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Experimental Gerontology, 2010

Niki Chondrogianni, , Suzanne Kapeta^a, Ioanna Chinou, Katerina Vassilatou, Issidora Papassideri and Efstathios S. Gonos

^a National Hellenic Research Foundation, Institute of Biological Research and Biotechnology, 48 Vassileos Constantinou Avenue, Athens 11635, Greece
^b University of Athens, School of Pharmacy, Division of Pharmacognosy and Chemistry of Natural Products, Zografou Campus, Athens 15771, Greece
^c Korres S.A. Natural Products, 57th Athens-Lamia National Road, 32011, Inofyta, Greece
^d Department of Cell Biology and Biophysics, University of Athens, Athens, Greece

Received 20 January 2010;
revised 31 May 2010;
accepted 1 July 2010.
Available online 7 July 2010.

Abstract

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 primary fibroblasts. 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.