Why are older adults far more at risk from COVID or flu?

Scientists have uncovered a potential explanation for why older individuals experience more severe outcomes from infections like COVID-19 or influenza. A study led by researchers at the University of California, San Francisco, published in the journal *Immunity*, highlights the role of aging lung cells in amplifying immune reactions.

Focus has shifted to fibroblasts, structural components of the lungs, which were found to unintentionally contribute to a phenomenon called “inflammaging.” This refers to the persistent, mild inflammation that accompanies age-related decline. The research suggests these cells may act as key players in the process, sending signals that lead to exaggerated immune responses.

Aging lungs and immune system interaction

By altering fibroblasts in young mice to emit signals typical of aged lungs, the team investigated whether these signals could trigger harmful inflammation in otherwise healthy tissue. The experiment revealed that such signals prompted immune activation, drawing cells from the bloodstream and forming clusters of inflamed cells. Notably, some of these immune cells, identified by the GZMK gene, were linked to severe cases of COVID-19 but did not effectively combat the virus.

When these GZMK cells were eliminated, young mice resisted infection without developing advanced symptoms. This implies that the aging lung tissue itself may be responsible for the inflammation, rather than the virus alone. Fibroblasts have also been implicated in conditions like COPD, where they contribute to chronic lung inflammation.

“We were surprised to see lung fibroblasts collaborating with immune cells to drive inflammaging. This opens up fresh possibilities for interventions before severe inflammation escalates to the point of requiring intubation,” remarked Tien Peng, MD, a professor of medicine at UCSF and the study’s lead author.

In a further step, the researchers analyzed lung tissue from hospitalized patients with severe COVID-19-related ARDS. They observed similar inflamed cell clusters as in the mouse model, with more pronounced clusters in critically ill individuals. Healthy donors, however, did not exhibit these findings.

The results suggest that targeting GZMK cells could offer a novel strategy to alleviate age-related inflammation. Future therapies may be designed to disrupt this cycle, potentially reducing the risk of severe respiratory complications in older adults.