Numerous longevity studies
Introduction
First, it is necessary to know that it is longevity. According to the Royal Spanish Academy (RAE), Lonévo is what reaches an advanced age. Longevity has always been a very interesting topic, and in which numerous studies have been focused by scientists who understood the importance of it. It is known that longevity is related to cell biology, because we can find the explanation in cells. The shortening of telomeres in eukaryotes is the explanation that seems more successful, because in prokaryotic organisms, where this shortening does not occur, no death occurs.
Developing
As commented by a teacher, eukaryotic cells have numerous advantages over prokaryotes thanks to sexual reproduction (such as variability), but they paid a high price, which is death. Actually, it is known that longevity does not depend on a single factor, but it could be said that it depends in 20% of the genetics of each person and 80% of the lifestyle. As for lifestyle, it should be noted that hypercaloric diets, sedentary lifestyle, or factors that generate oxidative stress such as tobacco consumption or excess physical exercise.
They have a reduction in longevity. Longevity and History, since ancient times, there are stories about people who exceeded the 100 -year barrier. The Greek historian Diogenes Laercio, an astronomer called Hiparco de Nicea who claimed that the Democritus philosopher of Abdera lived 109 years (470. C. or 460 a. C. – 370 a. C. or 360 a. C.). Although it does not seem likely, one of the facts that can support this, is that Greek thinkers used to live more than 90 years. Like this case.
Other others are also documented, such as cnosa epimenides that are said to live 154 years and even more, although in this case it is not verified. As for the human being, there has been an increase in life expectancy (average of the amount of years that a certain absolute or total population lives in a certain period) since data are available. If in the Middle Ages the life expectancy was approximately 50 years, it is currently 71.4 years worldwide. However, for certain countries there is a greater life expectancy.
As they are Andorra with 83.51, Japan with 82 years, Spain with 81 years, the Hong Kong region, China with 81.6 years, Iceland with 80.7 years and Switzerland with 80.5 years. Next, an image is shown where half -life expectancy is seen in 2012 in the world: but it is not necessary to go back to the Middle Ages to see the notorious increase in life expectancy. We simply have to see the increase that this has experienced between the twentieth and twenty -centuries: this increase is due to progress in medicine, such as the production of new and better medicines.
Manufacture of new medical instruments, advances in surgical operations, vaccines, disease diagnosis, medical treatments, etc. Another important reason is hygiene, with the improvement of pipes and pipes in the urban nuclei, food health controls, the manufacture of soaps and more effective detergents, and their most widespread use, sterilization of medical instruments, etc. These are just some of the examples that have caused this increase in life expectancy, but there are more.
In spite of everything said, it is important. Longevity Genes Project. Nir Barzilai is a director at the Albert Einstein School of Medicine in New York in the field of aging. But in addition to the aforementioned, Nir Barzilai is the director of the known as "Longevity Genes Project". This project was born in 1998, and is based on analyzing the genetic material of people who have exceeded 100 years of age.
More specifically, so far the genetic material of 670 Jews has been analyzed with an age greater than 100 years. Choosing this population is that it is a homogeneous population, which greatly facilitates research work. One of the cases that Dr. Barzilai repeats the most in his numerous conferences, is that of the Kahn brothers, which appear in the lower image: these 4 brothers have a common fact that made them special, because they have already died. This particularity is that they all lived more than 100 years.
This was observed with perplexity by the researchers, since it led them to think that there should be one or more genes in their genome to provide that "blessing" to all of them. On the other hand, another event that reinforced this idea is that the lifestyles they had practiced during their lives were not healthy, since they had smoked during much of their life and some of the brothers had barely exercised in their life. Observing the genome of individuals under study, it was observed that they had a mutation in a gene associated with higher levels of high density cholesterol.
Also commonly called good cholesterol. Another uniqueness observed in many of the centenarians, is the incorrect functioning of the growth hormone. A low amount of this hormone seems to increase longevity, as is observed in animals, since for example, the ponies live more than horses. Studies carried out, the human being raises two great inconveniences when carrying out this type of studies in it: on the one hand, the well -known ethical, which greatly restricts experimentation with the human being.
On the other hand, there is the disadvantage that the life expectancy of the human being is very high, so it leads a literal life, the realization of the research and observation of the results. This last inconvenience collides strongly with the methodology that is usually used in experimental science, since individuals are always sought in which the results can be clearly distinguished, that the process is not very expensive and that it does not have been obtaining results for long.
For all the above, the most frequent thing is to choose model organisms, which are widely studied species, usually because it is easy to maintain and reproduce in a laboratory environment and has particular experimental advantages;And above all, that allow us to understand how certain biological phenomena take place in other organisms, or at least give an idea of it. In the experiments carried out so far, the organisms used are: Caenorhabditis Elegans (nematode), Aserina Podospora, Saccharomyces Cerevisiae, Drosophila Melanogaster and Mus musculus (mouse), which are observed below.
Regarding the methodology, it should be mentioned that mutations are induced in the organisms, through different techniques, which are those that appear in the following table, and that will be explained below: Mutagenesis: It consists of producing mutations in the DNA. In some cases, directed mutagenesis was performed, which consists in causing specific mutations in specific sequences or points of the DNA. To do this, a primer is synthesized with the desired mutation. Subsequently, this feeding primer with the monocatenary DNA molecule containing the gene to be modified.
