Aging and inflammation may not go hand in hand, study suggests

A new study helps reveal why some vaccines, including those for COVID-19 and influenza, are less effective in older adults than they are in younger people — and it may fundamentally shift our understanding of aging.

Traditionally, scientists have attributed the reduced vaccine response seen in older adults to a decline in the immune system with age. Many have pointed to persistent, low-grade immune activation — a process dubbed "inflammaging" — as one driver of this decline.

But a new study that compared the immune systems of older and younger adults found no consistent increases in biological markers of inflammation with age. Instead, aging appears to reprogram T cells — important immune cells that help train a type of white blood cell, called B cells, to produce antibodies in response to viruses and vaccines.

The findings, published Oct. 29 in the journal Nature, suggest that inflammation may not be as fundamental to the aging process as scientists previously thought.

"We think inflammation is driven by something independent from just the age of a person," Claire Gustafson, an assistant investigator at the Allen Institute for Immunology and one of the lead authors of the study, said in a statement.

Alan Cohen, an associate professor of environmental health sciences at Columbia University who studies aging and inflammation, said the new findings support a more nuanced view of "inflammaging."

The idea that inflammation increases with age "may be true on average in industrialized populations," said Cohen, who was not involved in the work. "But it won't be true for everyone, and it won't be true in every population," he told Live Science.

Cohen cautioned that the participants in the new study were drawn entirely from Palo Alto, California, and Seattle — both highly industrialized areas. Having found significant differences in inflammation between adult populations from Italy, Singapore, Bolivia and Malaysia, he said such findings may not hold up across different environments.

"I certainly wouldn't take this as, 'Oh look, now they've shown definitively there's no change in inflammation with age,'" Cohen said. "I would take it more as, here's an example of a population that doesn't appear to be doing the same things that we have typically expected."

T cell changes are not driven by inflammation

In the interest of improving older adults' responses to vaccines, Gustafson and her colleagues looked at how T cells change with age.

First, they compared younger adults (ages 25 to 35) with an older group (ages 55 to 65, or people at what the researchers call the "cusp of aging.") For two years, the researchers followed 96 healthy volunteers in these age groups, collecting blood samples from each participant eight to 10 times and monitoring their immune systems before and after their annual flu vaccinations. Then, they expanded their research to include a second group of 234 adults ranging in age from 40 to over 90.

To examine the immune system across these groups, the team used single-cell RNA sequencing, which enabled them to look at a type of genetic material called RNA inside each immune cell. RNA reflects which proteins a cell is making at a given moment. The team also used high-dimensional plasma proteomics, which maps the proteins circulating in blood, and spectral flow cytometry,which identifies and counts immune cells by their molecular "fingerprints."

The researchers spotted distinct differences in memory T cells — immune cells that "remember" past infections and help the body respond faster the next time a pathogen shows up.

In older adults, increasing numbers of memory T cells shift into a state that changes how they respond to threats — by changing their interaction with B cells. When memory T cells are not working as they should, B cells become less effective at producing antibodies in response to infections or vaccines, the study found. Meanwhile, the memory T cells of young adults were adept at responding quickly and ramping up the expected antibody response.

These immune changes seem to happen independently of inflammation and of infections with latent viruses, which stay in the body after the initial infection and may go dormant, not causing any overt symptoms. Infections with these viruses, such as cytomegalovirus (CMV), are often blamed for weakening the immune system with age. However, the study found that people under 65 who had experienced a CMV infection at some point in their life did not have signs of faster immune aging or increased levels of inflammatory proteins.

Cohen remains cautious about the study authors' conclusions, noting that the most significant changes in the immune system tend to occur after age 65. "If you don't see a change in inflammation between 25 to 35 versus 55 to 65, is that really because inflammation isn't changing with age, or just because they didn't get old enough to see something?" he questioned.

The researchers said these findings could eventually help scientists design vaccines that compensate for age-related immune changes, thus better protecting older adults. They also think the results could be useful for designing treatments that restore immune function in old age.