Regulation of ageing by DAF-16/FOXO, its cofactors, and the chromatin landscape.
Dr Christian Riedel from The European Research Institute for the Biology of Ageing (ERIBA) will be visiting the Institute.
Ageing and age-related diseases have become major determinants to human health and longevity. Fortunately, ageing is extensively regulated, and thus the study of the underlying mechanisms may identify important means to prevent or delay it. Ageing is controlled by several signalling pathways that upon dire conditions induce stress responses, which increase the organism’s durability and longevity and thus its chances of survival. Central player to many of these pathways is the transcription factor DAF-16/FOXO, which relays low insulin-like signalling (as a sign of nutrient deprivation) but also other pro-longevity stimuli into the expression of stimulus-specific sets of stress response genes. Despite its importance, much about the mechanisms by which DAF-16/FOXO’s specifies and regulates its target genes has remained elusive. Using the model system C. elegans, we recently identified ~30 cofactors to DAF-16/FOXO, all of which are essential for DAF-16/FOXO to fulfil its appropriate physiological roles. By focusing on one of them, the chromatin remodeller SWI/SNF, we could show that DAF-16/FOXO employs chromatin remodelling at its target promoters as a means to induce transcription. We are now extending this work by exploring the mechanistic involvement of the remaining DAF-16/FOXO cofactors as well as the chromatin landscape in ageing regulation.