Research shows that immune resilience counters important drivers of illness, mortality

What if we investigated the factors that maintain health, namely the concept of respect (derived from the salus in Roman mythology), rather than focusing solely on the driver of the disease (etiology)?

The idea of ​​respect through immune resilience refers to the mechanism by which the body counters sick drivers, and can play a role in preventing illness and affects lifespan. This concept has been explored in a recent study led by Sunil K. Ahuja, MD, professor of medicine at the University of Texas Health, San Antonio (UT Health, San Antonio), Thera Rozanolong School of Medicine, and is the director of the San Texas Veterans Health System, the Veterans Veterans Medical Center in San Antonio.

Since the dawn of civilization, humans have encountered inflammatory challenges such as infectious diseases. Properly regulated inflammation is essential to protect against threats and help with survival. However, inflammation is also associated with many diseases and mortality. This may have contributed to the emergence of the power of health promotion benefits, including immune resilience, which helps reduce the harmful effects of inflammation.

Ahuja and his team’s multi-year interdisciplinary study was published in Senescent Cells on April 23, 2025, examining this biological mechanism and its potential impact on healthspan and lifespan.

A study titled “15-year survival benefits: immune resilience as a respectful doggenic force in healthy aging” reveals that immune resilience is not fixed, but is measurable and adaptable. The team identified T-cell factor 7 (TCF7) expression as a key component of immune resilience. Higher TCF7 levels and associated markers were correlated with improved health outcomes, improved disease resistance, and durable vaccine responses.

“Pathogenic Triad”: Balance

“Our research shows that immune resilience is associated with TCF7, a central master regulator that maintains T cell health,” said Muthu Manoharan, MS, co-author and senior research scientist at UT Health San Antonio.

This study proposes that TCF7-associated immune resilience may counterbalance what the authors call the “pathogenicity triad”: inflammation (chronic inflammation caused by aging), immune aging, and cellular aging. Immunological resilience can decrease over time due to environmental threats (infection, trauma, etc.) or internal stressors (e.g., myocardial ischemia). Like dams that protect cities from floods, immune resilience can act as a biological barrier, reducing the risk of Triads overwhelming the body.

“When the association decreases and the pathogenesis appears, this can cause disease-promoting inflammation and immune aging conditions,” Ahuja explained. “Individuals with TCF7-linked immune resilience appear to be better at resisting inflammatory stressors and maintaining a low inflammatory immune profile that promotes improvement in survival and health.”

Three immune resilience trajectories

By analyzing data from over 17,500 individuals, the team identified three immune resilience paths during inflammatory stress.

Immune Resilience Parents: Maintain high resilience and potentially counter the Triad. Reconstructing Immune Restoration: Recovering during recovery experiences a temporary decrease in resilience. Degradation of immune resilience: indicates a sustained loss of resilience and a sustained increase in the burden of the pathogenic triad.

“Throughout lifetimes, inflammatory humiliation like infectious diseases can gradually reduce immune resilience. Some individuals can remain resilient for longer than others,” says Pharmd, Pharmd, co-author and associate professor at the University of Texas at Austin.

“Warranty period” for aging and immune resilience

This study highlights three lifetime processes that affect health. It is republic production, pathogenesis, and aging. A decrease in immune resilience that can potentially be exacerbated by a triad may increase susceptibility to age-related diseases.

“Disease vulnerability is different from that of losing health. This allows the emergence of disease processes. Aging and age-related diseases are clear,” says Nathan Harper, senior bioinformatics at the Veterans Health Center for Personalized Healthcare.

But even robust immune resilience is limited. At about the age of 70, the protective effect begins to fade. Manoharan’s threshold term “failed respect.”

Window of Potential Intervention Opportunities

This study found that participants from a large US population who have strong immune resilience at age 40 have a survival advantage of 15.5 years over less resilient people. By the age of 70, the longevity trajectory had converged, eliminating this advantage.

The findings imply that immune resilience may be revisable from birth to about 70 years. Lifestyle changes, medications, or future immunotherapy may delay age-related diseases and expand health spans.

“There are biologically modifiable windows for opportunities for intervention, such as diet, exercise, and drugs. Beyond this window, improving health spans is even more challenging,” Lee said.

Towards proactive health management

“Like cholesterol testing, we imagine a future in which immune resilience is routinely evaluated,” says Justin Meunier, BS, bioinformatics at the Center for Personalized Medicine. “Optimal immune resilience is associated with a unique blood biomarker profile that reflects higher levels of growth and immune factors and lower levels of inflammation.”

Lee added that personalized plans based on immune resilience status will help you actively prevent illness.

A new perspective on aging

TCF7-linked immune resilience represents novel and modifiable properties in aging studies. Unlike traditional biomarkers associated with disease and inflammation, this immune program may allow for personalized, collaborative interventions.

Ahuja teamwork shifts focus from inevitable decline to optimisable resilience. Future strategies to readjust immune resilience could shift health care from disease treatment to maintaining health.