Aging Essay, Research Paper

Aging: The Different Theories of How it Works

This report outlines the main theories of how the process of aging works. Since researchers have not discovered a universally-accepted theory of aging, the theories discussed are potential explanations of how we age. The likelihood of each hypothesis is considered roughly equal. The different theories discussed focus on the workings of different parts of the body, from the molecular level of DNA mutations and replication, to the organism level of becoming ?worn out.?

Aging is a very complex and gradual process, and its ongoing operation is present to some degree in all individuals. It is a journey to the maturity, as well as to the degeneration of the body. Because aging affects every part of the body, many different steps are involved and various types of reactions occur. Changes in DNA take place, which can and often do affect the way the body functions; harmful genes are sometimes activated, and necessary ones deactivated. A decrease in important body proteins like hormones and certain types of body cells is almost inevitable. These, among many, are characteristic changes that take place in our bodies as time moves on and aging continues.

At present, a universal explanation for how we age or why we age does not exist, but there are many theories to explain this puzzle, and they are supported by continuous research. In this report, some of the how theories of aging will be examined. Among them are theories concerning spontaneous mutations, damage from free radicals, the clock gene, cellular aging, a weakened immune system, wear and tear, and hormonal and neuroendocrinous changes.

Spontaneous Mutations

The spontaneous mutations theory, also known as the somatic mutation hypothesis, states that the crucial events that cause aging are mutations. These are changes in a cell=s DNA, which are passed on to daughter cells during mitosis. Since genes on DNA code for specific proteins, mutated genes may produce defective proteins, which do not work properly. Many proteins can be affected, such as enzymes, proteins comprising muscle tissue, and a recently discovered type of protein called transcription factors, which bind to DNA and regulate the individual activities of genes themselves.

Physical mutagens are substances that increase the chance of mutation and include such physical phenomena as x-rays and radioactivity from radium. The atomic bombs dropped on Hiroshima and Nagasaki in Japan are examples of physical mutagens that caused an increase in the number of cases of leukemia. Certain chemicals and radiation cause mutations to occur in DNA by giving off high energy particles. These particles collide with the DNA and knock off atoms of the DNA randomly, damaging it. DNA consists of sequences of four possible nitrogenous bases: adenine, guanine, cytosine, and thymine, paired so that adenine always pairs with thymine, and guanine always pairs with cytosine. As cells repair the damaged DNA, a different DNA base is often substituted. This base-substitution is known as a point mutation and can cause the production of a defective or damaged protein.

Apart from being caused by radiation or chemicals, mutations also occur spontaneously but at lower rates. Physicist Leo Szilard and biochemist Denham Harmon proposed that because most mutations are harmful, the more spontaneous mutations that arise, the more abnormalities that arise as defective proteins are produced. These could ultimately kill an individual (Ricklefs and Finch, 1995, 20). Although it has been proven that many proteins undergo alterations during aging, the spontaneous mutations theory is not the cause (Ricklefs and Finch, 1995, 21). It has, however, been proven that DNA is chemically altered during aging. Modifications in DNA bases, called I-spots, have been found to increase in number during aging. Besides I-spots, another modified base known as 8-hydroxyguanine, the DNA base guanine with an added OH group, has also been found to increase during aging. It is unclear how changes such as these arise, but similar changes seem to be caused be exposure to mutation-causing chemicals, some of which are found in tobacco smoke (Ricklefs and Finch, 1995, 21).

Another factor supporting the spontaneous mutations theory may lie in the temporal occurrence of genetic mutations. Certain cancers and abnormal growths seem to appear more frequently as the process of aging continues. Two tumour suppressor genes called p16 and p53 are responsible for slowing cell proliferation, and therefore keep certain cells from becoming cancerous. However, if they become mutated, they do not carry out their function properly so cells with these mutations begin to grow and divide quickly, causing cancer and other growths (Ricklefs and Finch, 1995, 22).

Werner?s syndrome is a disorder that significantly accelerates the aging process starting at around 20 years of age. Molecular geneticist Gerard Schellenburg has suggested that the function of the enzyme helicase, which normally unzips the DNA double helix before replication and removes randomly occurring mutations like base substitutions, does not function properly in people afflicted with Werner?s. Therefore, the unzipping of the DNA double helix is disrupted and mutations are overlooked (Lafferty et al., 1996, 60).

