Telomere length: A marker of disease susceptibility?

doi:10.1016/j.bbi.2013.08.004

Brain, Behavior, and Immunity

Volume 34, November 2013, Pages 29-30

https://doi.org/10.1016/j.bbi.2013.08.004 Get rights and content

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Cohen et al. highlight important behavioral influences on cell aging which could have broad implications for infectious disease susceptibility.

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Association between telomere length and experimentally induced upper respiratory viral infection in healthy adults
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Cohen, S., Janicki-Deverts, D., Turner, R.B., Marsland, A.L., Casselbrant, M.L., Li-Korotky, H.-S., Epel, E.S., Doyle,...

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Cited by (18)

Telomere length and salivary cortisol stress reactivity in very preterm infants
2019, Early Human Development
Citation Excerpt :
Telomeres are the end-cap of chromosomes, they shorten at each cell replication, and their erosion rate is highly affected by the exposure to early stressful life conditions in humans [20]. Although research to date has been mainly retrospective in this field, literature suggests that adults who report early exposures to adverse conditions (e.g., childhood trauma and neglect) exhibit shorter telomeres in peripheral blood compared to controls without history of adversities [21,22]. Moreover, increased TL erosion predicted salivary cortisol stress reactivity in children exposed to maternal depression [23].
During the Neonatal Intensive Care Unit (NICU) stay, very preterm (VPT) infants are exposed to life-saving yet pain-inducing skin-breaking procedures (i.e., NICU pain-related stress) which contribute to the programming of hypo-responsive HPA axis development during the first months of life. Unfortunately, to date the mechanisms linking NICU pain-related stress and altered HPA axis regulation are only limitedly known. Telomere length (TL) regulation is an epigenetic mechanism previously shown to be affected by early stress exposures and capable of associating with HPA axis reactivity in children. In VPT infants, NICU pain-related stress was found to associate with decreased TL from birth to discharge, but there is no evidence for the association between TL and HPA axis in these infants. In this study, we prospectively examined the relationship between NICU pain-related stress and HPA axis reactivity to an age-appropriate socio-emotional condition (i.e., the Still-Face Procedure, SFP) in healthy VPT infants at 3-month corrected age. NICU pain-related stress was computed as the ratio between the number of skin-breaking procedures and length of NICU stay. A differential score (i.e., ∆TL) was obtained subtracting TL at birth from TL at discharge. A normalized (log10) cortisol reactivity index (CRI) was obtained by averaging post-stress (20 min after SFP) salivary cortisol sample on baseline value. A regression model controlling for neonatal and socio-demographic confounders showed that ∆TL was the only significant predictor of CRI. Although preliminary, these findings contribute to our knowledge of the mechanisms linking early exposures to adversity and later in life regulation of the HPA axis in VPT infants.
Telomere length and telomere repeating factors: Cellular markers for post-traumatic stress disorder-like model
2016, Journal of Affective Disorders
Citation Excerpt :
Telomere repeating factor 1 (TRF1) and telomere repeating factor 2 (TRF2) are the two major proteins among telomere-binding proteins, which negatively regulate the telomere length (van Steensel and de Lange, 2002; Ancelin et al., 2011; Mahalingam et al., 2011). Previous longitudinal studies indicated that a shorter telomere length was closely associated with the susceptibility of disease, age-related disease, and high risk of early death (Armanios and Blackburn, 2012; Cohen, Janicki-Deverts et al., 2013; Kiecolt-Glaser et al., 2013). The latest studies showed that the mental traumatic stress was also associated with the shortening of telomere length, besides the biochemical stimulations (such as oxidative stress and inflammation) (Epel et al., 2004; Damjanovic et al., 2007).
The aim of the present study was to explore the telomere length of peripheral blood leukocytes from a rat model of post-traumatic stress disorder (PTSD), as well as the expression level of telomere-binding protein in the hippocampal CA1 region.
The PTSD model was established with 42 adult male Wistar rats. The relative telomere length of the leukocytes was measured by real-time fluorescence quantitative polymerase chain reaction, and the expression levels of telomere repeating factor 1 (TRF1) and telomere repeating factor 2 (TRF2) in the hippocampal CA1 region of the PTSD rat model were determined by immunofluorescence technology. The covariance analysis of repeated measurements by the mixed model approach was used for the telomere length analysis. The comparison of averaged data among groups was performed using least significant difference and analysis of variance. The Student’s t test or the Mann–Whitney U test was used for intragroup comparison. The association study among groups was conducted using the Spearman test.
The shortening speed of telomere length significantly accelerated in rats after Single Prolonged Stress (SPS) stimulation (P<0.05). The expression levels of TRF1 and TRF2 increased with the progress of PTSD, and the expression peak was shown in day 14, which was significantly different from the control group (P<0.05).
