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A History of the Study of Life Extension Products

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  • A History of the Study of Life Extension Products

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    Life extension is a problem of all times and peoples.

    In evolution, this problem appears namely in humans. Realizing the immortality of living nature due to the reproduction of mortal organisms and possessing the instinct of self-preservation and survival, man has always tried to resolve this contradiction between life and death.

    Mankind in all epochs has shown a heightened interest in the means of preserving youth, health, and achieving superlongevity.

    The search for these means was undertaken in ancient China, India, Greece, Egypt, among the great civilizations of Central and South America.

    Traces of these searches are lost in the mists of time and go back to ancient history. In the oldest Chinese medical manuscript book (4,000 BC), there is a lot of discussion about aging.

    Hippocrates (460-377 BC) in his "Aphorisms" and Aristotle in his treatises "On youth and old age" expressed views on the causes of aging and gave advice on a healthy lifestyle. No special elixirs are given in these works.

    To prolong life, the ancient Egyptians consumed large quantities of garlic.

    Thinkers and doctors of different eras paid a lot of attention to the treatment of diseases of old people and generalized the experience of prolonging life.

    Avicenna (980-1037) summarized the achievements of medicine of previous generations in this matter.

    We find descriptions of the means of rejuvenation and immortality in the manuscripts of medieval alchemists. But neither the elixirs of life nor the philosopher's stone allowed the outstanding alchemists themselves to live longer than 100 years.

    The super-long life of people mentioned in ancient books is apparently exaggerated since archaeological evidence suggests that ancient people lived no longer than modern humans.

    The species limit of life expectancy has not been overcome.

    At the end of the 19th century, in connection with the works of A. Weismann, the science of the nature of aging appeared in biology.

    Outstanding biologists of the time were involved in research into the biology of aging and rejuvenation. Many experiments have been carried out on life extension and rejuvenation in invertebrates.

    From the results of these experiments, important theoretical conclusions were drawn about the nature of aging.

    Further, systematic studies to extend the life of mammals and humans begin.

    For 100 years, a huge amount of material on the biology of aging has been accumulated, however, less than 1% of works are devoted to solving the main problem of gerontology - life extension, in which data on the influence of various factors on the lifespan of humans and animals have been obtained.

    The greatest contribution to the increase in the average lifespan of the population of some countries was made by social factors, environmental conditions, and medical advances, which is not associated with a slowdown in aging as such.

    These factors made it possible to come very close to the biological limit of lifespan, which is almost reached in a number of developed countries.

    The use of geriatric agents is aimed at preventing many diseases that accompany aging.

    Some scientists believe that at a huge cost, treating major diseases of the elderly will add about 10 years to life.


    Thus, mankind has practically exhausted the possibilities of increasing the lifespan by traditional medical means, and the problem of developing means and methods of radical impact on the aging process itself comes to the fore.


    Many known agents increase the life expectancy of animals and humans.

    At the same time, the maximum lifespan does not increase, which implies that these agents are aimed at correcting the pathological consequences of aging but not at the fundamental processes of aging as such.

    In many life extension experiments, various lines of short-lived laboratory animals with known hereditarily fixed diseases were used.

    If the remedy is effective for these diseases, then the life expectancy of animals increases without affecting the aging process. Such experiments are the majority. Such errors lead to contradictory results.

    Some influences cause signs of rejuvenation in humans and animals, while the maximum lifespan does not increase or even decreases.

    This situation explains a fairly widespread pessimistic position on the possibility of obtaining means of radical prolongation of human life.

    For example, an expert analysis of the current state and prospects for the development of gerontological research, presented by 39 leading gerontologists of the world in the early 90s, showed that most experts consider the possibility of increasing human maximum lifespan an unrealistic task.


    Various methods, techniques, and systems of life extension are currently being investigated.


    According to their effectiveness on the aging process, these methods and means can be divided into 2 groups: increasing the average lifespan and the maximum lifespan and increasing only the average lifespan.