Moreover, DNA occasionally loses one or more bases through the process of spontaneous deletion. This type of mutation seriously affects the mitochondria of the cell, a main source of energy within the cell. Mitochondria have their own DNA, mtDNA, which allows them to self-replicate. The mtDNA encodes for enzymes found within the mitochondria which help produce ATP, energy-storing molecules. During aging, the amount of mtDNA that possess lost segments of DNA increases. Although still unproven, it is believed that this abnormal mtDNA may cause defects in energy production. Most mtDNA deletions occur in brain, muscle, and other tissue with little cell division. By the end of one?s lifespan, certain parts of the brain consist of as much as 3% abnormal mtDNA (Ricklefs and Finch, 1995, 22).

Many characteristics of aging have been proven to develop as a result of spontaneous mutations. However, many other changes associated with aging cannot be adequately explained by this theory.

Damage from Free Radicals

A free radical is a fragment of a molecule or atom that contains at least one unpaired electron. Because unpaired electrons are unstable, an uneven electrical charge is created and the electrons attract those of other atoms or molecules to become stable and rectify the electrical imbalance. As they gain electrons from other molecules, they modify the other molecules. In this way, free radicals can damage DNA, and it is known that damaged DNA is involved in the aging process.

Free radicals can be formed when atoms collide with one another, as in the impact of x-rays or UV radiation from sunlight on living cells. They can start a chain reaction in which atoms or molecules snatch electrons from one another. This process of losing electrons is known as oxidation. Though oxidative damage can be slowed through the help of enzymes and the absorption of free radicals by antioxidants like vitamins E and C, free radicals continue to cause damage, however little, to DNA (Kronhausen et al., 1989, 78).

Cross-linking, or large-scale fusion of large cell molecules, is involved in a process responsible for the wrinkling of skin, the loss of flexibility, and rigor mortis. It occurs when little or no antioxidant activity is present to alleviate the rapid stiffening of body tissues (Kronhausen et al., 1989, 74). In older individuals, oxidized proteins in tissues have been found, and when proteins become oxidized, they usually become inactive. Lipids, which constitute a large part of the cell membrane, may also become oxidized, thereby reducing the fluidity of the cell membrane. Also, it is possible that vascular diseases are caused by oxidative damage since oxidized lipids in the blood cause arteries to thicken abnormally (Ricklefs and Finch, 1995, 24). In addition, some scientists believe that difficulty in, or slowness of movement (when we age), as well as tremors associated with the aging disease called Parkinson=s disease are caused by oxidative damage (Ricklefs and Finch, 1995, 26). The neurotransmitter dopamine, found in the brain is damaged by free radicals produced by enzymes during the removal of dopamine from the synapses of the brain. During aging, damaged mtDNA is thought to collect in parts of the brain with high dopamine concentrations and is thought to be caused indirectly by the presence of these free radicals (Ricklefs and Finch, 1995, 25). Some regions of the brain high in dopamine and damaged mtDNA happen to be the basal ganglia, the parts that aids in movement control (Ricklefs and Finch, 1995, 25).

A Free Radical Reaction with Glucose

As the body continues its normal survival processes, insulin becomes less effective in encouraging the uptake of glucose from the blood. In this way, the body develops insulin resistance. This condition is similar to the more serious type of diabetes called maturity-onset diabetes, or type II diabetes. If diabetes was left untreated, the excess glucose in the bloodstream would not be taken into cells because of insulin resistance. Instead, the excess glucose in the blood would react with hemoglobin in a free radical reaction through a process called non-enzymatic glycation. Other proteins such as collagen and elastin, which make up the connective tissues between our brain and skull, and in our joints, can also become glycated. Once this occurs, they stop functioning properly. The result of this is that diverse compounds called advanced glycosylation end products (AGEs) become attached to proteins. The combination of AGEs with proteins forms a sticky substance that could dramatically reduce joint movement, clog arteries, and cloud tissues like the lens of the eye, leading to cataracts (Lafferty et al., 1996, 56). Once glycated proteins are formed, they can cause further damage by interacting with free radicals from other sources (Ricklefs and Finch, 1995, 26).

The Lethal Clock

A gene called clock-1, which was believed to determine an organism=s lifespan was found in small organisms and a very similar gene has also recently been found in humans (Lafferty et al., 1996, 58). Although it is uncertain whether the clock genes affect how susceptible cells are to infections, or if they control the actual aging process, it is generally agreed upon that these genes have something to do, either directly or indirectly, with aging (Allis et al., 1996, 64).

It has been proposed in the clock theory that the demise of brain cells, of which we lose thousands each day, is due to regular, programmed cellular destruction, and not to random *accidents= (Keeton, 1992, 50). As cells divide, the number of divisions that they undergo is monitored and kept track of. After a certain number of divisions, the clock genes are triggered and may produce proteins responsible for cell destruction (Keeton, 1992, 50).

