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- Gardner, Michael, et al.
(författare)
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Gender and telomere length : Systematic review and meta-analysis
- 2014
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Ingår i: Experimental Gerontology. - : Elsevier. - 0531-5565 .- 1873-6815. ; 51, s. 15-27
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Forskningsöversikt (refereegranskat)abstract
- Background: It is widely believed that females have longer telomeres than males, although results from studies have been contradictory. Methods: We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression. Results: Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p = 1.00) or cell type (p = 0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error. Conclusions: Telomere length is longer in females thanmales, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required. (C) 2013 Published by Elsevier Inc.
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| 5. |
- Nordfjäll, Katarina, et al.
(författare)
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Large-scale parent-child comparison confirms a strong paternal influence on telomere length
- 2010
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Ingår i: European Journal of Human Genetics. - Basel : Karger. - 1018-4813 .- 1476-5438. ; 18:3, s. 385-389
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Tidskriftsartikel (refereegranskat)abstract
- Telomere length is documented to have a hereditary component, and both paternal and X-linked inheritance have been proposed. We investigated blood cell telomere length in 962 individuals with an age range between 0 and 102 years. Telomere length correlations were analyzed between parent-child pairs in different age groups and between grandparent-grandchild pairs. A highly significant correlation between the father's and the child's telomere length was observed (r=0.454, P<0.001), independent of the sex of the offspring (father-son: r=0.465, P<0.001; father-daughter: r=0.484, P<0.001). For mothers, the correlations were weaker (mother-child: r=0.148, P=0.098; mother-son: r=0.080, P=0.561; mother-daughter: r=0.297, P=0.013). A positive telomere length correlation was also observed for grandparent-grandchild pairs (r=0.272, P=0.013). Our findings indicate that fathers contribute significantly stronger to the telomere length of the offspring compared with mothers (P=0.012), but we cannot exclude a maternal influence on the daughter's telomeres. Interestingly, the father-child correlations diminished with increasing age (P=0.022), suggesting that nonheritable factors have an impact on telomere length dynamics during life.
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| 7. |
- Nordfjäll, Katarina, et al.
(författare)
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The individual blood cell telomere attrition rate is telomere length dependent.
- 2009
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Ingår i: PLoS genetics. - : Public Library of Science. - 1553-7404. ; 5:2, s. e1000375-
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Tidskriftsartikel (refereegranskat)abstract
- Age-associated telomere shortening is a well documented feature of peripheral blood cells in human population studies, but it is not known to what extent these data can be transferred to the individual level. Telomere length (TL) in two blood samples taken at approximately 10 years interval from 959 individuals was investigated using real-time PCR. TL was also measured in 13 families from a multigenerational cohort. As expected, we found an age-related decline in TL over time (r = -0.164, P<0.001, n = 959). However, approximately one-third of the individuals exhibited a stable or increased TL over a decade. The individual telomere attrition rate was inversely correlated with initial TL at a highly significant level (r = -0.752, P<0.001), indicating that the attrition rate was most pronounced in individuals with long telomeres at baseline. In accordance, the age-associated telomere attrition rate was more prominent in families with members displaying longer telomeres at a young age (r = -0.691, P<0.001). Abnormal blood TL has been reported at diagnosis of various malignancies, but in the present study there was no association between individual telomere attrition rate or prediagnostic TL and later tumor development. The collected data strongly suggest a TL maintenance mechanism acting in vivo, providing protection of short telomeres as previously demonstrated in vitro. Our findings might challenge the hypothesis that individual TL can predict possible life span or later tumor development.
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| 8. |
- Svenson, Ulrika, et al.
