Association of adult lung function with accelerated biological aging

Abstract

Lung function, strongly associated with morbidity and mortality, decreases with age. This study examines whether poor adult lung function is associated with age accelerations (AAs). DNA methylation (DNAm) based AAs, lifespan predictors (GrimAge and plasminogen activator inhibitor 1-PAI1) and their related age-adjusted measures were estimated from peripheral blood at two time points (8-to-11 years apart) in adults from two cohorts: SAPALDIA (n=987) and ECRHS (n=509). Within each cohort and stratified by gender (except for estimators from GrimAge and PAI1), AAs were used as predictors in multivariate linear regression with cross-sectional lung function parameters, and in covariate-adjusted mixed linear regression with longitudinal change in lung function and meta-analysed.AAs were found cross-sectionally associated with lower mean FEV1 (Forced Expiratory Volume in one second) (AA-residuals:P-value=4x10^-4; Intrinsic Epigenetic AA:P-value=2x10^-4) in females at the follow-up time point only, and the same trend was observed for FVC (Forced Vital Capacity). Both lifespan and plasma level predictors were observed strongly associated with lung function decline and the decline was stronger in the follow-up time points (strongest association between FEV1 and DNAmAge GrimAge:P-value=1.25x10^-17).This study suggests that DNAm based lifespan and plasma level predictors can be utilised as important factors to assess lung health in adults.

Keywords: DNA methylation; age acceleration; epigenetic clock; lung function; respiratory health.

Figure 1

Cross-sectional meta-analysis results for FEV₁ of males and females in SAPALDIA and ECRHS. (A) Mean change in FEV₁ (mL) per year of intrinsic epigenetic age acceleration at baseline; (B) Mean change in FEV₁ (mL) per year of intrinsic epigenetic age acceleration at follow-up. The estimates have been measured with 95% confidence interval in mL/year.

Figure 2

Linear mixed model meta-analysis results for FEV₁ of males and females in SAPALDIA and ECRHS for two time points (baseline and follow-up). The estimates have been measured with 95% confidence interval in mL/year.

Figure 3

Age stratified analyses comparing association between lung and age accelerations. (A) Comparison between association between FEV₁ and age accelerations (AAres and IEAA); (B) Comparison between association between FVC and age accelerations (AAres and IEAA). X-axis represents stratifications by 10 years intervals. Y-axis represents the estimates (changed in lung function per year of epigenetic age acceleration in mL/year) from the linear models with 95% confidence intervals.