Metabolic Signaling as a Driver of T Cell Aging.

Aging significantly diminishes T cell immunity, increasing susceptibility to infections and reducing vaccine efficacy in older individuals. Metabolism plays a key role in T cell function, shaping their energy requirements, activation, and differentiation. Recent studies highlight altered metabolic signaling as a pivotal factor in T cell aging, influencing the ability of T cells to maintain quiescence, respond to activation, and differentiate into functional subsets. Aberrant metabolic pathways disrupt the quiescence of aged T cells and skew their differentiation toward short-lived, pro-inflammatory effector T cells while hindering the generation of long-lived memory and T follicular helper cells. These changes contribute to a hyper-inflammatory state, exacerbate chronic low-grade inflammation, and compromise immune homeostasis. In this review, we explore how metabolic signaling is altered during T cell aging and the resulting functional impacts. We also discuss therapeutic approaches aimed at restoring proper T cell differentiation, improving vaccine responses, and rejuvenating immune function in older populations.