Lower ACE2 expression in children relative to adults may discuss why COVID-19 is less widespread in kids, and the expression and distribution of the ACE2 receptor may be appropriate for the development and diagnosis of COVID-19. When telomeres end up being seriously short, they are picked up as DNA breaks and trigger DNA damage action pathways. DAdda di Fagagna working at IFOM in Milan and CNR-IGM in Pavia and colleagues either inhibited the basic DNA damage reaction by targeting ATM, a major enzyme of the DNA damage response path, or they prevented the telomeric DNA damage action specifically using telomeric antisense oligonucleotides (tASO). Both approaches avoid ACE2 gene and protein upregulation following telomere damage in aging cultured cells and in mice. The group also utilized a cell culture design in which the DNA damage action is activated particularly at telomeres in the absence of telomere shortening, with the very same results.
Lower ACE2 expression in kids relative to adults may explain why COVID-19 is less prevalent in children, and the expression and distribution of the ACE2 receptor may be appropriate for the development and prognosis of COVID-19. The research study findings now reveal that ACE2 protein expression is elevated in aging human and mouse lungs, consisting of in alveolar epithelial type II cells (ATII). In the lungs, ACE2 is primarily found on the surface area of ATII cells, and these cells are thus likely the main target of SARS-CoV-2 infection in the lungs.
When telomeres end up being seriously short, they are noticed as DNA breaks and trigger DNA damage reaction paths. DAdda di Fagagna working at IFOM in Milan and CNR-IGM in Pavia and coworkers either hindered the general DNA damage response by targeting ATM, a significant enzyme of the DNA damage response pathway, or they prevented the telomeric DNA damage action specifically using telomeric antisense oligonucleotides (tASO). Both approaches prevent ACE2 gene and protein upregulation following telomere damage in aging cultured cells and in mice.
ACE2 likewise has a role in the regulation of blood pressure and the balance of salts and fluids and is revealed in other human tissues, for instance the heart and kidney. The findings reported here might hence likewise have more comprehensive medical ramifications beyond COVID-19..
Further research study is required to establish whether decreasing ACE2 expression has helpful results on SARS-CoV-2 infection rates and on the intensity of COVID-19 symptoms in vivo designs. Further work likewise needs to be brought out to understand how DNA damage response signaling leads to increased Ace2 gene expression.
Recommendation: “DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging” by Sara Sepe, Francesca Rossiello, Valeria Cancila, Fabio Iannelli, Valentina Matti, Giada Cicio, Matteo Cabrini, Eugenia Marinelli, Busola R Alabi, Alessia di Lillo, Arianna Di Napoli, Jerry W Shay, Claudio Tripodo and Fabrizio dAdda di Fagagna, 2 December 2021, EMBO Reports.DOI: 10.15252/ embr.202153658.
DNA damage signaling caused by aging telomeres increases the expression of ACE2, the human SARS-CoV-2 cell receptor.
They further reveal that ACE2 expression increases upon telomere shortening or dysfunction– common trademarks of aging– in cultured human cells and in mice. This increase depends on a DNA damage action generated by inefficient telomeres.
