Memory T cell aging and rejuvenation

Aging reshapes T cell immunity, as evidenced by eroding naive diversity and remodeled memory hierarchies. This generates an experienced yet constrained repertoire, with weakened protection against novel infections and malignancies and blunted vaccine responsiveness. However, the pace and extent of decline vary widely between individuals. Such heterogeneity signals a recalibration of immune priorities that favors persistence over plasticity of memory T cells. Here, we discuss how aging shapes memory T cell compartments-from repertoire contraction and differentiation to altered metabolic, transcriptional, and epigenetic states. We further examine how chronic inflammation, antigen persistence, and niche remodeling converge to drive dysfunction or resilience. Finally, we outline strategies to rejuvenate T cell immunity during aging to preserve adaptive competence across the lifespan.