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Anti-Aging: How to Liver Longer & Healthier - Part I - Definition, Theories of Aging & Types of Free Radicals & Antioxidants

By:   |   Jul 08, 2018   |   Views: 22   |   Comments: 0


Human aging is a biological process, no one can stop, but delay it. It is possible that one person has a physiological younger than his or her biological if one engages in healthy living life style and eating healthily by increasing the intake of good healthy food such as whole grain, fruits, vegetables, beans and legumes, etc. and reducing the consumption of harmful foods, such as saturated fat, trans fat, artificial ingredients, etc.

Theories of aging

What cause aging? The question that has been asked throughout the human history, but it doesn't seem to get any answer but raises many more unanswered questions. While many theories try to answer the question by related aging to tear and wear of the body, others deal with how the organs and systems in the body develop and deteriorate overtime, etc.

1. Somatic mutation theory

In this theory, aging is due to our inherited genes that come directly from our parents. Since the conception occurred, our body cells continue to divide and replication themselves. Since the division and replication are a life long precess at some point, for what ever reason, if cells division and replication can process incorrectly, leading to mutation of incorrect copy of DNA. Although the cause of this incorrect process are unknown, but researchers found that exposures to toxins, radiation or ultraviolet light, artificial ingredients, unhealthy life style, etc. can increase the risk of cells mutation and the cells copied incorrectly can mutate themselves, leading to accumulation of incorrect gene cells that trigger a chain reaction of an auto-catalytic nature in producing more and more fincorrect gene cell, until it finally is brought under controlled, this processes can lead to aging. As an organism, the immune system tries to destroy or scavenger these mutated genes but at some points, it is over whelming, leading chronic age related diseases.

2. Error catastrophe theory

The error catastrophe of aging was originally proposed by Leslie Orgel in 1963. Our body immune system helps to maintain the structural integrity of DNA not only for cell survival but also for the transfer of correct genetic information to the daughter cells. Error catastrophe indicated that alterations DNA and the incorrect placement of amino acids in protein synthesis could result in a progressive degradation aging as a result of these abnormal protein are no longer functioning as chemical passengers or signallers.

3. Protein glycosylation
Protein glycosylation is a result of chemical reaction of glucose with varies proteins, including enzyme, elastin and collagen in the blood. The cross linked protein glycosylation leads to cell to cell adhesion causing stiffness and rigidity of individual cells, reducing the cells function in taking nutrients and expelling waste.
If the cross link protein glycosylation occurs in the elastin and collagen, it will cause brittle skin, causing aging, but it happens in the organs it will be more serious and sometimes life threatening.

4. The neuroendocrine theory
First proposed by Professor Vladimir Dilman and Ward Dean MD, this theory postulates on wear and tear of the neuroendocrine system. In neuroendocrine system, the master pituitary gland secrets hormones to direct other glands in secreting their hormones and works conjunction with the hypothalamus glands form a command post in the nervous system in closely direct the function of most of the body functions.
but as we age, the hypothalamus loses its ability as a hormone regulator as its receptors of which uptake other gland hormones become less sensitive to them, including sex hormones, DHEA, serotonin, melatonin, etc.
As for cortisol, a hormone secreted by the adrenal glands due to stress, is produced with abundance as we age.

5. Immune system decline theory
As we age, our immune system is weakening that cause us become vulnerable to the dangerous pathogens, including microbial and viral invasion. Within the immune system, the thymus glands which play an important role in helping formation of the immune system scavenger that reduces the function of immune system further that allow irregular cell growth cause of aging spot, tumors, cancer, infection, inflammation and onset of chronic illness.

6. Genetic programming theory
Genetic programming theory proposes that aging is programmed as the cells cycle in our body are also genetic program since their inception. the explanation is that all the cells are undergoing certain time in division over the a said amount of time before dying, leading to conclusion that people with the long live genetic program live longer than others who do not.
The theory also emphasizes the genetic diseases as a result of genetic programming diminished life span, regardless external and internal influence.
Further refinement of the programmed senescence theory was developed by Bernard Strehler, who proposed that as cells are program to perform specific functions within the organism that cause them to lose some of the ability to duplicate their genetic information, leading to aging.

