Biologist's look at the roots of our aging

Hello!

The following text was originally typed as a continuation of this dialogue , but the size of the answer exceeded all imaginable dimensions, and considering that there is a demand on Habré for the topic of the origins of aging and death from it, I decided to issue his (answer) as a separate article.

Disclaimer: if it seems to you that the text is directed to a specific person, and not the audience as a whole, then it is so, but I will not change anything.
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This article is written entirely from the head, which is called in one breath (although in three installments), because it contains the minimum number of links and pictures - please understand and forgive, or write in a comment, maybe I will correct something.

Instead of a prologue: Appeal to phenik`s . I looked back at our dialogue and realized that I was building the wrong communication, something I ask a lot of uncomfortable questions, forcing you to go into a dull defense (because apparently we went in a circle) and do not highlight your position. Sorry, I'll try to fix it.

I don’t even know where to start, so I’ll start, perhaps, from the most distant and abstract area. You incorrectly apply thermodynamics to biology. It seems to you that chaos (I will deliberately avoid the word entropy wherever possible) created in the environment will certainly have to "defeat" the biosystem (after all, we are all waiting for thermal death). But this is not true, on the contrary, these exotic chemical reactions learned to benefit from the surrounding chaos and turned into biological systems, and the vector of development of these systems is mainly aimed at isolation (in fact, independence, but in the context of our dispute "isolation" is more correct the word itself from the external environment and the increasingly effective use of this environment (and its fluctuations) in its own needs. If you look at the molecular standard of living, you will see that basically we live by Brownian motion and cunning juggling with ions, hydrophobicity and hydrophilicity. You will see that it is not oxidation that inevitably damages cellular structures, and the cell effectively uses redox reactions for its own needs.

Immediately make a reservation, I do not claim that the chaos created around the biosystem is unable to damage it anyway, I try to emphasize that this chaos is a normal environment for biosystems, and that, in the aggregate, biosystems derive much more benefit from chaos than they receive harm, otherwise they simply would not exist.

If we stand at the point of view that the environment inevitably destroys the body (modern, continuously adapting to the environment in which it has lived for the last 3.5 billion years), and moreover destroys so effectively that the body exists only a moment against the background of history, then we will have to admit that life could not have originated in such an aggressive environment as on planet Earth. Or you will have to explain at least some approaches how the life was protected from such an impact. Why modern organisms, stuffed with repairing systems at all levels of an organization, cannot last even a century, consistently accumulating damage and collapsing, and some kind of life span, which by definition does not have such mechanisms, managed not only to avoid these problems, but also to develop to the extent that do we call life? (It smacks of divine intervention).

Another aspect of the view is the inevitable accumulation of damage. I do not like this argument because it is more philosophical than practical, but it is very suitable for this part. If I (or someone else) will meticulously finish off the answer to the question of what life is and what death is, bravely tearing off the husks of words, then sooner or later I will have to admit that there is certainly death, but any living individual of any kind there is a continuous line of cell colonies living for 3.5 years. You see, what is the case, no species has a stage of “unlife” in its development / reproduction (we will leave viruses and the like behind brackets). It does not matter if you share, bud, reproduce with the help of sperm or sperm, you have seeds or eggs, in any case, all these intermediate agents between generations are alive in all "areas" of development. (I know, adherents of the theory of damage accumulation will answer, as usual, that the germ cells are specifically additionally protected from damage or live too short a life or are inactive for some time or ... to accumulate damage, but here’s a question (we’re trying to think systemically) if the protection mechanism is in principle feasible and is used by many species, what prevents the species from applying these mechanisms to the whole organism?)

Metabolism.

You and what is metabolism represent yourself distorted through thermodynamics. And this is not true, thermodynamics was standing here from the side. Metabolism is a combination of all processes in the body, and not a measure of the speed of physical (thermal) processes. Moreover, in full agreement with what I wrote above (biological systems have a vector to ever increasing isolation from the external environment), metabolism naturally (as a reflection of the totality of all processes) invariably rises from less complex organisms to more complex ones (if only because that in more complex systems there are more processes). That is, it is not the metabolic rate that determines how the body lives, but the body determines its own metabolic rate with its life.

