Abstract

As research into cognitive aging progresses, it has become increasingly clear that it is a multifactorial process influenced not only by neuronal changes but also by systemic immune alterations. One potential upstream contributor to immunological senescence, including “inflammaging,” is age-associated loss of thymic tissue and thymic function. This overview summarizes the current literature that investigates the relationships between age-related alterations in thymic function, peripheral immune dysfunction, and cognitive decline. It discusses mechanistic pathways involving reduced naïve T-cell output, persistent inflammatory signaling, blood–brain barrier (BBB) dysregulation, microglial activation, and neurovascular alterations. In addition, emerging evidence from population-based neuroimaging and biomarker studies demonstrates associations between systemic inflammatory profiles and structural correlates of brain aging. Collectively, this body of work supports a systems-level framework linking thymic involution to cognitive trajectories across the lifespan; however, causal relationships in humans remain incompletely established. Future longitudinal studies of immune contributions to cognitive aging, incorporating multi-omics approaches, immunome mapping, AI-based predictive modeling, and thymic imaging, may further clarify these relationships and enable the development of neuroimmune-targeted strategies to promote healthy aging and improve healthspan

Keywords

thymic involution, cognitive aging, neuroimmune interactions, immunosenescence, inflammaging, microglia, blood–brain barrier, brain aging, immunome, artificial intelligence, healthspan