As people age, the risk of severe flu and COVID-19 increases significantly. A new study by scientists at the University of California, San Francisco explains why.

The research, published in the journal Immunity, shows that aging lung cells can themselves trigger an excessive inflammatory response, turning a relatively mild infection into a serious illness.

The researchers focused on fibroblasts—structural cells that maintain the shape and integrity of lung tissue. Under normal conditions, they support proper airway function. However, in the experiment, scientists artificially activated aging signals in these cells in young mice. This led to an unexpected result: clusters of inflammatory cells began forming in the lungs, including a specific group of immune cells marked by GZMK, previously identified in severe cases of COVID-19.

The study found that a key role is played by the NF-κB signaling pathway, which is associated with age-related diseases. Under its influence, fibroblasts activate macrophages, which then attract additional immune cells from the bloodstream into the lungs. Notably, GZMK-positive cells do not effectively fight infection but can damage tissue and intensify inflammation. As a result, the lungs of young mice begin to respond to infection as severely as those of older individuals.

When scientists removed these cells through genetic intervention, the lungs’ resistance to infection was restored. This suggests that the aging process itself can drive pathological inflammation—a phenomenon known as “inflammaging.”

Additional confirmation came from the analysis of lung tissue from elderly patients with severe COVID-19 and acute respiratory distress syndrome. The same inflammatory cell clusters were found, and their number directly correlated with disease severity. These changes were not observed in healthy donors.

The authors believe that interactions between lung cells and the immune system create a feedback loop that sustains inflammation even after the virus is cleared. This opens up new possibilities for therapies aimed at blocking this mechanism before a critical condition develops.