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Shorter Telomeres (shorter + telomere)
Selected AbstractsShorter telomeres are associated with mortality in those with APOE ,4 and dementiaANNALS OF NEUROLOGY, Issue 2 2006Lawrence S. Honig MD Objective Reduced telomere length may be a marker of biological aging. We hypothesized that telomere length might thus relate to increased risk for dementia and mortality. Methods This nested case,control study used stored leukocyte DNA from 257 individuals (mean age, 81.4 ± 7.9 years; 64.6% female; 44.7% Hispanic, 33.5% non-Hispanic black, and 21.8% non-Hispanic white). Our assay used real-time polymerase chain reaction, with two separate reactions amplifying telomere sequence and reference single copy gene (ribosomal-protein-P0), providing a calculated telomere-to-single copy gene (T/S) ratio. Results Mean telomere length was shorter among subjects dying during follow-up than in those surviving (0.453 ± 0.211 vs 0.525 ± 0.226 [± standard deviation]; p < 0.009). It was also shorter in those with Alzheimer's disease compared with control subjects (0.458 ± 0.207 vs 0.516 ± 0.229; p < 0.03). For participants with Alzheimer's disease, compared with those with the longest telomeres, the mortality odds ratio (OR) was 4.8 (95% confidence interval [CI], 1.7,13.8) in those with intermediate-length telomeres and 7.3 (95% CI, 2.4,22.0) in those with the shortest telomeres. The presence of an ,4 allele also increased the mortality OR, with an OR of 5.8 (95% CI, 1.3,26.4) for intermediate-length telomeres and an OR of 9.0 (95% CI, 1.9,41) for the shortest telomeres. Interpretation Our findings suggest that leukocyte telomere length is related to both dementia and mortality and may be a marker of biological aging. Ann Neurol 2006; [source] The association between leukocyte telomere length and cigarette smoking, dietary and physical variables, and risk of prostate cancerAGING CELL, Issue 4 2009Lisa Mirabello Summary Telomeres consist of nucleotide repeats and a protein complex at chromosome ends that are essential to maintaining chromosomal integrity. Several studies have suggested that subjects with shorter telomeres are at increased risk of bladder and lung cancer. In comparison to normal tissues, telomeres are shorter in high-grade intraepithelial neoplasia and prostate cancer. We examined prostate cancer risk associated with relative telomere length as determined by quantitative PCR on prediagnostic buffy coat DNA isolated from 612 advanced prostate cancer cases and 1049 age-matched, cancer-free controls from the PLCO Cancer Screening Trial. Telomere length was analyzed as both a continuous and a categorical variable with adjustment for potential confounders. Statistically significant inverse correlations between telomere length, age and smoking status were observed in cases and controls. Telomere length was not associated with prostate cancer risk (at the median, OR = 0.85, 95% CI: 0.67, 1.08); associations were similar when telomere length was evaluated as a continuous variable or by quartiles. The relationships between telomere length and inflammation-related factors, diet, exercise, body mass index, and other lifestyle variables were explored since many of these have previously been associated with shorter telomeres. Healthy lifestyle factors (i.e., lower BMI, more exercise, tobacco abstinence, diets high in fruit and vegetables) tended to be associated with greater telomere length. This study found no statistically significant association between leukocyte telomere length and advanced prostate cancer risk. However, correlations of telomere length with healthy lifestyles were noted, suggesting the role of these factors in telomere biology maintenance and potentially impacting overall health status. [source] Race/ethnicity and telomere length in the Multi-Ethnic Study of AtherosclerosisAGING CELL, Issue 3 2009Ana V. Diez Roux Summary Telomere length has emerged as a marker of exposure to oxidative stress and aging. Race/ethnic differences in telomere length have been infrequently investigated. Leukocyte telomere length (LTL) was assessed 981 white, black and Hispanic men and women aged 45,84 years participating in the Multi-Ethnic Study of Atherosclerosis. Direct measurement and questionnaire were used to assess covariates. Linear regression was used to estimate associations of LTL with race/ethnicity and age after adjustment for sex, income, education, smoking, physical activity, diet and body mass index. On average blacks and Hispanics had shorter telomeres than whites [adjusted mean differences (standard error) in T/S ratio compared to whites: ,0.041 (0.018) for blacks and ,0.044 (0.018) for Hispanics]. Blacks and Hispanics showed greater differences in telomere length associated