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Quercetin, while used in combination with dasatinib as a senolytic therapy capable of destroying senescent cells, is not meaningfully senolytic on its own. One argument as to why this is the case is that compounds of this class are not very bioavailable – in other words that quercetin, suitably modified, or delivered in a different manner, would be senolytic enough to form a basis for therapy. Researchers here take the approach of coating nanoparticles with quercetin molecules, and find that the resulting particles can selectively kill senescent cells in cell culture, unlike quercetin alone. This is a promising demonstration, particularly if we consider that it might be applied to the much more senolytic flavenoid fisetin, but it is always best to wait for animal data before becoming too excited by any given approach.
Cellular senescence may contribute to aging and age-related diseases and senolytic drugs that selectively kill senescent cells may delay aging and promote healthspan. More recently, several categories of senolytics have been established, namely HSP90 inhibitors, Bcl-2 family inhibitors and natural compounds such as quercetin and fisetin. However, senolytic and senostatic potential of nanoparticles and surface-modified nanoparticles has never been addressed.
In the present study, quercetin surface functionalized Fe3O4 nanoparticles (MNPQ) were synthesized and their senolytic and senostatic activity was evaluated during oxidative stress-induced senescence in human fibroblasts in vitro. MNPQ promoted AMPK activity that was accompanied by non-apoptotic cell death and decreased number of stress-induced senescent cells (senolytic action) and the suppression of senescence-associated proinflammatory response (decreased levels of secreted IL-8 and IFN-β, senostatic action). In summary, we have shown for the first time that MNPQ may be considered as promising candidates for senolytic- and senostatic-based anti-aging therapies.