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This has been attributed to selenium's ability to reduce DNA damage and oxidative stress, boost your immune system, and destroy cancer cells 8. A review of 69 studies that included over , people found that having a high blood level of selenium was associated with a lower risk of certain types of cancer, including breast, lung, colon, and prostate cancers 9. However, some research suggests that supplementing with selenium may reduce side effects in people undergoing radiation therapy.

For example, one study found that oral selenium supplements improved overall quality of life and reduced radiation-induced diarrhea in women with cervical and uterine cancer A diet rich in selenium may help keep your heart healthy , as low selenium levels have been linked to an increased risk of heart disease.

For example, a review of 16 controlled studies including over , people with heart disease showed that taking selenium supplements decreased levels of the inflammatory marker C-reactive protein CRP. Additionally, it increased levels of glutathione peroxidase, a powerful antioxidant This indicates that selenium may help lower heart disease risk by reducing inflammation and oxidative stress in your body. Oxidative stress and inflammation have been linked to atherosclerosis, or the buildup of plaque in arteries.

Atherosclerosis can lead to dangerous health problems like strokes, heart attacks, and heart disease Incorporating selenium-rich foods into your diet is a great way to keep levels of oxidative stress and inflammation to a minimum. Thus, finding ways to prevent this degenerative disease is imperative.

One small study found that supplementing with one selenium-rich Brazil nut per day improved verbal fluency and other mental functions in patients with mild cognitive impairment Selenium is important for the proper functioning of your thyroid gland. In fact, thyroid tissue contains a higher amount of selenium than any other organ in the human body This powerful mineral helps protect the thyroid against oxidative damage and plays an essential role in the production of thyroid hormones.

A healthy thyroid gland is important, as it regulates your metabolism and controls growth and development An observational study including over 6, people found that low serum levels of selenium were associated with an increased risk of autoimmune thyroiditis and hypothyroidism One review concluded that taking selenium supplements daily for three months resulted in lower thyroid antibodies.

Your immune system keeps your body healthy by identifying and fighting off potential threats. These include bacteria, viruses, and parasites. Selenium plays an important role in the health of your immune system. This antioxidant helps lower oxidative stress in your body, which reduces inflammation and enhances immunity. Studies have demonstrated that increased blood levels of selenium are associated with enhanced immune response. On the other hand, deficiency has been shown to harm immune cell function and may lead to a slower immune response Studies have also associated deficiency with an increased risk of death and disease progression in people with HIV, while supplements have been shown to lead to fewer hospitalizations and an improvement in symptoms for these patients Additionally, selenium supplements may help strengthen the immune system in people with influenza, tuberculosis, and hepatitis C These airways become inflamed and begin to narrow, causing symptoms like wheezing, shortness of breath, chest tightness, and coughing Asthma has been associated with increased levels of oxidative stress and inflammation in the body Due to selenium's ability to reduce inflammation, some studies suggest that this mineral may help reduce asthma-related symptoms.

In fact, one study showed that asthmatic patients with higher levels of blood selenium had better lung function than those with lower levels For example, one study found that giving people with asthma mcg of selenium per day reduced their use of the corticosteroid medications used to control their symptoms The following foods are great sources 33 , 34 :. The amount of selenium in plant-based foods varies depending on the selenium content of the soil in which they were grown.

For example, one study showed that the selenium concentration in Brazil nuts varied widely by region. Although selenium is necessary for good health, getting too much can be dangerous. In fact, consuming high doses of selenium can be toxic and even fatal. Brazil nuts contain a very high amount of selenium. An in-depth understanding of the role of antioxidants involved in redox modulation of inflammation would provide a useful approach for potential interventions, and subsequently promoting healthy longevity.

In the last few decades, several models have been suggested to define the interconnection and the biological pathways of aging Dice, Based on the oxidative stress hypothesis, oxidative damage is not solely triggered by the unrestricted ROS production, but it also caused by other oxidants, such as reactive lipid species and reactive nitrogen species RNS.

The hypothesis of oxidative stress highlights the crucial role of antioxidant defenses as an important component of the overall redox balance of the organism. However, several studies demonstrated that avoiding oxidative stress damage does not increase longevity Buffenstein et al. Oxidative stress is considered as an imbalance between pro- and antioxidant species, which results in molecular and cellular damage Conti et al.

Mitochondria are major organelles that are accountable for generation of energy through oxidative phosphorylation to generate adenosine triphosphate ATP , a molecule which is crucial for cellular actions Weinberg et al. During this process, ROS are generated as by-products for the partial four-electron reduction of O 2 to produce water molecule, which is the last electron acceptor in the ATP generation process Ambrosio et al. Nearly 0. In the normal healthy state, the generation and oxidation of ROS occur in a controlled manner.

By contrast, the ROS production is increased under high-stress conditions or under disease states. The ROS generated from aerobic respiration caused a cumulative oxidative damage in macromolecules, including lipids, DNA, and proteins, which subsequently lead to cells death Scheibye-Knudsen et al. An alteration of the redox status and the dysregulation of the immune system during aging may lead to the elevation of systemic inflammatory status.

Both of these processes caused the activation of inflammatory mediators via oxidative stress-induced redox imbalance. Unresolved chronic inflammation during aging may serve as a pathophysiologic association which converts normal functional changes to the age-related degenerative diseases Viola and Soehnlein, Oxidative stress is reinforced by several reactive species, including H 2 O 2 , singlet oxygen, other radicals, and non-radicals, which are consistently produced in the body due to the aerobic metabolism, and thereby potentially altering basic structural components such as proteins, lipids, and nucleic acids Weidinger and Kozlov, Template biosynthesis of polypeptide chains on ribosomes usually does not produce a functional protein.

The newly developed polypeptide chain must undergo certain chemical modifications outside the ribosome. Thus, these modifications are most often accompanied by enzymes and take place after all the information supplied by the template RNA mRNA has been read, that is after mRNA translation. These additional processes are known as posttranslational modifications. There are four primary groups of protein functions which require posttranslational modification of amino acid residue side chains.

The functional activity of several proteins requires the presence of certain prosthetic groups covalently bound to the polypeptide chain. These are usually involving complex organic molecules which take part in the protein activity for instance, the transformation of inactive apoproteins into enzymes.

Another important group of modifications is protein tags, which provide intracellular localization of proteins such as marking the proteins for transport to the proteasome, where they will be proteolyzed and hydrolyzed. Additionally, some of the posttranslational modifications regulate biochemical processes by varying enzymatic activity Knorre et al. Among all the antioxidant enzymes, glutathione peroxidase is the most powerful biological antioxidative reductant Cross et al. Collectively, maintaining a healthy redox balance status is crucial for the physiological acid-base buffer system in the body for the optimal homeostatic cellular activities.

