Why COVID-19 Is More Harmful For Elderly People? Study Blames Aging Telomeres

Researchers have provided one possible molecular explanation for the increased sensitivity of elderly people to SARS-CoV-2, the virus that causes COVID-19.

Elder people have higher risk of hospitalization and death from COVID.

Available data suggests that elderly people are more susceptible to SARS-CoV-2, the coronavirus that cause COVID-19 disease. When infected by the virus, older people are also more likely to experience severe symptoms and have higher risk of hospitalization and death, than the younger population. But why COVID-19 is more harmful for elderly people remains unclear.

In a new study published by EMBO Reports, a group of Italian and American researchers has provided one possible molecular explanation for the increased sensitivity of elderly people to SARS-CoV-2. Aging telomeres might be making them more susceptible to the virus, they said.

Telomeres are the regions at the ends of linear chromosomes that protect chromosomes from damage.

The researchers found that the expression of ACE2, the cell receptor for the virus which is essential for mediating cell entry of the virus, increases in the lungs of aging mice and humans. In cultured human cells and in mice, the ACE2 expression further increases upon telomere shortening or dysfunction -- common hallmarks of aging.

Aging telomeres causes DNA damage response signaling

Aging is associated with telomere shortening, and when telomeres become critically short, they activate DNA damage response pathways. This may lead to increased ACE2 protein expression in the elderly, and thereby increase their susceptibility to SARS-CoV-2, the researchers suggested.

In the lungs, ACE2 is mostly found on the surface of alveolar epithelial type II cells (ATII), and thus they are likely the primary target of SARS-CoV-2. In the new study, ACE2 protein expression was found elevated in aging human and mouse lungs, including in ATII cells.

According to the researchers, it could be the DNA damage response activation, rather than telomeric shortening per se, that is responsible for ACE2 upregulation.

Targeted therapeutic approaches for the elderly

Understanding the mechanism of higher susceptibility to SARS-CoV-2 infection in the elderly may help in developing targeted therapeutic approaches, such as use of tASO-mediated inhibition of the telomeric DNA damage response, the experts noted.

However, they also underscored the need to determine whether reducing ACE2 expression has beneficial effects on COVID-19 infection rates and on the severity of the symptoms in in vivo models.

COVID-19 is less prevalent in children compared to adults. Lower ACE2 expression in children may explain this, the scientists added.