The dream of eternal life
To overcome or at least postpone old age and death, it is necessary to know what the aging process is. Gerontology studies its mechanisms at all levels, from molecules and cells to the body and society, including psychological and social aspects of aging (Greek: γέροντος – old man). The change of generations and the death of an individual is a necessary condition for the evolution of multicellular organisms. The mechanisms of aging are complex and diverse, and several alternative groups of theories of aging, which partly contradict each other and partly complement each other, focus on individual aspects of these mechanisms. Dry theories
Molecular genetic theories are divided into two large groups. Some scientists consider the aging process to be a natural, hereditarily programmed result of the development of the body. But so far only certain elements of this program are known – regulatory genes that change the activity of RNA and protein synthesis by other genes at all stages of the organism's existence, from the first divisions of the egg to the last breath. Others believe that aging is the result of the accumulation of random mutations, errors in the system of storing and transmitting genetic information. They are right, as it often happens, both those and others, and many of the third.
Telomeric theory In 1961, the American gerontologist L. Hayflick found that "in vitro" skin cells – fibroblasts – can divide no more than 50 times.
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How telomerase worksTelomeres are necessary for the start of DNA replication (doubling): an RNA seed is attached to them, with which the synthesis of the second strand, complementary to the first, begins on each of the strands of the DNA double helix.
After each cell division, a part of the terminal nucleotides on each of the newly formed chromosomes is irretrievably lost along with the RNA seed. When sooner or later the chromosome uses up all the nucleotides of its telomeres, the cell will not be able to divide and dies after a while.
In the embryo, in the progenitor cells of spermatozoa and eggs and tumor cells, the telomerase enzyme completes the areas of telomeres that remain without paired nucleotides.
It consists of several protein globules and an RNA strand, in which (in humans) there is only one significant (complementary telomeric) sequence per 450 bases.
With its help, at the last stages of chromosome doubling, telomerase joins the beginning of the DNA section doomed to death, completes a small segment of complementary nucleotides, moves one step to the end of the chromosome – and so on until it restores the original length of the telomere.
The second, complementary strand of the end section of DNA is completed by DNA polymerase and the rest of the complex of enzymes, due to which DNA strands are doubled during cell division.
Elevation (ontogenetic) theory In the early 1950s, the famous Russian gerontologist V.M. Dilman put forward and substantiated the idea of the existence of a single regulatory mechanism that determines the patterns of age-related changes in various homeostatic (maintaining the constancy of the internal environment) systems of the body.
According to Dilman's hypothesis, the main link in the mechanisms of both development (Latin elevatio – rise, in a figurative sense – development) and subsequent aging of the body is the hypothalamus – the "conductor" of the endocrine system. The main cause of aging is an age–related decrease in the sensitivity of the hypothalamus to regulatory signals coming from the nervous system and the endocrine glands.
According to Dilman, aging and related diseases are a by–product of the implementation of the genetic program of ontogenesis – the development of the organism. The ontogenetic model of age-related pathology has opened up new approaches to the prevention of aging and age-related diseases that are the main causes of death: heart disease, malignant neoplasms, strokes, metabolic immunosuppression, atherosclerosis, diabetes mellitus of the elderly and obesity, mental depression, autoimmune and some other diseases. It follows from the ontogenetic model that if the state of homeostasis is stabilized at the level reached by the end of the development of the organism, it is possible to slow down the development of diseases and natural senile changes and increase the specific limits of human life. If only I knew how to stabilize and slow them down…
Stochastic (probabilistic) theoriesAccording to this group of theories, aging is a consequence of the accumulation of random mutations in chromosomes, errors in copying DNA during cell division and the deterioration of DNA repair mechanisms – correcting these errors.
Theory of free radicalsAlmost simultaneously put forward by D. Harman (1956) and N.M. Emanuel (1958), the free radical theory explains the mechanism of not only aging, but also many related pathological processes – cardiovascular diseases, weakened immunity, brain function disorders, cataracts, cancer and some others.
