Faculty Opinions recommendation of Influences on the reduction of relative telomere length over 10 years in the population-based Bruneck Study: introduction of a well-controlled high-throughput assay.

2012 ◽  
Author(s):  
Neal Young
Keyword(s):  
Telomere Length ◽  
High Throughput ◽  
Population Based ◽  
Relative Telomere Length ◽  
High Throughput Assay

scholarly journals Relative Telomere Length and Cardiovascular Risk Factors

Biomolecules ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 192 ◽  
Author(s):  
Moritz Koriath ◽  
Christian Müller ◽  
Norbert Pfeiffer ◽  
Stefan Nickels ◽  
Manfred Beutel ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Telomere Length ◽  
Ldl Cholesterol ◽  
Smoking Status ◽  
Hdl Cholesterol ◽  
Population Based ◽  
Relative Telomere Length

(1) Background: Telomeres are repetitive DNA sequences located at the extremities of chromosomes that maintain genetic stability. Telomere biology is relevant to several human disorders and diseases, specifically cardiovascular disease. To better understand the link between cardiovascular disease and telomere length, we studied the effect of relative telomere length (RTL) on cardiovascular risk factors in a large population-based sample. (2) Methods: RTL was measured by a real-time quantitative polymerase chain reaction in subjects of the population-based Gutenberg Health Study (n = 4944). We then performed an association study of RTL with known cardiovascular risk factors of smoking status as well as systolic and diastolic blood pressure, body mass index (BMI), LDL cholesterol, HDL cholesterol, and triglycerides. (3) Results: A significant correlation was shown for RTL, with age as a quality control in our study (effect = −0.004, p = 3.2 × 10−47). Analysis of the relation between RTL and cardiovascular risk factors showed a significant association of RTL in patients who were current smokers (effect = −0.016, p = 0.048). No significant associations with RTL were seen for cardiovascular risk factors of LDL cholesterol (p = 0.127), HDL cholesterol (p = 0.713), triglycerides (p = 0.359), smoking (p = 0.328), diastolic blood pressure (p = 0.615), systolic blood pressure (p = 0.949), or BMI (p = 0.903). In a subsequent analysis, we calculated the tertiles of RTL. No significant difference across RTL tertiles was detectable for BMI, blood pressure, lipid levels, or smoking status. Finally, we studied the association of RTL and cardiovascular risk factors stratified by tertiles of age. We found a significant association of RTL and LDL cholesterol in the oldest tertile of age (effect = 0.0004, p = 0.006). (4) Conclusions: We determined the association of relative telomere length and cardiovascular risk factors in a population setting. An association of telomere length with age, current smoking status, as well as with LDL cholesterol in the oldest tertile of age was found, whereas no associations were observed between telomere length and triglycerides, HDL cholesterol, blood pressure, or BMI.

scholarly journals An Optimised Step-by-Step Protocol for Measuring Relative Telomere Length

2020 ◽  
Vol 3 (2) ◽  
pp. 27 ◽  
Author(s):  
Mugdha V. Joglekar ◽  
Sarang N. Satoor ◽  
Wilson K.M. Wong ◽  
Feifei Cheng ◽  
Ronald C.W. Ma ◽  
...  
Keyword(s):  
Telomere Length ◽  
Large Population ◽  
Single Copy ◽  
Population Based ◽  
Fragment Analysis ◽  
Real Time Quantitative Pcr ◽  
Disease States ◽  
Relative Telomere Length ◽  
Health And Disease

Telomeres represent the nucleotide repeat sequences at the ends of chromosomes and are essential for chromosome stability. They can shorten at each round of DNA replication mainly because of incomplete DNA synthesis of the lagging strand. Reduced relative telomere length is associated with aging and a range of disease states. Different methods such as terminal restriction fragment analysis, real-time quantitative PCR (qPCR) and fluorescence in situ hybridization are available to measure telomere length; however, the qPCR-based method is commonly used for large population-based studies. There are multiple variations across qPCR-based methods, including the choice of the single-copy gene, primer sequences, reagents, and data analysis methods in the different reported studies so far. Here, we provide a detailed step-by-step protocol that we have optimized and successfully tested in the hands of other users. This protocol will help researchers interested in measuring relative telomere lengths in cells or across larger clinical cohort/study samples to determine associations of telomere length with health and disease.

scholarly journals Telomere length: population epidemiology and concordance in Australian children aged 11–12 years and their parents

BMJ Open ◽  
2019 ◽  
Vol 9 (Suppl 3) ◽  
pp. 118-126 ◽  
Author(s):  
Minh Thien Nguyen ◽  
Kate Lycett ◽  
Regan Vryer ◽  
David P Burgner ◽  
Sarath Ranganathan ◽  
...  
Keyword(s):  
Telomere Length ◽  
Globin Gene ◽  
Venous Blood ◽  
Single Copy ◽  
Population Based ◽  
Cross Sectional Study ◽  
Telomeric Dna ◽  
Cross Sectional ◽  
Relative Telomere Length ◽  
Parent Child

