Interaction between Autophagy and Senescence in Pancreatic Beta Cells

SIMPLE SUMMARY: Cellular senescence is a state of replication arrest in response to different stimuli and has a wide range of effects on pancreatic beta cells. Accumulation of senescent cells impairs beta cell function and worsens the prognosis of diabetes. Macroautophagy is a lysosomal degradation pathway with the primary role of maintaining cellular homeostasis by clearing stress-inducing factors. It plays a context-dependent role in beta cells and the pathophysiology of diabetes. Even though these two processes converge in different signaling checkpoints our understanding of their relationship remains inconclusive. Filling this gap will enable us to grasp the full extent to which these pathways interact, leading to a better understanding of beta cell biology and diabetes. Addressing the questions related to these stress-induced mechanisms may open new research pathways in preventing and slowing diabetes and ameliorating beta cell functionality and health by means of novel therapeutic agents. ABSTRACT: Aging leads to an increase in cellular stress due to the fragility of the organism and the inability to cope with it. In this setting, there is a higher chance of developing different cardiometabolic diseases like diabetes. Cellular senescence and autophagy, both hallmarks of aging and stress-coping mechanisms, have gained increased attention for their role in the pathophysiology of diabetes. Studies show that impairing senescence dampens and even prevents diabetes while the role of autophagy is more contradictory, implying a context- and disease-stage-dependent effect. Reports show conflicting data about the effect of autophagy on senescence while the knowledge about this interaction in beta cells remains scarce. Elucidating this interaction between autophagy and senescence in pancreatic beta cells will lead to an identification of their respective roles and the extent of the effect each mechanism has on beta cells and open new horizons for developing novel therapeutic agents. To help illuminate this relationship we will review the latest findings of cellular senescence and autophagy with a special emphasis on pancreatic beta cells and diabetes.