12 Jan Short Telomeres LInked to More Severe COVID-19 Disease
MedicalResearch.com Interview with:
Dr. Maria A. Blasco, PhD
Director of the Spanish National Cancer Research Centre
Head of the Telomeres and Telomerase Group – CNIO
MedicalResearch.com: What is the background for this study?
Response: In my group we have previously described that telomere dysfunction in alveolar type II (ATII) cells in the lung is sufficient to induce pulmonary fibrosis in mice, thus demonstrating that these cells, which have a role in lung regeneration, are at the origin of the disease (Povedano et al., Cell Reports, 2015). Indeed, we further demonstrated that telomere elongation in these cells by using a gene therapy strategy based on telomerase activation, was sufficient to stop the progression of pulmonary fibrosis induced by short telomeres in mice (Povedano, eLife, 2018).
MedicalResearch.com: What are the main findings?
Response: These findings demonstrate a causal role of short telomeres in origin of the disease. Interestingly, the Sars-cov-2 virus mainly infects ATII cells in the lung, and a consequence of such infection is the induction of pulmonary fibrosis in the more severe cases. Thus, we hypothesized that infection of the lungs by the Sars-cov-2 virus could lead to an increased turn-over of these cells, leading to telomere shortening. In those patients with already shortened telomeres (ie., old patients), the viral infection could lead to telomere exhaustion in ATII cells, lack of lung regeneration, and induction of pulmonary fibrosis.
MedicalResearch.com: What should readers take away from your report?
Response: We find a significant statistical correlation between disease severity and presence of shorter telomeres. Those patients that have the more severe disease including severe respiratory distress tend to have shorter telomeres than those with longer telomeres. These results support our hypothesis that the viral infection could be interacting with telomere length in leading to more severe disease.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Our results suggest that those patients with shorter telomeres are more likely to develop more severe complications, such as fibrotic lesions in the lung. Also our work suggests that telomerase activation and telomere elongation specifically targeted to ATII cells could be a potential treatment for pulmonary fibrosis in ex Covid-19 patients.
MedicalResearch.com: Is there anything else you would like to add?
Response: We have recently generated a newCo, Telomere Therapeutics, with the objective of developing a telomerase-based gene therapy for the treatment of pulmonary fibrosis associated to short telomeres.
Raul Sanchez-Vazquez, Ana Guío-Carrión, Antonio Zapatero-Gaviria, Paula Martínez, Maria A. Blasco. Shorter telomere lengths in patients with severe COVID-19 disease. Aging, 2021; DOI: 10.18632/aging.202463
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