Moreover, significant alterations in epigenetic patterns are linked to aging and age-related illnesses [6], and Tregs are prone to epigenetic alterations that change as we age. Aged mice have been demonstrated to have higher levels of suppressive Treg function when Cytosine Phosphate Guanosine (CpG) sites upstream of the Recombinant Fork head Box Protein P3 (Foxp3) enhancer are hypomethylated [27]. In the elderly, Treg function is unaffected or even improved, and they are more prone to infection and malignancy, consistent with enhanced Treg function. And because of Treg dysfunction [29], they are also more prone to autoimmune disease [30], [31]. The number and function of Treg increased or enhanced with age, and pTreg differentiation decreased with age. During age, the quantity of CD8+Treg and CD4+Treg cells increases, which lowers the adaptive immune response. At the same time, the expression levels of Foxp3 and CD45RA are lower in CD8+ CCR7+ Treg in the elderly, suggesting that the suppressive capacity of these cells is diminished and may contribute to autoimmune disease in the elderly development [32]. Dysfunction of aged CD8+ and CD4+ Treg cells may support age-related subclinical inflammation, termed “inflame-aging” [33].
