Computational biology in human aging : an omics data integration approach

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Computational biology in human aging : an omics data integration approach

Title: Computational biology in human aging : an omics data integration approach
Author: Akker, Erik Ben van den
Publisher: Department of Medical Statistics and Bioinformatics, Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Issue Date: 2015-02-18
Keywords: Integrative Data Analysis
Whole-Genome Sequencing
Gene Expression
Abstract: Throughout this thesis, human aging and its relation to health are studied in the context of two parallel though complementary lines of research: biomarkers and genetics. The search for informative biomarkers of aging focuses on easy accessible and quantifiable substances of the body that can be used to predict the early signs of deteriorating health, prior to the development of overt age-related disease. The challenge in this field is to translate the molecular changes captured by omics platforms to the age-associated deterioration observed at the whole body-level. In this thesis, new integrative methodology was developed that lead to the identification of gene expression networks that serve as biomarkers for aging and mortality. The second part of this thesis is aimed at identifying genetic determinants that predispose to a decelerated rate of aging and an extension of life span. Using whole genome sequencing data created in 218 nonagenarians of the Leiden Longevity Study we observed that a long life is not necessarily hampered by potentially premalignant somatic mutations in either TET2 or DNMT3A. In addition, genetic variation at chr13q34 attenuating the thyroid function, may be beneficial at middle age, but seems to contribute causally to increased mortality above 90 years.
Description: Promotores: P.E. Slagboom, M.J.T. Reinders, Co-Promotor: M. Beekman
With Summary in Dutch
Faculty: LUMC
Citation: Akker, E.B. van den, 2015, Doctoral Thesis, Leiden University
ISBN: 9789462950849
Sponsor: The Medical Delta Netherlands Consortium for Healthy Ageing

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