ObjectivesTo (1) describe the epidemiology of child and adult telomere length, and (2) investigate parent–child telomere length concordance.DesignPopulation-based cross-sectional study within the Longitudinal Study of Australian Children.SettingAssessment centres in seven major Australian cities and eight selected regional towns; February 2015 to March 2016.ParticipantsOf 1874 participating families, telomere data were available for analysis for 1206 children and 1343 parents, of whom 1143 were parent–child pairs. There were 589 boys and 617 girls; 175 fathers and 1168 mothers.Outcome measuresRelative telomere length (T/S ratio), calculated by comparing telomeric DNA (T) level with the single copy (S) beta-globin gene in venous blood-derived genomic DNA by quantitative real-time PCR.ResultsMean T/S ratio for all children, boys and girls was 1.09 (SD 0.56), 1.05 (SD 0.53) and 1.13 (SD 0.59), respectively. Mean T/S ratio for all parents, fathers and mothers was 0.81 (SD 0.37), 0.82 (SD 0.36) and 0.81 (SD 0.38), respectively. Parent–child T/S ratio concordance was moderate (correlation 0.24). In adjusted regression models, one unit higher parent T/S ratio was associated with 0.36 (estimated linear regression coefficient (β); 95% CI 0.28 to 0.45) higher child T/S ratio. Concordance was higher in the youngest parent-age tertile (β 0.49; 95% CI 0.34 to 0.64) compared with the middle (β 0.35; 95% CI 0.21 to 0.48) and oldest tertile (β 0.26; 95% CI 0.11 to 0.41; p-trend 0.04). Father–child concordance was 0.34 (95% CI 0.18 to 0.48), while mother–child was 0.22 (95% CI 0.17 to 0.28).ConclusionsWe provide telomere length population values for children aged 11–12 years and their mid-life parents. Relative telomere length was shorter in adults than children, as expected. There was modest evidence of parent–child concordance, which diminished with increasing parent age.

scholarly journals A novel pooled-sample multiplex luminex assay for high-throughput measurement of relative telomere length

2018 ◽  
Vol 30 (4) ◽  
pp. e23118 ◽  
Author(s):  
Farzana Jasmine ◽  
Justin Shinkle ◽  
Mekala Sabarinathan ◽  
Habibul Ahsan ◽  
Brandon L. Pierce ◽  
...  
Keyword(s):  
Telomere Length ◽  
High Throughput ◽  
Luminex Assay ◽  
Relative Telomere Length ◽  
Pooled Sample

scholarly journals Glucocorticoids, state-dependent reproductive investment and success in the face of danger in a long-lived bird

2020 ◽  
Author(s):  
Kristina Noreikienė ◽  
Kim Jaatinen ◽  
Benjamin B. Steele ◽  
Markus Öst
Keyword(s):  
Predation Risk ◽  
Telomere Length ◽  
Clutch Size ◽  
Body Condition ◽  
Nest Predation ◽  
Hatching Success ◽  
Reproductive Investment ◽  
Trade Off ◽  
Relative Telomere Length ◽  
Future Reproduction

AbstractGlucocorticoid hormones may mediate trade-offs between current and future reproduction. However, understanding their role is complicated by predation risk, which simultaneously affects the value of the current reproductive investment and elevates glucocorticoid levels. Here, we shed light on these issues in long-lived female Eiders (Somateria mollissima) by investigating how current reproductive investment (clutch size) and hatching success relate to faecal glucocorticoid metabolite [fGCM] level and residual reproductive value (minimum years of breeding experience, body condition, relative telomere length) under spatially variable predation risk. Our results showed a positive relationship between colony-specific predation risk and mean colony-specific fGCM levels. Clutch size and female fGCM were negatively correlated only under high nest predation and in females in good body condition, previously shown to have a longer life expectancy. We also found that younger females with longer telomeres had smaller clutches. The drop in hatching success with increasing fGCM levels was least pronounced under high nest predation risk, suggesting that elevated fGCM levels may allow females to ensure some reproductive success under such conditions. Hatching success was positively associated with female body condition, with relative telomere length, particularly in younger females, and with female minimum age, particularly under low predation risk, showing the utility of these metrics as indicators of individual quality. In line with a trade-off between current and future reproduction, our results show that high potential for future breeding prospects and increased predation risk shift the balance toward investment in future reproduction, with glucocorticoids playing a role in the resolution of this trade-off.

scholarly journals Development of a High-Throughput Screening Assay to Identify Inhibitors of the SARS-CoV-2 Guanine-N7-Methyltransferase Using RapidFire Mass Spectrometry

2021 ◽  
pp. 247255522110006
Author(s):  
Lesley-Anne Pearson ◽  
Charlotte J. Green ◽  
De Lin ◽  
Alain-Pierre Petit ◽  
David W. Gray ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Mutational Analysis ◽  
Nonstructural Protein ◽  
Translation Efficiency ◽  
Screening Assay ◽  
High Throughput Screening Assay ◽  
Starting Point ◽  
Approved Drugs ◽  
High Throughput Assay

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) represents a significant threat to human health. Despite its similarity to related coronaviruses, there are currently no specific treatments for COVID-19 infection, and therefore there is an urgent need to develop therapies for this and future coronavirus outbreaks. Formation of the cap at the 5′ end of viral RNA has been shown to help coronaviruses evade host defenses. Nonstructural protein 14 (nsp14) is responsible for N7-methylation of the cap guanosine in coronaviruses. This enzyme is highly conserved among coronaviruses and is a bifunctional protein with both N7-methyltransferase and 3′-5′ exonuclease activities that distinguish nsp14 from its human equivalent. Mutational analysis of SARS-CoV nsp14 highlighted its role in viral replication and translation efficiency of the viral genome. In this paper, we describe the characterization and development of a high-throughput assay for nsp14 utilizing RapidFire technology. The assay has been used to screen a library of 1771 Food and Drug Administration (FDA)-approved drugs. From this, we have validated nitazoxanide as a selective inhibitor of the methyltransferase activity of nsp14. Although modestly active, this compound could serve as a starting point for further optimization.

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