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This theory postulates that there is a sequence of events written into the Genome that leads to age changes, much as similar instructions, written into the genetic message, lead to orderly expression of developmental sequences. The discovery by Hayflick and Moorhead, that cultured normal human cells have a finite ability to replicate and function, has provided the best evidence in support of this theory. My hypothesis on ageing in agreement with this principle, adds the following:
- Developmental changes that occur through genomic instructions are directly dependent on chemical signals received from the environment. As an example, fetal development is mainly controlled by the hormonal and blood constituents of the environment that surrounds the fetus.
- After birth, hormonal signals for growth and development could be modified though changes in the chemistry of the environment. The period of growth and maturation could be modulated by environmental changes, like caloric intake, temperature, light or chemical composition of the atmosphere. External factors could be direct inducers of the genes governing development, maturation, and ageing
- Experimental gerontology confirms the above through various specific examples
- Univoltine Lepidoptera generally has a total life span of 1 year from egg to imaginal death after laying eggs. Exceptionally, some butterflies living in high mountains where atmospheric oxygen is lower than at sea level, their larval stage is considerably extended, and their life span increases to 3 years.
- In plants, senescence could be delayed as much as eight times by modifying light cycles. By manipulating the environment the annual plant (one year life span) Xantium pensylvanicum was successfully maintained for over 8 years by exposing them to continuous long days of less than 8 hours dark period.
- When juvenile hormone is added at the time of molting in cecropia silkworm additional molting stages are added, prolonging the developmental stages of the insect's life.
- Various experiments have demonstrated that by retarding the period of growth though caloric restriction, the total life span of experimental animals was doubled.
- These experiments have demonstrated that life span is specific to each species, as long as the environmental factors surrounding the life of the species is maintained unchanged. Alterations in the environment can produce significant variations in life span.
- The purpose of this dissertation is to demonstrate that from all environmental factors affecting development and life span, the one with the greatest power to change and modify the length of life is directly related to the volume of oxygen present in the biosphere.
One of the arguments I would like to introduce in support of this idea is based on the science of paleontology. The fossil record gives precise data of several animals that were able to reach levels of height, weight, and life span twenty to thirty times those of present day animals.
- THE FOSSIL RECORD DEMONSTRATES THE EXISTENCE OF DINOSAURS AND OTHER ANIMALS LIKE THE TAPINOCEPHALID (1000 Kg’s; 30 foots height), TITANOSUCHUS (1500 kg’s 40 foots height) OF GREAT HEIGHT, WEIGHT, AND LIFE SPAN. THE DISAPPEARANCE OF THESE SPECIES HAS PRESENTLY NO RECOGNIZED SCIENTIFIC EXPLANATION.
Through the hypothesis that I have elaborated, a rational explanation is given to this geological phenomenon. I have based my hypothesis on the established geological fact that atmospheric oxygen pressure in pervious ages when the above mentioned animals lived, was much lower than the actual oxygen pressure
My hypothesis sates that the low atmospheric oxygen pressure that existed in the Mesozoic Era, allowed animals to reach longer periods of maturation and development. Consequently, animals living in a low oxygen atmosphere were able to grow for longer periods, and their lifespan reached 10 to 20 times present levels.
Distinguished gerontologists consider that the cessation of the growth period could be considered as a universal signal to indicate initiation of senescence. By prolonging the period of growth, life span is increased.
Increases in the level of atmospheric oxygen induce a shorter and quicker period of growth. The opposite occurs when levels of atmospheric oxygen decrease. The period of growth is prolonged. In a low oxygen atmosphere, animals are capable of reaching greater levels of height, weight, and life span. The whole process of maturation and development slows down.
In the Jurassic Period, Mesozoic Era, where a low oxygen atmosphere existed, the growth period of animals continued for three to four hundred years, the total life span reached eight hundred years or more. (Color Plate 4, Page 32)
In modern geological times, atmospheric oxygen has considerably increased, due to the expansion of photosynthesis and augmentation of the earth's plant mass. This ecological change, has produced a progressive shortening of the period of animal growth. As a result, animals reduced their height, weight, and life span.
