Authors
Yi Zhu, Tamara Tchkonia, Tamar Pirtskhalava, Adam C Gower, Husheng Ding, Nino Giorgadze, Allyson K Palmer, Yuji Ikeno, Gene B Hubbard, Marc Lenburg, Steven P O'Hara, Nicholas F LaRusso, Jordan D Miller, Carolyn M Roos, Grace C Verzosa, Nathan K LeBrasseur, Jonathan D Wren, Joshua N Farr, Sundeep Khosla, Michael B Stout, Sara J McGowan, Heike Fuhrmann‐Stroissnigg, Aditi U Gurkar, Jing Zhao, Debora Colangelo, Akaitz Dorronsoro, Yuan Yuan Ling, Amira S Barghouthy, Diana C Navarro, Tokio Sano, Paul D Robbins, Laura J Niedernhofer, James L Kirkland
Publication date
2015/8/1
Journal
Aging cell
Volume
14
Issue
4
Pages
644-658
Description
The healthspan of mice is enhanced by killing senescent cells using a transgenic suicide gene. Achieving the same using small molecules would have a tremendous impact on quality of life and the burden of age‐related chronic diseases. Here, we describe the rationale for identification and validation of a new class of drugs termed senolytics, which selectively kill senescent cells. By transcript analysis, we discovered increased expression of pro‐survival networks in senescent cells, consistent with their established resistance to apoptosis. Using siRNA to silence expression of key nodes of this network, including ephrins (EFNB1 or 3), PI3Kδ, p21, BCL‐xL, or plasminogen‐activated inhibitor‐2, killed senescent cells, but not proliferating or quiescent, differentiated cells. Drugs targeting these same factors selectively killed senescent cells. Dasatinib eliminated senescent human fat cell progenitors, while quercetin was …
Scholar articles
YI Zhu, T Tchkonia, T Pirtskhalava, AC Gower, H Ding… - Aging cell, 2015