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Comprehensive study of aging and free radicals
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From time immemorial, aging, though being a normal physiological phenomenon experienced by the human body, has always been an enigma to the mankind.Concepts of Immortality , freedom from aging and ways to regain the qualities of youth or Rejuvenation have been the unsolved mysteries that has haunted the human race and most sought after for centuries by countless scholars , philosophers , academicians , scientists, researchers from all societies who dedicated their lives into the research to solve this very mystery. Efforts to devise methods, practices and drugs to prevent aging and be free from the jaws of imminent death have always been futile.Alchemists from all over the globe, for centuries worked towards the preparation of “Elixir of life” to overcome aging and death. But their research and studies did prove that noble metals like gold, silver, Platinum had many beneficial properties for the human physiology. Aging in humans refers to a multidimensional process of physical, psychological and social change. Aging is an accumulation of damage to macromolecules , cells, tissues and organs resulting in a continuous progression of detrimental changes that occur in the human physiology or body that ultimately culminates in death. Aging is characterized by the declining ability to respond to stress , increasing homeostatic imbalance and increased risk of age associated diseases.Death is the ultimate imminent consequence of aging. The process of senescence is complex, and may derive from a variety of different mechanisms and exist for a variety of different reasons. Much of the illness , disability, and chronic diseases associated with aging process are avoidable through known preventive measures. Rejuvenation is the procedure for reversing the aging process, thus regaining youth. Free radicals are known to be the major cause for aging and age related diseases in the human body. All the major research and studies are aimed at these free radicals and their effects. Anti-Aging Medicines Much of anti-aging medicine has been concerned with the use of nutritional supplements to extend lifespan. The idea that anti-oxidant supplements such as Vitamin C , Vitamin E , Lipolic acid and N-acetylcysteine , might extend human life, stems from the free radical theory of aging . After years of experimenting with anti-oxidants, Dr. Denham Harman was able to establish that they can extend mean lifespan , but he was unable to demonstrate an effect on maximum lifespan. Antioxidant nutrients or supplementation with the minerals such as Platinum, selenium , chromium and zinc are more effective and have extended maximum lifespan. Key measures to reduce the rate or progress of aging and onset of age related diseases include calorie restriction , practicing a healthy lifestyle (e.g., regular physical activity, eating healthy foods, avoiding tobacco use, living in pollutant free ecology and the use of early detection practices (e.g., screening for breast, cervical, colorectal cancer, diabetes and its complications, depression ). Scientific advances & recent research and studies into this subject with various present day state of art modern technology proved that platinum with its anti-oxygen radical action and anti-aging properties, does have an edge over other noble metals and other drugs. This known fact was of no importance to mankind due to the unavailability of route of administration of Platinum into the human body.But with the advent of Nanotechnology, this issue has been solved with Platinum. Colloidal Platinum nanoparticles has been termed as the de facto messiah in the war on aging. Anti-aging efforts today have led us to Tissue engineering (using stem cells to grow new tissue), organ transplants , and artificial tissue or organs with Nanotechnology, genetic engineering, and pharmaceutical research contributing as well. Anti-aging medicines has tended to focus on age conscious consumer’s desires to look good, feel good, and live as long as possible. Anti-aging medicines has tended to focus on hormone therapies , supplements, skin care treatments (Example: Skin resurfacing, Botox treatments, Argireline based products), and plastic surgery . In the future however, rejuvenation may become reality through stem cells, biochemical repair and / or nanotechnology. Many biomedical gerontologists and life extensionists believe that future breakthroughs in tissue rejuvenation with stem cells , organs replacement (with artificial organ or Xenotransplantation and molecular repair will eliminate all aging and age related diseases, as well as, allow for the complete rejuvenation to a youthful condition. Oxygen free radicals or Reactive Oxygen Species or ROS While oxygen is essential for our survival, the relatively high reactivity of oxygen enables it to form free radicals readily. It is the unique architecture of the oxygen molecule that accounts for much of its behavior in free radical reactions which renders it particularly susceptible to one electron reductions which produce potentially highly reactive toxic derivatives , the so-called activated oxygen species. Oxygen contains two unpaired electrons and preferentially accepts single electron as consequence. A huge quantity of highly reactive free radicals is generated from oxygen in the living systems as an unavoidable consequence of aerobic respiration. The free-radical theory of aging states that organisms age because cells accumulate free radical damage over time. In general, a "free radical" is any molecule that has a single unpaired electron in an outer electron shell. Dr. Denham Harman argued that oxygen free radicals produced during normal respiration would cause cumulative damage which would eventually lead to organism’s loss of