    The first group is of the greatest interest.

    The applied influences are of a different nature: physical, chemical, and others. In this article, we discuss the most studied means and methods known in gerontology.






    PHYSICAL FACTORS







    Electromagnetic fields


    It was found that under the influence of an electrostatic field (ESP) of a negative charge of a low voltage, the average lifespan of mice increased by 10% [6].

    The effect of an ESP with a voltage of 15 kV / m on male CBA mice was studied.

    The life expectancy of animals in the field of negative charge was 34.9%, and that of the animals was 41% higher than that of the controls. But CBA mice have a high incidence of tumors.

    The specific maximum lifespan of mice (not highly cancerous) has a value of 1030-1070 days.

    In this experiment, the maximum lifespan (1049 days) did not exceed the species limit, and the effect was obtained by reducing the incidence of tumors under the influence of an electrostatic field.

    From 1939 to the present, a number of experimental studies have been carried out showing the effect of constant magnetic fields on the lifespan and survival of various animal species.

    In the experiments of Van Dyck (1965) and M. Halpern (1966), a shortening of the life of rats and mice placed in a shielded space was observed, where the intensity of the geomagnetic field was reduced several times.

    A strong magnetic field of more than 100 kOe did not significantly affect the survival of mice and monkeys (Beischer, 1964).


    However, numerous clinical and experimental studies show that prolonged exposure to strong constant magnetic fields in humans causes damaging effects.


    In the numerous experiments of Barnoti (1959-1964), as well as McLean (1959), Perepechin (1974), and others, it was found that constant magnetic fields from 100 to 4200 Oe contributed to an increase in the life expectancy of mice, rats and other animal species, while the development of tumors was significantly slowed down ...

    Apparently, this can explain the prolongation of the life of animals in these experiments.

    A variable magnetic field had a greater effect on the experiments. The head of old rats (18-32 months old) was exposed to a field with an induction of 3.2-4.5 mT and a frequency of 50 Hz.


    The purpose of the experiments was to create a nonspecific adaptive activation reaction in animals.


    1-2 weeks after the start of the exposure, the animals showed signs of rejuvenation, and after 2-8 months, the experimental rats could be distinguished from young ones by their appearance only by their size.

    They were more mobile; sparse, yellow, coarse wool was replaced by white, soft, thick; the yellowish sclera of the eyes turned bright pink; the skin has changed from rough and thick to soft and elastic; the thymus was enlarged, the sexual cycle returned to normal.

    Nothing was reported about the maximum lifespan. There are no such facts in the literature on magnetobiology.

    These experiments are of interest for studying the possibility of using the activation reaction as a way to prolong human life.







    Ionizing radiation


    Large doses of various types of radiation usually lead to a reduction in the lifespan of many species of animals and humans.

    However, at low doses, radiation can contribute to an increase in the life expectancy of animals by 10–20% [8], and this effect is better manifested when the body is irradiated than the head.

    A number of authors explain the prolongation of life in these experiments by the suppression of the development of tumors and infections, a decrease in body temperature, metabolism and reproductive function.





    CHEMICAL AND MEDICINAL PRODUCTS







    Many chemicals are known to affect the lifespan. Their selection for research and testing for the effect of prolonging life is usually based on certain concepts and hypotheses of aging.





    Antioxidants


    The use of antioxidants is based on the binding of free radicals - reaction compounds with an unpaired electron, arising in the process of metabolism, the number of which increases with age (Harman's hypothesis, 1956-1968).

    These radicals, damaging high-molecular compounds of chromatin (DNA, RNA), collagen, and other proteins, causing lipid peroxidation of cell membranes, can disrupt the metabolism in the body.


    Mammals have a powerful antioxidant system that regulates the action of free radicals, but the effectiveness of this system decreases with age.


    To test his hypothesis, D. Harman studied a number of antioxidants in short-lived strains of mice (that is, with hereditarily fixed pathology). The life extension was small.

