Fig. 2

A model for the possible implication of IL-7 receptor alpha (IL-7Rα) and effector memory (EM) CD8⁺ T cells expressing distinct levels of IL-7Rα as biomarkers of aging. IL-7Rα^high and ^low EM (CCR7⁻) CD8⁺ T cell subsets with distinct characteristics, including the expression of CD27, CD28, CD57, CX3CR1 and CXCR1 as well as the production of inflammatory and cytotoxic molecules (e.g., TNF-α, IFN-γ, granzymes, perforin, and granulysin), are present in human peripheral blood (see Table 1 for summary of cellular characteristics). The differential expression of IL-7Rα is regulated by DNA methylation and chromatin accessibility in the IL7RA gene promoter. Alterations in DNA methylation and chromatin accessibility in CD8⁺ T cells occur with aging, contributing to altered expression of IL7RA signaling molecules, inflammatory cytokines, and cytotoxic molecules. The frequency of IL-7Rα^low EM CD8⁺ T cells in peripheral blood increases with aging while the frequency of IL-7Rα^high EM CD8⁺ T cells decreases