Relative Telomere Length Research Articles

Abstract P144: The Modification Effect of Genetic Variants on the Association Between Dietary Red Meat Intake and Telomere Length

Background: Telomeres are repetitive nucleotide sequences (TTAGGG) combined with associated protein at the end of eukaryote chromosomes. They shorten with each cell division and thus can act as a biomarker of cellular aging. Many factors can influence telomere length, including nutrition, physical activity and other lifestyle factors. However, the effects of diet, such as consumption of red meat on telomere length, is controversial. In East-Asians, the effect of red meat on telomeres as well as the modification effect of red meat on the association between genetic variants and telomeres are largely unknown. Method: Study included 20,011 individuals with complete information. Relative telomere length was determined using monochrome multiplex quantitative PCR (qPCR) and expressed as T/S ratio from 20,011 participants of the prospective Singapore Chinese Health Study (SCHS) Dietary information was collected using a semi-quantitative food frequency questionnaire. Red meat consumption was first adjusted for total energy intake by linear regression and then dichotomized based on median value. Telomere length was standardised by z score transformation. Linear regression was used to test the association between telomere length and red meat consumption. Interaction analyses were performed by introducing the interaction term (red meat x SNP) in the same regression model with adjustment for age, gender, total energy intake and population structure as covariates. Result: Higher intake of red meat was significantly associated with longer telomere length in SCHS (β = 0.027, se = 0.013, p = 0.042). Red meat intake can modify the association between rs7536250 and telomere length (β = -0.170, se = 0.025, p int = 1.35 х 10 -11 ). Rs7536250 was intergenic and found to affect the expression level of several genes through expression quantitative trait loci (eQTL), some of which are known to be involved in T-cell activation, apoptosis and programmed cell death. Conclusion: The association between red meat intake and telomeres is consistent with some previous findings. We also found that genetic variant can modify the association between dietary red meat intake and telomere length.

Association between Leucocyte Telomere Length and Risk of Hearing Loss in the General Population: A Case-Control Study in Zhejiang Province, China.

Limited studies have assessed the relation between telomere length and risk of hearing loss; moreover, they have reported equivocal associations. In the first case-control study, the subjects were chosen from the general population of Zhejiang province in order to assess the association between leucocyte telomere length and risk of hearing loss from 2016 to 2018. A total of 817 cases (55.93 ± 8.99 years) and 817 age-, sex- and residential city-matched controls (55.91 ± 9.03 years) were included for analysis. In the multivariable models, individuals in the top quartile of relative telomere length (RTL) had an odds ratio (OR) for hearing loss of 0.53 (95% confidence intervals [CI], 0.38–0.74) compared to those in the bottom quartile, and specifically, the OR was 0.45 (95% CI, 0.28–0.73) in females. In females, the risk of hearing loss decreased by 46% as RTL doubling increased; the standard deviation of RTL was associated with a 29% decrease in hearing loss risk. Additional analysis showed significant difference between participants in the female mild hearing loss group and corresponding controls. These results suggest that telomere length is associated with hearing loss in the general population, particularly in females with mild hearing loss. Telomere length might be a potential predictive biomarker of hearing loss at early stage.

Physical Activity and Telomeres in Old Age: A Longitudinal 10-Year Follow-Up Study

Background:Telomeres are crucial parts of chromosomes that protect the genome. They shorten every time the cell replicates, and shorter telomeres have been associated with increasing age and with many health behaviours. There is inconclusive evidence on the association between physical activity (PA) and telomere length. Objectives: To examine how leisure-time PA (LTPA) is associated with telomere length and telomere attrition during 10 years of follow-up in elderly people. Design: This study is a 10-year prospective follow-up study. Method: For this prospective study, we examined 1,014 subjects (mean age at baseline 60.8 years) from the Helsinki Birth Cohort Study (HBCS). Relative leukocyte telomere length (LTL) was measured with a quantitative real-time PCR and LTPA with a validated questionnaire. Multiple linear regression analyses were used to assess the association between sex-specific LTPA quartiles and LTL at baseline and change in LTL over 10 years. The analyses were adjusted for age, educational attainment, smoking, body fat percentage, oestrogen exposure in women and for follow-up time when applicable. Results: At baseline, volume of LTPA was not associated with LTL in men (p = 0.66) or in women (p = 0.33). Among women, however, higher volume of LTPA at baseline was associated with greater shortening of LTL (p for linearity 0.040) during the 10-year follow-up. No association was found among men (p for linearity 0.75). Conclusions: Our findings suggest that PA has a sex-specific role in regulation of telomere length in the aging process as in our study a high volume of LTPA in elderly women, but not in men, was associated with more rapid telomere attrition.

