Programmed cell death
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This theory assumes that every organism has a programmed "internal clock", defining a specific time of life for each species. It is supposed that physiological instructions are encoded in the genes, not only controlling the processes of growth and maturation, but also gradually reducing the activity of cells, eventually leading to their death.
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The cessation of cell life processes occurs through its necrosis or apoptosis
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Necrotic changes are usually accidental and uncontrolled. Necrotic lesions of cells arise as a result of infections with viruses, they are the result of mechanical or chemical damage. The changes taking place in cells concern mainly cytoplasmic organelles, mitochondrial swellings, disturbances of osmotic regulation without fundamental changes in nuclear chromatin.
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Apoptosis, or programmed cell death, remains under the influence of genetic control
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It is believed that there is a gene or genes responsible for this phenomenon in the genome of each cell. Mutations of mitochondrial DNA interfere with the functioning of the respiratory chain and cause excessive formation of reactive oxygen species that damage the cell. It has been proven that reactive oxygen species can, among other things, cause beta-amyloid deposition in nerve cells and induce programmed cell death. Apoptosis proceeds with the condensation of nuclear chromatin and DNA fragmentation. The endoplasmic mesh is stretched. The nematodes break down, and after some time apoptotic bodies from the cell are formed from them. Here they are eaten by macrophages. Apoptosis is accelerated by some physical factors (radiation, temperature, free radicals).
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In this context - aging is neither a disease nor a disability - it should be considered as a physiological process
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Mechanism of programmed cell death
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Cells, as they perform increasingly complex functions, that is more and more diverse, gradually lose the ability to divide. It is a natural mechanism of regeneration of cells, tissues and the whole organism. So if the cell loses the ability to divide within a certain time, it degenerates and then dies.
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The most divisible and divergent cells lose the earliest capacity to divide
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Such are, for example, specialized nerve cells or glandular cells - endocrine. The nerve cells are the fastest to divide, and this occurs in humans about the age of two. Cells that build connective tissue - fibroblasts - also gradually lose their ability to divide.
In vitro studies of cell culture have shown that fibroblasts have a strictly limited lifetime. Human cells in vitro typically divide up to 50 times. Probably this fact is part of the genetic program of aging. The important and perhaps even decisive role of genes in the aging process can be demonstrated by rare cases of prodrugia, where premature aging leads to the death of patients around 20 years of age, and more frequent cases of Down syndrome, where premature aging is observed in patients around 40 years of age.
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Stem cells - they have an eternal ability to divide
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Stem cells are found in adult mammals in the bone marrow and other tissues and are used to renew them. In contrast, cells that are already diversified into tissue retain eternal "youth" and the ability to divide. At the University of Kentucky, research was carried out on stem cells isolated from the bone marrow of various strains of laboratory mice. It was established that the length of their life can determine the life expectancy of the entire organism.The focus was on the evaluation of the efficiency of DNA repair processes in these cells in various mouse strains.
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It is known, based on previous research, that DNA is constantly threatened by damage, under the influence of ultraviolet radiation or free radicals
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Each cell of the organism therefore has mechanisms to repair it. Accumulation of mutations in the cell may lead to the development of cancer, but above all, it initiates apoptosis processes in it. It was observed that the stem cells in mice that had the longest life expectancy had the best DNA repair mechanisms. We also managed to identify the DNA areas responsible for this feature. It turned out that several of them overlap with those DNA fragments that were previously associated with the lifespan of mice. Currently, specific genes responsible for this dependence are sought. It has been observed that in mice, changes in the gene, which is involved in aging and cancer, also cause premature activation of ovarian follicles containing eggs and faster depletion of their resources. This in turn resembles premature menopause. It is known that premature disappearance of ovary work affects about 1 percent. women aged 30 to 39 and leads to the onset of menopause and infertility. The research was carried out on genetically altered mice, which were both copies of the FOXO3a gene. They observed that with age, the females had fewer and fewer offspring, and at the age of 15 weeks, which corresponds to early adulthood in humans, they were already infertile. Said gene activating the work of ovary mice caused that after activation the ovarian follicles worked very briefly. Premature activation of more follicles led to faster exhaustion in mice.
This phenomenon is compared to pouring grains of sand in an hourglass. The author believes that as the hourglass contains a certain number of grains, which pour out gradually by measuring the time, so the ovarian follicles of women are gradually activated, and the egg cells released into the fallopian tube. Menopause occurs when all grains are shedding. In mice studied this phenomenon occurred at a much faster rate. The reason was the lack of active FOXO3a gene, which inhibits the processes of activation of the follicles until the female sexual maturity is reached. According to the authors, it remains to be checked whether women with premature menopause also have changes in this gene. Perhaps a better understanding of the FOXO3a gene will result in knowledge about aging processes. It is known that premature menopause in women is accompanied by many symptoms of premature aging.
