Telomere Length In Blood Cells Research Articles

#2973 COVID-19 increased hemodialysis patients’ mortality, relation with inflammation and telomere attrition

Abstract Background and Aims An increased risk of mortality and hospitalization has been consistently demonstrated in patients with CKD who are additionally affected by corona virus disease 19 (COVID-19). In this study, we tried to identify predictive factors of mortality and hospitalizations, especially the ratio of neutrophils to lymphocytes (NLR), lactate dehydrogenase (LDH), c-reactive protein (CRP), disease status of COVID-19, telomere length in peripheral blood cells (TL) and 2-year risk score. Method A total of 130 chronic hemodialysis patients, were enrolled in the present study and followed up for 18 months. Routine laboratory parameters including LDH, were determined by standard automated methods, redox status parameters SOD and O2. - Using spectrophotometric methods.TL was determined using the modified Cawthon method and was calculated as the T/S ratio. Kaplan-Meier analysis was used to test survival predictors. Results Patients in deceased group (30%) were significantly older (p <0.001), with higher body mass index (BMI), (p < 0.01) than survived patients. Also, patients in the deceased group had higher levels of LDH, NLR index, CRP compared to survivors. Lower lymphocytes and shortened TL were characteristic of these patient groups, but the deceased group had the lowest lymphocytes (p < 0.005) and telomeres (p<0.002), and had the highest NLR (0.004). The difference in 2-years risk score also was significant (p < 0.001), with higher scores in the deceased group. Kaplan-Meier survival analysis showed six parameters were significant predictors in the following order of significance: COVID-19 status, 2-years risk score, NLR, TL, CRP, LDH. Using binary logistic regression analysis Summary risk score, a combination of these six parameters revealed as the best predictor of patients’ survival in this group of parameters (Log rank=25.4, P < 0.001). Conclusion Independent predictors of mortality in chronic haemodialysis patients are higher NLR, CRP, LDH, Lower lymphocytes and shortened TL, and COVID -19 made the situation even worse by significantly arising these patients’ mortality rate.

Telomere Dynamics in Livestock.

Telomeres are repeated sequences of nucleotides at the end of chromosomes. They deteriorate across mitotic divisions of a cell. In Homo sapiens this process of lifetime reduction has been shown to correspond with aspects of organismal aging and exposure to stress or other insults. The early impetus to characterize telomere dynamics in livestock related to the concern that aged donor DNA would result in earlier cell senescence and overall aging in cloned animals. Telomere length investigations in dairy cows included breed effects, estimates of additive genetic control (heritability 0.12 to 0.46), and effects of external stressors on telomere degradation across animal life. Evaluation of telomeres with respect to aging has also been conducted in pigs and horses, and there are fewer reports of telomere biology in beef cattle, sheep, and goats. There were minimal associations of telomere length with animal productivity measures. Most, but not all, work in livestock has documented an inverse relationship between peripheral blood cell telomere length and age; that is, a longer telomere length was associated with younger age. Because livestock longevity affects productivity and profitability, the role of tissue-specific telomere attrition in aging may present alternative improvement strategies for genetic improvement while also providing translational biomedical knowledge.

Telomeres in clinical diabetes research – Moving towards precision medicine in diabetes care?

The early prediction of health outcomes for people with diabetes mellitus is desirable, as are adjunct therapies to reduce the related chronic complications and risk of premature death. The length of telomeres, protective caps on chromosome ends, is influenced by genetic and acquired factors, and shorter telomeres have been associated with and predictive of adverse cardiometabolic outcomes. Many studies have shown associations between telomere length in white blood cells (WBC) and diabetes per se and its chronic complications, and some studies show that telomeres do not always progressively shorten in people with diabetes. With the pandemic of diabetes and taking into consideration the calculations of residual risk using existent risk equations, additional tests to stratify subject risk are desirable. In this evolving era of precision medicine for people with diabetes, this ‘global biomarker’ of WBC telomere length may be useful to help predict health outcomes, to monitor health status, and may be a therapeutic target. We comment on the field of telomere investigations in diabetes, including recommending areas for further clinical research.

Comparison of Telomere Length between Buccal Cells and Blood Cells.

