Senolytic Compounds Reduce Epigenetic Age of Blood Samples in Vitro

Senolytics are a group of small molecules that specifically target senescent cells by interfering with their anti-apoptotic signaling pathways and inducing apoptosis. Studies have shown that senolytic treatments can selectively remove senescent cells, reduce proinflammatory cytokines and prolong t #senolytics Rationale behind our study Most of the in vitro studies performed to date have been based on modelling the senescence system by artificially inducing DNA damage through radiation or inflammatory cytokines to show that senolytics have the potential to eliminate these cells. There is a lack of studies to quantify and understand senolytic treatment in primary blood samples and especially in healthy aging humans. Therefore, we hypothesized that targeting these cells with senolytic drugs may have the potential to reduce epigenetic aging and other markers associated with senescence. Key Findings Epigenetic age reduction: A three-day senolytic treatment of human peripheral blood mononuclear cells (PBMCs) in vitro showed a reduction in epigenetic age as measured by DNA methylation changes in age-associated regions. Elimination of senescent cells: Senolytic treatment resulted in a decrease in senescent markers such as senescence-associated β-galactosidase with C12FDG and p16INK4a expression, as well as a shift within blood cell composition. Effective senolytic compounds: Four drugs showed an overall effect on both epigenetic age and cellular senescence: JQ1 is an effective inhibitor of the BET family that targets the DNA repair pathway of the non-homologous end joining. The other three drugs, RG7112, AMG232 and nutlin-3a, are MDM2 inhibitors that disrupt with the interaction between p53 and MDM2, leading to a stabilized p53 and promoting apoptosis in senescent cells. Dr. Noor Gajraj is a leading educator and physician in his field. He has practiced medicine for more than 25 years in the United Kingdom and the United States. He has been an Associate Professor of Anesthesiology and Pain Management at U.T. Southwestern Medical Center in Dallas. He is a board certificated by the American Board of Anesthesiology, the American Board of Pain Medicine, and the American Academy of Pain Management. He has authored over 100 publications and delivered more than 500 lectures.