Free Radical/Oxidative - Hypothesis of Aging

Free radicals are the short-living chemicals in the body that have an unpaired electron. This means that they are very dangerous as they can behave in an erratic manner which can be very damaging to the effective functioning of the body. Most chemicals in the body have a slow reaction time and work within the speed framework of the metabolic system, which controls the speed at which the body reacts to internal events. These rules are regulated by enzymes, which are special proteins that control chemical reactions. This is not the case with free radicals; instead, free radicals cause rapid and indiscriminate reactions with whatever cellular structures happen to get in their way, thereby inflicting damage as a result.

Free radicals are an intrinsic part of most living creatures. All higher organisms create energy by oxidizing fuel (burning energy slowly), including fats and carbohydrates. They are burned in special biological microreactors that are known as mitochondria. The energy they produce is stored in the form of ATP (adenosine triphosphate), a universal biological fuel. Unfortunately, this process often creates extremely toxic products known as free radicals. Free radicals can also be produced by eternal factors as well. These include ozone, x-ray, UV rays, and so on.

DNA damage

All cellular structures are vulnerable to attack by free radicals. For example, damage to DNA caused by those aggressive chemicals can cause mutations, the cessation or disruption of gene functioning. This kind of damage can mutate the functions of the genes and result in cancer. In addition, the cell membrane is susceptible to radical attack because it is high in unsaturated fatty acids. Free radicals make the membrane of the cells brittle, rigid, and no longer water-tight, in other words, defective.

During the evolutionary process, organisms have developed a way to protect themselves from free radical attack and its harmful results. Several enzymes are part of the prevention of damage. These include; superoxide dismutase (SOD), which neutralizes superoxide radicals, catalase which neutralizes hydrogen peroxide; and glutathione peroxidase, which neutralizes lipids and other peroxides. Cells are also protected by various antioxidants, including selenium, glutathione, melatonin, vitamins C and E, among others. Despite such a strong defensive system, a few free radicals always manage to remain intact and cause cellular damage. The level of damage is higher if the antioxidant defenses are lowered due to stress, malnutrition, illness, or age.

The theory that free radicals might be responsible for the aging process was first suggested in the 50s by Dr. Denham Harman. It was considered to be an interesting hypothesis for many years. Over time, scientists gathered together a substantial body of research to support this idea. As a result, it is considered to be one of the most substantive theories on aging.

The level of damage done by free radicals seems to be proportionate in relation to the individual's metabolic rate (the rate at which calories are burned). The metabolic rate of a rat is generally seven times that of a human being. In studies, it has been shown that rats have a rate of free radical attacks 10 times greater than in humans. It was further proved that when you keep the rats in conditions of severe food deprivation that their metabolic rates fall, and their life span increases accordingly. This could be one of the reasons that humans have a longer life span than rats.

The primary site of free radical damage is the DNA found in the mitochondria. Mitochondria are small membrane-enclosed regions of a cell that produce the chemicals a cell uses for energy. Mitochondria are the "energy factory" of the cell. Every cell contains a huge set of molecules called DNA which provide chemical instructions for a cell to function. This DNA is discovered in the nucleus of the cell, which serves as the "command center" of the cell, as well as in the mitochondria. The cell automatically fixes much of the damage done to nuclear DNA. However, the DNA in the mitochondria cannot be readily fixed.

There is an increasingly large body of evidence that shows that free radical damage increases with age. One example is that a two-year-old rat has twice as many oxidative lesions (damage caused by free radicals) than a younger rat has. In addition, the concentration of mutation in the lymphocytes of older people is about 9 times greater than that found in the lymphocytes of infants. Werner syndrome and progeria are two human diseases that accelerate the aging process. Both are associated with a raised level of oxidized (radical damaged) proteins. Age-related pigments (such as lipofuscin, which in reality is a concentration of molecular waste) that build up in the cells as humans age is thought to be a product of oxidative damage to the proteins and lipids. Low levels of these pigments are not a problem, but as their concentration gets denser, then they start to stifle the cells. The buildup of waste pigments can be retarded by the use of antioxidants.

