scholarly journals Mathematical modelling of telomere length dynamics

2019 ◽  
Vol 80 (4) ◽  
pp. 1039-1076 ◽  
Author(s):  
Jonathan A. D. Wattis ◽  
Qi Qi ◽  
Helen M Byrne
Keyword(s):  
Cell Division ◽  
Normal Distribution ◽  
Telomere Length ◽  
Dna Sequences ◽  
Discrete Models ◽  
Telomere Shortening ◽  
Threshold Length ◽  
Normal Ageing ◽  
Log Normal ◽  
Successive Generations

AbstractTelomeres are repetitive DNA sequences located at the ends of chromosomes. During cell division, an incomplete copy of each chromosome’s DNA is made, causing telomeres to shorten on successive generations. When a threshold length is reached replication ceases and the cell becomes ‘senescent’. In this paper, we consider populations of telomeres and, from discrete models, we derive partial differential equations which describe how the distribution of telomere lengths evolves over many generations. We initially consider a population of cells each containing just a single telomere. We use continuum models to compare the effects of various mechanisms of telomere shortening and rates of cell division during normal ageing. For example, the rate (or probability) of cell replication may be fixed or it may decrease as the telomeres shorten. Furthermore, the length of telomere lost on each replication may be constant, or may decrease as the telomeres shorten. Where possible, explicit solutions for the evolution of the distribution of telomere lengths are presented. In other cases, expressions for the mean of the distribution are derived. We extend the models to describe cell populations in which each cell contains a distinct subpopulation of chromosomes. As for the simpler models, constant telomere shortening leads to a linear reduction in telomere length over time, whereas length-dependent shortening results in initially rapid telomere length reduction, slowing at later times. Our analysis also reveals that constant telomere loss leads to a Gaussian (normal) distribution of telomere lengths, whereas length-dependent loss leads to a log-normal distribution. We show that stochastic models, which include a replication probability, also lead to telomere length distributions which are skewed.

Telomere dysfunction in prostatic carcinogenesis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10021-10021
Author(s):  
A. M. Joshua ◽  
B. Vukovic ◽  
I. Braude ◽  
A. Evans ◽  
J. Srigley ◽  
...  
Keyword(s):  
Telomere Length ◽  
Dna Sequences ◽  
Specific Binding ◽  
In Situ Hybridisation ◽  
Intraepithelial Neoplasia ◽  
Great Promise ◽  
Fluorescence In Situ Hybridisation ◽  
Telomere Shortening ◽  
Prostate Intraepithelial Neoplasia ◽  
Prostatic Epithelium

10021 Background: Telomeres are composed of tandemly repeated DNA sequences (TTAGGG) and specific binding proteins located at the ends of eukaryotic chromosomes. They stabilize chromosomal ends; telomere shortening is an important mechanism of genomic instability and can lead to end-to-end chromosomal fusion, rearrangements and cell death. Here we evaluate the hypothesis that telomere shortening contributes to the development of prostate cancer (CaP). Methods: We used telomeric, centromeric and chromosome specific peptide-nucleic acid probes with z-stacked quantitative fluorescence in-situ hybridisation analysis to initially analyse 15 radical prostatectomy specimens and then subsequently sextant core biopsies from 80 men obtained in 1998–2001 containing high-grade prostate intraepithelial neoplasia (HPIN) only. The biopsy cohort outcome is blinded to prevent experimental bias and has a minimum follow-up of 2 years with 41 men diagnosed subsequently with CaP and 39 men without CaP on rebiopsy. Regions of interest were identifying with an overlying haematoxylin and eosin slide. Results: We found a significant decrease in telomere length in both HPIN and CaP in comparison to normal prostatic epithelium accompanied by elevated rates of aneusomy. Telomere erosion in HPIN was more common in regions of the prostate-containing CaP. We now have analyzed ∼4000 cells of matching HPIN and surrounding stroma. Preliminary analysis demonstrated that the median telomere length in HPIN is approximately 27% of the surrounding stroma with upper and lower quartiles being 16% and 38% respectively. Logistic regression analysis is in progress to determine whether the length of the shortest telomeres or the average telomeric length in a sample predicts for subsequent diagnosis of CaP. Secondary analyses are examining the effect of telomere length on the interval to the diagnosis of CaP, the effect of age on telomere length and the eventual Gleason score. Conclusions: Analysis of telomere length holds great promise for developing improved prognostic markers in prostatic carcinogenesis. This is a first of its kind study in the field. No significant financial relationships to disclose.

scholarly journals Can telomere length predict bone health? A review of current evidence

