From Ouroboros, a look at research into internal changes in T cells with aging, some the mechanisms driving the ongoing depletion of the naive T cell population, some not: "The adaptive immune response requires waves of T-cell clonal expansion on contact with altered self and contraction after elimination of antigen. In the case of persisting antigen, as occurs for example in cytomegalovirus or Epstein-Barr virus infection, this critical process can become dysregulated and responding T-cells enter into a dysfunctional senescent state. Longitudinal studies suggest that the presence of increased numbers of such T-cells is a poor prognostic factor for survival in the very elderly. ... These pathways and affected genes may play a significant role in driving the cellular senescent phenotype and warrant further investigation as potential biomarkers of aging and senescence. These genes may additionally provide targets for intervention. ... A possible mechanism for some age-related transcriptional changes is provided by Das et al., who describe the negative effect of oxidation (both experimental and age-related) on the proteasome. ... These results suggest that the decrease in proteasomal activities observed during aging may be secondary to oxidative stress and underlie immune senescence."