Role of Redox Imbalance in the Molecular Mechanisms Responsible for Immunosenescence

The elderly suffer impairments to their immune system, evidenced by higher susceptibility to infections, cancer, and many diseases believed to be autoimmune in nature. A dysregulated overexpression of many proinflammatory cytokines also occurs with aging, as does the synthesis of enzymes that control expression of inflammatory lipid mediators and reactive oxygen species. An inappropriate activation of redox-controlled transcription factors, like nuclear factor-κB, occurs in many tissues from aged donors, and has been linked to excesses in cellular oxidative stress. Recently, the peroxisome proliferator-activated receptor-α (PPARα) has been evaluated for its effects on inflammatory and adaptive immune processes. PPARα provides redox-balancing influences on various lymphoid cell types and their inducible responses. We recently discovered that PPARα transiently suppresses the transcription of γ-interferon (IFNγ) by inhibiting the induction of T-bet. We now report that PPARα expression in CD4+ T cells is affe...