Trying to add “thermodynamic metabolism” to old age, you are trying to prove that the higher the speed, the shorter is life, but this is just because you are not familiar with biology, in essence this postulate is absurd.


First, yes, there is some traceable regularity, but this regularity is from the “why there are more red pencils than green ones” area. You can count the pencils and state the fact that yes, there are more red ones, but there are not necessarily any underlying causes of these differences. Or another example - if you are black, then your nose is very likely wider than most people in the world, but if you have a wide nose, this does not mean that you are black. You see, it is not the width of the nose that determines the race or the color of the skin, but the race also determines the color of the skin and the width of the nose. You can build a graph where you apply a scale of skin color to one axis, and a different width of the nose to another axis, and the Excel will obediently draw a straight line indicating the relationship. This is how the dependence of the metabolic rate and the maximum lifetime was derived, that is, it is the same owl stretched over the globe.

Secondly, living systems in their evolution tend to increase their isolation from the environment. So, warm-bloodedness is an adaptation developed for protection from the environment (more precisely, for the independence of the metabolic rate from the external temperature, but in our cases it’s the same thing), and not for the metabolism to overclock and kill us. That is, the appearance of warm-bloodedness, should (in fact, not "should", but it is), on the contrary, stabilize all chemical reactions in the body and therefore more effectively resist the influence of the external environment by supporting (repairing) the organism.

If we take a look at the graphs given by you:



then we will immediately see a lot of interesting things that do not fit into your concept. I would have much to complain about, but the amount of text limits me, I will give one, but the most obvious example. Only mammals are noted in the graphs (well, the stricter the sampling frame is, the easier it is to find a correlation), but what happens if we add birds (warm-blooded among other things)? For example, all sorts of sparrows and tits by weight, like mice, by metabolism and overtake rodents (to fly with wings - not to dig with their paws), but they live small-fingered for about 5-15 years. And now we compare with the fish of the same mass - it became even worse! They live about like birds 5-10 years old, but their metabolism is much lower than even rodents.

How would you dismiss these "anomalies" by stating:

The connections are intricate (remember that this is a self-developing system), but the main contribution to the NRM is made by the intensity of metabolism, other factors only modulate it ... ... There are also individual adaptations related to lifestyle. Also affects the effectiveness of managing homeostasis ...
... The main contribution to their NRM is low metabolic rate, and its optimal regulation ... ... Plus, of course, individual adaptations of these species.

But on the contrary, I will tell you that there are a lot of exceptions, in your theorem, is it not logical to assume that, as you put it, individual lifestyle-related adaptations reflect their metabolic rate? Not a high metabolic rate determines our warm-bloodedness, but our warm-bloodedness determines the metabolic rate. But the very warm-bloodedness is due to adaptation to the environment. And here we smoothly turn to the environment, that is to say to ecology.

Ecology

You misunderstand what ecology is. Ecology in biology is not “someone spilled oil - ecology is bad,” ecology is the relationship of the species with each other and the environment. So when you write:

In the open spaces of savannah, the mouse and the elephant live in the same environmental conditions.

We understand two things, the first is that your idea of ​​ecology is based on mass media imposed by "green" and relate exclusively to human ecology. Secondly, you completely misunderstood what I meant when I wrote that the maximum lifespan depends (including) on ​​the ecology of the species.

Well, we already have an elephant and a mouse, let's use their example to figure out what the ecology of a species is (briefly and with a bias in the causes of the lifetimes of these species). Living on the open spaces of the same savanna, the elephant and the mouse have completely different ecology. The elephant is a large herd of herbivores by size and has no natural enemies. Elephants have a complex social structure that manifests itself in the formation of groups in which the young grow. Usually, an elephant bears one elephant (once in several years), the gestation period is more than a year, after birth the young are protected until they reach puberty for 3-4 years (for a long time, even by mammalian standards). In cases of lack of food, water, other resources, elephants can make long migrations over long distances in search of the necessary resources.

What kind of environmental conclusions can be drawn from here relating to the lifespan. The absence of the press from the side of predators leads to the fact that it is not required to constantly replenish the population from loss.

