Patients in whom Covid-19 is severely affected have significantly shorter telomeres, according to a study carried out by researchers from the National Center for Oncological Research (CNIO) in collaboration with the HCOVID-IFEMA Campaign Hospital, which is published in Aging magazine. The work, directed by Maria A. Blasco and whose first authors are Raúl Sánchez and Ana Guío-Carrión, postulates that the shortening of telomeres as a result of viral infection prevents tissue regeneration and that therefore a significant part of patients suffer prolonged sequelae.
The Telomeres and Telomerase Group of the CNIO, led by Blasco, has been investigating the role of telomeres in tissue regeneration for decades. Ltelomeres are structures that protect chromosomes within each cell of the body. Its length is known to be an indicator of aging: each time the cell divides, the telomeres shorten, until it reaches a point where they cannot exert their protective function and the damaged cell stops dividing.
Throughout life, cells constantly divide to regenerate tissues, and when they no longer do so, because telomeres are too short, the body ages.
Researchers have shown in recent years, in mice, that this process can be reversed by activating the production of the enzyme telomerase, responsible for lengthening telomeres.
Activation of telomerase is effective in treating diseases associated with aging and telomere damage, such as pulmonary fibrosis, in animals.
In pulmonary fibrosis, the lung tissue develops scars and becomes rigid, causing a progressive loss of respiratory capacity.
The CNIO group has shown in previous studies that a cause of the disease is damage to the telomeres of cells that must regenerate lung tissue, type II alveolar pneumocytes. And these cells are precisely those that the SARS-CoV-2 coronavirus infects in lung tissue.
“When I read that type II alveolar pneumocytes were involved in Covid-19, I immediately thought that telomeres could have a role,” says Blasco.
In their work on Aging, the researchers note: “It came to our attention that a common consequence of SARS-CoV-2 infection appears to be the induction of a fibrosis-like phenotype in the lungs and kidneys, suggesting that the viral infection could be depleting the regenerative potential of the tissues ”.
The authors propose that it is the short telomeres that make tissue regeneration difficult after infection. As Blasco explains, “we know that the virus infects type II alveolar pneumocytes and that these are the relevant cells to regenerate the lung; we also know that if they have telomeric damage they cannot regenerate, inducing fibrosis.
This is what is seen in patients with lung lesions after Covid-19: “We think they develop pulmonary fibrosis because they have shorter telomeres and this limits the regenerative capacity of their lungs.”
The data presented in the publication in Aging provide evidence in favor of this hypothesis, finding an association between greater severity of Covid-19 and shortening of telomeres.
As in the general population, the patients studied the Average telomere length decreases with increasing age. Furthermore, as the most seriously ill patients are also the oldest, there is also a correlation between greater severity and shorter telomere length.
It was not predictableThe most important thing is that the telomeres of the most seriously ill patients will also be shorter regardless of age.
The researchers write: “It is interesting that we also found that patients with more severe conditions due to Covid-19 have shorter telomeres at different ages, compared to those with mild disease.”
These data suggest that “one of the markers of aging, such as the presence of short telomeres, may have a role in the severity of the Covid-19 disease,” they add.
The purpose of the researchers now is to demonstrate a causal relationship between shorter telomere length and pulmonary sequelae of Covid-19. To do this, they will infect mice with short telomeres and incapable of producing telomerase with SARS-CoV-2; Without this enzyme, telomeres cannot be repaired, and as a consequence lung tissue regeneration cannot take place.
If the hypothesis of Blasco’s group is correct, mice without telomerase and short telomeres should develop pulmonary fibrosis more severely than normal mice.
«Since short telomeres can be lengthened again by telomerase, and that in previous work we have shown that telomerase activation has a therapeutic effect in diseases related to short telomeres, such as pulmonary fibrosis, it is tempting to speculate that this therapy could improve some of the pathologies that remain in Covid-19 patients once the viral infection is overcome, such as pulmonary fibrosis.