Anti-ageing and rejuvenating effects of quercetin

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 for 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 antioxidant 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.

18α-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression inCaenorhabditiselegansand Neuronal Cultures

“…The observed dependence is in agreement with studies in human (10,15,27) and yeast cells (7,32) and in multicellular organisms (8,46,55,58). It is, however, noteworthy that with the exception of quercetin (10) and 18a-GA (27) in all other mentioned studies, proteasome activation was achieved through genetic manipulation.…”

Cellular senescence in aging and age-related disease: from mechanisms to therapy

“…In combination with quercetin, a plant flavonoid with lifespan-extending antioxidant and proteosome activating properties in worms 157–160 and cytoprotective effects in mice 161 , dasatinib exhibits senolytic activity in cultured cells. In old mice, these compounds were shown to improve parameters of cardiac and vascular function, although the extent to which senescent cell killing occurred and contributed to these effects is unknown.…”

Dietary antiaging phytochemicals and mechanisms associated with prolonged survival

“…Interestingly, recessive mutation of the gene age-1 or daf-2 (encoding for the IGF-1 receptor in C. elegan ), two key players in the metabolic pathway to regulate the rate of aging, abolished the lifespan-extension effect of quercetin in C. elegans [58,59], suggesting that quercetin may prolong lifespan in the worms through inhibiting, either directly or indirectly, the age-1 and daf-2-mediated pathways. A recent study reported that quercetin and its derivative quercetin caprylate can rejuvenate senescent fibroblasts and increase their lifespan via activating proteasome [60]. Quercetin is reported as the most potent reactive oxygen species (ROS) scavenger of ROS in the flavonoid family and quercetin has over 6 times the antioxidant capacity than the reference antioxidant trolox or vitamin C [61–63].…”