Longevity Briefs: Vaccination Against Shingles Is Associated With Slower Biological Ageing

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Previous studies have suggested that there is an association between certain vaccinations and reduced risk of age-related disease. While it is sometimes possible to use clever tricks to demonstrate that this association is likely to be causation, many studies face the problem that people who get vaccinated tend to be better educated, wealthier, and more likely to engage in a healthy lifestyle than unvaccinated people. This makes it hard to prove that vaccines caused a reduction in disease risk, even if there are plausible biological explanations.

Proposed explanations for these extra benefits of vaccination unsurprisingly centre around the immune system. For example, studies have suggested that repeated reactivation of dormant viruses like varicella‑zoster virus (which causes shingles) might accelerate the progression of age-related diseases and ageing in general by causing inflammation. In this study, researchers investigate whether there is an association between receiving the shingles vaccine, inflammation and biological age. As opposed to chronological age (the number of years since you were born), biological age is an estimate of how biologically old your cells are. This is determined by how certain markers (usually epigenetic changes) compare with the population average for your age.

The discovery:

Researchers used data from the U.S. Health and Retirement Study including 3,884 adults aged 70+ in 2016 and for whom the vaccination status for shingles was known. They analysed data from blood tests (such as immune cell counts), physical measures like blood pressure, and biological ageing estimates using multiple epigenetic clocks. These are algorithms that use DNA methlyation – the addition of molecular ‘tags’ to the DNA molecule that alter how genes are read without changing the genetic code itself – in order to estimate whether an individual is ageing at a slower or more rapid pace than expected. They also measured transcriptomic ageing, which is a measure of whether patterns of gene expression resemble those typical of a younger or older individual. Using all this data, participants were scored in 7 domains: inflammation; innate and adaptive immunity; cardiovascular hemodynamics; neurodegeneration; epigenetic and transcriptomic ageing.

After adjusting for confounding factors like socioeconomic status and age, researchers found that vaccinated individuals had significantly lower inflammation scores, slower epigenetic ageing and less transcriptomic ageing compared to unvaccinated people. However, vaccinated people also appeared to have more aged adaptive immune systems (the component of the immune system that targets specific pathogens and ‘remembers’ them in case of subsequent infection). Researchers found that these effects were time-sensitive, with the strongest epigenetic and transcriptomic benefits occurring about three years after vaccination, with some benefits persisting beyond that. Some of the innate immunity and inflammation changes were only statistically significant four or more years post‑vaccination. This doesn’t necessarily mean a causal link (biological ageing naturally appears to speed up and slow down at certain points throughout life and vaccination age is not random), but it does make the results more convincing.

The implications:

These results provide further hints that vaccines could have benefits beyond preventing infectious disease, potentially dampening chronic inflammation and shifting molecular ageing markers in ways associated with better long‑term health. The finding that adaptive immunity score was higher (worse) should be interpenetrated with some caution, as due to the way this score was calculated, it may not actually represent worse immune function (in brief, immune memory is increasingly ‘overloaded’ with age, so a useful expansion of immune memory in response to vaccination can make it look like the adaptive immune system is ageing faster).

We should also be aware that the link with biological age is an association with another association. Even though efforts were made to control for confounding factors, this study cannot prove that the shingles vaccine causes slower biological or transcriptomic ageing measurements, and these measurements are themselves only estimates of true biological ageing that happen to correlate with health.

We will need to wait some time for definitive proof that the shingles vaccine slows biological ageing, but previous studies have already produced some convincing evidence for health benefits beyond protection against shingles. This study found that people in Wales who were eligible to receive the shingles vaccine (due to being born after the cutoff date) were around 20% less likely to get dementia compared to those who were ineligible, after controlling for age. The fact that eligibility was the variable here makes it likely that this protection against dementia was caused by the vaccine, as there’s no reason people born a few days after the cutoff date should be more health-conscious than those born a few days earlier, yet they were still significantly less likely to get dementia.