Eternal life: tomorrow or never?
All about our relationship with aging
The life expectancy of a person increases with each new epoch. If it was a big problem for a person in the Middle Ages to live up to 50 years, now 90 is not the limit. Gerontology is preparing for a scientific breakthrough — scientists invent medicines for old age, study ageless animals and aging mechanisms, put forward new hypotheses. PostNauka asked gerontologists Alexander Khokhlov and Valery Novoselov to tell us why we are getting old and whether there are ways to avoid it.
Aging and the science of it
Aging is a decrease in the vitality of the body with age. Aging is a set of age-related changes that lead to an increase in the probability of death. This is the classical definition that authorities in the field of gerontology adhere to, but in the philistine environment it is often ignored and interpreted incorrectly. "How to fight aging" and "how to prolong life" are different questions. Prolongation of life may not be related to the effect on aging.
Gerontology is translated from ancient Greek as "the science of the elderly." The British gerontologist Alexander Comfort in the book "Biology of Aging" expressed the idea that the name is not quite correct: in fact, this is not a science about old people, but about aging, that is, about how old people become. Gerontology studies the mechanisms of aging. That is why she should clearly understand what aging is, but there is no general opinion on this issue among gerontologists. British gerontologist Aubrey de Grey, for example, believed that aging is the accumulation of DNA damage, although, in fact, it is only a mechanism — damage does accumulate, but their accumulation does not mean that a person immediately ages.
(In fact, De Grey names 7 causes of aging: "extracellular debris", "intracellular debris", cell death and atrophy, mutations in the nucleus and mitochondria, cell aging, cross–links between biopolymer molecules - VM).
Mercedes-Benz invested a lot of money in the study of aging: they were interested in how cars age. It turned out that their aging is very similar to the aging of humans. With age, they also increase the likelihood of a serious breakdown: the longer the mileage, the more likely it is that the breakdown will be fatal. There is such a risk, even if the car is in the garage — it still deteriorates. However, if the car is repaired all the time, its worn-out parts are replaced, then it will "live" almost indefinitely. See how the limousines of the 30s of the twentieth century look, which are carefully cared for by their owners!
Unlike cars, living organisms have the ability to "fix" themselves on their own. This is provided by the processes of repair (DNA, membranes, etc.) and regeneration. This allows some animals (for example, freshwater hydra) to live for a very long time without aging at all. Unfortunately, the more highly organized living objects are, the more tissues and organs they have that cannot be "repaired" with 100% efficiency.
Mechanisms of aging
When we talk about the mechanisms of aging, it is important to remember that they must be universal, i.e. they must explain the aging of any organisms — protozoa, bacteria, mammals, birds, etc. Some scientists associate it with the microbiota, however, there are living objects that do not have a gastrointestinal tract, but they still age.
Apparently, the most widespread concept to date corresponds best to the requirement of universality, according to which the primary cause of aging is the accumulation of errors in the genome.
The well—known gerontologist Fritz Vertsar [1], founder of the journal Gerontology, believed that it was all about collagen - supposedly its molecules are "cross-linked" during aging (so-called cross-linking occurs between them), and connective tissue increasingly shields the tissues and cells that it surrounds. As a result, nutrients penetrate there worse, and then the corresponding cellular structures, including DNA, change.
In recent years, the theory of programmed aging has regained some popularity. She talks about the implementation of a program in the body that must necessarily lead to aging. A child is born, grows, changes, becomes an adult — develops — but, as gerontologists-"programmers" believe, we also have a special program for subsequent aging.
The famous Russian gerontologist Vladimir Dilman, like many other scientists, recognized the existence of only a program for the development of the body, arranged in such a way that after its implementation, the emerging "side effects" necessarily lead to age-related diseases (cancer, diabetes, cardiovascular diseases) and aging.
Researcher Bernard Strehler wrote one of the fundamental books on gerontology, "Time, Cells and Aging", in which he suggested that there are four characteristics of aging — gradualness, destructiveness, endogeneity and universality. Endogeneity (from other Greek. ἔνδον - inside and γένεσις — origin) means that aging will occur in any case — even under the most favorable conditions, with the most heroic health. This mechanism is embedded in all our physiological reactions, metabolism, epigenetic (including inherited) changes. That is why it is very difficult to deal with age-dependent diseases and with the mechanisms of aging, where there are signs of cascading, it is not clear what is the cause and what is the consequence.
