Factors impacting human telomere homeostasis and age-related disease

Gilley, David; Herbert, Brittney Shea; Huda, Nazmul; Tanaka, Hiromi; Reed, Terry

doi:10.1016/j.mad.2007.10.010

Cited by 63 publications

(50 citation statements)

References 84 publications

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“…There is potential for selection bias in the use of employees in the Control group and patients in the comparison groups. Factors such as stress were not measured and could serve as potential confounders to our analysis, although stress alone, thought to contribute to more rapid telomere attrition, is unlikely to be a more significant factor in our Control group than our comparison groups (54,55). Lastly, the timing of blood collection in this study (at first clinic visit or within the first several months of treatment) correlates well with previous studies, and no difference was observed in telomere length with regards to chemotherapy; however, a confounder may exist in the timing of the blood collection resulting in telomere lengthening in both our High-and Low-Risk Case groups and our High-Risk Unaffected group.…”

Section: Discussionmentioning

confidence: 99%

Longer Relative Telomere Length in Blood from Women with Sporadic and Familial Breast Cancer Compared with Healthy Controls

Gramatges

Telli

Balise

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Telomeres cap the ends of chromosomes and are composed of a series of noncoding hexamer repeats. Telomeres protect the integrity of DNA coding sequences and are integral to the maintenance of genomic stability. Previous studies have shown an association between shortened lymphocyte telomeres and increased risk for specific cancers. However, the association between telomere length and breast cancer risk is less clear. We examined the relative telomere length (RTL) in blood from women with no personal or family history of cancer (controls) compared with different populations of women with breast cancer and women at high genetic risk for developing breast cancer. RTL was determined as the telomere to single gene copy number ratio assessed by quantitative PCR. Breast cancer cases (low risk, n = 40; high risk, n = 62) had significantly longer RTL compared with unaffected controls (n = 50; mean RTL = 1.11 versus 0.84; P < 0.0001). The assessment of risk by RTL quartile showed an increased risk for breast cancer with each longer quartile, with the most significant risk observed in the longest quartile (odds ratio, 23.3; confidence interval, 4.4-122.3; P < 0.0003). Women without breast cancer but at high risk due to family history (n = 30) also showed longer telomeres than controls (mean RTL = 1.09 versus 0.84; P < 0.0001). Our analysis supports previous findings of longer RTL in breast cancer cases compared with controls, and is the first to observe longer RTL in women without breast cancer identified as high risk based on family history. Cancer Epidemiol Biomarkers Prev; 19(2); 605-13. ©2010 AACR.

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Section: Discussionmentioning

confidence: 99%

Longer Relative Telomere Length in Blood from Women with Sporadic and Familial Breast Cancer Compared with Healthy Controls

Gramatges

Telli

Balise

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Findings from the human studies are inconsistent and estimates of heritability vary widely, partly as a consequence of variable sample sizes, differences in the ages at which parent and child telomere length are measured, and the difficulty in accounting for maternal effects and shared environments in the analyses (Gilley et al, 2008). The most reliable data produce heritability estimates in the region of 45%, which clearly indicates a considerable non-genetic component to the inheritance pattern (Baird et al, 2006;Huda et al, 2007;Baird, 2008b;Fraga, 2009).…”

Section: Reviewmentioning

confidence: 99%

Organismal stress, telomeres and life histories

Monaghan

2014

Journal of Experimental Biology

197

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Most organisms, including ourselves, are exposed to environmental stressors at various points during life, and responses to such stressors have been optimised by evolution to give the best fitness outcomes. It is expected that environmental change will substantially increase long-term stress exposure in many animal groups in the coming decades. A major challenge for biologists is to understand and predict how this will influence individuals, populations and ecosystems, and over what time scale such effects will occur. This requires a multi-disciplinary approach, combining studies of mechanisms with studies of fitness consequences for individuals and their descendants. In this review, I discuss the positive and negative fitness consequences of responses to stressful environments, particularly during early life, and with an emphasis on studies in birds. As many of the mechanisms underlying stress responses are highly conserved across the vertebrate groups, the findings from these studies have general applicability when interpreted in a life history context. One important route that has recently been identified whereby chronic stress exposure can affect health and longevity over long time frames is via effects on telomere dynamics. Much of this work has so far been done on humans, and is correlational in nature, but studies on other taxa, and experimental work, are increasing. I summarise the relevant aspects of vertebrate telomere biology and critically appraise our current knowledge with a view to pointing out important future research directions for our understanding of how stress exposure influences life histories.

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“…However, there are to our knowledge no such studies conducted on any other species. With analyses of data on mixed-age individuals it is not possible to control for potential environmental effects, which can seriously bias the heritability estimates [24] and hamper our understanding of how genetic and non-genetic factors contribute to early life telomere length. The inability to control for environmental effects can potentially explain the large range of estimates of heritability of telomere length in different studies, and e.g.…”

Section: Introductionmentioning

confidence: 99%

Maternal and genetic factors determine early life telomere length

et al. 2015

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In a broad range of species-including humans-it has been demonstrated that telomere length declines throughout life and that it may be involved in cell and organismal senescence. This potential link to ageing and thus to fitness has triggered recent interest in understanding how variation in telomere length is inherited and maintained. However, previous studies suffer from two main drawbacks that limit the possibility of understanding the relative importance of genetic, parental and environmental influences on telomere length variation. These studies have been based on (i) telomere lengths measured at different time points in different individuals, despite the fact that telomere length changes over life, and (ii) parent-offspring regression techniques, which do not enable differentiation between genetic and parental components of inheritance. To overcome these drawbacks, in our study of a songbird, the great reed warbler, we have analysed telomere length measured early in life in both parents and offspring and applied statistical models (so-called 'animal models') that are based on long-term pedigree data. Our results showed a significant heritability of telomere length on the maternal but not on the paternal side, and that the mother's age was positively correlated with their offspring's telomere length. Furthermore, the pedigree-based analyses revealed a significant heritability and an equally large maternal effect. Our study demonstrates strong maternal influence on telomere length and future studies now need to elucidate possible underlying factors, including which types of maternal effects are involved.

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Factors impacting human telomere homeostasis and age-related disease

Cited by 63 publications

References 84 publications

Longer Relative Telomere Length in Blood from Women with Sporadic and Familial Breast Cancer Compared with Healthy Controls

Longer Relative Telomere Length in Blood from Women with Sporadic and Familial Breast Cancer Compared with Healthy Controls

Organismal stress, telomeres and life histories

Maternal and genetic factors determine early life telomere length

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