Human aging
Cells theory
Cells aging is the body's physiological function in the degradation and decline in the overall performance of the disorder, the life of the process is irreversible.
The human body is made up of cells organized to form the cell chemicals are constantly in motion both inside and outside environmental impact damage occurs, resulting in functional decline and degenerative aging. Cell aging and death are natural phenomena metabolism. Cellular senescence is an objective reality.
Like with metabolism, cellular senescence is the objective law of cell life activities. Of multicellular organisms, cell aging and death and the body's aging and death are two different concepts, the aging body does not mean that all cell aging, cell senescence, but is closely related with the aging of the body.
Studies have shown that modern mankind is faced with three kinds of aging: The first is physiological aging, is the emergence of growth with age, physiological degradation, which is the universal law of all life. The second is pathological aging, that is due to internal or external causes pathologic changes in the body, the aging phenomenon occurs in advance, this is also known as premature aging. The third is psychological aging, mental activity is physical activity the more advanced form of physical movement, the human variety of reasons, often have a "premature aging" state of mind affect the body's overall function.
Cells in normal environmental conditions occur dysfunction, gradually moving towards the phenomenon of death.
Aging is a universal law of biological cells as the basic unit of living organisms, are constantly new and aging death.
Aging is a process that the length of the cell's life, it is different with the type of organization, but also by environmental conditions.
Higher action has a maximum split number of cells, cell division once they reach this number will die. Division of the largest number of animal cells vary, the human cells 50 to 60 times. In general, the number of cell division and the largest animal is proportional to the average life expectancy. Cell senescence occurs when moisture decreased age pigment - fat brown pigment accumulation, activity decreased metabolic rate slows down a series of changes.
On cell aging, there are many hypotheses, including genetic factors, said cell damage theory, theory of aging and other biological macromolecules, but they can not satisfactorily solve the problem.
Study of cellular aging by aging can understand some of the laws, the understanding of aging and eventually find ways to postpone aging will have important significance. Cell aging issue is not only a major biological problem, and is a major social problem. As the first scientific development and continue to clarify the aging process, the average human life expectancy will continue to be extended.
But there will be corresponding social aging and cardiovascular disease, cerebrovascular disease, cancer, arthritis and other age-related increase in incidence of disease problems. Therefore, the problem of aging research is the future of life science research is an important issue. The vast majority of cells in vivo, to go through the undifferentiated, differentiation, aging, death, and several phases. Visible cell aging and death is a normal phenomenon of life. We know that every moment has cells in vivo aging, death, and also that the proliferation of new cells to replace them. For example, the body's red blood cells per minute to a few million to tens of millions of deaths as much as the same time can produce large amounts of new red blood cells by-up.
Free radical theory
Free radicals are a class of transient formation of atoms with unpaired electrons or functional groups, commonly found in biological systems.
The types and large quantities, is highly reactive intermediate transition state. Such as O2 ˉ • •, OH • and a variety of reactive oxygen intermediates (reactive oxygen metabolite ROM), free radicals exist in normal cells of defense systems, including enzymes and non-enzymatic systems. The former, such as: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), non-enzymatic system of vitamin E, such as the electron acceptor quinone.
Chemical properties of active free radicals can attack the body's biological DNA, proteins and lipids and other macromolecules, resulting in injury, such as DNA fragmentation, cross-linked, base hydroxylation. Protein denaturation and inactivation, membrane lipid oxidation of unsaturated fatty acids and reduced mobility. Experiments show that the DNA OH8dG increases with age. OH8dG specificity of base pairing completely lost, not only OH8dG was the wrong time; the adjacent cytosine is also wrong copy.
Large number of experiments to prove real, superoxide dismutase and increased activity of antioxidant enzymes can slow the aging body. Sohal et al (1994, 1995), ultra dismutase and catalase gene into fruit flies, the transgenic plants than the wild type more than one of these two gene copies, resulting in genetically modified strains significantly increased activity , and the highest average age for extended lifespans.
Somatic mutation theory
That the induced and spontaneous mutation accumulation and loss of functional genes, reducing the functional protein synthesis, leading to cell aging and death. Such as radiation can lead to young mammals symptoms of aging, and individuals is very similar to normal aging.
Theory of DNA damage repair
Exogenous physical and chemical factors, the basic freedom of endogenous DNA damage can lead to.
