Researchers at the University of California, San Francisco have identified how aging lungs contribute to severe flu and COVID-19 outcomes in older adults. Their study shows that lung fibroblasts trigger excessive inflammation, forming damaging clusters of immune cells. The findings, published in Immunity on March 27, suggest potential new treatments.
A team led by Tien Peng, MD, a professor of medicine at UCSF and member of the Cardiovascular Research Institute and Bakar Aging Research Institute, examined changes in lung fibroblasts, which maintain lung tissue structure. In young mice, activating an aging-related stress signal via the NF-κB pathway caused these cells to signal macrophages, drawing in ineffective immune cells marked by the GZMK gene. These clusters damaged lung tissue, mimicking severe responses seen in older adults during infections, leading to worse illness outcomes even after removing GZMK cells genetically improved tolerance in the mice. Peng noted, 'We were surprised to see lung fibroblasts working hand-in-hand with immune cells to drive inflammaging. It suggests new ways to intervene before patients progress to severe inflammation that can require intubation.'