functionality, and ultimately, death. In later years, the free radical theory was expanded to not only include aging per se, but also age associated diseases. Free radical damage within cells has been linked to a range of disorders including Cancer, Arthritis, Atherosclerosis, Alzheimer’s disease and Diabetes. Free radical is also a cause of degenerative diseases. This involvement is not at all surprising as free radical chemistry is an important aspect of Phagocytosis, Inflammation and Apoptosis. Cell suicide or apoptosis, is the body's way of controlling cell death and involves free radicals and redox signaling. Redox factors play an even greater part in other forms of cell death such as Necrosis or Autoschizis. More recently, the relationship between disease and free radicals has led to the formulation of a greater generalization about the relationship between aging and free radicals. In its strong form, the hypothesis states that aging per se is a free radical process. The hypothesis holds that the degenerative diseases associated with aging generally involve free radical processes and that, cumulatively, these make you age. Platinum, a noble metal, when ingested and provided to the human body in permissible quantities, prevents free radicals from oxidizing sensitive biological molecules, reduce the formation of free radicals — will slow the aging process and prevent age related diseases. Free Radical Theory of Aging According to the Free Radical Theory, oxidative damage initiated by reactive oxygen species is a major contributor to the functional decline that is characteristic of aging. Free radicals and oxidants such as singlet oxygen that is not a free radical are commonly called reactive oxygen species (ROS) and are such highly reactive molecules that they can damage all sorts of cellular components. ROS can originate from exogenous sources such as ultraviolet (UV) and ionizing radiation or from several intracellular sources. The idea that free radicals are toxic agents was first suggested by Rebecca Gerschman and colleagues (Gerschman et al.,1954). By far, one of the most popular theories of aging is the Free radical theory of aging. This theory was first proposed by Dr. Denham Harman in 1956 (Harman 1956; Harman 1981). Postulates of Free Radical Theory Of Aging: The postulates of this theory states that aging results from an accumulation of changes caused by reactions in the body initiated by highly reactive molecules known as free radicals. There is a single basic cause of aging modified by genetic and environmental factors and that free radical reactions are involved in the aging and disease. A major premise in this theory is that free radicals / ROS and their precursors may be produced endogenously (within the body) through normal cell metabolic processes, or exogenously (outside the body) from sources such as cigarette smoking. There is an increase in the metabolic rate can also generate an explosion in the quantity of free radicals or reactive oxygen species (ROS). The oxygen free radical (super oxide radical) can be converted to even more damaging radicals by a chain reaction. Our bodies use oxygen to convert food items such as fat and sugar into energy and in this process, oxygen is converted to water, and each water molecule normally takes up four electrons. However some oxygen may escape before the conversion is complete, and this results in about 2% of the oxygen having an electron deficit. These particles are called free radicals or superoxide radicals. Due to their high reactivity, ROS can damage other molecules and cell structures. In the parallelism between cancer incidence and age, it is probably due, at least in part, to the increasing level of endogenous free radical reactions with age, coupled with the apparently progressively diminishing capacity of the immune system to eliminate the altered cells (Levin & Kidd, 1985). The oxidative damages generated and induced by free radicals (ROS) are believed to accumulate and become a major cause of aging, disease development or death (reviewed in Beckman and Ames , 1998). Fortunately, our bodies have some protective mechanisms against the harmful effects of free oxygen radicals and other even more powerful radicals such as the peroxides and hydroxyl radicals. The body's defense mechanisms against these free radicals are referred to as antioxidants. The protective mechanisms are enzymes and antioxidants. Some enzymes in the human body are capable of neutralizing the oxygen free radicals as soon as they are formed.The best known of such enzymes is called SOD / superoxide dismutase. SOD and other enzymes convert super oxide and prevent damage to lipids and to the DNA. This mechanism slows down in later part of the life. Hence, the damages may accumulate and become visible as the process of aging, when tissues lose their elasticity. When the amount of antioxidants in the body is insufficient to battle the free radicals, these ROS / reactive free oxygen radicals induce alterations in the structures of tissues and their functions, easily react with vital molecules in the body, such as DNA, causing mutations (alterations) in the sequence of genetic material which in turn could lead to the development of diseases especially cancer. Practically every type of moleculelike DNA, protein, lipid, carbohydrate, can be a target and thus be damaged by a "hit" by a highly reactive radical. Health stress and balance When the stresses of one side outweigh the beneficial inputs from the other side, then the equilibrium is lost. Minute levels of chemicals and stress can precipitate acute symptoms. Using this analogy, all forms of stress can contribute to illness. Good free Radicals These free radicals are common and important components in the biological systems and they are in fact very essential for the maintenance of life. Free radicals perform many crucial functions