Abstract
Background: Asthma is a complex pulmonary inflammatory disease which is common among older adults. Aging-related alterations have also been found in structural cells and immune cells of asthma patients. Nonetheless, the underlying mechanism by which differenced aging-related gene contributes to asthma pathology remains unclear. Of note, DNA methylation (DNAm) has been proven to play a critical mechanism for age-related gene expression changes. However, the methylation changes of aging-related genes in asthma patients are still obscure. Methods: First, changes in DNAm and gene expression were detected with multiple targeted bisulfite enrichment sequencing (MethTarget) and qPCR in peripheral blood of 51 healthy controls (HCs) and 55 asthmatic patients. Second, the correlation between the DNAm levels of specific altered CpG sites and the pulmonary function indicators of asthma patients was evaluated. Last, the receiver operator characteristic (ROC) curve and principal component analysis (PCA) were used to identify the feasibility of the candidate CpG sites as biomarkers for asthma. Results: Compared with HCs, there was a differential mRNA expression for nine aging-related genes in peripheral blood of asthma patients. Besides, the methylation levels of the nine aging-related genes were also altered in asthma patients, and a total of 68 CpG sites were associated with the severity of asthma. Notably, 9 of the 68 CpG sites were significantly associated with pulmonary function parameters. Moreover, ROC curve and PCA analysis showed that the candidate differential methylation sites (DMSs) can be used as potential biomarkers for asthma. Conclusions: In summary, this study confirmed the differentially expressed mRNA and aberrant DNAm level of aging-related genes in asthma patients. DMSs are associated with the clinical evaluation indicators of asthma, which indicate the involvement of aging-related genes in the pathogenesis of asthma and provide some new possible biomarkers for asthma.
Highlights
Asthma is a chronic and complex pulmonary inflammation disease which is characterized by aberrant immune responses to allergen, reversible airflow obstruction, and airway hyperresponsiveness (AHR)
Accumulative studies have demonstrated the involvement of aging in the parthenogenesis of chronic pulmonary diseases, including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary diseases (COPD)
It has been confirmed that antiaging strategies can improve pathological processes such as airway inflammation and airway remodeling in asthma patients (Conte et al, 2015)
Summary
Asthma is a chronic and complex pulmonary inflammation disease which is characterized by aberrant immune responses to allergen, reversible airflow obstruction, and airway hyperresponsiveness (AHR). The pathological changes in asthma resemble those in COPD, such as airway remodeling, chronic inflammation, and decreased lung function (Zhou-Suckow et al, 2017; Aghasafari et al, 2019). Aging-related changes have been found in structural cells and immune cells of asthma patients. The aging of different targeted cells can contribute to the pathobiology of asthma, including airway inflammation, airway remodeling, and decreased lung function (Wang et al, 2020). Aging-related alterations have been found in structural cells and immune cells of asthma patients. The underlying mechanism by which differenced aging-related gene contributes to asthma pathology remains unclear. The methylation changes of aging-related genes in asthma patients are still obscure
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