Relative Leukocyte Telomere Length Research Articles

Relative leucocyte telomere length is associated with incident end-stage kidney disease and rapid decline of kidney function in type 2 diabetes: analysis from the Hong Kong Diabetes Register

Aims/hypothesisFew large-scale prospective studies have investigated associations between relative leucocyte telomere length (rLTL) and kidney dysfunction in individuals with type 2 diabetes. We examined relationships between rLTL and incident end-stage kidney disease (ESKD) and the slope of eGFR decline in Chinese individuals with type 2 diabetes.MethodsWe studied 4085 Chinese individuals with type 2 diabetes observed between 1995 and 2007 in the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data. rLTL was measured using quantitative PCR. ESKD was diagnosed based on the ICD-9 code and eGFR.ResultsIn this cohort (mean ± SD age 54.3 ± 12.6 years) followed up for 14.1 ± 5.3 years, 564 individuals developed incident ESKD and had shorter rLTL at baseline (4.2 ± 1.2 vs 4.7 ± 1.2, p < 0.001) than the non-progressors (n = 3521). On Cox regression analysis, each ∆∆Ct decrease in rLTL was associated with an increased risk of incident ESKD (HR 1.21 [95% CI 1.13, 1.30], p < 0.001); the association remained significant after adjusting for baseline age, sex, HbA1c, lipids, renal function and other risk factors (HR 1.11 [95% CI 1.03, 1.19], p = 0.007). Shorter rLTL at baseline was associated with rapid decline in eGFR (>4% per year) during follow-up (unadjusted OR 1.22 [95% CI 1.15, 1.30], p < 0.001; adjusted OR 1.09 [95% CI 1.01, 1.17], p = 0.024).Conclusions/interpretationrLTL is independently associated with incident ESKD and rapid eGFR loss in individuals with type 2 diabetes. Telomere length may be a useful biomarker for the progression of kidney function and ESKD in type 2 diabetes.Graphical abstract

Gender Difference in Associations Between Telomere Length and Risk Factors in Patients With Stroke.

Multiple risk factors of stroke are associated with telomere length shortening. Although leukocyte telomere length (LTL) is shorter in patients with stroke, the heterogeneity is high. Risk factors may be differentially associated with LTL in male and female patients contributing to the heterogeneity. However, the gender difference in associations between LTL and risk factors in stroke patients has not been investigated. In this study, we investigated the gender difference in associations between LTL and risk factors in 312 stroke patients. Real-time quantitative PCR was used to determine relative LTL, and multiple linear regression analysis was applied for association analyses. We found that LTL was negatively associated with triglyceride (TG) in all patients [β(95% CI) = −0.69 (−1.26, −0.11), P < 0.05] after adjusting confounders. Importantly, LTL was negatively associated with lack of exercise [β(95% CI) = −1.80 (−3.12, −0.49), P < 0.05] and LDL levels [β(95% CI) = −3.22 (−6.05, −0.390), P < 0.05] in male patients, while LTL was negatively associated with dyssomnia [β(95%CI) = −2.00 (−3.96, −0.07), P < 0.05] and diabetes [β(95%CI) = −2.13 (−4.10, −0.27), P < 0.01] in female patients. Our study showed that LTL is differently associated with risk factors in male and female patients with stroke, indicating that gender difference should be considered when LTL is potentially applied as an index of risk and prognosis for stroke. Our study also provides an insight into that gender differences should be considered when developing intervention strategies for stroke prevention and treatment.

Association between telomere length and mitochondrial copy number and cancer risk in humans: A meta-analysis on more than 300,000 individuals.

In the last decades the association of leukocyte telomere length (LTL) and mitochondrial copy number (mtDNAcn) with cancer risk has been the focus of many reports, however the relation is not yet completely understood. A meta-analysis of 112 studies including 64,184 cancer cases and 278,641 controls that analysed LTL and mtDNAcn in relation to cancer risk has been conducted to further our understanding of the topic. Stratified analyses for tumor type were also performed. Overall, no association was observed for all cancer combined neither for LTL nor mtDNAcn. Significant associations were detected for these biomarkers and specific cancer type; however, a large degree of heterogeneity was present, even within the same tumor type. Alternatives approaches based on polymorphic variants, such as polygenic risk scores and mendelian randomization, could be adopted to unravel the causal correlation of telomere length and mitochondrial copy number with cancer risk.