2020 ◽  
Author(s):  
Sok Kuan Wong ◽  
Soelaiman Ima-Nirwana ◽  
Kok-Yong Chin
Keyword(s):  
Cell Division ◽  
Telomere Length ◽  
Dna Sequences ◽  
Bone Health ◽  
Bone Cells ◽  
Epidemiological Studies ◽  
Telomere Maintenance ◽  
Current Evidence ◽  
Base Pairs ◽  
Age Related

Telomeres are repetitive DNA sequences located at the end of chromosomes, which serve as a protective barrier against chromosomal deterioration during cell division. Approximately 50–200 base pairs of nucleotides are lost per cell division and new repetitive nucleotides are added by the enzyme telomerase allowing telomere maintenance. Telomere shortening has been proposed as an indicator for biological ageing, but its relationship with age-related osteoporosis is ambiguous. We summarize the current evidence on the relationship between telomere length and bone health in experimental and epidemiological studies, which may serve as a scientific reference for the development of novel diagnostic markers of osteoporosis or novel therapeutics targeting telomere and telomerase in bone cells to treat osteoporosis.

scholarly journals CORRELATION OF TELOMERE LENGTH SHORTENING WITH SMOKING

2021 ◽  
Vol 9 (1) ◽  
pp. 211-215
Author(s):  
María Emilia Vidargas Rubio ◽  
Dra. Iliana Herrera ◽  
Dra. Abigail Valdez Bartolo ◽  
Dra. Ivette Buendia Roldan
Keyword(s):  
Telomere Length ◽  
Mexico City ◽  
Dna Sequences ◽  
Passive Smoking ◽  
Chemical Compounds ◽  
Study Groups ◽  
Minimal Length ◽  
Exposed Group ◽  
Rt Pcr ◽  
Telomere Shortening

Background:  Telomeres are DNA sequences that can be found at the ends of chromosomes, and prevent them from being damaged, they show shortening every time with the cell division, and when it is below a minimal length, the cells interrupt their cell cycle. Cigarette smoke contains chemical compounds that contribute to the oxidative damage in cells. Method: subjects over 65 years old belonging to the INER ageing cohort, residents of Mexico City and asymptomatic respiratory patients were studied. A questionary was applied on demographic characteristics, smoking habits (active and passive), and the study groups were identified as active smoking (AS), passive smoking (PS) and non-exposed subjects (NE). Telomere length was measured in a serum sample using the quantitative method based on RT-PCR. Results: We compared clinical data and telomere length of 333 subjects, showing that non-exposed group are below the 10th percentile, with the smallest telomere size (NE 1.38 + 0.36 vs PS 1.50 + 0.40 and AS 1.41 +0.43). Conclusion: There is no evidence that telomere shortening have increased as a result of active or passive smoking. It is suggested that smoking is not the only one responsible for the presence of shorter telomeres.

Prediction of Haemoglobin Level by Some Probability Distribution

2020 ◽  
Vol 9 (1) ◽  
pp. 84-88
Author(s):  
Govinda Prasad Dhungana ◽  
Laxmi Prasad Sapkota
Keyword(s):  
Probability Distribution ◽  
Normal Distribution ◽  
Goodness Of Fit ◽  
Continuous Variable ◽  
Hemoglobin Level ◽  
Chi Square ◽  
Chi Square Test ◽  
Log Normal ◽  
Two Parameters ◽  
Best Fit

 Hemoglobin level is a continuous variable. So, it follows some theoretical probability distribution Normal, Log-normal, Gamma and Weibull distribution having two parameters. There is low variation in observed and expected frequency of Normal distribution in bar diagram. Similarly, calculated value of chi-square test (goodness of fit) is observed which is lower in Normal distribution. Furthermore, plot of PDFof Normal distribution covers larger area of histogram than all of other distribution. Hence Normal distribution is the best fit to predict the hemoglobin level in future.

Highlighting the Correlation Between Telomere Shortening and the Susceptibility to the Novel SARS-CoV-2 Virus (COVID-19)

2020 ◽  
Author(s):  
Aml Ghanem
Keyword(s):  
Telomere Length ◽  
Stress Responses ◽  
Viral Infections ◽  
Deep Understanding ◽  
The Elderly ◽  
The Novel ◽  
Telomere Shortening ◽  
Infection Pathways ◽  
And Gender ◽  
Demographic Distribution

COVID-19 is a global crisis that requires a deep understanding of infection pathways to facilitate the development of effective treatments and vaccines. Telomere, which is regarded as a biomarker for other respiratory viral infections, might influence the demographic distribution of COVID-19 infection and fatality rates. Viral infection can induce many cellular remodeling events and stress responses, including telomere specific alterations, just as telomere shortening. In brief, this letter aims to highlight the connection between telomere shortening and susceptibility to COVID-19 infection, in addition to changes in telomeric length according to the variation of age and gender of confirmed cases with COVID-19 infection. To sum up, the correlation is revealed from the available data that connect telomere length and COVID-19 infection, demonstrated in the fact that the elderly patients and males are more susceptible to COVID-19 due to shortening in their telomere length.