in our bodies in controlling the flow of blood through our arteries, to fighting infection, to keeping our brains alert and in focus. Phagocytic cells are involved in body's defense, produce and mobilize oxygen free radicals to destroy the bacteria and other cells of foreign matter which they ingest. Similar to antioxidants, some free radicals at low levels are signaling molecules - they are responsible for turning on and off genes. Some free radicals such as nitric oxide and superoxide are produced in very high amounts by immune cells to poison viruses and bacteria. Some free radicals kill cancer cells. Many cancer drugs are actually designed to increase the production of free radicals in the body. Increased levels of detrimental / Harmful Free Radicals The susceptibility of a given tissue or cell to damage from oxidated stresses is largely determined by the net balance between factors acting to promote oxidation and those that exert reduction reactions such as antioxidants. Both emotional and physical stress are likely to contribute to oxidative stress due to the tendency of the catechol hormones epinephrine , norepinephrine and cortisol to be oxidized to form free radical derivatives. Increased level of other naturally occurring chemicals and hormones in the body, break down to form free radicals and increased oxidation occurring as a result of increased metabolism within the cells of the muscles and the body. Estimated number of oxidative attacks or hits per day per human cell are about 10,000. One can gain an understanding into the magnitude of the numbers of free radical-antioxidant reactions which can occur within the body, when we multiply the number of oxidative attacks or hits per day per human cell by the trillions of cells in the body. Free radicals are also produced in significant quantities by the spontaneous oxidation of biological molecules in so-called auto-oxidation reactions which commonly involve non-enzymatic electron transfers. Free oxygen radical formation or Reactive Oxygen Species formation An atom is most stable & considered to be "ground" when every electron in the outermost shell has a complimentary electron that spins in the opposite direction. By definition, a free radical is any atom (e.g. oxygen, nitrogen) or a group of atoms with at least one unpaired electron in the outermost shell / orbit of the nucleus, and is capable of independent existence. Free oxygen radicals : Free oxygen radicals or reactive oxygen species or ROS are chemical molecular species which are extremely reactive by virtue of having unpaired valence shell electronsand easily formed when a covalent bond between entities is broken and one electron remains with each newly formed atom . It is the unpaired electron which is responsible for the instability and reactivity characteristic of free radicals. Oxidation is a process whereby a molecular species loses an electron. Reduction is a process whereby a molecular species gains an electron. Many of the cases of beneficial or detrimental effects of metals in living systems is a consequence of its tendency to stimulate an electron transfer and free radical production through its valance flexibility. During metabolism, free oxygen molecule leftovers are produced that are called Free oxygen radicals (oxygen molecules with unpaired electron). There are many types of radicals, but those of most concern in biological systems are derived from oxygen. Any free radical involving oxygen can be referred to as Reactive Oxygen Species (ROS). ROS form as a natural byproduct of the normal metabolism of oxygen and have important roles in cell signaling. Oxygen-derived radicals are generated constantly as part of normal aerobic life. They are formed in mitochondria as oxygen is reduced along the electron transport chain. Reactive oxygen species are also formed as necessary intermediates in a variety of enzymatic reactions. Oxygen centered free radicals contain two unpaired electrons in separate orbitals in the outer shell. This electronic structure makes oxygen especially susceptible to radical formation. Spreading the damage Simply by losing or gaining an electron, any non radical compound can be converted to a free radical form and thereby undergo dramatic changes in its physical properties and chemical properties. Once initiated, free radicals tend to propagate by taking part with other, usually less reactive species. When free radicals steal an electron from a surrounding compound or molecule a new free radical is formed in its place. In turn the newly formed radical then looks to return to its ground state by stealing electrons with antiparallel spins from cellular structures or molecules. Thus the chain reaction continues and can be "thousand of events long." These chain reaction compounds, generally have longer half lives and therefore extended potential for cell damage. Thus, the toxicity of a single radical species may be amplified with subsequent reactions. Oxidative Damage While ROS are produced as a normal by-product of cellular metabolism, excessive amounts can cause deleterious effects. Normally, the oxygen is reduced to produce water. However, in about 0.1-2% of electrons passing through the chain, oxygen is instead prematurely and incompletely reduced to give the superoxide radical-O2-, can inactivate specific enzymes or initiate lipid peroxidation in its HO2 form. Sequential reduction of molecular oxygen (equivalent to sequential addition of electrons) leads to formation of a group of reactive oxygen species that includes Superoxide anion / Oxygen Ions /O2 ,Peroxides / hydrogen peroxide / H2O2, Hydroxyl radical / Free Radicals / HO, Singlet oxygen / 1O2, Singlet Oxygen is an excited form of oxygen in which one of the electrons jumps to a superior orbital following absorption of energy. ROS can be both: Inorganic and Organic All these are partially reduced species of