Transcriptome profiling of lungs from young and aged hamster

Older age is one of the strongest risk factors for COVID-19 morbidity and mortality. Here, we sought to determine whether age-associated cellular senescence contributes to the severity of COVID-19 by studying the well-established golden hamster model of SARS-CoV-2-driven lung disease. We found that aged hamsters (22 months of age) accumulate senescent cells in the lungs and that the senolytic drug ABT-263 depletes these cells at baseline and during a SARS-CoV-2 infection. Relative to young hamsters (2 months of age), aged hamsters had a greater viral load during the acute phase of infection and displayed higher levels of sequelae during the post-acute phase. Interestingly, early treatment with ABT-263 was associated with a significantly lower pulmonary viral load, an effect associated with lower angiotensin converting enzyme 2, the receptor for SARS-CoV-2, and an amelioration of COVID-19-like lung disease in aged (but not young) animals. ABT-263 treatment of aged animals was also associated with lower pulmonary and systemic levels of senescence-associated secretory phenotype factors. Furthermore, early removal of senescent cells reduced the longer-term pulmonary inflammation. These data demonstrate the causative role of age-associated pre-existing senescent cells on the pathologic severity of experimental COVID-19. Transcriptome analysis has been performed on lung tissue derived from 3 independent Aged (22 months old) Hamster and 4 independent Young Hamster (2 months old)