Telomere length associates with chronological age and mortality across racially diverse pulmonary fibrosis cohorts

Abstract

Pulmonary fibrosis (PF) is characterized by profound scarring and poor survival. We investigated the association of leukocyte telomere length (LTL) with chronological age and mortality across racially diverse PF cohorts. LTL measurements among participants with PF stratified by race/ethnicity were assessed in relation to age and all-cause mortality, and compared to controls. Generalized linear models were used to evaluate the age-LTL relationship, Cox proportional hazards models were used for hazard ratio estimation, and the Cochran–Armitage test was used to assess quartiles of LTL. Standardized LTL shortened with increasing chronological age; this association in controls was strengthened in PF (R = −0.28; P < 0.0001). In PF, age- and sex-adjusted LTL below the median consistently predicted worse mortality across all racial groups (White, HR = 2.21, 95% CI = 1.79–2.72; Black, HR = 2.22, 95% CI = 1.05–4.66; Hispanic, HR = 3.40, 95% CI = 1.88–6.14; and Asian, HR = 2.11, 95% CI = 0.55–8.23). LTL associates uniformly with chronological age and is a biomarker predictive of mortality in PF across racial groups.

17-year follow-up of association between telomere length and all-cause mortality, cardiovascular mortality in individuals with metabolic syndrome: results from the NHANES database prospective cohort study

“…Numerous studies have shown that shortened telomere length increased the risk of all-cause mortality [ 10 , 24 , 25 ]。In a study involving 472,432 participants from the UK Biobank, Schneider et al found that shortened LTL was positively correlated with all-cause mortality as well as disease-specific mortality for respiratory, digestive, circulatory, musculoskeletal, and infectious diseases [ 6 ]. Konstantin G Arbeev analyzed three European cohorts including a total of 3259 individuals and revealed that the risk of death from any cause increased by 1.34 times for every 1 kb decrease in LTL [ 10 ].…”

Interstitial lung disease: a review of classification, etiology, epidemiology, clinical diagnosis, pharmacological and non-pharmacological treatment

“…A growing body of evidence shows that genetic factors play a role in some of ILD onset ( 74 , 75 ). It is now understood that certain inherited traits, such as rare pathogenic variants in genes associated with telomere maintenance and surfactant production ( 76 ), common single nucleotide polymorphisms ( 77 ), and reduced leukocyte telomere length can contribute to an increased risk of ILD ( 78 ).…”

“…This trend is particularly evident in IPF, where the disease predominantly affects individuals over the age of 65 ( 26 ). The association between aging and ILDs can be partially attributed to the biological process of telomere shortening ( 75 , 78 ). Telomeres, protective caps at the end of chromosomes, naturally shorten as individuals age, contributing to cellular senescence and reduced regenerative capacity ( 75 , 78 ).…”

“…The association between aging and ILDs can be partially attributed to the biological process of telomere shortening ( 75 , 78 ). Telomeres, protective caps at the end of chromosomes, naturally shorten as individuals age, contributing to cellular senescence and reduced regenerative capacity ( 75 , 78 ). In IPF and possibly other ILDs, accelerated telomere shortening due to genetic factors or environmental exposures can lead to premature lung aging and increased vulnerability to fibrotic processes.…”

“…In IPF and possibly other ILDs, accelerated telomere shortening due to genetic factors or environmental exposures can lead to premature lung aging and increased vulnerability to fibrotic processes. Studies have found that men over 65 exhibit the most significant telomere shortening, correlating with the highest risk for developing IPF ( 75 , 78 ). However, it's essential to consider that aging affects lung physiology and immune responses in both genders, contributing to a general increase in ILD susceptibility among older adult ( 91 ).…”