DNA methylation perturbations may link altered development and aging in the lung

Area of Science:

• Epigenetics
• Developmental Biology
• Pulmonology

Background:

• Fetal DNA methylation patterns during lung development may influence adult lung health and aging-related diseases.
• Previous research has not fully explored these enduring impacts.

Purpose of the Study:

• To investigate the association between genome-wide DNA methylation and age in both fetal and adult lung tissues.
• To identify overlapping age-associated methylation patterns and their functional implications.
• To examine the influence of factors like in-utero smoke exposure, sex, and smoking history on these associations.

Main Methods:

• Multi-variate linear regression models were used to analyze DNA methylation data from fetal (n=78) and adult (n=160) lung tissues.
• Covariate adjustment and phenotype-based effect modification testing were performed.
• Functional enrichment analysis utilized the Genotype-Tissue-Expression (GTEx) project.

Main Results:

• 244 age-associated differentially methylated positions and 878 regions overlapped between fetal and adult lung tissues.
• Hyper-methylated CpGs were enriched in transcription factor activity and developmental processes.
• Hypo-methylated CpGs were linked to oxido-reductase activity and VEGFA-VEGFR2 signaling.
• Significant age-by-sex and age-by-pack-years interactions were observed in adult lung tissue.

Conclusions:

• DNA methylation patterns in transcription factors established during fetal lung development are recapitulated in adult lung tissue with aging.
• These findings suggest molecular mechanisms linking early-life developmental disruptions to age-associated lung diseases.