English
中文Introduction
The complex and multifactorial nature of aging has been widely studied in recent years, during which time researchers have proposed numerous hypotheses to attempt to explain this complicated process. A plethora of theories exist which contribute to the evidence. Despite this, the fundamental factors behind the aging process have yet to be completely understood (Trosko, 2003). Semsei (2000) acknowledges that a complete overview of the theories of aging is difficult, due to the abundance of existing research, but it is widely agreed that the theories can be separated into separate categories; genetic and evolutionary program theories that explain intrinsic modifications; and molecular, cellular and biochemical error theories that explain extrinsic modifications (Trosko, 2003; Gavrilov & Gavrilov, 2001; Semsei, 2000). Internal program theories include evolutionary theories, biological clock theories, and programmed cell death theories. Semsei (2000) provides an overview of the most pertinent theories, and describes their fit amongst the different types of hypotheses. External program theories include those biological clock theories and the evolutionary theories. System theories that relate to error include disease theories, neuroendocrine theories, immune theories, free radical theory, waste accumulation theory and the crosslinking theory. Mutation theories relating to error include dioxyribonucleic acid (DNA) mutations, protein mutations, collagen crosslinks and sugar crosslinks (Semsei, 2000).
The Theories of Aging in Relation to Disease
As noted previously, the wide range of evidence based research aiming to understand the process of aging varies widely, and all existing theories and notions cannot be covered succinctly. However, inspection of the research reveals how several theories interlink, which further emphasises the multifactoral and complex nature of the aging phenomenon. In depth investigation of the various types of existing evidence is crucial in order to gauge a complete understanding of how these processes interact with one another.
The Wear and Tear Theory, first introduced by Weismann in 1882 (Trosko, 2003), aims to provide explanation as to how and why the body’s cells and organs ability to renew and repair decreases with age. This theory relates to the ability to resist the effects of toxins in the environment, diet, and illness, and how this ability decreases with age (Panno, 2006; Takahashi, Kuro & Ishikawa, 2000; Martin, 1997). As a result, the cells and the body become damaged over time, leading to an inability to resist diseases that would not necessarily have such severe consequences for the young, such as influenza, or leading to diseases relating to the organs of the body. This theory has been widely accepted as an explanation for why aging may occur but does not explain the specific biological processes which occur as result of these wear and tear processes. The Wear and Tear Theory relates to the changes in the body’s resistance to recovery towards injury or disease. The Neuroendocrine Theory, (Dilman & Dean, 1992), extends this theory to include the changes in the biochemical and hormonal activities controlled by the hypothalamus within the brain (Panno, 2006; Dilman & Dean, 1992). The hypothalamus regulates and controls the release of numerous hormones from within organs and glands inside the body, and also reacts to the hormonal changes actively occurring throughout the whole of the body (Panno, 2006). Analogous to the Wear and Tear Theory, the Neuroendocrine Theory purports that the ability of the hypothalamus to accurately regulate hormonal activities decreases with age. The reduction in the ability of the hypothalamus to precisely secrete hormones as required is also affected by the loss of sensitivity in the hormone receptors (Panno, 2006; Moberg & Moberg, 2001). The efficiency and efficacy of the hormone secretions is reduced as a result of the sensitivity loss, and additionally, the quantity of hormones secreted by the hypothalamus decreases as a result of these functional difficulties (Moberg & Moberg, 2001). There are various medications that can be prescribed which aim to resensitise the receptors.
The Neuroendocrine Theory expands upon the Wear and Tear Theory in that it aims to explain damage to hormonal activity with age. Specifically, the effect of the hormone cortisol upon the hypothalamus has been cited as a possible damaging factor on the hypothalamus (Panno, 2006; Dilman & Dean, 1992). Cortisol, a hormone responsible for stress, and released from the adrenal glands, is a hormone whose secretions are known to increase with age (Panno, 2006). Cortisol is purported to damage the regulational activities of the hypothalamus (Dilman & Dean, 1992). The damage caused to the hypothalamus results in increased secretions of cortisol, which in turn continues to damage the hypothalamus, which affects the ability of the hypothalamus to control the hormonal activities accurately and effectively, which ultimately leads to hormonal imbalance. (Dilman & Dean, 1992). Medications can be prescribed to replace hormones, and to decelerate the accretion of cortisol.