People are not cells, tissues, or organs; they are much more than the sum of all these things put together. And in this integrative superstructure, it is difficult to trace cause-and-effect relationships. Therefore, it is likely that new ones will be added to the Streler criteria over time.
Biomarkers of aging
Biological age is a virtual quantity that has nothing to do with passport age. If a person is 70, and he, as they say, "looks 30", it means that his physiological indicators, by which we are used to assess age — for example, the number of wrinkles on the skin, posture, dental condition, etc. — correspond on average to the indicators of a 30-year-old person in a particular population. In experimental conditions, we are based not on our visual experience, but on the corresponding calibration curves linking the passport age and various biological characteristics.
The term "biological age" as the concept of measuring aging was finally "legitimized" by gerontologist Alex Comfort in the 1960s: "The method of short-term measurement of the rate of human aging is now necessary and possible. He could bring a lot of useful things to fundamental research on slowing down age-related changes from animals to humans: he would provide important experience and knowledge about aging, different from mortality. Already existing agents can affect the rate of aging, but which cannot be detected with the available capabilities."
How is calibration performed? For example, they take mice of different ages and measure the number of hairs of wool per square centimeter. This number of hairs is deposited along the ordinate axis, and age is placed along the abscissa axis. A calibration curve is obtained. Then they take a mouse whose age they want to determine, and count its hairs — and find a point on the curve corresponding to the number of hairs and age.
There is a multiple model for calculating biological age, in which several different indicators are entered — for example, blood test data, lung volume, pulse wave propagation speed, activity of certain enzymes, etc. There is no absolute value of biological age.
In the 16th WHO report "On Aging and Health" it was noted [2] that today many elderly people are in good physical and mental condition, because they lead a healthy lifestyle. Our environment is also improving. And life expectancy is a connection between the external environment, its changes and the person himself. But aging still does not move away. It happens that young—looking people die very early - for example, professional athletes who have a lot of problems with joints and with the heart.
Nevertheless, it should be understood that an increase in life expectancy does not always mean maintaining the quality of life and health. If sick people hardly survived in the conditions of Sparta, then a modern developed and humane society gives them the opportunity to live for a long time. And the main task of gerontology is not only to increase life expectancy, but also to improve its quality. Because now, although people have begun to live longer, but at the expense of the period of old age — the time of infirmity, illness and the need for care.
Centenarians among humans and animals
Centenarians, as a rule, can be found in certain areas of the planet. Firstly, these are the so-called "blue zones" where people have a healthy diet and little stress — for example, Abkhazian centenarians are surrounded by reverence, they are not nervous, they are not tired.
"Blue zones" are regions where there is a high concentration of centenarians. The term was coined by a group of scientists in their article "Definition of a geographical area characterized by extreme longevity on the island of Sardinia" for the journal Experimental Gerontology in 2004. Since then, in addition to Sardinia, some other territories have been added to the list of "blue zones", including the Okinawan Islands in Japan and the Greek island of Ikaria. However, their reliability requires verification, since centenarians were born in the times before The First World War, when it was possible to change records in documents.
The second option is the opposite. For example, centenarians from the Altai Mountains. Imagine: the XIX century, a poor family, 20 children, 19 of them die and the one who is able to survive in harsh conditions survives. From such adapted children, a population of centenarians arises — in fact, this is artificial selection.
As for ageless animals, they are divided into several types according to the nature of the survival curves. The first die exponentially (the rate of dying is constant). An example is most animals in the wild, they just don't have time to grow old. The second is dying according to the "square survival curve". This happens, for example, in mayflies: they live for one day and are programmed to die at the same time. Another option is organisms whose survival curve is horizontal, they do not die at all. This is, for example, an ordinary freshwater hydra (Hydra vulgaris, Hydra magnipapillata). She does not age, but usually dies from other causes [3]. It is assumed that if she creates ideal conditions, she will live forever. In 2014, an article was published in the journal Nature [4]. In which the authors calculated that the population of freshwater hydra can survive for at least 1400 years.