oxygen that are all toxic. However, suitable control mechanisms have evolved so that steady state concentration of potentially toxic oxygen derived free radicals are kept in check and relatively low in number under normal physiological conditions. Mechanism Of Action Reactive Oxygen Species tend to react with human cells , in turn causing a chain reaction damaging live human cells. The damage that is done by free radicals features the chemical reaction known as Oxidation . The free radical attacks on tissue that cumulates into a situation known as Oxidative stress. The electron transport chain (ETC), which is found in the inner mitochondrial membrane of the cell, utilizes oxygen to generate energy in the form of adenosine triphosphate (ATP). Oxygen acts as the terminal electron acceptor within the ETC. Anywhere from 2%-5% of the total oxygen intake during both rest and exercise have the ability to form the highly damaging superoxide radical via electron escape. During exercise oxygen consumption increases 10 to 20 fold to 35-70 ml/kg/min. In turn, electron escape from the ETC (electron transport chain) is further enhanced. Thus, when calculated, 0.6 to 3.5 ml/kg/min of the total oxygen intake during exercise has the ability to form free radicals . Electrons appear to escape from the ETC at the ubiqunone-cytochrome c level . Unfortunately, there are other ways in which hydroxyl radicals can be formed. There are several other kinds of free radicals, especially the superoxide radical, that can be produced in other ways. Sources Of Free Radicals Free radicals (oxidants) originate from two major sources that is Endogenous (within the body) and Exogenous (outside the body) Endogenous free radicals Endogenous free radicals are produced in the body by 4 different mechanisms from Mitochondria, enzymes, in the human brainand by auto-oxidation of catechols etc. Mitochondria, regions of the cell that manufacture chemical energy, produce free radicals and are the primary sites for free radical damage. Free oxygen radicals can be produced from the normal ongoing metabolism of oxygen-requiring nutrients especially from the electron transport system in the mitochondria. The intracellular powerhouses-mitochondria which produce the universal energy molecule, Adenosine triphosphate (ATP) normally consume oxygen in this process and convert it to water. Free radicals also arise in the course of normal essential internal cellular function, also called metabolism. Metabolic processes require many chemical reactions that involve free radical action. The joining of chains of amino acids (polymerization) to form proteins, or the polymerization of glucose molecules into the polysaccharide glycogen, for instance, involve free radical action. In the course of metabolism, due to incomplete reduction of the oxygen molecule, unwanted by-products like important and potentially dangerous free radicals are produced such as Superoxide anion, Hydrogen peroxide and Hydroxyl radical It has been estimated that more than 20 billion molecules of oxidants per day are produced by each cell during normal metabolism. In case of inefficient cell metabolism, the quantity of free radicals produced inside the body is beyond imagination. Bruce Ames and his colleagues, leading scientists in the field, claim that free oxygen radicals /ROS/ Oxidants generated by mitochondria are the major source of oxidative lesions that accumulate with age. Endogenous free radicals are also produced from a number of normally functioning enzymes such as Xanthine oxidase, Cytochrome P450 ,Monoamine oxidase and Nitric oxide synthase Endogenous free radicals are also produced in the brain.The production of free radicals is caused by the autoxidation of norepinephrine and dopamine . The autoxidation of catechols to quinones generates reduced forms of molecular oxygen for example superoxide and hydrogen peroxide. White blood cells such as neutrophils specialize in producing oxygen radicals, which are used in host defense to kill invading pathogens. Cells exposed to abnormal environments such as hypoxia (shortage of oxygen in the human body) or hyperoxia (above normal concentration of oxygen within the human body) generate abundant and often damaging reactive oxygen species. Exogenous sources of free radicals Air pollution Major contributors are Industrial waste ,Cigarette smoke ,Car Exhausts. Many pollutants are metabolized by enzymes of the endoplasmic reticulum system to free radical intermediaries in efforts by the system to detoxify them via the single electron reduction or single electron oxidation thereby exacerbating the localized oxidative stress. Normal diets like diets containing plant foods with large quantities of certain compounds such asPhenols ,Caffeine causes production of free radicals. Ionizing Radiation exposure UV rays,X-rays,Gamma rays Ionizing radiation is well known to generate oxygen radicals within biological systems. Interestingly, the damaging effects of radiation are higher in well oxygenated tissues than in tissues deficient in oxygen. Some molecules are sensitive to light and other radiation, becoming electronically excited as they absorb radiant energy. Radiant energy can boost one electron of a matched pair from a lower orbital to a higher orbital without changing its skin thereby creating two unfilled orbitals each with a single electron and establishing the single state.Such radiation acts by breaking linkages between atoms, leaving the radicals with their unpaired electrons to wreak their damage. An electron can emit and absorb light. When an electron absorbs light, it gets "excited”, and can move toward an outer orbit, or fly away. The outer, more loosely held electron becomes more susceptible to removal by oxidizing agents. Radiant energy can therefore make a molecule more reactive both as an electron donor and as an electron receptor. Oxygen is a