Regulation And Effect Of Telomerase And Telomeric Length In Stem Cells

2020 ◽  
Vol 15 ◽  
Author(s):  
Basak Celtikci ◽  
Gulnihal Kulaksiz Erkmen ◽  
Zeliha Gunnur Dikmen
Keyword(s):  
Telomere Length ◽  
Somatic Cells ◽  
Telomere Maintenance ◽  
The Other ◽  
Telomerase Reverse Transcriptase ◽  
Human Telomerase Reverse Transcriptase ◽  
Telomere Shortening ◽  
Maintenance Mechanism ◽  
Associated Diseases ◽  
Human Telomerase

: Telomeres are the protective end caps of eukaryotic chromosomes and they decide the proliferative lifespan of somatic cells, as the guardians of the cell replication. Telomere length in leucocytes reflects telomere length in other somatic cells. Leucocyte telomere length can be a biomarker of human ageing. The risk of diseases, which are associated with reduced cell proliferation and tissue degeneration, including aging or aging-associated diseases, such as dyskeratosis congenita, cardiovascular diseases, pulmonary fibrosis and aplastic anemia, are correlated with an increase in short telomeres. On the other hand, the risk of diseases, which are associated with increased proliferative growth, including major cancers, is correlated with long telomeres. In most of the cancers, a telomere maintenance mechanism during DNA replication is essential. The reactivation of the functional ribonucleoprotein holoenzyme complex [telomerase] starts the cascade from normal and premalignant somatic cells to advanced malignant cells. Telomerase is overexpressed during the development of cancer and embryonic stem cells, through controlling genome integrity, cancer formation and stemness. Cancer cells have mechanisms to maintain telomeres to avoid initiation of cellular senescence or apoptosis, and halting cell division by critically short telomeres. Modulation of the human telomerase reverse transcriptase is the ratelimiting step for the production of functional telomerase and the telomere maintenance. Human telomerase reverse transcriptase promoter promotes its gene expression only in tumor cells, but not in normal cells. Some cancers activate an alternative lengthening of telomeres maintenance mechanism via DNA recombination to unshorten their telomeres. Not only heritability but also oxidative stress, inflammation, environmental factors, and therapeutic interventions have an effect on telomere shortening, explaining the variability in telomere length across individuals. There have been a large number of publications, which correlate human diseases with progressive telomere shortening. Telomere length of an individual at birth is also important to follow up telomere shortening, and it can be used as biomarkers for healthy aging. On the other hand, understanding of cellular stress factors, which affect stem cell behavior, will be useful in regeneration or treatment in cancer and age-associated diseases. In this review, we will understand the connection between stem cell and telomere biology, cancer, and aging-associated diseases. This connection may be useful for discovering novel drug targets and improve outcomes for patients having cancer and aging-associated diseases.

scholarly journals TERRA: A Novel Biomarker of Embryo Quality and Art Outcome

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 475
Author(s):  
Maria Santa Rocca ◽  
Ludovica Dusi ◽  
Andrea Di Nisio ◽  
Erminia Alviggi ◽  
Benedetta Iussig ◽  
...  
Keyword(s):  
Telomere Length ◽  
Dna Sequences ◽  
Male Fertility ◽  
Embryo Quality ◽  
Assisted Reproductive Technologies ◽  
Biological Clock ◽  
Reproductive Technologies ◽  
Age Related ◽  
Non Coding Rna ◽  
First Time

Telomeres are considered to be an internal biological clock, and their progressive shortening has been associated with the risk of age-related diseases and reproductive alterations. Over recent years, an increasing number of studies have focused on the association between telomere length and fertility, identifying sperm telomere length (STL) as a novel biomarker of male fertility. Although typically considered to be repeated DNA sequences, telomeres have recently been shown to also include a long non-coding RNA (lncRNA) known as TERRA (telomeric repeat-containing RNAs). Interestingly, males with idiopathic infertility show reduced testicular TERRA expression, suggesting a link between TERRA and male fertility. The aim of this study was to investigate the role of seminal TERRA expression in embryo quality. To this end, STL and TERRA expression were quantified by Real Time qPCR in the semen of 35 men who underwent assisted reproductive technologies (ART) and 30 fertile men. We found that TERRA expression in semen and STL was reduced in patients that underwent ART (both p < 0.001). Interestingly, TERRA and STL expressions were positively correlated (p = 0.010), and TERRA expression was positively associated with embryo quality (p < 0.001). These preliminary findings suggest a role for TERRA in the maintenance of sperm telomere integrity during gametogenesis, and for the first time, TERRA expression was found as a predictive factor for embryo quality in the setting of assisted reproduction.

