July 19-25 2021
A specially designed treatment for elderly people?
Age is one of the principal risk factors in the majority of chronic illnesses such as cancer, diabetes, and heart disease. The COVID-19 pandemic has demonstrated the particular vulnerabilities of elderly people. Reducing the impact of age may, therefore, allow more effective treatment of SARS-CoV-2.
Cellular senescence is the biological process of cell aging, which causes modifications in their morphology, their gene expression, and their metabolism, and confers a certain resistance to programmed cell death (apoptosis). The senescent cells accumulate with age and secrete pro-inflammatory factors leading to chronic inflammation in elderly people. American researchers (at the University of Minnesota, Robert and Arlene Kogod Center on Aging, Rochester) have shown that these cells may be a cause of numerous harmful consequences of COVID-19 in elderly patients, and that new medicines that allow senescent cells to be eliminated may reduce serious cases.
The researchers firstly analysed the in vitro response of senescent cells when infection by a pathogen was simulated. They thus showed that senescent cells have much greater expression of inflammatory factors in response to infection than healthy cells. They then simulated infection with the spike protein of SARS-CoV-2, also in vitro, and came to the same conclusions.
In order to determine if results would be identical in vivo, the scientists simulated infection in young and old mice. The preceding results were confirmed: the senescent cells have a hyper-inflammatory response to infection. In addition, there was much greater mortality in the older mice than the younger ones when infection took place.
The senescent cells must therefore contribute substantially to the cytokine storm observed in serious cases of SARS-CoV-2 infection, which causes organ failure in sick patients. In addition, the senescent cells reduce antiviral defences, which facilitates the entry of the virus into other, non-senescent, cells.
The scientists then investigated which would be the most appropriate treatment. They tested senolytics, an anti-senescent cells medicine. These molecules, which are still under study, kept mice alive for longer, with no undesirable side-effects. The researchers thus showed that these compounds enabled senescence and inflammation to be reduced, and for survival times after infection to be extended. It is clear that these treatments facilitate the elimination of senescent cells in aged organisms.
In conclusion, the accumulation of senescent cells in elderly patients enhances conditions for chronic inflammation and reduces antiviral defences, predisposing these patients to numerous illnesses. In addition, they facilitate the entry of SARS-CoV-2 into neighbouring, non-senescent cells. Senolytics reduce inflammation and prolong life after infection, by facilitating the lysis (or destruction) of senescent cells. Since these cells increase susceptibility to infection by SARS-CoV-2, this new treatment may bring new hope in the fight against COVID-19.