Significant Difference In Telomere Length Research Articles

Reduced T-Cell Thymic Export Reflected by sj-TREC in Patients with Coronary Artery Disease.

Immunologic dysfunction was recently found to be one of the most important mechanisms underlying the initiation and development of atherosclerosis. Thymus involution can contribute to immune disturbance and disequilibrium of T-cell subsets. This study aimed to explore whether recent thymic emigration (RTE) is impaired in patients with coronary artery disease (CAD). Content of signal-joint T cell receptor excision circles (sj-TREC) in T lymphocytes, a molecular marker of RTE, was assessed among CAD patients and age-matched controls. Monochrome multiplex quantitative PCR method was used to assess the samples' telomere length in order to exclude the potential influence of T cell proliferation on the dilution of sj-TREC. Patients were grouped according to Gensini score (GS) (low, GS ＜18; intermediate, GS 18-41; high, GS ＞41). Ordinary logistic regression models were used to determine potential risk factors for CAD and GS tertiles. Average copy numbers of sj-TREC per 10(6) T lymphocytes among patients with unstable angina, stable angina, and controls were 726±429, 1213±465, and 1795±838, respectively (P＜0.001). However, there was no significant difference in telomere length among groups. Moreover, the content of sj-TREC in the high GS group was most significantly reduced than the low GS group (P＜0.001). Multivariate logistic regression analysis revealed that lower sj-TREC was independently associated with the progression of CAD (OR=0.44, P＜0.001) and higher GS (OR=0.4, P＜0.001). Impaired RTE could be partly responsible for CAD development. Mechanisms may be involved in the disturbance of T lymphocyte compartment and interruption of maintained immune tolerance resulting from thymus involution.

Chronic and acute effects of endurance training on telomere length.

Telomere shortening is considered a cellular marker of health status and biological ageing. Exercise may influence the health and lifespan of an individual by affecting telomere length (TL). However, it is unclear whether different endurance exercise levels may have beneficial or detrimental effects on biological aging. The aims of the study were to assess both chronic and acute effects of endurance training on TL after an exceptional and extreme trail race. TL was assessed in 20 endurance athletes (17 males; age = 45.4 ± 9.2 years) and 42 age- and gender-matched sedentary controls (32 males; age = 45.9 ± 9.5 years) with quantitative real-time PCR at baseline conditions. Of the 20 runners enrolled in the 'Tor des Géants ®' ultra-distance trail race, 15 athletes (12 males; age = 47.2 ± 8.5 years) were re-evaluated at the intermediate point and 14 athletes (11 males; age = 47.1 ± 8.8 years) completed the competition and were analysed at the final point. Comparison between the two groups (endurance athletes vs. sedentary controls) revealed a significant difference in TL (1.28 ± 0.4 vs. 1.02 ± 0.3, P = 0.005). TL was better preserved in elder endurance runners compared with the same age control group (1.3 ± 0.27 vs. 0.91 ± 0.21, P = 0.003). TL was significantly reduced at the intermediate (0.88 ± 0.36 vs. 1.11 ± 0.34, P = 0.002) and final point compared with baseline measurements (0.86 ± 0.4 vs. 1.11 ± 0.34, P = 0.0006) for athletes engaged in the ultra-marathon race. Our data suggest that chronic endurance training may provide protective effects on TL attenuating biological aging. Conversely, acute exposure to an ultra-distance endurance trail race implies telomere shortening probably caused by oxidative DNA damage.

Telomere length and telomerase in a well-characterized sample of individuals with major depressive disorder compared to controls