scholarly journals A Universal Model for the Log-Normal Distribution of Elasticity in Polymeric Gels and Its Relevance to Mechanical Signature of Biological Tissues

Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 64
Author(s):  
Arnaud Millet
Keyword(s):  
Elastic Modulus ◽  
Normal Distribution ◽  
Biological Tissues ◽  
Force Microscopy ◽  
Polymeric Gels ◽  
Atomic Force ◽  
Clear Explanation ◽  
Log Normal ◽  
Log Normal Distribution

The mechanosensitivity of cells has recently been identified as a process that could greatly influence a cell’s fate. To understand the interaction between cells and their surrounding extracellular matrix, the characterization of the mechanical properties of natural polymeric gels is needed. Atomic force microscopy (AFM) is one of the leading tools used to characterize mechanically biological tissues. It appears that the elasticity (elastic modulus) values obtained by AFM presents a log-normal distribution. Despite its ubiquity, the log-normal distribution concerning the elastic modulus of biological tissues does not have a clear explanation. In this paper, we propose a physical mechanism based on the weak universality of critical exponents in the percolation process leading to gelation. Following this, we discuss the relevance of this model for mechanical signatures of biological tissues.

scholarly journals Natural variation in plant telomere length is associated with flowering time

2021 ◽  
Author(s):  
Jae Young Choi ◽  
Liliia R Abdulkina ◽  
Jun Yin ◽  
Inna B Chastukhina ◽  
John T Lovell ◽  
...  
Keyword(s):  
Life History ◽  
Telomere Length ◽  
Flowering Time ◽  
Dna Sequences ◽  
Genome Wide Association Study ◽  
Genomic Analysis ◽  
Life History Strategies ◽  
Length Variation ◽  
Chromosomal Structure ◽  
Chromosome Integrity

Abstract Telomeres are highly repetitive DNA sequences found at the ends of chromosomes that protect the chromosomes from deterioration during cell division. Here, using whole genome re-sequencing and terminal restriction fragment assays, we found substantial natural intraspecific variation in telomere length in Arabidopsis thaliana, rice (Oryza sativa), and maize (Zea mays). Genome-wide association study (GWAS) mapping in A. thaliana identified 13 regions with GWAS-significant associations underlying telomere length variation, including a region that harbors the telomerase reverse transcriptase (TERT) gene. Population genomic analysis provided evidence for a selective sweep at the TERT region associated with longer telomeres. We found that telomere length is negatively correlated with flowering time variation not only in A. thaliana, but also in maize and rice, indicating a link between life history traits and chromosome integrity. Our results point to several possible reasons for this correlation, including the possibility that longer telomeres may be more adaptive in plants that have faster developmental rates (and therefore flower earlier). Our work suggests that chromosomal structure itself might be an adaptive trait associated with plant life history strategies.

scholarly journals Telomere Shortening and Accelerated Aging in US Military Veterans

2021 ◽  
Vol 18 (4) ◽  
pp. 1743
Author(s):  
Jeffrey T. Howard ◽  
Jud C. Janak ◽  
Alexis R. Santos-Lozada ◽  
Sarah McEvilla ◽  
Stephanie D. Ansley ◽  
...  
Keyword(s):  
Telomere Length ◽  
Military Service ◽  
Accelerated Aging ◽  
Cellular Aging ◽  
Veterans Health ◽  
Cvd Risk ◽  
Base Pairs ◽  
Telomere Shortening ◽  
Race Ethnicity ◽  
Service Data

A growing body of literature on military personnel and veterans’ health suggests that prior military service may be associated with exposures that increase the risk of cardiovascular disease (CVD), which may differ by race/ethnicity. This study examined the hypothesis that differential telomere shortening, a measure of cellular aging, by race/ethnicity may explain prior findings of differential CVD risk in racial/ethnic groups with military service. Data from the first two continuous waves of the National Health and Nutrition Examination Survey (NHANES), administered from 1999–2002 were analyzed. Mean telomere length in base pairs was analyzed with multivariable adjusted linear regression with complex sample design, stratified by sex. The unadjusted mean telomere length was 225.8 base shorter for individuals with prior military service. The mean telomere length for men was 47.2 (95% CI: −92.9, −1.5; p < 0.05) base pairs shorter for men with military service after adjustment for demographic, socioeconomic, and behavioral variables, but did not differ significantly in women with and without prior military service. The interaction between military service and race/ethnicity was not significant for men or women. The results suggest that military service may contribute to accelerated aging as a result of health damaging exposures, such as combat, injury, and environmental contaminants, though other unmeasured confounders could also potentially explain the results.

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