Authors
Yi Zhu, Tamara Tchkonia, Heike Fuhrmann‐Stroissnigg, Haiming M Dai, Yuanyuan Y Ling, Michael B Stout, Tamar Pirtskhalava, Nino Giorgadze, Kurt O Johnson, Cory B Giles, Jonathan D Wren, Laura J Niedernhofer, Paul D Robbins, James L Kirkland
Publication date
2016/6/1
Journal
Aging cell
Volume
15
Issue
3
Pages
428-435
Description
Clearing senescent cells extends healthspan in mice. Using a hypothesis‐driven bioinformatics‐based approach, we recently identified pro‐survival pathways in human senescent cells that contribute to their resistance to apoptosis. This led to identification of dasatinib (D) and quercetin (Q) as senolytics, agents that target some of these pathways and induce apoptosis preferentially in senescent cells. Among other pro‐survival regulators identified was Bcl‐xl. Here, we tested whether the Bcl‐2 family inhibitors, navitoclax (N) and TW‐37 (T), are senolytic. Like D and Q, N is senolytic in some, but not all types of senescent cells: N reduced viability of senescent human umbilical vein epithelial cells (HUVECs), IMR90 human lung fibroblasts, and murine embryonic fibroblasts (MEFs), but not human primary preadipocytes, consistent with our previous finding that Bcl‐xl siRNA is senolytic in HUVECs, but not preadipocytes …
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