20-26 September 2021
Cellular senescence is a factor in pathology
SARS-CoV-2 causes infection of the upper respiratory passages causing respiratory disease or even multiple organ failure that can lead to death. These pathologies are a priori the result of over-activation of the immune system, known as a cytokine storm, rather than infection by the virus itself. The entry of a virus, SARS-CoV-2 for example, into a cell, causes numerous disruptions, pushing the cell to senescence in response to this stress. Senescence is the biological process of cell ageing that brings about changes in their morphology, the expression of their genes, their metabolism, and which gives them a certain resistance to programmed cell death, or apoptosis. Researchers in Berlin and in Austria have looked into whether senescence is involved in the cytokine storm that is at the origin of serious cases of COVID-19.
The researchers firstly tested for signs of cellular senescence provoked by viruses using an in vitro model. 5 days after infection, they observed that the cells were releasing a number of inflammatory and coagulation factors, typical markers of senescence. The scientists then investigated whether these factors secreted by the senescent cells were to be found in patients infected with SARS-CoV-2. They analysed the nasopharyngeal and pulmonary tissues of patients who had died from COVID-19. These markers were indeed found in the upper respiratory tract, being involved in the recruitment of immune cells to the lung and causing tissue damage that can lead to respiratory disease. Senescent cells could therefore be a therapeutic target in the fight against COVID-19 and the prevention of serious illness, as other studies have already shown.
Senolytics are a new class of drugs that selectively clear senescent cells. In order to determine the impact of this treatment, the researchers tested it on hamsters and mice infected with SARS-CoV-2. The senolytics in question significantly reduced the pro-inflammatory and pro-coagulant factors in these animal models. Tests on humans are encouraging, showing that these drugs also lead to reductions in severe forms of the illness.
In conclusion, the scientists showed that infection by the virus sets off a senescent cellular response. This response is linked to the production of inflammatory and coagulant factors that are involved in pulmonary disease and multiple organ failure. The consequences of cellular senescence seem to be reduced by treatment with senolytic drugs, but clinical trials are still taking place.