molecule which can become activated photodynamically. Singlet oxygen generated in this manner is thought to mediate many of the pathogenic manifestations of photodynamic damage. The biological toxicities of x-rays and gamma rays probably are mediated photo - oxidatively. Light in ultra-violet wavelengths initiates sunburn by similar mechanisms as does over-exposure to other portions of the visible spectrum. Activation of an organic molecule by light or other radiant energy from the atmosphere can initiate singlet electron transfers to ambient oxygen thereby generating highly reactive oxygen species. Radiation can be an important generator of free radicals in biological systems. Trace metals Lead,Mercury,Iron Copper ,Cadmium The mechanisms of heavy metals toxicity through electron transfer most often involve the cross linking of the sulfhydral groups of proteins.Lead and other heavy metals can also generate free radicals directly from molecular oxygen in a two step process to produce superoxide anion. In the continued presence of the heavy metal, the superoxide anions formed can then combine with protons in the dismutation reaction generating hydrogen peroxide in the process.Heavy metals are also able to catalyze the generation of the highly toxic hydroxyl radical from superoxide anion and hydrogen peroxide. Chemical poisoning Chemical poisoning of many kinds promotes free radicals, as does excessive oxygen intake from inhaling pure oxygen. Free radicals are produced as a consequence of the metabolism of many foreign chemicals and some endogenous compounds. Wide range of drugs Body's necessity to break down a wide range of drugs to safer substances (detoxification) also involves free radical production. A number of drugs have oxidizing effects on cells and lead to production of oxygen radicals. The poisonous nature or toxicity of many chemicals and drugs is actually either due to their conversion to free radicals or to their effect in forming free radicals. Bond cision Free radicals can also be produced from relatively stable molecules by bond cision through the introduction of various energy sources. Bond cision occurs when the bond is broken to produce two free radicals. Chlorine, for example, a chlorine molecule Cl2 with the introduction of energy such as heat, x-ray, or UV, can be broken into two separate chlorine atom free radicals. Hydrogen peroxide HO2 or other hyper oxides can be degraded to free radicals by similar bond cision mechanisms. Ozone Ozone, although not a free radical, promotes the formation of free radicals and when breathed into the lungs can destroy the fluid lining of the lungs, the nasal passages and the buccal cavity / oral cavity. Asbestos Recently the development of asbestos related diseases have been related to free radical damage. The asbestos particle is an unwieldy structure with jagged edges. When it is inhaled into the airways the cells of the immune system recognise it as a foreign body and they send out specific cells called leukocytes to deal with the asbestos particles. However, the asbestos particles are too large and awkwardly shaped for the leukocytes to control but they don’t stop. One of the weapons of the immune cells is to use free radicals to destroy foreign invaders.Leukocytes become locked into a battle with the asbestos particle by injecting free radicals which paradoxically causes further damage, damage that never heals and it is critically inflamed ,ultimately leading to lung cancer or a plaque of dead tissue on the lungs. FR / Free Oxygen Radical quenchers When vitamin E quenches a free radical it becomes a weaker free radical itself. The network antioxidants will, however, donate electrons to vitamin E bringing it back to its antioxidant state. The same occurs with vitamin C & glutathione when they quench free radicals and themselves become weak free radicals. These antioxidants can be recycled back to their antioxidant by lipoic acid and vitamin C. Fat soluble vitamin E and coenzyme Q10 protect the fatty portion of the cell membrane from free radical attack while the watery portions of the cell or blood, which is primarily water, are accessible only to the water soluble antioxidants such as vitamin C and glutathione. Recent studies in nanotechnology have proved that Platinum Nanoparticles too have the better reactive oxygen species (ROS) quenching ability when compared to rest of the antioxidants. This has come into light due to the research by Prof.Miyamoto of the Department of Integrated Biosciences, Graduate school of Frontier Sciences, University of Tokyo, Japan The combination of oxidative damage by exogenously and endogenously produced free radicals has ominous consequences for body tissues. Biological Effects of ROS on Cell Metabolism Reactive Oxygen Species are generated in a number of reactions essential to life . The various effects of ROS on cell metabolism have been well documented in a variety of species. Beneficial Effects of ROS Various benefecial effects of reactive oxygen species include the rolesthey play in redox signaling or oxidative signaling, intercellular and intracellular signaling, positive effects such as the induction of host defense genes , mobilization of ion transport systems , Platelets involved in wound repair and blood homeostasis release ROS to recruit additional platelets to sites of injury (It provides a link to the adaptive immune system via the recruitment of leukocytes), Phagocytic cells generate radicals to kill invading pathogens,functions as mitogens (addition of superoxide or hydrogen peroxide to a variety of cultured cells leads to an increased rate of DNA replication and cell proliferation). Harmful Effects of ROS on Human Cells ROS causes harmful effects on human cells like aging and increased rate of aging of the human body, damages Nucleic Acids-—DNA &RNA, may cause mutations, damages proteins(oxidation of amino