Older adults face higher risks from COVID and flu due to ageing lung cells that trigger destructive inflammation, according to a University of California, San Francisco study published in Immunity.
Researchers discovered that lung structural cells called fibroblasts send age-related distress signals that activate immune cells-particularly those marked by the GZMK gene. These cells don’t fight infection but instead damage lung tissue, creating inflamed cell clusters similar to those seen in severe respiratory illness.
In experiments, young mice engineered to emit these signals developed advanced infection symptoms. But when GZMK cells were removed, their lungs resisted damage-pointing to ageing lung tissue itself as the inflammation source.
Analysis of lung tissue from elderly COVID patients with acute respiratory distress syndrome (ARDS) confirmed the same inflamed clusters. Healthy donor lungs showed none.
“We saw during COVID that our most vulnerable patients no longer had the infection but still had persistent and devastating lung inflammation,” said Dr. Tien Peng, UCSF professor and senior author. “This circuit of dysfunction between lung and immune cells makes for a promising new therapeutic target.”
The findings suggest future therapies could target GZMK cells or fibroblast signaling to curb inflammaging-chronic inflammation linked to ageing-and prevent progression to critical illness.