The shortening speed of the telomere length of peripheral blood leukocytes accelerated in PTSD rats, and the expression levels of TRF1 and TRF2 increased in hippocampus, both of which were closely associated with the pathological progress of the PTSD-like model and unfavorable prognosis.
Do telomeres have a higher plasticity than thought? Results from the German Chronic Kidney Disease (GCKD) study as a high-risk population
2015, Experimental Gerontology
Citation Excerpt :
In line with these characteristics, short telomere length is associated with several cardiovascular risk factors in the general population. This observation has led to the assumption that reduced telomere length is an indicator of biological age and a potential marker and/or predictor of CVD risk and progression (Kiecolt-Glaser et al., 2013; Codd et al., 2013; Willeit et al., 2010; Brouilette et al., 2007; Raschenberger et al., 2015b). Recent data indicate that telomere shortening with age and disease is not a one-way development.
Telomere length is considered as a biological marker for aging. It is expected that telomeres shorten with age and with conditions associated with oxidative stress and inflammation. Both are present in patients with chronic kidney disease (CKD) who have a very high cardiovascular risk. We investigated whether CKD duration is associated with relative telomere length (RTL) in 4802 patients from the German Chronic Kidney Disease (GCKD) study. We measured RTL in each sample in quadruplicates using a quantitative polymerase chain reaction (qPCR). We observed a U-shaped association of RTL with CKD duration: the longest RTL was found in those 339 patients who reported the shortest disease duration (< 6 months) and shorter RTL in 2108 patients with duration between 6 months and less than 5 years. Most importantly, those 2331 patients who reported a CKD duration of 5 years and more had significantly longer RTL compared to those with intermediate CKD duration (6 months to less than 5 years): mean 0.954, 95%CI 0.946–0.961 versus 0.937, 95%CI 0.929–0.944, p = 0.002). Due to the cross-sectional nature of the study these surprising results have to be considered with caution and as hypothesis-generating. Whether the longer RTL in patients with long-lasting disease is caused by an activation of telomerase to counteract the shortening of RTL due to oxidative stress and inflammation or whether they are caused by a survival bias needs to be investigated in longitudinal studies. Our data are in support of a higher plasticity of shortening and elongations of RTL as until recently anticipated.
Association of relative telomere length with cardiovascular disease in a large chronic kidney disease cohort: The GCKD study
2015, Atherosclerosis
Citation Excerpt :
Short TL is associated with several cardiovascular risk factors in the general population such as age, male gender, obesity, hypertension, diabetes and smoking [14,15]. This observation has led to the assumption that reduced TL is an indicator of biological age and a potential marker and/or predictor of CVD risk and progression [16,17]. Shortened TL has been shown to be associated with CVD [18,19] and both are highly prevalent in older adults.
Chronic kidney disease (CKD) affects 10–15% of the general population and affected individuals are at an increased risk for cardiovascular disease (CVD). Since telomere length is considered to be involved in biological aging, we tested whether relative telomere length (RTL) might be a marker for these two diseases.
The German Chronic Kidney Disease (GCKD) study is an ongoing prospective cohort study including patients with CKD of moderate severity. RTL was measured by qPCR in 4955 out of 5217 GCKD patients at baseline.
RTL was distributed in the cohort with a mean ± SD of 0.95 ± 0.19. CVD was present in 1266 patients. Each decrease of RTL by 0.1 unit was associated with a higher probability for prevalent CVD: OR = 1.06, 95% CI 1.02–1.11, p = 0.007 (adjusted for age, sex, eGFR, BMI, ln-CRP, smoking, hypertension, diabetes, and lipids). Similar findings were observed for history of specific CVD entities, such as coronary artery disease (OR = 1.05, p = 0.025), myocardial infarction (OR = 1.08, p = 0.013) and percutaneous transluminal coronary angioplasty (OR = 1.06, p = 0.032). The strongest associations were found for interventions at the carotid arteries (OR = 1.25, p = 0.001) as well as aortic aneurysms (OR = 1.22, p = 0.001).
In the presence of CKD there is a significant association between shorter RTL and CVD manifestations. RTL appears to be a marker reflecting changes in homeostasis associated with CKD that may contribute to the excess CVD risk.
Nutritional components as mitigators of cellular senescence in organismal aging: a comprehensive review
2022, Food Science and Biotechnology
Updated understanding of cancer as a metabolic and telomere-driven disease, and proposal for complex personalized treatment, a hypothesis
2020, International Journal of Molecular Sciences

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^☆: Work on this paper was supported in part by NIH Grants CA158868, CA131029, AG038621, and CA172296, as well as Ohio State Comprehensive Cancer Center Core Grant CA16058, and NCRR Grant UL1RR025755.

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Brief CommentaryTelomere length: A marker of disease susceptibility?☆

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Brain Behav. Immun.

Brain Behav. Immun.

Mutat. Res.

Association between telomere length and experimentally induced upper respiratory viral infection in healthy adults

JAMA

Brief Commentary
Telomere length: A marker of disease susceptibility?☆