Getting older doesn’t just raise your risk for respiratory infections — it may actually change how your lungs respond to them in a dangerous way.
If you’re 65 or older, your chances of being hospitalized from respiratory infections as a result of flu or COVID are significantly higher. Worse, the risk of dying from these illnesses rises sharply with age.
Now, researchers from the University of California San Francisco (UCSF) say they may have uncovered one reason why: a hidden “double whammy” of inflammation inside aging lungs that can turn a routine infection into something far more serious.
How aging and lung inflammation trigger a dangerous cycle
Scientists have long known that aging is linked to chronic, low-grade inflammation — a process often called inflammaging.
Inflammaging refers to the gradual increase in persistent, low-level inflammation that develops with age. It’s been linked to many chronic diseases of aging and can also disrupt how the immune system responds to infections.
But exactly how this plays out inside lung tissue hasn’t been fully understood.
To investigate, UCSF researchers studied structural lung cells called fibroblasts, which help maintain the lungs’ airways and air sacs.
When these cells were engineered to activate an age-related distress signal in young mice, something striking happened: the lungs began behaving like those of older individuals.
Clusters of immune cells formed in the lung tissue, including a subset expressing a gene called GZMK — previously observed in severe respiratory illness.
“We were surprised to see lung fibroblasts working hand-in-hand with immune cells to drive inflammaging,” said senior author Dr. Tien Peng.
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What Happens in the Lungs During Inflammaging
The researchers found that this process is driven in part by the NF-kB pathway — a key inflammation signaling system in the body.
Here’s how the cycle appears to unfold:
- Fibroblasts send distress signals through the NF-kB pathway
- These signals activate macrophages, a type of immune cell
- Additional immune cells rush into the lungs from the bloodstream
- Some of these cells express GZMK and contribute to tissue damage
While these immune cells aren’t the original cause of infection, they can worsen the damage once inflammation ramps up.
In the study, once these immune cell clusters formed, the lungs of young mice responded to infection as if they were much older, developing more severe symptoms.
But when researchers removed the GZMK-expressing cells, the lungs were better able to withstand infection.
This suggests that aging lung tissue itself may help drive the inflammatory response that leads to more serious illness.
Why aging and lung inflammation in older age
To see if this process also occurs in humans, the researchers examined lung tissue from older patients hospitalized with COVID-related acute respiratory distress syndrome (ARDS).
They found that the tissue contained clusters of cells similar to those seen in the mice, and that the sicker the patient, the more inflamed the clusters were. By contrast, lung tissue from healthy donors had none.
Based on these results, a future therapy could target these immune cells to fend off the damaging spiral of inflammaging.
“We saw during COVID that our most vulnerable patients no longer had the infection but still had persistent and devastating lung inflammation,” Peng says. “This circuit of dysfunction between lung and immune cells makes for a promising new therapeutic target.”
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Why this discovery matters
Aging lungs may already be primed for inflammation. When a respiratory infection strikes, the immune system can overreact — creating a cycle where inflammation causes more harm than the infection itself.
This “inflammation double whammy” may be a key reason respiratory infections become more dangerous with age — and why taking steps to manage inflammation before illness strikes could make a meaningful difference.
How to Protect Your Lungs From Age-Related Inflammation
One is to up your intake of omega-3 fatty acids. Previous research has shown that higher levels of omega-3s in the blood correlate with better lung function and a reduced rate of decline in lung function.
Fatty fish, like salmon, tuna and sardines, are great sources of omega-3s, and to get the optimum level, you should have them at least a couple times a week.
Here are some other things you can do to quell inflammaging:
- Adopt an anti-inflammatory diet. Studies show diets like the Mediterranean diet can lower C-reactive protein (CRP) levels by as much as 20%. CRP is a marker of chronic inflammation in the body.
- Take vitamin C. Research suggests that taking 1,000 mg of vitamin C per day can reduce CRP levels by 25%.
- Supplement fish oil or krill oil, especially if you don’t eat fatty fish regularly, to significantly lower CRP levels.
- Add anti-inflammatory herbs. Both turmeric and ginger contain compounds that reduce inflammation and substantially cut CRP levels, according to several studies.
- Vitamin D intake. People with very low vitamin D levels are hospitalized more often for respiratory infections. Research has shown that daily or weekly supplementation halved the risk of acute respiratory infections.
Sources:
This Could Be Why COVID and Flu Are So Dangerous to the Elderly — UCSF
NF-κB-activated fibroblasts orchestrate inflammaging and emergence of pro-inflammatory granzyme K+ T cells — Immunity