This report offers a comprehensive overview of the main theories on the aging process. As there is no universally accepted theory, these discussed theories serve as potential explanations for aging, with each hypothesis holding approximately equal likelihood. The focus of the explored theories ranges from DNA mutations and replication at the molecular level to wear and tear on the organism level. Aging is a gradual and complex process that affects every individual to some extent, encompassing both maturation and deterioration of the body. It involves multiple steps and reactions due to its impact on the entire body. DNA changes can occur, influencing body functions by activating harmful genes while deactivating necessary ones. With age, important body proteins such as hormones and specific types of cells tend to decrease, which is nearly unavoidable. These characteristic changes happen progressively throughout aging; however, a universal
...explanation for aging or its causes remains undetermined. Nevertheless, ongoing research supports several theories related to aging that will be examined in this report: spontaneous mutations, damage caused by free radicals, clock gene involvement, cellular aging processes, weakened immune system function, wear and tear effects on the body, as well as hormonal and neuroendocrine changes.The theory of spontaneous mutations posits that DNA mutations occurring during mitosis are responsible for aging. These mutations can result in dysfunctional proteins, affecting enzymes, muscle tissue proteins, and transcription factors. Physical mutagens like x-rays and radioactivity increase mutation likelihood by causing damage through high-energy particle collisions with DNA. The atomic bombings of Hiroshima and Nagasaki resulted in a rise in leukemia cases due to physical mutagens. DNA is composed of adenine, guanine, cytosine, and thymine bases paired s
that adenine always pairs with thymine and guanine always pairs with cytosine. When damaged DNA is repaired by cells, a different base is often substituted, known as a point mutation. This substitution can lead to defective or damaged protein production. Spontaneous mutations occur at lower rates compared to those caused by radiation or chemicals.
Physicist Leo Szilard and biochemist Denham Harmon proposed that an increase in spontaneous mutations leads to more abnormalities as defective proteins are produced ultimately potentially causing death (Ricklefs & Finch, 1995 ,20). While it has been proven that many proteins undergo changes during aging, the theory of spontaneous mutations is not the cause (Ricklefs & Finch, 1995 ,21).During the aging process, it has been demonstrated that DNA undergoes chemical changes. The number of I-spots, which are modifications in DNA bases, increases with age. Additionally, a modified base called 8-hydroxyguanine, which is guanine with an added OH group, also rises during aging. The cause of these alterations remains unclear; however, exposure to mutation-causing chemicals like those found in tobacco smoke can lead to similar changes (Ricklefs and Finch, 1995, 21).
The occurrence of genetic mutations supports the theory that spontaneous mutations contribute to aging. As the aging process continues, certain cancers and abnormal growths become more common. Tumor suppressor genes p16 and p53 play a role in impeding cell proliferation to prevent the development of cancerous cells. Nevertheless, if these genes undergo mutations, they lose their proper function and result in rapid cell growth and division leading to the formation of cancer and other growths (Ricklefs and Finch , 1995 , 22).
Werner's syndrome is a condition that accelerates the aging process starting at approximately
20 years old. Molecular geneticist Gerard Schellenburg has suggested that individuals with Werner's syndrome possess dysfunctional helicase enzymes responsible for unzipping the DNA double helix before replication as well as eliminating random mutations such as base substitutions.The disruption of DNA double helix unzipping and inadequate addressing of mutations can lead to various consequences (Lafferty et al., 1996, 60). Additionally, occasional spontaneous deletion of DNA bases can significantly affect the mitochondria, which are essential for cellular energy production. These mitochondria contain mtDNA that enables replication. The mtDNA in mitochondria plays a crucial role in producing enzymes necessary for creating ATP, a molecule that stores energy. As individuals age, there is an increase in the presence of mtDNA segments with missing DNA, potentially causing deficiencies in energy production. Most deletions of mtDNA occur in tissues such as the brain and muscles that have limited cell division capabilities. In certain brain regions towards the end of life, abnormal mtDNA can constitute up to 3% (Ricklefs and Finch, 1995, 22). Although spontaneous mutations explain many age-related changes, there are still other changes not fully accounted for by this theory. Free radicals are fragments of molecules or atoms with at least one unpaired electron that create an electrical charge imbalance due to their instability. These free radicals seek stability by attracting electrons from other atoms or molecules and thereby modifying them potentially leading to DNA damage involved in aging processes. Collisions between atoms caused by x-rays or UV radiation from sunlight hitting living cells can generate free radicals.
