Because the age-related phenotypic differences between SAMP8 and SAMR1 mice begin to be evident after approximately 6 months of age45,46,47, we injected 7-m SAMR1 and SAMP8 mice with sulfonic-Cy7Gal and found a stronger fluorescent signal in the urine of SAMP8 vs. SAMR1 mice (Fig. 3f). We next decided to test whether the sulfonic-Cy7Gal probe could indeed be providing an in vivo readout of cell senescence, by comparing urine fluorescence with markers of senescence at the cell level in SAM mice. After euthanasia, we extracted the kidneys and livers, and their isolated cells were incubated ex vivo with the cell-trapped WOS-Cy7Gal probe or intracellularly immunostained for p16 or lamin B1 prior to their analysis by flow cytometry. In agreement with the levels of fluorescence in the urine of the animals, we found higher levels of β-Gal activity in SAMP8 vs. SAMR1 mice with the WOS-Cy7Gal probe (Fig. 4a). Likewise, we could observe higher proportions of cells with detectable levels of p16 and reduced levels of lamin B1 in cell dissociates from the organs of SAMP8 mice (Fig. 4b, c). These data indicated a good correlation between the end-point measurement of cell senescence with well-accepted markers and the in vivo global detection of β-Gal activity with the sulfonic-Cy7Gal probe in urine.