You begin to fuss and avoid direct answers. Let's do it again:
Let's say mice living in laboratories around the world are kept closest To optimal conditions which still cannot be identical(for some people the light stays on for two hours longer, for others the cage is one mouse larger, for others the food is more fortified, for others it is natural, etc.), but still everyone dies at the same time. How so?
This experiment with mice (which you refer to) is too promoted in such discussions, and before that it was heavily promoted by the press (you promised somewhere above to provide links to a description of the experiment). I don't have much confidence in his results for several reasons. Firstly, the mice did not obtain food for themselves, neither in the control nor in the experimental group. Secondly, it is not very clear how exactly the mice were kept - all separately or together (apparently separately). Thirdly (and in fact the main ones), the phrase “Moreover, the thicker the mouse was initially, the more noticeable the effect,” generally reduces the significance of the experiment to the level of diet researchers. It is completely unclear what kind of mice these were and why some of them were “thicker” and for what reason.
You understand that if a fat person is forced to lose weight, then statistically we will prolong his life and reduce the number of “age-related diseases” such as heart attacks, and the fatter the person was initially, the higher the effect will be! That is, we changed the concepts and took the “sick” overweight people, led them to more healthy state, and concluded that hunger extended their life, although in fact it was the extra food that shortened it.

For understanding:

I know about these and similar experiments on different organisms, With biological point In view of all of them, they all have an alternative explanation; you need to understand the methodology of each of them in order to say something specific. In addition, flirting with metabolism will certainly have an effect, because, as I already mentioned, everything that happens inside biosystems is metabolism. If you want to discuss specifically the experiment with mice, then you need to look at what’s going on there.

Like turning off immunity? A man lived for forty or fifty years, left offspring, can he be used up?
Maybe so, but not reliably, he can still survive, he is more tenacious than a human) but the accumulation of violations (increase in entropy), without special measures there is no way around it, 100% will die, roughly speaking, according to the laws of physics, although they may live longer.

Why, despite all the advances in medicine, we still cannot step over the 120-year mark?

Already answered this question. These are the lucky ones with cats. Metabolic levels were on average consistently low due to living conditions. Again, this is the main factor, there are other, individual ones.

In addition, information about the max. cont. Lives themselves are not representative for many species, they are difficult to estimate correctly, and they are often known for several individuals.

Well, let's move on to our immortals. That is, you do not reject the fact of the existence of immortality obtained through natural, evolutionary means. But you insist that it’s all about “primitivism.”
Let me start with the fact that HeLa cells still remain human in almost everything. Before the era of induced pluripotent cells, a significant part (if not the overwhelming majority) of research worldwide was carried out on HeLa cells,

Something like that

In 1955, HeLa cells became the first human cells to be cloned, and the use of HeLa cells began around the world: in studies of cellular metabolism in cancer; studying the process of cell aging; causes of AIDS; features of the human papillomavirus and others viral infections; exposure to radiation and toxic substances; gene mapping; in testing new pharmacological drugs; testing cosmetics; polio vaccines.
For decades, the HeLa cell culture has been widely used as a simple model for creating more visual versions of complex biological systems. Even the USSR sent them into space along with other animals, and even the famous Dolly appeared thanks to the development of the cloning method on HeLa cells.

P.S. My field season has begun, and therefore I can disappear for a long time, don’t blame me.
P.P.S.

the opponent looks at the phenomenon as if from the outside, without going particularly into the mechanisms, that is, phenomenologically.

• You begin to fuss and avoid direct answers. Let's say it again: Let's say that mice living in laboratories around the world are kept closest to optimal conditions, which still cannot be identical, but they still all die at the same time. How so?

  What is one term? Even if they are from the same litter, were kept identically, and were not sick, there will still be individual scattering, as some of the more active ones ran around the aquarium, while others preferred to sit still and stare at the experimenter, waiting for food) They live 1-2 years, in identical conditions may die within days or months.
  

  This experiment with mice...

