Cell-fate determination, cellular senescence and aging

Cellular senescence, a genetically controlled program arresting cell division, is activated in most cells after reaching their limit for proliferative capacity. Cancer cells override the senescence program and thus acquire an unlimited proliferative potential. The molecular mechanisms triggering cellular senescence largely overlap with conserved cellular signalling pathways, which become activated in response to DNA damage. The elucidation of these DNA damage signalling pathways and the identification of novel signal transducers is a main focus of our work. This includes DNA damage-responsive kinases (ATM, HIPK2), the p53 tumor suppressor and PML nuclear bodies (Crone et al., 2011; Bitomsky et al., 2013; Conrad et al., 2015; click here for further details). In addition, we are using epigenetic profiling to investigate DNA methylation changes associated with cellular senescence and aging. Examples include the identification of age-related DNA methylation changes in human hematopoietic stem cells and human skin (Bocker et al., 2011; Raddatz et al., 2013). Our current work addresses the role of the DNA damage response in the establishment of age-related methylation changes and the role of epigenetic mechanisms in the determination of cell fates following DNA damage.