    The most effective antioxidants, mercaptoethylamine, increased the life expectancy of animals by 26%, and butyloxytoluene - by 45%, mainly due to the slowing down of the development of tumors; the animal's life cycle did not increase.

    When these antioxidants were exposed to mice of long-lived and disease-resistant strains, no prolongation of life was observed [12].

    It was concluded that antioxidants do not slow down the aging process.

    Numerous experiments on mice of short-lived lines were carried out. 2-mercaptoethylamine, epigid, ionol, ethoxyquin, dimethylaminoethanol, centrophenoxine, and other antioxidants were used.

    Exposure began at young, middle, and older ages of animals. It was shown that the lifespan after the start of exposure increased by 11-26%.

    In other animal lines, experiments with the use of ascorbic acid, glutathione, tocopherol, and sulfur-containing amino acids did not reveal the effect of these antioxidants on the lifespan [7].

    In the experiments of other authors, exposure to tocopherol, ascorbic acid, ionol, and methionine led to a reduction in the life of animals.


    In many studies on invertebrates (nematodes, insects, etc.), it was found that the effect of antioxidants decreases with age, and in old animals, they do not affect the aging process.


    Some antioxidants (vitamins C, E, A) are used in geriatric practice.

    There are observations that when people were exposed to ascorbic acid after 75 years, there was an increase in the statistical indicator of life expectancy up to 102 months with a duration of 70 months in the control group.

    Analysis of the accumulated data on the study of antioxidants allows us to conclude that with the help of antioxidants it is not possible to achieve a significant slowdown in aging and an increase in the maximum lifespan.

    However, many of them are official drugs and are effective for various diseases, necessary for the normal functioning of the body and health promotion.

    Therefore, the use of antioxidants is also justified to increase human life expectancy. Antioxidants are now widely used in medicine.







    Latirogens


    Bjorksten's hypothesis [5] associates aging with the formation of cross-links in DNA, collagen, and other proteins by covalent and hydrogen bonds.

    Bjorksten isolated a bacterial enzyme that breaks down these crosslinks. Its administration to mice increased their average lifespan, which, as the author believed, slowed aging.

    Then a group of substances was found - latirogens, which prevent the formation of crosslinks, in particular, collagen molecules of connective tissue: penicillamine, semicarbazide, aminopropionitrile, and others.

    In experiments on rats, mice, and other animals, it has now been proved that latirogens, by inhibiting the formation of cross-linking, have practically no effect on the maximum lifespan of animals [12].






    Chelates

    Bjöksten (1951) suggested that transition metals (calcium, aluminum, etc.), participating in the process of cross-linking of high molecular weight compounds, play an important role in aging.

    To bind these metals and slow down the aging process, a group of substances has been proposed - chelates: ethylenediaminetetraacetic acid (EDTA) and its salts, unitiol, penicillamine, and others.

    EDTA is the most studied among them.

    In numerous experiments, the use of Na2EDTA salt as a chelate and geroprotector showed that EDTA does not interfere with the aging process, increases life expectancy (rats by 20-25%) and animal survival by reducing the incidence of tumor formation, infectious-inflammatory, and other diseases, it slows down the development of atherosclerosis, hypertension, and hypercholesterolemia.

    In general, metal crosslinking does not accelerate the aging process, since the exclusion of calcium from the diet did not affect the lifespan of the mice.






    Adaptogens

    These are tonics that increase the adaptive capacity and resistance of the body to various factors.

    For these purposes and to slow down age-related changes, tinctures and extracts of plants are often used: ginseng, eleutherococcus, rhodiola, leuzea, aralia.


    However, their use is limited, since most adaptogens are contraindicated in hypertension and other diseases of the elderly.


    Exaggerated attention to these and some other plants (euphorbia, Adams' rhododendron, high gastrodia, and others) as “elixirs of life” is often explained by a cosmetic effect or a stimulating effect on certain processes in the body.

