The Increase In Longivity

The increase in longivity

Introduction

One of the main studies that concentrate the attention of a large number of scientists is that of the effect of a hypocaloric diet on longevity. For a considerable period of time, it is known that this type of diet increases longevity. The mechanism is the brooch that has left this theory, although in recent years great advances have been made. It is interesting to mention that in the present work, it has already been commented that yeasts in the retrograde response "opt" for a hypocaloric diet, constituting this one of the roads that lead him to increase his longevity.

Developing

The percentage of survival (ordered axis) is represented compared to age in months (abscissa axis). This corresponds to an experiment that was conducted with mice to which a different diet was provided. Some mice received a normal diet, a second group of mice received a food with a caloric restriction of 10%;Another group, a food with a 50 %caloric restriction;And a final group, with a 60% restriction. As can be seen, as caloric restriction increases.

There is an increase in the half -life that mice reaches. Already at the time of carrying out the experiment, the results surprised, but the determination of the physiological processes and mechanisms that lead to this remained pending subject. So far, what has been concluded and seems more likely, is the following: as seen in the image, the caloric restriction, on the one hand, makes insulin levels and the insulin growth factor reduce, whichleads to AKT activation (serine protein/treonine kinase) and this in turn, to the inhibition of mTor.

On the other hand, the absence of glucose generated by the caloric restriction, active A AMPK (amp activated kinase protein), which inhibits MTOR. Finally, the caloric restriction also generates an increase in the concentration of NAD+, which activates SIRT-1 (Sirtuin), which active in turn autophagy. All these ways, have as a final result the increase in longevity. The explanation of each of the roads that appear in the image is shown: MTOR: The objective mechanism of rapamycin appears in two of the roads. 

This molecule receives its name from the fact that it is inhibited by rapamycin (medicine). There are two types of MTOR: MTORC1, which is known that its inhibition increases longevity;and MTORC2, whose inhibition is dangerous, as it controls the suppression of hepatic insulin mediated gluconeogenesis. In fact, rapamycin treatment increased the longevity of mice that were used in an experiment. It is known that what this molecule really does is delay the appearance of the diseases associated with age, and it is in this way that the longevity increases.

MTORC1 Controls the SER / THR KINASA ULK1, which regulates the formation of autophagosomes and the autophagic flow MTORC1 actively suppresses autophagy by phosphorylation of ULK1 and, consequently, the inhibition of MTORC1 induces autophagy. This, what allows the damaged organelles to be eliminated and can be replaced by new structures, which leads to the prevention of degenerative diseases associated with aging. MTORC inhibits RNM translation, since phosphorylates translation inhibitors.

The inhibition of this molecule also increases longevity due to the fact that the translation of MRNA decreases, with the reduction of oxidative stress that that entails. MTORC1 inhibition is used as immunosuppressive therapy to limit T -cell activation and prevent transplant rejection after organ transplant. On the contrary, the inhibition of MTORC1 increases the memory responses of CD8 + cells that are criticism for viral defense. In short, these are all the effects generated by MTORC1.

SIRT1: Sirtuin are enzymes, more specifically unbit of histone -dependent histones, which regulate the longevity in two ways. This enzyme is activated in the presence of NAD+ and inhibits in the presence of NADH. Therefore, when a caloric restriction occurs, breathing is increased as a method of obtaining energy, to replace the decrease in carbohydrates in the body. As a result of this breathing there is a displacement of the balance towards the production of NAD+, which activates this enzyme.

The activation of this enzyme, what it does is promote autophagy, which contributes to the degradation of broken or old structures, and their replacement with new organelles, and thus avoid the appearance of degenerative diseases. This syrucine is a counterpart in mammals from the Sir2 enzyme, which follows the same mechanism, but in this case, in yeasts and nematodes. Apart from this counterpart, there are another 6 mammals. Apart from the foregoing on the enzyme that encodes the SIRT1 gene, it is also necessary to comment that it has a global effect on the very positive organism. 

For example, it is known that in the brain and in the central nerve system, neurodegeneration decreases, interacting with Foxo and P65 among others. As for the heart, it is known to decrease inflammation and increase cardioprotection. In the liver increases the oxidation of fatty acids and gluconeogenesis, interacted with LXR, PGC-1α and PPARα. On the other hand, in white adipose tissue lipogenesis decreases through its interaction with Pparγ. In the pancreas, insulin secretion increases, by interaction with Foxo and UCP2. 

Finally, in skeletal muscle causes an increase in insulin sensitivity and insulin oxidation. All this is summarized in the following image: all these effects, contribute as a whole to increase the global protection of the organism, delaying and avoiding many of degenerative diseases such as Parkinson, Alzheimer’s, etc. Medications, to this day, possible drugs or drugs that are related to the increase in longevity have emerged.

