Life extension, part 3 - Modern views on the aging process





…… because fearing death is nothing but thinking that you know what you do not know. After all, no one knows neither what death is, nor whether it is the greatest of benefits for man, but everyone fears it, as if they probably know that it is the greatest of evils. But is this the most shameful ignorance of thinking that you know what you do not know? ……

Plato's “Apology of Socrates”



  1. How does modern science see aging?
  2. Do we have a chance to survive until the moment when the medicine appears allowing to cancel old age and prolong active life up to 120 and more years?
  3. What should I do right now?


Attempting to give an answer to these questions under the cut, we continue the journey on technologies and concepts of Life extension.







Small introduction



So, this is the third article from the series of studies about the extension of life. I remind you that these articles are written in research mode and are intended for some kind of data classification + personal motivation to continue research.







How I see such a format work - I began to take the “Introduction to Biology - The Secret of Life” course at the Massachusetts Institute of Technology to raise the level of education in this area, I study a lot of literature and continue to dive into the subject. And it becomes more and more interesting!







Also in the comments we discuss the details of the articles, which allows us to improve them and in the following articles to deal with emerging issues, so do not hesitate to write them.







Feel free to rate and say thanks if you think this is useful. So you increase the chances of continuation.







And let me remind you that the goal is not only to prolong life, but also “to live it so that later it would not be excruciatingly painful for purposelessly lived years”. That is, we want to keep our brain and body active and vigorous until the moment when consciousness is disconnected from the carrier in order not to become a burden for loved ones and others, but, on the contrary, to bring benefit and joy to everyone. That is, the goal is not eternal life, but the extension of the active phase of our life.







Thanks I want to thank:







  1. For comments Z3RG1 They helped me a lot and opened up a whole area for study. Thank!
  2. For the translation of Robert Sapolsky's lectures - this is a huge job that opens up access to a large body of knowledge - thanks!


List of literature: down under the spoiler, as it turned out very large.







The article itself is not only a compilation based on read literature, but also a study that poses questions that I plan to study further.







Mechanisms of aging - a modern view of the process



Evolution, as a result of which we, people, were formed, lasted for about 4 billion years. All this time, organisms have become more complex and, at a certain point in this super-complex process, we appeared.







We, as humans, at the moment all possess an incredibly complex organism and brain and are trying to understand why we are aging and dying. Inside this phrase are hidden two questions:







  1. Why should I grow old - read become weak, worse moving, worse thinking. How can I reduce these signs of aging to death?
  2. Why should I die at about 90 years old? How can I extend my life, for example, to 120 years?


Modern science is closely studying these questions, but due to the fact that we are a very complex system in which everything is infinitely interconnected, there is still no single and simple answer and it is not clear whether it is possible in principle.







However, we have deeply got into the basics of the work of our body and cells, and today, one of the main causes of aging and death, researchers call mitochondrial disruption. Notice, not the main or only reason, but simply one of the main ones.







What is mitochondria?











Mitochondria is a two-membrane organnell (permanent formation inside the cell), which is present in almost all of our cells. One of the main functions of mitochondria is the synthesis of ATP (adenosine triphosphate) .

About ATP, you can remember one thing - this is the main component for energy-consuming reactions in the cell, on the day our body synthesizes about 40 kg. this substance.







The ATP molecule exits the mitochondria into the cell where it participates in the reactions and splits into elements. These elements (decay products) go back to the mitochondria, where they are again connected to ATP.







Chemically, the process is organized in the following way - glucose and oxygen enter the inlet, carbon dioxide, water and ATP go to the exit. The two processes of our body - nutrition (and output), breathing (and exhalation) just supply and remove the substances of this chemical process.







From Wikipedia:

In the body, ATP is one of the most frequently updated substances; so, in humans, the life span of one ATP molecule is less than 1 min. During the day, one ATP molecule undergoes an average of 2,000–3,000 cycles of resynthesis (the human body synthesizes about 40 kg of ATP per day, but contains about 250 g at each particular moment), that is, there is almost no ATP stock in the body and for normal life it is necessary to continuously synthesize new ATP molecules.