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Doctor of Medicine Janusz Krzyżowski
Psychiatrist
Private office tel. 22 833 18 68
00-774Warszawa, Dolna 4 lok. 15
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With increasing age, the susceptibility of the heart to the development of many diseases increases
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This phenomenon can be explained by the apoptosis of myocardial cells. It has been observed that the heart is one of those organs whose function begins to subside at the earliest. Testing the hearts of rats aged 6, 16 and 24 months. In humans it corresponds to 20, 55 and 75 years. In the mitochondrial rats isolated from the heart cells, the stages of energy production needed for cells were studied. It turned out that the cardiac muscle cells of older animals released more cytochrome C than the cells of younger rats. There was also an increase in the level of Bcl-2 protein that controls the release of cytochrome C. It has been known from previous studies that it is released from the mitochondria after damage and initiates processes leading to apoptosis. This one plays an important role in removing unneeded cells (eg old and damaged) and potentially dangerous cells like cancer cells from the body. According to the authors, their observation may partially explain the increased percentage of dying heart muscle cells in older individuals.
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Currently, it is estimated that in older men, not suffering from heart disease and without elevated pressure, about 30% of myocardial cells die.
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Researchers underline that establishing the relationship between suicidal deaths and cardiac death is extremely important as they are the leading cause of death in developed countries.
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Natural suicide cell death is the defense of the body against cancer
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It has been accepted so far, and it was almost a dogma in biology that mammalian cells grow and divide until they reach a certain state in which their divisions naturally cease.It's as if their internal mechanism of the cell has stopped working. Then its appearance and functioning undergo profound changes and after some time dies and is replaced by subsequent generations of younger sisters. It would be a natural defense of the body against the processes in these aging cells leading to their transformation into cancer cells. When mutations accumulate in them, apoptosis is forced on cells. The main measure of cell lifetime is the structures at the ends of chromosomes, called telomeres.
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Eternally young Schwann cells
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They were found in the nerve tissue of rat cells that do not enter into the period of old age. The influence of altered cell growth conditions on their telomeres was not observed. They were called Schwann cells. They can be divided after isolation and placement in the farm many times and after numerous divisions did not show morphological signs of aging and did not differ morphologically from young cells. In addition, they did not detect the presence of the beta-galactosidase enzyme specific form of aging cells. It turned out that this "immortality" of Schwann cells depends on the culture conditions - they were subject to aging processes in medium rich in growth factors. These experiences have enormous significance for aging research.
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It is known that at each division of the stem cells of the chromosome tip, the so-called telomeres are slightly shortened in daughter cells.
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Gradually, telomeres reach such a length at which subsequent divisions can no longer occur. The shortening of telomeres seems to be a kind of clock that measures the life time of cells and tissues and controls the aging processes. In people suffering from so-called congenital dyskeratosis, i.e. faulty keratosis, accelerated shortening of telomeres, premature development of many diseases associated with older age and deaths at an early age. Crowthon and the team, conducting telomere research, found that people with shorter telomeres were more likely to develop old-age diseases and had nearly twice the risk of dying in the next 15 years, compared to people who had longer telomeres. Among the most common causes of death, the researchers included heart disease and pneumonia associated with decreased immunity in the elderly.
People with shorter telomeres had a 3 times higher risk of death due to heart disease and an 8-fold higher risk of dying from an infectious disease, mainly pneumonia. The risk of death from cancer and stroke was also greater in this group, but these were not statistically significant differences. In addition, people in the group with longer telomeres lived between 4 and 5 years longer than people with shorter chromosomal ends. Crowthon believes that immune cells with short telomeres can not divide quickly in response to infection, which is crucial for their proper function. Lange is convinced that the link between shortening telomeres and aging of the body has evolved to prevent frequent divisions of older cells that are more likely to turn into cancer cells.
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It is known that stem cells have two remarkable features that distinguish them from other cells.
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First of all, they have the ability to transform into all other cells in the body - that is, stem cells, as well as blood and neurons, can arise from stem cells. Secondly, stem cells retain the ability to divide, so that the pool of these cells in the body remains eternally young. In recent years, very intensive research on stem cells has been carried out because they can be used to treat many diseases. However, to be able to use well cell cultures of stem cells, it is necessary to know well the mechanisms responsible for their unique characteristics. It seems that they have been able to identify the mechanism responsible for the eternal youthfulness of spermatozoon stem cells. In the fruit fly, the sperm cells divide in such a way that one daughter cell remains the stem cell, while the other becomes the precursor of the sperm. It turned out that to maintain a stable stem cell line, an enzyme activating a transcription factor is necessary, which has the ability to penetrate into the cell nucleus and turn on / off different genes in the cell.
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