Aging & systems immunology: Uncovering biomarkers of healthy aging

Why do some people stay healthy and resilient as they age while others become more vulnerable to disease?

Those healthy individuals tend to have strong immune responses to vaccinations and other medical treatments. They get sick less frequently than other older adults. Ucar aims to shed light on the underlying biology.

“Who has a strong immune system and who doesn’t and what discriminates those two populations? We want to understand the biological drivers of that heterogeneity,” Ucar said.

To get to the root of that, her team’s research focuses in part on how older individuals respond to different formulations of seasonal flu and bacterial pneumococcal vaccines.

Precision aging in practice

“Our hypothesis is that individuals with healthier immune systems respond better to vaccines, while those with unhealthy immune systems tend to respond poorly,” said Sathyabaarathi Ravichandran, a postdoctoral associate in Ucar’s lab. “We use vaccines as an intervention model to understand the features of healthy immune aging.”

In the simplest terms, vaccines teach your immune system how to recognize and fight an illness before you’re exposed to it. While many adults mount strong responses to seasonal flu vaccines, about one third of people have either a weak immune response or none at all. That number increases with age.

Vaccination is a powerful model for studying healthy immune aging. Because vaccines provide a controlled immune challenge, they offer a window into the strength of immune responses.

Ucar’s team hopes that by identifying the baseline immune features (biomarkers) present before vaccination, they can predict whether someone will respond well to a vaccine — or whether they might respond better to one formulation over another. These insights support the emerging field of precision vaccinology, which aims to tailor vaccine strategies to individual immune profiles rather than relying on a one‑size-fits-all approach.

“If we have biomarkers of healthy aging, you can identify individuals who are at high risk,” Ucar said. “That’s important for personalized treatments, but it also helps us have a better understanding of what’s different in healthy and unhealthy aging.” That understanding, she said, could give scientists a roadmap of pathways, genes and cell types that could eventually let them “improve the immunity of people who are not healthily aging.”

The long-term goal is to identify immune signatures associated with healthy aging versus immune decline — knowledge that could inform not only vaccination strategies but broader approaches to disease prevention in older adults.  

Learn more