Telomere length (TL) in blood cells is commonly used as a proxy for TL in other tissue types. The source of DNA of adequate quality and quantity is important for TL analysis. Compared to blood cells, buccal cells easy for genomic DNA preparation would facilitate the rapid and reliable TL analysis. However, the feasibility of buccal cells for TL analysis remains yet unestablished. We characterized TL of buccal cells and blood cells collected from 52 individuals using buccal cell swabs and fingertip sticks. Relative TL (RTL) determined by quantitative PCR showed that there is a strong correlation between buccal RTL and blood RTL (r=0.877, p<0.001), suggesting that buccal cells are adequate sources of DNA for TL analysis. The validity of sampling using buccal cell swabs provides simple operation and good reproducibility for TL analysis, that overcomes the discomfort and risk of infection caused by blood sampling.

Telomeres do not always shorten over time in individuals with type 1 diabetes

AimsWe aimed to determine how white blood cell (WBC) telomeres and telomere length change over time are associated with health status in type 1 diabetes. MethodsRelative telomere length (rTL) was measured in WBC DNA from two time-points (median 6.8 years apart) in 618 individuals from the Finnish Diabetic Nephropathy Study by quantitative PCR, with interassay CV ≤ 4%. ResultsBaseline rTL correlated inversely with age and was shorter in men. Individuals in the shortest vs. longest rTL tertile had adverse cardiometabolic profiles, worse renal function, and were prescribed more antihypertensive and lipid-lowering drugs. While overall rTL tended to decrease during the median 6.8-years of follow-up, telomeres shortened in 55.3% of subjects, lengthened in 40.0%, and did not change in 4.7%. Baseline rTL correlated inversely with rTL change. Telomere lengthening was associated with higher HDL-Cholesterol (HDL-C), HDL-C/ApoA1, and with antihypertensive drug and (inversely) with lipid-lowering drug commencement during follow-up. Correlates of rTL percentage change per-annum (adjusted model) were baseline BMI, eGFR, previous retinal laser treatment, HDL-C, and HDL-C/ApoA1. ConclusionsTelomere length measurements may facilitate the treatment and monitoring of the health status of individuals with type 1 diabetes.

Measurement and initial characterization of leukocyte telomere length in 474,074 participants in UK Biobank.

Leukocyte telomere length (LTL) is a proposed marker of biological age. Here we report the measurement and initial characterization of LTL in 474,074 participants in UK Biobank. We confirm that older age and male sex associate with shorter LTL, with women on average ~7 years younger in 'biological age' than men. Compared to white Europeans, LTL is markedly longer in African and Chinese ancestries. Older paternal age at birth is associated with longer individual LTL. Higher white cell count is associated with shorter LTL, but proportions of white cell subtypes show weaker associations. Age, ethnicity, sex and white cell count explain ~5.5% of LTL variance. Using paired samples from 1,351 participants taken ~5 years apart, we estimate the within-individual variability in LTL and provide a correction factor for this. This resource provides opportunities to investigate determinants and biomedical consequences of variation in LTL.

The Association between 25-Hydroxyvitamin D Concentration and Telomere Length in the Very-Old: The Newcastle 85+ Study.

(1) Introduction: vitamin D may maintain the telomere length, either directly or via the inflammation effect and/or modulating the rate of cell proliferation. Whilst results from cross-sectional studies investigating the association between 25(OH)D concentration and telomere length have been mixed, there is a dearth of data from prospective studies which have assessed these associations. This study aimed to examine the association between 25(OH)D concentration in plasma and telomere length in blood cells in very-old adults (≥85 years old) at baseline, 18 months and 36 months by controlling for related lifestyle factors. (2) Methodology: our prospective cohort study comprised 775 participants from the Newcastle 85+ Study who had 25(OH)D measurements at baseline. Plasma 25(OH)D was stratified as <25 nmol/L (low), 25–50 nmol/L (moderate) and >50 nmol/L (high). Peripheral blood mononuclear cell telomere length was measured by quantitative real-time polymerase chain reaction at baseline, 18 and 36 months from baseline. (3) Results: a positive significant association was found between 25(OH)D concentration and telomere length amongst very-old participants at baseline (95% CI = 12.0–110.3, B = 61.2 ± 5.0, p = 0.015). This association was negative at 18 months (95% CI = −59.9–−7.5, B = −33.7 ± 13.3, p = 0.012) but was non-significant at 36 months. (4) Conclusion: Circulating 25(OH)D concentration shows inconsistent relationships with telomere length over time in very-old (85+ year old) adults.

