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白细胞端粒长度与囊性纤维化患者疾病严重程度的关系及其损耗。

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

机构信息

Centre for Environmental Sciences, Hasselt University, Hasselt, Belgium.

Department of Chronic Diseases and Metabolism (CHROMETA), Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium.

出版信息

Aging (Albany NY). 2024 Aug 29;16(16):11809-11823. doi: 10.18632/aging.206093.

DOI:10.18632/aging.206093
PMID:39213174
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11386922/
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 FEV was associated with longer LTL, with a stronger effect in men (5.08% longer LTL) compared to women (0.41% longer LTL). A higher FEV/FVC ratio was associated with 7.05% (=0.017) longer LTL in men. CF asthma, as defined by the treatment with inhaled corticosteroids, was associated with -6.65% shorter LTL (=0.028). Men homozygous for the ΔF508 genotype showed a -10.48% (=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 (-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.

摘要

囊性纤维化 (CF) 的特征是慢性气道炎症和过早衰老。白细胞端粒长度 (LTL) 作为生物衰老的标志物与 CF 之间的联系尚不清楚。我们研究了 168 名 CF 患者的疾病严重程度和 LTL，其中 85 名患者进行了第二次回顾性 LTL 评估。FEV 越高，LTL 越长，男性的效果更强（LTL 长 5.08%），而女性的效果较弱（LTL 长 0.41%）。FEV/FVC 比值越高，男性的 LTL 就越长 7.05%（=0.017）。根据吸入皮质类固醇的治疗，CF 哮喘与 LTL 缩短 -6.65%（=0.028）相关。ΔF508 基因型纯合子男性的 LTL 比杂合子短 -10.48%（=0.026）。观察到 LTL 缩短与年龄呈基因型特异性的非线性关联。ΔF508 基因型纯合子患者的 LTL 随年龄的相关性缩短更为明显（-交互作用=0.044）。这项工作表明，CF 患者的疾病严重程度对 LTL 有负面影响，男性的影响略大。ΔF508 的纯合基因型可能在 CF 患者的 LTL 损耗中起作用。了解 CF 患者中加速生物衰老的因素可以深入了解可以延长 CF 患者整体生活质量的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4403/11386922/e6ac11fea562/aging-16-206093-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4403/11386922/6ba9936d9fa1/aging-16-206093-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4403/11386922/e6ac11fea562/aging-16-206093-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4403/11386922/6ba9936d9fa1/aging-16-206093-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4403/11386922/e6ac11fea562/aging-16-206093-g002.jpg

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本文引用的文献

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Human telomere length is chromosome end-specific and conserved across individuals.人类端粒长度具有染色体末端特异性，且在个体间保持保守。
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白细胞端粒长度在囊性纤维化儿童和成人中未缩短，但与临床特征相关——一项横断面研究
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Maternal pre-pregnancy body mass index and newborn telomere length.孕妇孕前体重指数与新生儿端粒长度
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