Figure 1 shows the effect of oxidative stress and the interaction of aging and age-related diseases. Figure 1. Effect of oxidative stress and the interaction of aging and age-related diseases. Mitochondrial function decline and oxidative stress response in aging may subsequently contribute to age-related diseases. Inflammaging is a chronic, low-grade, and systemic inflammation in aging, which is occurred in the absence of overt infection Franceschi and Campisi, Chronic inflammation is usually derived from the damaged cells or macromolecules due to an inadequate elimination or increased production.

The ability of gut to sequester harmful microbes declines with age. Therefore, some of the harmful products that produced by the microbial constituents of the human body, such as gut microbiota, is capable to permeable into surrounding tissues Biagi et al. Senescence, a cellular response to stress and other damage Franceschi and Campisi, Persistent senescent cells have been associated with aging or age-related diseases via secretion of proinflammatory cytokines that alter the tissue microenvironment or modify the function of normal cells Baker et al.

Increased inflammation may also derive from the stimulation of coagulation system. Coagulation is regarded as a part of the inflammation system. Aging promotes the hypercoagulable state and increased the risk of arterial and venous thrombosis in the elderly Franceschi and Campisi, Additionally, aging also alters the immune system, which is subsequently leading to inflammaging. Adaptive immunity decreases with age; conversely, innate immunity demonstrated minute changes in mild hyperactivity Santoro et al.

The response of innate immunity might increase when adaptive immunosenescence progresses. These age-related changes could be due to the lifelong exposure to antigens and pathogens, as well as intrinsic changes in immune cells Stephenson et al. Numerous age-related diseases undergo the inflammation process, which is a risk factor in or partly of disease development DeBalsi et al.

For instance, several age-related diseases including diabetes, dementia, metabolic syndrome, osteoporosis, cancer, arthritis, and cardiovascular diseases have been recognized as inflammatory disorders Tan et al. The interaction between inflammation and oxidative stress is tightly associated with the prostaglandins PGs biosynthetic pathway that produces reactive species Kawahara et al. PGs are lipid metabolites of arachidonic acid which have strong proinflammatory responses with pathogenic activities.

For example, certain PG metabolites act as an active mediator of inflammation. While, some of the reactive species produced from PGs metabolism may exacerbate inflammation and induce tissue damage Blaser et al. The production of reactive species via PG synthesis pathway contributes significantly to the overall reactive species pool in both pathological and normal states, especially during aging Nita and Grzybowski, Research evidence has suggested that the molecular inflammatory process plays a vitally important role during the aging process and age-related diseases Davalli et al.

Under high- stress circumstances, proinflammatory genes encode proinflammatory proteins, including chemokines, growth factors, and cytokines. Aging is also linked to the elevation of inflammatory cell monocytes and neutrophil counts and C-reactive protein CRP levels Tang et al. High IL-6 plasma levels were shown to have a greater likelihood of mortality, morbidity, and disability in the elderly Puzianowska-Kuznicka et al. In addition, compelling evidence suggests that DNA damage response DDR signaling is a predominant mechanism associated with the build-up of DNA damage, aging, and cell senescence Malaquin et al.

This study indicates the involvement of epigenetic modifications such as small, non-coding RNAs and microRNAs, which contributes to post-transcriptional regulation. Moreover, microRNAs may also be harnessed as an innovative tool to identify target senescent cells and to develop therapeutic interventions that can delay the proinflammatory programme stimulated in senescent endothelial cells Prattichizzo et al.

Progerias or accelerated-aging syndromes are partially recapitulated normal aging Burtner and Kennedy, Most of the accelerated-aging syndromes are induced by modification of nuclear envelope or by defects in DNA repair systems. Werner syndrome is the most common accelerated-aging syndrome derived from DNA repair defects, caused by the mutations of Werner syndrome ATP-dependent helicase WRN , a gene coding for a protein implicated in telomere maintenance and homology-dependent recombination repair Osorio et al.

Compared to HGPS, the onset of Werner syndrome is slightly slower, in which the pathology accompanies with Werner syndrome resembles a premature aging. Clinical pathology of Werner syndrome starting from 10 to 20 years of age including early graying, short stature, hair loss, and bilateral cataracts. The cellular phenotypes linked to the Werner syndrome demonstrate significant overlap with laminopathies. The delay in 53BP1 recruitment to DSBs in these cells and the accumulation of irreparable damage may be a potent physiological genotoxic stress in individuals with HGPS.

Collectively, increased levels of DNA damage may have important consequences in vivo. Antioxidants control the autoxidation by interrupting the propagation of free radicals or by inhibiting the formation of free radicals via different mechanisms. The most effective antioxidants are those possessing the ability to interfere with the free radical chain reaction.

The radical intermediate is then stabilized by the resonance delocalization of the electron within the aromatic ring Wojtunik-Kulesza et al. Antioxidant plays a central role in the termination of oxidative chain reactions by removing the free radical intermediates Gholamian-Dehkordi et al. Many studies indicate that cellular redox status is crucial for ROS-mediated signaling and mitochondrial function Fang et al. Depletion of intracellular glutathione GSH markedly promotes mitochondrial ROS production and triggers mitochondrial membrane depolarization Lohan et al.

Appropriate intracellular levels of ROS plays a crucial role in physiological redox signaling via activation and regulation of endogenous defenses by protecting cells from nitrosative, oxidative, and electrophilic stress Moldogazieva et al. Indeed, supplementation with exogenous antioxidants depletes exercise-triggered improvements in insulin sensitivity and antioxidant gene expression Ji et al.

Additionally, overexpression of thioredoxin Trx has been demonstrated to inhibit the progression of insulin resistance in both type 1 and type 2 diabetes in vivo Yamamoto et al.

7 Science-Based Health Benefits of Selenium

Recent findings suggest that a protective role of Nrf2 on oxidative stress in aging de Oliveira et al. Depletion of Nrf2 activity has been identified to contribute to the development of age-related diseases Cuadrado et al. Several studies as reported by Tan et al. Indeed, a unique complex of bioactive constituents can provide protection against oxidative stress, which can cause in inflammation Tan et al. In support of this, numerous epidemiological studies including European paradox study Bellizzi et al.

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In this regard, the antioxidant capacity in natural products has drawn attention among scientists in academia and industry in the prevention of age-related diseases. Figure 2 summarizes the dietary intake of antioxidants in relation to oxidative stress in aging. Figure 2. The balance of antioxidants and oxidative stress in aging. An inevitable by-product from aerobic respiration, reactive oxygen species ROS at the appropriate level is beneficial and essential for normal cell signaling and cellular immunity. Similarly, reactive nitrogen species RNS can be physiologically useful.

This phenomenon is suffered by elderly and thereby promoted abnormal cell death, inflammation and subsequently contributes to age-related diseases. Substantial evidence has demonstrated the importance of antioxidants intake from dietary nutrients to replenish low level of antioxidants especially endogenous antioxidant such as glutathione and coenzyme Q10 in the body.

