Aging is a consequence of development
How does aging begin
Vadim Gladyshev, Post-science
We know for sure that aging ends when the body dies, but the question of the beginning of aging looks more complicated. When I ask the audience at conferences about the beginning of aging, regardless of whether they are experts in the field of aging or ordinary people, all the answers are divided into six different categories. Someone says that aging begins during the fertilization period – minus 0.75 years. Others say that at the time of birth – 0 years. Still others say that during the period of the lowest mortality in humans, this is the age of about nine years. Someone says that aging begins from the time of puberty – 12-13 years. Another group of people says that aging begins when development ends – at about 20 years old. And the remaining group believes that aging begins when visual features associated with old age become noticeable: wrinkles, alopecia ("baldness") and others. But in fact, even within the scientific community there is not one dominant idea.
Minimum chance of dying
We tried to test experimentally when aging begins. First we need to consider mortality.
It is often said that something gets old, the probability of death of which is higher tomorrow than today. In this case, it is clear that in old age the body dies with a high probability. If you look at this dependence at an earlier age, the probability will be less. The point of minimum probability can be called the beginning of aging.
If we consider the entire curve for the whole age, then it has a U-shaped shape. The probability of death is very high at the beginning of life, and then it gradually falls and reaches a minimum of nine years, but then begins to grow again. Nine years is a very mysterious figure, because it is not connected with any biological process, so many scientists are confused by the fact that this figure is a kind of turning point. Another point that confuses scientists: if aging is associated with an increased probability of mortality and this probability drops at the beginning of life, it means that a person becomes younger after birth and up to nine years.
A couple of years ago I gave a theoretical lecture at the Harvard Faculty of Systems Biology. The professor sitting in the front row said: "Of course, since the probability of death decreases at the beginning of life, then, of course, the body is younger." Then I asked him: "Let's take a child who is one year old and a child who is five years old. Which one of them is younger?" The Professor replied: "A five-year-old is less likely to die, which means he is younger." But it doesn't make sense: a five-year-old should be older than a one-year-old. As a result, if we consider the beginning of aging according to the probability of mortality, it turns out nonsense.
For the second approach, we decided not to look at total mortality, but only at mortality from age-dependent diseases: heart disease, cancer, sepsis and others. When we studied this dependence, we also got a U-shaped curve. The probability of such diseases was at the beginning of life, after birth it falls, and then after nine years it begins to grow again. It turned out that not only cancer and heart disease, but also regular visits to the doctor, not related to prevention, also have a U-shaped curve.
What is aging?
For the next study, we decided to study the essence of aging. To begin with, we looked at the age dynamics of the processes that are the most important. The most important process is the accumulation of damage. The increase in the amount of damage occurs as a consequence of life. Active metabolism produces damage, and they accumulate. We began to study two types of damage.
The first damage is mutation. When we looked at the mutations, no U-shaped dependence was found. Mutations are few at the beginning of life, and over time they gradually grow. The second point is epigenetic changes that are associated with cytosine methylation. The lesions on these cytosines also do not have a U-shaped curve, they also gradually accumulate with age.
If you look at the damage itself, the essence of aging, it turns out that aging begins at the beginning of life. Based on this study, the exact age cannot be called, it is exactly before birth. And the failure in mortality in the ninth year of life occurs as the intersection of two curves. One curve is mortality due to aging, which is very small and gradually increases with age. The second is early mortality, which is not associated with aging. Early mortality has several components. For example, aneuploidy is a developmental error. Another important component is mutations in organisms. Not somatic mutations that accumulate with age, but initial, hereditary mutations.
Early mortality
To study early mortality, we took the maternal and paternal genome. We found that on average a person has seven very harmful mutations that destroy genes. And a child may have an average of seven mutations, because it acquires half from each parent. But in a situation where a child has inherited twelve mutations, they will lead to harmful consequences, and the child may die at the beginning of life. This is a terrible event for everyone, but from a scientific point of view, this process allows you to remove harmful mutations from the population.
The process of removing harmful mutations is important for the human population. Consider a situation where a child inherits mutations from both parents, but de novo mutations also enter his body. These may be mutations from sperm or eggs that live in the body and accumulate mutations during life. On average, 50 to 100 new mutations are added in each generation. In fact, most of the genome is not so important, but about 10% of the genome are functionally important areas where mutations also fall. Then with each generation our gene pool should be worse and worse, but this does not happen, because there is selection. Natural selection makes it possible to remove mutations from the population, although selection is weaker every year, because medicine helps the weak and sick. In any case, there remains a selection associated with the end of the reproductive period, because about 80% of people have children. But this selection is not so strong, so it helps selection at the beginning of life – early mortality, which allows you to remove harmful mutations from the population. These two types of selection allow humanity to exist.
Why doesn't everyone die from damage?
It is important to understand that aging goes in parallel with the development process, but it is not a continuation of development, it is a completely different process. Aging is a consequence of development. The body develops, and because it lives, it begins to age. On the one hand, it's bad, but on the other hand, it's good. If these are two different processes, then you can try to influence one without affecting the other. This gives us new opportunities to fight aging.
If aging is associated with the accumulation of damage, then how does life exist on Earth at all? Damage accumulates as a consequence of life not only in organisms that age, but also in organisms that do not age. For example, in hydra, the probability of mortality does not increase with age, there are no other signs of aging either. So they don't age. In fact, this is due to the fact that the damage cannot be removed, because there are too many of them relative to other biological processes, but they can be diluted. Organisms used this important process when life first appeared on Earth. The first protocells were already thinking about how to dilute the damage.
Imagine an organism has some kind of function, during the existence of a generation, two damage molecules have arisen due to the use of this function. Then the cell split, and now two new cells have one damage each. The cell continues to live, two molecules accumulate in each one again, and then it separates again. If the rate of damage accumulation is not higher than the rate of their dilution, then the cell will not even know about these damages. This process of division explains why life exists on Earth at all.
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