Influence of Telomere Length on the Achievement of Deep Molecular Response With Imatinib in Chronic Myeloid Leukemia Patients.

Tyrosine kinase inhibitors have dramatically changed the outcome of chronic myeloid leukemia (CML), and nowadays, one of the main treatment goals is the achievement of deep molecular responses (DMRs), which can eventually lead to therapy discontinuation approaches. Few biological factors at diagnosis have been associated with this level of response. Telomere length (TL) in peripheral blood cells of patients with CML has been related to disease stage, response to therapy and disease progression, but little is known about its role on DMR. In this study, we analyzed if age-adjusted TL (referred as “delta-TL”) at diagnosis of chronic phase (CP)-CML might correlate with the achievement of DMR under first-line imatinib treatment. TL from 96 CP-CML patients had been retrospectively analyzed at diagnosis by monochrome multiplex quantitative PCR. We observed that patients with longer age-adjusted telomeres at diagnosis had higher probabilities to achieve DMR with imatinib than those with shortened telomeres (P = 0.035 when delta-TL was studied as a continuous variable and P = 0.047 when categorized by the median). Moreover, patients carrying long telomeres also achieved major molecular response significantly earlier (P = 0.012). This study provides proof of concept that TL has a role in CML biology and when measured at diagnosis of CP-CML could help to identify patients likely to achieve DMR to first-line imatinib treatment.

Growth acceleration results in faster telomere shortening later in life.

There is a wealth of evidence for a lifespan penalty when environmental conditions influence an individual's growth trajectory, such that growth rate is accelerated to attain a target size within a limited time period. Given this empirically demonstrated relationship between accelerated growth and lifespan, and the links between lifespan and telomere dynamics, increased telomere loss could underpin this growth-lifespan trade. We experimentally modified the growth trajectory of nestling zebra finches (Taeniopygia guttata), inducing a group of nestlings to accelerate their growth between 7 and 15 days of age, the main phase of body growth. We then sequentially measured their telomere length in red blood cells at various time points from 7 days to full adulthood (120 days). Accelerated growth between 7 and 15 days was not associated with a detectable increase in telomere shortening during this period compared with controls. However, only in the treatment group induced to show growth acceleration was the rate of growth during the experimental period positively related to the amount of telomere shortening between 15 and 120 days. Our findings provide evidence of a long-term influence of growth rate on later-life telomere shortening, but only when individuals have accelerated growth in response to environmental circumstances.

Relative Telomere Length in Peripheral Blood Cells and Hypertension Risk among Mine Workers: A Case-Control Study in Chinese Coal Miners.

Hypertension is a common chronic disease in middle-aged and elderly people and is an important risk factor for many cardiovascular diseases. Its pathogenesis remains unclear. Epidemiological studies have found that the loss of telomere length in peripheral blood cells can increase the risk of coronary heart disease, myocardial infarction, and other diseases. However, a correlation between loss of telomere length and hypertension has not been established. In this study, we aimed to explore the association between telomere length and the risk of essential hypertension (EH) in Chinese coal miners. A case-control study was performed with 215 EH patients and 222 healthy controls in a large coal mining group located in North China. Face-to-face interviews were conducted by trained staff with the necessary medical knowledge. Relative telomere length (RTL) was measured by a quantitative real-time PCR assay using DNA extracted from peripheral blood. In the control group, the age-adjusted RTL was statistically significantly lower in miners performing hard physical labour compared with nonphysical labour (P = 0.043). A significantly shorter age-adjusted RTL was found in the control group of participants who consumed alcohol regularly compared with those who do not consume alcohol (P = 0.024). Age-adjusted RTL was negatively correlated with body mass index (BMI) and alcohol consumption. Hypertension was also found to be significantly correlated with factors such as age, BMI, alcohol consumption, smoking, and tea consumption. Our results suggest that RTL is associated with hypertension in coal miners.