And it is also interesting and important for understanding the mechanisms of aging that mitochondria have their DNA. It is called Mitochondrial DNA (mtDNA or mtDNA). How was this possible?

If you read the textbook of biology 11 class of 2015, then there it is described like this:

Some primary heterotrophs have symbiotic relationships with aerobic bacteria. Having seized them, heterotrophs began to use them as power stations. Thus arose modern mitochondria. These symbionts gave rise to animals and fungi.







There are other theories, but this is not really important for us now. The only important thing is that this mtDNA also encodes proteins and RNA.







Interestingly, about 200,000 years ago there lived a so-called Mitochondrial Eve from which we all inherited Mitochondrial DNA (mtDNA or mtDNA).







So, as a result of this introduction, we get that in almost every cell in our body there are mitochondria, which are separate organelles with their DNA and supply us with ATP, the main “fuel” for carrying out reactions in the cells. Figuratively, mitochondria are sometimes called “cell power plants”.







We now turn to the modern theories about how aging and the disruption of the work of mitochondria are connected.







Theory # 1: Free radical theory of aging (mitochondrial free radical theory of aging (MFRTA))



This theory is already outdated and it is believed that it does not explain the causes of aging. Therefore, only the fight against free radicals, the problem of aging can not be solved.







According to this theory, one of the main causes of the appearance of signs of old age are reactive oxygen species (ROS) (born radical species (ROS)), which are a by-product of the oxidation reaction. The resulting ROS react with cell molecules, damaging them. And this leads to apoptosis of the cell.







In principle, all this is normal and our body is constantly updating (for example, wounds on the skin, visible part). However, some of the tissues are almost not renewed (cartilage, tendons, crystalline in the lens), and there apoptosis gradually leads to the manifestation of signs of aging to all familiar ones.







Also, the second part of the problem of elevated ROS levels is that the likelihood of DNA damage and cell transformation into cancer increases. And if this happens, then everything becomes bad.







This theory was quite strong for some time, however, contradictions gradually accumulated, which this theory did not explain and now it is not a “cake”.







Contradictions:







  1. From the point of view of this theory, an increase in the level of antioxidants in cells should reduce (slow down) the appearance of signs of old age and increase longevity. However, in a number of experiments (list of numbers 19–28) it was shown that this not only does not increase the lifespan, but sometimes reduces it.







  2. Also, according to this theory, the life expectancy of different animals should be different. The more ROS are produced in mitochondria, the shorter the life span. However, this is not confirmed. For example, ordinary mice live for about 3-4 years, and bare diggers are 25-30 years old. At the same time, the level of ROS in them is almost the same.







  3. There is no age-related changes (signs of old age) in naked mole rats, but the level of oxidative stress in them is much higher than in aging mice (list of literature 29)









Based on this, at the current stage it is concluded that ROS are not side, undesirable products of mitochondria, but important signaling molecules that promote longevity. (list of literature 30-31)







Theory No. 2 Disruption of activity (dysfunction) of mitochondria with age.



With increasing age, the number of mitochondria in cells decreases (the list is 34, 35) and, at the same time, the number of copies of mtDNA in mitochondria decreases. Also, the productivity of the mitochondrial transport system decreases by approximately 40% (list of literature 36-38)







That is, the signs of old age, which we see and feel, are associated with a decrease in the number of mitochondria (there are fewer energy-producing organelles) + with a decrease in the productivity of the rest.







This theory explains why we observe signs and sensations of aging. However, although these violations are associated with age-related changes, the root cause of their appearance is unknown. That is, these disorders (reducing the number of mitochondria, DNA and conductivity) may not be the cause of aging, but one of its mechanisms, which starts working because of something else.







