Shingles Vaccination Is Associated With Slower Aging

An analysis of over 3800 older adults found that shingles vaccination is associated with lower inflammation scores, slower epigenetic and transcriptomic aging, and a lower composite biological aging score [1].

Beneficial side effects

Vaccines are developed to prevent specific diseases, such as polio, measles, hepatitis, and many others. However, recent data suggest that some adult vaccines may have unintended yet beneficial effects. For example, vaccines against herpes zoster (shingles), influenza, and pneumococcus were linked to reductions in the risk of age-related diseases, such as dementia and cardiovascular diseases [2, 3, 4].

This initial data sparked the interest of other researchers, including the authors of this study, to investigate this topic further. The study’s authors specifically focused on the shingles vaccine, which protects against a viral infection caused by the reactivation of the chickenpox virus.

The researchers used data from the nationally representative U.S. Health and Retirement Study of 3,884 adults 70 years old and up in order to address the impact of shingles vaccination (specifically an earlier version called Zostavax) on seven biological aging domains: inflammation, innate and adaptive immunity, blood flow forces (cardiovascular hemodynamics), neurodegeneration, and epigenetic and transcriptomic aging that affect gene expression.

Vaccinating against aging

Analysis of the data, after adjusting for demographic, socioeconomic, and health-related factors, showed significant associations between shingles vaccination and three of the seven biological aging domains: lower inflammation scores and slower epigenetic and transcriptomic aging.

The lower observed inflammation scores suggest reduced chronic inflammation. In the elderly, chronic inflammation, often referred to as “inflammaging,” contributes to multiple age-related conditions such as heart disease, frailty, and cognitive decline.

“By helping to reduce this background inflammation — possibly by preventing reactivation of the virus that causes shingles, the vaccine may play a role in supporting healthier aging,” said Research Associate Professor of Gerontology Jung Ki Kim, the study’s first author. “While the exact biological mechanisms remain to be understood, the potential for vaccination to reduce inflammation makes it a promising addition to broader strategies aimed at promoting resilience and slowing age-related decline.”

Beyond inflammation, gene expression and epigenetic profiles were also positively affected by vaccination. Epigenetic age acceleration was assessed using DNA methylation-based aging clocks, which are used to measure biological age, assess the rate of aging, and evaluate the risk of various health outcomes, including mortality, frailty, and chronic diseases.

Since aging affects multiple systems in the body, the researchers created a composite biological aging score by integrating information across six domains into a single measurement; the adaptive immunity domain was excluded due to unexpected results, which could have obscured meaningful effects. Shingles vaccination was associated with a lower composite biological aging score, suggesting that this vaccine affects multiple bodily systems.

Overall, “This study adds to emerging evidence that vaccines could play a role in promoting healthy aging by modulating biological systems beyond infection prevention,” said Kim.

Unexpected results

However, not all measured components showed improvements. The authors reported that, contrary to their expectations, vaccination was associated with higher adaptive immunity scores, reflecting poorer adaptive immune function. This was difficult to interpret, and the lack of additional biomarkers prevented the researchers from testing some of their hypothesized explanations. They also suggest the possibility that vaccination might simultaneously have protective and potentially adverse effects.

The lack of effect of the shingles vaccine on neurodegeneration biomarkers was also rather surprising, given previous links between shingles vaccination and reduced dementia incidence. However, the researchers believe that the biomarkers they used, which reflect long-term damage, might not capture the direct effect of the vaccination on dementia; instead, the effect might be indirect, such as through reduced inflammation, which is more dynamic.

The long-term effects

While vaccination is a one-time intervention, it may have long-term effects. An analysis of the impact of vaccination over time shows that reduced epigenetic and transcriptomic aging, as well as composite biological aging scores, are present in peopple who had recently received the vaccine and in people who had received it 4 or more years earlier. While the persistence of epigenetic and gene expression effects suggests a potential for long-term effects, those effects may diminish over time, since both DNA methylation and gene expression changes were greater in people vaccinated more recently. However, this needs further investigation.

Regarding different domains of aging, the initial three years post-vaccination were not associated with changes in other measured domains. However, three or more years after vaccination, the researchers observed an association with lower inflammation and innate immunity scores, but poorer adaptive immune function. The researchers point out that these observations might suggest that the impact of the shingles vaccine on the immune system and inflammatory responses unfolds slowly over time, thereby impacting the immune system in the long term.

Beyond preventing illnesses

“These findings indicate that shingles vaccination influences key domains linked to the aging process,” said study coauthor Eileen Crimmins, USC University Professor and AARP Professor of Gerontology. “While further research is needed to replicate and extend these findings, especially using longitudinal and experimental designs, our study adds to a growing body of work suggesting that vaccines may play a role in healthy aging strategies beyond solely preventing acute illness.”

This is promising, especially since this intervention was effective even in the older population (people studied here were over 60 when they received the vaccine), who are usually less responsive to interventions. However, it remains to be determined whether stronger effects would be observed if a younger population (in their 50s) were to receive the vaccine or if participants received a newer formulation of the shingles vaccine (Shingrix).

This study also raises a very important question of whether interventions not designed to target aging have geroprotective effects. If so, some of them, such as the shingles vaccine, might be low-cost interventions with the potential to positively influence biological aging and extend healthspan.

Literature

[1] Kim, J. K., & Crimmins, E. M. (2026). Association between shingles vaccination and slower biological aging: Evidence from a U.S. population-based cohort study. The journals of gerontology. Series A, Biological sciences and medical sciences, glag008. Advance online publication.

[2] Shah, S., Dahal, K., Thapa, S., Subedi, P., Paudel, B. S., Chand, S., Salem, A., Lammle, M., Sah, R., & Krsak, M. (2024). Herpes zoster vaccination and the risk of dementia: A systematic review and meta-analysis. Brain and behavior, 14(2), e3415.

[3] Bukhbinder, A. S., Ling, Y., Hasan, O., Jiang, X., Kim, Y., Phelps, K. N., Schmandt, R. E., Amran, A., Coburn, R., Ramesh, S., Xiao, Q., & Schulz, P. E. (2022). Risk of Alzheimer’s Disease Following Influenza Vaccination: A Claims-Based Cohort Study Using Propensity Score Matching. Journal of Alzheimer’s disease : JAD, 88(3), 1061–1074.

[4] Addario, A., Célarier, T., Bongue, B., Barth, N., Gavazzi, G., & Botelho-Nevers, E. (2023). Impact of influenza, herpes zoster, and pneumococcal vaccinations on the incidence of cardiovascular events in subjects aged over 65 years: a systematic review. GeroScience, 45(6), 3419–3447.