Leukocyte telomerase concentration is inversely associated with central wave reflection in patients with hypertension

Abstract Introduction Telomere length and telomerase are biomarkers of aging and cardiovascular diseases. Arterial stiffness is associated with vascular age and higher risk of cardiovascular diseases. Decreased reparative cell's potential may cause vascular ageing and predispose to the progression of hypertension. Objective To determine association leukocyte telomerase concentration (TC) and relative telomere length (RTL) with arterial stiffness in hypertensive patients. Material and methods The study included 120 people (70 patients with uncomplicated arterial hypertension (AH) and 50 normotensive individuals). Mean age of hypertensives was 54.8±9.3 and of normotensives was 50.2±9.73 years. Dietary habits, smoking, level of physical activity, body mass index, waist circumference, presence of obesity, blood pressure (BP) level, family history of cardiovascular deseases, depressive episodes and psychological stress according the international questionnaires, glucose; cholesterol, angiotensin II, renin and aldosteron in blood were assessed in the participants. Aortic BP, aortic pulse pressure, augmentation index (AIx), AIx adjusted for heart rate 75 beats per minute (Aix@HR75), pulse wave velocity (PWV) were determined by the applanation tonometry. RTL of peripheral blood leukocytes was performed by real-time PCR. The leukocyte TC was measured using the enzyme immunoassay. Results There were no differences between patients with AH and normotensives in both leukocyte TC (4.9 (4.0; 8.0) versus 6.2 (4.1; 9.4), p=0.281) and RTL (0.94 (0.86; 1.0) versus 0.96 (0.83; 1.0), p=0.978). In hypertensive and normotensive groups the mean systolic aortic BP were 130.6±17,7 and 109.9±11.7 mmHg (p&amp;lt;0.001), aortic pulse pressure – 41.5±9,7 and 33.6±10,4 mmHg (p&amp;lt;0.001), Aix@HR75 – 16.0 (7.0; 28.0) and 27.0 (13.0; 35.0)% (p=0.004), PWV –7.9±1.4 and 8.1±1,7 m/s (p=0.409) respectively. In patients with AH the mean leukocyte TC was lower with an increased Aix@75 (&amp;gt;25%) in contrast to the group of patients with normal Aix@75 (4.45 (3.9; 7.8) versus 7.97 (4.6; 10.0) ng/ml; p=0.043). Based on the multivariate logistic regression analysis independent factors influencing on the Aix@75 were leukocyte TC &amp;lt;5 ng/ml with the family history of AH (OR=1.9, 95% CI: 1.1–3.4; p=0.036), the degree of AH combined with decreased salt sensitivity (OR=3.1; 95% CI: 1.3–7.5; p=0.010) and age (OR=1.2; 95% CI: 1.1–1.2; p=0.001). Conclusions Decrease of the leukocyte telomerase concentration associated with the raise of augmentation index in patient with uncomplicated AH. As a parameter of central wave reflection the augmentation index may considered as an early sign of biological and vascular aging in hypertension. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The state program of scientific research “Fundamental and applied sciences for medicine”

Association between body temperature and leukocyte telomere length in Korean middle-aged and older adults.

OBJECTIVESData on associations between body temperature (BT) and leukocyte telomere length (LTL), which has been widely used as a biomarker of cellular senescence in recent epidemiological studies, are limited. Therefore, this study aimed to explore the associations between a normal BT range (35.0-37.5°C) and LTL via 6-year longitudinal observations of 2,004 male and female adults aged 50 or older.METHODSBT was obtained by measuring the tympanic temperature, and relative LTL was determined by real-time polymerase chain reaction. Robust regression analysis was used to evaluate the association between the baseline and follow-up LTL values and their differences.RESULTSA significant inverse association was found between BT and LTL at baseline. The regression coefficient estimate was -0.03 (95% confidence interval, -0.07 to -0.001; p<0.05). This association was stronger in participants with a body mass index >25 kg/m2 and males (p<0.01). However, there were no associations between BT and LTL at follow-up or BT and 6-year longitudinal differences in LTL.CONCLUSIONSThese findings suggest that having a high BT between 35°C and 37.5°C (95°F and 99°F) may be detrimental for obese individuals in terms of biological aging.