Leukocyte telomere length (LTL) is a marker of cellular turnover and oxidative stress. Studies suggest major depressive disorder (MDD) is associated with oxidative stress, but examinations of MDD and LTL have yielded mixed results, likely because of differences in measurement methods and unmeasured confounding. This study examined LTL and telomerase activity in 166 individuals with MDD compared to 166 age- and gender-matched matched controls free of any psychiatric disorder, using well-validated assays and clinical assessment methods, and controlling for a range of potential confounders. Subjects aged 18 to 70 were evaluated by trained raters and provided blood for LTL and telomerase activity measurement. LTL was assayed using Southern blot and replicated with qPCR, and telomerase activity was assayed with a repeat amplification protocol using a commercial kit. There was no significant difference in telomere length for individuals with MDD [mean (SD)=9.1 (3.0)kbp] compared to controls [mean(SD)=8.9(2.5)kbp] measured by Southern blot (p=0.65) or by confirmatory qPCR (p=0.91) assays. Controlling for potential confounders did not alter the results. Telomerase activity did not differ by MDD diagnosis overall (p=0.40), but the effect of MDD was significantly modified by gender (t(299)=2.67, p=0.0079) even after controlling for potential confounders, with telomerase activity significantly greater only in males with MDD versus controls. Our well-characterized, well-powered examination of concurrently assessed telomere length and telomerase activity in individuals with clinically significant, chronic MDD and matched controls failed to provide strong evidence of an association of MDD with shorter LTL, while telomerase activity was higher in men with MDD [corrected].

Analysis of telomere attrition in bipolar disorder

BackgroundTelomeres can be considered a marker of biological aging. Studies have suggested that telomere shortening may be associated with aging related diseases and also psychiatric disorders. ObjectivesInvestigate whether bipolar disorder (BD) and its clinical specificities are associated with telomere shortening. MethodsEighty-five BD patients and 95 healthy controls were paired for age, sex and educational level. Volunteers were submitted to a psychiatric interview and clinical evaluation. Patients and controls were compared as a whole sample and within specific telomere range (short and long telomeres). Intrapatients group comparison involved type of BD and comorbidities. A Real Time Quantitative PCR was performed in order to verify leukocytes telomere length. ResultsBipolar disorder patients presented shorter telomeres when compared to controls (p<0.001). However, there was no significant difference in telomere length between different BD subtypes. When two groups of patients (long and short telomeres) were compared, only panic disorder showed an association with telomere categories (χ2=6.91; p=0.009; OR=4.27). LimitationsIt was not possible to collect information about time since diagnosis, which limited conclusions regarding BD chronicity and telomere length. Furthermore, medication interference upon telomere length was not controlled. ConclusionsResults suggest that BD is associated with reduced telomere length. Also, panic comorbidity may represent an additive risk factor. Understanding aspects that contribute to determination of telomere size in bipolar patients allows us to understand what the impact on telomeres size is, which is a health vulnerability marker.

Telomere length in human blastocysts

This is a retrospective study aiming to assess telomere length in human embryos 4days post fertilization and to determine whether it is correlated to chromosomal ploidy, embryo developmental rate and patient age. Embryos were donated from patients undergoing treatment in the assisted conception unit. Seven couples took part, generating 35 embryos consisting of 1130 cells. Quantitative fluorescent in-situ hybridization (FISH) measured the telomere length of every cell using a pan-telomeric probe. Conventional FISH on six chromosomes was used to assess aneuploidy in the same cells. Maternal and paternal age, referral reason, embryo developmental rate and type of chromosomal error were taken into account. Chromosomally abnormal cells were associated with shorter telomeres than normal cells for embryos that were developmentally slow. Cells produced by women of advanced maternal age and those with a history of repeated miscarriage tended to have substantially shorter telomeres. There was no significant difference in telomere length with respect to the rate of embryo development 5days post fertilization. Telomeres play an important role in cell division and shorter telomeres may affect embryonic ploidy. Reduced telomere length was associated with aneuploid cells and embryos from women of advanced maternal age.This study assessed telomere length in human embryos 5days post fertilization. Telomeres are found at the ends of chromosomes and protect them from degradation. Many embryos cultured in vitro are not able to implant to the maternal womb for reasons that are not always understood. We were, therefore, trying to determine whether the telomere length in each of the embryo cells affects its chromosomes and embryo development and/or is affected by patient age and reproductive history. Embryos were donated from patients undergoing treatment in the assisted conception unit. Seven couples took part, generating 35 embryos consisting of 1130 cells. The telomere length of all chromosomes was established in each embryonic cell. Six chromosomes mostly found abnormal in embryos that fail to implant, miscarriages and stillbirths were investigated in terms of whether they had the correct number. Maternal and paternal age, reproductive history, embryo developmental rate and type of chromosomal error were taken into account. Chromosomally abnormal cells had shorter telomeres than normal cells in embryos that were developmentally slow. Cells produced by women of advanced maternal age and those with history of repeated miscarriage tended to have substantially shorter telomeres. There was no significant difference in telomere length with respect to the rate of embryo development 5days post fertilization. Telomeres play an important role in cell division and shorter telomeres may affect embryo development and implantation. Reduced telomere length was associated with aneuploid cells and embryos from women of advanced maternal age.

