Aging Lung Cells Linked to Severe COVID, Flu in Elderly

UCSF study finds lung fibroblasts can trigger excessive immune response in older adults.

Mar. 28, 2026 at 2:19am by Ben Kaplan

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A new study led by researchers at the University of California, San Francisco has found that aging lung cells, specifically fibroblasts, can drive excessive immune responses in older adults that make them much more likely to become seriously ill from the flu or COVID-19. The findings provide insights into the inflammation that accompanies aging and suggest potential new therapeutic targets to counter the damaging spiral of "inflammaging" before patients progress to severe illness.

Why it matters

Older adults are at a much higher risk of severe illness and hospitalization from influenza and COVID-19 compared to younger populations. This study helps explain the biological mechanisms behind this increased vulnerability, which could lead to new treatments to protect the elderly from these dangerous respiratory illnesses.

The details

The researchers engineered the lung's structural cells, called fibroblasts, to turn on an age-related distress signal in young mice. This signal led the lungs to form clusters of inflamed cells, including some marked by the GZMK gene, which was previously associated with severe COVID-19 cases. When the scientists eliminated these GZMK-positive cells in the mice, their lungs were able to better withstand an infection. The team also examined lung tissue from older COVID-19 patients and found similar clusters of inflamed cells, with the sickest patients having the most. This suggests the aging lung tissue itself is driving harmful inflammation.

  • The study was published on March 27, 2026 in the journal Immunity.
  • The research was led by Tien Peng, MD, a professor of Medicine at UCSF.

The players

Tien Peng

A professor of Medicine and a member of the Cardiovascular Research Institute and Bakar Aging Research Institute at UCSF, who was the senior author of the study.

Nancy Allen

A clinical fellow in the Pulmonary and Critical Care Division in the UCSF Department of Medicine, who is the first author of the paper.

UCSF

The University of California, San Francisco, which is exclusively focused on the health sciences and dedicated to promoting health worldwide through advanced biomedical research, graduate-level education, and excellence in patient care.

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What they’re saying

“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.”

— Tien Peng, Professor of Medicine, UCSF

“We saw during COVID that our most vulnerable patients no longer had the infection but still had persistent and devastating lung inflammation. This circuit of dysfunction between lung and immune cells makes for a promising new therapeutic target.”

— Tien Peng, Professor of Medicine, UCSF

What’s next

The researchers plan to further investigate the specific mechanisms by which aging lung fibroblasts trigger excessive immune responses, with the goal of developing new therapies that can target this process and protect the elderly from severe illness due to influenza, COVID-19, and other respiratory infections.

The takeaway

This study provides important insights into why older adults are at such high risk for serious complications from the flu and COVID-19, revealing how changes in the lungs associated with aging can drive harmful inflammation. By understanding this underlying biology, researchers may be able to develop new interventions to mitigate the disproportionate impact of these respiratory illnesses on the elderly population.