Administration of exogenous minerals, organosulfur compounds, vitamins, carotenoids, polyphenols and endogenous antioxidant antioxidant cofactor such as coenzyme Q10; and low molecular weight antioxidant: glutathione have shown to maintain the antioxidant defense and subsequently leads to healthy longevity. Mitochondria-targeted antioxidants have great potential against the damage caused by ROS generation. The ability of mitochondria-targeted antioxidants confers greater protection against oxidative damage has been attributed to their abilities to cross the phospholipid bilayer of mitochondria and thus eliminating ROS Oyewole and Birch-Machin, In principle, a broad range of antioxidants could be targeted to mitochondria via conjugation of triphenylphosphonium TPP moiety Smith and Murphy, In particular, ubiquinol MitoQ is the best-characterized antioxidant targeted to mitochondria by conjugation to the TPP cation Smith and Murphy, The role of MitoQ will be described in the ubiquinone section.

Low molecular weight antioxidants such as minerals, vitamins, carotenoids, cofactors, glutathione, and polyphenols are crucial for antioxidative defense mechanisms of cells and organisms Grune et al. Ascorbic acid vitamin C and tocopherol vitamin E are the most important low molecular weight antioxidants that cannot be synthesized by a human Podda and Grundmann-Kollmann, There are several molecules that are synthesized in the human body and possess an antioxidant effect including glutathione, lipoic acid, uric acid, taurine, keto acids, melatonin, coenzyme Q, and melanins.

Among these antioxidants, glutathione is one of the major cellular antioxidant Sifuentes-Franco et al. Glutathione is a pivotal antioxidant present in the microorganisms, plants, and animals. Glutathione prevents the cell damage induced by ROS including lipid peroxides, peroxides, free radicals, and heavy metals Pisoschi and Pop, Glutathione can scavenge ROS via non-enzymatic and enzymatic reactions.

The non-enzymatic antioxidant activity is contributed by the free thiol group of glutathione Winterbourn, Additionally, glutathione also detoxifies oxidants and electrophiles via enzymatic reactions which involve glutathione reductase, glutathione peroxidase, and glutathione-S transferase Farhat et al. Glutathione plays a crucial role in regulating redox state of the cell, specifically via modulation of the proper tertiary structure of proteins through thiol-disulfide exchange concomitantly with glutaredoxin and protein disulfide isomerases Ye et al.

Besides antioxidant properties, glutathione also involves hormones metabolisms such as estrogens, leukotrienes, and prostaglandins and signal transduction for transcription Rotar et al. Alteration of glutathione concentration has been linked to adverse health impacts such as dysregulation of cell proliferation, transcription of detoxification enzymes, and apoptosis Aquilano et al. Glutathione is categorized as a non-essential nutrient for humans, as it can be synthesized in the body from the amino acids such as L-glutamic acid, L-cysteine, and glycine Lu S.

The structure of glutathione consists of gamma peptide bond linked to a tripeptide between the amine group of cysteine and carboxyl group of the glutamate side-chain Figure 3. The carboxyl group of cysteine is linked to a glycine by peptide bond Gu et al. Sulfur is the second chalcogen after oxygen in the periodic table with a vacant 3d orbital. Figure 3. Molecular structures of glutathione, polyphenols flavonoid, flavonol, flavone, flavanone, anthocyanidin, and isoflavones , and beta-carotene.

Homeostasis of intracellular glutathione is not solely regulated by de novo synthesis, but it also by several factors including cellular export, utilization, and recycling Lu S. This redox cycle is recognized as the glutathione cycle which comprises of glutathione, together with other redox-related enzymes acts as the first defense against overproduction of harmful ROS in addition to repairing ROS-induced damage Schieber and Chandel, There are three groups of enzymes involve in the glutathione cycle, namely glutathione reductase, glutathione oxidase, and glutathione peroxidase Reczek and Chandel, By serving as an electron donor, glutathione reduces disulfide bonds formed between proteins and cytoplasm to cysteines.

In this process, two molecules of glutathione are converted to an oxidized form, either glutathione oxidase or glutathione peroxidase. Once oxidized, glutathione reductase is capable to regenerate glutathione from glutathione disulfide via NADPH-dependent process Reczek and Chandel, Further, glutathione tends to react with cysteine residues in proteins through the formation of mixed disulfides. Yet, these unstable molecules can easily be reverted to a normal state by glutathione S-transferase Carvalho et al.

Alternatively, the cells export glutathione disulfide to the extracellular medium to restore redox imbalance Heidari et al. Indeed, the de novo synthesis of glutathione is essential for adaptive response toward oxidative stress. Many toxic by-products produced from normal cellular metabolism processes can be detoxified by glutathione.

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A toxic compound, methylglyoxal, generated from the glycolytic process is implicated in ROS production Chan et al. Glutathione detoxifies methylglyoxal by serving as a cofactor of enzyme glyoxalases Nahar et al. Besides scavenging ROS, glutathione is also involved in protecting against reactive nitrogen species-mediated damage Cassia et al. The modulation of glutathione metabolism is a useful adjuvant therapy for many diseases such as cardiovascular diseases, diabetes, and brain disorders.

A study analyzed of cardiovascular disease cases involving individuals revealed that glutathione can affect the risk of cardiovascular diseases Shimizu et al. The data showed that the total plasmic glutathione content is lower in cardiovascular diseases patients cerebral infarction and cerebral hemorrhage compared to healthy subjects Shimizu et al. Further, glutathione peroxidase was found to be inversely correlated with cardiovascular disease risk Espinola-Klein et al. Although research has demonstrated a negative association between glutathione peroxidase and cardiovascular disease risk, not all data demonstrated such a link.

Mills et al. Maintaining a normal level of glutathione is important for diabetic patients. Intake of glutathione in patients with type 2 diabetes mellitus increase the platelet constitutive nitric oxide synthase activity and reduce plasminogen activator inhibitor-1 PAI-1; Martina et al. PAI-1 is an inhibitor of fibrinolysis which increases the risk of thrombosis Tofler et al. This study indicates that glutathione may play a vital role in the pathophysiology of diabetes.

Further, nephropathy is a life-threatening complication suffered by both Type 1 and Type 2 diabetes patients Hadjadj et al. Diabetic nephropathy is often linked to low renal glutathione levels. Dietary supplementation with glutathione has been demonstrated to protect against pathologies associated with diabetic nephropathy Lash, In the brain, glutathione is only presented in millimolar concentrations, and thus makes this organ prone to oxidative damage compared to other tissues in the body Settineri et al.

A disruption in glutathione homeostasis could induce oxidative stress and lead to neurodegenerative diseases including Parkinson's disease Mischley et al. Parkinson's disease is a dopamine deficiency condition resulted from the destruction of dopaminergic neurons in the midbrain region Zucca et al. ROS is generated during dopamine normal metabolism Guo et al.

