DNA Telomere Length Research Articles

Biomarkers and Redox Balance in Aging Rats after Dynamic and Isometric Resistance Training.

Aging muscle is prone to sarcopenia and its associated telomere shortening and increased oxidative stress. Telomeres are protected by a shelterin protein complex, proteins expressed in response to DNA damage. Aerobic exercise training has shown to positively modulate these proteins while aging, but the effects of resistance training are less clear. This investigation was to examine the role of dynamic and isometric RT on markers of senescence and muscle apoptosis: checkpoint kinase 2, 53 kDa protein, shelterin telomere repeat binding 1 and 2, DNA repair, telomere length and redox state in the quadriceps muscle. Fifteen 49-week-old male rats were divided into three groups: control, dynamic resistance training, and isometric resistance training. Dynamic and isometric groups completed five sessions per week during 16 weeks at low to moderate intensity (20-70% maximal load). Only dynamic group decreased expression of 53 kDa protein, proteins from shelterin complex, oxidative stress, and improved antioxidant defense. There was no difference among groups regarding telomere length. In conclusion, dynamic resistance training was more effective than isometric in reducing markers of aging and muscle apoptosis in elderly rats. This modality should be considered as valuable tool do counteract the deleterious effects of aging.

The association between mitochondrial DNA copy number, telomere length, and tubal pregnancy

Growing evidence has demonstrated association between the occurrence of tubal ectopic pregnancy (TP) and oxidative stress (OS) status, in which mitochondria and telomeres play important roles. However, little is known about the underlying correlation between TP and the mitochondrial DNA copy number (mtDNAcn) or telomere length (TL) abnormalities. In this study, we found OS level was elevated in TP patients. We hierarchically detected the relative mtDNAcn and TL of villi from normal pregnancy (NP) and TP samples according to different gestational age, fetal sex, maternal age, and BMI. The results revealed that the relative mtDNAcn was significantly lower in the villi in the TP group compared with the NP cohort, which was negatively correlated with OS status. In the NP group, the mtDNAcn in the female subgroup was apparently lower than that in the male subgroup, while no statistical difference was found in the mtDNAcn in the TP group between the female and male subgroups. Moreover, the relative TL in the TP group was at a similar level to the NP group, and no statistical correlation was observed between relative TL and OS level. In summary, our findings indicate that the abnormal level of mtDNAcn rather than TL is correlated with TP, which provides new insights into the mechanism of TP.

The role of Rif1 in telomere length regulation is separable from its role in origin firing.

To examine the established link between DNA replication and telomere length, we tested whether firing of telomeric origins would cause telomere lengthening. We found that RIF1 mutants that block Protein Phosphatase 1 (PP1) binding activated telomeric origins but did not elongate telomeres. In a second approach, we found overexpression of ∆N-Dbf4 and Cdc7 increased DDK activity and activated telomeric origins, yet telomere length was unchanged. We tested a third mechanism to activate origins using the sld3-A mcm5-bob1 mutant that de-regulates the pre-replication complex, and again saw no change in telomere length. Finally, we tested whether mutations in RIF1 that cause telomere elongation would affect origin firing. We found that neither rif1-∆1322 nor rif1HOOK affected firing of telomeric origins. We conclude that telomeric origin firing does not cause telomere elongation, and the role of Rif1 in regulating origin firing is separable from its role in regulating telomere length.

Effects of fermented rice bran on DEN-induced oxidative stress in mice: GSTP1, LINE-1 methylation, and telomere length ratio.

