Genetic and biomarker studies of human longevity

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Genetic and biomarker studies of human longevity

Title: Genetic and biomarker studies of human longevity
Author: Deelen, Joris
Publisher: Department Molecular Epidemiology, Faculty of Medicine / Leiden University Medical Center (LUMC), Leiden University
Issue Date: 2014-06-25
Keywords: Genetics
Aging
Longevity
Prospective mortality
Genome-wide association study
Gene set analysis
Biomarker
Leukocyte telomere length
Abstract: The aim of this thesis was to identify novel lifespan regulating loci that influence human longevity and population mortality. To this end, we performed two genome-wide association studies, one of long-lived individuals from the family-based Leiden Longevity Study (LLS) and an extended one of long-lived individuals from multiple cohorts of European descent. Using the latter, we identified two genome-wide significant loci, the TOMM40/APOE/APOC1 locus and an intergenic locus on chromosome 5q33.3. In addition, our gene set analysis with the LLS data showed that genetic variation in genes involved in the insulin/IGF-1 signaling and telomere maintenance pathways is associated with human longevity. Since our genetic studies identified a limited number of longevity loci, we additionally examined whether leukocyte telomere length (LTL) could be used as a biomarker of healthy aging. We showed that LTL meets three of the four criteria for a biomarker of healthy aging in the LLS, i.e., LTL changes with chronological age and is associated with health, in this case immune-related parameters, and prospective mortality. To identify novel longevity loci, future research may benefit from a better definition of the healthy aging phenotype, combining study designs, and the use of novel methods and technologies, such as next-generation sequencing.
Description: Promotores: P. Slagboom, R.G.J. Westendorp, Co-promotor: M. Beekman
With summary in Dutch
Faculty: LUMC
Citation: Deelen, J., 2014, Doctoral thesis, Leiden University
ISBN: 9789088919060
Sponsor: Netherlands Consortium for Healthy Ageing (NGI 050-060-810)
Handle: http://hdl.handle.net/1887/26946
 

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