Aging is a complex phenomenon, resulting from damage accumulation, the increased deregulation of biological pathways, and a loss of cellular homeostasis, all of which lead to a functional decline in the organism over time. Interestingly, aging is not a static process but it is highly regulated by an interconnected signaling network that predominantly regulates the activity of aging-preventive stress response and longevity promoting pathways. In this thesis, I provided new mechanistic insights into the transcriptional regulation of genes that promote stress resistance and longevity. For this work, I used the model organism C. elegans and focused on maybe the most central aging-regulatory signaling pathway known to date, namely insulin/IGF-like signaling (IIS) with its downstream transcription factor DAF-16/FOXO. By showing and evaluating genetic and biochemical interactions between DAF-16 and some of its essential cofactors and regulators, we gained important new insights into how DAF-16 is regulated and targets its downstream genes. Hopefully, this information provides new mechanistic avenues towards interventions against the aging process and resultant age-related diseases.
|Qualification||Doctor of Philosophy|
|Place of Publication||[Groningen]|
|Publication status||Published - 2018|