  There are really a lot of them, with different settings and results. One of . As for “fat” mice, we will not divide destructive changes into correct ones, associated with oxidative stress or radiation, and incorrect ones, associated with other factors, such as obesity, leading to atherosclerotic vascular disorders. Even if the cause of obesity is genetic, the disorders can be combated by eliminating them. This applies to any disorder, at any level, from molecular to organ, and they are often related. You can read about all types of violations considered within the SENS program on the resource in articles and. As an example, testing senolytic drugs to remove senescent cells. You can see about the removal of atherosclerotic deposits (more precisely, the decomposition of oxidized cholesterol) in this article. If the example of fasting does not seem to be indicative, then castration leads to an increase in food production. life by 15-25% different types, including humans. This is also associated with a decrease in metabolism due to low testosterone, see. The effect is similar to fasting.
  

  From the very beginning of communication, I have been trying to get a direct answer from you, how, in the light of your beliefs, will you explain that each species has its own very specific (without any “little studied”) lifespan?

  What do beliefs have to do with it? Only facts and logic. In short, it all started at the beginning of the last century with the measurement of basal metabolism in individuals of different animal species, cat. led to the discovery of its relationship with some of their characteristics, in particular mass, as well as mass with max. cont. life (LLP). On this basis, the Rate-of-living theory was put forward. However, the real mechanism of the relationship between metabolism and aging and MPV was proposed in the 50s in the free radical theory of aging (lots of facts!), and its further development in the form of the mitochondrial free radical theory of aging. Details of the development of these ideas can be found in Nick Lane's book Energy, Sex, Suicide, available online.
  Also the reason degenerative changes in the body associated with various pathologies, especially with age, ultimately there is an energy deficiency in supplying tissues, organs and systems of the body. These changes may be accompanied by damage associated with intense external influences various types and infections.

  Basic metabolism and thermodynamic limitations

  If we look at the accumulation of disturbances in an aging organism from the point of view of physics, specifically thermodynamics, then this phenomenon can be considered as a decrease in the flow of energy into an open nonequilibrium system, leading to an increase in its entropy and evolution to a final equilibrium state with a max. entropy - death. As an example, see the thermodynamic model for assessing human life expectancy, using the assumption of influence long fasting at Zotin's. The resulting value of 160 years is somewhat overestimated. However, detailed models are simplified, with a large number assumptions, the author acknowledges this, and defines the requirements for a more accurate description:

  so that, firstly, the thermodynamics of nonlinear nonequilibrium processes is created and, secondly, thermodynamics must be combined with sciences dealing with problems of organization and self-organization, i.e. Thermodynamics of organized systems was created. Both are still far from complete.

  Using basic exchange for describing the thermodynamics of living systems is applicable in a linear approximation, near points of a stable nonequilibrium state, including stationary ones. The measurement itself is basic. exchange is made in inpatient conditions peace. A description of its application to living systems, for calculating entropy from heat production (per unit of mass), including within the framework of the Prigogine-Viam theory of growth and development of organisms, can be found in the book “Biophysics” by Rubin, in Section II. Thermodynamics of biological processes, paragraphs 2 and 4. However, due to the complexity of metabolic reactions and the linear nature of the approximations, it is not yet possible to calculate the real dynamics of entropy (for all its components) at all periods of the life cycle. Also the size of the base. exchange may change with age. Additionally, heat generation is influenced by the level of optimal regulation of homeostasis by the central nervous system. The greater the mass of the brain (more precisely, the coefficient of encephalization), the more effectively the regulation will be carried out. It is carried out most effectively in higher mammals, and especially in humans. Basic exchange is the basis for entropy estimates from below, maximum exchange for estimates from above, and vice versa for NRM estimates. It is possible in the future that the use of various biomarkers of disorders (aging), such as lipofuscin, as data on them is accumulated, will allow us to develop more adequate models of the dynamics of entropy accumulation in the body, and thereby theoretically make calculations of the life expectancy of individuals of different species.
  To summarize, we can say that in physics there is no fundamental prohibition on the value of the MLP of living systems, but there are restrictions associated with the achieved level of organization, cat. can be assessed by their characteristics, including thermodynamic ones. I advise you to find on the Internet the publication by A. Zotin “Patterns of growth and energy metabolism in the ontogenesis of mollusks”, and find time to read it, a lot can become clearer with the position of genetic miracles in the general physical outline) There is no simplification or any kind of reductionism, in the end, the laws of conservation operate at all levels.
  

