Oxidative stress has been assumed to notably contribute to aging. The oxidative stress theory of aging hypothesizes that age-related decline in physiological performance is caused by a slow continual accumulation of oxidative damage to biomolecules, which grows with age and is associated with life expectancy decline of organisms. Oxidative damage contributes to multiple hallmarks of aging and drive multiple age-related diseases. Thus, telomeres are highly sensitive to oxidative damage. 318, 319 Therefore, oxidative damage may cause telomere attrition, which accelerates aging and augments the risk of age-related diseases. Oxidative stress has been defined as an imbalance between the production of oxidants and their elimination by antioxidants, leading to disturbance of redox signaling and control, and/or molecular impairment. According to the oxidative stress theory of aging, damages caused by free radicals are the main reason of aging and a shorter lifespan. ROS are highly reactive species, mainly including free radicals comprising at least one unpaired electron -superoxide radicals (O2-•), hydroxyl radicals (•OH) and hydrogen peroxides (H2O2) -and have been believed to be the primary source of endogenous oxidative stress damage. It is widely agreed that the largest part of ROS are produced by the electron transport chains of mitochondria during regular oxidative respiration in addition to numerous intracellular pathways. The principal process of ROS production in mitochondria can be schematically described as O2 → O2 -• → H2O2 → •OH. Furthermore, ROS are generally produced by mitochondria, throughout physiological and/or pathological processes. Thus, O2•-can be formed by cellular respiration, by lipoxygenases and cyclooxygenases via the arachidonic acid metabolic pathway, and by endothelial and inflammatory cells. In the electron transport chain, oxygen molecules have been reduced into O2-• with a leak of electrons, with the formation of superoxide being the initial step in a cascade reaction of other ROS generation. When generated, it can be catalyzed by the super oxidize dismutase (SOD) into H2O2. Next, in the presence of reduced form transition cation (Fe 2+ or Cu + , known as a Fenton reaction) or myeloid peroxide, H2O2 further converts to •OH. Meanwhile, H2O2 can also be reduced into H2O by the enzymatic antioxidants such as catalase and glutathione peroxidase. Haptoglobin steadily binds hemoglobin with strong affinity, inhibiting the release of heme iron from hemolysis into systemic circulation, therefore terminating Fenton reaction and avoiding the production of •OH. Mitochondrial dysfunction upon aging results in increased ROS, thus causing enhanced oxidation of biomolecules (proteins, DBA, lipids) and opens a positive feedback loop of aging damage (Figure ). Noteworthy, examining the hypothesis of oxidative stress in aging and diseases have disclosed controversial results. There is sizeable evidence that macromolecular oxidative damage raises with age and seems to be related to life expectancy in multiple organisms. Yet, a direct relationship between oxidative damage and aging has not been conclusively established. In fact, the role of ROS in the body is complex, and its effects on health vary largely along with changing ROS levels. Within physiological levels, ROS facilitate the preservation of cellular homeostasis and performance. Therefore ROS levels can exhibit both favorable and detrimental effects, as suggested in the concept of mitohormesis. Oxidative stress may result in damage to various classes of biomolecules including lipids, proteins, and nucleic acids. Polyunsaturated fatty acid (PUFA), especially those with a higher number of double bonds, are highly susceptible to lipid peroxidation by an autocatalytic oxidative chain reaction. Peroxidation of phospholipids in lipid membranes may result a decline in membrane fluidity and permeability, and thus inactivation of membrane receptors, resulting in cell apoptosis. Moreover, lipid radicals generated during oxidation can form a multitude of harmful end products, including reactive aldehydes, alkanes, and alkenes. Proteins are also key targets for ROS. Protein oxidation includes: (i) oxidative alteration of amino acid residues, particularly cysteine and methionine; (ii) fragmentation as a result from oxidative cleavage of the peptide backbone; (iii) production of protein carbonyl derivatives; (iv) protein crosslinks generation. Protein oxidation may cause changes in their three-dimensional structures, alteration of their physiological features such as enzyme performances and signal transduction, and further proteolytic degradation or aggregation of proteins, partial unfolding and modified conformation. ROS, specifically the hydroxyl radicals, can incite oxidative damage to the nuclear DNA, including: base mutation, strand breaking, DNA-protein crosslinking, and DNA-adducts formation. Overall, hydroxyl radicals can react with DNA bases and sugar-phosphate backbone, leading to inaccurate base pairing and further common mutations. Hydroxyl radicals can also react with the deoxyribose moiety resulting in loss of DNA bases and DNA breaks. Such breaks are documented risk factors of genome instability, cell cycle disruption, and cell death. DNA-protein crosslinks involving thymine and tyrosine in the nucleoprotein complex of histones and DNA can also be activated by the hydroxyl radicals.