Journal of the American Chemical Society
Madrid, 5 July, 2017
This system is based on a probe that selectively "lights up" in senescent cells. It has been developed by researchers at the UPV, CNIO, CIBER-BBN and the University of Cambridge
The elimination of senescent cells reverses long-term degenerative processes and extends longevity. Therefore, there has been great interest in strategies that detect and eliminate them in recent years
Researchers from the the Spanish National Cancer Research Centre (CNIO), the Universitat Politècnica de València (UPV), the Centre for Biomedical Research in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) and Cambridge University have developed a new system that allows the detection of senescent cells in vivo without damaging tissue. Their paper has been published in the Journal of the American Chemical Society.
The main objective of cellular senescence is to avoid the proliferation of damaged or stressed cells and, at the same time, initiate tissue repair. However, when the damage persists or during ageing, the tissue repair process becomes inefficient and senescent cells tend to accumulate. This accumulation affects tissue functions and accelerates ageing.
"It has been shown that the elimination of senescent cells improves a variety of diseases associated with ageing, reverses long-term degenerative processes and extends longevity. Consequently, strategies capable of identifying and removing senescent cells have become increasingly interesting in recent years,” says Manuel Serrano, a researcher at the CNIO.
In their paper, researchers at the University of the Basque Country, CNIO, CIBER-BBN and Cambridge University have developed a new probe capable of detecting senescent cells in an in vivo model. "The probe significantly and selectively increases fluorescence in senescent cells," says Beatriz Lozano, a researcher at the Interuniversity Institute of Molecular Recognition Research and Technological Development (IDM) at the Universitat Politècnica de València.
"Chemically speaking, the probe consists of a fluorophore attached to a galactose using a histidine linker. When the probe enters a senescent cell, it hydrolyses, resulting in increased fluorescence, which is the signal we detect by exciting it with a laser. However, when the probe enters a normal cell (non-senescent), no signal is observed," says Ramón Martínez Máñez, director of the Institute IDM-UPV and scientific director at the CIBER-BBN.
The probe has some properties that means it can be excited by absorbing two photons, which means far less laser energy is required to view the tissue than in conventional probes. In addition, the two-photon technique reduces tissue damage and provides greater penetrability.
"The probe is injected intravenously in animals with senescent and non-senescent melanoma tumours, and the signal is observed very selectively in senescent tumours only. Animals with senescent tumours did not display any signal in any other organ or tissue," says Beatriz Lozano.
The probe is potentially applicable to other models of senescence; various research groups have already begun to test the probe on their biological models.
Together with the IDM Institute, several groups have participated in this project, such as the Tumour Suppression Group of the Spanish National Cancer Research Centre (CNIO), and the Cancer Centre Early Detection Programme, of the University of Cambridge.
An OFF–ON Two-Photon Fluorescent Probe for Tracking Cell Senescence in Vivo. Beatriz Lozano-Torres, Irene Galiana, Miguel Rovira, Eva Garrido, Selim Chaib Andrea Bernardos, Daniel Muñoz-Espín, Manuel Serrano, Ramón Martínez-Máñez and Félix Sancenón (Journal of the American Chemical Society 2017). DOI: 10.1021/jacs.7b04985