Research Paper Volume 16, Issue 16 pp 11809—11823

Leukocyte telomere length and attrition in association with disease severity in cystic fibrosis patients

Dries S. Martens1, *, , Elise J. Lammertyn2, *, , Pieter C. Goeminne3, , Kristine Colpaert4, , Marijke Proesmans5, , Bart M. Vanaudenaerde2, , Tim S. Nawrot1,6, , Lieven J. Dupont2,4, ,

  • 1 Centre for Environmental Sciences, Hasselt University, Hasselt, Belgium
  • 2 Department of Chronic Diseases and Metabolism (CHROMETA), Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium
  • 3 Hospital VITAZ Sint-Niklaas, Sint-Niklaas, Belgium
  • 4 Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium
  • 5 Department of Pediatrics, Pediatric Pulmonology, University Hospital of Leuven, Leuven, Flanders, Belgium
  • 6 Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
* Equal contribution

Received: December 19, 2023       Accepted: July 15, 2024       Published: August 29, 2024      

https://doi.org/10.18632/aging.206093
How to Cite

Copyright: © 2024 Martens et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Cystic fibrosis (CF) is characterized by chronic airway inflammation and premature aging. The link with leukocyte telomere length (LTL) as a marker of biological aging is unclear. We studied disease severity and LTL in 168 CF patients of which 85 patients had a second retrospective LTL assessment. A higher FEV1 was associated with longer LTL, with a stronger effect in men (5.08% longer LTL) compared to women (0.41% longer LTL). A higher FEV1/FVC ratio was associated with 7.05% (P=0.017) longer LTL in men. CF asthma, as defined by the treatment with inhaled corticosteroids, was associated with -6.65% shorter LTL (P=0.028). Men homozygous for the ΔF508 genotype showed a –10.48% (P=0.026) shorter LTL compared to heterozygotes. A genotype-specific non-linear association between LTL shortening and chronological age was observed. Stronger age-related LTL shortening was observed in patients homozygous for the ΔF508 genotype (P-interaction= 0.044). This work showed that disease severity in CF patients negatively influences LTL, with slightly more pronounced effects in men. The homozygous genotype for ΔF508 may play a role in LTL attrition in CF patients. Understanding factors in CF patients that accelerate biological aging provides insights into mechanisms that can extend the overall life quality in CF-diseased.

Abbreviations

CF: Cystic Fibrosis; CFTR: Cystic Fibrosis Transmembrane Conductance Regulator; COPD: Chronic Obstructive Pulmonary Disease; FEV1: Forced Expiratory Volume in 1 second; FVC: Forced Vital Capacity; ICS: Inhaled Corticosteroids; IPF: Idiopathic Pulmonary Disease; LTL: Leukocyte Telomere Length; SD: Standard deviation; TP1: Timepoint 1; TP2: Timepoint 2.