Metal co-exposures and telomere length in Bangladeshi children

BACKGROUND AND AIM: Telomeres are non-coding DNA sequences that protect the ends of chromosomes and preserve genetic material during cell division. Telomere length is associated with the occurrence and progression of common chronic diseases. In younger populations, telomere length may represent a biomarker of disease susceptibility. Growing evidence suggests that environmental factors, such as metals, can substantially impact the mechanisms that control telomere length. METHODS: We investigated the association between a panel of metals measured in toenail samples by inductively-coupled plasma mass spectrometry and leukocyte relative telomere length (RTL) measured by Luminex assay, among 472 five- to seven-year-old children enrolled in the Bangladesh Environmental Research in Children's Health (BiRCH) cohort. RESULTS:Of the 18 metals tested, statistically significant correlations with RTL were observed with toenail arsenic (tAs) and mercury (tHg). In linear regression models adjusted for child age, sex, and father’s age at child’s birth, a doubling of log2-transformed tAs was associated with a -0.022 (95% CI: -0.033, -0.011; p=0.0001) decrease in RTL. Similarly, a doubling of log2-transformed tHg was associated with a -0.020 (95% CI: -0.032, -0.007; p=0.002) decrease in RTL. Similar associations were observed using co-exposure regression models including both tAs and tHg, adjusted for covariates. In this model, we observed independent, negative associations of both log2-transformed tAs and tHg with RTL, such that a doubling of tAs was associated with a -0.019 (95% CI: -0.031, -0.007; p=0.003) decrease in RTL and a doubling of tHg was associated with a -0.015 (95% CI: -0.028, -0.002; p=0.02) decrease in RTL. CONCLUSIONS:Our study suggests that both As and Hg may independently influence RTL, with detectable associations in early- to mid-childhood. Further studies are needed to confirm our findings and investigate the potential long-term impacts of As- and Hg- exposure associated telomere shortening in childhood on health outcomes in adult life. KEYWORDS: metals, telomeres, toenails, Bangladesh, children

Neighborhood socioeconomic status and biomarkers among participants in the US-based Health Professionals’ Follow-Up Study and Nurses’ Health Study

BACKGROUND AND AIM: Neighborhood socioeconomic status (nSES) may affect human health through stress pathways, but few studies to date have investigated this hypothesis. We studied the association between nSES and multiple biomarkers of cellular aging and inflammation. METHODS: We used data from several nested case-control studies conducted within two US-based cohorts of men and women. Blood samples were collected for a subset of participants ten years after enrollment (1989/90 for NHS, 1996 for HPFS). Relative leukocyte telomere length (rLTL) was assayed using quantitative polymerase chain reaction. Inflammatory biomarkers (c-reactive protein (CRP), interleukin-6 (IL-6), soluble tumor necrosis factor receptor 2 (sTNFR-2)) were assessed. Nine census tract measures of income, home value, earnings from rent and dividends, education, and demographics in 1990 were assigned to each participant’s address (home for NHS, home or work for HPFS) at the time of blood draw. We z-scaled component measures, and then summed together to create a nSES score. Associations between nSES and log-transformed biomarkers were estimated using linear regression models adjusted for individual level demographics, disease history, and lifestyle factors. RESULTS:Participants with available biomarker data ranged from 9,481 (IL-6) to 15,400 (CRP). Women (57.4 years) were younger than men (62.5 years). Adjusted models revealed no association between nSES and rLTL in women (β for 1-unit increase in nSES z-score=0.001, 95% CI: -0.003, 0.005) or men (β=0.001, 95% CI: -0.001, 0.003). However, in women, higher nSES was associated with lower circulating levels of CRP (β=-0.008, 95% CI: -0.013, 0.002), IL-6 (β=-0.006, 95% CI: -0.010, 0.002), and sTNFR-2 (β=-0.002, 95% CI: -0.004, -0.0004). In men, nSES was not associated with CRP, but weaker inverse associations for IL-6 (β=-0.004, 95% CI: -0.010, 0.001) and sTNFR-2 (β=-0.004, 95% CI: -0.006, -0.0013) were observed. CONCLUSIONS:Findings suggest that inflammation, rather than cellular aging, may mediate stress-related consequences of nSES. KEYWORDS: Built environment, internal exposome, socio-economic factors, cancer and cancer-precursors, environmental epidemiology

Shortened leukocyte telomere length as a potential biomarker for predicting the progression of atrial fibrillation from paroxysm to persistence in the short-term.