7. Hayflick limit
The Hayflick limit (or Hayflick Phenomena) theory discovered by Leonard Hayflick and a biologist in 1966. In vitro study, the number of times fibroblast diploid cells will divide before it stops. The discover is conferring a major hypothesis if the cell division can prolong in a infinite matter without conditions which cause damage of the cells, then organism can liver forever.
Stem cells
Since stem cells can continue to regenerate new cells for the entire lifespan of the organism, without limit, thus constituting a notable exception to the Hayflick limit theory.
Cancer cells
Cancer cell in biological aspect, have found a way around the limit by becoming a group of immortalized cells produced from cell division that have no limit as to how many times this immortalized cell division might take place.

8. The telomerase theory
The tolomerrase theory is a continuation of support to the Hayflick limit (or Hayflick Phenomena) theory involved in telomeres and telomerase. Telomeres are the structure at the end of the chromosome. As each time the cell divides, its telomeres is shortened, at certain length, the cell stops division and goes into senescence.
The experiment shows, the cell senescence can be reversed by controlling the genes of telomerase autocatalytic nature, which in turn, promotes the forever cell division capacity

9. The free radical theory
A free radical is any atom or molecule that has a single unpaired electron in an outer shell and highly reactive to react with other cell, which in turn, causes oxidative damage to the enzymes, other protein, unsaturated fatty acid, phospho-lipids, DNA and RNA, etc., leading to aging of the organisms, as a result of widespread damage due to set of a chain reaction auto-catalytically after attacking the lipid bilayers of the cell walls.

10. Other theories
a. Rate of living and lifespan
Rate of living is defined that a bigger organism, the longer it lives with human is one of the exception due to its slower rate of metabolism and lower rate of free radical activity, leading to low levels of age lipid pigment, resulting in longer life span. Experiment show that there 100,000 free radicals hit everyday in rat, comparing 10, 000 in human.
b. Caloric restriction
Caloric restriction hypothesis suggested in a study of young rat showed that if a rat is put into restricted diet with given of necessary nutrients, it lives longer than those were allowed to eat freely. With the result also the same in the old rat, the theory also suggest eating less may cause less toxins in the body that affects the immune system and reduces the risk of hormone change, leading to free radicals cause of aging.
c. Age spots
Age spots are mainly composed of lipofuscin and lipopigment caused by reaction of free radical and peroxidation, leading to the formation of age spot, as a result of oxygen species interact with autophagocytic degradation occurring inside the lysosomes.
d. Protein oxidation
Protein oxidation cay affect protein function in normal and pathological processes as a result of postranslation protein being alter by reduce oxygen species (ROS) cause of damage to enzyme, leading to dysfunction of its role resulting in aging.
e. Fast track of aging
The theory suggest that there are many of diseases and syndromes of which can contribute to faster track to aging
* Hutchison-Gilford syndrome
It is an extremely rare genetic condition wherein symptoms resembling aspects of aging are manifested at an early age. Those born with progeria typically live to thirteen years, although many have been known to live into their late teens and early twenties and rare individuals may even reach their forties due to genes mutation.
*Werner syndrome
It is Adult progeria, an disorder causes the appearance of premature aging. The syndrome does not develop until they reach puberty is caused by autosomal recessive disorder due to alter gene on chromosome 8.
f. Altered genes
Alter genes are the work of Friedman and Johnson 1988 " .... the effect of elevated expression of SIR2 in yeast appears to be conserved in C. elegans (Tissenbaum & Guarente 2001) and Drosophila (Rogina & Helfand 2004), and mutations in genes encoding components of the target of rapamycin (TOR) pathway also extend the lifespan in all four organisms... "
"... It was originally suspected that extension of lifespan by reduced IIS might turn out to be a worm peculiarity. This was because mutations in genes in the IIS pathway can also cause the worms to enter a type of developmental arrest (dauer), normally seen only in response to low food or crowding (Riddle & Albert 1997). Dauer larvae are long lived, and the long life of IIS mutant adult worms could therefore have been a result of re-expression in the adult of the genes that make the dauer larva long lived...."
g. Free radical connection
Free radical is any atom or molecule that has a single unpaired electron in an outer shell and accumulation of free radical damage over time can cause aging. Theory is first proposed by Denham Harman in the 1950sand in the 1970s extended the idea to implicate mitochondrial production of reactive oxygen species into the 1970s. Study showed that mutant strains of the roundworm that are more susceptible to free radicals have shortened life spans, and those with less susceptibility have longer lifespan
If free radical causes damage to the DNA repaired enzymes, it can increase the risk of unrepaired DNA damage, leading protein synthesis incorrectly. In fact, free radicals can inflict damage to all cells in body such as endocrine glands, leading to decreasing of hormone secretion, resulting in aging and Kupffer cell in liver, causing endotoxins accumulated in the blood, leading to more free radicals attacks the immune system, etc.