According to this theory, the cause of cell dysfunction is the free radicals necessary for many biochemical processes – reactive oxygen species synthesized mainly in mitochondria – the energy factories of cells.
If a free radical molecule leaves the intracellular structure where it is needed, it can damage DNA, RNA, proteins, and lipids. Nature has provided a mechanism of protection against excess free radicals: in addition to superoxide dismutase and some other enzymes synthesized in mitochondria and cells, many substances entering the body with food have an antioxidant effect – including vitamins A, C and E. Regular consumption of vegetables and fruits and even a few cups of tea or coffee a day will provide you with a sufficient dose polyphenols, which are also good antioxidants. Unfortunately, an excess of antioxidants – for example, in case of an overdose of biologically active additives – is not only not useful, but can even enhance oxidative processes in cells.
Aging is a mistake The hypothesis of "aging by mistake" was put forward in 1954 by the American physicist M. Szilard.
Investigating the effects of radiation on living organisms, he showed that the effect of ionizing radiation significantly shortens the life span of humans and animals. Under the influence of radiation, numerous mutations occur in DNA that initiate aging symptoms such as gray hair or cancerous tumors. From his observations, Szilard concluded that mutations are the direct cause of aging of living organisms. However, he did not explain the fact of aging of people and animals who were not exposed to radiation.
His follower L. Orgel believed that mutations in the genetic apparatus of a cell can either be spontaneous or arise in response to the effects of aggressive factors – ionizing radiation, ultraviolet radiation, exposure to viruses and toxic (mutagenic) substances, etc. Over time, the DNA repair system wears out, resulting in aging of the body.
Is this theory crazy enough? It is curious that the author of the classic telomeric hypothesis (now a theory) in 2003 decided that it did not explain the causes of aging, and put forward another, a redusomal one.
However, no one has seen these very rare copies of the end segments of chromosomal DNA surrounded by proteins. And more recently, Olovnikov invented an even more fantastic theory of aging – moongravity. Both of them have received neither experimental confirmation nor the approval of colleagues. As, for example, the "chaonogens" discovered "on the tip of a pen" by the famous St. Petersburg scientist Yu.B.Vakhtin – intracellular genetic parasites, illegally multiplied copies of DNA molecules of various sizes and complexity, which, according to his personal and unconfirmed opinion, go out into protoplasm, multiply in it, mutate, bring chaos to work the genome determines the aging and death of living systems, not only cell populations and individuals, but also entire populations of organisms and even species. If these chaonogens really existed, they could be found and neutralized. And this is also the least crazy of the theories of aging…
Hundreds of more or less scientific theories in general are reduced to one of the listed main options, and there is no doubt that all these mechanisms are involved in the aging process. The search for the "elixir of immortality" is also complicated by the fact that it is simply impossible to turn off any of the aging mechanisms. Suppressing the activity of free radicals, it is easy to overdo it and disrupt the processes of cellular respiration. It is impossible to find a specific "aging gene" in principle – the development and aging of the body is controlled by many genes. And numerous "anti–aging genes" and "cancer genes" are (very simplistically) either the same genes, or they are so interconnected that it is better not to interfere in the process of their interaction. But this does not mean that you can stop looking for effective methods of prolonging life.
Tree of LifeIf there is an old man, I would kill him, if there is no old man, I would buy him!
(it seems to be an eastern proverb)
In the endless game of evolution, the pieces on the board are species, and individuals are of no interest – except as carriers of mutations useful for the survival of the species in these conditions. Therefore, nature, by and large, is indifferent to the fate of the organism after it has produced offspring. The extreme degree of such indifference is male spiders and mantises, which the females eat immediately after or even during fertilization, or salmon fish, after spawning, floating up with their bellies downstream. In mammals, the survival strategy of a species usually involves caring for offspring, sometimes quite a long time, but the period of old age in nature does not last long: Akela missed ... Caring for the elderly is characteristic only of the genus Homo: hundreds of thousands, or even millions of years, a few old people were of great value for the survival of the species as information carriers.
