Achilles Heels of Senescent Cells: From Transcriptome to Senolytic Drugs

The healthspan of mice is enhanced by selectively killing senescent cells using a transgenic suicide gene. Achieving the same using small molecules would have a tremendous impact on quality of life and burden of age-related chronic diseases. As senescent cells resist apoptosis, we used microarrays to identify transcripts and pathways that differ between senescent and non-senescent preadipocytes, and might be involved in resistance to apoptosis. Primary human abdominal subcutaneous preadipocytes were isolated from 8 healthy lean kidney donors. All subjects were matched by age,gender and BMI. The protocol was approved by the Mayo Clinic Foundation Institutional Review Board for Human Research. Preadipocytes were radiated at 10 Gy to induce senescence or were sham-radiated. From senescent cells RNA was isolated 20 days after irradiation.