    Direct experiments indicate that only a few adaptogens (extracts of ginseng, eleutherococcus, licorice root) increased the life expectancy of rats by no more than 10%, practically without affecting the maximum lifespan.








    Biostimulants, cell and tissue therapy preparations


    Biostimulants are formed under certain conditions in isolated tissues of animal and plant origin.

    In geriatric practice, the following preparations are used: aloe extract, suspension, and extract of the placenta, peloidodistillate, peloidlnum, pyrogenal, prodigiosan, and others.

    Skin grafting and some tissues of other people is also used.

    They have a stimulating effect on metabolic processes, a regulatory effect on the functions of the central nervous system, cardiovascular, endocrine, and other systems, activate recovery and regeneration processes, slow down the development of atherosclerosis and arthritis.

    For example, the effect of aloe extract on people over 71 with cerebrosclerosis reduced headache, dizziness, and improved memory.

    Treatment with placenta drugs had a normalizing effect on the central nervous system, metabolism, organs of vision, endocrine, cardiovascular and immune systems, slowed down the development of atherosclerosis and polyarthritis.

    Many drugs obtained from various animal tissues are successfully used in veterinary medicine to reduce the morbidity and mortality of animals.

    Some drugs, according to observations in experimentы and in agricultural practice, can cause anti-aging effects on certain organs and systems of animals, but these drugs do not have a noticeable effect on lifespan.

    The group of biostimulants includes a number of cytotoxic sera: antireticular (ACS), antiovarial, anti-testicular, and others, which are used in geriatrics. ACS has a positive effect on the connective tissue system (treatment of arthritis), cardiovascular, nervous, endocrine, immune, hematopoietic systems, which indicates an increase in the overall resistance of the body.

    However, there is no convincing evidence about the effect of ACS on the human lifespan.

    This also applies to some stimulants of inorganic and other origin: oil growth substance, shilajit (mumie, moomiyo).

    For example, it has been reported that the use of oil growth substance causes increased performance, " rejuvenation” of the skin, darkening of gray hair, and the growth of new hair on the head and eyebrows.

    A thorough study on rabbits and humans did not reveal the effect of oil growth substance on the aging process. In geriatrics, oil growth substance is not used.



    The history of studying biostimulants in connection with human rejuvenation is interesting.


    In 1899, 72-year-old French physiologist C. Brown-Séquard gave himself several injections from the testes of young dogs and rabbits and felt as if he had grown 30 years younger.

    However, after 5 years he died. The effect was temporary. But other doctors started using this method. E. Steinakh (1920) reported that in experiments on rats, rabbits, and rams they succeeded in rejuvenating and prolonging the life of animals.

    Rejuvenation was expressed in the fact that old animals straightened up, their motor activity increased, eyes opened, which became clear, new hair began to grow, fur became thicker, softer, and sexual function was restored.

    V. Garms (1921) reported 4-fold transplantation of testes from a 3-month old dachshund dog to a 17-year-old male dachshund with pronounced signs of senility.

    The effects described above were observed, but several weeks after the next transplant, signs of senile decrepitude appeared, and after the 4th transplant, the effect was not observed.

    The experiment lasted 200 days. It indicates the extension of the life of the animal and the limit of the possibility of the method.

    For the purpose of rejuvenation, E. Steinakh performed transplantation of the gonads of young animals and monkeys to humans. According to their descriptions, the patients ' signs of senile decrepitude disappeared.

    In some cases, these transplants gave a very effective, but short-term result, followed by a rapid decrepitude of the body.

    There were many failures, for which this method was sharply criticized and was banned.

    There are many poorly studied means of tissue therapy. So, there was a report that elephant skin is now being sold in pharmacies in East Asia, which is recommended to the elderly as a tonic and rejuvenating agent.

    The idea of ​​using it is taken from ancient legends: supposedly old predators, having eaten the skin of an elephant, looked younger and something similar happened to people.

    This observation requires experimental verification.

