The lifelong exposure of antigens and stressors results in chronic oxidative stress situation in the organism. The free radicals and reactive oxygen species (ROS) with high reactivity produced by our cells under oxidative stress will cause oxidative damage in biomolecules. The oxidative damage leads to the releases of both damage-associated-molecular patterns (DAMPs) and intracellular cytokines. DAMPs activate pathogen recognition receptors (PRRs) and non-PRRs. Intracellular cytokines activate signalling pathways downstream of PRRs. Activation of these receptors results in the upregulation of cytokines and chemokines, which are released to recruit and activate additional inflammatory cells and cause the systemic and chronic sterile inflammation. The regulatory system, especially immune systems play an important role in homeostasis maintenance in the organism. The cells of immune systems are very vulnerable to oxidative damage. Once the homeostasis is destroyed, an imbalance between inflammatory and anti-inflammatory networks will occur. Genetic factor also is an important factor of oxi-inflamm-aging and age-related diseases. Many genes are involved in oxidative stress, inflammation process, and the genomic variations within most of these genes might produce different effects on oxi-inflamm-aging. The polymorphism of ApoE genes can affect the antioxidant and immunomodulatory/anti-inflammatory properties of the organism. ApoE genotype-phenotype is associated with the progress and prognosis of oxi-inflamm-aging, age-related diseases as well. Anti-inflammation together with regulation of the expression of ApoE might be an efficient method against oxi-inflamm-aging. Based on our previous studies, the progresses in these areas are reviewed.