Cellular Aging

In 1961, a discovery made by Leonard Hayflick showed that normal, diploid cells from such continually Areplaced@ parts of the body as skin, lungs, and bone marrow, divide a limited number of times. Although the cells stop dividing at the point just before DNA synthesis, they do not die. The longer-lived the species, the more divisions the cells undergo. As the age of an individual increases, the number of potential divisions decreases (Ricklefs and Finch, 1995, 29). This discovery was found using fibroblasts, or cells found in the connective tissues throughout the body. The cells were placed in a laboratory dish under sterile conditions and allowed to grow and divide until they filled the dish. Then some of these cells were placed in a new dish until it was filled. The number of Areplatings@ necessary until the cells no longer grew and filled the dish represented the number of cell divisions (Ricklefs and Finch, 1995, 29).

It is not known why the cells stop dividing, but these AHayflick limits@ may be caused by some genes responsible for halting the division of neurons during developmental stages (Ricklefs and Finch, 1995, 30).

This limited number of cell divisions is often thought of as cellular aging (Lafferty et al., 1996, 55), a microcosm of the process of gradual, yet, actual deceleration and deterioration of the body.

Though remarkable discoveries support the fact that cells stop dividing, this theory does not seem to recognize why cells stop dividing.

Shortened Telomeres

The theory that shortened telomeres are involved in aging is an extension of the cellular aging theory. Telomeres are highly repetitive sequences of nucleic bases found at the tips of chromosomes. They contain only a few genes. Their function is to protect chromosomes in a manner similar to Athe way a plastic cuff protects a shoelace@ (Lafferty et al., 1996, 57). After each DNA replication, telomeres on the daughter chromosomes become shorter than those on the parent strand. So after enough replications, which happens to be the Hayflick limit, the telomeres have become strikingly diminished and cell reproduction ceases. It has been theorized that at this point, genes previously protected by telomeres become revealed and produce proteins that aid in the deterioration of tissue, characteristic of the aging process (Lafferty et al., 1996, 57).

To back up this theory, researchers have found that cells that do not stop dividing, such as sperm cells and many cancer cells, do not lose telomere DNA. These cells possess an enzyme called telomerase, which maintain telomeres (Lafferty et al., 1996, 57). If this is true, then with an extra boost of telomerase, DNA may replicate many more times and in turn, we may be able to live longer. Yet instead of slowing or stopping the process of aging, this possibility may only prolong it, since it has already been accepted that damaged, not a shortage of, DNA plays a large role in aging.

The Body?s Weakened Immune System

During aging, the efficiency of the immune system declines. Normally, novel antigens, foreign molecules found on the surface of viruses and bacteria, activate the production of antibodies secreted by white blood cells, or lymphocytes, called B-cells. The antigens act to neutralize the virus or bacteria, rendering it harmless. If the novel antigens are missed by the antibodies, a Aback-up@ process comes into play. Macrophage cells safeguard the body and envelope foreign antigens that they later expose to T-cells for destruction. The pieces of virus that the macrophages pick up trigger the appropriate T-cell, which in turn replicates, producing more copies of itself. These T-cells, called memory T-cells, can recognize and destroy cells infected with the virus (Ricklefs and Finch, 1995, 35).

These two methods of protecting the body from invasion make up the primary immune response, and this is the component of the immune system that decreases in efficiency as we age. The secondary response is the body=s resistance against pathogens it has already met.

The reason for the decline in the immune system=s efficiency is that over time, we come in contact with more viral and bacterial infections so that more of our T-cells have been stimulated, converted to memory T-cells, and therefore, used. That is, they cannot be used to fight off any new viruses or bacteria that invade the body. It is possible that the total number of T-cells is set early in life. If this is so, then as we grow older, having already fought off a number of infections, we have a smaller amount of Aunemployed@ T-cells available to fight of infections that come our way (Ricklefs and Finch, 1995, 34).

In addition to the decrease in unused T-cells, antibodies used against the body=s own proteins are occasionally made. This faulty process is common in autoimmune diseases like multiple sclerosis (Ricklefs and Finch, 1995, 36).

Whereas this theory of how we age is a very practical one, it almost assumes that older people die as a result of infections, no matter how mild, because of a weakened immune systems. This is often, not so.

