AMPK-mediated senolytic and senostatic activity of quercetin surface functionalized Fe3O4 nanoparticles during oxidant-induced senescence in human fibroblasts

Abstract

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.

Treatment with Modified Extracts of the Microalga Planktochlorella nurekis Attenuates the Development of Stress-Induced Senescence in Human Skin Cells

“…A cellular model of hydrogen peroxide-induced senescence was considered, as described previously [17,19]. Briefly, BJ and HEK cells were treated with 100 µM hydrogen peroxide for 2 h, and then water and ethanolic extracts were added for up to 7 days to analyze their protective effects.…”

“…Every 48 h, a fresh medium containing microalgal extracts was added. After 7 days of hydrogen peroxide removal, senescence-associated beta-galactosidase (SA-beta-gal) activity was assayed as described previously [17,19]. The effect of water and ethanolic extracts alone (pro-senescence activity) was also investigated.…”

“…We used a cellular model of stress-induced premature senescence that is based on the incubation of cells with 100 µM hydrogen peroxide for 2 h, followed by a 7-day culture without an oxidant [17,19]. After treatment, about 90% population of BJ cells and 95% population of HEK cells were characterized by senescence-associated beta-galactosidase (SA-beta-gal) activity ( Figure 9).…”

Plant-Derived Molecules α-Boswellic Acid Acetate, Praeruptorin-A, and Salvianolic Acid-B Have Age-Related Differential Effects in Young and Senescent Human Fibroblasts In Vitro

“…Cell cycle analysis: The cells were treated with 1 µM ABC, PTA, or SAB for 24 h, and DNA-based cell cycle analysis was performed using Muse ™ Cell Analyzer and Muse ™ Cell Cycle Kit according to the manufacturer's instructions (Merck Millipore, Warsaw, Poland) [42,43].…”

“…The method for cell sample preparation, separating proteins by polyacrylamide gel electrophoresis and transferring to blotting membranes was as described earlier [42,43]. Primary and secondary antibodies used in this study were: anti-p53 (1:1000, MA5-12557, Thermo Fisher Scientific, Waltham, MA, USA), anti-SOD1 (1:500, PA523245, Thermo Fisher Scientific, Waltham, MA, USA); anti-LC3B (1:1000, 2775, Cell Signaling Technology, Danvers, MA, USA); and horseradish peroxidase-conjugated secondary antibody (1:50000, Sigma Aldrich, Poznan, Poland).…”