acids in proteins), damages Lipids(oxidations of polysaturated fatty acids). A hydrogen is abstracted from the fatty acid by hydroxyl radical, leaving a carbon-centered radical as part of the fatty acid. That radical then reacts with oxygen to yield the peroxy radical, which can then react with other fatty acids or proteins, damages all macromolecules, causes damage to cell membranes ( mitochondrial and endomembrane system), which is initiated by a process known as lipid peroxidation. A common target for peroxidation is unsaturated fatty acids present in membrane phospholipids. Peroxidation of membrane lipids causing effects like increased membrane rigidity, decreased activity of membrane-bound enzymes (Ex:Sodium Pumps), altered activity of membrane receptors, altered permeability , directly attacks membrane proteins affecting membrane function, induces lipid-lipid, lipid-protein and protein-protein crosslinking affecting membrane function,oxidatively inactivate specific enzymes by oxidation of co-factors and role in apoptosis (programmed cell death,if too much damage is caused to mitochondria of the cell. Redox signaling is also implicated in mediation of Apoptosis or programmed cell death. Harmful / Negative Effects of ROS on Human Physiology ROS causes aging, decline in memory capabilities with age, decrease in organism’s or fitness of the human body --accumulation of ROS & oxidative damage that follows is a contributor for senescence, various age related pathologies like, cancer,damage to the hereditary material (DNA), in a normal cell may cause it to become a cancer cell,increase in the likelihood of cancer and congenital disorders, neurodegenerative diseases (like Amyotrophic Lateral Sclerosis,Parkinson's Disease, Alzheimer's Disease, Lou Gehrig’s disease), Cardiovascular diseases like Atherosclerosis (Blockage of the coronary arteries by gradual thickening of the arterial walls) Ischaemic Injury ( Examples : Stroke & Acute Myocardial Infarction),Chronic degenerative diseases (like Arthritis , Rheumatoid arthritis), Cognitive Dysfunction(problems with memory, learning and the ability to concentrate , due to accumulation of oxidative damage), Hearing Impairment via Cochlear damage induced by elevated sound levels, Congenital deafness in both animals and humans, Cataracts, Diabetes Mellitus, Ischemic reperfusion injury]] ,Impairement of Defense Mechanisms & immunity),Ototoxicity due to drugs such as cisplatin, certain toxicities, Inflammation(one of the commonest kinds of bodily disorder is associated with free radical production, but the free radicals are probably the cause of the inflammation rather than the effect. However, the body actually uses free radicals to kill bacteria within the scavenging cells of the immune system, the phagocytes and when excessive numbers of phagocytes are present in an inflamed area ,the free radical load almost certainly adds to the tissue damage, making everything worse. In a heart attack, for instance, when the supply of oxygen and glucose to the heart muscle / myocardium is cut off, the real damage to the muscle is caused by the vast numbers of free radicals that are produced. Evidence for free oxygen radical involvement in aging The evidence for free radical / ROS involvement in aging is more correlative than direct. However, there is increasing evidence for the accumulation of damaged DNA over time and the modification of proteins and other molecules. It is calculated that endogenously generated oxygen free radicals make about 10,000 oxidative interactions or hits with DNA per human cell per day (Ames et al, 1993). These modifications and damage to such vital molecules would be expected to ultimately lead to deficiencies in normal functions on a massive scale that is aging. The least contested, extensive animal studies on aging clearly demonstrates that calorie restriction substantially slows the rate of aging. Furthermore, it also delays the onset of age associated diseases. Weindruch (1996) concluded that caloric restriction slows aging primarily by an associated decrease in oxygen free radicals produced by the mitochondria. Recent studies indicate that the therapeutic manipulation of reactive oxygen species or free oxygen radicals metabolism can actually extend the total life span of mice to a significant degree. This was the first time that life span has been successfully altered experimentally by treatment. Modern day studies and technological advancements in research also proves that ingestion of platinum nanoparticles provides much needed protection against the harmful effects of reactive oxygen species , delays the onset of aging, reduces the rate & progression of aging, provides protection against age associated diseases and increases the life span of an individual. Monitoring Reactive Oxygen Species It is difficult to measure or monitor the highly reactive oxygen species in vivo.Hence, most of the evidence for their roles is from the identification of products or changes induced by antioxidant chemicals--largely indirect evidence.Several newer methods, such as in vivo spin trapping, have become available to monitor oxygen free radical flux and quantitative oxidative damage. In Brain Injury:Using a combination of these newer methods collectively focused on one model, recent studies and results show that oxidative damage plays a key role in brain injury that occurs in stroke. Subtle changes, such as oxidative damage-induced loss of glutamine synthetase activity, may be a key event in stroke induced brain injury. In Carcinogenesis:Oxygen free radicals may play a key role in carcinogenesis by mediating formation of base adducts, such as 8-Oxoguanine or 8-hydroxyguanine, which can now be quantitated to very low levels. Evidence is presented that a new class of free radical blocking agents, nitrone spin-traps, may help not only to clarify if free radical events are