Relative Leukocyte Telomere Length Research Articles

Elevated tissue status of omega-3 fatty acids protects against age-related telomere attrition in fat-1 transgenic mice

Leukocyte telomere length (LTL) is a biomarker of aging that may be influenced by dietary factors. Omega-3 fatty acids (n-3 FA) have been suggested to affect LTL. However, research on this effect has been inconclusive. The aim of the study was to test the hypothesis about the positive effect of n-3 FA on LTL. Fat-1 transgenic mice, which can convert omega-6 fatty acids (n-6 FA) to n-3 FA and have elevated levels of endogenous n-3 FA in their tissues, were used to study the effects of n-3 FA on LTL at different ages. Blood samples from 10-month-old wild-type (WT) mice (n=10) and fat-1 mice (n=10) and 3-month-old WT mice (n=5) and fat-1 mice (n=5) were used to measure relative and absolute LTL. The levels of proteins critical for telomere maintenance were examined by Western blot analysis. Fat-1 transgenic mice had longer leukocyte telomeres than their WT siblings, suggesting a slower rate of age-related telomere shortening in fat-1 mice. In animals aged 10 months, the LTL was significantly longer in fat-1 than in WT mice (mean±SEM; relative LTL: WT=1.00±0.09 vs. fat-1: 1.25±0.05, P=0.031; absolute LTL: WT=64.41±6.50 vs. fat-1: 78.53±3.86, P=0.048). The difference in LTL observed in three-month-old mice was insignificant, however the mean LTL was still longer in fat-1 mice than in the WT mice. Fat-1 mice also had abundant levels of two shelterin proteins: TRF1 (27%, P=0.028) and TRF2 (47%, P=0.040) (telomeric repeat binding factor 1 and 2) compared to WT animals. This study, for the first time in a unique animal model free of dietary confounders, has demonstrated that increased levels of n-3 FA in tissues can reduce telomere attrition. The data presented indicate the possibility of using omega-3 fatty acids to reduce accelerated telomere attrition and, consequently, counteract premature aging and reduce the risk of age-related diseases.

Investigating the Relationship between Telomere-Related Gene Variants and Leukocyte Telomere Length in Optic Neuritis Patients.

Optic neuritis (ON) is a condition marked by optic nerve inflammation due to various potential triggers. Research indicates a link between telomeres and inflammation, as studies demonstrate that inflammation can lead to increased telomere shortening. Aim: We aimed to determine the associations of telomere-related telomeric repeat binding factor 1 (TERF1) rs1545827, rs10107605, and telomeric repeat binding factor 2 (TERF2) rs251796 polymorphisms and relative leukocyte telomere length (LTL) with the occurrence of ON. Methods: In this research, a total of 73 individuals diagnosed with optic neuritis (ON) were studied and the control group included 170 individuals without any health issues. The DNA samples were obtained from peripheral blood leukocytes, which were purified using the DNA salting-out technique. Real-time polymerase chain reaction (RT-PCR) assessed single-nucleotide polymorphisms (SNPs) and relative leukocyte telomere lengths (LTL). The data obtained were processed and analyzed using the "IBM SPSS Statistics 29.0" program. Results: Our study revealed the following results: in the male group, TERF2 rs251796 (AA, AG, and TT) statistically significantly differed between the long and short telomere group, with frequencies of 65.7%, 22.9%, and 2.0% in long telomeres, compared to 35.1%, 56.8%, and 8.1% in the short telomere group (p = 0.013). The TERF2 rs251796 CT genotype, compared to CC, under the codominant genetic model, was associated with 4.7-fold decreased odds of telomere shortening (p = 0.005). Meanwhile, CT+TT genotypes, compared to CC under the dominant genetic model, were associated with 3.5-fold decreased odds of telomere shortening (p = 0.011). Also, the CT genotype, compared to CC+TT, under the overdominant genetic model, was associated with 4.4-fold decreased odds of telomere shortening (p = 0.004). Conclusions: The current evidence may suggest a protective role of TERF2 rs251796 in the occurrence of ON in men.

Study of association of leptin with leukocyte telomere length in a Chinese rural population

