286 Oxidative Stress Modulation by Carnosine in Scaffold Free Human Dermis Spheroids Model: A Proteomic Study

Carnosine is an endogenous dipeptide with antioxidant and scavenger properties, shown to prevent aging photoaging process by in vivo vitro models on different human tissues. Here advanced quantitative proteomic approach (high-resolution mass spectrometry network analyses) was applied a 3D scaffold-free dermal spheroids model investigate the biological responses induced carnosine dermis. Primary fibroblasts from 50-years-old donor were seeded hanging drops develop dermis spheroids. After treatment 150 μM L-carnosine for 7 14 days, collagen type III expression evaluated immunofluorescence whole mount tissues high-resolution Z-stacks. Proteomic analysis performed nLC MS/MS (orbitrap Fusion) after proteins extraction trypsin digestion. Collagen localization confirmed preservation of physiological phenotype label free proteomics provides wide description dynamic behaviour through extracellular matrix (ECM) modulation over time. In long term culture progressive senescent profile reached upregulation oxidative stress proteins. positive effect mitochondria metabolism, ECM assembly, apoptosis restoring younger profile: 204 differentially regulated increased remodelling (basigin TMSB4X), cell-matrix interactions, cellular fate tissue architecture. ROS signalling reduction activation antioxidant/detoxification genes (MGST3 GSTP1) protection against aging. Miniaturized scaffold combination provide predictive complete profiling personalized therapies.