Dynamics of Telomere Length in Different Age Groups in a Latvian Population

The shortening of telomeres with ageing is a well-documented observation; however, the reported number of nucleotides in telomeres varies between different laboratories and studies. Such variability is likely caused by ethnic differences between the populations studied. Until now, there were no studies that investigated the variability of telomere length in a senescent Latvian population of the most common mitochondrial haplogroups, defined as H (45%), U (25%), Y chromosomal N1c (40%) and R1a1 (40%). Telomere length was determined in 121 individuals in different age groups, including a control group containing individuals of 20-40 years old and groups of individuals between 60-70 years old, 71-80 years old, 81-90 years old, and above 90 years old. Telomere length was determined using the Southern blot telomeric restriction fragment assay (TRF). Decreased telomere length with ageing was confirmed, but a comparison of centenarians and individuals between 60-90 years of age did not demonstrate a significant difference in telomere length. However, significant variability in telomere length was observed in the control group, indicating probable rapid telomere shortening in some individuals that could lead up to development of health status decline appearing with ageing. Telomere length measured in mononuclear blood cells (MNC) was compared with the telomere length measured in whole peripheral white blood cells (WBC) using TRF. Telomere length in MNC was longer than in WBC for the control group with individuals 20 to 40 years old; in contrast, for the group of individuals aged 65 to 85 years old, measured telomere length was shorter in MNC when compared to WBC.

Healthy aging-related decrease of expression of the SIRT1 and SIRT3 might be a result of epigenetic drift

Results.–Nonagenarians had the same ADL scores as octogenarians but their IADL scoreswere higher (P=0.040). In univariate analyses, nonagenarians showed significative decrease in TREC compared to octogenarians (113.5±18.4 vs. 180.5±26.5, P<0.05). Therewas no significant difference in telomere length (40.3±2.1 vs. 43.5±1.8, P=0.25). Key conclusions.– Our data show that nonagenarians present telomere length and TREC with minimal decrease compared to octogenarians. The nonagenarians could be more robust regarding a better oxidative status and a slower decrease of their telomere and TREC number. Further research including a larger and more representative sample of patients is needed to confirm these data.

Aging of healthy humans is associated with a decreased expression of the IGF-1R and FOXO1 genes and with altered expression of their interacting miRNAs

Results.–Nonagenarians had the same ADL scores as octogenarians but their IADL scoreswere higher (P=0.040). In univariate analyses, nonagenarians showed significative decrease in TREC compared to octogenarians (113.5±18.4 vs. 180.5±26.5, P<0.05). Therewas no significant difference in telomere length (40.3±2.1 vs. 43.5±1.8, P=0.25). Key conclusions.– Our data show that nonagenarians present telomere length and TREC with minimal decrease compared to octogenarians. The nonagenarians could be more robust regarding a better oxidative status and a slower decrease of their telomere and TREC number. Further research including a larger and more representative sample of patients is needed to confirm these data.

Telomere shortening in Ph-negative chronic myeloproliferative neoplasms: A biological marker of polycythemia vera and myelofibrosis, regardless of hydroxycarbamide therapy

