Genetic determinants of healthy longevity

Leiden Repository

Genetic determinants of healthy longevity

Type: Doctoral Thesis
Title: Genetic determinants of healthy longevity
Author: Mooijaart, Simon Pieter
Publisher: Department of Gerontology and Geriatrics, Faculty of Medicine, Leiden University
Issue Date: 2007-12-04
Keywords: Aging
Longevity
Human
Vitamin D Receptor
Apolipoprotein E
Mortality
Abstract: Lifespan in under genetic control. In this thesis we translated genes regulating lifespan in model organisms to humans. First we identified DAF-12 as a critical gene for lifespan regulation in the nematode worm C. elegans. Then we found that the Liver X Receptors and the Vitamin D Receptor are the most similar human proteins. We tested these genetic variation in these human genes in the Leiden 85-plus Study and found them to associate with with lifespan and cognitive decline respectively. Apolipoprotein E is a target gene of the Liver X Receptor. We found that plasma levels of apolipoprotein E associated with increased risk of cardiovascular mortality, cognitive decline and stroke in a manner independent of classical cardiovascular risk factors. Finally we reviewed the evidence from human candidate gene studies. We conclude that the use of model organisms provides useful directions for research into the genetics of human longevity. However, as the human signalling systems are more complex and our environment is different from that of model organisms, it is unclear to what extent results obtained in model organisms can be extrapolated to humans.
Description: Promotores: R.G.J. Westendorp, P.E. Slagboom, Co-promotor: D. van Heemst
With Summary in Dutch
Faculty: LUMC
Citation: Mooijaart, S.P., 2007, Doctoral Thesis, Leiden University
ISBN: 9789090224374
Sponsor: THE WORK DESCRIBED IN THIS THESIS WAS FUNDED BY AN INNOVATIVE ORIENTED RESEARCH (IOP) GRANT FROM THE DUTCH MINISTRY OF ECONOMIC AFFAIRS (GRANT NUMBER IGE01014).
Handle: http://hdl.handle.net/1887/12477
 

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