BackgroundPrevious studies have demonstrated the relationship between adipocyte factors, insulin resistance, and other indicators with telomere length. However, these studies did not consider the influence of changes in different indicators on telomere length over time. Therefore, the aim of this study is to elucidate the impact of changes in adipocyte factors, HOMA-IR, and other indicators on the dynamic variation of telomere length.MethodsThe data were from a cohort study conducted in Ningxia, China. A total of 1624 subjects were analyzed. Adipokines and relative leukocyte telomere length (RLTL) were measured, and changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), Homeostatic Model Assessment for β-Cell Function (HOMA-β), and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated. Generalized linear models evaluated associations between changes in adipokines and RLTL changes. Furthermore, univariate analyses examined the effects of changes in adipokines and insulin resistance indicators on ΔRLTL.ResultsThe research findings indicate that females generally have shorter telomeres compared to males. In comparison to the low-level group of Δleptin (LEP), the high-level group of ΔLEP shows a negative correlation with ΔRLTL (B=-1.32, 95% CI (-2.38, -0.27)). Even after multivariable adjustments, this relationship persists (B=-1.31, 95% CI (-2.24, -0.23)). Further analysis reveals that after adjusting for ΔHOMA-IR, ΔHOMA-β, and ΔQUICKI, the high-level group of ΔLEP still exhibits a significant negative correlation with ΔRLTL (B=-1.37, 95% CI (-2.43, -0.31)). However, the interaction effects between ΔHOMA-IR, ΔHOMA-β, ΔQUICKI, and ΔLEP do not affect ΔRLTL.ConclusionsElevated levels of leptin were significantly correlated with shortened telomere length. This suggests that increased leptin levels may impact overall individual health by affecting telomere length, underscoring the importance of measures to reduce leptin levels to mitigate the onset and progression of related diseases.

Evaluating Leukocyte Telomere Length and Myeloid-Derived Suppressor Cells as Biomarkers for Prostate Cancer.

Leukocyte telomere length (LTL) and myeloid-derived suppressor cells (MDSC) are associated with aging and the development and progression of cancer. However, the exact nature of this relationship remains unclear. Our study aimed to investigate the potential of LTL and MDSC as diagnostic biomarkers for prostate cancer while also seeking to deepen our understanding of the relationship of these potential biomarkers to each other. Our study involved patients undergoing a prostate biopsy. We analyzed the relative LTL in genomic DNA obtained from peripheral blood leukocytes as well as the percentage of MDSC and their subtypes in peripheral blood mononuclear cells (PBMC). Our evaluation focused on examining the relationship between LTL and MDSC and pathological diagnoses as well as investigating the correlation between LTL and MDSC levels. In our study of 102 participants, 56 were pathologically diagnosed with localized prostate cancer (cancer group), while 46 tested negative (control group). The cancer group exhibited significantly shorter LTL in comparison to the control group (p = 0.024). Additionally, the cancer group showed a tendency towards a higher percentage of monocytic MDSC (M-MDSC), although this difference did not reach statistical significance (p = 0.056). Our multivariate logistic regression analysis revealed that patients with shorter LTL and higher percentages of M-MDSC had a 2.98-fold (95% CI = 1.001-8.869, p = 0.049) and 3.03-fold (95% CI = 1.152-7.977, p = 0.025) increased risk of prostate cancer diagnosis, respectively. There was also a significant negative correlation between LTL and M-MDSC. (r = -0.347, p < 0.001). Our research has established a correlation between LTL and MDSC in patients undergoing biopsy for prostate cancer. Notably, we observed that individuals with localized prostate cancer tend to have shorter LTL and a higher percentage of M-MDSC prior to their diagnosis. These findings suggest that LTL and M-MDSC could potentially serve as adjunctive biomarkers for the early diagnosis of prostate cancer.

Abstract 6144: A polymorphic TERT tandem repeat creating an expandable intronic G4 quadruplex is associated with TERT expression, relative leukocyte telomere length and cancer risk

Abstract A multi-cancer GWAS region at human chromosome 5p15 encodes telomerase reverse transcriptase (TERT). One of the GWAS signals is rs10069690-T, which creates an alternative intron 4 splicing site, co-producing full-length (FL) and truncated INS1b transcript for dominant-negative telomerase-nonfunctional TERT. A variable number tandem repeat (VNTR6-1, 38 bp repeat unit) within intron 6 remains uncharacterized in relation to GWAS signals and cancer risk. We hypothesized that VNTR6-1 might contribute to GWAS signals represented by rs10069690. We scored VNTR6-1 and rs10069690 in short-read WGS data (n=3,202) from the 1000 Genomes Project with a machine learning model using the GLMnet engine, and in phased long-read assemblies (n=544). We defined two VNTR6-1 groups: Short (24-27 copies) and Long (40.5-66.5 copies); the VNTR6-1-Long group was preferentially linked with rs10069690-T compared to C allele (p=2.53E-13). We show that haplotypes of rs56345976 and rs33961405 alleles can predict VNTR6-1 groups. We imputed VNTR6-1 in UK Biobank controls (n=351,634), PLCO cancer cases and controls (n=100,445), and African Burkitt lymphoma cases (aBL, n=79). Functional studies in aBL tumors revealed a suggestive association between reduced total TERT expression, rs10096690-T (p=0.035) and VNTR6-1-Long (p=0.053). VNTR6-1 forms a G4 quadruplex structure sensitive to G4 stabilizing ligands, altering the ratio between FL-TERT and a dominant-negative TERT-β isoform in isogenic cell lines with/without VNTR6-1. In GTEx and TCGA, several metrics related to cell proliferation and telomerase activity correlated positively with FL-TERT expression and negatively with TERT-β expression. We created a composite marker with 0, 1 or 2 copies of the FL-TERT-associated haplotype (VNTR6-1-Short/rs10069690-C) to capture the effects of these variants that negatively affect TERT expression and telomerase activity. The number of copies of the VNTR6-1/rs10069690 haplotype was associated with relative leukocyte telomere length in UK Biobank controlling for sex and age (β=0.049, p=8.75E-78). This marker was also associated with a reduced risk of bladder and prostate cancer but an increased risk of breast, endometrial, ovarian, thyroid cancer, and glioma in PLCO. Our findings reveal that germline variants VNTR6-1-Long/rs10069690-T underlie the multi-cancer GWAS signal and jointly decrease TERT expression and telomerase activity, potentially reducing the risk of some cancers by limiting cell growth. However, decreased telomerase activity could deregulate stem cell-driven tissue regeneration and genome integrity, increasing the risk of other cancers. Our findings unveil novel mechanisms of cancer susceptibility and propose therapeutic avenues for targeting TERT isoform ratios to modulate telomerase activity and its cellular effects. Citation Format: Oscar Florez-Vargas, Michelle Ho, Max Hogshead, Chia-Han Lee, Kaitlin Forsythe, Brenen Papenberg, Kristine Jones, Wen Luo, Kedest Teshome, Cornelis Blauwendraat, Mikhail Kolmogorov, Stephen J. Chanock, Mitchell J. Machiela, John Schneekloth, Shahinaz Gadalla, Sharon A. Savage, Sam M. Mbulaiteye, Ludmila Prokunina-Olsson. A polymorphic TERT tandem repeat creating an expandable intronic G4 quadruplex is associated with TERT expression, relative leukocyte telomere length and cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6144.