10. Hormone depletion
The researchers found that if an decrease or absence of the pituitary gland hormones mice is given enough amount of pituitary hormones, it lives longer than a control group of normal mice as it stimulates the production of growth and other hormones such as prolactin, adrenocorticotropic hormone, thyroid-stimulating hormone, etc.

11. etc.

Most Common Types of Free Radicals
Free radicals are atoms, molecules, or ions with unpaired electrons through chemical bonds with other atoms or molecules during a chemical reaction. They may have positive, negative or zero charge. The unpaired electrons cause radicals to be highly chemically reactive in the human body, leading to aging and cancers.
1. Hydroxyl radical (OH)
The hydroxyl radical, is the neutral form of the hydroxide ion (OH-). It is produced from the decomposition of hydroperoxides (ROOH) by the reaction of an elevation in energy level above an arbitrary baseline energy state molecular oxygen with water.
The hydroxyl radical is highly reactive and has a very short in vivo half-life of approx. 10ˆ'9 s. This makes it a very dangerous compound to the organism. Hydroxyl radical cannot be eliminated by an enzymatic reaction and can damage virtually all types of macromolecules: carbohydrates, nucleic acids (mutations), lipids (lipid peroxidation) and amino acids, that makes it a very danger compound to shorten the life span of human being.

2. Superoxide anion radical (O2-)
A superoxide anion is a compound that possesses an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge with the chemical formula O2ˆ' with one unpaired electron, leading to the generating of superoxide anion free radical.
Mutations in the gene coding for the NADPH oxidase cause immune deficiency chronic granulomatous disease, leading to extreme susceptibility to infection and pathogenesis of many diseases, including aging.

3. Singlet oxygen
Singlet oxygen is the common name used for the diamagnetic form of molecular oxygen (O2), which is less stable than the normal triplet oxygen. In biological study, species, Singlet oxygen causes oxidation of LDL cholesterol and resultant cardiovascular effects.
Since singlet oxygen with activation by light can produce severe photosensitivity of skin, leading to skin defects.

4. Hydrogen peroxide
Hydrogen peroxide (H2O2) is the simplest peroxide, a clear liquid, slightly more viscous than water, that appears colorless in dilute solution. It is considered a highly reactive oxygen species because of its strong oxidizing capacity.
Hydrogen peroxide
A study published in Nature found that hydrogen peroxide plays a role in the immune system by signalling the white blood cells to converge on the site of damage. The process leads to white blood cells did not accumulate at the site of damage, but somewhere else if the gene in production of hydrogen peroxide is altered, causing higher levels of hydrogen peroxide and white blood cells in their lungs accumulation in the lung than healthy people.

5. Lipid peroxyl free radical
Lipid peroxidation is a process in which free radicals steal electrons from the lipids in cell membranes, most often affecting polyunsaturated fatty acids, resulting in damaging to the cell membrane, which consists mainly of lipids, because of chain reaction after initial oxidating by producing even more lipid peroxyl free radicals if not bought under controlled fast enough.

6. Nitric oxide
Nitric oxide is a chemical compound with chemical formula NO. Even though, low levels of NO production are important in protecting liver from ischemic damage and contribute to proper smooth muscle contraction and growth, but its free radical and toxic nature can cause DNA damage and inflammation.