  And in general, I already mentioned above, I will repeat again: lifespan has a correlation with many things, and the correlation is much better seen between lifestyle, ecology of the species, care for offspring, than the connection with metabolic rate.

  The connections are intricate (remember that this is a self-developing system), but the main contribution to the MPV is the metabolic rate, other factors only modulate it. In the vastness of the savannah, mice and elephants live in the same environmental conditions. There are also individual adaptations related to lifestyle. The effectiveness of homeostasis management also affects the cat. associated with brain mass.
  I’ll try again to show the final result using facts. I found the AnAge database online, cat. contains the data we need on many types - mass, basic. exchange and NRM. That’s actually why I decided to write an answer; I didn’t want to initially, because... our discussion went in circles.

  Here is a graph of the dependence of the magnetic field on mass, cat. I found it online, built using data from this database, as an example

  The trend is quite clearly visible. I built a regression graph:
  I noted the situation of man, the bowhead whale, and the bogeymen of longevity - the Naked Mole rat and Brandt's bat) Indeed, the latter jump out from the general trend. A person benefits even more from the contribution of brain mass, thanks to optimal control of heat exchange (homeostasis). A person can choose behavioral strategies that optimize metabolic rate, for example, optimize calorie intake by choosing a diet, avoid stress loads changing the way of life, using the achievements of civilization, etc. Now let’s see how the metabolic rate for the same species affects the MFL:
  Due to the fact that the main The exchange for many species was not measured and there were fewer points (230). Basic exchange taken for units. mass of individuals of the species (specific value), this is an important point. The man still flies out of the data cloud, but the Naked Mole-Rater and the Vampire Mouse (in the database there is no data on the main exchange of Brandt’s Nightfly, so I took the vampire mouse close to it. There is also no basic exchange of whales, but this is still that epic the picture is their measurement)) although they are distant from the main trend, they are on the edge of the cloud, and do not fly out of it, as in the previous one. graphics. It confirms what I wrote in the previous post. comment referring to the wiki. The main contribution to their BRM is made by low metabolic rate and its optimal regulation. Unfortunately, this database does not contain information on the brain mass of species to calculate the coefficient. encephalization, and see the dependence on it. Plus, of course, individual adaptations of these species, cat. actually interest researchers. These include neotenic traits for humans and goals. mole rat (if you remember in one of the previous comments he proposed the idea of ​​​​increasing the active period of a person’s life by slowing down growth between the ages of 20 and 40, using a genome hack a la neoteny). For years. mice are adaptations similar to those found in birds.
  Let's try to estimate the percentage of contribution to the main NRM. exchange and individual adaptations for different species. The regression line marks the contribution of the main. exchange, deviation contribution ind. adaptations. Let's check for some species located on the regression line. Marked the house. mouse, Damara minnow and sloth bear. Indeed, judging by the wiki, they do not have any features related to metabolic functions and other adaptations, i.e. the basic metabolic mechanism determines 100% of their RMF. Now let's look at the species below the regression line. What could be the reason for a reduced ROM? The white-bellied shrew and Greater red musk shrew (I couldn’t find a Russian translation) belong to the shrew family:

  Shrews have a very high metabolic rate. Every day they need to consume an amount of food that exceeds their own weight by 1.5-2 or more times. Therefore, shrews feed almost continuously, and their sleep breaks are very short. The smaller the shrew, the more periods of sleeping and feeding there are during the day; Thus, in the tiny shrew, the day is divided into 78 intervals. A shrew left without food quickly dies: small species - in just 7-9 hours (small shrew in 5.5 hours). Shrews do not hibernate, but with a lack of food, short-term torpor may occur with a decrease in body temperature.