Mediterranean Diet and Telomere Length: A Systematic Review and Meta-Analysis

Accelerated telomere shortening has been associated with several age-related diseases and/or decreased lifespan in humans. The Mediterranean diet (MedDiet) is considered to be 1 of the most recognized diets for disease prevention and healthy aging, partially due to its demonstrated anti-inflammatory and antioxidative properties which may impact on telomere length (TL). The aim of this meta-analysis was to determine the associations between MedDiet adherence and TL maintenance. MEDLINE-PubMed and Cochrane databases were searched up to December 2018 for studies evaluating the association between MedDiet adherence and TL in blood cells. Two reviewers, working independently, screened all titles and abstracts to identify studies that met the inclusion criteria [cross-sectional, case-control, and prospective cohort studies and randomized clinical trials (RCTs) published in English and excluded nonoriginal articles]. Data were pooled by the generic inverse variance method using the random effects model and expressed as standardized mean difference (SMD). Heterogeneity was identified using the Cochran Q test and quantified by the I2 statistic. A total of 8 original cross-sectional studies were included for the quantitative meta-analysis, comprising a total of 13,733 participants from 5 countries. A positive association between adherence to the MedDiet and TL was observed in all meta-analyses, with the exception of those conducted only in men: SMD (95% CI) of 0.130 (0.029; 0.231) for all subjects, 0.078 (0.005; 0.152) for women, and 0.095 (-0.005; 0.195) for men. Only 1 prospective cohort study and 1 RCT were identified, therefore, we could not undertake a meta-analysis for these study designs. The present meta-analysis of cross-sectional studies demonstrates that higher MedDiet adherence is associated with longer TL. At the same time, larger and high-quality prospective studies and clinical trials are warranted to confirm this association.

Impaired reproductive function and fertility preservation in a woman with a dyskeratosis congenita.

To determine the impact of accelerated telomere shortening on the fertility parameters and treatment outcomes of a woman with dyskeratosis congenita (DKC). A case study of the clinical data, blood, discarded oocytes, and arrested embryos of a woman with DKC and donated cryopreserved embryos from unaffected patients. Mean telomere length in blood cells was analyzed by flow cytometry-fluorescence in situ hybridization (flow-FISH) and qPCR. The load of short telomeres in blood cells was measured by universal single telomere length analysis (Universal STELA). The mean telomere length in embryos was analyzed by single-cell amplification of telomere repeats (SCATR) PCR. Comparison of clinical parameters revealed that the DKC patient had reduced anti-Mullerian hormone (0.3 vs 4.1 ± 5.7ng/ML), reduced oocytes retrieved (7 vs 18.5 ± 9.5), reduced fertilization rate, and reduced euploidy rate relative to unaffected patients. Additionally, mean telomere length in DKC embryos were shorter than unaffected embryos. However, hormone treatment led to increased leukocyte telomere length, while the load of short telomeres was also shown to decrease during the course of treatment. We demonstrate for the first time the direct detrimental impacts of short telomeres on female fertility. We further demonstrate positive effects of hormone treatments for people with telomere disorders.

Lymphocyte homeostasis is maintained in perinatally HIV-infected patients after three decades of life

BackgroundWhile immunosenescence, defined as reduced production of new lymphocytes, restriction of T-cell receptor repertoire and telomeres shortening, has been extensively evaluated in HIV-infected children and adults, no data about these parameters are available in perinatally-infected patients with very long-lasting HIV infection.MethodsWe compared thymic and bone marrow output, telomere length (measured by Real-Time PCR) and T-cell receptor repertoire (determined by spectratyping) of 21 perinatally HIV-infected subjects (with a median of 27 years of infection) with those of 19 age-matched non-perinatally HIV-infected patients and 40 healthy controls. All patients received a combined antiretroviral therapy.ResultsWhile thymic and bone marrow output were not different among the analyzed groups, telomere length in peripheral blood cells and T-cell receptor diversity were significantly lower in HIV-perinatally and non-perinatally infected individuals compared to healthy controls.ConclusionsIn HIV-infected subjects, a normal thymic output together with a reduced telomere length and a restricted T-cell receptor repertoire could be explained by the shift of newly produced cells into memory subsets. This phenomenon may allow to control viral infection and maintain peripheral homeostasis.