The decline of glutathione levels in Alzheimer's patient was associated with downregulation of glutathione homeostasis Braidy et al. Parkinson's patients suffer depletion of glutathione levels coupled with an increase of ROS within the midbrain Mischley et al. Removal of ROS by glutathione can facilitate the regulation of redox potential of the midbrain.

In a clinical condition, patients with Parkinson's disease were improved following supplementation of reduced glutathione Mischley et al. As opposed to the role of the other antioxidants, glutathione has a complex function in the cancer cells. The level of glutathione was elevated in several human cancer cells such as colon, bone marrow, breast, and lung cancers. In colon cancer cells, the mRNA and protein expressions of glutathione and enzyme involved in the metabolism of glutathione were significantly higher as compared to the normal colonic cell line Kim et al.

Similarly, the study reported by Harris et al. Interestingly, glutathione synthesis is only effective during the early stage of cancer, it is not observed in the established tumor Nguyen et al. Due to glutathione antioxidant activity, there has been a tremendous interest in the study of glutathione and its related compounds in diseases suffered by elderly.

The vital role played by glutathione is nonetheless worth study in-depth in order to understand the pathophysiology pathway underlying in age-related diseases. Polyphenols also known as polyhydroxyphenols are characterized by the multiples of phenol structural units Nascimento-Souza et al. The numbers and characteristics of these phenol structures contribute to the unique features of polyphenol compound in term of chemical, physical, and biological Scalbert and Williamson, In brief, polyphenols are secondary metabolites Kabera et al.

Polyphenols also affect the flavor, color, and odor which contribute to the sensory perception of the food Ju et al. Of all polyphenolic compounds, the flavonoid is the most common polyphenol classes Nascimento-Souza et al. Flavonoids are comprised of the most studied group of polyphenol. The basic structure of flavonoid is a diphenylpropane skeleton, which composed of two benzene rings rings A and B connected by three-carbon chains that form a closed pyran ring heterocyclic ring containing oxygen, ring C; Das et al.

The structure of flavonoids is denoted as C6-C3-C6 Das et al. Flavonoids are subdivided into different subgroups flavonols, flavones, flavanonols, flavanones, catechins, anthocyanins, and chalcones; Figure 3 based on the carbon and the degree of unsaturation Gonzales et al. The physiological function of the flavonoids is depends on the structural characteristics as well as the pattern of glycosylation and hydroxylation of the three rings Gonzales et al.

There are around 6, flavonoids that form the colorful pigments of herbs, fruits, vegetables, and medicinal plants. Flavonoids are known for its broad spectrum of health-promoting effects on human and animal Panche et al. The antioxidative, antimutagenic, anti-inflammatory, and anticarcinogenic properties coupled with their abilities to regulate key cellular enzyme function have drawn attention from the pharmaceutical industry, which attempts to design the prevention and treatment of certain diseases Panche et al.

The antioxidant activities of flavonoids include 1 scavenging ROS Shokoohinia et al. The low redox potential of flavonoids enables the reduction of highly oxidized free radicals such as superoxide, alkoxyl, hydroxyl, and peroxyl radicals by proton donation Kovacic and Somanathan, Flavonoids inhibit the enzymes such as xanthine oxidase Nile et al. Therefore, the ability of flavonoids in chelating trace metals plays an important role in the oxygen metabolism Catapano et al. Flavonoids have beneficial biochemical and antioxidant effects in relation to several oxidative stress-induced diseases in elderly for instance cancer Chien et al.

Several flavonoids such as naringin Ahmad et al. Flavonoids were found to negatively correlate with several types of cancer in human based on numerous studies.


In woman aged 75 years old and above, high total flavonoids intake reduced the risk of cancer mortality compared to those with low total flavonoids consumption Ivey et al. A decrease in breast cancer risk among postmenopausal women was found to be associated with flavonoids intake specifically, flavanols, flavones, flavonols, and lignans Fink et al.

While for colorectal cancer, He and Sun found that 2 flavonoid subclasses, namely procyanidins and isoflavones exert preventive effects toward the risk of colorectal cancer. However, there was limited evidence of the lower risk of colorectal cancer via flavonoid consumption He and Sun, ; Grosso et al. Many studies demonstrated that a flavonoid-rich diet is related to a lower risk of cardiovascular disease. Flavonoids prevent cardiovascular disease via a few mechanisms such as antioxidant, anti-inflammatory, antiplatelet, and increasing high-density lipoprotein HDL level Nunes et al.

A study found that the intake of soy isoflavone reduces the risk of cardiovascular disease due to chronic inflammation. Studies have shown the ability of isoflavone to alleviate hypertension via modulation of vasodilation. Isoflavone improves brachial artery flow through interaction with the estrogen-response element of genes related to endothelial NO synthase Ramdath et al. Compared to those who consume placebo, supplementation of isoflavone in postmenopausal women for 6 months improved endothelial vasodilation and lowered the cellular adhesion molecules such as E-selectin, ICAM-1, and vascular cell adhesion protein 1 Colacurci et al.

A recent study by Grosso et al. These data suggest that dietary flavonoids as natural cardiovascular protectors. Diabetes mellitus is suffered by elderly and can lead to severe complication such as diabetic peripheral neuropathy. A study reported by Ganugapati et al. Quercetin is another bioflavonoid available in red wine and many plants. Intake of quercetin was shown a neuroprotective effect in the diabetic rats against high glucose-induced injury on the glia and myenteric neurons at the cecum.

In another study, Kwak et al. Many studies revealed that flavonoids from cocoa Swinton et al. Emerging evidence has suggested that flavonoids protect against neural injuries and degeneration in Alzheimer's disease and dementia. Further, increased cerebral brain blood flow by flavonoids may also enhance cognition Grassi et al. Together, the evidence showed that flavonoids have outstanding potential to block the initiation and progression of age-related diseases and pathologies. High intake of flavonoids should be included in the dietary of elderly via supplementation or flavonoid-rich containing food.

Table 1 summarizes some of the clinical trials of antioxidants in preventing age-related diseases and the failure of clinical trials involving antioxidants. Table 1. Clinical studies conducted in several antioxidants and their effects in age-related diseases. The only animals known to produce carotenoids are spider mite Tetranychus urticae and the red pea aphid Acyrthosiphon pisum , which have acquired the ability to synthesize the carotenoids from fungi via gene transfer Du et al.

In general, carotenoids absorb wavelengths between and nanometers, thus the compounds appear in yellow, orange, or red color Gauger et al. Currently, there are more than carotenoids that have been discovered to perform a range of functions Paliwal et al. Carotenoids are divided into two classes, namely carotenes and xanthophylls based on their chemistry constitute Yaroshevich et al. Most carotenoids are tetraterpenoids, derive from 8 isoprene molecules and contain 40 carbon atoms Harrison and Curley, All carotenoids have polyisoprenoid structure comprised of a long-conjugated chain adjacent toward the multiple double bonds with near symmetry on the central double bond.