Associations between ZNF676, CTC1 Gene Polymorphisms and Relative Leukocyte Telomere Length with Myopia and Its Degree.

The interaction between environmental and genetic factors that influence eye growth, regulated by vision, contributes to the development and progression of myopia. This dynamic interaction significantly contributes to the multifaceted development and progression of myopia, a prevalent ocular condition. Our study delves into the associations between ZNF676 and CTC1 gene polymorphisms and their impact on the relative leukocyte telomere length (relative LTL) in myopia, as well as its degree. By unravelling these underpinnings in conjunction with environmental influences, we aim to enhance our understanding of the complex mechanisms that drive the onset and severity of myopia. This study included patients with myopia and ophthalmologically healthy subjects. DNA was extracted from peripheral venous blood by the salting out method. Genotyping of ZNF676 rs412658 and CTC1 rs3027234, as well as the measurement of relative LTL, were conducted using a real-time polymerase chain reaction method (RT-PCR). The data obtained were statistically analyzed using the "IBM SPSS Statistics 29.0" software program. The results show that myopic patients who are homozygous for the rs3027234 rare allele genotype of the CTC1 gene have statistically significantly shorter relative LTL compared to patients with the CC and CT genotypes. Also, men with the CTC1 rs3027234 TT genotype have statistically significantly longer leukocyte telomeres than women with the same genotype. The respective median (IQR) of the relative LTL for women and men is 0.280 (0.463) vs. 0.696 (0.440), with a p-value of 0.027. The myopia group with the ZNF676 rs412658 CC genotype has statistically significantly shorter leukocyte telomeres than the control group with the same genotype (age ≤ 29), and the p-value is 0.011. Also, the myopia group with the ZNF676 rs412658 CT and CTC1 rs3027234 CT genotypes have statistically significantly longer leukocyte telomeres than the control group with the same genotypes (age > 29), with p-values that are, respectively, 0.016 and 0.012. The evaluation of the genotype distributions of the polymorphisms in the myopia patients showed that ZNF676 rs412658 CT genotype carriers have 4-fold decreased odds of high myopia occurrence (OR = 0.250; CI: 0.076-0.826; p = 0.023). Also, the evaluation of the allele distributions of the polymorphism under the additive genetic model in the myopia group showed that the ZNF676 rs412658 T allele was associated with similar odds of high myopia (OR = 0.269; 95% CI: 0.090-0.807; p = 0.019). The comprehensive p-value, assessing the relative LTL of subjects across the different levels of myopia, signifies a statistical difference in the relative LTL among individuals with varying degrees of myopia. There was a statistically significant difference in relative LTL between mild and moderate myopia degrees (0.819 (1.983) vs. 0.083 (0.930), p = 0.007). CTC1 rs3027234 TT may be considered a protective genotype for telomere shortening in men, while the overall telomere shortening might be linked to the worse myopia degree. The ZNF676 rs412658 T allele may protect against a high myopia occurrence.