I have developed this new hypothesis on ageing, which now explains the environmental modifications for the previous existence, and then disappearance of animals of great height, volume and life span.
I have arrived at this conclusion after integration of two established scientific facts:
1. Paleontology, which has confirmed through fossil record the existence of animals of more than a hundred times the height and weight of present animals.
2. Atmospheric sciences, have firmly established a gradual rise of oxygen from 0.01 percent in the Precambrian Era, to 1 percent in the Paleozoic Era. This increased progressively until the Recent Era, with levels of 20.9 percent (at seal level)
I have presented the idea that increases in oxygen levels, caused physiological changes in animal development, which shortened the period of growth and decreased animal life span.
In accordance with the program theory of ageing, the hypothesis I present here, agrees with the idea that genomic instructions trigger the cessation of growth and signals the initiation of senescence. The present hypothesis adds, that those genomic signals which indicates cessation of growth, and initiation of senescence, emerge quicker when there is a high oxygen pressure in the environment, and are delayed when environmental oxygen decreases.
Human diploid cells in culture present a unique model system for examining the effects of oxygen and free radicals at the cellular level. Leonard Hayflick discovered that cultured and human animals cells have a finite life span in terms of the number of populations they can achieve. After approximately 50 sub-cultivations, cell growth slows gradually until the cell population deteriorates and dies. These particular phenomena are considered as ageing at the cellular level. A great number of experiments evaluate the effect of different factors on cell ageing, in view of the relationship between cell and human ageing.
Alterations in the environment of the cell culture on which experimental cells grow, mimic the effects the same variables might produce in the whole organism.
Trying to find experimental results at the cellular level that will demonstrate the deleterious effects that high oxygen pressures should have in human culture cells, I extensively reviewed the literature on the subject. I was pleased to find two scientific publications that appeared a few years after the remarkable Hayflick experiments.
The first article: "Low oxygen concentrations extend the life span of cultured human diploid cells" published in Nature.
The second paper confirming similar results was published in the Journal of Cell Physiology a year later.
In both experiments, life span of human cells in culture was considerably increased when the oxygen partial pressure, applied to the cell culture, was reduced to half of the normal ambient oxygen pressure. The normal environmental oxygen pressure is 20 percent. In the experiment oxygen pressures were reduced to 10 percent, 5 percent and 1 percent. The authors concluded that "the potential for long term growth in culture of normal diploid cells, may be appreciable enhanced by more exact control of environmental factors." I think the initial paper published in Nature is of great value because the experiments were done with various air chemical concentrations of the elements carbon dioxide, nitrogen and oxygen. It provides us with a basic standard research protocol for further life span experiments on which different air compositions be applied on experimental populations of insects and mammals. Further to these two main publications, some other cell culture experiments were done by different research groups mainly to study the shortening of the cell's life span when higher than average atmospheric oxygen pressures, were applied to the sealed environment in which cells were cultured.
According to my opinion, the experiment published in Nature has the greater scientific merit, because it used a range of gas concentration variables with slight changes between them. In contrast further work by other research groups used only extremes, maximum and minimum oxygen concentrations without intermediate variables.
The program theory of ageing assumes that life span is determined by genetic factors intrinsic to each species and present in the Genome of the individual and in each cell.
My hypothesis attempts to demonstrate that those genetic factors have a wide adaptation range and could be amplified or reduced by stimulus from the chemistry of the environment. Oxygen, the main surrounding element, plays a crucial role.
I intend to demonstrate that in previous ages when oxygen had not accumulated in large amounts, size, weight and life span of animals were five or more times higher than in present days. Since the Jurassic Period in the Mesozoic Era, when dinosaurs populated the earth, atmospheric oxygen pressure has had a remarkable augmentation.
In my research proposal I have suggested experiments to which animals be submitted, to live in different chemical compositions of air. When oxygen is reduced to about two thirds of the actual atmospheric pressure, I expect to be able to observe an increase in life span, as in the findings with human diploid cells when exposed to a range of reduced oxygen pressures. (Color Plate 2, Page 19)
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