N-diethylnitrosamine (DEN), a well-known carcinogen, not only induces excessive reactive oxygen species but also suppresses DNA methylation. This study investigated the effect of fermented rice bran (FRB) treatment on DEN-induced oxidative stress through DNA methylation and telomere length analysis. To evaluate the potential protective role of FRB in oxidative stress, two different doses of FRB, DEN, and their combination were administered to mice that were preadapted or not to FRB. Glutathione-S-transferase P1 (GSTP1) methylation levels significantly decreased at 2 and 24hr after FRB and DEN co-administration in mice with and without pre-adaptation. Moreover, GSTP1 mRNA was upregulated under DEN-induced oxidative stress. Furthermore, changes in long interspersed nuclear element-1 methylation were observed from the viewpoint of genomic instability. In addition, FRB preadapted mice displayed a lower telomere length ratio than the non-adapted mice, suggesting that FRB adaptation offers advantages over the non-adapted conditions in terms of inflammation suppression. PRACTICAL APPLICATIONS: DEN induces excessive ROS, which is associated with oxidative stress on DNA and other cellular components, resulting in inflammation. This study shows that FRB may alleviate DEN-triggered oxidative stress, based on changes in GSTP1, LINE-1 methylation, and telomere length ratios, thereby, revealing the potential of dietary intervention during inflammation. Furthermore, this study furthers the current understanding of DNA methylation mechanisms underlying the antioxidant and anti-inflammatory effects of functional food components. These results indicate that dietary inclusion of FRB may help decrease oxidative DNA damage and its associated inflammation at early stages of a disease.

Aberrant Telomere Length in Circulating Cell-Free DNA as Possible Blood Biomarker with High Diagnostic Performance in Endometrial Cancer.

To investigate the diagnostic performance of relative telomere length (RTL) in cell-free DNA (cfDNA) for endometrioid endometrial cancer (EC). We measured RTL in cfDNA of 40 EC patients (65 ± 12years) and 31 healthy controls (HC) (63 ± 13years), excluding in both groups other oncologic and severenon-oncologic diseases to limit confounders. Circulating cfDNA was extracted from serum using the QIAamp DNA Blood Mini kit (Qiagen, Hilden, Germany). After the quantitative real-time polymerase chain reaction, telomere repeat copy number to single-gene copy number ratio was calculated. RTL in cfDNA was found to be significantly lower in EC patients than in HC (p < 0.0001). The diagnostic performance of cfDNA RTL was estimated with receiver operating characteristics (ROC) curve analysis, which showed a diagnostic accuracy for EC of 0.87 (95% CI: 0.79-0.95, p < 0.0001). The cutoff cfDNA RTL value of 2.505 (T/S copy ratio) reported a sensitivity of 80.0% (95% CI: 64.35-90.95) and a specificity of 80.65% (95% CI: 62.53-92.55). Significant differences of RTL among EC stages or grades (p = 0.85 and p = 0.89, respectively) were not observed. Our results suggest that cfDNA RTL analysis may be a diagnostic tool for EC detection since the early stage, whilst its diagnostic performance seems unsatisfactory for cancer progression, staging, and grading. However, further studies are needed to confirm these preliminary findings. In particular, future investigations should focus on high-risk patients (such as those with atypical endometrial hyperplasia) that may benefit from this tool, because TL shortening is not specific for EC and is influenced by other oncologic and non-oncologic diseases.

A pH-responsive colorimetric detection of human telomerase RNA based on a three-dimensional DNA amplifier

Human telomerase RNA (hTR), one of the essential components of telomerase, serves as a reverse template to add repeated segments of (TTAGGG)n to the 3′ end of telomere DNA for maintaining the length of telomere DNA, endowing cells indefinite proliferation capability. Expression level of hTR displays a close relationship with tumor grade. Inspired by the mechanism of urease hydrolyzing urea to release ammonia and elevate the pH value of the sample solution, we developed a facile and novel pH-responsive colorimetric strategy for hTR detection by incorporating catalyzed hairpin assembly (CHA) onto the magnetic beads (MBs). The CHA process was initiated by target hTR and recycled via toehold binding and branch migration, thereby abundant urease being anchored on the surface of MBs. After separated by an external magnetic field, the assembled urease catalyzed the hydrolysis of urea to release a large amount of ammonia, which gave rise to a remarkable pH signal. Thus, quantification of hTR was achieved by measuring the solution pH via a hand-held pH meter or visualizing the solution color with the assistance of the pH indicator phenol red. The proposed sensing platform exhibits excellent performance toward hTR with a detection limit as low as 41 pM and a remarkable sequence selectivity, being able to differentiate a single mismatch in the target DNA. The pH-responsive colorimetric sensing platform contributes to introducing pH-related portable strategies into the detections of numerous universal biomarkers such as nucleic acids and proteins.

