Leukocyte telomere length associates with prospective mortality independent of immune-related parameters and known genetic markers

Joris Deelen; Marian Beekman; Veryan Codd; Stella Trompet; Linda Broer; Sara Hägg; Krista Fischer; Peter E Thijssen; H Eka D Suchiman; Iris Postmus; André G Uitterlinden; Albert Hofman; Anton J M de Craen; Andres Metspalu; Nancy L Pedersen; Cornelia M van Duijn; J Wouter Jukema; Jeanine J Houwing-Duistermaat; Nilesh J Samani; P Eline Slagboom

doi:10.1093/ije/dyt267

Leukocyte telomere length associates with prospective mortality independent of immune-related parameters and known genetic markers

Int J Epidemiol. 2014 Jun;43(3):878-86. doi: 10.1093/ije/dyt267. Epub 2014 Jan 14.

Authors

Joris Deelen¹, Marian Beekman², Veryan Codd³, Stella Trompet⁴, Linda Broer², Sara Hägg³, Krista Fischer³, Peter E Thijssen², H Eka D Suchiman³, Iris Postmus², André G Uitterlinden⁴, Albert Hofman³, Anton J M de Craen³, Andres Metspalu³, Nancy L Pedersen³, Cornelia M van Duijn², J Wouter Jukema², Jeanine J Houwing-Duistermaat³, Nilesh J Samani³, P Eline Slagboom²

Affiliations

¹ Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands, Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, Leiden, The Netherlands, Department of Cardiovascular Sciences, University of Leicester, Leicester, UK, Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands, Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Estonian Genome Center, University of Tartu, Tartu, Estonia, Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands and Department of Medical Statistics, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands, Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, Leiden, The Netherlands, Department of Cardiovascular Sciences, University of Leicester, Leicester, UK, Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands, Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Estonian Genome Center, University of Tartu, Tartu, Estonia, Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands and Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands [email protected].
² Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands, Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, Leiden, The Netherlands, Department of Cardiovascular Sciences, University of Leicester, Leicester, UK, Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands, Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Estonian Genome Center, University of Tartu, Tartu, Estonia, Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands and Department of Medical Statistics, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands, Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, Leiden, The Netherlands, Department of Cardiovascular Sciences, University of Leicester, Leicester, UK, Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands, Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Estonian Genome Center, University of Tartu, Tartu, Estonia, Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands and Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands.
³ Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands, Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, Leiden, The Netherlands, Department of Cardiovascular Sciences, University of Leicester, Leicester, UK, Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands, Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Estonian Genome Center, University of Tartu, Tartu, Estonia, Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands and Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands.
⁴ Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands, Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, Leiden, The Netherlands, Department of Cardiovascular Sciences, University of Leicester, Leicester, UK, Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands, Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Estonian Genome Center, University of Tartu, Tartu, Estonia, Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands and Department of Medical Statistics, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands, Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, Leiden, The Netherlands, Department of Cardiovascular Sciences, University of Leicester, Leicester, UK, Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands, Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Estonian Genome Center, University of Tartu, Tartu, Estonia, Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands and Department of Medical Statistics, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Molecular Epidemiology, Leiden University Medica

Abstract

Background: Human leukocyte telomere length (LTL) decreases with age and shorter LTL has previously been associated with increased prospective mortality. However, it is not clear whether LTL merely marks the health status of an individual by its association with parameters of immune function, for example, or whether telomere shortening also contributes causally to lifespan variation in humans.

Methods: We measured LTL in 870 nonagenarian siblings (mean age 93 years), 1580 of their offspring and 725 spouses thereof (mean age 59 years) from the Leiden Longevity Study (LLS).

Results: We found that shorter LTL is associated with increased prospective mortality in middle (30-80 years; hazard ratio (HR)=0.75, P=0.001) and highly advanced age (≥90 years; HR=0.92, P=0.028), and show that this association cannot be explained by the association of LTL with the immune-related markers insulin-like growth factor 1 to insulin-like growth factor binding protein 3 molar ratio, C-reactive protein, interleukin 6, cytomegalovirus serostatus or white blood cell counts. We found no difference in LTL between the middle-aged LLS offspring and their spouses (β=0.006, P=0.932). Neither did we observe an association of LTL-associated genetic variants with mortality in a prospective meta-analysis of multiple cohorts (n=8165).

Conclusions: We confirm LTL to be a marker of prospective mortality in middle and highly advanced age and additionally show that this association could not be explained by the association of LTL with various immune-related markers. Furthermore, the approaches performed here do not further support the hypothesis that LTL variation contributes to the genetic propensity for longevity.

Keywords: Leukocyte telomere length; familial longevity; genetics; human; immune-related markers; prospective mortality.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Aging / immunology*
Biomarkers
Family*
Female
Health Status
Humans
Immunoproteins / analysis
Inflammation Mediators / blood
Leukocytes / immunology*
Longevity / immunology*
Male
Middle Aged
Prospective Studies
Telomere / immunology*

Substances

Biomarkers
Immunoproteins
Inflammation Mediators

Abstract

Publication types

MeSH terms

Substances

Grants and funding