Geroscience is a very active field in biomedicine. Monitoring the rate of aging requires effective ways to measure systemic changes that can be used as biomarkers of decline progression. An increased prevalence of cell senescence seems to be linked to the deterioration of various organs, yet pinpointing exclusive markers for cell senescence remains a challenging endeavor. Among the available markers, lysosomal β-Gal enzymatic activity stands out as one of the most commonly used indicators of cell senescence12,55. Consequently, various probes have been recently devised to provide a means of detecting this state within isolated cells, biopsies, or whole organisms through imaging techniques17,18,19,20,21. It is worth noting that senescence-associated β-Gal activity is not due to a specific β-Gal enzyme or a different lysosomal pH, but a higher activity resulting from increased lysosomal mass and increased expression of Glb1, the gene encoding the lysosomal β-Gal enzyme. Therefore, the design of a probe specifically tailored to exclusively detect β-Gal activity of senescent cells is difficult to achieve and most of the probes currently available rely on the recognition of increased levels of β-Gal enzymatic activity in these cells56. A second challenge so far is to develop a biomarker that can be easily monitored. One promising approach in the field involves detecting biomarkers from easily accessible biofluids using the simplest possible detection systems57,58. In this context, one innovative strategy pursues the design of fluorogenic probes (in an OFF state) that can be transformed by the action of certain biomarkers (i.e. an enzyme) in cells and tissues to give a final fluorescent product (in an ON highly emissive state) that can diffuse out of the cells and has a rapid renal clearance, thus allowing its detection in the urine using a simple fluorimeter59. Based on this concept, we report herein the case of detection of lysosomal β-Gal using the fluorogenic probe sulfonic-Cy7Gal. We show that cell-entrapped (WOS-Cy7Gal) and diffusible (sulfonic-Cy7Gal) forms of this probe produce a brighter emission in cells undergoing replicative or induced senescence. We provide evidence of the reliability of the sulfonic-Cy7Gal probe to monitor an experimentally controlled load of cellular senescence in vivo by using BALB/cByJ mice bearing breast cancer tumors treated with senescence-inducing chemotherapy. We also show that the fluorophore intensity in urine correlates with age progression and age-associated anxiety in mice during natural and accelerated aging. In addition, the probe allows a non-invasive monitoring of the effects of senolytic treatment. Interestingly, our data reveals that senolytic treatments based on the pharmacological use of agents that eliminate senescent cells are transient. These findings demonstrate that renal clearable fluorogenic probes are a versatile modular tool that opens new opportunities to develop simple diagnoses in urine for a variety of diseases where abnormal enzymatic activity is a biomarker. We anticipate that this technology can also be applied in the monitoring of therapeutic treatments. Such adaptive detection system could also be applicable in low-resource environments and might democratize access to advanced and sensitive diagnoses.