This study aimed to assess the role of leukocyte telomere length (LTL) in the development of atrial fibrillation (AF) among Chinese patients.This is a cross-sectional study. A total of 350 patients from June 2016 to December 2017 were retrospectively analyzed. These included 219 AF patients and 131 with sinus rhythm in the control group. Quantitative real-time PCR was used to measure relative LTL.The relative LTLs of all subjects (n = 350) ranged from 0.4 to 2.41 (0.98 ± 0.29), showing a significant negative correlation (P < .001) with age. The AF-group had significantly shorter LTLs (0.93 ± 0.26 vs 1.07 ± 0.33, P < .001) and were older (61.50 ± 6.49 vs 59.95 ± 6.17, P = .028) than controls. LTLs among patients with persistent AF (PsAF), paroxysmal AF (PAF), and controls were significantly different (P < .001), with LTLs of PsAF patients being the shortest and controls being the longest. After adjusting for possible confounding factors, the PsAF group still showed significantly shorter LTLs than the PAF and control groups (P = .013 and P = .001, respectively). After an 18-month follow-up, 20 out of 119 PAF patients had progressed into PsAF and a relative LTL of ≤0.73 was an independent predictor for progression of PAF into PsAF.LTL was found to be shorter in patients with AF than in age-matched individuals with sinus rhythm and positively correlated with severity of AF. LTL shortening could be an independent risk factor for progression from paroxysmal AF to persistent AF in the short term.

The association between relative leukocyte telomere length of prostate cancer patients at diagnosis with cancer prognostic parameters

Objectives: In this study, relative leukocyte telomere length (LTL) was investigated as a prognostic marker to evaluate association of LTL at the time of diagnosis and prostate cancer-specific survival, metastasis-free survival, overall survival, with castrate-resistant prostate cancer (CRPC). Materials and Methods: In this retrospective cohort study, pertinent data from 81 patients were collected. Patients underwent prostate cancer (PCa) treatment procedures determined by staging and current recommendation. Blood samples from suspected PCa patients were obtained before the initiation of diagnosis and treatment. LTL was determined by the quantitative polymerase chain reaction method. Relative LTL was compared to the main clinical outcome measures. Prostate cancer-specific survival, metastasis-free survival, overall survival and CRPC were calculated retrospectively, for a mean follow-up period of 30 months. Results: This analysis showed relative LTL was not associated with tumor stage, Gleason score, grade group, metabolic disease, or smoking. However, older age was significantly associated with short LTL (p &lt; 0.001). All main outcomes were not associated with LTL. In contrast, a subgroup analysis of patients who underwent primary androgen deprivation therapy (ADT) showed a CRPC association with relatively long LTL (p = 0.039). To our knowledge, these results are novel and give further strength to our hypothesis that relative LTL might be used as a prognostic marker in PCa especially in patients who will receive primary ADT. Conclusion: Aging was significantly associated with relatively short LTL. There was no significant association between LTL in PCa patients at diagnosis and cancer-specific survival, metastasis-free survival, or overall survival. However, patients who underwent ADT treatment alone showed CRPC associated with relatively long LTL.

Daily Oral Supplementation with 60 mg of Elemental Iron for 12 Weeks Alters Blood Mitochondrial DNA Content, but Not Leukocyte Telomere Length in Cambodian Women.

