A blood-based aging clock suggests that herpes zoster vaccination may moderately slow the molecular aging process in later life without obvious effects on neurodegeneration or cardiovascular health.
3D illustration of varicella zoster virus or varicella zoster virus (VZV). Image credit: Tatiana Shepeleva / Shutterstock. Association between shingles vaccination and delayed biological aging: evidence from a US population-based cohort study
In a recent study published in Journals of Gerontology, Series A: Biological Sciences and Medicineresearchers analyzed data from a nationally representative cohort. us To determine whether the shingles vaccine is associated with delayed biological aging in adults aged 70 years and older. Study results revealed that vaccinated people had a significantly better profile of systemic disease. inflammationepigenetic aging, and transcriptomic aging were more pronounced than in unvaccinated peers, and although the effect size was statistically robust, it was modest in magnitude.
Of note, vaccination was associated with a reduction in the composite biological aging score, suggesting a systemic benefit, although no significant associations were observed for specific blood biomarkers of neurodegeneration or cardiovascular hemodynamics. These findings add to the body of evidence demonstrating the health benefits of vaccination beyond immunology and highlight the potential for herpes zoster vaccination to serve as a putative molecular-level “geronprotective” intervention, even in the absence of evidence of direct effects on clinical aging outcomes.
Vaccines and the biology of aging
Since their discovery in 1796, vaccines have been primarily viewed as specific tools designed to train the immune system against a single pathogen, such as: COVID-19 (new coronavirus infection) vaccine against SARS-CoV-2 Vaccines against viruses and shingles varicella zosterthe virus that causes chicken pox and shingles.
However, recent epidemiological studies are increasingly pointing to ‘off-target’ effects of vaccination, suggesting that certain vaccines may reduce long-term risks such as dementia and cardiovascular disease. These trials have spurred research aimed at investigating the hypothesis that vaccines may affect fundamental biological processes of aging that are reflected in molecular and cellular biomarkers rather than obvious disease endpoints.
One such process is “inflammation.” This is a chronic, low-grade inflammation that naturally increases with age and contributes to many age-related diseases, including cardiovascular disease.CVD) and cancer. Through past research, varicella zoster It remains latent in the body after childhood chickenpox infection and can reactivate later in life, promoting systemic inflammation.
As a result, the authors of this study hypothesized that by suppressing reactivation of this virus, the shingles vaccine could reduce the body’s overall inflammatory burden and slow the molecular clock exacerbated by inflammation, thereby potentially slowing biological aging as measured by validated aging biomarkers.
Study design and population
In this study, research on health and retirement (HRS), a large-scale, long-term project to track older adults in the United States (us). Notably, unlike previous studies on this topic that relied primarily on medical records, the current study used direct analysis of blood samples to quantify biological aging.
The study sample cohort consisted of 3,884 participants aged 70 years and older, with sociodemographic data and blood samples obtained from the 2016 Venous Blood Study.
Measuring biological aging
In this study, we measured biological aging by examining seven different biological domains: inflammation, innate immunity, adaptive immunity, cardiovascular hemodynamics (blood pressure and pulse), neurodegeneration, epigenetic aging, and transcriptomic aging, and used a composite biological aging score derived from all domains except adaptive immunity.
As a result, participants’ blood samples were analyzed for three main things. biomarker Category.
Epigenetic clocks measure chemical changes, DNA specifically correlated with mortality and physiological decline (methylation) using the GrimAge and DunedinPACE clocks.
Transcriptome age (Trama) represents high-resolution measurements of gene expression profiles associated with immune function and somatic stress responses.
Inflammatory markers include C-reactive protein (CRP) and interleukin 6 (IL-6), which has been previously established as a marker of systemic inflammation.
Inverse probability of treatment weighting (IPTW) was used to adjust for sociodemographic factors such as education, income, smoking history, and chronic disease to better isolate associations with vaccination status.
Association between vaccination and aging biomarkers
Analysis of studies revealed that shingles vaccination was significantly associated with rejuvenation of biological profile across several areas. The most robust result emerged from epigenetic clock analysis, where vaccinated individuals showed significantly slower epigenetic (b = -0.17, p = 0.0001) and transcriptomic (b = -0.19, p < 0.0001) aging compared to unvaccinated individuals, indicating a relative difference in the pace of aging rather than a reversal of the aging process.
Analysis of inflammatory markers revealed that vaccination was further associated with lower inflammation scores (b = −0.14, p = 0.0027), supporting the hypothesis that the vaccine may reduce the chronic inflammatory load associated with latent viral activity.
When does the effect of vaccination appear?
When researchers looked at the timing of vaccination, they observed a clear pattern. improvement DNA Methylation (epigenetic aging) and gene expression (transcriptomic aging) were most pronounced among participants vaccinated within the past three years. In contrast, the association with inflammation and lower innate immunity scores emerged later and became significant only among those vaccinated more than four years ago.
Unexpectedly, the authors note that shingles vaccination was associated with a higher adaptive immunity score, which in the framework of this score indicates lower adaptive immune function, a finding that requires further investigation.
Invalid findings regarding neurodegeneration and cardiovascular measurements
Despite previous reports linking the shingles vaccine with reduced risk of dementia, the current analysis did not reveal a significant association between vaccination and specific blood biomarkers of neurodegeneration, such as neurofilament light chain.NfL), glial fibrillary acidic protein (GFAP), phosphorylated tau, or amyloid beta ratio. Similarly, no significant associations were observed for cardiovascular hemodynamic measurements, highlighting the disconnect between molecular aging markers and established clinical risk indicators.
interpretation and implications
This study provides biological evidence that herpes zoster vaccination is associated with a delay in aging-related changes at the molecular level. By potentially suppressing latent viral reactivation, this vaccine appears to reduce systemic inflammation and slow measures of epigenetic and transcriptomic aging without demonstrating direct effects on neurodegenerative or cardiovascular biomarkers.
Notably, participants in this study were likely vaccinated with Zostavax, an older attenuated live attenuated shingles vaccine. A new recombinant vaccine, Shingrix, is hypothesized to be more immunogenic and may offer even greater age-related benefits, but this is still speculative and requires direct investigation.
Because the biomarker data are cross-sectional and derived from observational analyses, the authors caution that residual confounding cannot be completely ruled out and that long-term, experimental studies are needed to confirm causality and determine whether these molecular associations translate into meaningful clinical benefit.