Epigenetic Aging May Be A Biomarker for Respiratory Disease

Adults with wheezing mainly caused by chronic pulmonary conditions showed significantly accelerated epigenetic aging than those without wheezing, based on data from more than 2000 individuals.

Increasing evidence indicates that aging contributes to the risk for chronic respiratory diseases, but the impact of epigenetic changes stemming from DNA methylation has not been well studied, wrote Javier Perez-Garcia, MD, of Stanford University, Stanford, California, and colleagues.

In a study published in the European Respiratory Journal, the researchers used data from the National Health and Nutrition Examination Survey (NHANES) to analyze the association between epigenetic age acceleration in whole-blood and chronic respiratory diseases.

The study population included 2346 adults aged 50 years or older, with a mean age of 65.1 years, and approximately half were women; 39.3% of participants identified as White, 29.0% as Mexican American, 21.8% as Black, 6.4% as other Hispanic, and 3.5% as other/multiracial. The researcher analyzed self-reported phenotypes of wheezing, wheezing attacks, asthma, current asthma, asthma exacerbations, emphysema, chronic bronchitis, and age of onset for chronic obstructive pulmonary disease (COPD). 

Overall, 13.8% reported wheezing in the past year, 8.4% had COPD, and 10.6% had asthma. Those with no chronic respiratory conditions served as control Individuals. Epigenetic age was measured using chronological age clocks (HorvathAge, HannumAge, and SkinBloodAge) and health span clocks (PhenoAge, GrimAgeMort, and GrimAge2Mort). The researchers also examined pace of aging using DunedinPoAm and measured DNA methylation telomere length.

Overall, participants with wheezing in the past year had accelerated epigenetic aging compared to those without wheezing. Individuals with wheezing were 3.1 years older based on GrimAge2Mort and 2.7 years older based on GrimAgeMort. Those with wheezing also had a shorter average telomere length (-77.6 bp) and a 4.2% greater pace of aging than nonwheezers.

The subset of individuals with COPD had a 2.0-year increased GrimAgeMort, 2.0-year increased GrimAge2Mort, and 3.4% higher rate of aging than those without COPD. Among patients with COPD, those with onset of disease before 40 years of age showed more epigenetic aging than those with late onset COPD.

Among the patients who ever had asthma, the researchers found a small epigenetic age acceleration of 0.7 years on GrimAgeMort and 0.8 years on GrimAge2Mort. A small but not significant acceleration in aging also appeared among individuals with chronic bronchitis.

However, the subtype of COPD patients with emphysema also showed significant accelerated aging, with a mean age 4.4 years and 4.2 years older based on GrimAge2Mort and GrimAgeMort, respectively.

“Notably, although only a few associations reported in this study were sensitive to adjustments for smoking and SES [socioeconomic status], most of the reported associations of epigenetic ageing with wheezing and COPD (including disease subtype and age of onset) remained robust in sensitivity analyses, supporting no confounding effect of smoking, BMI, SES, and blood cell counts,” the researchers wrote.

When the results were stratified by sex, a significant association appeared in males for accelerated pace of aging and COPD and for reduction in telomere length associated with wheezing. These differences could be related to biological, social, and environmental factors, and more research is needed to tease out the underlying sex-specific ageing mechanisms in respiratory diseases, the researchers noted.

The study findings were limited by several factors including the cross-sectional design and the use of self-reports, they added. However, the results support the potential of epigenetic aging measures as biomarkers for respiratory diseases across the lifespan and validate previous studies associating COPD and asthma with epigenetic aging, they concluded.

Clinical Utility Still to Come

Recent studies have shown the association between faster epigenetic aging and poorer respiratory health, said Arianne K. Baldomero, MD, pulmonologist and assistant professor of medicine at the University of Minnesota, Minneapolis, in an interview.

“Exploring how aging processes contribute to chronic respiratory diseases could reveal novel treatment approaches and support the development of therapies,” she said.

The findings of the current study align with previous research showing an association between faster epigenetic aging and poorer respiratory health outcomes, Baldomero noted.

However, “while larger increases in epigenetic age suggest higher risk, we still need more studies to determine what changes are clinically meaningful and how these findings should inform clinical practice and public health,” Baldomero told Medscape Medical News.

“The study’s cross-sectional design limits its ability to determine whether accelerated epigenetic aging causes respiratory disease or vice versa, and reliance on self-reported data may introduce bias in disease classification,” said Baldomero. Clinically, the meaning of a 1- to 4-year increase in epigenetic age acceleration for individual patients remains unclear, she added. “While larger increases do suggest higher risk and faster biological aging, more research is needed to define what changes in epigenetic age are truly clinically relevant,” she said.

The study was supported by supported by the National Institute of Environmental Health Sciences and the National Institute on Minority Health and Health Disparities of the National Institutes of Health. Perez-Garcia disclosed receiving funding from the Spanish Ministry of Universities, unrelated to the current study.

Baldomero had no financial conflicts to disclose.