Blagoskonny's new paper - https://www.oncotarget.com/article/28049/text/ - suggests modest lifespan benefit from Dasatinib quercetin combo is from a mini-ramapycin mTOR inhibition like effect; suggesting it won't stack on top of rapamycin and in theory could cause unwanted mTOR inhibition.
Blagosklonny makes the point that senescent (sen) cell markers shown in senolytics studies are based on low accuracy markers which may not prove senolysis of parnechymal cells, and rather are just macrophages having their p16 or SABG positivity reduced.
SABG+ve/P16 in biopsy is poor specificity for sen cell status as no forced culture or cell ID is involved, and macrophages are everywhere. To read sen cell papers one should see evidence of a sen cell marker (sensitivity) AND a cell ID marker (specificity) e.g. FACS CDs or some specific stain or enzyme fluorescence; with some culture+cellID as gold standard; I guess you can FACS biopsies to validate histological imaging that the SABG/P16+ves are not macrophages but cell ID based parenchyma... and then try and culture them post FACS
So fluorogenic SABG+ve CD8 T cells on FACS (presumably) is probably high accuracy as its got cell ID, so I can carry on using that as a red bone marrow age marker... everything else is preclinical though until we can do MRI ideally e.g. 13C HP MRS CSI MRI to see sen cells on preferably 7T MRI..a project which seemed to get stalled in 2014, no response from the professor radiologist leading that to my team yet...
Maybe I can create reference ranges for campisi senolysis marker https://www.longevity.technology/first-non-invasive-biomarker-to-track-and-verify-senolytics/ based on standard age related response to a fixed dose of purported senolytic, and use it to estimate % sen cell load in that senolytics target organ profile
Similar to GRAIL cfDNAm there may be a senesncent cell GRAIL based on cfDNAm, which can tell you which organs have sen cells above a set cut off and be used to choose and validate therapy; maybe organ specific surface markers leak into blood as an alternative to cfDNAm
These guys are thinking the same as me RE benefit of FACS, and give a nice review of all the new surface markers and ways of selective targeting of sen cells; notably they dont mention senolysis syndrome.. if you remove all sen cells in an organ you might instantly die lol so need senorejuvants (convert sen cells to normal cells) preferably or triple sen cell therapy (dubbed by me) of senomorphic + senolytic + parenchymal replacement method https://www.mdpi.com/2073-4409/10/7/1740