Due to what hydra and some similar species of coelenterates do not age? The fact is that hydra has so-called i-cells, an analogue of stem cells that multiply all the time, that is, it is completely renewed all the time. Thus, in a few days (about a week), she may not have a single old cell left. Therefore, if it is placed in ideal conditions, it will live indefinitely — for example, at the gerontologist Daniel Martinez, the hydra lived for more than 4 years [5].
Gerontologist Caleb Finch introduced the concept of negligible aging in 1990 - imperceptible aging. This is how turtles and bowhead whales age — very slowly, almost imperceptibly.
A separate story among centenarians is the naked digger (Heterocephalus glaber). This animal lives for a very long time and ages very slowly, and there are no reliable biomarkers of its aging today. There are problems with the number of individuals in the samples used. Some experiments were done literally on one or two animals, and this is not enough for statistics.
Geroprotectors and cognitive training: is it possible to postpone aging
Humanity as a population will steadily age, and this "demographic aging" will be associated with a continuous increase in the proportion of elderly senility. By 2100, Japan will lose up to 40 million people due to aging and depopulation. And by 2050, that is, in just 29 years, the number of people over the age of 60 will be [6] approximately 2 billion people.
Senility is a geriatric syndrome, in ICD 10 it goes under the code R54 and means that a person has low adaptive capabilities, he is at a low level of viability and has a high dependence on the help that he needs constantly.
Part of aging is cognitive aging, because we are aging not only physically, but also mentally, and this also needs to be monitored — for example, at a young age to do a genetic analysis for polymorphisms. This is especially important for those who have relatives with Alzheimer's disease — in this case, the risk of Alzheimer's disease increases by 4 times.
Dietary changes, physical activity, and cognitive training are important. It is known that people with higher education live longer. If cognitive changes pass into the stage of dementia, then it accelerates all diseases.
However, all this will only slow down mental aging, but it cannot be completely removed. The fact is that we lose 3% of neurons every 10 years, and it is unlikely that we will be able to compensate for their loss in the near future. The synapse-the architecture of the brain is perhaps even more complex than DNA: according to various estimates, there are 100 or 86 billion neurons in it, each of which has up to hundreds of thousands of connections — and it is very difficult to delay the loss of these connections.
In the hope of delaying aging, scientists are developing geroprotectors — drugs that are designed to increase the maximum life expectancy. Thus, the properties of geroprotectors were attributed to nutrition restriction mimetics and antioxidants.
However, it is worth noting that the American biochemist Clive McCay, who for the first time experimentally investigated the beneficial properties of dietary restriction, conducted experiments on Fisher rats prone to the development of spontaneous tumors. And it cannot be ruled out that the diet suppressed carcinogenesis, and this prolonged the rats' life. Antioxidants were tested on special rats prone to accelerated aging. Among other things, their generation of free radicals was enhanced, and the antioxidant simply acted as a medicine and allowed them to live longer.
Geroprotective for a person could be recognized as any effect that improves his functional state, reduces the need for care, pushes age-dependent diseases.
If we talk about human gerontological research, the problem is not only that there are ethical restrictions when conducting experiments on humans. The point is also that in fact the only reliable way to measure something is longitudinal studies (long-term studies of a specific large group of subjects), which require a lot of time and money, as well as solving a huge number of organizational problems. The longest research in this area was conducted by Duke University from 1955 to 1976 [7]. During this time, scientists observed the natural (normal) aging of people from 60 to 90 and from 46 to 70, fixing various physiological, biomedical parameters, as well as socio-economic factors.
The data from these studies give scientists reason to assume that life expectancy does not depend on clinical blood parameters, but on the number of social and family ties, their density and quality.
Literature
- Robert, L. Fritz Verzár was born 120 years ago: His contribution to experimental gerontology through the collagen research as assessed after half a century. 2006
- World report on Ageing and Health / World Health Organization 2015
- Khokhlov, A.N. On the immortal hydra. Again. Moscow Univ. Biol.Sci. Bull. 69, 153–157. 2014
- Jones O. et al. Diversity of ageing across the tree of life. Nature. 2014
- Martínez D. Mortality patterns suggest lack of senescence in hydra. Exp Gerontol. 1998
- Aging and health / WHO
- Busse E. Duke University Longitudinal Studies of Aging. Z Gerontol. 1993
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