The purpose of this study was to investigate telomere length (TL) in Ph-negative chronic myeloproliferative neoplasms (Ph-neg-CMNs), and the possible association of TL with disease progression and hydroxycarbamide (HU) treatment. TL was analyzed in peripheral blood samples from 239 patients with Ph-neg-CMNs, including polycythemia vera (PV), essential thrombocythemia and myelofibrosis (MF), and compared with age-matched healthy control subjects (CTR), along with some cases of secondary erythrocytosis (SE). More than half of the patients with CMN received at least 1 year of cytoreduction, mainly HU, before TL analysis. JAK2 mutation analysis was performed as well. TL was significantly shortened in patients with CMN compared with CTR (p < 0.0001). PV and MF showed the most pronounced decrease (p < 0.0001), whereas both essential thrombocythemia and SE showed no significant difference in TL compared with CTR. A short TL correlated with JAK2-V617F allele burden greater than 50% (p = 0.0025), age (p = 0.0132) and diagnosis of PV (p = 0.0122). No correlation was found with disease duration, history of thrombosis, cytoreductive treatment, antiaggregation agents, adverse cytogenetics, phlebotomies, or time to evolution to MF. In summary, TL is distinctly shortened in PV and MF, and it inversely correlates with JAK2V617F allele burden. In addition, HU is unlikely to contribute to telomere erosion. Lastly, PV and SE significantly differ in TL. Therefore, TL could be an additional diagnostic marker to identify and monitor Ph-neg-CMN patients.

Association of telomere length (TL) with clinical outcomes in patients with colorectal carcinoma (CRC).

418 Background: Telomeres (T) consist of thousands of copies of TTAGGG tandem repeats capping the ends of the chromosome. T along with enzyme telomerase provides protection against any threats to the genome that might arise as a consequence of “end replication problem.” During aberrant cell proliferations the normal check points of cell cycle is compromised leading to unrestricted cell division with extremely short T and subsequent genomic instability. Studies have linked short TL with premalignant and malignant stages of CRC carcinogenesis. However, the relation of TL to the clinical outcomes has not been conclusively determined. In this study we evaluated the association of TL with clinical outcomes in a cohort of 75 CRC patients. Methods: Tumor DNA was isolated from formalin fixed paraffin embedded specimens. TL was measured by using a qRT-PCR method that provided the relative T copy number, compared to reference copy number of the housekeeping gene, β-Globin, which resulted in a T/S ratio. One T/S ratio unit is equivalent to a mean TL of 4,270 base pairs (BP). Results: From 75 patients, 122 tissue samples were identified (66 primary, 52 metastases, 29 matched pairs). Age at diagnosis (&gt;/&lt; median) had a statistically significant difference in TL (mean BP 4700 vs. 4374; p=0.05) with shorter TL in the advanced age. Females had longer TL compared to men (mean BP 4722 vs. 3669 respectively; p=0.04). Shorter TL was associated with shorter progression free survival (PFS) for patients treated with cetuximab/panitumumab (3963 vs. 5295 p=0.04). There was a trend towards increased overall survival (&gt;/&lt; median) with longer TL (4934 vs. 4117; p=0.08). We failed to find a difference in the TL between primary and metastatic sites in the 29 patients with paired samples. Conclusions: TL is a potential biomarker predictive of clinical outcome (PFS) for patients treated with cetuximab/panitumumab. Tumor TL reduces with advancing age and appears to be sex dependent. Further studies to validate TL’s predictive role in patient outcomes are underway.

Is socioeconomic status associated with biological aging as measured by telomere length?

It has been hypothesized that one way in which lower socioeconomic status (SES) affects health is by increasing the rate of biological aging. A widely used marker of biological aging is telomere length. Telomeres are structures at the ends of chromosomes that erode with increasing cell proliferation and genetic damage. We aimed to identify, through systematic review and meta-analysis, whether lower SES (greater deprivation) is associated with shorter telomeres. Thirty-one articles, including 29 study populations, were identified. We conducted 3 meta-analyses to compare the telomere lengths of persons of high and low SES with regard to contemporaneous SES (12 study populations from 10 individual articles), education (15 study populations from 14 articles), and childhood SES (2 study populations from 2 articles). For education, there was a significant difference in telomere length between persons of high and low SES in a random-effects model (standardized mean difference (SMD) = 0.060, 95% confidence interval (CI): 0.002, 0.118; P = 0.042), although a range of sensitivity analyses weakened this association. There was no evidence for an association between telomere length and contemporaneous SES (SMD = 0.104, 95% CI: −0.027, 0.236; P = 0.119) or childhood SES (SMD = −0.037, 95% CI: −0.143, 0.069; P = 0.491). These results suggest weak evidence for an association between SES (as measured by education) and biological aging (as measured by telomere length), although there was a lack of consistent findings across the SES measures investigated here.

