Research area A:
Systems Biology of Longevity Pathways
The last two decadea have revolutionized our understanding of the molecular basis of the ageing process. Research into life span regulation of the nematode worm C. elegans has identified a number of specific pathways that mediate animal longevity. Interestingly, these pathways are evolutionarily highly conserved in budding yeast, fruit flies, mice and humans.
Life extension is triggered by several different manipulations including a modest reduction of insulin/IGF signalling, removal of the germline, reduced mitochondrial activity, increased HIF1-a activity as well as dietary restriction. Although these pathways appear to behave somewhat independently of one another, whether they converge on common mechanisms is currently unknown. Important questions remain: How are the different signalling pathways interconnected? Is there a common final effector pathway they converge on? Which modulators regulate the balance between the life extending effect and the detrimental effect due to reduced signalling activity? What is the role of the inevitable DNA damage in the ageing process?
The aim of research area A is to address these fundamental questions through unique systems biology approaches. The overarching theoretical challenge is to develop quantitative, dynamical models of interacting ageing related pathways, which quantify the output of one pathway, given external input and the state of other related pathways.