Transcriptomic studies in human ageing and longevity

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Transcriptomic studies in human ageing and longevity

Title: Transcriptomic studies in human ageing and longevity
Author: Passtoors, Willemijn Marie-Antoinette
Publisher: Molecular Epidemiology Section, Faculty of Medicine / Leiden University Medical Center (LUMC), Leiden University
Issue Date: 2013-12-19
Keywords: Healthy ageing
Ageing
Longevity
MTOR
ASF1A
IL7R
Gene expression
Transcriptomics
Abstract: The aim of this thesis was to identify in the human blood transcriptome, relevant pathways and potential biomarker profiles that associate with chronological age and discriminate between ‘healthy agers’ from long-lived families and normative ageing controls. Such profiles may harbor determinants of the biological ageing rate. We studied genome-wide gene expression profiles in blood of members of the Leiden Longevity Study (LLS) and replicated our findings by extended sampling within the unique LLS cohort. The findings of the exploratory analysis prompted us to investigate multiple genes in the IL7R and MTOR pathways for association with familial longevity. The results obtained by examining mRNA from blood samples brought us to study mTOR protein levels and signalling in primary skin fibroblasts from the corresponding donors in the LLS. Finally, to discover robust, biologically relevant gene networks as markers of chronological ageing in larger sample sizes, we performed an explorative network-based meta-analysis on large publicly available transcriptomic datasets. We have identified several networks, pathways and candidate genes potentially marking the biological age and the rate of ageing
Description: Promotor: P.E.Slagboom, Co-promotores: M. Beekman, J.M. Boer
With summary in Dutch
Faculty: LUMC
Citation: Passtoors, W.M.-A., 2013, Doctoral thesis, Leiden University
ISBN: 9789088917684
Sponsor: Netherlands Consortium for Healthy Ageing (NGI 050060810) and Unilever PLC
Handle: http://hdl.handle.net/1887/22948
 

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application/pdf Chapter 1 General introduction 147.3Kb View/Open
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application/pdf Chapter 9 Summary 127.1Kb View/Open
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application/pdf Curriculum Vitae_List of publications 153.3Kb View/Open
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