Telomere length predicts survival independent of genetic influences

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Aging cell (Impact Factor: 5.94). 01/2008; 6(6):769-74. DOI: 10.1111/j.1474-9726.2007.00340.x
Source: PubMed

ABSTRACT 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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Available from: Boo Johansson, Jul 29, 2015
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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.
    Reproductive biomedicine online 03/2015; DOI:10.1016/j.rbmo.2015.02.016 · 2.98 Impact Factor
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    • "(Bakaysa et al., 2007) "
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    • "(Bakaysa et al., 2007) "
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    ABSTRACT: Biomarkers of aging are essential to predict mortality and aging-related diseases. Paradoxically, age itself imposes a limitation on the use of known biomarkers of aging because their associations with mortality generally diminish with age. How this pattern arises is, however, not understood. With meta-analysis we show that human leucocyte telomere length (TL) predicts mortality, and that this mortality association diminishes with age, as found for other biomarkers of aging. Subsequently, we demonstrate with simulation models that this observation cannot be reconciled with the popular hypothesis that TL is proportional to biological age. Using the reliability theory of aging, we instead propose that TL is a biomarker of somatic redundancy, the body's capacity to absorb damage, which fits the observed pattern well. We discuss to what extent diminishing redundancy with age may also explain the observed diminishing mortality modulation with age of other biomarkers of aging. Considering diminishing somatic redundancy as the causal agent of aging may critically advance our understanding of the aging process, and improve predictions of life expectancy and vulnerability to aging-related diseases.
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