This basic acyclic structure can be altered by oxygen-rich functional groups Gabriel et al. The electron-rich conjugated system of the polyene structure allows the carotenoids function as efficient radical scavengers by quenching the singlet oxygen and trapping peroxyl radicals Nishino et al. Carotenoids are not only exerted antioxidant properties, they are also facilitated in the modulation of cell cycle, apoptosis, and cell differentiation Gloria et al.

Carotenoids are highly lipophilic molecules that reside intracellularly to shield the membrane from oxidative stress Fiedor and Burda, Carotenoids are well-recognized as an eye-sight protecting agent. Individual with vitamin A deficiency may acquire a permanent blindness known as xerophthalmia West, Carotenoids such as lutein and zeaxanthin which is localized in the eye macula may protect against harmful blue and near-ultraviolet light Ma et al. Age-related macular degeneration AMD is the main cause of blindness suffered by people aged 75 years and above in developed countries.

AMD accounts for nearly 8. Research findings have predicted that the percentage of patients with AMD tends to double between and Eisenhauer et al. Oxidative stress within the retina has been implicated in the pathogenesis of AMD. Compared to the other cells, non-proliferative postmitotic cells such as photoreceptors and retinal pigment epithelium cells are extremely sensitive to oxidative damage due to the absence of DNA damage detection systems Blasiak et al. Further, the macular environment can also stimulate ROS generation. The macula is continuously exposed to high oxidative stress from the high partial pressure of choriocapillaris and oxidized polyunsaturated fatty acids PUFAs of the retinal outer segments Schmidt-Erfurth, Compared to those who never or rarely consume carotenoids, individuals who consume a carotenoid-rich diet have a relatively low risk of age-related macular degeneration Eisenhauer et al.

The antioxidant and anti-inflammatory properties of lutein are not limited to only eyes but it also decreases the risk of cardiovascular diseases Maria et al. Previous studies have demonstrated that intake of lutein was inversely correlated with oxidized LDL, suggesting that lutein may protect against the development of atherosclerosis Kishimoto et al. Increased plasma lutein levels also decrease baseline blood pressure, which subsequently reduces the risk of hypertension Perrone et al.

The data from the previous study further demonstrated that lutein shields the myocardium from ischemia injury by reducing apoptosis and oxidative stress Maria et al. A meta-analysis conducted by Leermakers et al. However, Bjelakovic et al. Another common carotenoid, lycopene is widely accepted as a potent antioxidant and reduces the risk of certain cancers such as lung Aizawa et al.

Lycopene suppresses the progression of carcinogenesis via its anti-inflammatory actions Carini et al. A follow-up study conducted from to involving 49, of males revealed that higher lycopene intake can prevent prostate cancer Zu et al. The preventive role of lycopene toward cancer is more likely due to its antioxidant effect. Yet, the anticancer ability of lycopene is mediated through several mechanisms including modulation of cell cycle arrest, apoptosis, growth factor signaling, and phase II detoxifying enzymes Aizawa et al.

Bone loss in the elderly leads to osteoporosis. Studies in both human and animal models have suggested that carotenoids could reduce the risk of osteoporosis Rao and Rao, Carotenoids have shown a positive impact on bone cells. Another study conducted by Hayhoe et al. Carotenoids have been demonstrated to prevent many degenerative diseases induced by an oxidative stress such as Alzheimer's disease and dementia Mohammadzadeh Honarvar et al. The implication of carotenoids toward the pathophysiology of Alzheimer's disease and dementia has been extensively studied in both in vitro and in vivo models Masisi et al.

Carotenoids delay disease progression via multiple pathways such as suppress oxidative stress Wang et al. Beta-carotene is an Alzheimer's disease antagonist due to its high binding energy toward Alzheimer's disease-related receptors P53 kinase receptor and histone deacetylase; Krishnaraj et al. Data from the human studies revealed that higher plasma levels of lutein reduced the risk of Alzheimer's disease and dementia Feart et al. High level of carotenoids lutein, zeaxanthin, and lycopene in serum has also been associated with a lower risk of Alzheimer's disease mortality Min and Min, The health-promoting values of carotenoids revealed the link between carotenoid-rich diets and age-related illnesses.

The intake of raw tomato Solanum lycopersicum shields against cancers esophagus, stomach, colon, and rectum Berman et al. Based on the evidence, dietary intakes of certain antioxidants such as carotenoids can reduce the risk of age-related diseases. The effects of multiple carotenoids in diet offer healthy aging in term of nutrition. Minerals are naturally occurring elements with universal structures and definite chemical formulas. Dietary minerals are the chemical substances required by all living organisms. Adequate intake of each dietary mineral is essential to maintain physical health.

Minerals play a crucial role in bone formation, hormones synthesis, regulation of heartbeat and others Morris-Naumann and Wark, Most of the minerals in human diet come from food and drinking water.

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Mineral supplements are made available in the market for those who did not meet the daily dietary intake of mineral Schwalfenberg and Genuis, Dietary minerals are categorized into two different groups, which are macrominerals and trace minerals. Macrominerals including phosphorus, calcium, sodium, magnesium, potassium, and chloride in which the body needs in larger amounts.

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  7. By contrast, trace elements are dietary minerals that are required in minimal amounts for regular cellular function, such as copper, selenium, zinc, iodine, fluoride, and iron Siddiqui et al. Most of these trace elements are the functional part of enzymes. Yet, intakes of a large amount of trace elements are noxious to both human and animals Mikulewicz et al. For instance, trivalent chromium is responsible for glucose metabolism by acting as a cofactor for insulin action.

    However, massive inhalation of hexavalent chromium, a toxic industrial pollutant is carcinogenic to both animals and human. Chromium exposure has been associated with various cancers in lung, central nervous system, and gastrointestinal tract Bhattacharya et al. Minerals such as copper, magnesium, zinc, and selenium possess antioxidant properties. Zinc functions as an antioxidant in the body via regulation of glutathione metabolism Stelmach et al. The non-enzymatic antioxidants taking part in the first line of defense belong to preventive antioxidants.

    These antioxidants inhibit the formation of new reactive species by interacting with the transition metal ions Mironczuk-Chodakowska et al. Non-enzymatic antioxidants are not only involved in the first line of defense, it also involved in the second line of defense against ROS that is represented by molecules characterized by the ability to inactivate oxidants and radicals Mironczuk-Chodakowska et al. Abundance level of zinc can be found in the retina which implicated the antioxidant defense systems of the eye Ugarte et al. Zinc carries out its antioxidant functions and serves as a cofactor in enzymes such as retinol dehydrogenase, an enzyme for vitamin A cycle.

    Several studies have reported the importance of dietary zinc and age-related macular degeneration. A human study involving participants revealed that a low intake of zinc was associated with age-related macular degeneration Aoki et al. A follow-up study for 6 years including 3, participants had revealed a significant role of zinc in age-related macular degeneration Group, It has been shown that for individuals older than 55 years, zinc supplements may delay the development of age-related macular degeneration and vision loss Group, Similarly, a meta-analysis of 23, individuals demonstrated that dietary zinc blocks the progression of age-related macular degeneration and delay its progression Gorusupudi et al.