Then, with a polymerase DNA, the chain is elongated until a two -class molecule with the mutation is achieved. In addition to adding the punctual mutation, deletions (primers with deletion) and insertions (priming with the DNA to be added) can also be generated). Similarly, mutagenesis can also be performed with physical and chemical methods. Finally, mutated individuals are chosen. Molecular genetic strategies: they are similar to mutagenesis, except that in this case the mutations are directed to specific loci that are believed to be related to longevity.
Loci analysis of quantitative features (QTL, from the English Quantitative Trait loci): It consists of a very wide set of techniques that allow to locate the genes that are responsible for the phenotype that is sought. Selective breeding (English, Selective Breeding): Its methodology is to observe the different phenotypic variants of a population, choosing each generation, the most extreme ueotype. Associative Genetics (English, Associative Genetics): Determine the frequency with which different phenotypic variants appear in a population, based on it, on the most extreme phenotypes.
Thanks to these techniques, 35 genes were identified in these model organisms. These genes encode a wide set of protein, which following different routes and suffering different processes, give rise to aging. Although a priori it can be thought that there are innumerable aging mechanisms, although it seems to be like that, there is a convergence in the routes of the different organisms. These genes that have been mentioned, are shown below in a table, cataloged by organism.
The population of yeast is very interesting for the study, since each cell can be reproduced asexually by sprouting, so that it gives rise to an identical daughter cell every time, each of which in turn has that ability to return tobe divided. Thus, we are facing mortal individuals, but an immortal population. The importance of this is that chronological time cannot be used as a measure for the longevity of yeasts, and is used instead of this the number of divisions suffered by a cell until its death.
From the yeast study, it is concluded that there are four processes that measure decisively in longevity;These are: metabolic control, stress resistance, genetic deregulation and genetic stability. It is also necessary to mention that 2 aging mechanisms were detected in this body. The retrograde response is the name that receives one of the roads that determine the longevity of the yeast. Corresponds to intracellular signage from mitochondria to the nucleus. This route entails modifications in the expression of nuclear genes that encode for peroxisomes proteins.
Cytoplasm and mitochondria, always based on the functional state of the mitochondria. Some of the most outstanding changes involved, is the stimulation of gluconeogenesis, the use of acetate instead of glucose and the modification of the glioxylate cycle to obtain intermediaries of the Krebs cycle. As can be deduced from all these changes, what is sought is to use a less caloric carbon source to obtain energy. RAS2 is the gene that modulates this answer and the longevity that it provides.
It is known that this gene mentioned above exerts a negative regulation (acting in the cycle cycle cyclasa) to heat stress, so that when it is not present, there is a significant reduction of longevity. The overexpression of this gene is able to eliminate any harmful effect of stress on longevity. RAS1, RAS2 and HSP104 have a determining role in this protection, since producing in the individual a thermotolerance from an early age, significantly reduces the mortality rate.
Gene deregulation in the heterochromatic regions of the yeast genome near telomeres and in the loci of the type of silent mating also have a fundamental role in longevity. The histone genes Desacetylase RPD3 and HDA1, in addition to this, also silence the ribosomal DNA, which is very interesting, since it has been established that in aging there is an overexpression of ribosomal RNA, which gives rise to an excess of this, which, whichIn turn, form defective ribosomas, because the expression of RNA cannot be counteracted with protein synthesis.
To reach this conclusion, it has been observed that over the years there is an increase in ribosomal RNA levels, while a decrease in the protein synthesis rate, which would be explained with the previous theory. Sometimes, the recombination of the region that encodes for ribosomal RNA, results in circular fragments, which accumulate with age and can cause cell death, but the mechanism is not known. In the same way it is thought that these circular species are not important.
Since with the suppression of the Sir2 gene, the expression of ribosomal DNA also produces a reduction in longevity, but not those species. Sir2 controls numerous processes involved in longevity (mentioned above), to which it is necessary to add for example, the cell space organization and the transcriptional silencing dependent on chromatin. That is, we can establish that this gene is responsible for responding to the energy requirements of cellular processes, distributing resources.
Below is a diagram where the action of Sir2 is simplified: a very representative image of the commented about the circular species of ribosomal RNA is also attached: for the rest of the organisms similar results were observed so that the results will be passedobtained for human beings. The fact that the study for S has been explained more extensively. Cerevisiae corresponds to the fact that it is the body that gave more favorable results. Homo Sapiens, based on the information published by the project mentioned in point 3.
The following can be affirmed: these "genes of greatest longevity", are most likely hereditary, that is, they are transmitted from one generation to another. As already mentioned, LDL concentrations and high levels of HDL are usually associated with low concentrations. A mutation in the CETP enzyme (Cholesterol Ester reverse transferase) is associated with longevity genes, the gene that encodes this enzyme participates in Alzheimer’s prevention and cognitive deterioration.Another mutation, in this case in the apoprotein C-3 Apo-3 (APOC3).
It is able to increase about 4 years on the subjects that possess it, due to the fact that its lipoproteins are larger size.Telomeres (extremes of chromosomes), have a greater length in people who exceeded 100 years of age, which leads to thinking that there are mutations in telomere genes, and that they also go to offspring. There is a deletion in the adiponectin gene (adipoq) that also relates to an increase in longevity.
conclusion
This gene encodes for a peptide that in addition to causing a reduction in inflammation of the arterial wall, is able to enhance insulin activity. In several centennial women, polymorphisms have been observed in the route of insulin growth factor, which will be mentioned in the section next. As already mentioned at the beginning, there are demonstrations that organisms with relative dwarfism, it presents greater longevity.
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