  Those. the reduced value of MFL is associated with their extremely rapid metabolism. They are champions at this.
  Another example: The marsupial marten is a marsupial. There are many marsupials in this area of ​​the graph. Their metabolism is reduced and their temperature drops by several degrees. lower than that of placentals. On the contrary, according to the NRM, they should be above the registration line. The answer is that these mammals have less efficient metabolism and regulation of homeostasis compared to placentals. In particular, marsupials do not use brown fat for thermoregulation, but rather less efficient contractile thermogenesis. However, additional clarifying arguments are needed. The difficulty is that there is little information on marsupials and the peculiarities of their metabolism in RuNet.
  Thus, based on the schedule, the net contribution of the main exchange in NRM for goals. digger and years. mice make up 30-40 percent, the rest is ind. adaptation. As data becomes available for other species, future updates may be possible. It is also necessary to separate the contributions of adaptations associated with optimization of metabolism, such as hibernation and torpor (and they are significant, see), and other mechanisms such as neoteny.

  How does the NRM change with the evolution of species? Perhaps so. For example, for a mouse in the savannah, new long-term favorable conditions for feeding and reducing predation pressure arise due to climate change. Individuals with a longer growth duration begin to be selected, while their masses will be increased and the metabolic rate will be reduced. This will be accompanied by some morphological and lifestyle changes. When the niche is filled, i.e. food resources will begin to be consumed, and perhaps larger predators will appear, further selection based on growth duration will stop, and the new kind with an increased growth time, greater mass and, accordingly, a greater life span. Plus individual adaptations, cat. will also affect the NRM, like some amendments. It must be borne in mind that these adaptations themselves are often nothing more than some metabolic hacks specific to this type (such as hibernation, torpor, etc.), aimed at optimizing it, recycling waste, or restoring disorders associated with it.
  The opposite is also true - selection for a reduction in growth time, for example, with island isolation of a species, as in the case dwarf species elephants. They are fossils, but there are elephants about. Bornean, and African forest elephants, cat. smaller than the Asian and African elephants, respectively. It was not possible to find information on the lifespan of elephants (the information in AnAge is clearly outdated and incomplete), so the average lifespan is based on information from the wiki and Animalia. Reduced forms of elephants live 5 years less on average and reach sexual and physiological maturity earlier, i.e. grow faster. In general, it is logical that evolutionary changes begin with a nonspecific trait - the time of growth of the organism, and only then selection for species-specific traits is activated. Interestingly, it is possible to get a mouse from an elephant) nature made an “elephant from a mouse” (an ancient rodent)))

  I’ll also give you the opinion of an authority, if you don’t trust me) Moreover, an evolutionist, i.e. a supporter of the genetic approach to aging and MFA by definition. I mean A. Markov. On “Elements” there is an article of his dedicated to human life expectancy. It argues that centenarians are approaching max. possible continuation life. Here is what he writes about the nature of this limitation:

  The nature of the postulated “biological limit of longevity” is not discussed in detail by the authors, since this is a separate topic beyond the scope of the article. A good analogy is provided by gerontologist Jay Olshansky in a popular synopsis for the article under discussion. He writes that the biological limit to human longevity is of approximately the same nature as the limit to running speed. There is no special “genetic program” that has evolved through selection specifically to prevent us from running faster. The running speed limit is by-product other adaptations that have determined our anatomy and its associated biomechanical limitations. And just as new methods of training athletes could lead to new running speed records, future biomedical technologies could pave the way for new longevity records.
  The limit of longevity, about which we're talking about, cannot be a special adaptation that developed under the influence of selection (for example, so that old people timely make room in the sun for the young), because during almost the entire human history no one lived to such ages. Other aspects of human aging, such as the abrupt shutdown of female reproductive function long before the loss of vitality (see menopause), they can be independent adaptations. But not imminent death, guaranteed to occur upon reaching an age to which hardly a single primitive hunter lived.