Relationship between sperm telomere length and sperm quality in infertile men

Telomeres, noncoding and repetitive DNA sequences play a significant function in chromatin integrity. Telomere length is age-dependent in somatic cells, while it increases in sperm cell with age. Therefore, we aimed to assess sperm chromatin, leucocyte and sperm telomere length (LTL, STL) in spermatozoon of 38 infertile and 19 fertile men aged between 20 and 50years. Protamine deficiency (chromomycin A3 test), DNA fragmentation (TUNEL assay), lipid peroxidation (Bodipy probe) and telomere length (quantitative real-time PCR) were assessed. A significant decrease in mean of sperm concentration and motility and a significant increase in means of sperm abnormal morphology, DNA fragmentation, lipid peroxidation and protamine deficiency were observed in infertile compared with fertile men. In addition, the mean of LTL and STL were significantly shorter in infertile men compared with fertile individuals. We observed significant associations between telomere length with sperm concentration, DNA fragmentation and lipid peroxidation. We hypothesised that increased oxidative stress in spermatozoa of infertile men can result in abnormal packaging of chromatin, damage of DNA and shorter sperm telomere length. Together, these anomalies may account for fertility failure in these individuals.

Premature ageing following allogeneic hematopoietic stem cell transplantation.

Survivors of hematopoietic cell transplantation (HCT) have been shown to exhibit both clinical and biological features of accelerated ageing. Most studies used frailty measures, comorbidities for clinical assessment and several biological assessment of premature ageing. However, these tests are less suitable for age determination of individual patients. Recently, DNA methylation has emerged as a novel test to measure cellular age. In the present study, we assessed ageing in a cohort of 26 survivors of allogeneic HCT by frailty tests comprising the handgrip and 6 min walk tests and by biological tests including DNA methylation, telomere length and expression of p16INK4A and serum levels of IL-6. DNA methylation was evaluated both in blood and buccal epithelial cells. Physiological reserve was markedly reduced in transplant survivors, reflected by 6 min walk test. Increased IL-6 serum levels and p16ink4A correlated with accelerated ageing. Overall, the measured age of donor blood cells was significantly higher than these blood cells residing in their respective donors, as reflected by DNA methylation and by buccal epithelium methylation status. These clinical and biological observations suggest that allogeneic HCT is associated with accelerated ageing.

Telomere maintenance in interplay with DNA repair in pathogenesis and treatment of colorectal cancer.

Colorectal cancer (CRC) continues to be one of the leading malignancies and causes of tumour-related deaths worldwide. Both impaired DNA repair mechanisms and disrupted telomere length homeostasis represent key culprits in CRC initiation, progression and prognosis. Mechanistically, altered DNA repair results in the accumulation of mutations in the genome and, ultimately, in genomic instability. DNA repair also determines the response to chemotherapeutics in CRC treatment, suggesting its utilisation in the prediction of therapy response and individual approach to patients. Telomere attrition resulting in replicative senescence, simultaneously by-passing cell cycle checkpoints, is a hallmark of malignant transformation of the cell. Telomerase is almost ubiquitous in advanced solid cancers, including CRC, and its expression is fundamental to cell immortalisation. Therefore, there is a persistent effort to develop therapeutics, which are telomerase-specific and gentle to non-malignant tissues. However, in practice, we are still at the level of clinical trials. The current state of knowledge and the route, which the research takes, gives us a positive perspective that the problem of molecular models of telomerase activation and telomere length stabilisation will finally be solved. We summarise the current literature herein, by pointing out the crosstalk between proteins involved in DNA repair and telomere length homeostasis in relation to CRC.

