AbstractHomeostasis is a key feature of the cellular lifespan. Its maintenance influences the rate of ageingand it is determined by several factors, including efficient proteolysis. The proteasome is themajor cellular proteolytic machinery responsible for the degradation of both normal and damagedproteins. Alterations of proteasome function have been recorded in various biological phenomenaincluding ageing and replicative senescence. Proteasome activities and function are decreasedupon replicative senescence, whereas proteasome activation confers enhanced survival againstoxidative stress, lifespan extension and maintenance of the young morphology for longer inhuman primary fibroblasts. Several natural compounds possess anti-ageing/anti-oxidantproperties. In this study, we have identified quercetin (QUER) and its derivative, namelyquercetin caprylate (QU-CAP) as a proteasome activator with antioxidant properties thatconsequently influence cellular lifespan, survival and viability of HFL-1 primary humanfibroblasts. Moreover, when these compounds are supplemented to already senescent fibroblasts,a rejuvenating effect is observed. Finally, we show that these compounds promote physiologicalalterations when applied to cells (i.e. whitening effect). In summary, these data demonstrate theexistence of naturally occurring anti-ageing products that can be effectively used through topicalapplication.