Accelerated epigenetic aging worsens survival and mediates environmental stressors in fibrotic interstitial lung disease.

IF 16.6 1区医学 Q1 RESPIRATORY SYSTEM

European Respiratory Journal Pub Date : 2025-01-30 DOI:10.1183/13993003.01618-2024

Gillian C Goobie, Daniel-Costin Marinescu, Ayodeji Adegunsoye, Jean Bourbeau, Christopher Carlsten, Rachel L Clifford, Dany Doiron, Qingling Duan, Kevin F Gibson, Amanda Grant-Orser, Ana I Hernandez Cordero, Kerri A Johannson, Daniel J Kass, Sharon E Kim, Janice M Leung, Xiaoyun Li, Wan Tan, Chen Xi Yang, S Mehdi Nouraie, Christopher J Ryerson, Tillie L Hackett, Yingze Zhang

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引用次数: 0

Abstract

Background: The role of epigenetic aging in the environmental pathogenesis and prognosis of fibrotic interstitial lung disease (fILD) is unclear. We evaluated whether ambient particulate matter ≤2.5 μm (PM_2.5) and neighbourhood disadvantage exposures are associated with accelerated epigenetic aging, and whether epigenetic age is associated with adverse clinical outcomes in patients with fILD.

Methods: This multicentre, international, cohort study included patients with fILD from the University of Pittsburgh (UPitt, n=306) and University of British Columbia (UBC, n=170). Five-year PM_2.5 exposures were estimated using satellite-derived models. Neighbourhood disadvantage was calculated using U.S. and Canadian Census-based metrics. Epigenetic age difference (EAD=epigenetic age - chronological age) was calculated using GrimAge analysis of blood DNA methylation data. Linear models assessed associations of exposures with EAD. Cox models assessed associations of EAD with transplant-free survival. Causal mediation analysis evaluated EAD mediation of exposure-survival relationships.

Results: Median epigenetic age was 11.7 years older than chronological age in patients with fILD. In combined cohort analysis, each interquartile range (IQR) PM_2.5 increase was associated with 2.88 years (95%CI 1.39-4.38, p<0.001) increased EAD. In UPitt, each IQR neighbourhood disadvantage increase was associated with 1.16 years (95%CI 0.22-2.09, p=0.02) increased EAD. Increased EAD was associated with worse transplant-free survival (HR=1.17 per 1-year increase EAD, 95%CI 1.10-1.24, p<0.001), with EAD mediating 40% of PM_2.5-survival relationship and 59% of neighbourhood disadvantage-survival relationships. Epigenetic age was also more strongly associated with transplant-free survival than chronological age.

Conclusions: Epigenetic age acceleration is associated with worse survival and mediates adverse exposure impacts in fILD.

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来源期刊

European Respiratory Journal 医学-呼吸系统

CiteScore

27.50

自引率

3.30%

发文量

345

审稿时长

2-4 weeks

期刊介绍： The European Respiratory Journal (ERJ) is the flagship journal of the European Respiratory Society. It has a current impact factor of 24.9. The journal covers various aspects of adult and paediatric respiratory medicine, including cell biology, epidemiology, immunology, oncology, pathophysiology, imaging, occupational medicine, intensive care, sleep medicine, and thoracic surgery. In addition to original research material, the ERJ publishes editorial commentaries, reviews, short research letters, and correspondence to the editor. The articles are published continuously and collected into 12 monthly issues in two volumes per year.