The Influence of Telomere-Related Gene Variants, Serum Levels, and Relative Leukocyte Telomere Length in Pituitary Adenoma Occurrence and Recurrence

In this study, we examined 130 patients with pituitary adenomas (PAs) and 320 healthy subjects, using DNA samples from peripheral blood leukocytes purified through the DNA salting-out method. Real-time polymerase chain reaction (RT-PCR) was used to assess single nucleotide polymorphisms (SNPs) and relative leukocyte telomere lengths (RLTLs), while enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of TERF1, TERF2, TNKS2, CTC1, and ZNF676 in blood serum. Our findings reveal several significant associations. Genetic associations with pituitary adenoma occurrence: the TERF1 rs1545827 CT + TT genotypes were linked to 2.9-fold decreased odds of PA occurrence. Conversely, the TNKS2 rs10509637 GG genotype showed 6.5-fold increased odds of PA occurrence. Gender-specific genetic associations with PA occurrence: in females, the TERF1 rs1545827 CC + TT genotypes indicated 3.1-fold decreased odds of PA occurrence, while the TNKS2 rs10509637 AA genotype was associated with 4.6-fold increased odds. In males, the presence of the TERF1 rs1545827 T allele was associated with 2.2-fold decreased odds of PA occurrence, while the TNKS2 rs10509637 AA genotype was linked to a substantial 10.6-fold increase in odds. Associations with pituitary adenoma recurrence: the TNKS2 rs10509637 AA genotype was associated with 4.2-fold increased odds of PA recurrence. On the other hand, the TERF1 rs1545827 CT + TT genotypes were linked to 3.5-fold decreased odds of PA without recurrence, while the TNKS2 rs10509637 AA genotype was associated with 6.4-fold increased odds of PA without recurrence. Serum TERF2 and TERF1 levels: patients with PA exhibited elevated serum TERF2 levels compared to the reference group. Conversely, patients with PA had decreased TERF1 serum levels compared to the reference group. Relative leukocyte telomere length (RLTL): a significant difference in RLTL between the PA group and the reference group was observed, with PA patients having longer telomeres. Genetic associations with telomere shortening: the TERF1 rs1545827 T allele was associated with 1.4-fold decreased odds of telomere shortening. In contrast, the CTC1 rs3027234 TT genotype was linked to 4.8-fold increased odds of telomere shortening. These findings suggest a complex interplay between genetic factors, telomere length, and pituitary adenoma occurrence and recurrence, with potential gender-specific effects. Furthermore, variations in TERF1 and TNKS2 genes may play crucial roles in telomere length regulation and disease susceptibility.

Telomere Length in Survivors of Childhood Hematologic Malignancies

Background: Telomeres are involved in maintenance of genomic stability and DNA repair. Telomeres of hematopoietic cells shorten with age, and accelerated telomere shortening is seen with replicative stress, such as during administration of chemotherapy for the treatment of cancer. We aimed to analyze leukocyte relative telomere length (RTL) among survivors of childhood hematologic malignancies, and to evaluate the associations of RTL with disease characteristics, treatment, and chronic health conditions (CHCs). Method: This study was conducted at a single center in a retrospective cohort of survivors of childhood cancer diagnosed between 2000 and 2021 with a longitudinal follow-up of ≥1 year after cessation of treatment. The peripheral blood samples were collected between June 2022 and January 2023. This study enrolled survivors of childhood hematologic malignancies with the following criteria: diagnosis before the age of 19 years, continuous maintenance of clinical remission, compliance with regular clinical follow-up, and cessation of treatment more than one year before the start of the study. Considering that telomeres shorten with age, this study limited participants to those between 18 and 35 years of age at blood sampling. The telomere PNA Kit/Fluorescein isothiocyanate (FITC) for flow cytometry (Agilent Technologies, Singapore) was used for flow FISH for the measurement of leukocyte RTL. Result: Forty-three survivors of childhood hematologic malignancies with a median follow-up period of 73 months were recruited. Median age at diagnosis and at DNA sampling were 13.8 years (range, 6-18) and 22.6 years (range, 15-34), respectively. Survivors had leukemia (57.1%), lymphoma (31.4%), and myelodysplastic syndrome (11.4%). RTL in survivors of pediatric hematologic malignancies was not significantly shorter than the predicted value for age-matched references. There was no difference in RTL according to disease subtypes ( p=0.35). Survivors who experienced relapse had significantly shorter RTL than those who did not (7.6 ± 1.0 vs. 12.1 ± 5.0, p=0.009). Those who underwent allogeneic hematopoietic stem cell transplantation (HSCT) showed significant shortening of the RTL compared with those who did not (9.4 ± 4.1 vs. 12.6 ± 5.1, p=0.039). Total body irradiation (TBI) during pre-transplant conditioning did not influence the RTL (9.5 ± 3.8 with TBI vs. 12.1 ± 5.1 without TBI, p=0.117). Among the 15 patients who underwent allogeneic HSCT, those who developed acute graft-versus-host disease (GVHD) of grade II or higher had significantly shorter RTL than those who did not (6.8 ± 1.9 vs. 11.7 ± 4.1, p=0.013). Patients with chronic GVHD tended to have shorter RTL than those without GVHD, but the p-value was not statistically significant (7.1 ± 2.8 vs. 10.9 ± 4.2, p=0.088). Seventeen patients had CHCs, with 13 having grade I and 4 having grade II. Patients with grade II CHCs had significantly shorter RTL than those without CHCs or with grade I CHCs (7.1 ± 1.6 vs. 11.5 ± 5.3, p=0.041). When the influence of multiple CHCs on RTL was examined, survivors with ≥2 CHCs had shorter RTL, but this difference was not significant ( p=0.062). Conclusion: The overall RTL in survivors of childhood hematologic malignancy was not significantly shorter than the predicted values for age-matched references. However, patients who received allogeneic HSCT showed RTL attrition compared to those who did not receive HSCT. In addition, those who had GVHD showed augmented RTL attrition. Patients with grade II CHCs had shorter RTL compared to patients without or with grade I CHCs. Although there is currently no consensus on the extent and clinical significance of accelerated shortening of the RTL, the RTL may be a potential biomarker for determining CHCs in childhood hematologic malignancies.

