Abstract 1805 Insights into the functional role of ceramides in replicative senescence

Ceramides belong to the class of highly bioactive sphingolipids.Over the past years, ceramides have drawn considerable attention for their role as a secondary messenger in various cellular processes like apoptosis, senescence, autophagy, necroptosis, ER stress and cellular differentiation.Several studies have indicated that these different functions of ceramides are shaped by their structural and chemical properties and their dynamic spatial distribution within cells.However, emerging research highlights the critical importance of lipid synthesis, metabolism, and transport sites in modulating lipid function, reinforcing the idea that lipids' location within the cell can be important for determining function in addition to their chemical structure.While ceramides participate in multiple cellular processes, the mechanisms and consequences of ceramide accumulation have extensively been investigated in apoptosis.Studies have shown that ceramides accumulate at the mitochondria and facilitate mitochondrial membrane permeabilization by BAX, followed by the release of cytochrome c which activates caspases resulting in apoptosis.However, the localization of ceramide accumulation and protein partners involved in replicative senescence are unknown.This work focuses on identifying the mechanisms of ceramide accumulation in replicative senescence and provides insights into the mechanism by which ceramides induce senescence.Here I will present the results of a comparative analysis of the regulation of ceramides in apoptosis and senescence and highlight differences in ceramide biosynthesis and processing that might be responsible for ceramide's senescent activity.