There is limited evidence regarding the potential risk of untargeted iron supplementation, especially among individuals who are iron-replete or have genetic hemoglobinopathies. Excess iron exposure can increase the production of reactive oxygen species, which can lead to cellular damage. We evaluated the effect of daily oral supplementation on relative leukocyte telomere length (rLTL) and blood mitochondrial DNA (mtDNA) content in non-pregnant Cambodian women (18–45 years) who received 60 mg of elemental iron as ferrous sulfate (n = 190) or a placebo (n = 186) for 12 weeks. Buffy coat rLTL and mtDNA content were quantified by monochrome multiplex quantitative polymerase chain reaction. Generalized linear mixed-effects models were used to predict the absolute and percent change in rLTL and mtDNA content after 12 weeks. Iron supplementation was not associated with an absolute or percent change in rLTL after 12 weeks compared with placebo (ß-coefficient: −0.04 [95% CI: −0.16, 0.08]; p = 0.50 and ß-coefficient: −0.96 [95% CI: −2.69, 0.77]; p = 0.28, respectively). However, iron supplementation was associated with a smaller absolute and percent increase in mtDNA content after 12 weeks compared with placebo (ß-coefficient: −11 [95% CI: −20, −2]; p = 0.02 and ß-coefficient: −11 [95% CI: −20, −1]; p= 0.02, respectively). Thus, daily oral iron supplementation for 12 weeks was associated with altered mitochondrial homeostasis in our study sample. More research is needed to understand the risk of iron exposure and the biological consequences of altered mitochondrial homeostasis in order to inform the safety of the current global supplementation policy.

ASSOCIATION RELATIVE TELOMERE LENGTH AND TELOMERASE ACTIVITY WITH LIFESTYLE RISK FACTORS IN HYPERTENSIVE PATIENTS

Objective: To determine association relative telomere length (RTL) and telomerase activity with lifestyle risk factors in hypertensive patients (pts) and normotensive individuals. Design and method: 80 people (34 hypertensive patients and 46 normotensive individuals) were examined. Mean age of hypertensive pts was 55.5 ± 8.7 and of normotensives was 49.7 ± 9.9 years. Smoking status, alcohol abuse, level of physical activity, body mass index, waist circumference, presence of obesity, dietary habits, blood pressure (BP), glucose and cholesterol levels, depressive episodes and psychological stress were evaluated. Arterial stiffness performed by volume sphygmography with assessing cardio-ankle-vascular index (CAVI) and ankle-brachial index. The RTL of peripheral blood leukocytes performed by previously validated real-time PCR. Telomerase activity was determined by enzyme immunoassay. Results: The association was found between RTL and CAVI (r = −0.414; p = 0.021) in the group of hypertensive pts. However, there were no association with age, levels of glucose and cholesterol, BP, obesity, diet and psychological risk factors. Sedentary work was related with shortening RTL in hypertensive patients (p = 0.043) and in normotensives (p = 0.003). Telomerase activity was related with fruit consumption (r = 0.520; p = 0.004) in hypertensive patients. Among normotensives telomerase activity was associated with consumption of fish (r = 0.344; p = 0.024) and vegetables (r = 0.302; p = 0.004). In hypertensive patients and in normotensives also was found trend toward relation between telomerase activity with dietary salt (r = −0.312; p = 0.08 and r = −0.270; p = 0.07, accordingly). Conclusions: The data suggests that lifestyle risk factors such as sedentary work and rare fruit consumption can influence on RTL and telomerase activity in hypertensive pts as well as sedentary work, low intake of fish and vegetables in normotensive people.

Telomere attrition rates are associated with weather conditions and predict productive lifespan in dairy cattle

Telomere length is predictive of adult health and survival across vertebrate species. However, we currently do not know whether such associations result from among-individual differences in telomere length determined genetically or by early-life environmental conditions, or from differences in the rate of telomere attrition over the course of life that might be affected by environmental conditions. Here, we measured relative leukocyte telomere length (RLTL) multiple times across the entire lifespan of dairy cattle in a research population that is closely monitored for health and milk production and where individuals are predominantly culled in response to health issues. Animals varied in their change in RLTL between subsequent measurements and RLTL shortened more during early life and following hotter summers which are known to cause heat stress in dairy cows. The average amount of telomere attrition calculated over multiple repeat samples of individuals predicted a shorter productive lifespan, suggesting a link between telomere loss and health. TL attrition was a better predictor of when an animal was culled than their average TL or the previously for this population reported significant TL at the age of 1 year. Our present results support the hypothesis that TL is a flexible trait that is affected by environmental factors and that telomere attrition is linked to animal health and survival traits. Change in telomere length may represent a useful biomarker in animal welfare studies.