Patterns of change in telomere length over the first three years of life in healthy children

There is growing interest in the use of telomere length as a biomarker of health and a predictor of later morbidity and mortality. However, little is known about developmentally expected telomere erosion over the first years of life. This gap hinders our ability to interpret the meaning of relative telomere length and rate of attrition in relation to risk factors and health outcomes. The overall goal of this study was to examine the rate of relative telomere length attrition in a large, normative sample of healthy children (N = 630) followed from infancy to three years of age. A secondary goal was to explore associations between sociodemographic characteristics and telomere erosion over this time period. Relative telomere length was assessed from DNA in saliva samples collected in infancy (M = 8.6 months), age 2 years (M = 25.2 months), and age 3 years (M = 38.3 months). In the sample as a whole, relative telomere length decreased from infancy to 2 years but remained stable from 2 years to 3 years. Notably, increases in relative telomere length were observed in 29 % of children between infancy and 2 years of age and in 46 % of children between 2 and 3 years of age; 62 % of children showed both increases and decreases in relative telomere length across the study period. Females showed longer relative telomere length than males, regardless of timepoint. There was some evidence that parental age and family finances were associated with changes in child relative telomere length across time. Overall, the findings suggest that telomere length attrition is not uniform across the early years of life, with the most rapid attrition occurring during the first two years, and that increases as well as decreases in telomere length during this period are commonly observed.

Faster and Healthier: Relationship between Telomere and Performance in Master Athletes.

Aging is associated with increased oxidative stress, chronic inflammation, and decreased telomere length (TL). However, the lifestyle of master athletes can lead to a reduced risk of these conditions, and thus attenuates aging and performance deterioration. We aimed to analyze the relationships between TL and relative performance (RP), and their relation to adiposity, oxidative stress, and inflammation in endurance (END) and sprint/power (SPW) master athletes (MAs). Twenty-two world-class MAs visited the laboratory for anamnesis, anthropometrics, and blood sampling. Inflammatory and oxidative stress parameters were assessed using commercial kits. Relative TL was determined in leukocytes through qPCR analyses. A positive association was observed between RP and TL in both groups (SPW: r=0.641; END: r=0.685) and the whole sample (r=0.594). The IL6/IL10 ratio presented an inverse correlation with RP in the whole sample (r=-0.580). Body mass index also demonstrated a negative correlation with TL for the END group (r=-0.690) and the whole sample analysis (r=-0.455). Moreover, the IL6/IL10 ratio was negatively associated with strength/power training hours (r=-0.464), whereas the CAT/TBARS ratio was negatively associated with aerobic training hours (r=-0.482). In conclusion, TL of MAs was associated with RP regardless of the training model (endurance or sprint/power), and inflammation and adiposity were associated with shorter telomeres.

Perinatal taurine exerts a hypotensive effect in male spontaneously hypertensive rats and down‐regulates endothelial oxide nitric synthase in the aortic arch