Association between the dietary antioxidant index and relative telomere length of leucocytes in the Chinese population.

Dietary antioxidant indices (DAI) may be potentially associated with relative telomere length (RTL) of leucocytes. This study aimed to investigate the relationship between DAI and RTL. A cross-sectional study involving 1656 participants was conducted. A generalised linear regression model and a restricted cubic spline model were used to assess the correlation of DAI and its components with RTL. Generalised linear regression analysis revealed that DAI (β = 0·005, P = 0·002) and the intake of its constituents vitamin C (β = 0·043, P = 0·027), vitamin E (β = 0·088, P < 0·001), Se (β = 0·075, P = 0·003), and Zn (β = 0·075, P = 0·023) were significantly and positively correlated with RTL. Sex-stratified analysis showed that DAI (β = 0·006, P = 0·005) and its constituents vitamin E (β = 0·083, P = 0·012), Se (β = 0·093, P = 0·006), and Zn (β = 0·092, P = 0·034) were significantly and positively correlated with RTL among females. Meanwhile, among males, only vitamin E intake (β = 0·089, P = 0·013) was significantly and positively associated with RTL. Restricted cubic spline analysis revealed linear positive associations between DAI and its constituents' (vitamin E, Se and Zn) intake and RTL in the total population. Sex-stratified analysis revealed a linear positive correlation between DAI and its constituents' (vitamin E, Se and Zn) intake and RTL in females. Our study found a significant positive correlation between DAI and RTL, with sex differences.

Persistent dyslipidemia increases the longitudinal changes in telomere length

Background and aimsLeukocyte telomere length (LTL) as a ‘biological clock’ of aging is closely related to human health, its association with an aging-related disease, dyslipidemia, has been less studied and mainly focused on cross-sectional investigations.MethodsTwo rounds of information and blood collections were conducted on a cohort of 1624 individuals residing in rural Ningxia, located in northwest China, with an average time gap of 9.8 years. The relative telomere length (RTL) of peripheral blood leukocytes was assessed using real-time quantitative PCR. To investigate the association between dyslipidemia, blood lipid levels, and alterations in RTL, multiple linear regression and generalized linear models were employed.ResultsAfter conducting the follow-up analysis, it was observed that 83.3% of the participants in the study exhibited a reduction in telomere length, while 16.7% experienced an increase in telomere length. The results suggested that dyslipidemia at baseline or follow-up may increase longitudinal changes in telomere length, but it was more significant in the healthy group, especially in those aged ≥ 60 years. Furthermore, HDL-C levels in baseline and follow-up were found to be associated with longitudinal changes in telomere length, and lower HDL-C levels may be associated with increased longitudinal changes in telomere length.ConclusionsThe change in telomere length is correlated with dyslipidemia and its lipid indicators especially HDL-C. Persistent dyslipidemia and a reduction in HDL-C levels may be associated with elevated longitudinal fluctuations in telomere length.

Does physical activity moderate the association between shorter leukocyte telomere length and incident coronary heart disease? Data from 54,180 UK Biobank participants.