involved, but may help prevent the development of injury in certain pathological conditions. Nanotechnology Recent advancements in nanotechnology and various studies conducted using nanotechnology on the subject of free oxygen radicals by Japanese scientists have now proved that the effective use of noble metals like Platinum in nanoparticle form or platinum nanoparticles can actually block the formation and detrimental effects of free oxygen radicals on the human body. Prevention of harmful effects of free oxygen radicals In most cases the process for prevention of the detrimental effcts of free oxygen radicals is automatically controlled and the number of free radicals does not become dangerously high. The body has, throughout the course of millions of years of evolution, become accustomed to cope with free radicals and has evolved various schemes for doing so. But with the change in environment, ecology, lifestyle ,dietary habits etc, the need for prevention and protection from free radicals is more than ever before. To prevent free radical damage to cells , the following procedures can be employed like ingestion of various forms of noble metals or minerals like platinum nanoparticles which in turn removes reactive oxygen species or free oxygen radicals, liberal supplementation of antioxidants like vitamin A, vitamin C and vitamin E(The administration of antioxidants, which eliminate radicals, to laboratory animals fails to increase maximum lifespan), minerals like selenium, nutritional antioxidant cofactors like lipoic acid, use of chelating substances like chlorella and EDTA (to remove free-radical promoting toxic heavy metals), dietary restrictions. By eliminating free radicals from cells through genetic means and dietary restriction, laboratories have extended the maximum age or life span of laboratory animals. Mechanisms for Protection Against Radicals Life on earth evolved in the presence of oxygen, and necessarily adapted by evolution of a large battery of antioxidant systems. Under normal & ideal conditions , the damaging actions of ROS are minimized by abundant protective and repair mechanisms that cells possess. The chain reaction of damage in the human body caused by free radicals can be interrupted by platinum nanoparticles and antioxidants. Many studies have demonstrated that a diet predominant in vegetables and fruits is associated with a reduced risk of several age related serious diseases (a strong implication that they are also important in slowing the aging process). Platinum Nanoparticles Nanoparticles are presently created using nanotechnology like Nanoscale iron particles, colloidal gold (already in use for treatment of arthritis etc). Now, successful mineral supplements like Platinum nanoparticles used also in edible products like Platinum chewing gum , Nanogum , Platinum Gum, Gum Platinum, Platinum Water, Platinum Mouth Essence has shown promising results in the prevention of detrimental effects of oxygen free radicals and slowing down the process of aging. Platinum nanoparticles results in increased life span of the individual, increased immunity against diseases, reduced progression of the aging, reduced incidence of age associated diseases, rejuvenation of strength and immunity in the body, decreased rate of aging. Japanese scientists led by Prof.Miyamoto of the Department of Integrated BioSciences, Graduate school of Frontier Sciences, University of Tokyo, Japan succeeded in the creation of new generation colloidal platinum nanoparticles with reactive oxygen species(ROS)-quenching ability. This is quite similar in production to that of the colloidal gold. Previous researches by Prof.Miyamoto, a pioneer in the biochemistry of cell responsiveness, into the world's celebrated, magical , healing waters like Lourdes water in France, Nordenau water in Germany,Toracote water in Mexico & Hita Tenryo-sui water in Japan, proved that traces of transition metals could effectively quench reactive oxygen radicals in the body through a kind of catalytic reaction. Platinum, a noble and transition metal, is improvised as colloidal Platinum nanoparticles. Platinum nanoparticles remain active as catalysts even after mutiple reactions. Also, platinum catalyzed reduction creates water instead of oxides, making it safer for human consumption. These improvised colloidal Platinum nanoparticles have Anti-metabolic syndrome effect, Cardiovascular anti-aging effect and Antioxidative effect. Anti-Oxidants The chemistry in vivo is complex, and antioxidants under unusual circumstances can become pro-oxidants. This is possible in conditions where iron or copper are not in their normal non-catalytic state, as occurs in some diseases (Ex: hemachromatosis, iron overload) or following trauma. Thus, there is some concern about the net benefits of antioxidant supplements. The success of supplements in delaying aging or age associated diseases is still under extensive study. It seems clear at this time that protection against oxidative damage, as it relates to aging, is provided best by a diet of vegetables and fruits, not to be replaced by pills or capsules. The observations (Sohal & Weindruch, 1996) support a major role of oxygen free radicals in aging like overexpression of antioxidative enzymes retards the age-related accrual of oxidative damage or oxidative stress and extends the maximum life-span of transgenic Drosophila melanogaster,variations in longevity among different species is inversely correlated with the rates of mitochondrial generation of the superoxide anion radical and hydrogen peroxide, restriction of caloric intake lowers steady-state levels of oxidative stress and damage, retards age-associated changes, and extends the maximum life-span in mammals. Once again, the hypothesis argues that cells are continuously under oxidative stress, the antioxidant defenses are not fully efficient and consequently, there