7. Alkoxyl radical
Alkoxyl radical which is an alkyl (carbon and hydrogen chain) group singular bonded to oxygen can result in cellular damage caused by oxyfluorfen, a herbicide.

8. Peroxynitrite

Peroxynitrite is the anion with the formula ONOOˆ'reacted quikly with carbon dioxide, leading to forming of carbonate and nitrogen dioxide radicals. If the two radicals do not recombine to form carbon dioxide and nitrate, they can cause peroxynitrite-related cellular damage.

9. Etc.

A. Antioxidant enzymes
Antioxidant enzymes are chemical substances found in plants that can protect the body from damage of free radicals by terminating the chain reactions by removing free radical intermediates and inhibiting other oxidation reactions.
1. Catalase
Catalase is an enzyme, found in most living organisms that are exposed to oxygen helped to converse hydrogen peroxide (free radicals) to water and oxygen as a rate of 40 million molecules of hydrogen peroxide to water and oxygen each second, using either an iron or manganese cofactor.

2. Glutathione peroxidase
The function of glutathione peroxidase is to protect the organism from oxidative damage by reducing lipid hydroperoxides, an oxidation of lipid cell membranes which can easily break and form free radicals of the form RO and converting free hydrogen peroxide to oxygen and water.

3. Glutathione reductase
Glutathione reductase, an enzyme reduces pair of sulfur atoms glutathione to the a organosulfur compound form of antioxidant (consisting of three amino acids joined by peptide bonds) which helps to prevent damage of important cellular components caused by free radicals and peroxides.

4. Super oxide dismutase (both Cu-Zn and Mn)
Super oxide dismutase is an important antioxidant defense in nearly all cells exposed to oxygen by converting superoxide into oxygen and hydrogen peroxide depending on the metal cofactor such as both Cu-Zn and Mn.

B. Metals binding proteins
1. Ceruloplasmin
Ceruloplasmin, the major copper-carrying protein in the blood plays a role in iron metabolism. It prevents the oxidation that leads to the forming of oxidation from Fe2+ (ferrous iron) into Fe3+ (ferric iron) by exhibiting a copper-dependent oxidase activity, causing mutations in the ceruloplasmin gene cause of iron overload in the brain, liver, pancreas, and retina.

2. Ferritin
Ferritin, the protein produced by almost all living organisms, acts as a component to fight against iron deficiency and iron overload, keep in a soluble and non-toxic form and transport it to the body needs, including organs. It enhances the immune system in the presence of an infection or cancer and prevent the infectious agent attempts to bind iron to become free radicals by migrating from the plasma to within cells.

3. Lactoferrin
Lactoferrin, a multifunctional protein of the transferrin family, is one of the components of the immune system of the body by fighting against foreign invasion of bacteria and virus and lipid oxidation by inhibiting oxidation in a concentration-dependent manner even at concentrations beyond its capacity.

4. Metallotheinein
Metallotheinein, a family of cysteine-rich, low molecular weight proteins helps to bind both physiological heavy metals through the organosulfur compound of its cysteine residues. It also captures harmful superoxide and hydroxyl radicals by liberating the metal ions which were bound to cysteine.

5. Transferrin
Transferrin is a glycoprotein that binds iron very tightly but reversibly. It enhance the immune system in fighting against infection, inflammation by creating an environment low in free iron that impedes bacteria survival and cell oxidation.

6. Hemoglobin
Hemoglobin is the protein molecule in red blood cells that enhances the carrying of oxygen from the lungs to the body's tissues and return CO2 from the tissues to the lungs.
During oxidate stress, the cell membrane is protected by intraerythrocytic hemoglobin from the forming of free radical.

7. Myoglobin
Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates. The binding of oxygen by myoglobin is unaffected by the oxidation or chain of oxidative reaction in the surrounding tissue, thus reducing the free radicals damage caused by oxidate stress.

