Associations of lung function impairment and biological aging with mortality and cardiovascular disease incidence: findings from UK biobank participants

BackgroundLung function impairment, including preserved ratio impaired spirometry (PRISm) and airflow limitation (AL), is associated with increased risks of mortality and cardiovascular disease; however, the underlying biological mechanisms remain poorly understood. This study aimed to investigate t...

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Main Authors: Jiali Chen, Cheng Wang, Pengyu Duan, Yonghong Bi, Yao Meng, Weiyu Feng, Zhehao Jin, Hangbing Li, Huihui Wang, Xiaoyan Li, Kun Zuo, Xiangcheng Zhao, Longfei Li, Yuling Xing, Lan Luo, Yang Yu, Miao Yu, Muyan Cui, Bing Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Public Health
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Online Access:https://www.frontiersin.org/articles/10.3389/fpubh.2025.1635195/full
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author Jiali Chen
Cheng Wang
Pengyu Duan
Yonghong Bi
Yao Meng
Weiyu Feng
Zhehao Jin
Hangbing Li
Huihui Wang
Xiaoyan Li
Kun Zuo
Xiangcheng Zhao
Longfei Li
Yuling Xing
Lan Luo
Yang Yu
Miao Yu
Muyan Cui
Bing Zhang
author_facet Jiali Chen
Cheng Wang
Pengyu Duan
Yonghong Bi
Yao Meng
Weiyu Feng
Zhehao Jin
Hangbing Li
Huihui Wang
Xiaoyan Li
Kun Zuo
Xiangcheng Zhao
Longfei Li
Yuling Xing
Lan Luo
Yang Yu
Miao Yu
Muyan Cui
Bing Zhang
author_sort Jiali Chen
collection DOAJ
description BackgroundLung function impairment, including preserved ratio impaired spirometry (PRISm) and airflow limitation (AL), is associated with increased risks of mortality and cardiovascular disease; however, the underlying biological mechanisms remain poorly understood. This study aimed to investigate the mediating role of biological aging, as well as the interactions and joint effects of lung function impairment and biological aging on adverse health outcomes.MethodsA total of 349,456 UK Biobank participants (aged 40–69 years) were categorized into normal, PRISm, and AL groups based on baseline spirometric measurements. Biological aging was assessed using phenotypic age acceleration (PhenoAgeAccel) and frailty phenotype. PhenoAgeAccel was calculated using algorithms based on clinical biomarkers, and frailty was evaluated according to five established criteria. Cox proportional hazards models were used to assess the risks of all-cause mortality and CVD (including coronary artery disease, heart failure, and ischemic stroke). Mediation and interaction analyses further examined the associations between lung function impairment, biological aging, and adverse health outcomes.ResultsOver an average follow-up of 13.8–14.4 years, 28,059 deaths and 34,863 incident CVD cases were recorded. PhenoAgeAccel mediated 12.8–16.2% of the association between lung function impairment and mortality, compared to 7.0–12.0% for frailty. For CVD, the mediation proportions were 8.5–15.9% (PhenoAgeAccel) and 7.4–8.6% (frailty). Significant multiplicative and additive interactions were found between lung function impairment and biological aging, especially for mortality risk. The joint analysis revealed that participants with both impaired lung function and accelerated biological aging had the highest mortality and CVD risks.ConclusionBiological aging partially mediates the associations between lung function impairment and adverse outcomes, exhibiting synergistic interactions with impaired lung function. Thus, therapies targeting biological aging may complement conventional lung function promotion in reducing health disparities among aging populations.
