A quarter of the world’s population will be >60 years of age by 2050. More must be done to understand the intricacies associated with age-related pathology as we rapidly approach an aged society. With aging there is decrease in peripheral naïve CD8+ T cells with a simultaneous increase in CD44hi memory CD8+ T cells. Virtual-Memory T (Tvm) cells are antigen-naïve T cells that present a classical memory phenotype whilst also possessing innate-like immune function. Unlike other CD8 subsets, Tvm cell homeostasis is highly dependent on cytokines, as shown by their selective depletion in IL-15-/- mice. Tvm cells acquire TCR-associated defects in aged mice and humans, which could contribute to the overall decline in CD8 T cell function seen with aging. Tvm cells make up a large proportion of the naïve CD8+ T cell pool making them ideal targets for age specific therapeutic interventions. Here, we have performed ATAC-Seq analysis on young and aged CD8+ T cell subsets and have identified several key signatures selectively associated with age-related dysfunction. The aged-specific Tvm cell signature will be validated and the role of candidate genes involved in mediating the dysfunction assessed using a range of molecular and cellular techniques. Validated targets will be investigated for the capacity to block their inhibitory effects to mediate functional recovery in dysfunctional T cells. Collectively, this study will provide fundamental information on biological changes associated with advanced age in CD8+ T cells, which is essential for informed targeting to rejuvenate cellular immunity in the elderly.