DNA Methylation-Based Age Prediction and Telomere Length Reveal an Accelerated Aging in Induced Sputum Cells Compared to Blood Leukocytes: A Pilot Study in COPD Patients

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...

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Main Authors: Manuela Campisi, Filippo Liviero, Piero Maestrelli, Gabriella Guarnieri, Sofia Pavanello
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-07-01
Series:Frontiers in Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2021.690312/full
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author Manuela Campisi
Filippo Liviero
Piero Maestrelli
Gabriella Guarnieri
Sofia Pavanello
author_facet Manuela Campisi
Filippo Liviero
Piero Maestrelli
Gabriella Guarnieri
Sofia Pavanello
author_sort Manuela Campisi
collection DOAJ
description 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.
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spelling doaj.art-78918fb62f5d48c1b69e077b891283402022-12-21T19:59:42ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2021-07-01810.3389/fmed.2021.690312690312DNA Methylation-Based Age Prediction and Telomere Length Reveal an Accelerated Aging in Induced Sputum Cells Compared to Blood Leukocytes: A Pilot Study in COPD PatientsManuela Campisi0Filippo Liviero1Piero Maestrelli2Gabriella Guarnieri3Sofia Pavanello4Occupational Medicine, Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, University Hospital of Padua, Padua, ItalyOccupational Medicine, Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, University Hospital of Padua, Padua, ItalyOccupational Medicine, Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, University Hospital of Padua, Padua, ItalyRespiratory Pathophysiology Unit, Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, University Hospital of Padua, Padua, ItalyOccupational Medicine, Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, University Hospital of Padua, Padua, ItalyAging 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.https://www.frontiersin.org/articles/10.3389/fmed.2021.690312/fullDNA methylation ageage accelerationinduced sputumchronic obstructive pulmonary diseaselung agingtelomere length
spellingShingle Manuela Campisi
Filippo Liviero
Piero Maestrelli
Gabriella Guarnieri
Sofia Pavanello
DNA Methylation-Based Age Prediction and Telomere Length Reveal an Accelerated Aging in Induced Sputum Cells Compared to Blood Leukocytes: A Pilot Study in COPD Patients
Frontiers in Medicine
DNA methylation age
age acceleration
induced sputum
chronic obstructive pulmonary disease
lung aging
telomere length
title DNA Methylation-Based Age Prediction and Telomere Length Reveal an Accelerated Aging in Induced Sputum Cells Compared to Blood Leukocytes: A Pilot Study in COPD Patients
title_full DNA Methylation-Based Age Prediction and Telomere Length Reveal an Accelerated Aging in Induced Sputum Cells Compared to Blood Leukocytes: A Pilot Study in COPD Patients
title_fullStr DNA Methylation-Based Age Prediction and Telomere Length Reveal an Accelerated Aging in Induced Sputum Cells Compared to Blood Leukocytes: A Pilot Study in COPD Patients
title_full_unstemmed DNA Methylation-Based Age Prediction and Telomere Length Reveal an Accelerated Aging in Induced Sputum Cells Compared to Blood Leukocytes: A Pilot Study in COPD Patients
title_short DNA Methylation-Based Age Prediction and Telomere Length Reveal an Accelerated Aging in Induced Sputum Cells Compared to Blood Leukocytes: A Pilot Study in COPD Patients
title_sort dna methylation based age prediction and telomere length reveal an accelerated aging in induced sputum cells compared to blood leukocytes a pilot study in copd patients
topic DNA methylation age
age acceleration
induced sputum
chronic obstructive pulmonary disease
lung aging
telomere length
url https://www.frontiersin.org/articles/10.3389/fmed.2021.690312/full
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