New probe developed for simple, non-invasive detection of ageing rate

Sara Rojas, researcher at the Universitat de València
Sara Rojas, researcher at the Universitat de València
A research team from the Universitat de València, the Universitat Politècnica de València, the CIBER areas of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), and Neurodegenerative Diseases (CIBERNED) and the Research Centre -Príncipe Felipe- (CIPF) has developed a new probe to detect senescent cells in urine, which would help to monitor and better understand ageing-related processes and establish new strategies to reverse the degenerative processes associated with ageing.

As the team of researchers explains, one of the hallmarks of ageing is an increase in the frequency of senescent cells in most organs, leading to tissue dysfunction. The presence of these cells is also associated with numerous age-related diseases.

"The main goal of cellular senescence is to prevent the proliferation of damaged cells that can lead to cancer. However, when damage persists, or during ageing, senescent cells tend to accumulate abnormally, which affects tissue functions and accelerates ageing. Hence the importance of developing new systems that allow these cells to be detected simply and effectively," stresses Ramón Martínez Máñez, deputy director of the Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM) at the UPV and scientific director of CIBER-BBN.

After injection into mice, the probe developed by the team of researchers interacts with an enzyme that is particularly abundant in senescent cells to produce a fluorescent compound that is rapidly eliminated in the urine. "And depending on the intensity of the signal in the urine, we can know the load of senescent cells in the organism," stated Isabel Fariñas of the Universitat de València and deputy director of CIBERNED and researcher Mar Orzáez of the CIPF.

Their study also followed a senolytic treatment, with drugs that remove senescent cells and can rejuvenate tissues, and found that the intensity of the signal in the urine was related to the reduction of senescence in the animals and the reduction of age-related anxiety.

"When administered, a fluorophore is released that is ultimately excreted by the kidneys and can be measured in the urine. The intensity of the fluorophore indicates the level of cellular senescence load and we have seen that this correlates with age-related anxiety during ageing and senolytic treatment," explains Isabel Fariñas of the Universitat de València and deputy director of CIBERNED.

The results obtained by the team from the Universitat de València, the Universitat Politènica de València, CIBER-BBN, CIBERNED and the CIPF open a way to better understand ageing and its effects on health. "It could help us to develop more effective ways of tackling age-related problems, as well as to simply follow in urine treatments aimed at eliminating or reducing cellular senescence, even in humans," concludes Ramón Martínez Máñez.

Reference

Rojas-Vázquez, S., Lozano-Torres, B., García-Fernández, A. et al. A renal clearable fluorogenic probe for in vivo β -galactosidase activity detection during aging and senolysis. Nat Commun 15, 775 (2024). Doi: https://doi.org/10.1038/s41467­’024 -44903-1