Essential hypertension is considered to be a result of the interaction between genetic and environmental factors, including perinatal factors. Different advantageous perinatal factors proved to have beneficial long-lasting effects against an abnormal genetic background. Taurine is a ubiquitous sulphur-containing amino acid present in foods such as seafood. The antihypertensive effects of taurine have been reported in experimental studies and in human hypertension. We aimed to investigate the effects of perinatal treatment with taurine in spontaneously hypertensive rats (SHR), a known model of genetic hypertension. Female SHR were administered with taurine (3g/L) during gestation and lactation (SHR-TAU). Untreated SHR and Wistar-Kyoto rats (WKY) were used as controls. Long-lasting effects in offspring were investigated. Addition of taurine to the mother's drinking water reduced blood pressure in adult offspring. No differences were observed in cardiac hypertrophy. Findings on morphometric evaluations suggest that perinatal treatment with taurine would be partially effective in improving structural alterations of the aorta. Modifications in gene expression of Bcl-2 family members and upregulation of endothelial nitric oxide synthase in the aorta of 22-week-old male offspring were found. No differences were observed on relative telomere length in different cardiovascular tissues between SHR and SHR-TAU. Altogether results suggest that taurine programming, albeit sex specific, is associated with gene expression changes which ultimately may lead to improvement of aortic remodelling and enhanced endothelial function because of augmented nitric oxide (NO) production.

Association between shorter leukocyte telomeres and multiple sclerosis

Relative telomere length (TL) is regarded as a biomarker of biological age. Accelerated immune aging, as represented by TL reduction, has been demonstrated in autoimmune diseases, including multiple sclerosis (MS). However, it is still unresolved whether telomere shortening is the cause or the consequence of the pathogenic events underlying autoimmunity.Assessing TL in whole blood DNA samples in 138 MS patients and 120 healthy controls showed reduced TL in patients as compared with controls There seems to be a prelude of accelerated telomere shortening, which may increase the risk for development of MS.

Mitochondria and aging in older individuals: an analysis of DNA methylation age metrics, leukocyte telomere length, and mitochondrial DNA copy number in the VA normative aging study.

Population aging is a looming global health challenge. New biological aging metrics based on DNA methylation levels have been developed in addition to traditional aging biomarkers. The prospective relationships of aging biomarkers with mitochondrial changes are still not well understood. Here, we examined the prospective associations of mitochondrial copy number (mtDNAcn) with several aging biomarkers – DNAm-Age, DNAm-PhenoAge, DNAm-GrimAge, and leukocyte telomere length. We analyzed 812 individuals from Veteran Affairs Normative Aging Study (NAS) with available blood samples from 1999-2013. Whole blood mtDNAcn and relative leukocyte telomere length were measured via qPCR. DNA methylation was assessed and used to calculate DNAm-Age, DNAm-GrimAge, and DNAm-PhenoAge. Linear mixed models were used to quantify the associations of mtDNAcn with DNAm-Age, DNAm-GrimAge, DNAm-PhenoAge, and leukocyte telomere length. In multivariable cross-sectional analyses, mtDNAcn is negatively associated with DNAm-Age PhenoAge and DNAm-PhenoAge. In contrast, mtDNAcn is associated with prospective measures of higher DNAm-PhenoAge and shorter leukocyte telomere length. Our study shows that higher mtDNAcn is associated with prospective measures of greater DNAm-PhenoAge and shorter leukocyte telomere length independent of chronological age. This indicates a role for mitochondrial in aging-related disease and mortality, but not the departure of biological age from chronological age.

A Truncating Germline Mutation of TINF2 in Individuals with Thyroid Cancer or Melanoma Results in Longer Telomeres.