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.

Mutational profiling of POT1 gene and its interaction with TPP1 in cancer- A computational approach

Abstract Telomeres are specialized structures at the end of eukaryotic chromosomes that maintain genomic stability by preventing chromosomal rearrangements and thereby enabling semi-conservative replication of telomeric DNA. The length of telomeric DNA is retained by telomerase that balances between the processes that lengthen and shorten the telomeres. In human chromosomes, six telomere-associated proteins namely- TRF1, TRF2, POT1, RAP1, TIN2, and TPP1 form the shelterin complex, that is essential for maintenance of telomeric integrity. The human POT1 and TPP1 play a major role in protecting the ssDNA overhangs, formed due to the end replication problem. These proteins along with other repair complexes protect the telomere overhangs from cellular repair complexes. However, shelterin functionality can become compromised due to mutations in any of the six genes and can lead to unwarranted repair of the human telomeres. In cancer and transformed cells, telomerase activation replenishes the telomeres while also, recruiting repair proteins at the telomeres. With an aim to evaluate the functional consequence of non-synonymous single nucleotide polymorphisms (nsSNPs) in POT1 gene variants, and resulting changes that affect its interactions with TPP1, this research was carried out using computational tools. The overall outcomes revealed 16 POT1 gene mutations that were likely to impact the protein function. Of these 9 mutations, viz., P357S, H437P, V439G, P475L, G534C, P537S, F566C, M587T, and C591W showed that the altered POT1 function impacted its interaction with TPP1 protein. The binding affinity of POT1 with ssDNA overhangs was also changed. A wet-lab follow-up study using site-directed mutagenesis and yeast hybridization techniques can help exploit underlying mechanisms affecting stable association of these two shelterin components.

Water-soluble oligofluorenes bearing N1-alkylcytosine side chains as turn-on and turn-off materials in telomere DNA length sensing.

Water-soluble cationic and anionic oligofluorenes bearing N1-alkylcytosine side chains, namely OF-1 and OF-2, were synthesized. The photoluminescence (PL) intensity of an aqueous solution of OF-1 decreased on the addition of (TTAGGG)m as telomere DNA models. In contrast, the PL intensity of OF-2 increased on the addition of DNA.

Shortened telomere length is associated with unfair treatment attributed to race in African Americans living in Tallahassee, Florida.

Experiences of interpersonal discrimination are pervasive stressors in the lives of African Americans. Increased discrimination stress may cause premature aging. Telomere length (TL) is a plastic genetic trait that is an emerging indicator of cellular health and aging. Short TL is a risk factor for the earlier onset of disease. TL shortens with age, a process that may be accelerated by psychosocial stress. Our study explores the relationship between TL and experiences of discrimination in the form of self-reported unfair treatment (UT). Using a qPCR-based method, we measured TL in DNA from saliva samples provided by 135 African American adults from Tallahassee, FL. We developed discrimination measures using a modified survey that explores nine social domains of self-reported unfair treatment experienced both directly and indirectly. We used multiple regression to examine associations between UT and TL. We found that racial discrimination in the form of self-reported unfair treatment attributed to race (UT-Race-Self) is inversely associated with TL. The significant association between increased UT-Race-Self and shorter telomeres supports the hypothesis that psychosocial stress stemming from racial discrimination may affect TL. The potential impact of discrimination on TL may contribute to premature biological aging and racial health inequalities seen in African Americans.

The influence of polymorphisms of xenobiotic-metabolizing and DNA repair genes in DNA damage, telomere length and global DNA methylation evaluated in open-cast coal mining workers.