Telomere shortening is a biological aging hallmark. The effect of short telomere length may be targeted by increased physical activity to reduce the risk of multiple aging-related diseases, including coronary heart disease (CHD). The objective was to assess the moderation effect of accelerometer-based physical activity (aPA) on the association between shorter leukocyte telomere length (LTL) relatively in the population sample and incident CHD. Data were from the UK Biobank participants with well-calibrated accelerometer data for at least 6.5days (n = 54,180). Relative mean LTL at baseline (5-6years prior to aPA assessment) was measured in T/S ratio, using a multiplex quantitative polymerase chain reaction (qPCR) technology, by comparing the amount of the telomere amplification product (T) to that of a single-copy gene (S). aPA measures included total number of events (at least 10-s continued physical activity > 32 milligravities [mg]), total volume, mean duration, mean intensity, and peak intensity of all events. LTL, aPA measures, and their interactions were associated with incident CHD (mean follow-up 6.8years) using Cox proportional hazards models adjusting for covariates. Longer LTL (relative to the sample distribution) was associated with reduced incidence of CHD (adjusted hazard ratio [aHR] = 0.94 per standard deviation [SD] increase in LTL, [95% CI, 0.90 to 0.99], P = .010). Incidence of CHD was reduced by higher total volume of aPA (aHR = 0.82 per SD increase in LTL, [95% CI, 0.71 to 0.95], P = .010) but increased by higher total number of events (aHR = 1.11 per SD increase in LTL, [95% CI, 1.02 to 1.21], P = .020) after controlling for other aPA measures and covariates. However, none of the interactions between LTL and aPA measures was statistically significant (P = .171).

Neonatal administration of fenofibrate had no developmental programming effect on the lipid profile and relative leucocyte telomere lengths of adolescent rats fed a high-fructose diet postnatally.

Telomere length, a marker of ageing, is susceptible to developmental programming that may cause its accelerated attrition. Metabolic syndrome triggers telomere attrition. Fenofibrate, a peroxisome proliferator-activated receptor-alpha agonist, is protective against telomere attrition. We investigated the impact of fenofibrate administered during suckling on the lipid profile and leucocyte telomere lengths of rats fed a high-fructose diet post-weaning. Suckling Sprague-Dawley pups (n=119) were allocated to four groups and gavaged with either 10mL·kg-1 body mass 0.5% dimethyl sulfoxide, 100mg·kg-1 body mass fenofibrate, fructose (20%, w / v), or a combination of fenofibrate and fructose for 15 days. Upon weaning, each of the initial groups was split into two subgroups: one had plain water while the other had fructose solution (20%, w / v) to drink for 6 weeks. Blood was collected for DNA extraction and relative leucocyte telomere length determination by real-time PCR. Plasma triglycerides and cholesterol were also quantified. The treatments had no effect (p>0.05) on body mass, cholesterol concentration, and relative leucocyte telomere lengths in both sexes. Post-weaning fructose increased triglyceride concentrations (p<0.05) in female rats. Fenofibrate administered during suckling did not affect ageing nor did it prevent high fructose-induced hypertriglyceridaemia in female rats.

Association between leukocyte telomere length and COVID-19 severity

BackgroundInter-individual variations in the clinical manifestations of SARS-CoV-2 infection are among the challenging features of COVID-19. The known role of telomeres in cell proliferation and immune competency highlights their possible function in infectious diseases. Variability in telomere length is an invaluable parameter in the heterogeneity of the clinical presentation of diseases.ResultIn this study, our aim was to investigate the possible association between leukocyte telomere length (LTL) and COVID-19 severity. LTL was measured in 100 patients with moderate and severe forms of COVID-19 using the quantitative PCR (q-PCR) method. Statistical analysis confirmed a strong inverse correlation between relative LTL and COVID-19 severity.ConclusionsThese findings suggest that LTL can be a useful parameter for predicting disease severity in patients, as individuals with short telomeres may have a higher risk of developing severe COVID-19.

Chain-mediating effect of interaction between telomeres and mitochondria under oxidative stress in coke oven workers

Coke oven emissions (COEs) exposure leads to oxidative stress, an imbalance between oxidant production and antioxidant defence in the body, which then leads to shortened relative telomere length (RTL) and reduced mitochondrial DNA copy number (mtDNAcn), ultimately leading to ageing and disease. By analysing the relationship among COEs, oxidative stress, RTL and mtDNAcn, we investigated the chain-mediating effects of oxidative stress and telomeres on mitochondrial damage and mitochondria on telomere damage in coke oven workers. A total of 779 subjects were included in the study. Cumulative COEs exposure concentrations were estimated, and the RTL and mtDNAcn of peripheral blood leukocytes were measured using real-time fluorescence quantitative PCR. Total antioxidant capacity (T-AOC) was measured to reflect the level of oxidative stress. The data were statistically analysed using SPSS 21.0 software and discussed using mediation effect analysis. After adjusting for age, sex, smoking, drinking and BMI, generalised linear model revealed dose–response associations between COEs and T-AOC, RTL and mtDNAcn, respectively. (Ptrend < 0.05). The results of chain-mediating effect showed that the proportion of the chain-mediating effect of “CED-COEs→T-AOC→ RTL→mtDNAcn” was 0.82% (β = −0.0005, 95% CI = [-0.0012, −0.0001]), and the proportion of the chain-mediating effect of “CED-COEs→T-AOC→ mtDNAcn → RTL ″ was 2.64% (β = −0.0013, 95% CI = [-0.0025, −0.0004]). After oxidative stress is induced by COEs, mitochondria and telomeres may interact with each other while leading further to potential bodily damage. This study provides clues to explore the association between mitochondria and telomeres.