Prognostic Association of TERC, TERT Gene Polymorphism, and Leukocyte Telomere Length in Acute Heart Failure: A Prospective Study

BackgroundTelomere length and telomerase are associated in development of cardiovascular diseases. Study aims to investigate the associations of TERC and TERT gene polymorphism and leukocyte telomere length (LTL) in the prognosis of acute heart failure (AHF).MethodsTotal 322 patients with AHF were enrolled and divided into death and survival group according to all-cause mortality within 18 months. Seven single nucleotide polymorphisms (SNPs) of TERC and TERT were selected. Baseline characteristics, genotype distribution and polymorphic allele frequency, and genetic model were initially analyzed. Genotypes and the LTL were determined for further analysis.ResultsCompared to carrying homozygous wild genotype, the risk of death in patients with mutated alleles of four SNPs- rs12696304(G>C), rs10936599(T>C), rs1317082(G>A), and rs10936601(T>C) of TERC were significantly higher. The dominant models of above were independently associated with mortality. In recessive models, rs10936599 and rs1317082 of TERC, rs7726159 of TERT were independently associated with long-term mortality. Further analysis showed, in haplotype consisting with TERC - rs12696304, rs10936599, rs1317082, and rs10936601, mutant alleles CCAC and wild alleles GTGT were significant difference between groups (P<0.05). CCAC is a risk factor and GTGT is a protective factor for AHF patients. Relative LTL decreased over age, but showed no difference between groups and genotypes.ConclusionsThe SNPs of TERC and TERT are associated with the prognosis of AHF, and are the independent risk factors for predicting 18-month mortality in AHF.

Leukocyte Telomere Length in Patients with Multiple Sclerosis and Its Association with Clinical Phenotypes

Aging is a significant factor influencing the course of multiple sclerosis (MS). Accelerated telomere attrition is an indicator of premature biological aging and a potential contributor to various chronic diseases, including neurological disorders. However, there is currently a lack of studies focusing on telomere lengths in patients with MS. We measured the average leukocyte telomere length (LTL) in biobanked DNA samples of 40 relapsing-remitting MS patients (RRMS), 20 primary progressive MS patients (PPMS), and 60 healthy controls using a multiplex quantitative polymerase chain reaction method. Changes in LTL over a period of >10 years were evaluated in a subset of 10 patients. Association analyses of baseline LTL with the long-term clinical profiles of the patients were performed using inferential statistical tests and regression models adjusted for age and sex. The cross-sectional analysis revealed that the RRMS group was characterized by a significantly shorter relative LTL, on average, as compared to the PPMS group and controls. Shorter telomeres at baseline were also associated with a higher conversion rate from RRMS to secondary progressive MS (SPMS) in the 10-year follow-up. The LTL decrease over time was similar in RRMS patients and PPMS patients in the longitudinal analysis. Our data suggest a possible contributory role of accelerated telomere shortening in the pathobiology of MS. The interplay between disease-related immune system alterations, immunosenescence, and telomere dynamics deserves further investigation. New insights into the mechanisms of disease might be obtained, e.g., by exploring the distribution of telomere lengths in specific blood cell populations.

Leukocyte Telomere Length Is Not Reduced in Children and Adults with Cystic Fibrosis but Associates with Clinical Characteristics-A Cross-Sectional Study.

