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A team of researchers from the Universitat Politècnica de València, the Universitat de València, the CIBER Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) and Neurodegenerative Diseases (CIBER-NED) and the Centro de Investigación Príncipe Felipe (CIPF), has developed a new probe to detect senescent cells in urine, which could help to monitor and better understand the processes related to ageing and establish new strategies to reverse the degenerative processes associated with it. The research is published in the Nature Communications journal.

As the researchers explain, one of the hallmarks of ageing is the increased frequency of senescent cells in most organs, leading to tissue dysfunction. The presence of these cells is also associated with many 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 accumulate abnormally, affecting tissue function and accelerating ageing. This is why it is important to create new systems to detect these cells easily and effectively," says Ramón Martínez Máñez, deputy director of the Inter-University Research Institute for Molecular Recognition Research and Technological Development (IDM) at the UPV and scientific director of CIBER-BBN.

When injected into mice, the probe interacts with an enzyme particularly abundant in senescent cells, producing a fluorescent compound rapidly excreted in the urine. "And depending on the intensity of the signal in the urine, we can know the burden of senescent cells in the organism," points out Isabel Fariñas of the UV and deputy director of CIBERNED, and researcher Mar Orzáez of the CIPF.

Monitoring of senolytic treatments

In their study, they also monitored senolytic treatment with drugs that eliminate senescent cells and can rejuvenate tissues. They observed 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, which 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 UV and deputy director of CIBERNED.

The results obtained by the team from the Universitat Politècnica de València, Universitat de València, CIBER-BBN, CIBERNED and the Príncipe Felipe Research Centre open up 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 easy urinary treatments aimed at eliminating or reducing cellular senescence, even in humans," concludes Ramón Martínez Máñez.

References

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

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