    In addition to the effects mentioned above, zinc supplementation has been reported to suppress the oxidative stress in type 2 diabetes via several mechanisms. These favorable effects could be attributed to the activity of zinc which is involved in the insulin production, secretion, and action processes by acting as a catalytic cofactor for carboxypeptidase H enzyme. Carboxypeptidase H enzyme is responsible for the conversion of proinsulin inactive form into insulin active form. Further, zinc also facilitates the phosphorylation of the insulin receptor by transporting more glucose into the cells.

    In human studies, a significant decrease in plasma thiobarbituric acid reactive substances, an oxidative stress indicator was found in patients with type 2 diabetes supplemented with zinc Anderson et al. Zinc also improved insulin sensitivity and subsequently reduces the chronic hyperglycemia in type 2 diabetes mellitus Vashum et al. Overall, zinc plays a significant role as an antioxidant nutrient that regulates metabolic control in type 2 diabetes mellitus pathophysiology.

    Notably, data from epidemiologic studies found that dietary zinc intake may reduce the risk of cancer Costello and Franklin, Zinc suppresses the proliferation of cancerous cells via several mechanisms. In cancer cells, zinc inhibits mitochondrial terminal oxidation and respiration and stimulates apoptogenesis of mitochondria Costello and Franklin, Further, zinc also prevents the migration of malignant cells through activation of intracellular signaling pathways.

    In prostate cancer cells, zinc is accumulated in the expression of the zinc uptake transporter, ZIP1 Franklin and Costello, The accumulated zinc exerts its antiproliferative activity toward the prostate cancer cells via activation of MAPKs and inhibition the growth of cancer cells Beyersmann and Haase, The downregulation of cancer cell growth by zinc indicates that the therapeutic potential of zinc to regulate the growth of cancers. Taken together, minerals are a good antioxidant which is best supplied by ingesting specific foods rich with that chemical element of interest.

    The beneficial effect of mineral on aging is worth attention. However, an overdose of mineral intake is not recommended and may cause a detrimental impact on health. Ascorbic acid, also known as vitamin C, is one of the most ubiquitous hydrosoluble antioxidants. In physiological pH conditions, vitamin C exists mainly as an ascorbate anion Camarena and Wang, Ascorbic acid has 4 —OH groups Figure 4 that can donate hydrogen to an oxidizing system.

    Ascorbic acid is a cofactor for many enzyme-catalyzed reactions such as maintaining of connective and vascular tissue's integrity, enhancing the collagen biosynthesis and iron absorption, modulating the leukocyte and hematopoiesis functioning, neuroprotection, and hydroxylation of lysine and proline May and Harrison, ; Spector and Johanson, Figure 4. Data from both animal and population-based studies have shown that a correlation between the process of aging and reducing ascorbate levels in tissues Michels and Hagen, ; Dixit et al.

    A study reported by Al-Mahdawi et al. Research evidence has demonstrated the potential protective function of ascorbate in neurodegenerative diseases Barnham et al. Ascorbate supplementation markedly improves the differentiation of midbrain derived neural stem cell against dopaminergic neurons, which is associated with the TET-mediated 5hmC generation and Jmjd3 catalyzed loss of H3K27m3 He et al.

    In this regard, these findings imply that ascorbate plays a critical role in dopaminergic neuron differentiation Camarena and Wang, In addition to the effects mentioned above, ascorbic acid has the potential to protect against cancers. High concentration of ascorbic acid induces cytotoxicity against cancer cells in vitro Vuyyuri et al.

    Consistent with the data reported by Yun et al. Although the molecular link underlying ascorbic acid and anticancer activity require further elucidation, most of the experimental studies indicate that modulating oxidative stress could play a crucial role Badgujar et al. In this regard, a key mode of action to explain this relationship is via glucose transporter type 1 GLUT1 which increases uptake of the oxidized form of ascorbic acid, dehydroascorbate and subsequently depletes glutathione Yun et al.

    Compared to those who rarely or deficient in ascorbic acid, adults who supplemented with ascorbic acid is negatively associated with adiposity Hosseini et al. Several studies have corroborated this finding and found that ascorbic acid suppressed leptin stimulation from adipocytes, particularly in insulin-secreted cells Garcia-Diaz et al. Reduction in leptin may trigger a significant reduction in hypertension Lane and Vesely, Intriguingly, leptin deficiency is linked to the early-onset of obesity, indicating that ratio of leptin to insulin is fundamental in the homeostatic balance of fat and glucose metabolism Wabitsch et al.

    In a further study focused on cardiovascular disease outcomes, Wang et al. In another meta-analysis of randomized controlled trials, Ashor et al. Importantly, cellular adhesion molecules are biochemical markers of endothelial dysfunction concomitantly with inflammation. Ascorbic acid was effective by neutralizing the oxidized-low density lipoprotein oxLDL activity, which is known as the trigger of the initiator of atherosclerosis and inflammatory process in the endothelial tissue Ellulu, Notably, some research has emerged to suggest that ascorbic acid improved endothelial function in diabetic patients Ashor et al.

    The previous study stated that patients with diabetes had relatively low amounts of circulating ascorbic acid concentrations or known as latent scurvy Price et al. Taken together, ascorbic acid may be a useful nutritional intervention for the secondary prevention of age-related diseases. Vitamin E consists a group of eight structurally associated lipophilic chromanol congeners.

    Vitamin E usually found naturally in food including four tocopherols and four tocotrienols, all of which possess saturated and three double bonds in their phytyl tails, respectively. The activity of several protein kinases, and particularly of protein kinase C PKC sub-family members can be modulated in human neuronal cells supplemented with tocopherols and tocotrienols Galli et al. A study by Khanna et al. An emerging role for tocopherols and tocotrienols in response to neuroinflammation has been demonstrated and the occurrence of its positive effects on oxidative damage and Alzheimer pathology has been proposed.

    Further, research evidence indicates that tocopherols and tocotrienols are of benefit in the stimulation of phosphoprotein phosphatase 2A PP2A , a phosphatase that plays a crucial role in tau homeostasis which is lowered in human Alzheimer's disease brains Voronkov et al. Overall, both tocopherols and tocotrienols may induce therapeutic effects via modulation of enzymatic and non-enzymatic pathways to reduce the impairment of neurological function.

    Besides its effects on neuroinflammation, previous studies have demonstrated the role of this vitamin as a factor essential for other crucial functions and the development of organs and tissues for example bones, demonstrating the enormous functional potential of tocopherols and tocotrienols. In the context of osteoporosis, tocotrienols therapy has provided significant beneficial outcomes. Gamma-tocotrienol significantly enhanced the secretion levels of osteocalcin and osteonectin, increased alkaline phosphatase activity, and upregulated collagen type I mRNA and Runx2 protein expressions in osteoblastic MC3T3-E1 cells Xu et al.

