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Severe COVID-19 in the elderly may be due to ACE2 cell receptors in the lungs




COVID-19 infection It is known to have a more serious impact on the elderly.New research published in EMBO Report, We have discovered that this may be due to an increase in the viral cell receptor, ACE2.

During aging, telomere dysfunction is gradually built up, activating the DNA damage response and leading to an increase in the SARS-CoV-2 receptor ACE2. Increased expression of ACE2 in the lungs may explain the increased severity of COVID-19 infection in the elderly.

This study, conducted by Italian and American researchers, confirmed the presence of elevated ACE2 protein expression in the lungs of aged humans and mice. ACE2 is found primarily in alveolar epithelial type II cells (ATII) and may be targeted for COVID-19 infection. Researchers pointed out that the virus first attacks the lungs and the most common complication among COVID-19 patients is pneumonia (91% incidence).

Researchers used in vitro and in vivo models to recreate aspects of aging, such as telomere shortening and tissue damage. Telomeres that are too short activate the DNA damage response pathway. Researchers suppressed DNA damage by targeting ATMs with telomere antisense oligonucleotides (tASOs).

To confirm the increase in ACE2 in ATII cells, researchers used the double-marker immunofluorescent antibody method for ACE2 and ATII cells in lung samples of various ages (pro-SP-C in mice or TTF-1 in humans). ) Was carried out. Fluorescent antibody methods have shown that ACE2 expression in ATII lung cells increases with age. Similar increases were observed in other types of cells. The findings show that it is likely that it is not telomere shortening that causes upregulation of the ACE2 gene and protein, but activation of the DNA damage response.

The study points out that further research is needed to understand whether reducing ACE2 expression also reduces COVID-19 infection and severity. Since ACE2 is normally expressed not only in the lungs, but also in other organs, researchers thought the findings could extend beyond COVID-19.





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