with age than whites (adjusted mean differences in T/S ratio per 1 year increase in age ,0.0018, ,0.0047 and ,0.0055 in whites, blacks and Hispanics respectively). Differences in age associations were more pronounced and only statistically significant in women. Race/ethnic differences in LTL may reflect the cumulative burden of differential exposure to oxidative stress (and its predictors) over the lifecourse. [source] MSH2 deficiency abolishes the anticancer and pro-aging activity of short telomeresAGING CELL, Issue 1 2009Paula Martinez Summary Mutations in the mismatch repair (MMR) pathway occur in human colorectal cancers with microsatellite instability. Mounting evidence suggests that cell-cycle arrest in response to a number of cellular stresses, including telomere shortening, is a potent anticancer barrier. The telomerase-deficient mouse model illustrates the anticancer effect of cell-cycle arrest provoked by short telomeres. Here, we describe a role for the MMR protein, MSH2, in signaling cell-cycle arrest in a p21/p53-dependent manner in response to short telomeres in the context of telomerase-deficient mice. In particular, progressively shorter telomeres at successive generations of MSH2,/,Terc,/,- mice did not suppress cancer in these mice, indicating that MSH2 deficiency abolishes the tumor suppressor activity of short telomeres. Interestingly, MSH2 deficiency prevented degenerative pathologies in the gastrointestinal tract of MSH2,/,Terc,/, mice concomitant with a rescue of proliferative defects. The abolishment of the anticancer and pro-aging effects of short telomeres provoked by MSH2 abrogation was independent of changes in telomere length. These results highlight a role for MSH2 in the organismal response to dysfunctional telomeres, which in turn may be important in the pathobiology of human cancers bearing mutations in the MMR pathway. [source] Telomerase reverse transcriptase haploinsufficiency and telomere length in individuals with 5p, syndromeAGING CELL, Issue 5 2007Hong-Yan Du Summary Telomerase, which maintains the ends of chromosomes, consists of two core components, the telomerase reverse transcriptase (TERT) and the telomerase RNA (TERC). Haploinsufficiency for TERC or TERT leads to progressive telomere shortening and autosomal dominant dyskeratosis congenita (DC). The clinical manifestations of autosomal dominant DC are thought to occur when telomeres become critically short, but the rate of telomere shortening in this condition is unknown. Here, we investigated the consequences of de novo TERT gene deletions in a large cohort of individuals with 5p, syndrome. The study group included 41 individuals in which the chromosome deletion resulted in loss of one copy of the TERT gene at 5p15.33. Telomere length in peripheral blood cells from these individuals, although within the normal range, was on average shorter than in normal controls. The shortening was more significant in older individuals suggesting an accelerated age-dependent shortening. In contrast, individuals with autosomal dominant DC due to an inherited TERC gene deletion had very short telomeres, and the telomeres were equally short regardless of the age. Although some individuals with 5p, syndrome showed clinical features that were reminiscent of autosomal dominant DC, these features did not correlate with telomere length, suggesting that these were not caused by critically short telomeres. We conclude that a TERT gene deletion leads to slightly shorter telomeres within one generation. However, our results suggest that several generations of TERT haploinsufficiency are needed to produce the very short telomeres seen in patients with DC. [source] Telomere length and obesityACTA PAEDIATRICA, Issue 7 2008Raffaella Zannolli Abstract Aim: To assess the telomere length in apparently healthy obese and normal-weight subjects. Methods: Seventy-six Caucasian subjects were chosen including 53 children (age 8.2 ± 3.5 years) and 23 adults (age 40.5 ± 8.4 years). Among these, 22 (12 children and 10 adults) were obese with a body mass index (BMI, kg/m2) > 2 SD above the norm. Bioelectrical impedance analysis (BIA), measured with a multiple frequency analyzer, was used to estimate body composition. DNA extraction from white blood cells was used to estimate the telomere length by detection of terminal restriction fragments (TRF). Results: No difference was found between the TRF lengths of obese and normal children. Obese adults had shorter TRF lengths than adults who were not obese (mean TRF length difference, ,884.5; 95% confidence intervals ,1727 to ,41.8; t= 2.183; df = 17; p < 0.041). Conclusions: Obese adults have shorter telomeres than their normal-weight counterparts, while this phenomenon is not present in childhood. [source] | ||||||||||