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spelling doaj-art-75d1a5ca3d544e82a0bf9245b1ebfe202025-08-20T02:36:04ZengFrontiers Media S.A.Frontiers in Public Health2296-25652025-07-011310.3389/fpubh.2025.16351951635195Associations of lung function impairment and biological aging with mortality and cardiovascular disease incidence: findings from UK biobank participantsJiali Chen0Cheng Wang1Pengyu Duan2Yonghong Bi3Yao Meng4Weiyu Feng5Zhehao Jin6Hangbing Li7Huihui Wang8Xiaoyan Li9Kun Zuo10Xiangcheng Zhao11Longfei Li12Yuling Xing13Lan Luo14Yang Yu15Miao Yu16Muyan Cui17Bing Zhang18Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Environmental Hygiene, School of Public Health, Harbin Medical University, Harbin, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Environmental Hygiene, School of Public Health, Harbin Medical University, Harbin, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaBackgroundLung function impairment, including preserved ratio impaired spirometry (PRISm) and airflow limitation (AL), is associated with increased risks of mortality and cardiovascular disease; however, the underlying biological mechanisms remain poorly understood. This study aimed to investigate the mediating role of biological aging, as well as the interactions and joint effects of lung function impairment and biological aging on adverse health outcomes.MethodsA total of 349,456 UK Biobank participants (aged 40–69 years) were categorized into normal, PRISm, and AL groups based on baseline spirometric measurements. Biological aging was assessed using phenotypic age acceleration (PhenoAgeAccel) and frailty phenotype. PhenoAgeAccel was calculated using algorithms based on clinical biomarkers, and frailty was evaluated according to five established criteria. Cox proportional hazards models were used to assess the risks of all-cause mortality and CVD (including coronary artery disease, heart failure, and ischemic stroke). Mediation and interaction analyses further examined the associations between lung function impairment, biological aging, and adverse health outcomes.ResultsOver an average follow-up of 13.8–14.4 years, 28,059 deaths and 34,863 incident CVD cases were recorded. PhenoAgeAccel mediated 12.8–16.2% of the association between lung function impairment and mortality, compared to 7.0–12.0% for frailty. For CVD, the mediation proportions were 8.5–15.9% (PhenoAgeAccel) and 7.4–8.6% (frailty). Significant multiplicative and additive interactions were found between lung function impairment and biological aging, especially for mortality risk. The joint analysis revealed that participants with both impaired lung function and accelerated biological aging had the highest mortality and CVD risks.ConclusionBiological aging partially mediates the associations between lung function impairment and adverse outcomes, exhibiting synergistic interactions with impaired lung function. Thus, therapies targeting biological aging may complement conventional lung function promotion in reducing health disparities among aging populations.https://www.frontiersin.org/articles/10.3389/fpubh.2025.1635195/fullbiological agingcardiovascular diseasefrailtymortalitypreserved ratio impaired spirometry (PRISm)phenotypic age acceleration
spellingShingle Jiali Chen
Cheng Wang
Pengyu Duan
Yonghong Bi
Yao Meng
Weiyu Feng
Zhehao Jin
Hangbing Li
Huihui Wang
Xiaoyan Li
Kun Zuo
Xiangcheng Zhao
Longfei Li
Yuling Xing
Lan Luo
Yang Yu
Miao Yu
Muyan Cui
Bing Zhang
Associations of lung function impairment and biological aging with mortality and cardiovascular disease incidence: findings from UK biobank participants
Frontiers in Public Health
biological aging
cardiovascular disease
frailty
mortality
preserved ratio impaired spirometry (PRISm)
phenotypic age acceleration
title Associations of lung function impairment and biological aging with mortality and cardiovascular disease incidence: findings from UK biobank participants
title_full Associations of lung function impairment and biological aging with mortality and cardiovascular disease incidence: findings from UK biobank participants
title_fullStr Associations of lung function impairment and biological aging with mortality and cardiovascular disease incidence: findings from UK biobank participants
title_full_unstemmed Associations of lung function impairment and biological aging with mortality and cardiovascular disease incidence: findings from UK biobank participants
title_short Associations of lung function impairment and biological aging with mortality and cardiovascular disease incidence: findings from UK biobank participants
title_sort associations of lung function impairment and biological aging with mortality and cardiovascular disease incidence findings from uk biobank participants
topic biological aging
cardiovascular disease
frailty
mortality
preserved ratio impaired spirometry (PRISm)
phenotypic age acceleration
url https://www.frontiersin.org/articles/10.3389/fpubh.2025.1635195/full
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