DNA damage in older age increases expression of ACE2 and SARS-CoV-2 infection risk AgingCell DNA DNAdamage age infection SARSCoV2
By Nidhi Saha, BDSOct 26 2022Reviewed by Benedette Cuffari, M.Sc. A new Aging Cell study reports that impaired deoxyribonucleic acid repair capacity among elderly individuals increases expression of the angiotensin-converting enzyme 2 receptor that is used by the severe acute respiratory syndrome coronavirus 2 to gain entry into cells.
Several factors have been found to precipitate the disparity in response to SARS-CoV-2 infection among the elderly. These include differences in viral susceptibility among cell types, the presence of comorbidities, as well as different immune responses and capacities of individuals to combat infections.
About the study In the current study, researchers examine whether suppressing DDR or improving DNA repair capabilities in humans can reduce the viral load and tissue damage caused by SARS-CoV-2 infection. Calu-3-sgTERC cells were generated by CRISPR-Cas9-mediated deletion of the TERC gene, which encodes an RNA template for telomere replication by telomerase. To study the effect of DNA damage in vivo, researchers administered IR to young eight-week-old mice and VE-822 to older mice that were 12 months old.
Study findings ACE2 and SARS-CoV-2 expression levels were elevated by the age-related accumulation of DNA damage through the upregulation of c-Jun. DNA damage facilitates SARS-CoV-2 infection; therefore, inhibiting DDR reduces its impact. DNA damage suppressed ACE2 expression, as well as in vitro and in vivo viral infestations into the host cells, on DDR pathway inhibition.