Telomere length and aging-related outcomes in humans: A Mendelian randomization study in 261,000 older participants.

Inherited genetic variation influencing leukocyte telomere length provides a natural experiment for testing associations with health outcomes, more robust to confounding and reverse causation than observational studies. We tested associations between genetically determined telomere length and aging‐related health outcomes in a large European ancestry older cohort. Data were from n = 379,758 UK Biobank participants aged 40–70, followed up for mean of 7.5 years (n = 261,837 participants aged 60 and older by end of follow‐up). Thirteen variants strongly associated with longer telomere length in peripheral white blood cells were analyzed using Mendelian randomization methods with Egger plots to assess pleiotropy. Variants in TERC, TERT, NAF1, OBFC1, and RTEL1 were included, and estimates were per 250 base pairs increase in telomere length, approximately equivalent to the average change over a decade in the general white population. We highlighted associations with false discovery rate‐adjusted p‐values smaller than .05. Genetically determined longer telomere length was associated with lowered risk of coronary heart disease (CHD; OR = 0.95, 95% CI: 0.92–0.98) but raised risk of cancer (OR = 1.11, 95% CI: 1.06–1.16). Little evidence for associations were found with parental lifespan, centenarian status of parents, cognitive function, grip strength, sarcopenia, or falls. The results for those aged 60 and older were similar in younger or all participants. Genetically determined telomere length was associated with increased risk of cancer and reduced risk of CHD but little change in other age‐related health outcomes. Telomere lengthening may offer little gain in later‐life health status and face increasing cancer risks.

Association Between Leukocyte Telomere Length and Colorectal Cancer Risk in the Singapore Chinese Health Study.

OBJECTIVES:Telomeres and telomerase play important roles in maintaining chromosome integrity and genomic stability. To address a lack of consensus about the association between leukocyte telomere length and colorectal cancer, we investigated this association in the Singapore Chinese Health Study.METHODS:Relative telomere length in white blood cells was quantified using a validated quantitative polymerase chain reaction method in 26,761 participants, including 776 incident colorectal cancer cases. The Cox proportional hazard regression method was used to calculate the hazard ratio and the corresponding 95% confidence interval (CI) for colorectal cancer associated with longer telomeres.RESULTS:Longer telomeres were significantly associated with a higher risk of colorectal cancer (Ptrend = 0.02). Compared with the lowest quartile, subjects with the highest quartile of telomere length had a hazard ratio of 1.32 (95% CI: 1.08–1.62) for developing colorectal cancer. The corresponding elevation in rectal cancer risk for the highest quartile of telomere length was 71% (95% CI: 22–140, Ptrend = 0.02). There was no statistically significant association between telomere length and risk of colon cancer.DISCUSSION:This large cohort study of Singapore Chinese, the first study using a cohort study design with more than 26,000 participants that yielded 776 incidence colorectal cancer cases during 12 years of follow-up, provides evidence in support of longer telomeres being associated with a higher risk of colorectal cancer, particularly rectal cancer.

Association of telomere length with chronic exposure to ionizing radiation among inhabitants of natural high background radiation areas of Ramsar, Iran

Purpose: There are few areas in the world where ionizing radiation (IR) dose received by the public from radon gas and other radioactive elements are much higher than recommended limits. Telomere length is a potential biomarker of genomic instability due to oxidative stress from IR exposure. In this study, we investigated the impact of chronic exposure to environmental IR on relative telomere length (RTL) in white blood cells (WBC) among inhabitants of high background radiation areas (HBRA) of Ramsar, Iran.Materials and methods: One hundred and four individuals from HBRAs of Ramsar and 104 age-matched subjects from normal background radiation areas (NBRA) of Iran were enrolled in the study. The RTLs of WBC DNA samples were measured by a quantitative polymerase chain reaction (q-PCR) approach.Results: Mean RTL in HBRA and NBRA groups did not show any significant difference (1.21 ± 0.71 versus 1.22 ± 0.66, p = .306). After controlling for all demographic variables, less than 1% of the variances in RTL values were related to background radiation exposure.Conclusion: We conclude that chronic exposure to natural IR has no statistically significant effect on RTL among the inhabitants of HBRAs of Ramsar compared with a control group.

