Shingles Vaccine Linked to Slower Biological Aging in Landmark USC Study

A groundbreaking study from the University of Southern California Leonard Davis School of Gerontology has revealed that the shingles vaccine not only prevents the painful rash associated with herpes zoster but may also slow biological aging processes in older adults. Published in the Journals of Gerontology: Series A, the research analyzed data from over 3,800 Americans aged 70 and older, finding significant associations between vaccination and reduced inflammation, slower epigenetic and transcriptomic aging, and an overall lower composite biological aging score.

Lead author Jung Ki Kim, Research Associate Professor of Gerontology at USC, explained, "This study adds to emerging evidence that vaccines could play a role in promoting healthy aging by modulating biological systems beyond infection prevention." The findings suggest that by curbing chronic low-grade inflammation—known as inflammaging—the vaccine could help mitigate risks for age-related diseases like heart disease, frailty, and cognitive decline.

Understanding Shingles: The Varicella-Zoster Virus and Reactivation Risk

Shingles, or herpes zoster, results from reactivation of the varicella-zoster virus (VZV), the same pathogen responsible for chickenpox. After initial infection, VZV remains dormant in sensory nerve ganglia. In older adults or those with weakened immunity, it can reactivate, causing a painful rash, postherpetic neuralgia, and potential complications like stroke or dementia. The Centers for Disease Control and Prevention (CDC) estimates 1 million U.S. cases annually, primarily in adults over 50.

Two vaccines are available: Zostavax (live-attenuated, used pre-2017) and Shingrix (recombinant zoster vaccine, RZV, preferred since 2017). Shingrix boasts 90-97% efficacy against shingles in adults 50+, far surpassing Zostavax's 50-70%, with sustained protection over 7+ years. Despite CDC recommendations for two doses in adults 50+, uptake hovers around 30% nationally, highlighting a public health gap.

Decoding the USC Study: Methods and Data Sources

Leveraging the nationally representative U.S. Health and Retirement Study (HRS) from 2016, researchers examined blood samples, flow cytometry, and physical assessments from 3,884 participants aged 70+. Vaccination status (self-reported from 2008-2018, primarily Zostavax) was the key exposure. Seven biological aging domains were assessed via principal component analysis (PCA) on standardized biomarkers:

• Inflammation (IL-6, CRP, etc.)
• Innate immunity (NK cells, neutrophils)
• Adaptive immunity (T/B cell subsets)
• Cardiovascular hemodynamics (blood pressure, pulse)
• Neurodegeneration (GFAP, NfL, pTau181, Aβ42/40)
• Epigenetic aging (PhenoAge, GrimAge, DunedinPACE acceleration)
• Transcriptomic aging (TraMA acceleration)

A composite score combined six domains. Weighted linear regressions adjusted for age, sex, race/ethnicity, education, income, smoking, and multimorbidity, using inverse probability treatment weighting to counter healthy-user bias. Timing analyses stratified by years since vaccination (<3 vs. ≥4).

Key Findings: Quantified Slowing of Biological Aging Markers

Vaccinated individuals exhibited markedly slower aging:

No significant links for innate immunity, cardiovascular, or neurodegeneration. Effects were strongest within 3 years post-vaccination but persisted ≥4 years, particularly for molecular clocks.

Senior author Eileen Crimmins, USC University Professor and AARP Chair in Gerontology, noted, "These findings indicate that shingles vaccination influences key domains linked to the aging process."

Inflammaging: How VZV Reactivation Fuels Age-Related Decline

Inflammaging—chronic, sterile low-grade inflammation—drives many geriatric pathologies. Latent VZV contributes by periodic subclinical reactivations, prompting immune responses that elevate cytokines like IL-6 and CRP. Vaccination may preempt this, remodeling immune cells for reduced systemic inflammation. The USC study confirms lower inflammation scores in vaccinated groups, aligning with hypotheses that preventing reactivation curbs inflammaging.

This mechanism echoes prior research linking herpesviruses to accelerated aging via epigenetic dysregulation.

Epigenetic and Transcriptomic Clocks: Measuring Molecular Aging

Biological aging clocks quantify divergence from chronological age. Epigenetic clocks (e.g., Horvath, GrimAge) track DNA methylation patterns at CpG sites, reflecting gene regulation changes. Transcriptomic clocks analyze RNA expression shifts mirroring cellular senescence.

The study used PhenoAge/GrimAge acceleration and DunedinPACE for epigenetics, TraMA for transcriptomics. Vaccinated participants showed 17-19% slower acceleration, indicating vaccines might epigenetically "rejuvenate" molecular profiles.

Sustained Benefits and Unexpected Adaptive Immunity Findings

Timing mattered: Recent vaccination (<3 years) yielded strongest epigenetic/transcriptomic benefits (b=-0.21/-0.22), persisting long-term. Delayed inflammation reductions appeared ≥4 years post-vax. Higher adaptive immunity scores (poorer function) may reflect vaccine-induced T-cell shifts mimicking immunosenescence, warranting follow-up.

These domain-specific, time-varying effects underscore vaccines' nuanced impact on aging biology.

Connections to Dementia Prevention: Building Evidence

Prior studies report 17-51% dementia risk reductions post-shingles vaccination, via reduced neuroinflammation from VZV reactivation. The USC findings extend this, linking slower neurodegeneration-adjacent markers. No direct neurodegeneration association here may stem from cross-sectional limits or biomarker sensitivity.

Emerging data positions adult vaccines as healthy aging tools, alongside flu shots showing similar trends.

Study Limitations and the Path Forward for Aging Research

Cross-sectional design precludes causality; longitudinal trials needed. Pre-2017 data favored Zostavax over superior Shingrix. Unmeasured confounders possible despite adjustments. USC researchers call for replication, mechanism studies (e.g., VZV-specific immunity), and Shingrix-focused trials.

In gerontology, such work fuels demand for expertise in biodemography and molecular aging.Explore faculty positions in gerontology

Implications for Public Health and Higher Education

With 1-in-3 Americans 50+ facing shingles lifetime risk, boosting uptake could enhance population healthspan. USC's findings spotlight gerontology's role in translational research, attracting funding and talent to U.S. universities.

Programs like HRS exemplify interdisciplinary data driving discoveries, informing policy.USC Leonard Davis Gerontology

Careers in Gerontology: Opportunities in Aging Biology Research

The surge in aging research opens doors: faculty roles at USC-like institutions, postdocs in epigenetics, policy analysts. Demand grows for PhDs in gerontology/public health, with salaries $100k+ for professors. Craft your academic CV for these roles.

Photo by CDC on Unsplash

• Research Associate Professor (e.g., Jung Ki Kim's path)
• Tenure-track in biodemography
• NIH-funded aging labs

Looking Ahead: Vaccines as Pillars of Healthy Aging

USC's study reframes shingles vaccination as a proactive anti-aging strategy, urging higher uptake. For researchers, it heralds vaccines' multi-system benefits. Explore Rate My Professor for gerontology insights, higher ed jobs in aging, career advice, and university positions. Stay informed on breakthroughs shaping longevity science.