Evaluating the Cell-Type Specificity and Cellular Targets of Senotherapuetic Compounds with Unknown Mechanisms

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In early studies, have already established a workflow for the screening of candidate senolytic compounds in human using a cell viability assay. Using our screening workflow, we test panels of natural senolytic compounds for the ability to kill senescent cells. We have carried out initial senolytic screens in lung fibroblasts, monocytes, preadipocytes, and vascular smooth muscle cells. The most potent and specific overall senolytic compound thus far in gingerenone a, a ginger extract with senolytic activity in all cell types tested so far 40% effective in vascular smooth muscle cells and over 90% effective in all other cell types tested thus far. Flavonoid compounds showed cell-type specificity in their senolytic activities. For example, apigenin was most effective in monocytes but not other cell types. The first CETSA-MS studies are underway with the most effective and senescence-specific compounds from the senolytic screening studies.