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Cell biology

Senolytics

DESenolytika

Senolytics are drugs that hunt down and kill senescent "zombie" cells, the worn-out cells that pile up in your tissues with age. They spare healthy cells. They work by exploiting the survival tricks those cells rely on, like BCL-2 family proteins and PI3K/AKT signaling. One peptide, FOXO4-DRI, instead breaks up the FOXO4-p53 partnership. Each drug hits a different weakness, so they are not interchangeable. The most-studied candidates are dasatinib plus quercetin, fisetin, and navitoclax. In animals, short bursts improve physical function and extend healthspan. In humans the evidence is still stuck at early-phase trials. Using them outside a study is not established practice.

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Sources

  1. Zhu Y, Tchkonia T, Pirtskhalava T, et al. (2015). The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Celldoi:10.1111/acel.12344
  2. Hickson LJ, Langhi Prata LG, Bobart SA, et al. (2019). Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicinedoi:10.1016/j.ebiom.2019.08.069
  3. Chang J, Wang Y, Shao L, et al. (2016). Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nature Medicinedoi:10.1038/nm.4010
  4. Baar MP, Brandt RMC, Putavet DA, Klein JDD, Derks KWJ, Bourgeois BRM, Stryeck S, Rijksen Y, van Willigenburg H, Feijtel DA, et al. (2017). Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Celldoi:10.1016/j.cell.2017.02.031

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