    Several studies have also reached a similar finding, in which tocopherol and tocotrienol have an antiosteoporotic activity. Muhammad et al. Findings from a population-based study mirror some of those from preclinical data obtained from an in vivo study. In addition to the effects observed on neuroinflammation and osteoporosis, a beneficial effect of tocopherols and tocotrienols supplementation has also been documented on the incidence of cardiovascular disease. The formation of macrophage foam cells is a characteristic and an early onset of atherosclerosis Yang et al.

    The aortas of cholesterol-administered rabbits have typical atherosclerotic lesions and show increased in CD36 mRNA expression. Administration of tocopherols and tocotrienols decreased cholesterol-induced atherosclerotic lesions and downregulated CD36 mRNA expression. The decrease of CD36 scavenger receptor expression, indicating the role of tocopherols and tocotrienols in the reduction of foam cell formation and atherosclerosis Ozer et al. Indeed, data from a meta-analysis included randomized-controlled trials from to , including , participants demonstrated that a diet containing tocopherols and tocotrienols is negatively linked to cardiovascular mortality risk Schwingshackl et al.

    Rossato et al. The reduction of cytokine production has also been demonstrated in animal models of inflammation and in humans with arthritis Bhattacharya et al. Overall, tocopherols and tocotrienols might be promising tools for the alleviation of oxidative stress and preventing age-related diseases.

    The potential implications of tocopherols and tocotrienols on the age-related diseases worth of further investigation in comparative randomized clinical trials. Ubiquinone UQ , also known as coenzyme Q10, is synthesized within the body cells or can also be obtained from the diet Quinzii et al. Fish and meat are the richest sources of dietary UQ Pravst et al.

    UQ also can be found in liver, kidney, beef, heart, sardines, soy oil, and peanuts. UQ is a naturally occurring vitamin-like molecule formed from redox-active benzoquinone head group conjugated to a poly-isoprenoid side chain of species-specific length 6—10 subunits Wang and Hekimi, UQ is a potent antioxidant to neutralize ROS and protect the inner lining of the lymph, blood vessels, and endothelium Motohashi et al. However, UQ levels reduce with advancing age and subsequently develop to some of the symptoms related to aging.

    The reduction of UQ levels during aging could be one of the predominant factors to develop chronic diseases Motohashi et al. Figure 5. Molecular structures of ubiquinone and organosulfur compounds S- allylcysteine, diallyl sulfide, diallyl disulfide, and diallyl trisulfide.

    Compared to other tissue, heart muscle utilizes more energy and usually has the highest UQ level and a relatively sensitive to UQ deficiency. The weakening of the heart muscle may lead to the swelling of the lower legs and feet, lung, liver, and the lining of the intestine Motohashi et al. Heart failure is characterized by a loss of contractile function caused by energy depletion in mitochondria linked to a low level of UQ. It was evident that UQ oral supplementation alleviated the endothelial dysfunction and the cardiac contractility Peres et al.

    Congestive heart failure is associated with a low level of UQ in tissues and blood. An animal study showed that UQ reduces the lipid hydroperoxides concentration in atherosclerotic lesions and the atherosclerotic lesions in the aorta Littarru and Tiano, Frei et al. Previous study found that the lipid peroxidation rate of human low-density lipoprotein LDL is inhibited concomitantly with UQH2 administration following exposure to peroxyl radicals Stocker et al.

    Likewise, data from a population-based study reported that patients with heart failure who consume UQ had a lower risk of mortality in addition to increasing exercise capacity Lei and Liu, UQ supplementation may also improve the quality of life in patients with congestive heart failure Oleck and Ventura, In addition to the effects mentioned above, a beneficial role of UQ supplementation has also been observed on the incidence of type 2 diabetes. Data from randomized controlled clinical trials have demonstrated that supplementation with UQ can significantly improve vascular dysfunction and decrease the glycemic response Mantle, From the study reviewed, it showed that UQ reduces oxidative stress and did not lead to any adverse effects.

    A study by Raygan et al. UQ plays a central role in the cellular dysfunction of Parkinson's disease patients Zhu et al. UQ levels were relatively low in the plasma, platelet-mitochondria, and blood of Parkinson's disease patients Sohmiya et al. Treatment with UQ reduced the cellular pathophysiological alterations linked to a mitochondrial dysfunction in Parkinson's disease patients Cooper et al.

    WOA1 - Micronutrient formulations for concussive head injuries - Google Patents

    Shults et al. Overall, lipid profiles, systemic inflammation, and insulin sensitivity were improved after administration of UQ and thus may provide a useful approach for the alleviation of age-related diseases. To protect mitochondrial oxidative damage, several mitochondrial-targeted antioxidants have been developed and a great potential mitochondrial-targeted antioxidant is MitoQ. Much information indicates that the ubiquinol moiety of MitoQ can react with superoxide and protect against peroxynitrite Liu et al.

    Animal studies have revealed that MitoQ protects against oxidative damage such as hypertension Pak et al. A study by Junior et al. Emerging research evidence indicates that MitoQ may possess beneficial effects on tubular injury Dare et al. Despite the beneficial effects of MitoQ on neurodegenerative disease was reported in vivo , not all studies demonstrated such a link. Data from the double-blind clinical trial of Parkinson disease patients failed to show any benefit in delaying the pathologic process of Parkinson disease during 12 months administration of MitoQ Snow et al.

    Overall, these findings demonstrated that MitoQ might be promising tools for pathological changes of mitochondrial oxidative damage associated with age-related diseases. Organosulfur compounds mainly present in vegetable species belonging to Allium genus and Brassicaceae family. Functional organosulfur compounds in Allium have been used in folk and traditional medicine in the last centuries Petropoulos et al.

    Sulfur compounds from Allium play a critical role in defense Nwachukwu et al. Sulfur is the compound of Fe-S clusters and several amino acids for enzymes activity Gruhlke and Slusarenko, Organosulfur compounds Figure 5 usually present in onion, garlic, and Chinese chive, which may benefit a certain group of the population because they appear to combat oxidative stress associated age-related diseases such as cardiovascular disease Lu et al.

    Several studies reported by Arreola et al. Data reported by Liu K. In a further study focused on inflammation outcomes, Liu K. The data demonstrated that diallyl sulfide showed the most suppressive effect on NO production and iNOS expression, suggesting that it was linked to the number of sulfur atoms of the organosulfur compounds. Organosulfur compounds not only modulate glutathione and phase II enzymes and inhibit inflammatory mediators, they also inhibit several cancers. Previous findings suggest that a diet supplemented with diallyl trisulfide, diallyl disulfide, and diallyl sulfide suppressed cancers induced by chemical carcinogens Huang J.

