487 Lipidomic and proteomic analyses identify increased degradation of sphingolipids in prematurely senescent human dermal fibroblasts

A wide range of environmental factors (e.g. UV radiation, pollution) challenges skin homeostasis and its prolonged imbalance accelerates aging. Aged is characterized by presence senescent cells, which have a changed appearance phenotype, accumulate damaged biomolecules simultaneously produce mixture danger signaling molecules negatively affect their microenvironment activate the immune response. We previously described increased levels lysophosphatidylcholines, in both replicative vitro stress-induced premature (SIPS) fibroblasts. Global lipidomics with an UHPLC triple quadrupole MS/MS method confirmed lysophospholipid content SIPS Moreover, broader spectrum analyzed lipid classes revealed that phospholipids are not only senescence regulated lipids. In combination proteomic data analysis, upregulation sphingolipid degradation pathway`s enzymes, e.g. β-galactosidase or acid ceramidase, were recognized, supporting decreased amounts sphingolipids found cells` extracts. Predominant within identified lipids long-chain (C16) very-long chain (C24) acyl, together represent 70-80% cultured sphingolipidome we can see shift to acyls at expense acyls, suggesting elongation process regulated. Recognition structure function (epi-) lipidome contributes better understanding biological base phenotype. It also will allow us targeting consequences lipid-mediated modulation system therefore help find approaches how mitigate development associated pathologies.