학술논문
Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters
Document Type
Original Paper
Author
Delval, Lou; Hantute-Ghesquier, Aline; Sencio, Valentin; Flaman, Jean Michel; Robil, Cyril; Angulo, Fabiola Silva; Lipskaia, Larissa; Çobanoğlu, Ozmen; Lacoste, Anne-Sophie; Machelart, Arnaud; Danneels, Adeline; Corbin, Mathieu; Deruyter, Lucie; Heumel, Séverine; Idziorek, Thierry; Séron, Karin; Sauve, Florent; Bongiovanni, Antonino; Prévot, Vincent; Wolowczuk, Isabelle; Belouzard, Sandrine; Saliou, Jean-Michel; Gosset, Philippe; Bernard, David; Rouillé, Yves; Adnot, Serge; Duterque-Coquillaud, Martine; Trottein, François
Source
Nature Aging. 3(7):829-845
Subject
Language
English
ISSN
2662-8465
Abstract
Older age is one of the strongest risk factors for severe COVID-19. In this study, we determined whether age-associated cellular senescence contributes to the severity of experimental COVID-19. Aged golden hamsters accumulate senescent cells in the lungs, and the senolytic drug ABT-263, a BCL-2 inhibitor, depletes these cells at baseline and during SARS-CoV-2 infection. Relative to young hamsters, aged hamsters had a greater viral load during the acute phase of infection and displayed higher levels of sequelae during the post-acute phase. Early treatment with ABT-263 lowered pulmonary viral load in aged (but not young) animals, an effect associated with lower expression of ACE2, the receptor for SARS-CoV-2. ABT-263 treatment also led to lower pulmonary and systemic levels of senescence-associated secretory phenotype factors and to amelioration of early and late lung disease. These data demonstrate the causative role of age-associated pre-existing senescent cells on COVID-19 severity and have clear clinical relevance.
Delval, Hantute-Ghesquier, Sencio and colleagues demonstrate that depletion of age-associated senescent cells decreases pulmonary viral load and ameliorates early and late lung COVID-19 in a hamster model of aging.
Delval, Hantute-Ghesquier, Sencio and colleagues demonstrate that depletion of age-associated senescent cells decreases pulmonary viral load and ameliorates early and late lung COVID-19 in a hamster model of aging.