Some of the most prominent are the following: Resveratrol: It is a chemical obtained from natural plants that suffer an injury or that are attacked by insects or fungi, more specifically, a stylbenoid that can be obtained from the grape skin (In addition to other fruits), being for example in wine. Interestingly, this is one of the explanations of why it is recommended to have a glass of wine a day. This medicine is believed to prolong the life of animals. The most important research with this medicine was carried out in the nochobranchius guentheri fish. 

The half -life of this organism is 12 months and when treating them with this drug it was possible to increase this figure, without presenting side effects. The effect of this drug on cognitive and locomotive capacity was also wanted. In addition to protecting neurodegenerative diseases, resveratrol.

It also showed the quality of delaying the histological markers that are associated with aging, in the formation of lipofucsin and β-galactosidase activity of senescence. The operation of this medicine, in a summary way, is the activation of SIRT131 and PGC-1α, also improves the operation of mitochondria;So the mechanism indicated above would follow in section 5. The following diagram shows the numerous effects that are associated with this drug: Metformin: this medicine is well known.

Well, it is used for the treatment of type 2 diabetes and metabolic syndrome. It was suspected that this medicine could be used for longevity due to the fact that metabolic syndrome have premature aging, with the appearance of degenerative diseases, both cardiovascular and inflammatory disorders, and even cancer. This medicine reduces the risk of cancer by patients, in addition to age associated with age. Metformin activates ampk kinase proteins, which was mentioned in the caloric restriction section.

So it would mean a similar effect. It is known that you can also act by other ways, although this is the best known. Metformin partially inhibits the complex I of electronic transport chain, which leads to an alteration of mitochondria activity, which reduces ATP levels, in favor of AMP. Therefore, the energy levels of the cell decrease and to be able to maintain cell metabolism, what is done is to promote glycolysis to counteract this deficiency. On the other hand, it also results in the expression of antioxidant genes such as SKN-1 / NFR2 for activation of its transcription factors.

In addition to this, it has been proven that this medicine does not produce the formation of reactive oxygen species (ROS), which is very hopeful. Through AMPK, the effect commented in the hypocaloric diet section would be followed. These effects have been proven both in Caenorhabditis Elegans, and in laboratory mice. All this, as a reminder and summary, appears in the following diagram: in this section some advantages will simply appear, in fact the most prominent: an obvious longevity entails the survival of each person.

Something that humanity has been greeding for a long time, behind that, of immortality. What is pursued with the Longevity Genes project is to achieve successful aging. This concept means is to avoid or failing, delaying aging as it is known today, and replacing it with aging in which the cognitive and locomotive faculties are maintained without any deterioration, at the same timethat prevent all diseases associated with age. 

Get to detect the relationship of wild genes with degenerative diseases such as Alzheimer’s or Parkinson’s. Inc. of greater longevity, the advantages and positive aspects that emerge from this important advance have already been discussed, but it would not be appropriate to go through it without mentioning the negative points or aspects, since like everything in life, there are good thingsAnd bad things. Economics: One of the most stand out is that of the economic sector, because in a country like Spain.

Where there is a loss pension system, it would be almost impossible to be able to maintain this type of system. Taking into account that there would be an almost exponential increase in the inactive population, an equal increase in the active population would be necessary, which would mean a very serious problem, since we would approach an even deeper overpopulation. Planet Earth: a greater population number living at the same time, would lead to greater consumption of all types of resources, either to obtain energy, food, raw material for industry, etc. 

This would seriously undermine the integrity of our planet, to which the abysmal contamination linked to the processes of obtaining these resources would be added, which would have dire consequences, such as the acceleration of climate change, among others. Health: One of the biggest questions of this increase is how this change will affect the human being, that is, the organism must adapt to all these modifications. This would translate into a delay in aging and perhaps an extension of youth.

Which would occur due to a generalized change in the action of hormones, cell cycles, physiological processes, etc. Another question to this aspect is to know how more longevity will affect the development and functioning of human organs and tissues, since they would have to stay operational for longer, and as some scientists have pointed out, this could lead to very serious diseases such asresult of the exposure of cells to greater oxidative stress, motivated by a greater activity of these, leading to innumerable injuries. 

Employment: Focusing on Spain, where unemployment is a big problem, this would lead to retirement age delay, a fact that would cause an increasing need for employment production, and greater unemployment by the population, presumably from the region plusyoung of young people, and on the other, of the oldest population of the elderly. Possible rejection of the population: as is currently the case with transgenic foods, which are shown a unilateral rejection due to a large mass of world population, there is the possibility that the manipulation of human genes for the achievement of thismilestone.

conclusion

For the human being, it was declined by great olectives that firmly oppose the modification of the human genome. Although there are more negative factors derived from the greatest life expectancy, the most serious have been highlighted. But this section does not have to encourage a fear of this possibility, although at first it may seem that a chaotic scenario is drawn. As always happens, in parallel to experimentation and scientific process as a whole, there is an organism or commission that is responsible for designing a system compatible with this advance, as well as solutions that counteract all these problems.