The elephant is not the most plastic in the ecological plan, but the ability to find the necessary resources at considerable distances from the main pastures compensates for this drawback, which again saves on the population replenishment in cases of natural disasters and does not require an emergency increase in numbers.

Of the two above-mentioned points, it becomes clear why an elephant has such a long gestation and maturation (large offspring in the absence of limiting factors can dramatically increase the population size condemning it to excessive intra-specific competition (to put it simply - hunger)). And long-term gestation and maturation are already signs of long-lived species (why rush and spend a lot of resources at a time, if you can slowly and slowly rush to “collect” a new individual, while ensuring a stable population size). If we add deep socialization here, tied up also on the “leader” (for the picky on the “leader”) that distant pastures and watering can remember, it becomes clear why an elephant has such a long life - it is more convenient for the population from an ecological point of view.

We turn to the mice (abstract mice living in a shroud). A small animal that feeds on either vegetation or its fruits, often both. The species is under significant pressure from predators - a lot of enemies. The population is inactive, usually living in a confined space. In terms of food and habitat change, rodents are surprisingly plastic.

What can we pull out of this environmental feature? Essential press predators must be compensated for by the offspring. Hence the high rate of reproduction (here, both short pregnancy, and fast maturation, and multiple pregnancies in a short time, and the number of “puppies” from the female).

The limited range of a specific population and the inability to quickly migrate over long distances (they are small) make mice vulnerable to various disasters (flood, drought, and other diarrhea and gold), so rodents often have mechanisms for an urgent increase in population with the availability of resources and living space. As we have outlined above, a high reproduction rate has its own risks, in order to avoid overcrowding, mice have a behavioral mechanism of birth control and the immediate destruction of offspring.

High rate of reproduction, lack of care for the offspring (the young are almost immediately active), high pressure of predators - are environmental markers of short-lived species.

But what about the naked digger! He is long-lived. Let's understand (from an environmental point of view). Overwhelming numbers of rodents lead a burrowing or semi-underground lifestyle. But the naked excavators went further, and switched to a completely underground way of life. Such a cardinal change of habitat could not but affect the view. First of all, the diggers went into the darkness almost completely rid of the influence of predators. Since unlearning breathing is problematic, as well as winding a network of tunnels (albeit more), oxygen becomes a limited resource. The population responds with a number of measures, the main of which is birth control through a strict hierarchy that allows you to control both the birth rate and the distribution of resources. Since we consider only the ecology of the species, we will dwell on this point and compare the result. And so we have an almost colonial appearance with an abnormally low birth rate for our family. With coloniality, which, as noted above, low reproduction rates are environmental markers of longevity.

I think these examples should be enough, but since I still respond to your comment, we will go over the person as well.

You write:

The person jumps out even more due to the contribution of the brain mass, thanks to the optimal control of heat exchange (homeostasis). A person can choose behavioral strategies that optimize the intensity of metabolism, for example, optimize calorie intake by choosing a diet, avoid stress loads changing lifestyle, use the achievements of civilization, and so on.

Homeostasis is, of course, cool, I really do not know where you get that person manages homeostasis more optimally than a bear, for example, but God be with him - it does not matter. But you almost guessed with the mass of the brain, it is really one and indirect reasons for our longevity. Man is in many ways unique beast, our hypertrophied culture, and the overly complex social hierarchy demanded a huge brain from nature, in turn, a large brain volume caused a significant part of maturation to endure during the embryonic period (as they said in one old series “Try to pull out something that is pumpkin-sized through the fact that the size of an orange "). This led to another unique characteristic of the species - the longest period of postembryonic development. But the culture rushed up! After all, all this postembryonic development can be combined with the transfer of knowledge from the older generation to the younger one, which is very much promoted by complex social interactions.

