Abstract
Background: Severe asthma is more prevalent in the ageing adult population. Mitochondrial oxidative stress status has been implicated in this process.
Aims & Objectives: To investigate the correlation between mitochondrial function (OXPHOS) and cellular ageing signatures in subjects from the U-BIOPRED consortium.
Methods: We used gene set variation analysis (GSVA) to study OXPHOS and ageing signatures in blood (312 subjects), bronchial biopsies (108 subjects), bronchial brushings (147 subjects), sputum (120 subjects) and nasal brushings (89 subjects) from the U-BIOPRED cohort.
Results: The OXPHOS signature was enriched in the blood of severe asthmatics who smoked (adj.p=0.03) with a weak positive correlation with the ageing signature (r=0.32, p<10-9). The OXPHOS signature in bronchial brushings correlated with ageing signatures (r=0.5, p<10-5). OXPHOS was enriched in severe asthma biopsies to a greater extent in the smokers v's non-smokers despite the ageing signature being reduced in all asthmatics resulting in a negative correlation (r=-0.2, p=0.04). The OXPHOS and ageing signatures in sputum were both reduced in asthma and highly correlated (r=0.77, p<10-16). OXPHOS and ageing signatures did not correlate in nasal brushings.
Conclusion: The association between mitochondrial function and ageing gene signatures in severe asthma depends upon the compartment examined and is independent of the chronological age.
- Copyright ©the authors 2016