The following text discusses the harmful effects of free radicals and their impact on various bodily functions. Free radicals initiate a chain reaction
in which atoms or molecules take electrons from each other, leading to oxidation and oxidative damage. Enzymes and antioxidants, such as vitamins E and C, can mitigate this damage by absorbing the free radicals. However, even with assistance from these substances, DNA still experiences harm caused by free radicals (Kronhausen et al., 1989, 78). In addition to DNA damage, the fusion of cross-linking large cell molecules contributes to skin wrinkling, loss of flexibility, and rigor mortis when antioxidant activity is insufficient (Kronhausen et al., 1989, 74). The presence of oxidized proteins in inactive tissues commonly found in older individuals suggests that oxidative damage plays a role in age-related decline (Kronhausen et al., 1989). Oxidation can also affect lipids in cell membranes and reduce membrane fluidity. Furthermore, scientists propose that oxidized lipids in the blood may be responsible for vascular diseases characterized by abnormal thickening of arteries (Ricklefs and Finch, 1995, 24). Oxidative damage may also contribute to age-related movement difficulties and tremors seen in Parkinson's disease as enzyme-generated free radicals have the potential to harm dopamine—a neurotransmitter located in the brain—during its removal from brain synapses (Ricklefs and Finch ,1995 ,26). This accumulation of damaged mtDNA occurs primarily in brain regions with high dopamine levels during aging (Ricklefs and Finch ,1995 ,25).The basal ganglia, responsible for movement control (Ricklefs and Finch ,1995 ,25), is particularly affected by this phenomenon. As part of normal body processes, insulin's ability to promote glucose absorption from the bloodstream decreases over time. This can lead to a condition similar to type II diabetes or maturity-onset diabetes. If untreated, excess glucose in the blood cannot enter cells due to insulin resistance
and instead reacts with hemoglobin through non-enzymatic glycation - involving free radicals. Glycation can also impact collagen and elastin in connective tissues between the brain and skull as well as joints, compromising their functioning. These processes result in advanced glycosylation end products (AGEs) binding to proteins, forming a sticky substance that restricts joint movements, blocks arteries, and impairs tissues like the eye lens potentially causing cataracts (Lafferty et al., 1996, 56). Moreover, glycated proteins can interact with free radicals from other sources causing further harm (Ricklefs and Finch, 1995, 26). Clock-1 gene has been identified in small organisms determining lifespan; a similar gene has been found in humans (Lafferty et al., 1996, 58). The effect of clock genes on cell susceptibility to infections or direct control over aging process remains uncertain.It is widely accepted that cells are somehow involved in aging, either directly or indirectly (Allis et al., 1996, 64). According to the clock theory, brain cell decline – resulting in the loss of thousands of cells daily – is attributed to programmed cellular destruction rather than random accidents (Keeton, 1992, 50). Cells' division count is monitored as they divide. Once a certain number of divisions is reached, the clock genes are activated and may produce proteins responsible for cell destruction (Ricklefs and Finch, 1995, 29).
In 1961, Leonard Hayflick discovered that normal diploid cells in the skin, lungs, and bone marrow have a limited number of times they can divide. These cells do not die but stop dividing just before DNA synthesis. The number of divisions decreases with age. This discovery was made using fibroblasts found in connective tissues throughout the body (Ricklefs and Finch,
1995,29). The cells were grown and divided in a laboratory dish until they filled the dish. The point at which cells stop growing and filling the dish determines the number of cell divisions (Ricklefs and Finch, 1995, 29). The exact reason for this cessation in division is not yet understood but some speculate it may be linked to genes responsible for halting neuron division during development (Ricklefs and Finch, 1995, 30).The text discusses the concept of cellular aging and its relation to limited cell divisions. It mentions that this process, also known as cellular aging, involves the gradual slowing down and deterioration of the body. Although there is evidence supporting the idea that cells stop dividing, the exact cause remains partially understood. One theory suggests that shortened telomeres play a role in aging by building upon the concept of cellular aging. Telomeres are repetitive sequences found at chromosome ends that serve a protective function. After DNA replication, telomeres on daughter chromosomes gradually shorten until they reach their Hayflick limit, which marks when reproduction stops. When telomeres become too short, previously protected genes are exposed, leading to protein production that contributes to tissue deterioration and the aging process.