8. Etc.

C. Common antioxidants (scavengers)
1. Bilirubin
Bilirubin is a prosthetic group which helps to break down molecules into smaller units in releasing energy, excreted in bile and urine. It is a cellular antioxidant, by reverting to biliverdin, a green tetrapyrrolic bile pigment, once again when oxidized that inhibits the effects of mutagens.

2. Carotenoids
Carotenoids are organic pigments, occurring in the chloroplasts and chromoplasts of plants and some other photosynthetic organisms like algae, some bacteria.
a. Beta-carotene
Beta-Carotene, an organic compound and classified as a terpenoid, a strongly-coloured red-orange pigment in plants and fruits.
a.1. It is not toxic and stored in liver for the production of vitamin A that inhibits cancer cell in experiment. Beta-carotene also neutralize singlet oxygen before giving rise of free radicals which can damage of DNA, leading to improper cell DNA replication, causing cancers.
a.2. Cell communication
Researcher found that beta-carotene enhances the communication between cell can reduce the risk of cancer by making cells division more reliable.
a.3. Immune system
Beta-carotene promotes the immune system in identifying the foreign invasion such as virus and bacteria by increasing the quality of MHC2 protein in maintaining optimal function of white cells.
a.4. Polyunsaturated fat
Researchers found that beta-carotene also inhibits the oxidation of polyunsaturated fat and lipoprotein in the blood that reduce the risk of plaques build up onto the arterial walls, causing heart diseases and stroke.
a.5. There are more benefits of beta-carotene.

b. Alpha-carotene
Alpha-carotene, one of the most abundant carotenoids in the North American diet, is a form of carotene with a β-ring at one end and an ε-ring at the other. It is the second most common form of carotene which not only protects cells from the damaging effects of free radicals and enhances the immune system in fighting against bacteria and virus invasion, but also stimulates the communication between cells thus preventing irregular cell growth cause of cancers.

c. Beta-cryptoxanthin
Beta cryptoxanthin is an antioxidant, beside helping to prevent free radical damage to cells and DNA but also stimulates the repair of oxidative damage to DNA. it enhances the immune function infighting against inflammatory cause of polyarthritis, and irregular cell growth cause of cancer due to oxidation.

d. Lutein
Lutein is one of the most popular North American carotenoids. It is found in greens like kale and spinach as well as the yolk of eggs. Lutein is also found in the human eye. Getting enough lutein in your diet may help to fight off age related macular degeneration, an eye condition.
Researcher has shown that people who do not have enough lutein in their diet will not have enough lutein present in the muscular part of the eye. This is what likely leads to age related macular degeneration that can result in blindness.

e. Zeaxanthin
Zeaxanthin, a most common carotenoid alcohols found in nature, is one of the two primary xanthophyll carotenoids contained within the retina of the eye. Intake of foods provide zeaxanthin with lower incidence of age-related macular degeneration as a result of its function of reducing the risk oxidative stress.

f. Lycopene
Lycopene is a red carotene of the carotenoid group that can be found in tomatoes, watermelons, and grapefruits. This powerful antioxidant is believed to be a powerful fighter of prostate cancer. Lycopene has many anti-aging capabilities as well as one of the most powerful antioxidants in the carotenoid group.

3. Flavonoids
Flavonoids also known as Vitamin P and citrinare a yellow pigments having a structure similar to that of flavones occurred in varies plants. it has been in human history for over thousands of years and discovered by A. S. Szent-Gyorgi in 1930. As he used vitamin C and flavonoids to heal the breakage of capillaries, which caused swelling and obstruction of blood flow. Most plants have more than one group or type act as predominate.
Flavonoids process a property as antioxidants. it helps to neutralize many of reactive oxygen species (ROS), including singlet oxygen, hydroxyl and superoxide radicals.
Although nitric oxide is considered a free radical produced by immune system to destroy bacteria and cancerous cells, but when it is over produced, it causes the production peroxynitrite which may attack protein, lipid and DNA, Flavonoids inhibit NO production of peroxynitrite due to reduction of enzyme expression.
a. Quercetin
Quercetinis a plant-derived flavonoid found in fruits, vegetables, leaves and grains and studies show that quercetin may have anti-inflammatory and antioxidant properties as a antioxidant, quercetin scavenges free radicals, which damage cell membranes, cause mutation of cells with tampering DNA.

