Two‐Dimensional Design Strategy to Construct Smart Fluorescent Probes for the Precise Tracking of Senescence

The tracking of cellular senescence usually depends on the detection senescence-associated β-galactosidase (SA-β-gal). Previous probes for SA-β-gal with this purpose only cover a single dimension: accumulation enzyme in lysosomes. However, is insufficient to determine destiny because endogenous β-gal enriched lysosomes not related senescence, but also some other physiological processes. To address issue, we introduce our fluorescent including second lysosomal pH, since de-acidification unique feature senescent cells. With novel design, achieved excellent discrimination from cancer-associated β-gal, which enables them track as well tissue aging more precisely. Our crystal structures model E. coli mutant (E537Q) complexed each probe further revealed structural basis recognition.