Coal plants represent one of the main sources of environmental pollution due to the combustion process of this mineral and the consequent release of gases and particles which, in significant quantities, can lead to a potential risk to health and the environment. The susceptibility of individuals to the genotoxic effects of coal mining can be modulated by genetic variations in the xenobiotic detoxification and DNA repair processes. The aim of this study was to evaluate if xenobiotic metabolism polymorphism, base excision repair polymorphisms and non-homologous end joining repair polymorphism, could modify individual susceptibility to genomic instability and epigenetic alterations induced in workers by occupational exposure to coal. In this study, polymerase chain reaction was used to examine the polymorphic sites. The sample population comprising 70 coal mine workers and 71 workers non-exposed to coal. Our results demonstrated the effect of individual genotypes on different biomarkers evaluated. Significant decrease in % of global DNA methylation were observed in CYP1A1 Val/- exposed individuals compared to CYP1A1 Ile/Ile individuals. Coal workers who carried the XRCC4 Ile/Ile genotype showed decrease NBUD frequencies, while the XRCC4 Thr/- genotype was associated with decrease in Buccal micronucleus cells for the group not exposed. No influence of GSTM1 null, GSTT1 null, GSTP1 Ile105Val, hOGG1 Ser326Cys, XRCC1 Arg194Trp polymorphisms was observed. Thus, the current study reinforces the importance of considering the effect of metabolizing and repair variant genotypes on the individual susceptibility to incorporate DNA damage, as these processes act in a coordinated manner to determine the final response to coal exposure.

Effects of polycyclic aromatic hydrocarbon exposure and miRNA variations on peripheral blood leukocyte DNA telomere length: A cross-sectional study in Henan Province, China

Telomeres play a major role in human aging and disease, especially in most cancers. Telomere length was shortened in workers exposed to polycyclic aromatic hydrocarbons (PAHs) and influenced by individual genetic variations in telomere-binding proteins. MicroRNAs (miRNAs) can affect the progress of messenger RNA (mRNA) transcription; however, whether polymorphisms in miRNA can act on the telomere length is still unknown. Therefore, we aimed to explore the relationships between telomere damage and genetic polymorphisms in miRNA or environmental exposure. A total of 544 coke oven workers and 238 healthy controls were recruited. After collecting peripheral blood and extracting the genomic DNA of the study subjects, the telomere length (TL) in their leucocytes was detected by a real-time quantitative polymerase chain reaction (PCR), and polymorphisms in miRNAs were genotyped using the flight mass spectrometry technique. The concentrations of the four urine OH-PAHs were determined by high performance liquid chromatography (HPLC), and the Soxhlet extraction method was used to detect the concentration of coke oven emissions (COEs) in the air. We found that the peripheral blood leucocyte DNA TL was significantly shorter in the exposure group (0.75; 0.51, 1.08) than that in the control group (1.05; 0.76, 1.44) (Z = 7.692, P < 0.001). The total cumulative exposure dose (CED), 1-hydroxypyrene, 2-hydroxynaphthalene, and 3-hydroxyphenanthrene were significantly negatively correlated with TL (r = −0.307, P < 0.001; r = −0.212, P < 0.001; r = −0.110, P = 0.025; r = −0.251, P < 0.001, respectively). MiR-145 rs353291 GG, miR-30a rs2222722 CT/CC, and miR-197 rs1889470 AA could protect the telomere end in the exposed workers (P < 0.05). The interaction between miR-197 rs1889470 and the CED had an effect on TL (β = 0.066, P = 0.034). This is the first study to evaluate gene–environmental interactions for miRNA polymorphisms and PAH exposure in coke oven workers.