We hypothezied that telomere length is considerably altered in cystic fibrosis (CF) patients compared to healthy subjects (HS), and that leukocyte telomere length variation reflects the severity of CF. Relative telomere length (RTL) was assessed by qPCR in 70 children aged 5–10 (34 CF; 36 HS) and 114 adults aged 18–45 (53 CF; 61 HS). Telomere length was similar in CF and HS (median (interquartile range): 0.799 (0.686–0.950) vs. 0.831 (0.707–0.986); p = 0.5283) both in children and adults. In adults, women had longer telomeres than men (0.805 (0.715–0.931) vs. 0.703 (0.574–0.790); p = 0.0002). Patients treated with inhaled corticosteroids had a shorter RTL compared to those without steroid therapy (0.765 (0.664–0.910) vs. 0.943 (0.813–1.191); p = 0.0007) and this finding remained significant after adjusting for gender, age, BMI, and child/adult status (p = 0.0003). Shorter telomeres were independently associated with the presence of comorbidities (0.763 (0.643–0.905) vs. 0.950 (0.783–1.130); p = 0.0006) and antibiotic treatment at the moment of blood sampling (0.762 (0.648–0.908) vs. 0.832 (0.748–1.129); p = 0.0172). RTL correlated with number of multiple-day hospitalizations (rho = −0.251; p = 0.0239), as well as number of hospitalization days (rho = −0.279; p = 0.0113). Leukocyte RTL in children and adults with CF was not shorter than in healthy controls, and did not seem to have any potential as a predictor of CF survival. However, it inversely associated with the investigated clinical characteristics.

Dietary pattern and telomere length in preschool children in a middle-income country.

Telomere length (TL) has been associated with lifestyle and dietary pattern. However, the available evidence on this association in children is scarce, especially in low‐ and middle‐income countries (LMICs). Therefore, this study aimed to evaluate the association of dietary pattern and leukocyte TL (LTL) in preschool children, Sabzevar, Iran (2017). This cross‐sectional study was based on 187 preschool children (aged 5 to 7) recruited from 27 kindergartens. Nutrition information including amounts of consumed dairy products, meat and processed meat products, nuts and seeds, white bread and refined grains, fruits, vegetables, simple sugars, fats and drinks was obtained through a questionnaire. Linear mixed‐effects models were fitted with polymerase chain reaction (PCR) plate ID and kindergartens as random effects to estimate the association of each food group consumption with LTL, controlled for relevant covariates. Higher consumption of dairy products and sugar was associated with shorter LTL (β = −0.180, 95% confidence interval [CI]: −0.276, −0.085, P value <0.001 and β = −0.139, 95% CI: −0.193, −0.086, P value <0.001, respectively). An increase in consumption of fish, nuts and seeds, coloured fruits, green leafy vegetables, cruciferous vegetables and olive was significantly associated with the increase in relative LTL. The associations for the consumption of legumes, other fruits, yellow and orange vegetables, red meat, egg, white bread and refined grains, solid and liquid fats, processed meats, potato chips, carbonated drinks, tea (black) and soft drinks groups were not statistically significant. Our findings showed that there was an association between the consumption of certain food groups with LTL.

A Novel Association between YKL-40, a Marker of Structural Lung Disease, and Short Telomere Length in 10-Year-Old Children with Bronchopulmonary Dysplasia.

Extremely preterm infants are born with immature lungs and are exposed to an inflammatory environment as a result of oxidative stress. This may lead to airway remodeling, cellular aging and the development of bronchopulmonary dysplasia (BPD). Reliable markers that predict the long-term consequences of BPD in infancy are still lacking. We analyzed two biomarkers of cellular aging and lung function, telomere length and YKL-40, respectively, at 10 years of age in children born preterm with a history of BPD (n = 29). For comparison, these markers were also evaluated in sex-and-age-matched children born at term with childhood asthma (n = 28). Relative telomere length (RTL) was measured in whole blood with qPCR and serum YKL-40 with ELISA, and both were studied in relation to gas exchange and the regional ventilation/perfusion ratio using three-dimensional V/Q-scintigraphy (single photon emission computer tomography, SPECT) in children with BPD. Higher levels of YKL-40 were associated with shorter leukocyte RTL (Pearson’s correlation: −0.55, p = 0.002), but were not associated with a lower degree of matching between ventilation and perfusion within the lung. Serum YKL-40 levels were significantly higher in children with BPD compared to children with asthma (17.7 vs. 13.2 ng/mL, p < 0.01). High levels of YKL-40 and short RTLs were associated to the need for ventilatory support more than 1 month in the neonatal period (p < 0.01). The link between enhanced telomere shortening in childhood and structural remodeling of the lung, as observed in children with former BPD but not in children with asthma at the age of 10 years, suggests altered lung development related to prematurity and early life inflammatory exposure. In conclusion, relative telomere length and YKL-40 may serve as biomarkers of altered lung development as a result of early-life inflammation in children with a history of prematurity.

