Carnosine is an endogenous β-alanyl-L-histidine dipeptide endowed of antioxidant and carbonyl scavenger properties, able to significantly prevent the visible signs of aging and photoaging. To deeply investigate the mechanism of action of carnosine on human skin proteome, a 3D scaf-fold-free spheroids model of primary dermal fibroblasts from 50-years-old donor, was here adopted in combination with quantitative proteomics