    Cell therapy preparations obtained from embryonic tissues of cattle, pigs, and chickens, from fetuses and uteri of animals, from embryos and placenta, from embryo and chorion have greater biological activity.

    The mechanism of action of embryonic drugs is not well understood. They are used in geriatric practice in the treatment of various diseases of elderly patients.

    It was found that homogenates obtained from the embryonic tissues of various organs, after being introduced into the body, have an effect on the organs of the same name, that is, the drugs act selectively on organs and nonspecifically on the whole organism.

    After the introduction of embryonic drugs in the elderly, the general condition improves, the working capacity and mood increase, the function of various organs and systems normalizes.


    The practical application of the method of cell therapy to slow down aging is associated with a Swiss physician, MD Paul Niehans [3].


    He widely used cell therapy to “rejuvenate” people, among whom there were many wealthy celebrities: Pope Pius XII, W. Churchill, Charles de Gaulle, S. Moham, T. Mann, J. Rockefeller, Gloria Svenson, B. Baruch, and others.

    All of them survived to old age but did not reach 100 years old. In his works, P. Niehans did not report failures.

    Many of his patients were practically healthy people, looked after their health, and could live a long time without the help of Niehans. P. Niehans himself (having also become a wealthy celebrity) lived for 89 years.

    It should be noted that sometimes the use of embryonic drugs causes severe complications.

    Therefore, the American Medical Association recognized the method of cell therapy as dangerous.

    P.Stephan, a follower of Niehans, calls his method of rejuvenation “body repair” - a variant of tissue therapy associated with organ regeneration.

    The method does not contain a rigorous analysis of the results of such “body repair”.

    The creators of these methods, like Niehans himself, often deliberately and selflessly overestimated the effects of rejuvenation. All of these methods are undoubtedly among the most promising and require careful study.







    Immunotropic drugs


    The use of these agents and methods for slowing aging is based on a hypothesis linking the aging process with age-related changes in the immune system, and, first of all, with thymic involution in humans and animals.

    There is evidence that the hormonal substances of the thymus (thymic humoral factor, thymopoietin, thymosin, and others), as well as interleukin-2, isoprinosine, immunocytal, LPS (immunostimulant), azathioprine (immunosuppressant), thimex, and thymalin (other thymus extracts) slow down the involution of the thymus, have a normalizing effect on the functions of various systems, prevent the formation of tumors, stimulate the body's defenses, but do not have a noticeable effect on lifespan.

    For example, the effect of the immunomodulators thymalin and epithalamin at 3.5 months of age in rats increased the forthcoming life expectancy and life expectancy mainly by reducing the formation of tumors.

    In the elderly, both drugs act on the central mechanisms of (peptidergic) regulation, exerting a normalizing effect on the immune, neuroendocrine and genitourinary systems.

    There is a report that, in experiments on rats, the peptide immunomodulator thymogen caused an increase in the maximum lifespan of animals from 946 to 1048 days, and the average maximum lifespan did not change, although the drug slowed down the development of tumors.

    These data require verification.

    Thymus and bone marrow transplants from young to old mice were performed. The author reported that this resulted in a “rejuvenation” of the immune system and prolonged the life of animals.

    Other researchers pointed out that multiple transplants of the thymus at an older age (with aging) are ineffective, and multiple transplants of thymus from neonatal mice to mice during puberty slowed down the decrease in T-dependent functions of immunity and the development of diseases, while the average lifespan increased, and the average lifespan did not change.







    Hormones


    The study of the effect of hormones on lifespan is associated with the important role of the mechanisms of neuroendocrine regulation in the aging process.

    Attempts to rejuvenate humans and animals using transplants and extracts from the gonads (Brown-Séquard), apparently, more often led to a reduction in life, since in most experiments, for the convenience of the operation, male animals and elderly men were used.

    It has now been established that the introduction of testosterone reduces the lifespan of females and especially males of mammals. Some prolongation of the life of animals has been shown after administration of estradiol, oxytocin, vasopressin, and glucocorticoids.

