The effect of fisetin on the expression of some genes associated with aging in Drosophila melanogaster

Aging is a natural and physiological process for living organisms. Senescence, which is cellular aging, constitutes a process in which metabolic cell activity continues but the cells do not divide. Senescent cells that continue to be metabolically active secrete senescence-associated secretory phenotypes (SASP). These secretion components cause the organisms to increase the risk of contracting various diseases, especially chronic diseases. Senolytics are compounds that specifically eliminate cells that have undergone senescence by targeting them according to their various properties. In this thesis study, fisetin, a senolytic compound targeting the Bcl-2 family, was investigated using the model organism Drosophila melanogaster, commonly known as the fruit fly. Fisetin was applied to Drosophila at two different concentrations (0,002 M and 0,005M) across four time groups (7, 14, 21, and 28 days). The expressions of the mammalian sirtuin 1 homolog dsir2, dFOXO and dRPD3 genes, which are associated with aging, were analyzed by RT-qPCR method at different times and doses of fisetin. Statistical analysis of all data obtained was analyzed with the Duncan test (p < 0.05) with a 95% confidence interval using SPSS software 20.0 (IBM, Armonk, NY, USA). Protein protein interactions of the genes whose gene expressions were examined were also obtained using the Cytoscape software and digital expression profiles were obtained in different tissues with the TBtools program. As a result of the expression analyses, it was observed that the expression of the dsir2 gene was highest on the 7th day in the group treated with 0,005M fisetin, on the 14th day in the group treated with 0,002 M fisetin, on the 21st day in the group treated with 0,005M fisetin, and in the untreated control group on the 28th day. The highest gene expression for the dFOXO gene was found in the group applied 0,002 M fisetin on the 7th day, in the control group without fisetin application on the 14th day, in the group applied 0,005M fisetin on the 21st day, and in the control group without fisetin application on the 28th day and the highest gene expression for the dRPD3 gene was observed in the group applied 0,005M fisetin on the 7th day, in the group applied 0,002 M fisetin on the 14th day, in the group applied 0,005M fisetin on the 21st day, and in the control group without fisetin application on the 28th day.