Body memory in normal DNA repair mechanisms, DNA damage can be repaired, but with increasing age, this decline in repair capacity, leading to accumulation of DNA errors, and ultimately cell death of aging. DNA repair is not uniform, transcriptionally active genes are preferentially repaired in the same genes are preferentially repaired in the transcribed region, and thorough repair only occurs in DNA replication during cell division, which is the stem cells can cause eternal youth. Theory of natural cross-linking of biological molecules In arguing that the doctrine of the molecular mechanisms of aging organism, said: organism is an unstable chemical system, are dissipative structures.
System in a variety of biological molecules with a large number of active groups, they must react to the interaction of biological molecules tends to slow cross-linked to the stability of chemical activity.
Over time, the increasing degree of crosslinking, a lively group of biological molecules constantly reduce consumption, the gradual change in the original molecular structure, the accumulation of these changes will make the gradual emergence of tissue senescence. Biological molecules or genes of these changes on the one hand will show the role of different active or even completely change the gene product, on the other hand also interfere with RNA polymerase recognition, thus affecting transcriptional activity, showing the order of gene transcription activity and gradually loss, prompting cells to tissue type and regularity of the table and even the death of aging changes.
Natural cross-linking of biological molecules that demonstrate the molecular mechanisms of biological aging, the basic argument can be summarized as follows: First, a variety of biological molecules is not static, but over time according to certain natural patterns of the natural cross-linking.
Second, the natural biological molecules cross-linked to the slow link, the intermolecular bond energy increased gradually polymerized, solubility and swelling capacity decreased and the loss of the phenotypic characteristics of cells and tissue age.
Third, the natural cross-linking lead to inactivation of the gene order, so a specific mode of cell growth and differentiation, programmed to show the organism and mode of growth, development, aging and even death of the dynamics of history.
Doctrine of limited cell division
L.Hayflick (1961) reported that human fibroblasts in vitro proliferation when the number is limited.
Later, many experiments show that the normal animal cells either in vivo or in vitro, it split the total number of times there is a "very extreme." This value is called the "Hayflick" limit, also known as the maximum split number.
Such as human embryonic fibroblast proliferation in vitro when only 60 to 70 generations. Now generally agreed that the number of cells with telomere DNA length. 1991 Harley and other chromosome found in the telomeric DNA will increase with the number of cell divisions continue to shorten. DNA replication, telomeres shorten the period of time, when reduced to a certain extent to the Hayflick point, the cells stop replicating, and demise.
Data indicate that human fibroblast telomeres shorten each of 14 ~ 18bp, visible chromosomal telomeres with cell division counter function can divide the number of memory cells. Telomere length of the side together with the enzyme activity, the side is a reverse transcription polymerase enzyme that on its own synthesis of RNA as a template for telomeric DNA, the spermatogonial cells and tumor cells (such as Hela cells) in a more high-side gather activity, while normal cells in the low end of polymerase activity, was suppressed.
Theory of repeated gene inactivation
Eukaryotic genomic DNA gene repeat sequences not only increase the amount of information, but also the opportunity for molecular genetic information from damage in a way. Gene duplication is the major selective genome protective mechanisms, cellular senescence may also determine the speed of a factor, a duplicate copy of the gene is damaged or choose to turn off, the other copy is activated, until the last copy run, the cell due to lack of some important products of the decline. Mouse liver cells in repeated experiments show that transcription gradually decreased sensitivity with age. Number of mammalian rRNA genes decreased with age.
Genetic theory of aging
Statistical data show that children's life and the life of the parents, all kinds of animals have fairly constant average life expectancy and the highest life expectancy, adult progeria patients an average of 39 years of age of aging, 47-year-old end of life, infant progeria children In an age of apparent aging, premature age of 12 to 18 died. From this point of view of life depends primarily on species genetic material, DNA chain, there may be some "longevity genes" or "aging genes" to determine the individual's life limit.
Studies show that when cellular senescence, a number of senescence-associated genes (SAG) expression are particularly active, their expression levels are significantly higher than young cells, in human chromosome 1, chromosome 4 and chromosome ⅹ found on SAG.
With the nematode studies have shown that genes influence aging and life can indeed be limited, Caenrhabditis elegans average life expectancy of only 3.5 days, insect age-1 single-gene mutations can increase the average life expectancy of 65%, increase the maximum life span 110%, age-1 mutation type there is a strong antioxidant enzyme activity of H2O2, pesticides, ultraviolet radiation and high temperature tolerance is higher than the wild type. Of early aging syndrome helicase in vivo study found a mutation, the enzyme gene in the short arm of chromosome 8, called WRN gene, the AD study found that at least four gene mutation. Including amyloidal precursor protein gene (APP) mutations, resulting in easy-amyloid protein gene product β deposition in brain tissue, causing mutations.
