The European respiratory journalDec 7, 2023

How physical aging signs and genetic risk together relate to new cases of chronic lung diseases

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Apr 6, 2026

Abstract

is associated with a 52% increased risk of idiopathic pulmonary fibrosis per 5-year increase.

PhenoAgeAccel shows significant associations with increased risk of chronic respiratory diseases, including idiopathic pulmonary fibrosis, COPD, and asthma.
Each 5-year increase in PhenoAgeAccel correlates with a hazard ratio of 1.52 for idiopathic pulmonary fibrosis, 1.54 for COPD, and 1.18 for asthma.
Participants with high genetic risk and accelerated biological age exhibited the highest risk of developing IPF, COPD, and asthma.
Mediation analysis suggests that PhenoAgeAccel may mediate 10-20% of the relationship between smoking and chronic respiratory diseases.
Approximately 10% of the association between exposure to fine particulate matter and chronic respiratory disorders could also be mediated by PhenoAgeAccel.

Simplified

BACKGROUND: Accelerated biological ageing has been associated with an increased risk of several chronic respiratory diseases. However, the associations between phenotypic age, a new biological age indicator based on clinical chemistry biomarkers, and common chronic respiratory diseases have not been evaluated.

METHODS: We analysed data from 308 592 participants at baseline in the UK Biobank. The phenotypic age was calculated from chronological age and nine clinical chemistry biomarkers, including albumin, alkaline phosphatase, creatinine, glucose, C-reactive protein, lymphocyte percent, mean cell volume, red cell distribution width and white blood cell count. Furthermore, phenotypic age acceleration () was calculated by regressing phenotypic age on chronological age. The associations of PhenoAgeAccel with incident common chronic respiratory diseases and cross-sectional lung function were investigated. Moreover, we constructed polygenic risk scores and evaluated whether PhenoAgeAccel modified the effect of genetic susceptibility on chronic respiratory diseases and lung function.

RESULTS: The results showed significant associations of PhenoAgeAccel with increased risk of idiopathic pulmonary fibrosis (IPF) (hazard ratio (HR) 1.52, 95% CI 1.45-1.59), COPD (HR 1.54, 95% CI 1.51-1.57) and asthma (HR 1.18, 95% CI 1.15-1.20) per 5-year increase and decreased lung function. There was an additive interaction between PhenoAgeAccel and the genetic risk for IPF and COPD. Participants with high genetic risk and who were biologically older had the highest risk of incident IPF (HR 5.24, 95% CI 3.91-7.02), COPD (HR 2.99, 95% CI 2.66-3.36) and asthma (HR 2.07, 95% CI 1.86-2.31). Mediation analysis indicated that PhenoAgeAccel could mediate 10∼20% of the associations between smoking and chronic respiratory diseases, while ∼10% of the associations between particulate matter with aerodynamic diameter <2.5 µm and the disorders were mediated by PhenoAgeAccel.

CONCLUSION: PhenoAgeAccel was significantly associated with incident risk of common chronic respiratory diseases and decreased lung function and could serve as a novel clinical biomarker.

Key numbers

1.52

Increased Risk of IPF

Hazard ratio per 5-year increase in

5.24

Highest Risk for IPF with Genetic Risk

Hazard ratio for high genetic risk participants with high

20.1%

Mediation Proportion by

Mediation proportion for the association between smoking and IPF

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How physical aging signs and genetic risk together relate to new cases of chronic lung diseases

Abstract

Key numbers

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