DPP4 Assay - A Suggestion for Senescent-Cell-Burden Estimation
In doing self-experimentation with senolytic drugs like Fisetin and/or D+Q, we are attempting to reduce the body's burden of senescent cells to promote health and anti-aging. In this context, we badly need some straightforward accurate way of assessing in vivo the current senescent-cell burden of our bodies and of monitoring any changes the senolytic treatment are producing.
The present standard way of detecting the presence of senescent cells is by testing for the presence of the senescence-associated enzyme beta-galactosidase (SA-b-gal) in the cells. However, the SA-b-gal assay procedure seems to operate mainly in vitro. It involves sample staining and microscopy, it is destructive, and it is apparently used mainly in assessing the senescence of cell cultures or biopsies.
Perhaps there is an alternative. I recently came across a 2017 paper entitled "Identification of senescent cell surface targetable protein DPP4" by Kyoung Mi Kim, et al. The authors point out that the protein dipeptidyl peptidase 4 or DPP4 (aka DPPIV or CD26) is selectively over-expressed on the surface of senescent (non-proliferating) human diploid fibroblasts. Admittedly, it is not established whether such DPP4 over-expression is a characteristic of senescent cells in general. However, it has also been found that pleural and colorectal cancer cells over-express DPP4. This suggests that DPP4 surface over-expression is a general characteristic of senescent cells.
Assuming that this is the case, it seems to me that some quantity of the surface-expressed DPP4 proteins should end up in the bloodstream as soluble DPP4s proteins. Therefore, an assay of the concentration of DPP4s in blood serum might serve as an indicator of the general senescent-cell burden of the blood donor.
How difficult is it to measure DPP4 in the blood? Apparently, it's easy. A quick Google search indicates that there are many commercially available DPP4 Assay Kits for humans (and for mice) that cost ~$400-800, do 96 samples at once, and would work fine on blood samples.
I wonder if some organization like LifeExtension could be persuaded to provide low-cost DPP4 Assays, so that we could check directly whether our attempts to reduce our senescent cell count are having the desired effect.
I see from their website that Pacific Biomarkers, which seems to be located in Seattle not far from the Space Needle, lists DPPIV (i.e., DPP4) as one of the biomarkers they can do an assay on. Here's the link. They don't give prices for the DPPIV assays on their web site, and it appears that they are set up to service large-ish projects.Reply