    It was found that dehydroepiandrosterone, administered to mice in large doses, had a rejuvenating effect.

    This hormone in high doses causes side effects in humans. Dr. J. Gleser found a significant increase in the level of this hormone in persons engaged in the psychotechnique of transcendental meditation, especially in older men (23%) and women (47%), while the biological age decreased.

    Removing the pituitary gland usually shortens life. However, when mice were injected with cortisone, their maximum lifespan increased from 1120 to 1332 days [14].

    The effect in prolonging life, in this case, is associated with a decrease in the influence of tropic hormones of the pituitary gland and suppression of the function of the endocrine glands, in particular, a decrease in the level of thyroxine, as well as an effect on the immune system.

    Note that in experiments with fasting animals, the release of thyroid hormones is also suppressed, and lifespan increases. In other experiments, the administration of thyroxine in the neonatal period (before birth) to male rats led to a 2/3 decrease in the level of thyroid hormones in adult animals and to an extension of their life by 4 months. In females, the effect was lower [2].

    It is possible to extend the life of animals with a decrease in the level of thyroxine due to the restructuring of the mechanisms of thermoregulation, a decrease in metabolism and body temperature.

    In 1977 the existence of a “death hormone” was hypothesized which, after reaching puberty, begins to be secreted by the pituitary gland, causing a decrease in the susceptibility of body tissues to thyroid hormones in old animals and humans by about 3 times [16].


    This leads to the suppression of energy processes, causing a decrease in the function of the cardiovascular and immune systems.


    Removal of the pituitary gland and administration of thyroxine to old rats led to the restoration of the function of the immune and cardiovascular systems while causing some signs of rejuvenation. Denkla believed that this method would extend human life up to 400 years.

    This optimism is shared by other scientists who are intensively studying the mechanisms of neuroendocrine regulation of the aging process. The most effective is the effect on the hypothalamus.

    Thus, the transplantation of cells of the embryonic hypothalamus into the hypothalamic centers of old animals led to a change in the program of the organism's development and caused the effects of rejuvenation.

    Exposure to the hypothalamus of rats with the antidiabetic drug phenformin or epiphyseal extracts increased the life expectancy of animals by 25% without changing the maximum lifespan.







    Means of influencing the genetic apparatus


    In the world gerontological literature, about half of the works are devoted to the study of the genetics of aging.

    Several inhibitors of transcription and translation (actinomycin D, olivomycin, cycloheximide, and others) were tested to delay the pace of implementation of the genetic program, to reduce the synthesis of proteins - possible initiators of aging.

    The greatest effect was achieved when rats were injected with olivomycin: the average lifespan increased by 15.4%.


    Attempts to stimulate the activity of the aging genome using RNA and DNA preparations have not yielded significant results in prolonging life.


    B. Frank (1981) developed a method of rejuvenation, which he called RNA therapy. Treatment consists of three forms: a diet rich in nucleic acids, nutritional supplements (RNA from yeast), and organ-specific (administration of RNA from animal organs).

    Frank claimed that the thousands of old people he treated experienced an amazing sense of rejuvenation. He did not report on the extension of life. Experiments conducted by other scientists showed the inefficiency of this method.

    To prolong life, R. Walford (1990) proposed to transplant the “major histocompatibility complex” from long-lived mice into the oocytes of mice of short-lived lines using genetic engineering. The expected effect was associated with the effect on the immune system.

    In the book of the gerontologist and neurobiologist Caleb Finch "Longevity, Senescence, and the Genome" (1990), extensive literature is used (more than 4000 works) and the role of the genome in the aging of various species is most fully described.


    As a result, the author concludes that the achievements of genetic approaches to life extension are more than modest.


    In recent years, in the genetic direction of the study of aging, they started talking about the onset of a crisis, since many hypotheses were not confirmed.







    Vitamins and minerals


    To slow down age-related changes in geriatrics, vitamins and vitamin complexes are used. The effect of vitamins on lifespan was studied experimentally.