Background: Our genome sequencing analysis revealed a frameshift mutation in the shelterin gene TINF2 in a large family with individuals affected with papillary thyroid carcinoma (PTC) and melanoma. Here, we further characterized the mutation and screened for coding variants in the 6 shelterin genes in 24 families. Methods: Sanger sequencing was performed to screen for the TINF2 mutation in the key family. Quantitative reverse transcription-polymerase chain reaction (PCR) was used for TINF2 gene expression analysis. Exogenous expression and co-immunoprecipitation techniques were used for assessing TINF2 binding to TERF1. Relative telomere length (RTL) was quantified in DNAs from lymphocytes by using quantitative real-time PCR. Whole exome sequencing (WES) was performed in seven families with individuals affected with PTC and other cancer types. Screening for DNA variants in shelterin genes was performed by using whole genome sequencing data from 17 families and WES data from 7 further families. Results: The TINF2 mutation (TINF2 p.Trp198fs) showed complete co-segregation with PTC and melanoma in the key family. The mutation is not reported in databases and not identified in 23 other families we screened. The expression of TINF2 was borderline reduced in individuals with the mutation. The truncated TINF2 protein showed abolished binding to TERF1. The RTL in the individuals with the mutation was significantly longer when compared with those without the mutation from the same family as well as compared with 62 healthy controls. Among the 24 families, we identified 3 missense and 1 synonymous variant(s) in 2 shelterin genes (TINF2 and ACD). Conclusions: The rare frameshift mutation in the TINF2 gene and the associated longer telomere length suggest that dysregulated telomeres could be a mechanism predisposing to PTC and melanoma. DNA coding variants in shelterin genes are rare. Further studies are required to evaluate the roles of variants in shelterin genes in thyroid cancer and melanoma.

Protective role of selenium in the shortening of telomere length in newborns induced by in utero heavy metal exposure

The effects of toxic heavy metals, such as arsenic (As), cadmium (Cd), and lead (Pb), on telomere length (TL) have been reported previously. Although selenium (Se) is considered as an anti-oxidant which may detoxify the effects, there are no data on whether Se could protect against the TL-shortening effects of heavy metals. Thus, the aim of this study was to evaluate the protective role of Se against heavy metal-induced TL shortening. A birth cohort study was conducted in Myanmar in 2016, including 408 mother-infant pairs. First, pregnant women in the third trimester were interviewed concerning their socioeconomic, and pregnancy and birth characteristics using a pre-validated questionnaire. Maternal spot urine samples were collected after the interview. During the follow-up period (1–3 months), blood samples were collected from the umbilical cord at birth by local health workers. Metal concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS). TL was measured by quantitative real-time polymerase chain reaction (PCR). Relative TL was calculated as the ratio of telomere genes to single-copy genes. To evaluate the effect of Se on TL shortening, molar ratios were calculated. Linear regression analyses were performed to examine the associations between heavy metals and TL, individually and after adjustment for Se level. The effects of As, Cd, and Pb exposure on TL were smaller after adjustment for the Se level, especially for Pb (unadjusted β = −0.10; 95% CI: 0.18, −0.01; adjusted β = −0.03; 95% CI: 0.13, 0.05). On stratifying the data by Se concentration, there was no significant association between Cd or Pb exposure and TL in the high-Se group. Our study indicated a protective effect of Se against the TL shortening induced by heavy metal exposure, where the effect sizes were smaller after adjusting for the Se level, compared to individual metal exposure.

Yogurt and Streptococcus thermophilus metabolites ameliorated telomere attrition in D‐galactose‐induced ageing mice and t‐BHP‐challenged HepG2 cells

SummaryAntioxidant‐rich diets affect telomere length, an integrative marker associated with age‐related diseases. Yogurt exerts antioxidative capacity and is speculated to support healthy ageing. However, direct experimental evidence is missing. Here, the effects of yogurt and dairy‐fermenting bacteria on D‐galactose‐induced ageing mice and chemically challenged HepG2 cells were evaluated. Relative telomere length (RTL) in leucocyte and liver were significantly longer in yogurt (1.21 ± 0.07; 1.23 ± 0.11) and Streptococcus thermophilus group (1.18 ± 0.15; 1.13 ± 0.12). When t‐BHP‐challenged HepG2 cells were treated with digested yogurt and S. thermophilus, the senescence index (13.67 ± 3.30; 19.67 ± 2.87) were lower and RTL (1.25 ± 0.11; 1.18 ± 0.10) were longer than the model. Antioxidative effects were observed for yogurt and S. thermophilus metabolites, whereas milk and Lactobacillus rhamnosus metabolites showed minimal influence on RTL and oxidative stress. In conclusion, this study showed that yogurt and S. thermophilus metabolites ameliorated telomere attrition in ageing mice and t‐BHP‐challenged HepG2 cells, possibly by reducing oxidative stress.