Telomerase Activity Increased and Telomere Length Shortened in Peripheral Blood Cells from Patients with Immune Thrombocytopenia

To evaluate the telomere/telomerase system and its clinical significance in immune thrombocytopenia (ITP) patients. A total of 237 ITP patients, 20 SLE patients and 200 age-and sex-matched healthy controls were included in this study. CD4(+), CD8(+) and CD19(+) lymphocytes were purified by magnetic beads sorting from peripheral blood of 37 active chronic ITP patients and 22 age-and sex-matched healthy controls. Telomerase activity was assayed by Telo TTAGGG Telomerase PCR ELISA KIT. The relative telomere length of peripheral blood mononuclear cell (PBMC) was measured by a quantitative polymerase chain reaction-based method (Q-PCR) from 200 ITP patients and 178 age-and sex-matched healthy controls. Telomerase activity was increased in CD4(+), CD8(+) and CD19(+) lymphocytes from ITP patients compared to those from healthy controls (p = 0.000). The level of telomerase activity in CD19(+) lymphocyte was higher than those in CD4(+) and CD8(+) lymphocytes. Telomerase activity of CD19+ lymphocytes had a modest negative correlation with platelet count in ITP patients (p = 0.042). The relative telomere length of PBMC in ITP patients was significantly shorter than that in the healthy controls (p = 0.002). Telomere length of PBMC in active ITP patients was significantly shorter than that in the controls (p = 0.000) and a tendency to be shorter even in inactive ITP patients (p = 0.065). Moreover, the telomere length in refractory and non-refractory ITP patients were both significantly shorter than that in the controls (p = 0.025; p = 0.000). However no significant difference in telomere length of PBMC was found between refractory ITP patients and non-refractory ITP patients (p = 0.234). An abnormal regulating telomere/telomerase system might be involved in the pathogenesis of ITP. Further studies may elucidate whether the telomere length could be considered as a predictive biomarker for the prognosis of ITP.

A pilot study evaluating peripheral blood lymphocyte telomere length in elderly versus young patients with colorectal cancer (CRC).

512 Background: Telomere length (TL) is associated with aging as well as high cancer incidence. We conducted a pilot study to assess the TL of younger versus older (≥70 years) patients with CRC and its effect on survival. Methods: QPCR was used to analyze the relationship between telomere repeat copy number and single gene copy number (T/S ratio) on peripheral blood lymphocytes DNA of 94 CRC patients, and used as a surrogate value for relative TL. The primary aim of the study was to evaluate differences in TL between different age groups. Correlation with overall survival (OS) was the secondary aim. Samples were run in triplicate, and a standard curve was used to calculate the relative T/S ratio and account for plate to plate variability. Univariate statistical analyses were performed using the Mann-Whitney test for continuous variables and the log-rank test for OS. Multivariable analyses were performed using the Classification and Regression Trees methodology. A Type I error of 5% was used to determine statistical significance. Results: The mean relative TL was 0.95 (range 0.64-1.84). The assay demonstrated high correlation of technical replicates between plates (Pearson correlation: 0.96 and 0.81, for sample and control). Comparing patient under and over 70 years of age revealed a borderline significant difference in TL between the groups (mean TL 0.981 versus 0.925 respectively; p=0.067). Assessment using 4 age groups (50-60, 60-70, 70-80, &gt;80) demonstrated a statistically significant difference in TL between the youngest and the oldest age groups (mean TL 1.022 versus 0.874 respectively; p=0.02) with evidence of shorter TL with advanced age. Marginal relationship was seen between OS and age (p-value=0.066) with older patients exhibiting slightly poorer survival (hazard ratio of 1.03, 95% confidence interval (0.998, 1.065)). No correlation was noted between relative TL and OS in univariate and multivariable analysis. Conclusions: These results validate the ability of a qPCR-based assay to differentiate between younger and older CRC patients by TL. Ongoing studies are utilizing this methodology to evaluate the relationship of TL to treatment tolerance in elderly CRC patients.