(författare)
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Blood cell telomere length is a dynamic feature
- 2011
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Ingår i: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 6:6, s. e21485-
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Tidskriftsartikel (refereegranskat)abstract
- There is a considerable heterogeneity in blood cell telomere length (TL) for individuals of similar age and recent studies have revealed that TL changes by time are dependent on TL at baseline. TL is partly inherited, but results from several studies indicate that e.g. life style and/or environmental factors can affect TL during life. Collectively, these studies imply that blood cell TL might fluctuate during a life time and that the actual TL at a defined time point is the result of potential regulatory mechanism(s) and environmental factors. We analyzed relative TL (RTL) in subsequent blood samples taken six months apart from 50 individuals and found significant associations between RTL changes and RTL at baseline. Individual RTL changes per month were more pronounced than the changes recorded in a previously studied population analyzed after 10 years' follow up. The data argues for an oscillating TL pattern which levels out at longer follow up times. In a separate group of five blood donors, a marked telomere loss was demonstrated within a six month period for one donor where after TL was stabilized. PCR determined RTL changes were verified by Southern blotting and STELA (single telomere elongation length analysis). The STELA demonstrated that for the donor with a marked telomere loss, the heterogeneity of the telomere distribution decreased considerably, with a noteworthy loss of the largest telomeres. In summary, the collected data support the concept that individual blood cell telomere length is a dynamic feature and this will be important to recognize in future studies of human telomere biology.
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| 9. |
- Svenson, Ulrika, et al.
(författare)
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Breast cancer survival is associated with telomere length in peripheral blood cells
- 2008
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 68:10, s. 3618-3623
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Tidskriftsartikel (refereegranskat)abstract
- Telomeres are essential for maintaining chromosomal stability. Previous studies have indicated that individuals with shorter blood telomeres may be at higher risk of developing various types of cancer, such as in lung, bladder, and kidney. We have analyzed relative telomere length (RTL) of peripheral blood cells in relation to breast cancer incidence and prognosis. The study included 265 newly diagnosed breast cancer patients and 446 female controls. RTL was measured by real-time PCR, and our results show that the patient group displayed significantly longer telomeres compared with controls (P < 0.001). Age-adjusted odds ratios (OR) for breast cancer risk increased with increasing telomere length, with a maximal OR of 5.17 [95% confidence interval (95% CI), 3.09-8.64] for the quartile with the longest telomeres. Furthermore, RTL carried prognostic information for patients with advanced disease. Node positive (N+) patients with short telomeres (16 mm (median tumor diameter), short telomeres were associated with a significantly better outcome than longer telomeres (P = 0.006). Cox regression analysis showed that long RTL was a significant independent negative prognostic factor (hazards ratio, 2.92; 95% CI, 1.33-6.39; P = 0.007). Our results indicate that blood RTL may serve as a prognostic indicator in breast cancer patients with advanced disease.
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| 10. |
- Wikgren, Mikael, 1981-, et al.
(författare)
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APOE ε4 is associated with longer telomeres, and longer telomeres among ε4 carriers predicts worse episodic memory
- 2012
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 33:2, s. 335-344
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Tidskriftsartikel (refereegranskat)abstract
- Both leukocyte telomere length and the apolipoprotein ε4 allele have been associated with mortality, cardiovascular disease, cognition, and dementia. The authors investigated whether leukocyte telomere length was associated with APOE genotype or cognitive abilities in the context of APOE genotype. The setting for this cross-sectional study was 427 nondemented individuals aged 41–81 yr. The authors found that ε4 carriers overall exhibited significantly longer telomeres compared with non-carriers (difference of 268 bp, p = 0.001). This difference was greatest at the lower limit of the age span and nonsignificant at the upper limit, which translated into a significantly higher telomere attrition rate (p = 0.049) among ε4 carriers (37 bp/years) compared with non-carriers (21 bp/year). Further, longer telomeres among ε4 carriers significantly predicted worse performance on episodic memory tasks. No significant associations were found on tasks tapping semantic and visuospatial ability, or among ε3/ε3 carriers. In conclusion, APOE ε4 carriers had longer telomeres compared with non-carriers, but higher rate of attrition. Among them, longer telomeres predicted worse performance on episodic memory tasks. These observations suggest that the ε4 allele is associated with abnormal cell turnover of functional and possibly clinical significance.
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| 11. |
- Wikgren, Mikael, 1981-, et al.