    Vitamin E had no effect on the lifespan of mice of different strains (lmadfa, 1986).

    In the experiments of H.R. Massie on C57BL mice, the effect of vitamin C in increased doses led to an increase in the average lifespan by 20%, but the maximum lifespan did not change [4].

    The author concludes that vitamin C cannot significantly prolong a person's life, as L. Pauling believed.

    There are reports that vitamin A, more specifically retinol acetate, is proposed as an effective cosmetic "skin rejuvenation" associated with cell renewal, and is expressed in smoothing wrinkles and improving skin elasticity.

    In 1948, Romanian gerontologists K.Parkhon and A. Aslan used procaine, or gerovital H-3, containing a 2% solution of novocaine, to treat old people [1].

    The drug had a more pronounced effect in combination with decamevitum. For more than 35 years, the discussion on the possibility of prolonging life with the help of gerovital continued.

    Procaine has sometimes been touted as a miraculous "rejuvenating" agent while keeping silent about the potential for fatal complications.

    The effect of gerovital on Wistar rats led to an increase in the life expectancy of 20%, but the maximum lifespan did not change. A. Aslan noted that she had failed to prove the possibility of prolonging life with the help of gerovital.

    The American Medical Association, after a thorough study of Gerovital, declared its complete ineffectiveness.

    Another Romanian drug, aslavital, has been shown to be effective in the clinic and experimentally for slowing the development of cerebral atherosclerosis, coronary heart disease, and hypertension.

    Complexes of vitamins and microelements have a wider spectrum of action to slow down age-related changes.

    Thus, these drugs slow down the course of age-related changes but do not have a noticeable effect on lifespan

    H.Schroeder (1960-1974) experimentally studied the effect of 21 elements of the Periodic Table on lifespan. Chromium, yttrium, and palladium caused a significant increase in the animals' average lifespan. Other elements did not affect lifespan.





    BIOLOGICAL METHODS




    Food restriction



    Apparently, the first systematic experiments on mammals were carried out by T. Osborne (1915)).

    In experiments on rats, it was found that a calorie-restricted (by 20-30%) complete diet caused a significant extension of the life of animals.

    In 1930-43. intensive research was carried out by Mac Cay's group [9], then by M. Ross, K. Barrows, A. Everett, and others.

    In all experiments, an increase in lifespan by 40-100% was described under the influence of various conditions of restricting nutrition and even restricting one amino acid in the diet, tryptophan [18].

    It is characteristic that the experimental animals in adulthood retained for a long time the characteristics typical of the young. The greatest effect of prolonging life was achieved in those experiments when the effect was started from an early age.

    Nutritional restriction in mature and late ages was ineffective [28]. Some authors have noted a decrease in animal mortality at later stages of life and an increase in mortality at a young age.

    In recent years, there has been an increase in the number of studies in which only a small increase in the maximum lifespan was observed, especially in experiments on long-lived strains of mice and rats.

    Analysis of the array of works, which included 195 groups of animals, showed that under the influence of calorie-restricted diets in all experiments, the average lifespan and the maximum lifespan increased by an average of 15 and 16%, respectively, with a large scatter of lifespan values ​​in both sides of these average values.

    Nutritional restriction is a biological way of prolonging life since this effect inhibits the growth of young animals and changes their developmental program in such a way that the effect of slowing aging is manifested in mature and late ages.

    In starving rats, the period of puberty can increase 3 times.


    Analysis of literature data on lifespan and the duration of puberty in 200 species from 14 orders of mammals showed that there is a clear correlation between these parameters.


    This, in particular, can explain the prolongation of the life of animals in experiments with food restriction.

    In the USA, an experiment with fasting was performed on 30 thousand rats and mice (1990). It was found that the animals' metabolism and body temperature decreased.

    There was a slight decrease in the average lifespan of the control animals as compared to the average lifespan of intact animals, and the average lifespan of the experimental subjects increased in comparison with the control.