POT1-TPP1 differentially regulates telomerase via POT1 His266 and as a function of single-stranded telomere DNA length

Telomeres cap the ends of linear chromosomes and terminate in a single-stranded DNA (ssDNA) overhang recognized by POT1-TPP1 heterodimers to help regulate telomere length homeostasis. Here hydroxyl radical footprinting coupled with mass spectrometry was employed to probe protein-protein interactions and conformational changes involved in the assembly of telomere ssDNA substrates of differing lengths bound by POT1-TPP1 heterodimers. Our data identified environmental changes surrounding residue histidine 266 of POT1 that were dependent on telomere ssDNA substrate length. We further determined that the chronic lymphocytic leukemia-associated H266L substitution significantly reduced POT1-TPP1 binding to short ssDNA substrates; however, it only moderately impaired the heterodimer binding to long ssDNA substrates containing multiple protein binding sites. Additionally, we identified a telomerase inhibitory role when several native POT1-TPP1 proteins coat physiologically relevant lengths of telomere ssDNA. This POT1-TPP1 complex-mediated inhibition of telomerase is abrogated in the context of the POT1 H266L mutation, which leads to telomere overextension in a malignant cellular environment.

Telomere erosion in Sjögren's syndrome: A multi-tissue comparative analysis.

Acinar progenitor cells within salivary glands have decreased regenerative capacity and exhibit shorter telomeres in primary Sjögren's syndrome (pSS) patients. We investigated whether DNA of saliva, PBMCs, and labial salivary gland (LSG) biopsy tissue have shorter telomeres in pSS compared to controls. mRNA expression of genes associated with pSS pathogenesis (ETS1, LEF1, and MMP9), telomere DNA damage response (ATM), senescence (CDKN2A), telomerase inhibition (IFN-y, TGFβ1), and the shelterin complex (TPP1, POT1) were assessed in LSG tissue by qRT-PCR to examine potential defects in telomere maintenance. Relative telomere length in DNA of saliva, PBMCs, and LSGs from non-pSS sicca and pSS patients was measured using qPCR. Saliva DNA telomere length was further compared to healthy controls. Expression of genes affecting telomere maintenance was analyzed in LSGs using qRT-PCR. Primary Sjögren's syndrome patients have shorter telomeres in saliva DNA (n=21) than healthy controls (n=27) (P=.0035). ATM mRNA expression was higher in pSS LSG tissue (n=16) vs non-pSS sicca patients (n=13) (P=.0283) and strongly correlated with LEF1, TPP1, and POT1 (P<.01, r>0.6). Patients with pSS exhibited significant telomere erosion in saliva DNA. Overexpression of ATM in LSGs could represent a compensatory response to telomere shortening. The role of LEF1 in telomere erosion remains to be elucidated.

The association between polymorphisms in tankyrase gene and telomere length in omethoate–exposed workers

Peripheral blood leukocyte telomere length in omethoate–exposed workers is related to environmental exposure and single nucleotide polymorphisms (SNPs) in genes including p21, GSTM1, miR-145, etc. However, the roles of SNPs in tankyrase (TNKS) gene in telomere length are still unknown. The aim of this study was to explore the association between SNPs in TNKS gene and telomere length in omethoate–exposed workers. Telomere length in peripheral blood leukocyte DNA from 180 omethoate-exposed workers and 115 healthy controls was measured using Real-time quantitative polymerase chain reaction (PCR). Genotyping of the selected functional and susceptible SNPs was performed by the flight mass spectrometry based on PCR and single-base extension. The analysis of covariance was performed to find effects of SNPs on telomere length. Generalized linear models were used to analyze the environment, gene, and interaction on telomere length. The results showed that telomere length in the CG + CC genotypes in rs1055328 in TNKS gene was significantly longer than that in the wild homozygous GG genotype both in exposure group (P = 0.017) and in control group (P = 0.038) after adjusting the covariates. The variables kept in the generalized linear models included omethoate-exposure (β = 0.580, P = 0.001) and rs1055328 (CG + CC) in TNKS gene (β = 0.339, P = 0.002). The study suggests that the prolongation of telomere length is associated with omethoate-exposure and the CG + CC genotypes in rs1055328 in TNKS gene.