Some well-researched studies have provided the scientific community with good proof of the link between free radicals and aging. For example, it has been learned that mutations that destroy an individual gene (know as age-1) in Caenorhabditis elegans (a species of worm) will result in a 70% increase in life span. This is because worms with the mutant gene have higher levels of dismutase and catalase, the two key free radical blocking enzymes. The conclusion that could be drawn from this is that the gene destroyed by the mutations was encoded with inhibitors of the antioxidant systems that are resident in the cell. In a different study, selective breeding was used to produce Drosophila melanogaster (fruit flies) that had twice the normal lifespan. One key difference between the groups of fruit flies as that there was a higher level of superoxide dismutase in the long-life set.

Influence of radiation

An interesting conundrum arose in the early years of radiobiological study. (Radiobiology is the study of the effects of radiation on biology). It seems that low-level doses of radiation protected mammals from higher-level doses, as well as from other cellular stresses such as mutagens, toxins, and oxidants. However, it was later discovered that a short-term, low-level increase in the level of free radical formation caused by radiation could stimulate the cell's free-radical fighting systems (SOD, catalase, glutathione peroxidase), thus raising levels of resistance to future attack.

This doesn't mean that having regular X-rays in order to raise stress resistance to free radicals is a good idea. There is a much easier and healthy solution, exercise. Exercise can also act as a low to the mid-level free radical inducer. It makes sense that the more energy you burn, the more oxidative by-products you will produce. Regular moderate exercise levels will help stimulate the body's antioxidant defenses, which will remain at a raised level long after you have completed the exercise. Conversely, excessive exercise may inundate your antioxidant defenses, thereby accelerating aging. In other words, exercise is like everything else, best in done moderation.

A frequently asked question is: if one of the main agents of aging is free radical damage, why don't taking antioxidant supplements to have a greater impact on longevity. Sadly, it isn't quite that simple. Cells keep a level of equilibrium between the levels of free radicals and the level of activity in the antioxidants defense systems. This kind of protection can be challenging to maintain. Therefore, the body accepts a balance between the amount of damage it can tolerate and the level of antioxidant defense. Unfortunately, when you take antioxidants, the body reacts by lowering its internal production of antioxidants. This means that taking supplemental antioxidants does not reduce the risk of free radical damage.

Oxidative equilibrium

Scientific studies have shown that, for the most part taking supplemental antioxidants, in general, does not increase the maximal lifespan of mammals (a maximal lifespan is the longest that a species can live). Antioxidants have, however, been proved to increase the average lifespan. These results are in keeping with the theory of oxidative equilibrium. When oxidative equilibrium reaches a steady level, then the organism is more likely to live out its maximum lifespan. Supplemental antioxidants do not affect the maximum lifespan as they do not affect oxidative equilibrium. Alternatively, the more the oxidative equilibrium is upset over the course of an organism's lifespan, the shorter it is likely to live. In real life, people's antioxidant systems are often not maintained at a level of perfect equilibrium. (They are often attacked by high numbers of free radicals when exposed to toxins, cigarette smoke, stress, UV-rays, and other harsh conditions). This is one explanation why most humans do not often live to the maximal lifespan of 110-120 years. Supplemental antioxidants may help raise the average lifespan to a level closer to the maximum by producing extra free radical scavenging capacity, which reduces the disruptions of the oxidative equilibrium.

In the end, the goal is to raise the maximum lifespan; this will require the upgrading of oxidative equilibrium to a higher level. Sadly, at the moment, there is no way to do this.

Antioxidants

Another frequently asked question is: what antioxidant is the most effective? The answer is that no one antioxidant will protect you from all kinds of free radicals. As it is with most problems, different solutions work better for different problems. Therefore different antioxidants have a defensive approach against different free radicals. To have protection for all parts of the cell, you must have both water-soluble and fat-soluble antioxidants. That means that the most effective method of protecting against free radicals is to take a wide variety of antioxidants.

While taking a combination of antioxidants supplements may be an effective approach to fighting free radicals. Therefore the effects of aging, it may be easier and more pleasant to start with a healthy diet that includes a wide variety of vegetables and fruits. Various plant pigments, such as anthocyanins, carotenoids, and flavonoids, are recognized to be effective and versatile antioxidants. A diet rich in fruit and vegetables of different colors seems to give the best all-around antioxidant protection. Fresh and raw or slightly cooked fruit and vegetables are the best as cooking can deactivate the antioxidants in the ingredients. Additional supplements can be helpful, particularly in difficult conditions such as high levels of stress, illness, or a large amount of exposure to the sun.