Telomere length predicts survival independent of genetic influences. Aging Cell 6:769-774

Department of Biological Psychology, VU University Amsterdam, Amsterdamo, North Holland, Netherlands
Aging cell (Impact Factor: 6.34). 01/2008; 6(6):769-74. DOI: 10.1111/j.1474-9726.2007.00340.x
Source: PubMed


Telomeres prevent the loss of coding genetic material during chromosomal replication. Previous research suggests that shorter telomere length may be associated with lower survival. Because genetic factors are important for individual differences in both telomere length and mortality, this association could reflect genetic or environmental pleiotropy rather than a direct biological effect of telomeres. We demonstrate through within-pair analyses of Swedish twins that telomere length at advanced age is a biomarker that predicts survival beyond the impact of early familial environment and genetic factors in common with telomere length and mortality. Twins with the shortest telomeres had a three times greater risk of death during the follow-up period than their co-twins with the longest telomere measurements [hazard ratio (RR) = 2.8, 95% confidence interval 1.1-7.3, P = 0.03].

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    • "Interestingly, in addition to age, telomere shortening has repeatedly been reported under conditions of chronic psychosocial stress (Epel et al. 2004), including stress that occurs during childhood (Cohen et al. 2013; Price et al. 2013; Shalev et al. 2013; Mitchell et al. 2014). Furthermore, telomere shortening has also been predictive of future poor health (Epel et al. 2006; Fitzpatrick et al. 2007; Cohen et al. 2013) and mortality (Cawthon et al. 2003; Bakaysa et al. 2007). While the mechanisms by which this shortening occurs are still being explored, including the potential for increased cell replication or weakened telomerase activity following activation of stress response systems (Choi et al. 2008; Epel et al. 2010; Tomiyama et al. 2012), investigating telomere length in the context of stress and long-term behavioral and health outcomes may have implications for intervention research. "
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    ABSTRACT: Parent–child relationships with high conflict and low warmth and support are associated with later adverse behavioral and physiological child outcomes. These outcomes include shorter telomere lengths, the repetitive sequences at the ends of chromosomes that have been utilized as a biomarker for chronic stress. Our research group furthered this by exploring telomere length outcomes following a family-based prevention program and identified reduced telomere shortening 5 years post intervention among those originally exposed to nonsupportive parenting and randomized to the intervention condition. However, not all individuals respond equally, and a growing literature suggests genetic sensitivity to one's environment, with variations in the oxytocin receptor gene (OXTR) potentially influencing this sensitivity. We utilized data from African American youths (mean age 17) randomized to intervention (n = 100) or control condition (n = 91) with baseline assessments of genetic status and nonsupportive parenting, and 5-year follow-up assessments of telomere length. We found a significant three-way interaction between nonsupportive parenting, intervention condition, and OXTR rs53576 genotype. OXTR GG individuals, who are suggested to be more sensitive to their social environment, exhibited significantly more variability, evidencing the shortest telomeres when exposed to nonsupportive parenting and randomized to the control condition, and similar telomere lengths to non at-risk groups when randomized to the intervention. In contrast, those with the A allele showed no statistical difference in telomere lengths across parental and intervention conditions. Subsequent analyses suggest that these findings may be mediated through chronic anger, whereby GG individuals exposed to nonsupportive parenting and randomized to the control condition had a greater increase in chronic anger by study follow-up, compared to those in the intervention, and this change associated with greater telomere shortening. These findings highlight the importance of individual differences and potential role of genetic status in moderating the relationship between environmental contexts and biological outcomes.
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    • "A recent study incorporating data from the National Health and Nutrition Examination Survey (NHANES) 1999–2002, a large, nationally representative, ethnically and socioeconomically diverse sample, reported that sex, race-ethnicity, and socioeconomic status (SES) moderated the associations between TL and mortality in older individuals (Needham et al. 2012). However , while some human cohort studies have found shorter PBMC TL or LTL is associated with increased mortality (Cawthon et al. 2003; Martin-Ruiz et al. 2006; Bakaysa et al. 2007; Farzaneh-Far et al. 2008; Kimura et al. 2008; Epel et al. 2009; Astrup et al. 2010; Willeit et al. 2010b; Fitzpatrick et al. 2011; Honig et al. 2012; Lee et al. 2012; Weischer et al. 2012), others have not (Bischoff et al. 2006; Harris et al. 2006; Njajou et al. 2009; Strandberg et al. 2011). These inconsistencies in the literature may be due to differences in study cohorts, sample sizes, assay methods, and other methodological differences (Bojesen 2013). "
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    ABSTRACT: The Kaiser Permanente Research Program on Genes, Environment and Health (RPGEH) Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort includes DNA specimens extracted from saliva samples of 110,266 individuals. Because of its relationship to aging, telomere length measurement was considered an important biomarker to develop on these subjects. To assay relative telomere length (TL) on this large cohort over a short time period, we created a novel high throughput robotic system for TL analysis and informatics. Samples were run in triplicate, along with control samples, in a randomized design. As part of quality control, we determined the within-sample variability and employed thresholds for the elimination of outlying measurements. Of 106,902 samples assayed, 105,539 (98.7%) passed all quality control (QC) measures. As expected, TL in general showed a decline with age and a sex difference. While telomeres showed a negative correlation with age up to 75 years, in those older than 75 years, age positively correlated with longer telomeres, indicative of an association of longer telomeres with more years of survival in those older than 75. Furthermore, while females in general had longer telomeres than males, this difference was significant only for those older than age 50. An additional novel finding was that the variance of TL between individuals increased with age. This study establishes reliable assay and analysis methodologies for measurement of TL in large, population-based human studies. The GERA cohort represents the largest currently available such resource, linked to comprehensive electronic health and genotype data for analysis. Copyright © 2015, The Genetics Society of America.
    Full-text · Article · Jun 2015 · Genetics
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    • "go progressive shortening after each round of division in most somatic cells , and when telomeres reach a critical minimum length , cells stop dividing or undergo apoptosis . The lengths of telomeres in leukocytes is positively correlated with lifespan ; therefore , these telomeres have been proposed as a potential biomarker of biological ageing ( Bakaysa et al . , 2007 ; Fitzpatrick et al . , 2007 ; Kimura et al . , 2008b ; Oeseburg et al . , 2010 ) . In contrast , telomeres of sperm are length ened by the action of telomerase , which is expressed at high levels in spermatogonia , resulting in an increase in telo - mere length with age in human sperm ( Kimura et al . , 2008a ) ."
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    ABSTRACT: The ends of eukaryotic chromosomes contain specialized chromatin structures called telomeres, the length of which plays a key role in early human embryonic development. Although the effect of sperm preparation techniques on major sperm characteristics, such as concentration, motility and morphology have been previously documented, the possible status of telomere length and its relation with sperm preparation techniques is not well-known for humans. The aim of this study was to investigate the role of density gradient centrifugation in the selection of spermatozoa with longer telomeres for use in assisted reproduction techniques in 105 samples before and after sperm processing. After density gradient centrifugation, the average telomere length of the sperm was significantly longer (6.51 ± 2.54 versus 5.16 ± 2.29, P < 0.01), the average motile sperm rate was significantly higher (77.9 ± 11.8 versus 44.6 ± 11.2, P < 0.01), but average DNA fragmentation rate was significantly lower (11.1 ± 5.9 versus 25.9 ± 12.9, P < 0.01) compared with raw semen. Additionally, telomere length was positively correlated with semen sperm count (rs = 0.58; P < 0.01). In conclusion, density gradient centrifugation is a useful technique for selection of sperm with longer telomeres. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
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