Evaluation of the Effects of Quercetin and Dihydroquercetin on Cellular Behavior and Biomarkers of Senescence in Mesenchymal Stem/Stromal Cells Obtained from Elderly Patients

In recent years, there has been increasing evidence that it is possible to slow down the biological aging of the human body. It is known that slowing down aging processes can be achieved by increasing physical activity, dietary restrictions, and the use of chemical compounds that affect various aging mechanisms. Substances that allow selective elimination of senescent (aging) cells are called senolytics. In our work, we evaluated the effect of promising senolytics such as quercetin and dihydroquercetin on the behavior of senescent mesenchymal stem/stromal cells derived from elderly donors. BACKGROUND: The accumulation of senescent cells in human tissues and organs leads to a decrease in the ability of tissues to renew and function normally, which affects the aging of the organism as a whole and contributes to the development of age-associated diseases. Selective elimination of senescent cells using senolytics may be a potential therapeutic approach in the prevention of such diseases. AIM: The main aim of this study was to investigate the effects of promising senolytics (quercetin and dihydroquercetin) on the behaviour of senescent mesenchymal stem/stromal cells (sMSCs) derived from elderly donors. METHODS: During the study of the effect of senolytics on sMSCs, tests assessing such characteristics and aspects of cell behaviour as cell ageing markers, apoptosis, mitochondrial activity, and secretory activity were performed. We used the following research methods: light microscopy, fluorescence microscopy, real-time PCR with reverse transcription, timelapse, XTT test, ICC, and ELISA. RESULTS: In the heterogeneous population of primary isolated sMSCs obtained from elderly patients, cells with markers of cell aging (β-galactosidase, p21 expression, secretory senescence-associated phenotype (SASP)) prevail in comparison with the control. The addition of senolytics to sMSCs can contribute to the change of functional properties of these cells, including a decrease in the expression of p21 and production of SASP components, with dihydroquercitin having the most pronounced effect. CONCLUSION: Based on the obtained results of the study, the differences of the studied senolytics in the character of influence on the behavior of sMSCs were revealed, and the potential efficacy of these compounds for targeted elimination and functional changes of sMSCs was evaluated.