Abstract
Aging is the predominant risk factor for most degenerative diseases, including chronic obstructive pulmonary disease (COPD). This process is however very heterogeneous. Defining the biological aging of individual tissues may contribute to better assess this risky process. In this study, we examined the biological age of induced sputum (IS) cells, and peripheral blood leukocytes in the same subject, and compared these to assess whether biological aging of blood leukocytes mirrors that of IS cells. Biological aging was assessed in 18 COPD patients (72.4 ± 7.7 years; 50% males). We explored mitotic and non-mitotic aging pathways, using telomere length (TL) and DNA methylation-based age prediction (DNAmAge) and age acceleration (AgeAcc) (i.e., difference between DNAmAge and chronological age). Data on demographics, life style and occupational exposure, lung function, and clinical and blood parameters were collected. DNAmAge (67.4 ± 5.80 vs. 61.6 ± 5.40 years; p = 0.0003), AgeAcc (−4.5 ± 5.02 vs. −10.8 ± 3.50 years; p = 0.0003), and TL attrition (1.05 ± 0.35 vs. 1.48 ± 0.21 T/S; p = 0.0341) are higher in IS cells than in blood leukocytes in the same patients. Blood leukocytes DNAmAge (r = 0.927245; p = 0.0026) and AgeAcc (r = 0.916445; p = 0.0037), but not TL, highly correlate with that of IS cells. Multiple regression analysis shows that both blood leukocytes DNAmAge and AgeAcc decrease (i.e., younger) in patients with FEV1% enhancement (p = 0.0254 and p = 0.0296) and combined inhaled corticosteroid (ICS) therapy (p = 0.0494 and p = 0.0553). In conclusion, new findings from our work reveal a differential aging in the context of COPD, by a direct quantitative comparison of cell aging in the airway with that in the more accessible peripheral blood leukocytes, providing additional knowledge which could offer a potential translation into the disease management.
Highlights
The aging of the population, called the “gray” revolution, is undoubtedly an emerging social and public health problem
All patients underwent a physical examination, and lung function was assessed by spirometry recording forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), and forced expiratory volume in a 1-s (FEV1)/VC ratio defined as Tiffeneau index
The comparison of two groups (Mann–Whitney U-test) indicates that patients in LABA/LAMA therapy present higher values of FEV1 (p = 0.0003), FEV1% (p < 0.0001), FVC (p = 0.0003), VC (p = 0.0003), and TLC (p = 0.0008) and a lower systolic pressure (p = 0.036), than those with inhaled corticosteroid (ICS) therapy and LABA/LAMA
Summary
The aging of the population, called the “gray” revolution, is undoubtedly an emerging social and public health problem. Aging is an individual and very complex process characterized by a progressive decline in the body’s ability to respond to internal and/or external stressors [1]. This deterioration is the primary risk factor for major human degenerative pathologies, including cancer and cardiovascular, neurodegenerative, and respiratory diseases [1]. Chronic obstructive pulmonary disease (COPD) is one of the major causes of chronic morbidity [2] and the third leading cause of death worldwide which is projected to rise [3] because of the aging population. Not all individuals grow older in the same way [4]; chronological age may not be a reliable indicator of physiological decline [5]
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