Polycyclic aromatic hydrocarbons exposures and telomere length: A cross-sectional study on preschool children

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with shorter telomere length (TL), a marker of ageing at cellular level. However, the available evidence on this association among children is still scarce. We therefore aimed to assess, the relationship between urinary 1-hydroxipayrene (1-OHP), a marker of exposure to PAHs, and relative leukocyte TL (LTL) in children at preschool age. Our study was based on 200 children enrolled from 27 randomly-selected kindergartens in the city of Sabzevar, Iran (2017). 1-OHP levels in the participants' urine samples were measured using solid phase extraction (SPE) method and high-performance liquid chromatography (HPLC). Moreover, real-time PCR was used to measure the LTL in the participants’ blood samples. Linear mixed effects models, controlled for relevant covariates, were applied to investigate the association of 1-OHP concentration and LTL. The median (interquartile range (IQR)) of relative LTL and urinary 1-OHP were 0.83 (0.7) and 257 (375.5) ng/L, respectively. In the fully adjusted model, an IQR increase in urinary 1-OHP was related to −0.05 (95% confidence interval (CI): 0.09, −0.01, P-value = 0.02) decrease in relative LTL. This association was similar among boys and girls; however, we observed indications for a stronger association for those children whose parents had university education. Our study suggested an inverse relationship between urinary 1-OHP and LTL in children at preschool age. However, further longitudinal research with repeated measures of PAHs and LTL are needed to confirm these findings.

Telomere length shortening in hospitalized preterm infants: A pilot study.

Leukocyte telomere length is a biomarker of aging-related health risks. Hospitalized preterm infants frequently experience elevated oxidative stress and inflammation, both of which contribute to telomere shortening. Our aim was to examine changes in telomere length during neonatal intensive care unit (NICU) hospitalization in a cohort of preterm infants <32 weeks’ gestation. We conducted a longitudinal study of 10 infants (mean gestational age 27 weeks, range 23.5 to 29, at birth). We isolated DNA from dried blood spots and used Real Time Quantitative PCR to measure relative leukocyte telomere length in triplicate at three time points for each participant. From birth to discharge, infants experienced an average decline in relative telomere length of 0.021 units per week (95% CI -0.040, -0.0020; p = 0.03), after adjustment for gestational age at birth. Our results suggest a measurable decline in telomere length during NICU hospitalization. We speculate that telomere length change may convey information about NICU exposures that carry short- and long-term health risks.

Dynamics of leukocyte telomere length in adults aged 50 and older: a longitudinal population-based cohort study.

It is well established from previous cross-sectional studies that telomeres shorten with age. However, due to a considerable inter-individual variation in telomere length (TL), its relationship with biological aging is difficult to unpick. Longitudinal repeated assessments of TL changes within individuals should augment our understanding of TL dynamics in aging. This study disentangles within- and inter-individual effects of age on leukocyte telomere length (LTL) dynamics in a large population-based cohort of older adults. A total of 4053 subjects aged 50 and older from the WHO Study on global AGEing and adult health (SAGE) in Shanghai were studied. Relative LTL (T/S ratio) was measured at baseline (2009-2010) and follow-up (2017-2018) by quantitative real-time polymerase chain reaction. We used linear random slope models to analyze LTL dynamics in relation to age and sex and within-subject centering method to distinguish within- versus between-subject effects. We observed LTL shortening in 66.32%, maintenance in 11.23%, and elongation in 22.45% of the study participants. LTL declined significantly with age both cross-sectionally and longitudinally. More importantly, the longitudinal decline in LTL was much greater than the cross-sectional decline (- 0.017 (p < 0.001) versus - 0.002 (p < 0.001) per year). Furthermore, women had a lower within-subject LTL shortening rate than men (- 0.014 versus - 0.020 per year, p < 0.001). The within-individual longitudinal decline in LTL was much greater than the inter-individual cross-sectional decline, indicating that chronological age might impose a greater impact on LTL shortening than other influencing factors combined. Moreover, women showed a lower within-individual LTL shortening rate than men.