Humans are faced with some features that are not very willing to combine. In particular, it is necessary to defend oneself from predators and get food, often for the sake of this moving over considerable distances. At the same time, pregnant females lose their mobility in the later periods, which are not so short (we have one of the longest pregnancies), the young in general in such situations are vulnerable, and very young and young are not capable of transitions and protection even from the most miserable predators. . So it was necessary to allocate roles in the population. And here we get the social structure that we have: a part of the population (pregnant women and children) is sitting in a safe place, the getters carry food to them. But here is a new snag, who will pass on the experience to the young, if the one who generates and transfers it is often forced to be absent? Here comes to the aid of old age. That is, the full cycle of life becomes as follows: Birth, maturing (dwelling in a safe camp, processing food, making tools), maturity (protection, food extraction, bearing, caring for young (female)), old age (transfer of experience, protection, processing food, manufacturing tools, population management). That is, old age is the next stages of human life, and it is very important for the population. Probably this series seems to many to be far-fetched, I will not write much in proof of what has been written above (because I have already written so much already) - read something better in anthropology, I will just give a few of the most vivid examples that everyone can understand.

With a complex social structure with a complex hierarchy (where the main one is not one, but many, and subordination is on a heap of nuances), a mechanism of caste “recognition” is required (well, let it be desirable). The man chose the visual path - changes in the phenotype.
A teenager, even if he is strong, tall and handsome, still does not look like an adult man, even if this man is a weak little bug. There are no special biological reasons to grow a beard or a mustache to an adult and not to raise a young one, we could immediately be born with mustaches and beards, or grow them immediately after birth, but we have postponed this process to maturity for greater visibility "who's older." After walking with a mustache for a certain amount of time, our phenotype again undergoes changes, not as dramatically as when growing up, but the same drastically - the shape of the ears, nose, eyes, eyebrows, hair color or even their absence changes. And do not even try to prove to me that this happens as a result of damage. Firstly, the world is full of species that do not have phenotypic manifestations of old age, secondly, for example, there is this grandfather Wang:



Looking at his body and not seeing his face can and can be confused with thirty years old, but as soon as you see the face, you no longer doubt that this is a grandfather. It is difficult to imagine how selectively the damage accumulates solely on the face. In order not to be verbose, I will say that phenotypic changes are so stable that they are now used as aging biomarkers, and in some cases this is more accurate than picking in cell chemistry, for example, here

In addition to phenotypic age-related differences, we additionally get psychological (which is natural, because the role changes with age (read behavior)), this is well demonstrated by such well-established concepts as “why”, “youthful maximalism”, “settle down”, “fell into childhood” . You can look back at others or remember your youth. While you are young, you risk easily, you are daring and you are drawn to adventures, then you “settle down”, and in old age, many are drawn to a quiet sitting at home for some handmade hobby, such as picking in the garden.

Similar results: a person has one of the longest periods of maturation, has a special “post-fertile” age, a complex social structure, and all this is a marker of long-lived species.

In general, as can be seen from this small ecological analysis, the ecology of the species is a peculiar mirror of the evolution of this species. And this brings us to the next important topic of our trial.

Evolution

You somehow very one-sided and incomplete understand evolution. I would like to write about the reasons, but it is very long, eh. Go to the point. The adherents of the theory of damage accumulation and, as a consequence of the death of an organism, proceed from the primitive notion that selection works with a particular individual (may the trees for a non-politically correct word forgive me), hence the incorrect conclusion that immortality is an unconditional benefit that allows you to constantly spread your genotype and there are no immortal organisms, then evolution is not capable of generating immortality.

But the evolutionary process is much broader and works immediately on multiple levels of biosystem organization - from the intracellular-cellular, continuing on the individual, population, ecosystem, and finally ending the biosphere level (here, of course, you can argue with evolution there or not). In our discussion, we are primarily interested in population selection because it is here (mainly) that there is a selection for mortality.

A population is not just a convenient name for a cluster of individuals of one species. The population is the superorganism level of the organization of biosystems. The population has its own habitat, its ecology, its homeostasis, its reproduction, its lifespan (although many populations are conditionally immortal), genotype, phenotype, etc., in short, the population largely behaves like a whole organism. We are primarily interested in the genetics and phenotype of populations.

Among adherents of the theory of accumulation of errors, there is an opinion that there is no population selection or it is vanishingly small. This opinion is almost as ridiculous as the statement about the flat Earth. Therefore, I will not seriously argue here that populations are also subject to evolution, this is a closed question for biology for about fifty years. You can study this question yourself if you wish, a section of biology called “population genetics” deals with the evolution of populations. If you want to dig deeper, I was always impressed by Wright and Fisher , and the Hardy-Weinberg law is considered to be the fundamental law of this science - google, find which - any article is more decent or a textbook and read, there is no complicated mathematics.