Exceptionally Long-Lived Individuals (ELLI) Demonstrate Slower Aging Rate Calculated by DNA Methylation Clocks as Possible Modulators for Healthy Longevity.

Exceptionally long-lived individuals (ELLI) who are the focus of many healthy longevity studies around the globe are now being studied in Israel. The Israeli Multi-Ethnic Centenarian Study (IMECS) cohort is utilized here for assessment of various DNA methylation clocks. Thorough phenotypic characterization and whole blood samples were obtained from ELLI, offspring of ELLI, and controls aged 53–87 with no familial exceptional longevity. DNA methylation was assessed using Illumina MethylationEPIC Beadchip and applied to DNAm age online tool for age and telomere length predictions. Relative telomere length was assessed using qPCR T/S (Telomere/Single copy gene) ratios. ELLI demonstrated juvenile performance in DNAm age clocks and overall methylation measurement, with preserved cognition and relative telomere length. Our findings suggest a favorable DNA methylation profile in ELLI enabling a slower rate of aging in those individuals in comparison to controls. It is possible that DNA methylation is a key modulator of the rate of aging and thus the ELLI DNAm profile promotes healthy longevity.

Relative telomere length and mitochondrial DNA copy number variation with age: Association with plasma folate and vitamin B12

Telomere attrition and mitochondrial DNA variations are implicated in the biological aging process and genomic stability can be influenced by nutritional factors. This study aims to analyze the relative telomere length (rTL) and mitochondrial DNA copy number (mtCN) in aged individuals and their association with plasma folate and vitamin B12 levels. This community-based cross-sectional study involves 428 subjects (<60 years: 242 & ≥60 years: 186). Quantitative real-time PCR was used to measure rTL and mtCN variation, and radioimmunoassay to measure plasma folate and vitamin B12 levels. The subjects in the ≥60 years age group have significantly shorter telomeres and lower mtCN compared to the <60 years age group. A significant positive correlation was observed between the rTL and mtCN, and both of them were positively associated with plasma folate and vitamin B12 levels. In the ≥60 age group; folate and vitamin B12 positively correlated with rTL and vitamin B12 with mtCN. The study revealed a decline of rTL and mtCN with age in the Indian population and their association suggests that they may co-regulate each other with age. In conclusion, folate and vitamin B12 may delay aging by preventing the reduction in rTL length and mtCN.

Association between coffee drinking and telomere length in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Mounting evidence indicates that coffee, a commonly consumed beverage worldwide, is inversely associated with various chronic diseases and overall mortality. Few studies have evaluated the effect of coffee drinking on telomere length, a biomarker of chromosomal integrity, and results have been inconsistent. Understanding this association may provide mechanistic insight into associations of coffee with health. The aim of our study was to test the hypothesis that heavier coffee intake is associated with greater likelihood of having above-median telomere length. We evaluated the cross-sectional association between coffee intake and relative telomere length using data from 1,638 controls from four previously conducted case-control studies nested in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Coffee intake was assessed using a food frequency questionnaire, and relative telomere length was measured from buffy-coat, blood, or buccal cells. We used unconditional logistic regression models to generate multivariable-adjusted, study-specific odds ratios for the association between coffee intake and relative telomere length. We then conducted a random-effects meta-analysis to determine summary odds ratios. We found that neither summary continuous (OR = 1.01, 95% CI = 0.99–1.03) nor categorical (OR <3 cups/day vs. none = 1.37, 95% CI = 0.71–2.65; OR ≥3 cups/day vs. none = 1.47, 95% CI = 0.81–2.66) odds ratio estimates of coffee drinking and relative telomere length were statistically significant. However, in the largest of the four contributing studies, moderate (<3 cups/day) and heavy coffee drinkers (≥3 cups/day) were 2.10 times (95% CI = 1.25, 3.54) and 1.93 times as likely (95% CI = 1.17, 3.18) as nondrinkers to have above-median telomere length, respectively. In conclusion, we found no evidence that coffee drinking is associated with telomere length. Thus, it is unlikely that telomere length plays a role in potential coffee-disease associations.

