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

在早期的研究中，我们已经建立了一个使用细胞活力测定筛选人类候选抗衰老化合物的工作流程。使用我们的筛选工作流程，我们测试天然抗衰老化合物面板的能力，以杀死衰老细胞。我们对肺成纤维细胞、单核细胞、前脂肪细胞和血管平滑肌细胞进行了初步的衰老筛选。这是目前为止姜素酮a中最有效和最特异的抗衰老化合物，一种生姜提取物在所有类型的细胞中都有抗衰老活性目前为止，在血管平滑肌细胞中有40%的有效性在所有其他类型的细胞中有90%以上的有效性。黄酮类化合物的抗衰老活性具有细胞类型特异性。例如，芹菜素对单核细胞最有效，但对其他细胞类型无效。第一个ccetsa - ms研究正在进行中，从抗衰老筛选研究中获得最有效和衰老特异性的化合物。

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.