Geriatrics – the treatment of such typically senile diseases as cancer, heart and vascular diseases, osteoporosis, osteoarthritis, type 2 diabetes, Parkinson's and Alzheimer's diseases – is just the tip of the iceberg. And even the prevention of these and other old man's sores in gerontology is not the main thing.
If you think about it, the proverb "who does not smoke and does not drink, he will die healthy" is not so stupid. There is a normal, physiological aging – a gradual and late-onset extinction of body functions without diseases. But it is quite rare: most people have pathological aging, which occurs earlier than long-livers, and is associated with various diseases that worsen the quality of life, increase biological age and bring the arrival of the Destroyer of pleasure and the Separation of meetings closer.
The only reliable means to completely use up the resource released by nature, to prolong youth and adulthood as much as possible, and in old age to enjoy the fruits of autumn, and not to creak with gnarled branches and not to give an oak ahead of time is a healthy lifestyle, including rational nutrition and physical activity. No one doubts the benefits of limiting the caloric content of the diet – provided it is complete in composition.
On fruit flies, nematodes, rodents and other innocent victims of science, life extension with limited access to food has been shown for a long time and reliably. In order to get closer to people, in the three largest monkey houses in the USA, an experiment has been going on for almost 20 years on our closest relatives: a control group of monkeys eats as much as they want, and experienced researchers measure the ration by 40% less and estimate the biological age of those and others by three hundred indicators. According to preliminary data (all participants of the experiment are still alive), aging in starving monkeys is slowed down. However, even here there were side effects – for example, the experimental group "has a violation of reproductive function", which in translation from scientific means: with such feeding, you will drag your arms and legs, but you will not pull on amorous exploits…
The difficulty here is that all the necessary vitamins, trace elements and other micronutrients (biologically active substances contained in products in small quantities) can be obtained with food, for example, a logger or a bricklayer who spends 5-6 thousand calories a day and eats the same amount, and not fast food and refined "fast-soluble" products, but what the doctor-nutritionist prescribed. With sedentary work and two thousand calories, even with a properly formulated diet, the lack of micronutrients must be compensated by constant intake of multivitamins (it's easier with this, they differ from each other mainly in packages and shades of proportions – for pregnant women, smokers, the elderly, etc., and inside – all the same) and biologically active additives. Only in their choice, especially with the ugliness that, despite all the efforts of the Ministry of Health, is happening in this area in Russia, one should be guided not by one's own mind and especially not by advertising, but by the advice of a good doctor.
But man is a lazy creature by nature, and few people are able to carry out healthy lifestyle advice that has hardly changed since the time of Hippocrates. If only I still had a pill…
Pills for old age Unlike geriatric drugs (simply put, drugs for the treatment of specifically senile sores), geroprotectors should be taken starting from a young age.
Why "would"? If only because many of the dozens of substances that can undoubtedly increase the life expectancy of animals have known and pronounced side effects (for example, growth hormone – although many firms sell it, not too hiding, but still from under the floor or illegally include in the composition of "natural" dietary supplements). Some of those who make a bold experiment on themselves may live longer and feel 10 years younger, and some – exactly the opposite. With many drugs in animal experiments, this is how it turns out: the average life expectancy of the experimental group of mice may not change, but at the same time some of the animals die much earlier than the time allowed by nature, most live as long as the animals of the control group, and another part of the "lucky ones", with some individual characteristics of variants of genes unknown to science and, accordingly, metabolism, lasts 20-40% longer than the average life expectancy. Do you want to play Russian roulette? Many antioxidants have the effect of prolonging life in mice and rats, but not in humans, except perhaps vitamins C and E, and then – in physiological (those contained in multivitamin tablets), and not horse doses.