Shorter telomere length of white blood cells is associated with higher rates of aneuploidy in women undergoing in vitro fertilization

Telomeres are tandem repeats of the sequence TTAGGG located at the ends of chromosomes. Telomere shortening is a key mechanism of cell senescence and aging. Telomere shortening has been associated with decreased oocyte quality through disruption of chromosome alignment and spindle structure. In this study, we sought to evaluate whether the telomere length of cumulus cells (CC) or white blood cells (WBC) in an infertile population is associated with reproductive aging. Prospective cohort study. Women undergoing IVF between July 2017 and December 2018 were recruited for the study under Institutional Review Board approval. Blood and CC were collected at the time of oocyte retrieval. Genomic DNA was isolated and stored at -80°C. Telomere DNA length was measured by quantitative real-time PCR and normalized to AluYa5 sequence as an endogenous control for each sample. Linear regression was applied to determine if telomere length (TL) of WBC or CC was associated with patient age, number of oocytes retrieved, number of mature (M2) oocytes retrieved, blastulation rate, aneuploidy rate, serum anti-mullerian hormone (AMH), and serum estrogen (E2) level on day of hCG or GnRHa administration. TL data was available for WBC samples from 156 individuals and for CC samples from 142 patients. Data was available for both tissue types in 139 patients (age range 25.7 to 45.0 years, mean 35.0 ± 4.0 years). As expected, WBC telomere length declined with increasing age (p=0.006). In contrast, CC TL was equivalent in patients of all ages and failed to show anticipated age-related shortening. As such, CC TL was unrelated to any index of ovarian performance including number of oocytes retrieved (p=0.95), M2 oocytes retrieved (p=0.81), blastulation rate (p=0.98), aneuploidy rate (p=0.30), AMH level (p=0.32), or mid-cycle E2 level (p=0.77). Consistent with these data, CC TL was not associated with patient age (p=0.99). While WBC TL declined with increasing maternal age, it was a poor predictor of quantitative ovarian performance [total oocytes retrieved (p=0.47), number of M2 oocytes retrieved (p=0.30), AMH level (p=0.13), E2 level (p=0.36), and blastulation rate (p=0.48)]. However, TL of WBC samples was associated with embryonic competence as evidenced by aneuploidy rate (p=0.02), with shorter TL associated with higher aneuploidy. The TL of CC was not associated with patient age or any index of ovarian or embryonic performance. Declining WBC TL was associated with increasing maternal age and increasing rates of embryonic aneuploidy. Further studies are necessary to determine if changes in peripheral somatic cell TL are truly prognostic for aneuploidy rate within a given maternal age group or if this finding is simply reflective of a simultaneous change which occurs with age.

Telomere length in workers was effected by omethoate exposure and interaction between smoking and p21 polymorphisms

Omethoate is an organophosphorus pesticide that poses a major health hazard, especially DNA damage. The purpose of this study was to investigate the factors affecting telomere length in workers exposed to omethoate by analyzing the interaction between cell cycle gene polymorphism and environmental factors. The exposure group consisted of 118 workers exposed to omethoate for 8–10 years, the control group comprised 115 healthy people without occupational toxicant exposure history. The telomere length of genomic DNA from peripheral blood leucocyte was determined with real-time PCR. Polymerase chain reaction and restriction fragment length polymorphism was used to detect the polymorphisms in p53, p21 and MDM2 gene. The telomere length in the (CA + AA) genotypes for p21 rs1801270 polymorphism was longer than that in the CC genotype in control group (P = 0.015). The generalized linear model analysis indicated the interaction of the p21 rs1801270 polymorphic (CA + AA) genotypes and smoking has a significant effect on telomere length (β = −0.258, P = 0.085). The prolongation of telomere length in omethoate-exposed workers was associated with genotypes (CA + AA) of p21 rs1801270, and interactions of (CA + AA) genotypes and smoking factor.