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The topic for the September Edition of the Journal Club was the recent human trial of senolytic agents Dastatinib and Quercetin. For the researchers at the Mayo Clinic this was a follow on study from their previous human trial targeting IPF. This time the researchers ran a study to see how senolytics influenced diabetic kidney disease and if it actually removes senescent cells in humans.

The good news is that the senescent cell clearing therapy does indeed appear to work in a similar way to how it works in mice and is able to destroy harmful pro-inflammatory senescent cells which accumulate as we age. This study is admittedly small but it does suggest that these particular agents are effective in humans and not just mice and that they have potential for therapies aimed at delaying or even reversing some age-related conditions and diseases.

Reference

Hickson, L. J., Prata, L. G. L., Bobart, S. A., Evans, T. K., Giorgadze, N., Hashmi, S. K., … & Kellogg, T. A. (2019). Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine.

About the author

Dr. Oliver Medvedik

Oliver Medvedik, Co-founder of Genspace citizen science laboratory in Brooklyn NY, earned his Ph.D. at Harvard Medical School in the Biomedical and Biological Sciences program. As part of his doctoral work he has used single-celled budding yeast as a model system to map the genetic pathways that underlie the processes of aging in more complex organisms, such as humans. Prior to arriving in Boston for his doctoral studies, he has lived most of his life in New York City. He obtained his bachelor’s degree in biology from Hunter College, City University of New York. Since graduating from Harvard, he has worked as a biotechnology consultant, taught molecular biology to numerous undergraduates at Harvard University and mentored two of Harvard’s teams for the international genetically engineered machines competition (IGEM) held annually at M.I.T.
  1. October 3, 2019

    Those figures are suspicious. Someone appears to have mirrored the results graphs around the x-axis before and after. Meanwhile, my attempts to recreate the p values they got from eye balling the graph failed to establish significance.

    I’m not really suggesting any sort of scientific misconduct, at this point there’s no reason to jump to that, but it’s embarrassing that someone didn’t notice this, it really detracts from the otherwise promising results of the paper.

  2. October 3, 2019

    Good eye! I probably didn’t notice it the first time around when reading because I had a black and white printout. Although it’s not a perfect mirror as a few of the colored data points are shifted relative to the x axis, their y positions still are exactly mirrored, which is the relevant bit. So yes, it appears its a perfect mirror around the y axis between the two before and after data clusters.

    I’ll ask the authors for a clarification.

  3. October 15, 2019

    Good point, this is indeed very surprising. Also you would expect that they perform a paired t-test to determine statistical significance here rather than an unpaired t-test, given that the biopsies are from the same patients before/after treatment. Can you please keep us updated of an answer from the authors?

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