The long-term goal of this CRC 1454 is to understand what triggers metaflammation and how the associated cellular programming affects organismal physiology and pathology, with a particular focus on sterile inflammatory processes in lifestyle associated NCD. Taking advantage of the interdisciplinary and complementary expertise of the scientists participating in this CRC, we aim to uncover the causal relationships between the triggers of metaflammation and the resultant disease processes and paveinnovative paths of translating this knowledge into approaches to prevent the manifestation of metaflammation, and towards the development of therapies that block the most proximal events in the initiation of metaflammation and the downstream disease processes.‘Metaflammation and cellular programming’ will work along the following conceptual avenues: First, complex mechanisms and dysregulations, such as those involved in metaflammation, require systems approaches using experimental animal and human samples, across several levels ranging from molecular interactions, intracellular regulation, cell-to-cell communication, to organ-level regulation. Second, understanding early events in the induction of metaflammation is required for developing new approaches to delay the onset of common NCD, or even to prevent them, by modification of diseasepromoting lifestyle or environments.