Regulation of T Cell Senescence in Health and Diseases

Aging is accompanied by a progressive decline in immune function, a process termed immunosenescence, which affects both innate and adaptive immune compartments.Among these, the adaptive immune system-and particularly T cells-undergoes the most profound functional and phenotypic alterations, critically impairing host defense against infections, cancer, and vaccination responses.The age-associated decline of adaptive immunity is shaped by the divergent senescence pathways of CD4 + helper and CD8 + cytotoxic T cells.While both lineages enter a state of cell-cycle arrest, their distinct immunological roles dictate fundamentally different molecular triggers, metabolic adaptations, and functional outcomes.This review synthesizes these subset-specific differences, highlighting how DNA damagedependent mechanisms and DNA damage-independent processes drive distinct senescence phenotypes.Furthermore, we discuss how these differences contribute to immune system remodeling during aging and explore emerging therapeutic strategies targeting metabolic and signaling pathways to mitigate T cell senescence.