  Intuitively, both Olshansky and Markov correctly grasped that MPV is not associated with genetic limitations, but with some other mechanism, but they could not bring the idea to its logical conclusion. Apparently due to a subconscious attitude to explain everything using genetics)

  By the way, I learned about AnAge from this article, there is a link to another article by Markov, where it is reported. Take a look, there are the same graphs for mass and MFL. Only the author rearranged the axes and drew the dependence of mass on the MF) Apparently by analogy with the graphs of changes in human mass with age. It doesn't make sense for species. I have never seen a graph in this form in any publications; even the most inveterate geneticists plot the dependence of the MFL on mass, without confusing cause with effect. I can give a lot of links.
  

  Hela Cells

  Please explain once again the phenomenon of immortal near-human tissue? Why don't HeLa cells accumulate them? If the answer is the same as above (primitivism), then explain how (and where?) and what causes the “transfer” of damage from cells to the level of organs and systems? Why exactly do the cells of a finished organ accumulate damage?

  1. What does immortal mean? The question is philosophical. Even when cells are divided into genetically equivalent ones, it can be considered that the parent cell ceases to exist, i.e. formally dies. On the other hand, it is believed that cont. life for such cases is not defined, in comparison with sexual reproduction. In any case, they will not be immortal due to resource limitations. “Immortals” is a generalization (abstraction) of long-lived organisms. Sometimes they talk about the immortality of genes or populations, but these are theoretical constructs; individual organisms actually act.
  2. Cells die from accumulated disorders if they are irreversible (,). If reversible, then recovery occurs. Division also plays a role. If there are disturbances, but division occurs normally, then these disturbances are distributed among the daughter cells and can be eliminated in them; if not, then the cell dies (). This is the meaning of the growth of organisms. Cell divisions compensate for the loss of non-functional cells. When growth stops, only reparative mechanisms at all levels remain. These mechanisms themselves are subject to destruction, and their effectiveness decreases over time; see the chapter in this book dedicated to the age-related degradation of reparative mechanisms at the cellular level. This leads to the progressive accumulation of disorders at all levels, which constitutes the phenomenon of aging of the body.
  3. The accumulation of disorders in cells within a tissue is greater than in a single-celled organism, due to environment and specialization. This applies to the removal of decay products, heat removal, etc. Heat removal and damage associated with it are also relevant for microelectronics with increasing integration (there are special mechanisms to combat overheating). This is a consequence of thermodynamic limitations. Cell cultures also have similar problems.
  4. Hela cells are not an independent organism; their life is maintained in artificial conditions. Their “immortality” is connected:
  

  with the consequences of infection with the human papillomavirus HPV18. The infection caused triploidy of many chromosomes (the formation of three copies instead of the usual pair) and the splitting of some of them into fragments. In addition, as a result of infection, the activity of a number of cell growth regulators increased, such as telomerase genes (a regulator of cell “mortality”) and c-Myc (a regulator of the activity of the synthesis of many proteins). Such unique (and random) changes made HeLa cells record holders for growth speed and stability, even among other lineages cancer cells, of which there are several hundred today.

  That is, rapid reproduction does not allow the accumulation of disorders, unlike normal cells in the tissues of the body, and they do not perform specific functions, cat. lead to an accumulation of violations. This does not mean that they will not die if they accumulate damage. A clear analogy: a motor in a car will accumulate more damage and fail faster than the same motor on a stand running idling.
  

  My field season has begun

  Happy fishing..)
  Here is a study of fish showing that the accumulation of disorders in their bodies also occurs due to oxidative stress. Although, obviously, the aging process in fish differs from mammals, due to the specifics of metabolism. In one of the comments, someone wrote that some fish grow all their lives and die from lack of oxygen when they reach large sizes. This is due to the fact that body weight grows in proportion to the cube of size, and the area of ​​the gills is only proportional to the square. Same physical limitation leading to degradation and aging. Ultimately, the cause of aging and death is energy deficiency.