Researchers note that mitochondrial biogenesis is controlled at many levels simultaneously. For example, thyroid hormones, estrogens, glucocorticosteroids affect not only cell growth and cell division, but also the functioning of mitochondria. (list of literature 39-43)







The root cause (or a complex of reasons) due to which this is still to be found, however, today one can begin to try to stop the process of reducing the number of mitochondria in the cells or even reverse it.







Such accessible methods as special physical trainings and \ or restriction of nutrition are guaranteed to be suitable for all. (list of literature 44, 45)

We will also explore other options, you can watch the process in the telegrams channel or Vkontakte .







Theory # 3 Somatic (not inherited) mtDNA mutations.



As we found out at the beginning of the article, mitochondria have their own DNA, mtDNA.







Also, in theory No. 2, it was found that the basic signs of aging appear due to the disruption of the mitochondria. The current working theory sees one of the causes of these abnormalities in mtDNA mutations.







The 2017 article (from the list of 55 liters), which I technically cannot buy at the moment (I don’t go to the purchase process), this theory is described in the description beautifully and briefly.







The process of duplication and repair of mtDNA is produced by polymerase (Pol γ) which is encoded by “large” DNA from the main cell, inside which the mitochondria is located. Also in the process involved several other proteins.







Modern theory claims that the errors of this mechanism cause mutations of mtDNA, which in turn lead to mitochondrial dysfunction. (list of literature 1, 56, 57)







Moreover, there are already the first confirmations that it is the errors of this mechanism that lead to mitochondrial dysfunction, and not the damage caused by the process of life. (list of literature 58)







As soon as scientists have a complete understanding of the process and an evidence base, then targeted therapy + development of targeted drugs will immediately become possible.







Total



So, having considered these three theories, we can see how the views on the mechanisms and causes of aging are gradually developing. Moreover, this is only one part of the research areas, although it is one of the main ones at present.







We can also see that, as far as confirmation of various theories, science can develop, and we apply different methods of influence on our body, which will allow us to slow down / alleviate aging and reduce the risk of associated diseases.







For example, in theory number 2, the cause of the disturbance of the mitochondria was not found, but the physical expressions of these disorders were found. And by acting on them we can reduce the signs of aging and the risks of related diseases.







And here we come to questions No. 2 and No. 3 which were at the beginning of the article.







Do we have a chance to survive until the moment when the medicine appears allowing to cancel old age and prolong active life up to 120 and more years?



In no case do not want to predict anything and act as any analyst. Just when you begin to study aging and the cures for it, the question “When will the miracle pill appear?” Arises the very first.







Without predictions, I’ll just tell “news from the fields.”







News No. 1 Skulachev Vladimir Petrovich , Member of the Russian Academy of Sciences,



in his book “Life without old age” , he writes that the mitochondrial antioxidant skQ1, which has been delivered directly to mitochondria, has already been developed and tested in mice.







On its basis, eye drops are released, there are no tablets for the prolongation of youth, although if you read a book, everything is magical right there.







Doubts arise when studying what is happening in reality:







  1. Eye drops on the market for several years (launched on sale since 2012), but there is no research on how they work. There are private reviews and they are not very positive.







  2. On the official website there is no news and technical data. It is very similar to a failed project that gradually dies and moves by inertia.









At the same time, perhaps the team is simply not confused by the news and is completely immersed in scientific work. There are recent publications on the topic abroad.







  1. https://scienceblog.com/492213/scientists-slow-aging-artificial-antioxidant-skq1/
  2. http://medkoo.com/products/4508


Therefore, you just have to wait here, but if everything goes positive, then for several years we can expect Russian-made mitochondrial antioxidant.







News №2 MitoQ Antioxidant



Meanwhile, world science is also awake and has already released mitochondrial antioxidant.







