Immune resilience identified as key to healthy aging and longevity

A study published in Aging Cell has identified immune resilience as a key driver of salutogenesis-the active process of promoting health and well-being.

By analyzing data from 17,500 individuals across various life stages, investigators uncovered the importance of immune resilience involving TCF7, a gene essential for maintaining immune cell regenerative potential, in fostering healthy aging and longevity.

The research indicates that immune resilience counters three major factors of aging and mortality: chronic inflammation, immune system decline (immunosenescence), and cell death. This protective mechanism mitigates biological aging processes and confers survival advantages. For example, at age 40, individuals with poor immune resilience face a 9.7-fold higher mortality risk-a risk equivalent to that of 55.5-year-olds with optimal immune resilience, resulting in a 15.5-year survival gap.

Maintaining optimal immune resilience preserves youthful immune profiles at any age; enhances vaccine responses; and significantly reduces the burden of cardiovascular disease, Alzheimer's disease, and severe infections.

Midlife (ages 40–70) emerges as a pivotal window for longevity, with immune resilience reducing mortality by 69% during this period. However, after age 70, mortality rates converge between resilient and non-resilient groups, suggesting biological limits on lifespan extension. These findings underscore the importance of early midlife interventions to boost immune resilience to maximize healthspan.

While most aging research focuses on disease mechanisms and the biology of aging, our work highlights how immune resilience sustains salutogenesis-actively promoting health. This opens new avenues for strategies to enhance lifelong wellness."

Sunil K. Ahuja, MD, senior author of UT Health San Antonio and the South Texas Veterans Health Care System

Source:
Journal reference:

Manoharan, M. S., et al. (2025) The 15-Year Survival Advantage: Immune Resilience as a Salutogenic Force in Healthy Aging. Aging Celldoi.org/10.1111/acel.70063.

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