The text supports the notion that certain cells such as sperm cells and cancer cells possess an enzyme called telomerase which helps maintain telomere length. This enzyme has the potential to increase DNA replication and extend lifespans. However, it may not be able to halt or slow down aging due to damaged DNA being a significant factor in this process.
As individuals age, their immune system weakens resulting in reduced efficiency. B-cells normally produce antibodies upon detecting new antigens
on viruses and bacteria to neutralize these pathogensIf the antibodies do not recognize the new antigens, macrophage cells engulf them and present them to T-cells for destruction. Specific T-cells are activated by virus fragments and replicate themselves. These memory T-cells can identify and eliminate infected cells. This process forms the main immune response but becomes less effective with age. The secondary response is our body's defense mechanism against previously encountered pathogens.
The decrease in immune system efficiency is caused by increased exposure to viral and bacterial infections, which leads to stimulation and conversion of T-cells into memory T-cells. This leaves fewer available T-cells to fight new infections.
According to the text, it is suggested that early in life determines the total number of T-cells we have, resulting in a reduced pool of unused T-cells as we age. Additionally, autoimmune diseases like multiple sclerosis may occur when antibodies mistakenly target the body's own proteins.
However, infections are not always the cause of death in older individuals with weakened immune systems. Similar to machinery and equipment, our organs and cells gradually deteriorate due to use, and this aging process can be accelerated by excessive physical strain (Ricklefs and Finch, 1995, 34-36, 33).Individuals who frequently use their fingers for specialized tasks, such as typing, are more prone to developing carpal tunnel syndrome and other degenerative issues compared to those with less finger-specific tasks. However, lack of use can also lead to problems like muscle atrophy in older adults (Ricklefs and Finch, 1995, 33). Hence, it is widely accepted that moderate physical activity is beneficial for our bodies and does not contribute to degenerative issues. Regular and moderate body usage can only
delay certain problems but cannot maintain the body's performance at a consistent level over time. As we age, different parts of our body experience a loss of elasticity in connective tissues, resulting in reduced muscle performance and other effects (Ricklefs and Finch, 1995, 33). In 1900, the average life expectancy in the U.S. was believed to be limited to 47 years before experiencing bodily breakdown due to wear and tear. Thanks to advancements in technology and medicine, the life expectancy in the U.S. has significantly increased to around 76 years (Lafferty et al., 1996, 55). However, this increase does not mean that our bodies can withstand more wear and tear; it simply means that our bodies take longer to deteriorate compared to previous years. At a molecular level, lipofuscins or aging pigments increase in non-dividing cells due to oxidized lipids.According to Ricklefs and Finch (1995, 34), oxidative chemical reactions involving free radicals are suggested to be the cause of various changes in the body. The neuroendocrine system regulates hormonal secretions from glands like the pituitary gland, ovaries, and testes. During puberty, sex hormones such as estrogens and progesterone in women and androgens in men are produced triggered by the pituitary gland. Women undergo menopause which involves the cessation of hormone production resulting in different brain responses like hot flashes caused by increased blood flow to the skin (Ricklefs and Finch, 1995, 37). In addition to this, menopause leads to harmful effects such as osteoporosis due to accelerated loss of compact bone. Estrogen plays a crucial role in bone-mineral metabolism; therefore its absence increases the risk of fractures particularly among aging women (Ricklefs and Finch, 1995,
43). Similarly for men, aging is associated with an increase in abnormal sperm count, lower testosterone production, and impotence. These changes during aging are influenced by signals in the brain that control testosterone levels (Ricklefs and Finch, 1995, 44). Although primarily focused on explaining female aging characteristics,the hormonal and neuroendocrine theory applies to both menand women during their aging process since it is complex with multiple plausible theories regarding its mechanisms.It is possible that some of these theories may be interconnected or have a combined role in the process of aging. However, there is still some mystery surrounding how individuals transition from youth to old age due to the intricate and multifaceted nature of aging. Nonetheless, recent evidence supporting these theories offers opportunities for a healthier and longer life.
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