b. Rutin
Rutin is a citrus flavonoid glycoside found in buckwheat and glycoside of the flavonoid quercetin. It inhibits platelet aggregation, decreases the capillary permeability, makes blood thinner and improves circulation. As an antioxidant, it can reduce the cytotoxicity of oxidized LDL cholesterol caused by free radical that lowers the risk of heart diseases.

c. Catechin
Catechin is a natural phenol antioxidant plant and natural anti-bacterial substance. Study showed catechin as good free radical scavenging power inhibits ROS production, thus it can be useful to the development of alimentary strategies to prevent OTA-induced cytotoxicity in human.

d. Etc.

4. Uric acids
Uric acids may have a potential therapeutic role as an antioxidant becuase of its function of inducing oxidative stress, either through creating reactive oxygen species or inhibiting antioxidant systems.
High uric acid can cause arthritis, cardiovascular disease, diabetes, Metabolic syndrome, kidney stones, etc.

5. Thiols (R-SH)
Chemically, thiol, a organosulfur compound has strong odours resembling that of garlic. They are used as odourants to assist in the detection of natural gas. It presents in the amino acid cysseine which helps to the functioning of enzyme regulation, cell signaling, protein trafficking and control of gene expression. As a sulfide residue, thiol plays an important role in cell function of reversal oxidation by interacting with GSSG resulting in formation of intramucolar protein disulfide and GSG.

6. Coenzyme Q10
Coenzyme Q10 is discovered by Dr. Karl Folfers in 1957, beside promotes the chemical reaction, often by speeding it up or allowing it to proceed under less stringent conditions, it also enhances energy production by promoting the process of the production of ATP then serving as fuel for the cells and acts an antioxidant to prevent the generation of free radicals during this process.

7. Vitamin A, C, E. D.
a. Vitamin A
Vitamin A occurs in the form retinol and is best known for its function in maintaining the health of cell membrane, hair, skin, bone, teeth and eyes. It also plays an important role as an antioxidant as it scavenges free radicals in the lining of the mouth and lungs; prevents its depletion in fighting the increased free radicals activity by radiation; boosts immune system in controlling of free radicals; prevents oxidation of LDL and enhances the productions of insulin pancreas.

b. Vitamin C
Vitamin C beside plays an important role in formation and maintenance of body tissues, it as an antioxidant and water soluble vitamin, vitamin C can be easily carry in blood, operate in much of the part of body. By restoring vitamin E, it helps to fight against forming of free radicals. By enhancing the immune system, it promotes against the microbial and viral and irregular cell growth causes of infection and inflammation.
Vitamin C also is a scavenger in inhibiting pollution cause of oxidation.

c. Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols discovered by researchers Herbert Evans and Katherine Bishop. It beside is important in protecting muscle weakness, repair damage tissues, lower blood pressue and inducing blood clooting in healing wound, etc, it also is one of powerful antioxidant, by moving into the fatty medium to prevent lipid peroxidation, resulting in lessening the risk of chain reactions by curtailing them before they can starts.

d. Vitamin D
Reseacher found that vitamin D, a group of fat-soluble secosteroids is also a membrane antioxidant, with the ability to inhibit iron-dependent lipid peroxidation in liposomes compared to cholesterol.

Others antioxidants
1. Copper
Copper, an essential trace element is essential for the absorption and utilization of iron and distributed widely in the body and occurs in liver, muscle and bone. Deficiency of copper can often cause the anemia-like symptoms. However, ingesting too much of it can lead to generator of free radicals that can damage DNA .

1.1. Antimicrobial and viral Copper enhances the immune function in fighting against foreign invasion, such as bacteria and virus, thus reducing the risk of infection and imflammation by utilizing the absorption of oxygen and production of energy within cells.