Abstract 4220: Occupational pesticide use and relative leukocyte telomere length in the biomarkers of exposure and effect in agriculture study

Abstract Background: Previous epidemiologic studies have reported increased risks of certain cancers in relation to specific pesticide exposures, although the mechanisms underlying many of these associations remain poorly understood. Within the Biomarkers of Exposure and Effect in Agriculture (BEEA) study, a molecular epidemiologic investigation of pesticide applicators in Iowa and North Carolina, we examined whether occupational use of pesticides is associated with alterations in leukocyte telomere length. Telomeres are essential in maintaining chromosomal stability and altered telomere length has been linked to various malignancies. Methods: Relative telomere length (RTL) was measured using quantitative PCR in leukocytes from 1,539 male pesticide applicators ≥50 years of age. Using self-reported information on pesticide use, we characterized lifetime use of specific pesticides in terms of ever use and intensity-weighted lifetime days (IWLDs), a metric integrating total lifetime days of use and other factors influencing exposure. Multivariable linear regression models were used to estimate differences in geometric mean RTL (and corresponding 95% confidence intervals) by ever vs. never use of 48 pesticides and in exposure-response analyses for IWLDs of use of 46 pesticides, adjusting for age, state of residence, race/ethnicity, body mass index, and cigarette smoking status and pack-years. Results: Among ever users of the insecticides lindane and aldicarb, mean RTL was significantly longer compared to never users (p=0.01 and 0.03, respectively); in exposure-response analyses, we also observed a suggestive but non-statistically significant trend between increasing IWLDs of lindane use and longer RTL (p-trend=0.07). Higher IWLDs of use of the insecticide diazinon was also associated with longer RTL (p-trend=0.03) while increasing IWLDs of the insecticide heptachlor and the herbicide 2,4,5-TP were associated with shorter RTL (p-trends=0.04 and 0.03, respectively). Conclusions: This is, to our knowledge, the largest investigation of occupational pesticide use and RTL to date. Our findings provide novel evidence suggesting that use of certain pesticides could be associated with altered leukocyte telomere length. Notably, diazinon and lindane have previously been associated with increased risks of lung and lymphoid malignancies, respectively, and longer leukocyte telomere length has been implicated in the development of these cancers. Citation Format: Patricia A. Erickson, Vicky C. Chang, Casey L. Dagnall, Kedest Teshome, Mitchell J. Machiela, Kathryn H. Barry, Shahinaz M. Gadalla, Laura E. Beane Freeman, Gabriella Andreotti, Jonathan N. Hofmann. Occupational pesticide use and relative leukocyte telomere length in the biomarkers of exposure and effect in agriculture study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4220.

Abstract 3009: Measured and genetically-predicted leukocyte telomere length and lung cancer risk in the prospective UK Biobank

Abstract Telomere length is a biomarker reflective of aging and genomic instability. We previously found associations between longer measured leukocyte telomere length (LTL) and increased lung cancer risk in a pooled nested case-control study with 847 cases. Additionally, we reported that longer genetically-predicted telomere length (gTL) using a polygenic risk score (PRS) with 7 single nucleotide polymorphisms (SNPs) was associated with increased lung cancer risk among never-smoking Asian women. To investigate further, we conducted prospective cohort analyses of pre-diagnostic LTL and gTL in relation to risk of overall lung cancer and its subtypes in the UK Biobank. With over triple the number of cases, we had expanded statistical power to investigate lung cancer, adenocarcinoma (LUAD), and squamous cell carcinoma (SCC) among subgroups defined by smoking status and sex in this predominantly European study population. We analyzed 371,890 participants at baseline. Over the 12.36±1.64SD year follow-up, 2829 incident lung cancer cases were diagnosed, including 1078 LUAD and 487 SCC. LTL was measured using qPCR. Using European data, we calculated a weighted PRS for gTL. The PRS was derived from 130 linkage disequilibrium pruned SNPs (r2 &amp;gt; 0.01) associated with longer LTL in the UK Biobank. Multivariable Cox regression was used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of lung cancer in relation to log-transformed continuous and quartiles (Q) of LTL and gTL separately. Associations were estimated in the overall analytic sample and among smoking-sex subgroups. We conducted Mendelian Randomization (MR) analyses using MR-PRESSO with 130 genetic instruments to assess causal associations between LTL and lung cancer among Europeans.We found a strong dose-response relationship between longer LTL and increased lung cancer risk (p-trend= 2.6E-05), with the highest quartile being statistically significant (HRQ4vs.Q1=1.27, 95%CI: 1.15-1.42). The association was apparent for LUAD (p-trend=6.6E-10; HRQ4vs.Q1=1.78, 95%CI: 1.50-2.12), but not SCC. The lung cancer associations were prominent among never-smoking women (p-trend=4.0E-05) and never-smoking men (p-trend=2.0E-03). We also found dose-response relationships between longer gTL and risk of lung cancer (p-trend=4.2E-06) and LUAD (p-trend=2.1E-08). Additionally, we found evidence for causal associations between longer LTL and risk of lung cancer (HRper 1 SD gTL=1.87, 95%CI: 1.49-2.36, p=4.0E-07) and LUAD (HRper 1 SD gTL=2.45, 95%CI: 1.69-3.57, p=6.5E-06). Longer leukocyte telomere length potentially reflects biological processes relevant to the pathogenesis of lung cancer, particularly LUAD. Citation Format: Jason Yat-Yang Wong, Batel Blechter, Aubrey K. Hubbard, Jianxin Shi, Wei Hu, Mohammad Rahman, Shahinaz Gadalla, Mitchell Machiela, Nathaniel Rothman, Qing Lan. Measured and genetically-predicted leukocyte telomere length and lung cancer risk in the prospective UK Biobank [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3009.

