Today, we can consider with certainty, that the natural death of a human being is the logical termination of the aging process in the organism. But before proceeding with the discussion about aging in general, we should first clarify certain definitions and terminology. Biological aging of the human body starts much earlier than social aging. Both men and women during their most fruitful years can be considered old people. Their physical development practically comes to an end and the organisms begin to experience degradation. According to the most recent scientific data, this occurs between the ages of 24 and 32.
There are currently over 300 scientific theories regarding aging that can be traced to two basic principles: “Error Accumulation” and “Programmed Death”.
1. "Aging Hormone"
2. Free Radicals
3. Hayflick’s Limit
4. Apoptosis, or Cell Suicide
Charles Brown-Sikar, A famous doctor, suggested in 1889 a theory that the aging of the human body is a direct consequence of the general decrease in the hormone level. The word “hormone” was unknown to mankind at that time, but it was found that the rejuvenating effect of intramuscular injections of the extracts from dog or guinea pig testicles was astounding. As it turned out later, the rejuvenating effect of the genital glands was unfortunately short-termed and required periodic recurrence.
Much later, the American endocrinologist, U. D. Dencla, suggested another theory. His premise was that the human brain contains “a hormonal clock” that regulates the aging process. Dr. Dencla worked with young and old animals and extirpated the pituitary gland of some of the subjects. Moreover, he treated some animals with the thyroid gland hormone thyroxin. This hormone affects the cardiovascular and immune systems of human organisms. The failure of these systems is the leading cause of human death in most developed countries.
The results of this research suggested that the reason for the aging of rats should be explored in the pituitary gland. The removal of this gland slowed down the aging process and even reversed it. Dencla suggested that after reaching the virility stage, the pituitary gland starts to produce a certain hormone that brings about the aging process. He called this hypothetical hormone DECO (short for decreasing oxygen consumption, one of the characteristics of the aging cell). This discovery first initiated interest in the concept of an “aging hormone” or “death hormone”.
Today no one considers hormonal therapy as a panacea. Its application in medicine has found very limited usage. It is clear that hormonal therapy is only indirectly linked to our lifespan and that it cannot indefinitely alleviate the consequences of past years.
Many scientists commonly agree that one of the causes for aging is the effect of free radicals on cell structure. The result is manifested in the inability of cells to function normally. As paradoxical as it sounds, oxygen is the cell’s major adversary. To be more precise, the active forms of oxygen – the free radicals capable of destroying the cells from within.
Since the 1930’s it has been known that substantial oxidation is extremely dangerous for an organism. At that time, Professor Clive McCay experimented with rat populations. He found out that if their normal daily food ration was cut by one third, the rats’ lifespan increased by an astounding 50%. The theory of free radicals was not yet developed, but scientists realized the benefits of fasting. When the organism is forced to adapt to reduced food consumption, the cell’s metabolism is adjusted accordingly. At the same time, however, the efficiency of the cell’s metabolism is increased and there are less free radicals produced, thus less damage is done.
Here again the paradoxical fact of oxygen being a major adversary of cells is established. More precisely, these are active forms of oxygen - the free radicals - capable of destroying the cells from within. Berkeley Biologist Bruce Aims calculated that free radicals attack DNA molecules up to 10,000 times a day. Active forms of molecular oxygen not only damage DNA molecules, but also interfere with the mechanisms of its repair. An error that is not found and corrected may very well remain in the cell forever and can also be inherited by all future generations. While these errors do not happen very often (approximately once per billion replications of nucleotide chains), the damage that these errors bring about to cells become visible with time.
Additionally, the oxidation occurring in our cells is dangerous even without free radicals. It leads to the accumulation of biological garbage that interferes with the normal functions of cells. The additional hazards of free radicals are a detriment that may otherwise undermine the advantages of oxidation. Normally, chemically active oxygen molecules protect us from invasive agents such as viruses and bacteria. This process is regulated by antioxidants that control the amount of free radicals. In an aging organism that lacks natural antioxidants, the immune system doesn’t function properly. Under these conditions free radicals turn against the host organism, causing additional damage to the immune system. This leads to a number of diseases such as diabetes, cancer, arthritis, or Alzheimer’s disease.
In 1961 American biologist Leonard Hayflick discovered the principle of cell divisibility. The most important implication of this principle is that “critical” cells in human organisms (i.e. brain, heart, the nervous system) cannot divide indefinitely. The maximal number of cell divisions is on average 50±10 (the so called Hayflick’s Limit). Some scientists believe that the loss of a cell’s ability to reproduce is a major cause of aging.
The number of cell divisions is limited due to the fact that actual DNA replication occurs with a “loss” – the molecule is not copied completely. To a certain degree there is nothing dangerous about the process – the tips of chromosomes are protected by telomeres that are being clipped with every deficient replication. But sooner or later the moment comes when replicated DNA becomes non-functional.
At the same time, some cells in human beings can divide indefinitely, e.g. hematopoietic or cancer cells. In this case, the mechanism for limiting the number of cell divisions doesn’t work; even through telomerase that repairs DNA by elongating telomeres.
If cancer cells are practically eternal because of telomerase, why not change the DNA in such a way that all the cells without exception can restore telomeres? Unfortunately, such cell reconstructions could theoretically transfer into cancer cells. The increase in the number of divisions will inevitably lead to an increase in the amount of cell mutations and subsequently to the increased probability of its transformation into a cancer cell. That is the reason why Hayflick’s Limit is not an arbitrary number used by nature; but rather, the maximum number of cell divisions permitted while the risk of an average cell mutating into a cancer cell is still minimal.
Moreover, the simple increase in Hayflick’s Limit will not by itself significantly increase the human lifespan. Numerous experiments have shown that there are other factors that lead to or contribute to cell aging.
This discovery was based on a sensational presentation made by August Weisman back in 1851. He suggested that death is an instrument of evolution rather than just the result of a malfunction of a sophisticated system. Important discoveries were recently made in this field. New genes were found that code for proteins capable of inducing cell suicide. This discovery was awarded the Nobel Prize in 2002 for physiology and medicine.
Weisman’s ideas were not accepted by the scientific community at the time. His presentation was widely criticized but his hypothesis was supported by new discoveries made in the 1970’s. British scientists determined that a suicide program is implemented at the cell level. This idea was proven several years earlier. It became clear that most of the cells die after radiation exposure not because of the direct damage from radiation, but figuratively speaking, by their own will.
If one or even several cells can commit suicide, why can’t the organism as a whole do the same? It is well documented that bacteria infected with bacteriophages can be suicidal. It was also recently discovered that yeasts are capable of similar behavior. In more sophisticated organisms there are known examples of death being caused neither by age nor by external reason.
It turns out that apoptosis (the name of this newly discovered suicide program) is much more widespread than expected. Apoptosis is a major component of an organism’s defense against cancer. The cells adjacent to the ones that already have cancer initiate a suicidal program as protection from the spread of disease. The malfunction of this mass suicide program is the true reason for the onset of cancer. Similar suicidal programs are utilized in cells that an organism no longer requires. These mechanisms can also be traced at the subcellular level - e.g. mitochondria are prone to suicide.
Today, with a high degree of certainty , we can assert that death is not a natural termination of life activity. We could live much longer if our bodies were not preprogrammed for suicide.
It is clear at this time that there are more questions than answers regarding apoptosis. There is an opinion that death functions as a factor of a stricter natural selection or as an instrument of evolution. The natural death or more precisely, the preceding process of aging, helps with the inheritance of new attributes that would otherwise go unnoticed or be inherited too late. Death is not only an accelerator of evolution that we inherited from the animal world, it is an atavism that we can and must defeat.
