AgingAug 29, 2025

Bleomycin triggers cell aging and immune response activation without directly causing scarring in a lung fibrosis model

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 2, 2026

Abstract

Bleomycin treatment in lungs with induced usual interstitial pneumonia (iUIP) led to accelerated cell aging.

Lungs with iUIP showed signs of accelerated senescence after exposure to bleomycin.
Treatment with bleomycin resulted in decreased levels of the nuclear membrane component lamin B1.
Nuclear DNA fragments, indicated by γH2AX, were found leaking into the cytoplasm following bleomycin treatment.
This leaking DNA may potentially activate a specific immune response pathway (cGAS-STING).
Increased unresolved DNA damage was observed, correlating with advanced senescence and cell death.
No direct fibrotic effects were noted in either normal or iUIP lung slices after bleomycin treatment.

Simplified

Bleomycin is an effective anticancer agent that causes drug-induced interstitial pneumonia (IP). Medical history is a risk factor for adverse effects, particularly a history of IP and age-related fibrosis. Anti-cancer drugs for lung cancer with idiopathic pulmonary fibrosis (IPF) often aggravate pulmonary fibrosis. Thus, we examined the pathological effects of bleomycin, an anticancer drug, in precision-cut lung slices (PCLS) of lungs with usual interstitial pneumonia (UIP). We found that the lungs of mice with induced UIP (iUIP), which exhibit a pathology similar to that of IPF, underwent accelerated senescence. Treatment of iUIP PCLS with bleomycin reduced the nuclear membrane component lamin B1 and nuclear DNA with γH2AX leaked into the cytoplasm. This perinuclear DNA may activate NF-κB through the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. As a result, the unresolved DNA damage associated with the failure of DNA repair and senescence progression is more advanced in these cells. However,andexpression was not induced in either bleomycin-treated normal or iUIP PCLS, suggesting that there was no direct fibrotic effect on the lungs. We concluded that lungs with iUIP exhibited accelerated senescence following bleomycin treatment, leading to cell death. Col1a1Acta2

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CONFLICTS OF INTEREST: The authors declare no conflicts of interest related to this study.

PubMed

Bleomycin triggers cell aging and immune response activation without directly causing scarring in a lung fibrosis model

Abstract

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Competing interests

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Abstract

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Funding

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