405 Lyso-Pospholipids Contribute to the Inflammatory Nature of Senescent Dermal Fibroblasts

Abstract

With age, senescent cells accumulate in the skin, which is causatively linked to low-grade inflammation, decline in tissue function and changes in appearance. The senescence associated secretory phenotype(SASP), a cocktail of inflammatory proteins, majorly contributes to this phenomenon. Lipid signaling molecules are potent inflammation mediators and we have recently discovered lipid components of the melanocyte SASP, but there is limited knowledge on their contribution to skin aging and fibroblast senescence. Using mass spectrometry, we identified senescence associated lipid species of which two lysophosphatidylcholines (lyso-PCs) were the dominant and most highly regulated ones intracellularly in various senescence models. When non-senescent HDF were exposed to lyso-PCs, we observed a dose-dependent increase in SASP-protein secretion, which can act as chemoattractants on immune cells. Surprisingly, however, we found lyso-PCs to disturb pattern recognition receptor signaling in monocytes and to obstruct phagocytosis by macrophages. Therefore, these lipid members of the SASP may contribute to attracting immune cells, while then interfering with the recognition and removal of senescent cells by macrophages. This“look, don’t touch”phenomenon might help to explain the persistence and accumulation of senescent cells in tissues, despite the presence of immune cells.