Nevertheless, scientists are constantly engaged in the search for new and testing of already known geroprotectors. But the only reliable and generally recognized of them are, perhaps, only the plant adaptogens, proven by thousands of years of traditional medicine practice and included in the modern pharmacopoeia – means that strengthen the body as a whole and immunity in particular, from Aralia to Yathryshnik. None of the antioxidants, hormones, antidiabetic agents, substances that inhibit the activity of numerous "aging genes", cross-binding inhibitors that prevent the "sticking together" of biological macromolecules, etc. has yet been recommended for use, and we will not list them not so much for lack of space, as from unwillingness to tempt readers. Suddenly, someone, after reading that the favorite model of gerontologists, tiny nematode worms Caenorhabditis elegans, lived 30% longer on a substrate containing one of the antidepressants, will start getting recipes by hook or by crook and walking high? Then try another, the most recent (by time) news: in December 2007, Washington State University researchers Mark Roth and Dana Miller published no less amazing results: the same worms grown in an atmosphere containing 50 parts of hydrogen sulfide per million parts of air lived 70% longer than the control group! But they don't even hint at the constant carrying of a rotten egg in their breast pocket.
Finding a "Macropoulos remedy" that allows you to defeat old age with one pill is a hopeless task, but in recent years, the problems of gerontology have attracted increasing attention from researchers in various fields of life sciences. One may not believe in victory over death, but the search for methods of rejuvenation and prolongation of life continues as new data on the mechanisms of aging accumulate.
"Be realistic – demand the impossible" (Che Guevara) English geneticist and gerontologist Aubrey De Grey from the University of Cambridge claims that the average life expectancy of people in developed countries will soon grow to a thousand or more years, and by 2100 methods will be developed to extend human life to 5000 years.
This reminds the statement known to the older generation of our readers, "the current generation of Soviet people will live under communism"… But his views are shared by many, including a large group of scientists working in the SENS – Strategies for Engineered Negligible Senescence project, "The Strategy of Projected Negligible Aging."
To begin with, the so-called Group of Three Hundred established the Methuselah Mouse Prize (M-Prize). The prize fund of the project is now approaching $5 million.
The M-Prize is divided into two parts. The "Longevity Prize" is awarded for the maximum duration of a mouse's life. The way in which it is achieved is unimportant – the main thing is that a genetically modified and/or a mouse that has been on a diet and stuffed with pills since childhood preserves physical and mental health. The main prize will go to the one who creates a mouse super-long-lived, whose age will be equivalent to 150 human years. The "prize for rejuvenation" is waiting for a scientist who will be able to extend the life of mice to the same mark by starting the "treatment of old age" in the middle mouse age. In addition, the M-Prize rules describe in detail the awards for each successive achievement on the way to the cherished goal. The last record in the competition is 1819 days, almost five years (the normal life span of mice is a little more than two years). However, all genetically modified long-lived mice have side effects that are unacceptable to humans (not to mention that such experiments on humans are currently universally prohibited).
De Grey assures that in order for a person to achieve "near immortality", it is necessary to eliminate 7 types of molecular and cellular damage using genetic engineering methods – "extracellular debris", "intracellular debris", cell death and atrophy, mutations in the nucleus and mitochondria, cell aging, cross-connections between biopolymer molecules. His ideas may seem incredible – creating chromosomal copies of mitochondrial DNA and placing them in the cell nucleus (these copies will start working when their own mitochondrial DNA is damaged), replacing all stem cell populations with new ones once a decade, destroying intracellular and extracellular "slags" by introducing enzymes that destroy them into cells…
Thus, according to the author, technologies will be created that not only prevent old age, but also rejuvenate the body to the desired level. Aubrey de Grey claims that with sufficient funding for his programs, in 20 years people will cease to die a natural death. Fiction? But, as Beranger wrote,
Gentlemen, if the truth is holy
The world will not be able to find the way, –
Honor to the madman who will inspire
Mankind has a golden dream!
Alexander Chubenko
Portal "Eternal youth" http://www.vechnayamolodost.ruThe journal version of the article was published in Popular Mechanics No. 2-2008