(författare)
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Short Telomeres in Depression and the General Population Are Associated with a Hypocortisolemic State
- 2012
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Ingår i: Biological Psychiatry. - New York : Elsevier. - 0006-3223 .- 1873-2402. ; 71:4, s. 294-300
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Tidskriftsartikel (refereegranskat)abstract
- Background The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in stress regulation, and leukocyte telomere length (TL) has been suggested to represent a cumulative measure of stress. Depression is intimately related with stress and frequently exhibits a dysregulated HPA axis. We aimed to study the relationships between TL and biological and psychological facets of stress in recurrent major depressive disorder and controls. Methods Leukocyte TL was measured in 91 subjects with recurrent major depressive disorder and 451 control subjects. Stress was assessed from both a biological perspective, by assessing HPA axis function with a weight-adjusted very-low-dose dexamethasone suppression test (DST), and a psychological perspective, with self-report questionnaires. Results TL was shorter among patients compared with control subjects (277 base pairs, p = .001). Overall, short TL was associated with a hypocortisolemic state (low post-DST cortisol and high percentage of cortisol reduction after the DST) among both patients and control subjects but more pronounced among patients. This state, which was overrepresented among patients, was characterized by high familial loading of affective disorders among patients (p = .001) and high C-reactive protein levels among control subjects (p = .040). TL was also inversely associated with stress measured with the Perceived Stress Questionnaire (rs = −.258, p = .003). Conclusions Short TL is associated with depression and hypocortisolism. Because hypocortisolism has been shown to develop from chronic stress exposure, our findings corroborate the concept of TL as a cumulative measure of stress and provide novel insights into the detrimental role of stress in depressive illness and the general population.
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| 12. |
- Wu, Xuping, et al.
(författare)
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Telomerase antagonist imetelstat inhibits esophageal cancer cell growth and increases radiation-induced DNA breaks
- 2012
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Ingår i: Biochimica et Biophysica Acta. Molecular Cell Research. - : Elsevier BV. - 0167-4889 .- 1879-2596. ; 1823:12, s. 2130-2135
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Tidskriftsartikel (refereegranskat)abstract
- Telomerase is mainly active in human tumor cells, which provides an opportunity for a therapeutic window on telomerase targeting. We sought to evaluate the potential of the thio-phosphoramidate oligonucleotide inhibitor of telomerase, imetelstat, as a drug candidate for treatment of esophageal cancer. Our results showed that imetelstat inhibited telomerase activity in a dose-dependent manner in esophageal cancer cells. After only 1. week of imetelstat treatment, a reduction of colony formation ability of esophageal cancer cells was observed. Furthermore, long-term treatment with imetelstat decreased cell growth of esophageal cancer cells with different kinetics regarding telomere lengths. Short-term imetelstat treatment also increased γ-H2AX and 53BP1 foci staining in the esophageal cancer cell lines indicating a possible induction of DNA double strand breaks (DSBs). We also found that pre-treatment with imetelstat led to increased number and size of 53BP1 foci after ionizing radiation. The increase of 53BP1 foci number was especially pronounced during the first 1 h of repair whereas the increase of foci size was prominent later on. This study supports the potential of imetelstat as a therapeutic agent for the treatment of esophageal cancer.
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| 13. |
- wu, xuping, et al.
(författare)
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The effect of the telomerase antagonist Imetelstat in esophageal carcinoma
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Telomerase is mainly active in human tumor cells, which provides an opportunity for a therapeutic window on telomerase targeting. We sought to evaluate the potential of the thio-phosphoramidate oligonucleotide inhibitor of telomerase, Imetelstat, as a drug candidate for treatment of esophageal cancer. Our results showed that Imetelstat inhibited telomerase activity in a dose-dependent manner in esophageal cancer cells. After only one week of Imetelstat treatment, a reduction of colony formation ability of esophageal cancer cells was observed. Furthermore, long-term treatment with Imetelstat decreased cell growth of esophageal cancer cells with different kinetics regarding telomere lengths. Cell cycle analysis demonstrated that short-term treatment with Imetelstat resulted in increased percentage of cells in G1 phase. Short-term Imetelstat treatment also increased γ-H2AX and 53BP1 foci staining in the esophageal cancer cell lines indicating a possible induction of DNA double strand breaks (DSBs). We also found that pre-treatment with Imetelstat led to increased number and size of 53BP1 foci after ionizing radiation. The increase of 53BP1 foci number was especially pronounced during the first 1 h of repair whereas the increase of foci size was prominent later on. This study supports the potential of Imetelstat as a therapeutic agent for the treatment of esophageal cancer.
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