So what is the evolutionary advantage of death? What are you, brothers (!), Death is the strongest catalyst for evolution, so strong and revealing that we, speaking of the speed of evolution, measure it by generations, and not by time. Death in this case provides genetic / phenotypic plasticity of the population. It allows you to quickly occupy vacated ecological niches, to adapt to the pressure of the environment . After all, if you do not die, you cannot adapt to the changed conditions, and the conditions change over time. What turns the lack of plasticity and what does death here is well demonstrated by an intermountain spiny pine (it looks like an almost immortal species in truth). If you look at the range of this species,



it is clearly seen that these small arealchik of small populations used to merge into one large area.

But centuries passed, even millennia, glacial periods changed warm, the ecology of these territories changed dramatically - some species replaced others. And if adults, strong organisms (perhaps the largest organisms on Earth) are able to resist change and continue to live, then the growth of the shoots is no longer able to survive and develop normally in these territories. Here the last Methuselah will live to their ax / woodcutter or still natural death and the view from the planet will disappear. Unless, of course, a person does not help artificially.

Genetic / phenotypic plasticity, not the only advantage of death, another important advantage of population homeostasis. Other advantages of death can be found, but they will no longer be so universal, and will have species specificity (for example, feeding young stock with their own carcasses).

Well, well, since death is so beneficial to populations, then why are there immortal organisms? Well, in the first place, we figured out that even if such species exist, then in historical perspective they lose out in an evolutionary race. And secondly, there are conditionally immortal species, and this is somewhat different. Let's look at the example of the hydra. For a long time, theories on the hydra's immortality have been advanced and refuted, and Daniel Martinez put an end to a four-year experiment with different groups of hydras. Yes, the hydra is immortal if she arranges an eternal summer. But what do we see in natural populations? Hydra lives to fall, sexually fertilized leaves the "egg" and dies. That is, from an environmental point of view, the hydra is not at all immortal and its lifespan is a year (well, more precisely, from spring to autumn). Here the property of evolution is well manifested to use what is and not to touch a system that already works well.

There is also the famous jellyfish turritopsis (which is also a hydro-class class, by the way), also seems to be immortal. I will not waste your time and I will write without details, if you look at its life cycle, then immortality is as imaginary (and even more) than that of the hydra and is reduced to reproduction. There is no such thing that the individual would rejuvenate to the previous stage and remain the same individual (in the same body), and then the same individual matured again.

Instead of an epilogue.

Looking back at the topics already covered, I want to cry as many topics still remain (for example, telomeres, beloved by the Staroborians, who not only contract (and often not in all tissues), but in some species are lengthened, and in general do not agree very well with aging , about mitochondrial aging "to which there are also questions , about the fact that DNA methylation is not a consequence of old age, but a laid-in mechanism for changing gene expression, about the fact that it looks strange how the repairing systems that work well at a young age begin to break (that is, to accumulate damage?) strictly after puberty and strictly at the same age and regardless of the conditions , etc., etc.).

Looking at your time, I want to cry twice. We looked only at the tip of the iceberg, and I have no time to inspect the underwater part. Maybe you will find other information yourself, or maybe if you strongly ask, I will return with the second part (hardly), but this will not be until next year (February), but for now I would like to say a few words to the last.

I do not want to convince you that it is impossible to win old age, of course it is possible, but at the moment we don’t have any idea how old age works at the molecular level. Biologists in general do not really understand how gene expression is regulated in each particular case. And no one can say whether old age is hiding in a particular ancient DNA segment (hardly of course), or scattered over all genes in sub-program pieces (which would explain some features of old age), and until we understand these mechanisms old age and death will be inevitable. And all these people, who so easily promise you eternal youth thanks to their procedure, coenzyme, diet, and so on, are charlatans who are trying to sniff out their goods to you, or knock out another research grant (I admit that there are those who are sincerely mistaken,but it absolutely does not change anything). Someday mankind will deal with this mystery, but I am not afraid of our generation.

Good luck to you. And I wish you to live at least to the limit determined by nature.