DNA methylation-based age prediction and telomere length in white blood cells and cumulus cells of infertile women with normal or poor response to ovarian stimulation.

An algorithm assessing the methylation levels of 353 informative CpG sites in the human genome permits accurate prediction of the chronologic age of a subject. Interestingly, when there is discrepancy between the predicted age and chronologic age (age acceleration or “AgeAccel”), patients are at risk for morbidity and mortality. Identification of infertile patients at risk for accelerated reproductive senescence may permit preventative action. This study aimed to assess the accuracy of the “epigenetic clock” concept in reproductive age women undergoing fertility treatment by applying the age prediction algorithm in peripheral (white blood cells [WBCs]) and follicular somatic cells (cumulus cells [CCs]), and to identify whether women with premature reproductive aging (diminished ovarian reserve) were at risk of AgeAccel in their age prediction. Results indicated that the epigenetic algorithm accurately predicts age when applied to WBCs but not to CCs. The age prediction of CCs was substantially younger than chronologic age regardless of the patient’s age or response to stimulation. In addition, telomeres of CCs were significantly longer than that of WBCs. Our findings suggest that CCs do not demonstrate changes in methylome-predicted age or telomere-length in association with increasing female age or ovarian response to stimulation.

Telomere Length and Telomerase Complex Mutations Predict Fatal Treatment Toxicity after Stem Cell Transplantation in Patients with Myelodysplastic Syndrome

Introduction: Identifying patients at high risk of fatal treatment toxicity is a central challenge in hematopoietic stem cell transplantation (HSCT). Objective metrics that enable more accurate prediction of non-relapse mortality (NRM) could inform clinical decisions about timing and modality of HSCT. Short telomere length, mediated by inherited or acquired factors, impairs cellular response to genotoxic and replicative stress. We therefore evaluated the impact of recipient telomere length on clinical outcomes based on treatment intensity in patients with myelodysplastic syndrome (MDS) receiving HSCT.Methods: We used qPCR to measure relative telomere lengths in whole blood DNA samples from 1514 patients who received allogeneic HSCT for MDS and were enrolled in the Center for International Blood and Marrow Transplant Research Repository. Within the cohort, patients age 40 and older were grouped into those with short (<25th), intermediate (25-75th) or long (>75th percentile) telomeres. To evaluate germline determinants of telomere length, we sequenced 7 genes involved in telomere maintenance and mutated in dyskeratosis congenita: TERC, TERT, DKC1, TINF2, NHP2, WRAP53 and CTC1. Putative germline variants were classified as “rare” if the allele frequency was <0.001 in all Genome Aggregation Database (gnomAD) populations.Results: Among patients age 40 and older (n=1267), those with short (HR 1.52, 1.24-1.85, p<0.001) or intermediate (HR 1.35, 1.13-1.61, p<0.001) telomere length had poor overall survival compared with those having long telomeres (Fig 1A). In a competing risks regression model, the adverse effect of shorter telomeres was driven by a significantly higher risk of NRM among patients with short (HR 1.57, 1.20-2.06, p=0.001) and intermediate (HR 1.32, 1.03-1.69, p=0.03) telomere length. The association between telomere length and NRM was evident in patients receiving myeloablative (MAC, p=0.002) but not reduced-intensity conditioning (RIC, p=0.2) regimens (Fig 1B). We observed no association between telomere length and disease relapse in patients receiving MAC or RIC regimens. In a multivariable regression model, the prognostic significance of telomere length was independent of clinical and genetic factors, including age, Karnofsky performance status, hematologic parameters, IPSS-R risk category, donor mismatch, donor age, and TP53 mutation.We identified 40 patients (2.6% of the cohort) with rare germline TERT variants. Patients with rare TERT variants had significantly shorter telomeres than patients with common (p=0.001) or no (p<0.0001) TERT variants and were diagnosed with MDS at an earlier age than patients with common (52.2 vs. 58.4 years, p=0.01) or no (52.2 vs. 57.9 years, p=0.01) TERT variants. The domain distribution of rare TERT variants mirrored that of validated pathogenic germline TERT mutations, primarily affecting the reverse transcriptase and C-terminal extension domains. Rare variants in TERC (0.4%) and DKC1 (0.2%) were also associated with shorter telomeres (p=0.02 and p=0.04, respectively). In total, we identified germline telomerase complex mutations in 49 of 1514 MDS patients (3.2%), even though only 1 patient had a clinical diagnosis of dyskeratosis congenita. Together, patients with telomerase complex mutations had shorter overall survival than those without mutations (unadjusted p=0.008), attributable to a marked increase in the risk of early NRM among those receiving MAC (1 year cumulative incidence of NRM 48% vs. 26%, p=0.03). The impact of shorter telomeres on NRM was similar in patients with and without identified core telomerase complex mutations, suggesting that additional mechanisms of impaired telomere length maintenance may contribute to MDS pathogenesis and outcome.Conclusion: Recipient telomere length is independently associated with overall survival after allogeneic HSCT for MDS. Patients age 40 or older with shorter blood cell telomere length have a significantly elevated risk of early NRM with myeloablative conditioning regimens. Clinically unrecognized germline mutations in the telomerase genes TERT, TERC, and DKC1 define a distinct subset of adult patients with sporadic MDS and short telomeres who have poor transplant outcomes. Together, these results indicate that short telomere length in MDS patients mediates fatal treatment toxicity that may be attenuated by lower intensity conditioning approaches. DisclosuresAntin:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