Aerobic capacity and telomere length in human skeletal muscle and leukocytes across the lifespan.

A reduction in aerobic capacity and the shortening of telomeres are hallmarks of the ageing process. We examined whether a lower aerobic capacity is associated with shorter TL in skeletal muscle and/or leukocytes, across a wide age range of individuals. We also tested whether TL in human skeletal muscle (MTL) correlates with TL in leukocytes (LTL). Eighty-two recreationally active, healthy men from the Gene SMART cohort (31.4±8.2 years; body mass index (BMI)=25.3±3.3kg/m2), and 11 community dwelling older men (74.2±7.5years-old; BMI=28.7±2.8kg/m2) participated in the study. Leukocytes and skeletal muscle samples were collected at rest. Relative telomere length (T/S ratio) was measured by RT-PCR. Associations between TL, aerobic capacity (VO2 peak and peak power) and age were assessed with robust linear models. Older age was associated with shorter LTL (45% variance explained, P<0.001), but not MTL (P= 0.7). Aerobic capacity was not associated with MTL (P=0.5), nor LTL (P=0.3). MTL and LTL were correlated across the lifespan (rs=0.26, P=0.03). In healthy individuals, age explain most of the variability of LTL and this appears to be independent of individual aerobic capacity. Individuals with longer LTL also have a longer MTL, suggesting that there might be a shared molecular mechanism regulating telomere length.

DNA methylation levels and telomere length in human teeth: usefulness for age estimation.

In the last decade, increasing knowledge of epigenetics has led to the development of DNA methylation-based models to predict age, which have shown high predictive accuracy. However, despite the value of teeth as forensic samples, few studies have focused on this source of DNA. This study used bisulfite pyrosequencing to measure the methylation levels of specific CpG sites located in the ELOVL2, ASPA, and PDE4C genes, with the aim of selecting the most age-informative genes and determining their associations with age, in 65 tooth samples from individuals 15 to 85years old. As a second aim, methylation data and measurements of relative telomere length in the same set of samples were used to develop preliminary age prediction models to evaluate the accuracy of both biomarkers together and separately in estimating age from teeth for forensic purposes. In our sample, several CpG sites from ELOVL2 and PDE4C genes, as well as telomere length, were significantly associated with chronological age. We developed age prediction quantile regression models based on DNA methylation levels, with and without telomere length as an additional variable, and adjusted for type of tooth and sex. Our results suggest that telomere length may have limited usefulness as a supplementary marker for DNA methylation-based age estimation in tooth samples, given that it contributed little improvement in the prediction errors of the models. In addition, even at older ages, DNA methylation appeared to be more informative in predicting age than telomere length when both biomarkers were evaluated separately.

Association of Relative Leucocyte Telomere Length and Gene Single Nucleotide Polymorphisms (TERT, TRF1, TNKS2) in Laryngeal Squamous Cell Carcinoma.

The study aimed to evaluate associations of relative leukocyte telomere length (LTL) and polymorphisms of telomere length-associated genes TERT (rs2736098), TERT-CLPTM1L (rs401681), TRF1 (rs1545827, rs10107605) and TNKS2 (rs10509637, rs10509639) in patients with laryngeal squamous cell carcinoma (LSCC). The study consisted of 300 patients with LSCC and 369 healthy control subjects. Genotyping and relative LTL measuring were carried out using qPCR. Relative LTL was statistically significantly shorter in the G3 (tumor differentiation grade) subgroup of patients with LSCC compared to the G1 and G2 subgroups. Significant differences were found in genotype distributions of TERT rs401681 and TNKS2 rs10509639 between the study groups. TERT rs401681 C/T and T/T genotypes were associated with approximately 30% decreased odds of LSCC development. LTL was shorter in the G3 subgroup compared to the G2 and G1 subgroups of LSCC patients. TERT rs401681 and its C/T and T/T genotypes were associated with decreased odds of overall LSCC development.

Telomere length and 8-hydroxy-2-deoxyguanosine as markers for early prediction of Alzheimer disease.

