The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs

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…

• GF
  Glenn Foundation for Medical Research
• GC
  Georgia Clinical and Translational Science Alliance

  Award: UL1-TR000157
• NI
  National Institutes of Health

  Awards: AG013925, AG041122, AG043376, HL111121, AG031736, UL1-TR000157, DK050456, AG044396