Homeostasis is a key feature of the cellular lifespan. Its maintenance influences the rate of ageing and it is
determined by several factors, including efficient proteolysis. The proteasome is the major cellular proteolytic
machinery responsible for the degradation of both normal and damaged proteins. Alterations of proteasome
function have been recorded in various biological phenomena including ageing and replicative senescence.
Proteasome activities and function are decreased upon replicative senescence, whereas proteasome activation
confers enhanced survival against oxidative stress, lifespan extension and maintenance of the young morphology
longer in human primaryfibroblasts. Several natural compounds possess anti-ageing/anti-oxidant properties. In
this study, we have identified quercetin (QUER) and its derivative, namely quercetin caprylate (QU-CAP) as a
proteasome activator with anti-oxidant properties that consequently influence cellular lifespan, survival and
viability of HFL-1 primary human fibroblasts. Moreover, when these compounds are supplemented to already
senescent fibroblasts, a rejuvenating effect is observed. Finally, we show that these compounds promote
physiological alterations when applied to cells (i.e. whitening effect). In summary, these data demonstrate the
existence of naturally occurring anti-ageing products that can be effectively used through topical application.
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