Telomere dysfunction-related serological markers and oxidative stress markers in rheumatoid arthritis patients: correlation with diseases activity.

Rheumatoid arthritis (RA) is an inflammatory autoimmune polyarthritis with progressive destruction of the synovial joints associated with systemic manifestations. RA is characterized by infiltration of the synovial joints with inflammatory immune cells with premature immunosenescence. Shorter telomere length in the peripheral blood cells and increase in the oxidative stress have been detected in patients with RA. The aim of the present study was to study the association of markers of telomere shortening and oxidative stress with RA disease activity. Sixty-one RA patients and 15 healthy controls were enrolled in the study. Demographic data, clinical examination, and disease activity status were evaluated for the RA patients. Serum levels of chitinase and NAG (telomere markers) were determined by biochemical reactions using colloidal chitin and NAG as substrates, respectively. Nitric oxide and superoxide dismutase (oxidative stress markers) were determined colometrically and spectrophotometrically, respectively, in the sera of RA patients and controls. Results were correlated with disease activity. Indices of telomere shortening and oxidative markers were significantly higher in RA patients compared to controls. These indices were correlated with signs of disease activity (including number of swollen and tender joints, DAS-28, and inflammatory markers). Rheumatoid arthritis is a disease in which markers of telomere shortening and elevated oxidant stress correlate with disease activity.

Bovine telomere dynamics and the association between telomere length and productive lifespan

Average telomere length (TL) in blood cells has been shown to decline with age in a range of vertebrate species, and there is evidence that TL is a heritable trait associated with late-life health and mortality in humans. In non-human mammals, few studies to date have examined lifelong telomere dynamics and no study has estimated the heritability of TL, despite these being important steps towards assessing the potential of TL as a biomarker of productive lifespan and health in livestock species. Here we measured relative leukocyte TL (RLTL) in 1,328 samples from 308 Holstein Friesian dairy cows and in 284 samples from 38 female calves. We found that RLTL declines after birth but remains relatively stable in adult life. We also calculated the first heritability estimates of RLTL in a livestock species which were 0.38 (SE = 0.03) and 0.32 (SE = 0.08) for the cow and the calf dataset, respectively. RLTL measured at the ages of one and five years were positively correlated with productive lifespan (p < 0.05). We conclude that bovine RLTL is a heritable trait, and its association with productive lifespan may be used in breeding programmes aiming to enhance cow longevity.