TABLE 5.

The effects of sleep apnea on aging markers (leukocyte telomere length) and age-related diseases.

Author, year (ref.)	Conditions	Age in years	Study design	Total quality score#	Type of sleep apnea	Sleep apnea criteria	Aging markers	Results	Conclusion
Barceló et al., 2010	SA	49.5	Case-control	7	OSAS	AHI > 10	LTL	TL was significantly shorter in patients with OSAS than in controls. This difference persisted after adjustment for age, presence of cardiovascular and metabolic changes. TL was not related to the severity of OSAS.	TL in circulating leukocytes is shorter in patients with OSAS than controls. The mechanism of this observation is unresolved since it appears independent of chronological age, the severity of OSAS and/or the presence of cardiovascular or metabolic changes.
Carroll et al., 2019	SA	44–84	Cohort	9	OSA	AHI > 15	LTL	Severe obstructive sleep apnea was associated with shorter LTL. An exploratory analysis found that higher arousal index at Exam 5 was associated with greater LTL decline over the prior 10 years.	OSA was associated with shorter leukocyte telomere length. Individuals with high arousal frequency had greater leukocyte telomere attrition over the prior decade. These findings suggest that sleep apnea and sleep fragmentation are associated with accelerated biological aging.
Boyer et al., 2016	SA	46.8	Case-control	6	OSAS	AHI > 5/h	LTL	AHI and oxygen desaturation index were significantly related to telomere shortening.	Intermittent hypoxemia due to OSAS is a major contributor to telomere shortening in middle-aged men. Oxidative stress may explain this finding.
Kim et al., 2010	SA	5–10	Case-control	8	OSA	AHI > 1/hrTST	LTL	LTL was independently associated with AHI.	In pediatric OSA, LTL is longer rather than shorter. Children with OSA have reduced plasma catestatin levels and increased BP along with increased MRP 8/14 levels that exhibit AHI dependencies. Thus, catestatin and MRP 8/14 levels may serve as biomarkers for cardiovascular risk in the context of pediatric OSA. However, the implications of increased LTL in children with OSA remain to be defined.
							Catestatin	Children with OSA exhibited lower plasma catestatin.
							MRP 8/14	Children with OSA exhibited higher MRP 8/14 levels than controls
Kim et al., 2016	SA	45.6	Case-control	7	OSA	RDI ≥ 5	LTL	Significantly shortened TL was observed in the circulating leukocytes of the peripheral blood of OSA patients, and TL shortening was aggravated more acutely in an age- and BMI-dependent manner.	The results provided evidence that telomere length shortening or excessive cellular aging might be distinctive in circulating leukocyte of OSA patients.
Kwon et al., 2015	SA	58.9 years	Cohort	9	OSA	AHI ≥ 5	LTL	Sleep stability significantly reduced with shortened LTL in OSA patients.	The present study suggested that shorter LTL might contribute to reduced sleep stability by interacting with OSA severity due to the stress of chronic sleep fragmentation or invariant sympathetic activity by respiratory chemoreflex activation.
Polonis et al., 2019	SA	35.6 (cases) and 47.3 (controls)	Case-control	8	OSA	AHI ≥ 5	LTL	The OSA group had a higher likelihood of cancer but no clear evidence of an elevated incidence of MACE compared to the non-OSA group. There was no association between TL and MACE or cancer-risk.	The study warrants further investigation of any modulating effect of OSA on TL and the risk of MACE and cancer.
Polonis et al., 2017	SA	27–57	Case-control	7	OSA	AHI ≥ 5	LTL	There was no difference in telomere length between OSA and control group. The mean TL in moderate-to-severe OSA was significantly longer than in control group after adjustment for age, sex, BMI, hypertension, dyslipidemia and depression.	Moderate-to-severe OSA is associated with telomere lengthening. These findings support the idea that changes in TL are not unidirectional processes such that telomere shortening occurs with age and disease, but may be prolonged in moderate-to-severe OSA.
Riestra et al., 2017	SA	30–55	Case-control	9	OSA	High risk of having OSA if scores were positive for two or more of the three categories by Berlin questionnaire.	LTL	The study showed that LTL varied by OSA risk in women. Multiple linear regression analysis confirmed that women at higher risk for OSA presented shorter LTL compared to those at lower risk. These differences were not observed in men.	These findings suggest that OSA risk may contribute to the acceleration of cellular aging processes through telomere shortening.
Tempaku et al., 2016	SA	20–80	Case-control	8	OSAS	AHI > 5	LTL	LTL was significantly shorter in OSAS patients compared to controls.	The study indicates the presence of an association between LTL and OSAS and a significant impact of severity of OSAS in telomeres shortening.

^#Total quality score out of 9 for cohort/case-control and out of 7 for cross-sectional; SA, sleep apnea; OSA, obstructive sleep apnea; TL, telomere length; LTL, leukocyte telomere length; AHI, apnea–hypopnea index; RDI, respiratory disturbance index; qPCR, quantitative polymerase chain reaction; hrTST, hour of total sleep time; MRP, myeloid-related protein; ROS, reactive oxygen species; MACE, major adverse cardiac events.