1.2. Antioxidant enzyme Superoxide dismutase (SOD)
Copper is vital for the making of antioxidant enzyme, superoxide dismutase, an important antioxidant defense in nearly all cells exposed to oxygen by protecting the cell membranes from free radicals. In fact, it outcompetes damaging reactions of superoxide, thus protecting the cell from superoxide toxicity. Research found in experiment, Mice lacking SOD1(Superoxide dismutase [Cu-Zn]) develop a wide range of pathologies, including hepatocellular carcinoma, an acceleration of age-related muscle mass loss,an earlier incidence of cataracts and a reduced lifespan. Mice lacking SOD3(Extracellular superoxide dismutase [Cu-Zn] ) do not show any obvious defects and exhibit a normal lifespan, though they are more sensitive to hyperoxic injury and mice lacking SOD2 (Superoxide dismutase 2, mitochondrial) die before birth. The above result enhances the importance of the presence of copper in improving life span and living health in human as well.

2. glutathione (GSH)
Glutathione (GSH), a polypeptide of glycine, cysteine, and glutamic acid that occurs widely in plant and animal tissues beside is best known for its role in enhancing the immune system in protect our body from bacteria and virus, it also is an antioxidant that helps to prevent damage caused by oxidation of cellular components such as free radicals and peroxides by converting to its oxidized form glutathione disulfide (GSSG), leading to generation of antioxidant enzymes, glutathione peroxidases and peroxiredoxins of which reduces the risk of oxidative DNA damage and subsequently the individual's risk of cancer susceptibility.

Deficiency of Glutathione (GSH) causes hemolytic anemia, progressive degeneration of the spinal cord, disorders of the peripheral nervous system, diseases of the skeletal muscles, etc.

Intake with vitamin D increases glutathione levels in the brain and appears to be a catalyst for glutathione production.

3. Alpha lipoic acid
Alpha Lipoic Acid (ALA) is an organosulfur compound derived from octanoic acid. It has been used as over-the-counter nutritional supplements to treat a number of diseases and conditions. Alpha Lipoic Acid (ALA) not only is importance in preventing the symptoms of vitamin C and vitamin E deficiency, but also generates dihydrolipoic acid by reduction of antioxidant radicals.

Recent study showed that Alpha lipoic acid may have a therapeutic and anti-aging effects due to modulation of signal transduction and gene transcription, which improve the antioxidant status of the cell.

4. Manganese

Manganese is an essential trace nutrient in all forms of life. It is well known for its role in helping the body to maintain healthy skin and bone structure, but also acts as cofactors for a number of enzymes in higher organisms, where they are essential in detoxification of superoxide (O2ˆ', with one unpaired electron) free radicals.

Although, superoxide is biologically quite toxic and deployed by the immune system to kill invading microorganisms by utilizing the enzyme NADPH oxidase. Any Mutations in the gene coding for the NADPH oxidases cause an immunodeficiency syndrome.

Superoxide may contribute to aging via the oxidative damage that it inflicts on cells. In larger amounts, manganese can be poisoning to neurological damage which is sometimes irreversible.

5. Selenium
Selenium , a trace mineral plays an important and indirect role as an antioxidant by fulfilling its function as a necessary constituent of glutathione peroxidase and in production of glutathione, that inhibits the damage caused by oxidation of free radical hydrogen peroxide, leading to aging effects.

5.1. Heart health
Since it works synergism with vitamin E, it promotes heart health. Study showed by increasing the levels of glutathion, selenium decreases the risk of LDL oxidation, thus lowering the risk of plaque building up on the arterial walls, blood pressure and heart diseases.

5.2. Immune system
Selenium enhances the immune function that fighting off the attack of AID virus by promoting the function of interleukin 2 and T-cells.

5.3. Cancer
Study showed that levels pf selenium in blood test is associated with high rate of cancer, including skin cancer.

6. Zinc
Zinc is an essential mineral that is naturally present in some foods. The ability of zinc in inhibiting oxidative processes has been recognized for many years. Chronic effects, zinc enhances the introduction of metallothioneins, which help to capture the superoxide and hydroxyl radicals due to cysteine residues, resulting in lessening the risk of oxidative stress.
Over acute effects, zinc may reduce the postischemic injury to a variety of tissues and organs by involving the antagonism of copper reactivity as a result from its antioxidant functions.

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