The Free Radical Theory (Harman, 1981) concerns the electrical charges of molecules within the body, and, analogous to the Neuroendocrine Theory, relates to the theory of wear and tear upon the body. This theory suggests that some unbalanced molecules carrying an extra electrical charge may attack the composition of the body’s cells and membranes, resulting in interference of protein, DNA and ribonucleic acid (RNA), and a negative effect on the production of muscle mass and the destruction of cellular enzymes (Harman, 1981). It is important to note that this type of cellular activity is happening constantly, from birth, but younger bodies have a stronger ability to repair and to renew cells (see Wear and Tear Theory). As time progresses, its ability to resist and defend such cellular disruptions and modification become weaker, resulting in aging. Mutant cells lead to cancer and death, and effects of free radicals can also be seen on the skin, as the elastin and collagen become damaged. This theory relates to the chemical damage theories which suggest that chemical agents such as oxygen, carbon dioxide, nitrogen and sugars can generate peroxides and superoxide ions which may also affect cell electron composition, which damages the protein structures and damages DNA and RNA (Kirkwood, 1997).
The Free Radical Theory is further supported by the Mitochondrial Theory. The mitochondria produce adenosine triphosphate (ATP) which provides the body with its primary source of energy. Cell energy becomes generated by the mitochondria in a process which leads to the accumulation of free radicals, known to potentially damage cells, and hypothesised to be one of the leading causes of aging (Lithgow & Kirkwood, 1996). It is known that the mitochondria are deficient of the defence mechanisms that are known to resist the damage of free radicals and so are on the cells that become easily affected (Lithgow & Kirkwood, 1996). It is widely considered that cell damage which accumulates over a period of time can lead to the effects of aging, and therefore become a significantly contributing factor to the development of disease. It is also thought that new advances in the research of mitochondrial renewal and repair will be significantly important in understanding and tackling the process of aging.
Other important theories of aging include The Genetic Control Theory (Sharma & Talukder, 1979), which proposes the existence of a pre-determined program within each individual’s DNA which controls when a person ages and dies. This biological theory relates to systems failure (Gavrilov & Gavrilov, 2001), and the notion that each person has a time clock within them which predetermines when they will die. The notion of a program within the body which intrinsically controls over any external factors suggests that there may be limitations to this theory. The effect of external influences, such as the environmental, political, socio-cultural and economic factors, must be appreciated when considering this theory. Other theories, such as the free radical theory, have taken both the biological concept and external factors into consideration accepting the notion that both internal and external influences can affect cell renewal and regeneration (Kirkwood, 1997).
The genetic control theory relates to the Hayflick Limit Theory of gene regulation, proposed by Hayflick and Moorehead in 1962 (Hayflick, 1989; Juckett, 1987), is a widely regarded theory which purports that each single cell that is living within the heart, skin, lungs and muscles has a predetermined growth limit, or lifespan. It is hypothesised that cell division can occur approximately fifty times, before the cell simply dies. Hayflick (1989) suggested that slowing the rate of cell division could possibly limit the effects of aging, via modifications in diet and lifestyle.
Conclusion
Biological effects of cell modification, damage and renewal, along with effects of external influences of environmental factors have been considered. It is also evident that various theories have interlinking associations with others, and this notion of the multifactorial nature of the aging process is crucial to consider. Semsei (2000) demonstrates the complexity of the aging process, and states how the process of aging is ultimately determined by the effects of the external factors, such as the environment, diet, political, sociocultural and economic factors, and the internal factors, such as genetic composition. This research is important for understanding that, whilst no one theory exists to account for explanation of the whole of the aging process, the existing evidence is has been significantly important in contributing facts about aging. It is probable that no one theory will be able to provide a single explanation of how and why aging occurs, but it is the accumulation evidence that provides the basis for what we know about aging in relation to disease.