Association Between ApoE Phenotypes and Telomere Erosion in Alzheimer’s Disease

Although several reports suggest that Alzheimer's disease (AD) is associated with shortened telomere length, the clinical relevance of this has not yet been fully elucidated. This study was conducted to clarify the correlation of telomere length with clinical characteristics and ApoE phenotypes in 74 AD patients. Telomere length was determined from genomic DNA extracted from whole blood by quantitative real-time polymerase chain reaction. We found no significant difference in telomere length between the AD and non-dementia elderly control (n = 35) groups. Furthermore, no significant correlation was found among telomere length and the severity of cognitive decline and disease duration, age, or gender difference. However, telomere length was significantly shorter in AD patients with the ApoE4 homozygote than in those with the ApoE4 heterozygote (p < .001) and noncarriers (p < .001). These findings suggest that shortened telomere length may be associated with the ApoE4 homozygote in AD patients.

Telomere length of patients with major depression is shortened but independent from therapy and severity of the disease

Shortened telomere length has been observed in a variety of diseases. Our objective was to analyze mean telomere length of patients with major depressive disorder. A key question was whether telomere length varies in different groups of depressive patients. We obtained blood samples from patients with major depressive disorder (n = 54) and healthy subjects (n = 20). We isolated genomic DNA and measured mean telomere length using telomere restriction fragments and Southern blotting. We grouped patients according to the therapy they received including total antidepressant dose. Mean telomere length of the entire patient group (7.20 ± 0.61 kb) was significantly shorter than in the control group (7.55 ± 0.54 kb). We observed no significant difference in telomere length among the different patient groups, but each of these patient groups had significantly shorter telomeres than the healthy subjects. Further analysis revealed no significant association between telomere length and illness duration and between telomere length and the severity of depression, as determined by the Hamilton score. These results provide further evidence that major depressive disorder is associated with shortened telomeres. However, differences in the applied therapy, the duration of illness, or the severity of depression do not seem to have any influence on telomere length.

Alterations of telomere length in human brain tumors

Telomeres at the ends of human chromosomes consist of tandem hexametric (TTAGGG)n repeats, which protect them from degradation. At each cycle of cell division, most normal somatic cells lose approximately 50-100bp of the terminal telomeric repeat DNA. Precise prediction of growth and estimation of the malignant potential of brain tumors require additional markers. DNA extraction was performed from the 51 frozen tissues, and a non-radioactive chemiluminescent assay was used for Southern blotting. One sample t-test shows highly significant difference in telomere length in meningioma and astrocytoma with normal range. According to our results, higher grades of meningioma and astrocytoma tumors show more heterogeneity in telomere length, and also it seems shortening process of telomeres is an early event in brain tumors.

Telomere length in human adults and high level natural background radiation.

BackgroundTelomere length is considered as a biomarker of aging, stress, cancer. It has been associated with many chronic diseases such as hypertension and diabetes. Although, telomere shortening due to ionizing radiation has been reported in vitro, no in vivo data is available on natural background radiation and its effect on telomere length.Methodology/Principal FindingsThe present investigation is an attempt to determine the telomere length among human adults residing in high level natural radiation areas (HLNRA) and the adjacent normal level radiation areas (NLNRA) of Kerala coast in Southwest India. Genomic DNA was isolated from the peripheral blood mononuclear cells of 310 individuals (HLNRA: N = 233 and NLNRA: N = 77). Telomere length was determined using real time q-PCR. Both telomere (T) and single copy gene (S) specific primers were used to calculate the relative T/S and expressed as the relative telomere length. The telomere length was determined to be 1.22±0.15, 1.12±0.15, 1.08±0.08, 1.12±0.11, respectively, among the four dose groups (≤1.50, 1.51–3.00, 3.01–5.00 and >5.00 mGy per year), which did not show any dose response. The results suggested that the high level natural chronic radiation did not have significant effect on telomere length among young adult population living in HLNRA, which is indicative of better repair of telomeric ends. No significant difference in telomere length was observed between male and female individuals. In the present investigation, although the determination of telomere length was studied among the adults with an age group between 18 to 40 years (mean maternal age: 26.10±4.49), a negative correlation was observed with respect to age. However, inter-individual variation was (0.81–1.68) was clearly observed.Conclusions/SignificanceIn this preliminary investigation, we conclude that elevated level of natural background radiation has no significant effect on telomere length among the adult population residing in HLNRAs of Kerala coast. To our knowledge, this is the first report from HLNRAs of the world where telomere length was determined on human adults. However, more samples from each background dose group and samples from older population need to be studied to derive firm conclusions.

