This study investigates age-specific differences in the response of nasal epithelial cells (NECs) to SARS-CoV-2 infection in children (<12 years), adults (30–50 years), and older adults (>70 years). Using in vitro models, the researchers found that SARS-CoV-2 targets different cell types in each age group. In children, goblet inflammatory cells show high interferon responses and limited viral replication, while in older adults, basaloid-like cells increase, facilitating viral spread and fibrotic pathways. The study confirms that age-specific cell types are induced by integrating in vivo data, validating the in vitro model's ability to replicate early epithelial responses. Despite effective vaccines, age remains the greatest risk factor for severe COVID-19. Children rarely develop severe disease, while older adults have high mortality. The study highlights that SARS-CoV-2 entry factors like ACE2 and TMPRSS2 vary by age group, with older adults showing higher expression in secretory cells. In older adults, viral replication is more efficient, leading to increased infectious particles and fibrotic signaling. The study also shows that older adult NECs exhibit increased cell shedding and epithelial damage, associated with EMT and fibrosis. These findings suggest that age-specific changes in NECs contribute to SARS-CoV-2 pathogenesis, with older adults experiencing more severe outcomes due to altered repair pathways and increased viral spread. The study provides insights into age-related differences in SARS-CoV-2 infection and highlights the importance of understanding age-specific cellular responses for developing targeted therapies.This study investigates age-specific differences in the response of nasal epithelial cells (NECs) to SARS-CoV-2 infection in children (<12 years), adults (30–50 years), and older adults (>70 years). Using in vitro models, the researchers found that SARS-CoV-2 targets different cell types in each age group. In children, goblet inflammatory cells show high interferon responses and limited viral replication, while in older adults, basaloid-like cells increase, facilitating viral spread and fibrotic pathways. The study confirms that age-specific cell types are induced by integrating in vivo data, validating the in vitro model's ability to replicate early epithelial responses. Despite effective vaccines, age remains the greatest risk factor for severe COVID-19. Children rarely develop severe disease, while older adults have high mortality. The study highlights that SARS-CoV-2 entry factors like ACE2 and TMPRSS2 vary by age group, with older adults showing higher expression in secretory cells. In older adults, viral replication is more efficient, leading to increased infectious particles and fibrotic signaling. The study also shows that older adult NECs exhibit increased cell shedding and epithelial damage, associated with EMT and fibrosis. These findings suggest that age-specific changes in NECs contribute to SARS-CoV-2 pathogenesis, with older adults experiencing more severe outcomes due to altered repair pathways and increased viral spread. The study provides insights into age-related differences in SARS-CoV-2 infection and highlights the importance of understanding age-specific cellular responses for developing targeted therapies.