is an accumulation of oxidative damage over time. The implications are that the rate of aging is a function of the rate of free oxygen radical production, the adequacy of antioxidative defenses and the efficiency of repair systems. Some of these antioxidant molecules are present in all lifeforms examined, from bacteria to mammals, indicating their appearance early in the history of life. Many antioxidants work by transiently becoming radicals themselves. These molecules are usually part of a larger network of cooperating antioxidants that end up regenerating the original antioxidant. For example,Vitamin E becomes a radical, but is regenerated through the activity of the antioxidants vitamin C and glutathione. Enzymatic Antioxidants Three groups of enzymes play significant roles in protecting cells from oxidant stress like Superoxide dismutases,Catalase and Glutathione peroxidase. Superoxide dismutases (SOD) are enzymes that catalyze the conversion of two superoxides into hydrogen peroxide and oxygen. The benefit here is that hydrogen peroxide is substantially less toxic than superoxide. SOD accelerates this detoxifying reaction roughly 10,000-fold over the non-catalyzed reaction. SOD are metal containing enzymes that depend on a bound manganese, copper or zinc for their antioxidant activity. In mammals, the manganese containing enzyme is most abundant in mitochondria, while the zinc or copper forms are predominant in cytoplasm. Interestingly, SOD are inducible enzymes. Exposure of bacteria or vertebrate cells to higher concentrations of oxygen results in rapid increase in the concentration of SOD. Catalase is found in peroxisomes in eucaryotic cells. It degrades hydrogen peroxide to water and oxygen, and hence finishes the detoxification reaction started by SOD. Glutathione peroxidaseis a group of enzymes, the most abundant of which contain selenium. Glutathione is the most abundant antioxidant in the network. It is produced by the body from three amino acids found in food- glutanic acid, cysteine and glycine. Glutathione is found in virtually every cell and is an important weapon against reactive oxygen species or free oxygen radicals. However,when we reach the age of 40, our production of glutathione begins to decline. It can drop by almost 20% by the time we are sixty.At any age, low levels of glutathione have been linked to premature death and disease. These enzymes, like catalase, degrade hydrogen peroxide. They also reduce organic peroxides to alcohols, providing another route for eliminating toxic oxidants. In addition to these enzymes, glutathione S-transferase, ceruloplasmin, hemoxygenase and possibly several other enzymes may participate in enzymatic control of oxygen radicals and their products. Non-enzymatic Antioxidants Three non-enzymatic antioxidants of particular importance are Vitamin E , Vitamin C or ascorbic acid , Redox active molecules like Glutathione , Carotenoids and Cancer preventive foodstuffs Vitamin E is the major lipid soluble (Lipophilicity)antioxidant, and plays a vital role in protecting membranes from oxidative damage. Its primary activity is to trap peroxy radicals in cell membranes. It is one of the most effective antioxidant and is found in vegetable oils. It stops the chain reaction by becoming a radical itself, but since it is stable, no further damage is done. Vitamin C or ascorbic acid is a water soluble antioxidant that can reduce radicals from a variety of sources. It is abundant in citrus fruits and vegetables. It also appears to participate in recycling vitamine E radicals. Interestingly, vitamin C also functions as a pro-oxidant under certain circumstances. Glutathione may well be the most important intracellular defense against damage by reactive oxygen species. It is a tripeptide (glutamyl-cysteinyl-glycine). The cysteine provides an exposed free sulphydryl group (SH) that is very reactive, providing an abundant target for radical attack.Reaction with radicals oxidizes glutathione, but the reduced form is regenerated in a redox cycle involving glutathione reductase and the electron acceptor NADPH. In addition to these "big three", there are numerous other small molecules that function as antioxidants. like Thioredoxin, Bilirubin, Uric acid and Flavonoids that occur in abundance in Rooibos.Carotenoids: Lutein & Lycopene are known strong antioxidants members of the carotenoids (yellow, orange and red pigments that occur widely in plants and animals often giving them a bright coloration). Cancer preventive foodstuffs like Polyphenols and their in vivo effectiveness of many food constituents , is still not clear. Conclusion Most scientists agree that free radical damage is a major cause of aging and all degenerative conditions. The challenge that free radicals pose is great, and protecting oneself from their effects is absolutely essential for good health. The best strategy to deal with the harmful effects of reactive oxygen species or free oxygen radicals is to limit exposure and increase your ability to apprehend them by boosting your antioxidant supplies and supplements like Platinum nanoparticles. Due to a highly compromised environment, unhealthy food, etc., people have far more free radicals and far less metabolic antioxidant enzymes (decreasing with age, nutrient deficiency and cooked food consumption) than are needed for optimum health. Our natural free radical defense systems have been severely weakened, drained, and overrun. Consuming food cooked at normal temperatures creates significant amounts free radicals and also depletes our metabolic antioxidant enzymes (taking plant enzymes with cooked foods will help significantly). Cooked whole foods from the plant kingdom, however, still do contain significant amounts of usable, naturally occurring antioxidants (including phytochemicals / phytonutrients). 
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