Aging and cellular senescence significantly affect immune function, leading to increased susceptibility to diseases such as cancer and viral infections, including COVID-19. This decline in immune function is particularly evident in T cells, whose functions and phenotypes change significantly with age. The traditional view is that T cell senescence is related to irreversible DNA damage, but recent evidence suggests that mechanisms independent of DNA damage are also involved. Our study confirms that mitochondrial calcium dysregulation drives CD8 ⁺ T cell senescence. The results showed that RXR expression levels decreased with age and were consistent with human CD8 ⁺ The expression of aging-related genes in T cells was negatively correlated. In mice and humans CD8 ⁺ In T cells, loss of RXR triggers a senescence mechanism that is independent of DNA damage. From a mechanistic point of view, RXR deletion leads to a massive overload of calcium ions in mitochondria, and the use of drugs to inhibit this calcium overload can almost completely reverse the aging phenotype and significantly enhance CD8 ⁺ T cell-mediated anti-tumor immunity, and this effect is independent of exhaustion. These findings establish mitochondrial calcium overload as a key mechanism in inducing T cell senescence and provide a potential therapeutic target for enhancing immune function in a variety of age-related pathological conditions.