Shingles vaccination was linked to slower epigenetic and transcriptomic aging measures in adults aged 70 years or older, with associations observed beyond three years after vaccination, according to a recent study.
The shingles vaccination has been associated with differences across several biomarker-defined aging domains, prompting researchers to examine whether immunization may relate to biological aging processes beyond infection prevention. Vaccinated adults were associated with lower inflammation scores and more favorable overall biological aging profiles compared with unvaccinated peers, while no statistically significant associations were observed for cardiovascular hemodynamics or neurodegeneration biomarkers.
These findings were derived from an analysis of 3,884 adults aged 70 years or older who participated in the US Health and Retirement Study and completed biomarker assessments in 2016. Researchers analyzed shingles vaccination history collected before 2017 and examined its associations with biomarker-based measures of biological aging derived from blood, molecular, and physical assessments. Vaccination history was collected between 2008 and 2018, and biological measures were obtained from venous blood assays, flow cytometry, DNA methylation analyses, transcriptomic profiling, and standardized physical assessments.
Seven biological aging domains were defined a priori: inflammation, innate immunity, adaptive immunity, cardiovascular hemodynamics, neurodegeneration, epigenetic aging, and transcriptomic aging. Within each domain, principal components analysis was used to generate standardized factor scores, with higher values indicating worse aging profiles. A composite biological aging score was constructed by integrating six domains, excluding adaptive immunity because its associations differed in direction and could obscure broader aging signals.
To address potential healthy-user bias, the analysis incorporated stabilized inverse probability of treatment weights based on demographic characteristics, socioeconomic indicators, smoking history, chronic conditions, and cumulative influenza vaccination. Weighted linear regression models were adjusted for age, sex, race and ethnicity, education, income, smoking pack years, and multimorbidity.
After adjustment, shingles vaccination was associated with lower inflammation scores, slower epigenetic aging, slower transcriptomic aging, and a lower composite biological aging score. "Our study adds to a growing body of work suggesting that vaccines may play a role in healthy aging strategies," noted lead study author Jung Ki Kim, PhD, of the Davis School of Gerontology, University of Southern California, and colleagues.
In contrast, shingles vaccination was associated with higher adaptive immunity scores, reflecting poorer adaptive immune profiles within the study's scoring framework. Timing analyses indicated that associations with epigenetic, transcriptomic, and composite aging were most pronounced within 3 years of vaccination, with evidence of persistence beyond that period. Improvements in inflammation and innate immunity were observed among adults vaccinated more than 3 years earlier.
There were several limitations in the study. Biomarker data were cross-sectional, limiting causal inference and assessment of changes in biological aging over time. Vaccination status and timing were self-reported, introducing the potential for recall error and misclassification. To adjust for healthy-user bias in vaccine uptake, the researchers constructed stabilized inverse probability of treatment weights and fitted adjusted weighted regression models. The analysis was limited to the earlier live-attenuated shingles vaccine, and findings may not generalize to the newer recombinant formulation. Additionally, certain aging domains, including neurodegeneration, may require longer follow-up to detect meaningful associations.
The study was supported by the National Institute on Aging at the National Institutes of Health, and the researchers reported no conflicts of interest.