Background:Becoming shorter by each cell division, telomere length (TL) is regarded as a marker of cellular aging. Relative TL (T/S) depends on the quantitation of telomere hexamer repeat copy number normalized to autosomal single-copy gene copy number. TL is influenced by several factors, including oxidative stress (OS) and inflammation. This study aimed to investigate the possible role of TL and OS as markers for Alzheimer's disease (AD).Materials and Methods:One hundred and eighty participants were categorized into three groups. Group 1: Included 60 patients with AD. Group II: included 60 age-matched nondemented subjects. Group III (pregeriatric group): included 60 healthy controls with their ages ranging between 30 and 60 years. TL was determined by the quantitative Real time-PCR method, plasma levels of 8-OHdG by enzyme-linked immunosorbent assay, and total antioxidant capacity (TAC) by colorimetery.Results:In comparison to the other two groups, patients with AD showed shortened TL, increased plasma 8-OHdG concentration, and decreased TAC. The sensitivity of T/S ratio to predict AD was 86.67%, whereas the specificity was 96.67%. The sensitivity of 8-OHdG to predict AD was 96.67%, whereas the specificity was 86.67%.Conclusion:AD is associated with shortened TL and increased OS as manifested by decreased TAC and increased serum 8-OHdG. T/S and 8-OHdG could be used as early predictors for AD.

Alterations in telomere length and mitochondrial DNA copy number in human lymphocytes on short-term exposure to moderate hypoxia

Hypoxia is related to a variety of diseases, such as cardiovascular and inflammatory diseases and various cancers. Telomere length (TL) may vary according to the hypoxia level and cell types. To the best of our knowledge, no study has investigated the effect of moderate hypoxia on TL and mitochondrial DNA copy number (mtDNAcn) in human lymphocytes. Therefore, in this study, we analyzed the effect of moderate hypoxia on TL in correlation with mtDNAcn. This study included 32 healthy male nonsmoker’s subjects; in this cohort, we had previously studied sister chromatid exchange and microsatellite instability. Blood samples from each subject were divided into three groups: a control group and two experimental groups exposed to moderate hypoxia for 12 or 24 h. Relative TL and mtDNAcn were measured by a quantitative real-time polymerase chain reaction. The TL in the control group did not significantly differ from that in the experimental group subjected to hypoxia for 12 h; however, the TL in the 24 h hypoxia–treated experimental group was significantly higher than that in the control group. The correlation between TL and mtDNAcn was not statistically significant in the two hypoxic states. The increase in TL was observed on exposure to hypoxia for 24 h and not for 12 h; thus, the findings suggest that telomere elongation is related to hypoxia exposure duration. The mtDNAcn in the two experimental groups did not significantly differ from that in the control group. These observations suggest that mtDNAcn alterations show more genetic stability than TL alterations. To the best of our knowledge, this is the first in vitro study on human lymphocytes reporting an increase in TL and no alteration in mtDNAcn after short-time exposure to moderate hypoxia.

Association of Leukocyte Telomere Length and Genes Involved in its Regulation With Oral Carcinoma.

This study aimed to determine the relationship between the relative leukocyte telomere length (RLTL) and gene polymorphisms involved in its regulation with the occurrence of oral squamous cell carcinoma (OSCC). Patients with OSCC and healthy subjects were examined. Genotyping and RLTL measurement were carried out using rPCR. The OSCC group had longer telomeres than controls (p=0.001). Minor allele T at TERF1rs1545827 may increase RLTL shortening (p=0.047). TNKS2rs10509639 A/G and A/G+G/G genotypes were associated with a 2.6-fold increased odd (p=0.012) and a 2.4-fold increased odd (p=0.019) of RLTL elongation compared to A/A genotype. The A/G genotype was associated with a 2.6-fold increased odd (p=0.011) compared to the A/A+G/G genotypes. Each G allele was associated with a 2.1-fold increased odd of longer RLTL (p=0.036). Longer telomeres were found in patients with OSCC than in controls. The TERF1 rs1545827 and the TNKS2 rs10509639 polymorphisms were associated with an increase in RLTL.