Prenatal environment impacts telomere length in newborn dairy heifers

Telomere length is associated with longevity and survival in multiple species. In human population-based studies, multiple prenatal factors have been described to be associated with a newborn’s telomere length. In the present study, we measured relative leukocyte telomere length in 210 Holstein Friesian heifers, within the first ten days of life. The dam’s age, parity, and milk production parameters, as well as environmental factors during gestation were assessed for their potential effect on telomere length. We found that for both primi- and multiparous dams, the telomere length was 1.16% shorter for each day increase in the calf’s age at sampling (P = 0.017). The dam’s age at parturition (P = 0.045), and the median temperature-humidity index (THI) during the third trimester of gestation (P = 0.006) were also negatively associated with the calves’ TL. Investigating multiparous dams separately, only the calf’s age at sampling was significantly and negatively associated with the calves’ TL (P = 0.025). Results of the present study support the hypothesis that in cattle, early life telomere length is influenced by prenatal factors. Furthermore, the results suggest that selecting heifers born in winter out of young dams might contribute to increased longevity in dairy cattle.

Relative leukocyte telomere length in patients with chronic alcohol addiction depending on clinical and anamnestic characteristics

Relative leukocyte telomere length in patients with chronic alcohol addiction depending on clinical and anamnestic characteristics

Relative Leukocyte Telomere Length and Genetic Variants in Telomere-Related Genes and Serum Levels Role in Age-Related Macular Degeneration

Our study enrolled 342 patients with AMD and 177 healthy controls. Samples of DNA from peripheral blood leukocytes were extracted by DNA salting-out method. The genotyping of TERT rs2736098, rs401681 in TERT-CLPTM1 locus, TRF1 rs1545827, rs10107605, TNKS2 rs10509637, rs10509639, and TRF2 rs251796 and relative leukocyte telomere length (T/S) measurement were carried out using the real-time polymerase chain reaction method. Serum TERF-1 and TERF2 levels were measured by enzymatic immunoassay (ELISA). We found longer telomeres in early AMD patients compared to the control group. Additionally, we revealed that minor allele C at TRF1 rs10107605 was associated with decreases the odds of both early and exudative AMD. Each minor allele G at TRF2 rs251796 and TRF1 rs1545827 C/T genotype and C/T+T/T genotypes, compared to the C/C genotype, increases the odds of having shorter telomeres. Furthermore, we found elevated TERF1 serum levels in the early AMD group compared to the control group. In conclusion, these results suggest that relative leukocyte telomere length and genetic variants of TRF1 and TRF2 play a role in AMD development. Additionally, TERF1 is likely to be associated with early AMD.

Effects of Irvingia gabonensis Extract on Metabolism, Antioxidants, Adipocytokines, Telomere Length, and Aerobic Capacity in Overweight/Obese Individuals.

We investigated the effects of Irvingia gabonensis (IG) kernel extract on the metabolism, adiposity indices, redox status, inflammation, adipocytokines, blood leukocyte relative telomere length (RTL), and aerobic capacity of overweight/obese individuals. All participants used the first 12-week phase to monitor body weight. They were then randomly divided into two groups: (1) 300 mg IG or (2) placebo (PLA). Both groups took one tablet per day for 12 weeks. The variables were measured before supplementation and after 3, 6, and 12 weeks of supplementation. RTL and aerobic capacity were measured before and after 12 weeks. Compared with the PLA, the IG increased plasma vitamin C after supplementation at 6 (p &lt; 0.01) and 12 weeks (p &lt; 0.05) and serum adiponectin after 3 weeks (p &lt; 0.05). Compared with before supplementation, plasma malondialdehyde in the IG and serum leptin in the PLA were decreased after 12-week supplementation, without any differences between the groups. There were no differences between groups with respect to metabolism, inflammation, RTL, and aerobic capacity after the supplementation. We suggest that 12-week daily IG supplementation improved plasma vitamin C and adiponectin. The findings show the possible mechanism contributing to the effect of IG supplementation on a reduction in obesity-related complications.