Stress Accelerates Aging of the Immune System

Traumatic life events and everyday stress impair the body's immune cell mix prematurely.

It is commonly acknowledged that as people grow older, their immune systems deteriorate. The continuing COVID-19 pandemic, for example, has a substantially greater fatality rate among the elderly than among the young.

Immunosenescence is a term used to describe the slow degradation of the immune system caused by natural aging. However, you may know people who are quite ancient but in excellent health, or vice way, someone who is youthful but susceptible to diseases. What could explain the disparities in immune system strength among people of the same age?

According to a new University of Southern California (USC) study, stress — in the form of traumatic events, job strain, everyday stressors, and discrimination — accelerates immune system aging, potentially increasing a person's risk of cancer, cardiovascular disease, and illness from infections like COVID-19.

The study, which was published in the Proceedings of the National Academy of Sciences yesterday (June 13, 2022), could help explain discrepancies in age-related health, including the pandemic's disproportionate toll, and suggest potential intervention locations.

“As the world’s population of older adults increases, understanding disparities in age-related health is essential. Age-related changes in the immune system play a critical role in declining health,” said main study author Eric Klopack, a postdoctoral scholar at the University of Southern California's Leonard Davis School of Medicine. “This study helps clarify mechanisms involved in accelerated immune aging.”

As people age, the immune system naturally begins a dramatic downgrade, a condition called immunosenescence. With advanced age, a person’s immune profile weakens, and includes too many worn-out white blood cells circulating and too few fresh, “naive” white blood cells ready to take on new invaders.

Potential problems relating to stress and the immune system

Immune aging is linked to cancer, cardiovascular disease, increased pneumonia risk, vaccine efficacy, and organ system aging, among other things.

But what accounts for such stark health disparities among adults of the same age? Researchers at USC wanted to explore if they could find a link between lifelong stress exposure — a known driver to poor health — and immune system strength decline.

They combed through massive data sets from the University of Michigan's Health and Retirement Study, a national longitudinal study of older Americans' economic, health, marital, and familial status, as well as governmental and private support systems.

The researchers assessed answers from a nationwide sample of 5,744 persons over the age of 50 to determine their exposure to various forms of social stress. They completed a survey to measure their social stress experiences, which included stressful life events, chronic stress, everyday discrimination, and lifetime discrimination.

Flow cytometry, a lab method that counts and classifies blood cells as they pass one by one in a narrow stream in front of a laser, was used to assess the participants' blood samples.

People with greater stress levels had immunological profiles that seemed to be older, with fewer percentages of new disease fighters and larger percentages of worn-out white blood cells, as predicted. Even after adjusting for education, smoking, drinking, BMI, and race or ethnicity, the link between stressful life events and less ready-to-respond, or naïve, T cells remained robust.

Some sources of stress may be uncontrollable, but the researchers believe there may be a solution.

T-cells, an important component of immunity, develop in the thymus gland, which is located immediately in front of and above the heart. The tissue in the thymus diminishes with age and is replaced by fatty tissue, leading in a decrease in immune cell production. According to previous studies, lifestyle variables such as poor food and lack of exercise, both of which are linked to social stress, speed up this process.

“In this study, after statistically controlling for poor diet and low exercise, the connection between stress and accelerated immune aging wasn’t as strong,” Klopack added. “What this means is people who experience more stress tend to have poorer diet and exercise habits, partly explaining why they have more accelerated immune aging.” 

Stress and the immune system: Impact of diet and exercise 

Improving a person's diet and exercise habits as they get older may help counteract the immunological aging that comes with stress.

CMV (cytomegalovirus) may also be a target for intervention. CMV is a widespread, generally asymptomatic virus that has been linked to accelerated immune aging in humans. CMV, like shingles or cold sores, is mostly latent but can flare up at any time, especially when a person is under a lot of stress.

Statistically correcting for CMV positive in this study similarly attenuated the link between stress and immunological aging. According to the researchers, widespread CMV immunization might be a reasonably simple and potentially significant strategy for reducing the immunological aging consequences of stress.