Wear and Tear

Just as machinery and other equipment gets worn down through use, so too do our organs and cells. It is almost inevitable that once our first cells have developed and our organs begin functioning, they also begin a very gradual deterioration through use. In fact, heavy use of our organs and bodies can accelerate this deterioration we call aging (Ricklefs and Finch, 1995, 33). In typists, for example, carpal tunnel syndrome and other degenerative problems come about faster and more commonly than in those who do not exhibit such specialized use of their fingers. On the other hand, problems can also arise from lack of use. Muscle atrophy, which is noticed in the elderly is the result of a lack of muscle use (Ricklefs and Finch, 1995, 33). So assuming that moderate use of our bodies is healthy and will not promote any degenerative problems seems safe. Still, even regular, moderate use of one=s body, however long it can prevent certain problems, does not hold the body=s performance at the same level for very long. As aging continues, a loss of elasticity from the connective tissues in various parts of the body is experienced, and muscle performance, among other things, is reduced (Ricklefs and Finch, 1995, 33).

In 1900, the life expectancy in the U.S. was 47 years. It may be thought that this was the length of time the human body could withstand *wear and tear= before it Abroke down.@ Today, the life expectancy in the U.S. is about 76 years because of modern technology, and many beneficial medical breakthroughs (Lafferty et al., 1996, 55). This large increase in life expectancies does not necessarily mean that human bodies can endure heavier use, or more wear and tear, but that it takes longer for our bodies to deteriorate now than it did in previous years.

At the molecular level, lipofuscins, or aging pigments, appear with increasing frequency in non-dividing cells. Because they contain oxidized lipids, it has been theorized that they are products of oxidative chemical reactions such as those involving free radicals (Ricklefs and Finch, 1995, 34).

Modifications in Hormonal and Neuroendocrine Systems

The pituitary, ovaries, and testes are part of a system of glands that secrete hormones into the blood stream and which are controlled by the brain. This system is called the neuroendocrine system. At puberty, a signal is sent by the pituitary gland to the ovaries and testes, telling them to produce more sex hormones such as estrogens and progesterone in women and androgens in men. In women, menopause, a stage in which the reproductive system is shut down, is reached. From this point in a woman=s life these hormones are no longer produced and many changes are experienced. Because some neurons can become Aaddicted@ to estrogens, the absence of these hormones induces the brain to respond in different ways, such as sending a surge of blood to the skin. This is sometimes called a Ahot flash@ (Ricklefs and Finch, 1995, 37). Unlike hot flashes, a woman may experience harmful or dangerous changes because of menopause: osteoporosis, or the loss of compact bone is accelerated because bone-mineral metabolism is dependent on estrogen. Once this condition has reached a certain stage, it reduces the ability of bones to support body weight. It also immensely elevates the risk of bone fractures. In fact, as a woman increases in age, her risk of bone fracture due to osteoporosis increases exponentially (Ricklefs and Finch, 1995, 43).

In men, the number of abnormal sperm, incidence of lower testosterone production, and incidence of impotence have been found to increase with age. Because the brain controls the pulses of testosterone, it can be said that some of these changes arise because of different signals in the brain (Ricklefs and Finch, 1995, 44).

The hormonal and neuroendocrine theory collects evidence mostly from a female way of life, yet both men and women experience the aging process and many of the same characteristics that go with it.

The knowledge that the process of aging is very complex can be deduced from the simple fact that there are many entirely different, yet plausible, theories of how aging works. In fact, the possibility that several of these theories are connected, or play a combined part in aging is not far fetched. Yet because the process of aging is so multifarious, just how humans complete or even begin the transition from youth to old age remains a mystery to some extent. However, with new evidence and proof supporting some of these hypotheses, opportunities for a healthier, longer life may arise.

References

Allis, S. et al.., 1996. Older, Longer. Time Magazine. Fall 1996:60-64

Keeton, K. 1992. Longevity: the Science of Staying Young. Penguin Books USA Inc., New York, NY.

Kronhausen, E. et al. 1989. Formula for Life. William Morrow and Company, Inc., New York, NY.

Lafferty, E. et al., 1996. Can We Stay Young?. Time Magazine.

25/11/96:53-62

Ricklefs, R.E. and Finch, C.E. 1995. Aging; A Natural History. W.H. Freeman and Company, New York, NY.

Bibliography

Aging, The Concise Encyclopedia of Science and Technology, 1978 ed.

Allis, S. et al.., 1996. Older, Longer. Time Magazine. Fall 1996:60-64

Keeton, K. Longevity: the Science of Staying Young. New York, NY: Penguin Books USA Inc., 1992.

Kronhausen, E. et al., Formula for Life. New York, NY: William Morrow and Company Inc., 1989.

Lafferty, E. et al., 1996. Can We Stay Young?. Time Magazine.

25/11/96:53-62

Ricklefs, R.E. and Finch, C.E. Aging; a Natural History. New York, NY: W.H. Freeman and Company, 1995.

Segall, P. and Kahn, C. Living Longer, Growing Younger. Toronto, ON: Random House of Canada Limited, 1989. New York, NY: Random House Inc., 1989.