Cell fate decision in response to damage:the role of cellular adaptation, senescence and death in tissue homeostasis

Eukaryotic cells are equipped with adaptive responses that, in response to stress, can activate multiple mechanisms to restore homeostasis. In most cases, the damage is either prevented or reversed and the functional and structural integrity of the cell is preserved. However, in certain conditions, these adaptive systems fail to avoid the accumulation of damage, and this can lead to one of two main cell fates: cellular senescence or death. Both of these processes have an impact on organismal homeostasis; directly through the elimination/exclusion of cells that have been damaged beyond recovery, irreversibly infected, or potentially oncogenic, and indirectly by releasing a diverse set of molecules that can signal locally (paracrine) and systemically (endocrine). Although both of these fates play an important role in maintaining homeostasis at the organismal level, the choice between senescence and death was shown to have a significant impact on tissue homeostasis. In this thesis, we show that different environmental factors/stressors, such as oxidative stress, dietary interventions, cancer treatments, and viral infection have a significant effect on the development of cell death and/or senescence. Furthermore, we unraveled different potential mechanisms responsible for the decision between those two cell fates and the impact of this decision on tissue homeostasis, pathophysiological conditions, and potential pharmacological modulators of this balance