OP10 - Phospholipid oxidation of the skin and its role in stress response, autophagy and senescence

Abstract

Oxidation of lipids and proteins is not only a manifestation of aged skin but also potentially causative for age-related aesthetic decline and pathologic damage. Extrinsic oxidative stress, like UV radiation promotes the accumulation of reactive lipid oxidation products. To study which oxidation products are generated by UV other age promoting stressors and in replicative senescence of keratinocytes, fibroblasts and melanocytes, we performed lipidomic analysis of oxidized and non-oxidized phospholipids (PL) using a HPLC-tandem-MS method accompanied by transcriptomic and proteomic profiling. With that approach we could quantify several hundred oxidized lipid species in KC after acute physiological UVA stress, exposure to promoters of cellular senescence like Paraquat over replicative senescence and in aged skin. Oxidized phospholipids activate the antioxidant response system in the various compartments of the skin, they regulate macroautophagy and they fine tune the innate immune system, and they are candidate molecules to be comprised in the senescence associated secretory phenotype of sencescent skin cells.