Curcumin (CAS # 458-37-7) is the key active component of turmeric (Curcuma longa) root. It has been shown to exhibit antioxidant, anti-inflammatory, anti-neurodegenerative, and antitumor activities. 620, 621 Recently it has been implied that curcumin upregulates SIRT3 expression in skeletal muscle tissues 622 , as well as in the brain after stroke. Numerous other dietary polyphenols such as resveratrol, (-)epigallocatechin-3-gallate (EGCG) have been shown able to mitigate age-produced cellular damage via metabolic formation of ROS, via specific cell-signaling actions that may stimulate SIRT1 activity. Furthermore, polyphenolic compounds have proven inhibitory activity against chronic vascular inflammation related to atherosclerosis. 624 Melatonin (N-acetyl-5-methoxy tryptamine, CAS # 73-31-4) is a hormone secreted by the pineal gland and regulates sleep/wake cycles. It is a well-recognized antioxidant able to support healthy aging. The endogenous melatonin levels have been found to decrease upon aging and even stronger in certain neurodegenerative disorders, especially Alzheimer's disease, as well as in type 2 diabetes. It has been reported relevant to the attenuation of inflammaging in the brain. Studies have documented the ability of melatonin to increase SIRT levels against brain aging. 626, 627 β-Carotene (CAS # 7235-40-7) is a carotenoid, a micronutrient with numerous physiological functions. It is an antioxidant, which has been shown to inhibit the incidence and development of cancer. It also has an anti-inflammatory effect in various animal and cell models. Its anti-aging efficacy has been documented in vitro, using mesenchymal stem cells, as well as in vivo, in model animals. It was implied to inhibit aging by regulating the KAT7-P15 signaling axis. Other carotenoids, including α-and γ-carotenes, lycopene, lutein, β-cryptoxanthin, and zeaxanthin, are also known as effective natural antioxidants. Synergistic action of vitamins C and E, and carotenoids, has been reported to successfully prevent lipid peroxidation. 630 α-Lipoic acid (6,8-thioctic acid, CAS # 1200-22-2) is a dithiol, which acts as a coenzyme factor for certain redox reactions. It is synthesized in animals naturally and is essential for aerobic metabolism. Its efficiency in diseases associated with aging-provoked oxidative stress has been documented, so its dietary supplementation has been found beneficial. Lipoic acid has been also shown to activate SIRT1 and SIRT3 in peripheral tissues thus improving mitochondrial function and protecting against cardiac hypertrophy. Coenzyme Q10 (CoQ10, CAS # 303-98-0), a powerful antioxidant known to offer a variety of benefits to support healthy aging, is naturally produced in the body and is participating in energy production. It has attracted large-scale interest due to its crucial role in mitochondrial bioenergy, antioxidation, anti-aging, and immune system regulation. Upon aging, the production of CoQ10 declines, so it is necessary to supply additional amounts through foods such as meats, fatty fish (e.g., trout) and nuts (e.g., pistachios), or through dietary supplements. It has been reported to exert positive effects in enhancing age-produced deterioration of oocyte quality. 636 CoQ10 and selenium supplementation have been reported to increase serum Sirtuin1 levels 637 and to improve heart function in elderly. 638 L-Glutathione (GSH, CAS # 70-18-8) is an abundant antioxidant playing an essential role in protecting cells against oxidative stress-caused cellular damage. Declined glutathione levels are related to the typical characteristics of aging, as well as of a wide variety of pathological conditions, including neurodegenerative disorders. Thus, glutathione depletion seems to be important for the onset of Parkinson's disease. Furthermore, glutathione is important for body detoxification, it is also a successful immunostimulant and skin rejuvenator. 640 Antioxidant intake controversy. The reported inverse correlation between systemic levels of antioxidants and certain age-associated diseases has resulted in the perception that antioxidant supplementation is an effective prophylactic and therapeutic intervention for such aging pathologies. However, the therapeutic results of this strategy in clinical trials have been frequently disappointing. The interplay of both endogenous and exogenous antioxidants is complex and still not well understood. To successfully maintain the redox homeostasis, exogenous and endogenous antioxidants need to act synergistically. 642 A fine-tuned equilibrium between the oxidative and antioxidative processes in the organism is vital in preserving homeostatic stability. Thus, excessive antioxidant supplementation might turn out to be damaging for the delicate homeostatic control mechanisms resulting in health decline. Similarly to the hormesis-causing agents, antioxidants perform beneficially in certain concentration range, and their higher concentrations are typically toxic to organisms. The excessive levels of exogenous antioxidants may perturb the endogenous signaling pathways and thereby be harmful. In view of these contradictions, it is not surprising that conflicting data have been reported on the health outcomes of long-term antioxidant intake. This ambiguity is often referred to as 'antioxidant paradox'. 552 While benefits of dietary antioxidant supplementation appears to be clear in cases of high oxidative stress and endogenous antioxidant insufficiency, further research is necessary to clarify the potential risks and advantages linked to the supplement of antioxidants by healthy people.