J (Engl). 2010;123(4):463–470.
- SERRANO R., VILLAR M., GALLARDO N., CARRASCOSA JM., MARTINEZ C., ANDRÉS A. The effect of aging on insulin signalling pathway is tissue dependent: central role of adipose tissue in the insulin resistance of aging. Mech Ageing Dev. 2009;130(3):189–197.
- OU M-Y., ZHANG H., TAN P-C., ZHOU S-B., LI Q-F. Adipose tissue aging: mechanisms and therapeutic implications. Cell Death Dis. 2022;13(4):300.
- KUK JL., SAUNDERS TJ., DAVIDSON LE., ROSS R. Age-related changes in total and regional fat distribution. Ageing Res Rev. 2009;8(4):339–348.
- LIU W., WANG J., WANG M., HOU H., DING X., MA L., et al. Oxidative Stress Factors Mediate the Association Between Life’s Essential 8 and Accelerated Phenotypic Aging: NHANES 2005–2018. J Gerontol A Biol Sci Med Sci. 2024;79(1):1–9.
- XU S., HUANG X., WANG Y., LIU J., ZHANG W. The effect of dual antioxidant modification on oxidative stress resistance and anti-dysfunction of non-split HDL and recombinant HDL. Int J Biol Macromol. 2024;278(Pt 1):134632.
- YU X., SUN F., MING J., LIANG S., ZHANG W., WANG L., et al. Serum uric acid to high-density lipoprotein cholesterol ratio is a promising marker for identifying metabolic syndrome in nondiabetic Chinese men. Postgrad Med. 2023;135(7):741–749.
- ZHOU X., XU J. Association between serum uric acid-to-high-density lipoprotein cholesterol ratio and insulin resistance in patients with type 2 diabetes mellitus. J Diabetes Investig. 2024;15(1):113–120.
- WANG Y., XU Y., HU T., XIAO Y., WANG Y., MA X., et al. Associations of Serum Uric Acid to High-Density Lipoprotein Cholesterol Ratio with Trunk Fat Mass and Visceral Fat Accumulation. Diabetes Metab Syndr Obes. 2024;17:121–129.
- LIU Z., KUO P-L., HORVATH S., CRIMMINS E., FERRUCCI L., LEVINE M. A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study. PLoS Med. 2018;15(12):e1002718.
- PEJOVIC S., VGONTZAS AN., FERNANDEZ-MENDOZA J., HE F., LI Y., BIXLER EO. Effect of age on the association of obstructive sleep apnea with metabolic syndrome among obese and nonobese adults. J Clin Sleep Med. 2025;21(8):1371–1378.
- HOWARTH TP., KARHU T., LEPPÄNEN T., SAAD HB., BAHAMMAM A., NIKKONEN S. Five-year longitudinal changes in oxygen saturation parameters in Obstructive Sleep Apnoea: Impact of age, body mass index, and comorbidities. Sleep Med. 2026;143:108866.
- LI D., LIU Q., FAN X., QI K., SUN M., SONG J., et al. Hydrogen promoted mitochondrial autophagy and alleviated CIH-induced vascular endothelial cell senescence by regulating oxidative stress. Eur J Pharmacol. 2025;1005:178078.
- DUNIETZ GL., CHERVIN RD., TAUMAN R., SHAKLAI S., SANKARI A. OSA in Women: Associations With Reproductive Aging and Screening Challenges. Chest. 2026;169(3):803–812
- CASTILLO J., GARCÍA N., GÓMEZ F. Frailty and Genetics: Linking Molecular Aging to Clinical Vulnerability. J Gerontol A Biol Sci Med Sci. 2026; doi:10.1093/gerona/glag088.
- D’ANGELO GF., DE MELLO AAF., SCHORR F., GEBRIM E., FERNANDES M., LIMA GF., et al. Muscle and visceral fat infiltration: A potential mechanism to explain the worsening of obstructive sleep apnea with age. Sleep Med. 2023;104:42–48.
- GUO Y., MIAO Y., TAN J., ZHAO R., JIANG D., ZOU M., et al. Telomere dysfunction is associated with exacerbated intermittent hypoxia-induced cognitive deficits and nerve damage. Front Aging Neurosci. 2026;18:1758688.
- Abdeahad H., Moreno DG., Pontes Oliveira de Almeida AJ., da Silva Pontes LV., Lesniewski LA., Donato AJ. Aging and DNA damage are associated with the development of endothelial cell clonal expansion. Am J Physiol Heart Circ Physiol. 2026; doi:10.1152/ajpheart.00102.
- FAHL K., MAUAD T., DE BRITO JM., COSTA NSX., DANTAS DAS., DE SOUZA HP., et al. Upper airway microcirculation remodeling in obstructive sleep apnea is not driven by endothelial activation. Sci Rep. 2025;15(1):13355.
Language: English
Submitted on: Mar 7, 2026
Published on: May 18, 2026
Published by: N.G. Lupu Internal Medicine Foundation
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Keywords:
Related subjects:
© 2026 Jia Guo, Xiaona Wang, Ranran Zhao, published by N.G. Lupu Internal Medicine Foundation
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.