The Initial D+Q Study

  I became curious as to just how it was determined that the combination of Dasatinib and Quercetin in a 1:10 combination was an effective senolytic treatment.  There are very many compounds out there, and it was difficult for me to imagine how this particular combination could emerge from that vast range of possibilities.  Therefore, I tracked down the original source of the idea as a reference in a Kirkland paper.  The key paper was published in 2015 in the journal Aging Cell, vol. 14, pp. 644-658 by Yi Zhu, et al, and is entitled "The Achilles' heel of senescent cells:  from transciptome to senolytic drugs".  Here is a LINK to the .pdf of the paper.

  The authors noted that senolytic cells were somehow avoiding the natural process of aptosis that should have cleared them.  When they were eliminated at all, it was done by the immune system rather than the processes of aptosis or necrosis.  They hypothesized that senescent cells are using the same pathways employed by cancer cells to block the aptosis process.  Therefore, they suggested that a drug that prevents aptosis blockage should clear senescent cells.

  They tested 46 different candidate compounds on cell cultures of human senescent cells and found that Dasatinib (D) and Quercetin (Q) showed particular promise in clearing the senescent cell targets.  Further, they found that the actions of the drugs were somewhat complementary, with D being particularly effective on senescent preadipocyte cells (fat cells) and Q being particularly effective on senescent endothelial cells (blood-vessel lining cells).  They also determined that a 1:10 D+Q combination was more effective than either drug individually.  They then tested this combination on mice and found very positive results in extending health spans.

This is only a brief summary of a complex 15 page paper, but you can read it yourself for more details.

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