IMPORTANT! Please do not rush to buy it and drink, study the question deeply or wait a couple of weeks, an article on this subject will be published on Giktimes, and in the meantime the latest news (building blocks of a big article + technical details) will be in the telegrams channel or Vkontakte .







Manufacturer's website >>> At this link, if you can not wait to urgently buy, there will be a 10% discount, made an affiliate program. But again, wait. Especially if you are less than 40 years old and are not sick of anything - do not rush.

MitoQ Antioxidant on Amazon >>>







This drug, previously, causes some confidence:







  1. produced in New Zealand, the land of hobbits and victorious elfism.







  2. The first mention of the active substance on the pubmede dates back to 2003 as https://www.ncbi.nlm.nih.gov/pubmed/12882327 , that is, the substance has already been studied enough







  3. The substance delivered to the mitochondria is also very well studied. This is coenzyme q10 and it is often recommended as one of the components of the complex of additives for the preservation of the active body and brain. Read more about the Q10 in the first article .









Bottom line: So, as you can see, the chances for the emergence of a common medication that can prolong vigorous life and allow you to be active before the age of 90+ are quite real. Research is underway, and there is competition between different active substances, which is particularly encouraging.







What should I do right now?



We come to the last part of the article, where the theory comes into contact with reality and usually streamlined formulations are given, such as drink these supplements (the article is written by the manufacturer or I insert partner links) and get protection from this and that.







I cannot say for sure that all medicines do not work and there is no magic pill, but my common sense, observation of reality and the study of the subject says exactly that - the magic tablet (complex of tablets), which will decide everything at once - no. At the moment of existence, we are all mortal, both accidentally (at any time), and 100% naturally - from old age.







However, proven ways to prolong life, energy and mental alertness are available right now. About it there were two previous articles - one and two . Just by performing the points from them you can slow down the aging process, avoid many troubles and live intact until the advent of a new generation of drugs.







The plans for the future below - we are starting to develop a program that will analyze individual parameters and make recommendations for longevity and brain activity.







Plus, we will publish research, observations and conclusions in the form of final articles here on Giktayms.







Future plans



  1. Promised research article about MitoQ







  2. In the course of research, an interesting psychological-meditative life hack was invented, which, in theory, can greatly slow down aging and even reverse it. There are positive results of such studies + this life hacking is unique in that it will be a special meditation for 5 minutes, three times a day. We will do it for one year and measure once every three months the main indicators of the age of our body. And if the studies show physical rejuvenation, then we can recommend the technique in public.









Now we are at the stage of collecting the team and preparing the documentation, but soon everything will be open and fully accessible in the telegraph and on github - the project is planned to be completely open.

Those who are willing to experiment on mice imagine - wellcome.







  1. Creating a program for individual selection of what you need to take and do to extend the active phase of life. The data of the person are fed to the input, we get some personalized therapy at the output. This is the future, but not very distant, the preparation has already begun, everything will be written on Python, available on Github.


The advantage of such a program will be that with its development all new methods will be introduced there and, if they suit you, you will immediately learn about them.







All the latest news and research will be on the telegram channel or Vkontakte







Finally, a quote from Socrates and good luck to all and see you!







And let us judge, one more thing, how great is the hope that death is a blessing? To tell the truth, to die, means one of two things: either to stop being something, so that the deceased does not feel any sensation from anything, or it is a transition for the soul, moving it from here to another place, if you believe what they say about it. And if it was the absence of any sensation, it is like a dream, when they sleep in such a way that they do not even see anything in a dream, then death would be an amazing gain. I think, in fact, if someone had to take that night in which he slept so that he did not even have a dream, compare this night with the rest of the nights and days of his life and, after thinking, say how many days and he spent the nights in his life better and more enjoyable than that night, then I think not only every simple person, but the Great King himself would have found that it is worth nothing to count such days and nights compared to the rest. So if death is that, for my part, I will call it a purchase, because it somehow turns out that all life is no better than one night.

Plato Apology Socrates







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References for the article

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