    In support of this, an animal study has demonstrated that oral administration of diallyl trisulfide at a dosage of 1—2 mg per day for 13 weeks significantly suppressed the progression of invasive carcinoma and multiplicity of pulmonary metastasis Singh et al. Several studies have also reached a similar finding, in which diallyl trisulfide and diallyl sulfide have an antiproliferative activity against bladder, pancreatic, and skin cancers Ma H. Collectively, regular consumption of food rich in organosulfur compounds may become a safe and successful strategy to alleviate oxidative stress and improve age-related chronic disease conditions.

    Despite antioxidants pharmacological properties were reported in vitro and in vivo , some of the clinical expectations of antioxidant-based therapies have been frequently disappointed. Low stability and the poor aqueous solubility limit the therapeutic potential of antioxidants.

    Cognitive Function In Depth

    This complication has hampered the quantity of antioxidant absorbed, which severely limit its bioavailability. Nanotechnology has emerged as a promising drug delivery system Dehghanizade et al. Nanotechnology has received a great attention as it can resolve problems linked to the conventional therapeutic agents, such as lack of targeting capability, poor water solubility, systemic toxicity, and nonspecific distribution Sreelakshmi et al. Hence, the application of nanotechnology could enhance the efficacy and improve their bioavailability by increasing solubility, enhancing plasma half-life, preventing degradation in the intestinal environment, and elevating permeation in the small intestine Hu et al.

    Despite a large part of literature exploring on the accumulation and the origin of ROS, current antioxidant-based therapies lack of specificity for dysfunctional tissues, cells, and organelles, and thus may not reach an effective concentration at the target site of pathologic oxidative stress. Additionally, antioxidants target huge amounts of reactive oxygen intermediates and are unable to modulate specific intermediate in the oxidative reaction, and subsequently leading several therapeutic strategies are unfocused.

    Mitochondria-targeted antioxidants hold great promising and may serve as a useful approach for the alleviation of age-related diseases. However, further investigations are warranted to improve the potency of antioxidant-based therapies. Moreover, it is worth to underline the need of exploring the role of iron-mediated oxidative damage through Fenton reaction to further ascertain the contribution of mitochondrial dysfunction and iron accumulation to the progression and pathologic development of age-related diseases. Data available on the interaction between chelating agents and antioxidants are limited, and further investigation may lead to the development of potent therapeutic agents and novel biomarkers targeting specific disease tissues, additionally to identify the downstream mediators of oxidative pathways.

    Oxidative stress caused by an overproduction of ROS, mainly due to an imbalance of oxidative to reducing species. It has been suggested that excessive ROS production may lead to an upregulation of oncogene gene and the formation of mutagen compounds, which trigger proatherogenic activity and inflammation. Yet, longevity is not merely embedded in the genes; in fact, food rich in antioxidants may play an essential role in the immune system, production of cellular energy, as well as scavenge the ROS.

    The broad spectrum of processes in which the antioxidant molecules are involved suggests that a protective role of antioxidants in the pathogenesis of age-related diseases. Thus, an antioxidant can be a useful approach for healthspan extension as well as lifespan extension. Despite antioxidant may not serve as drugs, they hold great promising and indirectly provide leads in future use to combat age-related diseases.

    The potential implication of antioxidant in relation to age-related diseases to replace conventional therapies could be significant and is warranted to be elucidated in long-term clinical trials. MN edited the manuscript. HS wrote the manuscript. All authors read and approved the final manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Abbas, G. Aging mechanisms: linking oxidative stress, obesity and inflammation. Matrix Sci. Medica 1, 30— Afkhami-Ardekani, M.

    Effects of garlic on serum lipids and blood glucose of type 2 diabetic patients. Ahmad, S. Aizawa, K. Tobacco carcinogen induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation. Cancer , — Akash, M. Spice plant Allium cepa: Dietary supplement for treatment of type 2 diabetes mellitus.

    Al-Mahdawi, S. The emerging role of 5-hydroxymethylcytosine in neurodegenerative diseases. Frontiers Neurosci. Springer , — Google Scholar. Alvarez, L. The zinc-metallothionein redox system in human retina and RPE. Acta Ophthalmologica S Ambrogini, P. Ambrosio, G. Evidence that mitochondrial respiration is a source of potentially toxic oxygen free radicals in intact rabbit hearts subjected to ischemia and reflow. PubMed Abstract Google Scholar. Anderson, R. Potential antioxidant effects of zinc and chromium supplementation in people with type 2 diabetes mellitus.

    Micronutrients for the Prevention of Age-Related Diseases and Brain Dysfunction

    Antoniades, C. Vascular endothelium and inflammatory process, in patients with combined Type 2 diabetes mellitus and coronary atherosclerosis: the effects of vitamin C. Aoki, A. Aquilano, K. Glutathione: new roles in redox signaling for an old antioxidant. Frontiers Pharmacol. Arreola, R. Immunomodulation and anti-inflammatory effects of garlic compounds.

    Ashor, A. Effect of vitamin C on endothelial function in health and disease: a systematic review and meta-analysis of randomised controlled trials. Atherosclerosis , 9— Attwood, E. A survey of the haematological, nutritional and biochemical state of the rural elderly with particular reference to vitamin C. Age Ageing 7, 46— Badgujar, P. Fipronil induced oxidative stress in kidney and brain of mice: protective effect of vitamin E and vitamin C. Pesticide Biochem. Baker, D. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders.

    Nature , — Barnham, K. Neurodegenerative diseases and oxidative stress. Drug Discov. Bellizzi, M. Vitamin E and coronary heart disease: the European paradox. Berman, J. Nutritionally important carotenoids as consumer products. Beyersmann, D. Functions of zinc in signaling, proliferation and differentiation of mammalian cells. Biometals 14, — Bhattacharya, I. Efficacy of vitamin E in knee osteoarthritis management of North Indian geriatric population.

    Adv Musculoskeletal Disease 4, 11— Bhattacharya, P. Nutritional aspects of essential trace elements in oral health and disease: an extensive review. Scientifica Biagi, E. The aging gut microbiota: new perspectives. Ageing Res Rev. Biswas, S. Does the interdependence between oxidative stress and inflammation explain the antioxidant paradox? Bjelakovic, G. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases.

    Cochrane Database Syst. Blaser, H. Trends Cell Biol. Blasiak, J. Oxidative stress, hypoxia, and autophagy in the neovascular processes of age-related macular degeneration. BioMed Res. Block, M. BMC Neurosci. Blumberg, J. The alpha-tocopherol, beta-carotene cancer prevention study in Finland. Bozaykut, P. Free Radic. Braidy, N. Neuroprotective effects of citrus fruit-derived flavonoids, nobiletin and tangeretin in alzheimer's and parkinson's disease. CNS Neurol. Drug Targets 16, — Therapeutic approaches to modulating glutathione levels as a pharmacological strategy in Alzheimer's disease.

    Alzheimer Res. Brewer, M. Natural antioxidants: sources, compounds, mechanisms of action, and potential applications. Food Sci.