A research team led by Professor Ying Meng at Southern Medical University has pinpointed a key mechanism behind the age-related persistence of pulmonary fibrosis, a devastating and often fatal lung disease. In their new study, the scientists reveal that an age-associated drop in the protein fPRDM16 disables the lung's natural capacity to clear away scar tissue.
"We found that the problem isn't overproduction of collagen, but a failure in its disposal," said Dr. Jun Peng, the study's first author. "Aging lung fibroblasts lose their ability to 'eat' and digest collagen, causing fibrosis to persist rather than resolve."
The team discovered that the loss of fPRDM16 triggers a destructive feedback loop within cells. It simultaneously fuels oxidative stress from mitochondria and de-acidifies lysosomes, the cellular compartments responsible for breaking down engulfed collagen. This two-pronged dysfunction brings the collagen-clearing process to a halt.
When the researchers restored fPRDM16 in aged cells, they broke this vicious cycle. The treatment re-acidified lysosomes, mitigated mitochondrial oxidative stress, and most importantly, revived the fibroblasts' capacity to phagocytose collagen. "Rescuing fPRDM16 expression essentially rejuvenated the aged fibroblasts' healing function," said Professor Meng. "It normalizes the cellular environment and allows fibrosis to resolve."
These findings establish fPRDM16 as a promising new target for developing therapies aimed at reversing, rather than merely halting, persistent lung fibrosis in the elderly. Read the full article here: https://doi.org/10.1016/j.cmp.2026.02.002
Journal
Current Molecular Pharmacology
COI Statement
The authors declare that they have no known financial interests or personal relationships that could have appeared to influence the work reported in this paper.