npj agingJun 18, 2026

Different types of aging fibroblast cells link DNA damage to unexplained lung scarring

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 19, 2026

Abstract

Primary human lung fibroblasts from donors with idiopathic pulmonary fibrosis (IPF) show a distinct form of heterogeneity after DNA damage.

Cellular senescence is a state of cell stress that increases with age and is linked to age-related dysfunction.
Healthy and IPF lung fibroblasts exhibit subtle differences in their stress response over time following DNA damage.
Senescent IPF lung fibroblasts demonstrate an abnormal response in the transcriptional and protein levels related to DNA damage.
Analysis of gene networks identifies specific genes related to DNA damage repair and immune responses associated with senescent IPF cells.
A novel gene signature has been developed to identify disease-relevant senescence-associated cells in single-cell RNA sequencing data.

Simplified

Cellular senescence is a highly heterogeneous state of cell stress response that deleteriously accumulates with age and contributes to age-related dysfunction. While the heterogeneity across cell types is well documented, variation within the same cell type is only beginning to be understood. Here, we show primary human lung fibroblasts from either donors who are healthy or diagnosed with idiopathic pulmonary fibrosis (IPF) exhibit a subtle form of heterogeneity over time after DNA damage. Moreover, senescent IPF lung fibroblasts display a dysregulated transcriptional-protein DNA damage response (DDR). Weighted gene correlation network analysis (WGCNA) reveals unique and known targets linking senescent IPF lung fibroblast heterogeneity to genes associated with DNA damage and repair and cytokine and chemokine responses. We combine our healthy and IPF senescent gene expression datasets to develop a novel gene signature of senescence-associated genes that identify disease-relevant cells in human single-cell RNA-seq (scRNA-seq) data. Collectively, our results uncover human-relevant senescence signatures, highlight IPF-specific DDR, cytokine, and chemokine targets, and expand our understanding of how a dysregulated DDR contributes to senescent cell heterogeneity in IPF.

Full Text

Full text is available at the source.

View Full Text ↗

Funding

Competing interests

Competing interests: Akshay Pujari, Isaac Joshua, Corrigan Horton, Alberto Vitari, Alex Laslavic, and Marco Quarta are employees of and/or hold equity in Rubedo Life Sciences, Inc., which may benefit financially from the results of this work. The other authors declare no competing interests.

PubMed

Different types of aging fibroblast cells link DNA damage to unexplained lung scarring

Abstract

Full Text

Funding

Competing interests

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the longevity & aging brief