Graduate student Seoul National University College of Medicine, United States
Disclosure(s):
Jeong-Won Kim: No financial relationships to disclose
Introduction/Rationale: Immunosenescence contributes to infection risk, poor vaccine response, and chronic inflammation in older adults. Because chronological age does not reflect biological variability, clinical frailty offers a functional measure of physiological aging. Using the Korean Frailty Index (K-Frail), this study investigated frailty-associated immune signatures through integrated analyses of systemic inflammation and T cell profiles.
Methods: Peripheral blood was collected from young, healthy-, and frail-aged donors classified by K-Frail. PBMCs and plasma were analyzed for cellular and soluble immune factors. Multicolor flow cytometry assessed T cell subsets, senescence markers, and cytokine production. Plasma senescence-associated secretory phenotype (SASP) factors were quantified using a Luminex assay.
Results: Aging was characterized by reduced naïve and increased memory T cells with higher senescence marker expression. These phenotypic changes were comparable between healthy-aged and frail-aged groups, indicating limited additional T cell remodeling with frailty. However, functional assays revealed elevated frequencies of TNF-producing, polyfunctional CD8⁺ T cells (IFN-γ⁺MIP-1β⁺TNF⁺) in frail individuals. Systemic profiling identified a TNF-centered SASP network involving TNFR1, TNF-α, and IL-6, which was upregulated in frailty. TNFR1 levels and frequencies of polyfunctional CD8⁺ T cells correlated positively with K-Frail scores, linking TNF-associated inflammatory activity to frailty severity.
Conclusion: Frailty does not substantially augment peripheral T cell senescence beyond chronological aging but is characterized by a distinct immune signature featuring enhanced TNF-producing CD8⁺ effector responses and elevated TNF-related SASP factors. The parallel increases in TNFR1, TNF-producing CD8⁺ T cells, and frailty scores suggest a TNF-driven mechanism contributing to immune frailty, offering a potential target for inflammation-modulating interventions in aging.
