Emerging Mechanistic Links Between Fucosylation and Senescence in Lung Diseases

Abstract

Cellular senescence is increasingly recognized as a key driver of chronic lung diseases, contributing to persistent inflammation, impaired tissue repair, and pathological remodeling. In parallel, aberrant protein fucosylation has emerged as an important regulator of epithelial function and immune signaling in the respiratory tract. Recent evidence suggests that these processes may be mechanistically linked rather than independently dysregulated. In particular, core fucosylation mediated by fucosyltransferases, such as fucosyltransferases 8 (FUT8), can modulate receptor activity and amplify signaling pathways, including TGF-β/Smad and PI3K/Akt, that are central to the induction and maintenance of cellular senescence. These interactions may promote epithelial dysfunction, the senescence-associated secretory phenotype (SASP) production, and pro-fibrotic remodeling in diseases such as COPD, asthma, and idiopathic pulmonary fibrosis. In this review, we synthesize current knowledge on cellular senescence and fucosylation in chronic lung disease and highlight emerging evidence linking these processes through shared signaling networks. We further discuss the potential of the fucosylation-senescence axis as a source of novel biomarkers and therapeutic targets. This review is among the first to integrate emerging evidence linking aberrant fucosylation with cellular senescence signaling in chronic lung diseases, thereby providing a conceptual framework for future mechanistic and translational studies.

Keywords

Cellular senescence / Glycosylation / Fucosylation / Fucosyltransferases / SASP / asthma / COPD / IPF

Author Contributions

S.K.S., W.G., M.H., A.X. and P.G. collected data and wrote the manuscript. All authors read and approved the final version of the manuscript.

Ethics Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No datasets were generated or analyzed during the current study.

Funding

We gratefully acknowledge the support of Grants from the US National Institutes of Health (NIH) (1R01AI153331 and R01AI141642).

Declaration of Competing Interest

The authors have declared that no conflict of interest exists.

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