New Senolytics Targeting ß-Galactosidase

     The standard way of identifying senescent cells in vitro is to stain a tissue biopsy with a dye that turns the enzyme ß-galactosidase a dark blue, and then counting the population of blue cells as seen in a microscope.  This works because senescent cells are known to over-express ß-galactosidase.

    There's a new Nature Research paper by some researchers at Stanford and at Rubedo Life Sciences in which they take the idea of targeting the ß-galactosidase in senescent cells a couple of steps further than did the Chinese PZ work that I had mentioned earlier.

    First, they do the cute trick of bonding the firefly enzyme D-Luciferane to the sugar Galactose and injecting this into test mice.  The D-Luciferane is inactive until the attached Galactose is stripped away by ß-galactosidase.  When that happens, it is activated and the senescent cells light up under UV, so that one can do an optical scan for the presence of senescence.  They show great pictures of such in vivo bio-luminescent scans on test mice, showing their degree of senescence.  (Would anyone like to have their senescent cells lit up?)

    For senolytic treatment, they hitch the sugar Galactose to 5-Fluorouridine (5FU), a generic cell-killing chemotherapy drug used for cancer treatment.  This produces what they call "5FURGal".  They inject this into old mice and demonstrate enhanced performance levels that come close to those of young untreated mice.

     It is interesting that in the text and also on the Rubedo Life Sciences website, they emphasize that they are treating "frailty" (rather than "aging").  I take this as a maneuver to get around the FDA dictum that aging is not a treatable disease.  Presumably, frailty is a treatable condition, even if aging is not.