Telomere shortening and chromosomal instability in myelodysplastic syndromes

Telomere shortening and chromosomal instability are believed to play an important role in the development of myeloid neoplasia. So far, published data are only available on the average telomere length in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), but not on the telomere length of individual chromosomes. We used a new technique, telomere/centromere-fluorescence in situ hybridization (T/C-FISH), which combines fluorescence R-banding and FISH using a probe against the telomere repeats to measure the telomere length of each chromosome arm in 78 patients with MDS. In line with the previous results, patients with MDS showed significantly shorter telomeres than those of healthy controls. Telomere lengths did not differ significantly between distinct morphological subtypes of MDS. However, there was a significant difference in telomere length between patients with an isolated monosomy 7 and patients with a normal karyotype (P < 0.05). Notably, patients with an isolated monosomy 7 showed significantly longer telomeres than patients with a normal karyotype in many chromosome arms, among them 7p and 7q. Neo-telomeres were found in two patients with a complex karyotype, in one case at the fusion site of a dic(14;20). Normal and aberrant metaphases of the same patient did not differ in telomere length, thus indicating to telomere shortening as a basic mechanism affecting all hematopoietic cells in patients with MDS. In some MDS subtypes, like MDS with isolated monosomy 7, telomeres may be stabilized and even increase in length because of the activation of telomerase or alternative mechanisms.

Luminal and cancer cells in the breast show more rapid telomere shortening than myoepithelial cells and fibroblasts

Critically shortened, dysfunctional telomeres may play a role in the genetic instabilities commonly found in cancer. We analyzed 30 surgical specimens of invasive breast carcinoma from women aged 34 to 91 years and estimated telomere lengths as telomere-to-centromere ratio values in the 5 different cell types comprising breast tissue in order to clarify telomere length variations within and between individuals using our tissue quantitative fluorescence in situ hybridization method. We obtained 3 novel findings. (1) In corresponding normal tissues, telomere length decreased in the order myoepithelial cells > normal-appearing fibroblasts > luminal epithelial cells, and telomere lengths were characteristic in these 3 cell types within each individual. (2) As expected, cancer cells had significantly shorter telomeres than myoepithelial cells (P < .0001) and normal-appearing fibroblasts (P = .0161), but there was no significant difference in telomere length between luminal cells and cancer cells (P = .6270). (3) Fibroblasts adjacent to cancer had longer telomeres than normal-appearing fibroblasts distant from cancer (P < .0001). This study, which represents the first reported assessment of telomere length variations in the 5 cell types comprising breast tissue within and between individuals, revealed that normal luminal epithelial cells and cancer cells had the shortest telomeres. Our new findings indicate that telomeres of background luminal cells are as short as those of cancer cells. Tissue quantitative fluorescence in situ hybridization, applicable to analysis of individual cells in tissue sections, is considered to be a powerful technique with considerable promise for studies in oncology.

Telomere length is not predictive of dementia or MCI conversion in the oldest old

The contribution of telomere shortening to the onset of certain age-related diseases, such as dementia, and its role as a predictor of cognitive impairment remain unclear. We tested these hypotheses by analyzing telomere length in 449 inpatients in a large cohort of the oldest old (mean age 85 years) followed up yearly. No significant difference in telomere length was observed between cognitively normal patients (205), demented patients (195; 82 mixed dementia, 77 Alzheimer's disease and 21 vascular dementia) and patients (49) with mild cognitive impairment (MCI). Similarly, no significant differences in telomere length were found between patients with different etiologies or severities of dementia. Telomere length and change in cognitive status (from normal to MCI or dementia, or from MCI to dementia) were not associated after two years of follow-up. This longitudinal study in very old patients provided no evidence to suggest that telomere length could be used to distinguish between demented and non demented patients, regardless of the type of dementia, or to predict dementia or MCI conversion.