    L. Hayflick noted that experimental animals do not live unusually long. It's just that the control ones, overeating, age faster and live less.

    It is possible that in these experiments starvation is a factor in lowering body temperature and metabolism, under the influence of which growth retardation, changes in the development process, and aging retardation occur.

    It is well known that with a 3-day fast, the temperature of adult rats can drop to room temperature.

    A slowdown in aging is characteristic in the second half of the life of experimental animals, even without the restriction of nutrition during this period.

    It can be assumed that nutritional restriction by itself practically does not change the aging rate, but, influencing the development program of animals at an early age, it qualitatively changes metabolism in subsequent life.

    The effect of increasing lifespan was usually observed precisely in rats and mice, the development of which before puberty is very labile when nutrition is limited (growth retardation and puberty, decreased metabolism, and body temperature).


    In other species (rabbits, dogs, monkeys), these changes are less pronounced. No such changes were found in the human development program, however, during fasting, the body temperature decreases slightly.


    As for the level of metabolism, there is reason to expect that it will increase.

    If similar phenomena are manifested in a person before puberty, then fasting during this period may even lead to a reduction in subsequent life.

    Therefore, this method of extending life requires careful study.

    Moreover, a calorie-deficient diet, observed in some regions of the world, leads to profound metabolic disorders, especially at an early age, causes irreversible structural changes in the central nervous system, leading to a reduction in life.

    In the elderly, malnutrition in winter contributes to hypothermia and increased injury.

    There are reports that a 5-fold decrease in the amount of tryptophan in the diet increased the life expectancy of rats by 20% [40].

    The exposure changed the content of serotonin in the brain, which indicated a restructuring of the links of central regulation with a change in the ratio of neurotransmitters in the hypothalamus.

    A significant decrease in tryptophan in a person's diet at an early age may be accompanied by impaired growth processes, protein metabolism, and the development of pellagra.

    Some prolongation of a person's life by restricting nutrition can be achieved with exposure in the second half of life.

    This is confirmed by numerous data on human longevity. Here, apparently, restriction of nutrition helps to slow down age-related changes not by reducing metabolism, but by mitigating the stressor effect of the altered metabolism characteristic of the elderly.

    At the same time, it is important that food is limited and complete.







    Enterosorption


    The cholesterol hypothesis of aging claims that atherosclerosis is one of the main age-related diseases associated with an increase in blood cholesterol levels.

    With age, the sensitivity of some body systems to the effects of toxic substances also increases and intoxication processes intensify.

    It has been observed that animals with more reliable detoxification systems (microsomal oxidation) live longer.

    The function of this system weakens with age. Therefore, to slow down aging and prolong life, a method of enterosorption was proposed - removal of toxins and their metabolites, cholesterol, and atherogenic lipid fractions.

    The method consists in adding absorbents (sorbents) to food to cleanse gastrointestinal juices from toxins and other substances.

    The liquid part of these juices is filtered from the blood, and in the intestine is absorbed into the blood.

    A kind of hemosorption is formed (purification of the blood from toxins or lowering cholesterol levels).


    In rats aged 20 months, the addition of the carbon sorbent (nitrogen-containing coal) to the diet caused an increase in the average lifespan by 43.4%, the maximum lifespan - by 34.4%, a delay in age-related changes in the liver, kidneys, heart, intestines, and pancreas, a decrease in cholesterol and triglycerides in the liver, blood, and brain.


    Interestingly, earlier the American scientist A. Carrell expressed the idea that the blood of old animals contains a certain “death factor”.

    From an old decrepit dog, he removed 2/3 of the blood, carefully washed the erythrocytes in saline from the putative factor, and then poured it back into the animal.

    The dog's fur began to grow, motor activity increased sharply, and the sexual instinct was restored.

    However, this rejuvenation did not last long, and the aging factor could not be isolated.

    The enterosorption method has shown itself to be effective for the prevention of atherosclerosis of the vessels of the heart (coronary artery disease and heart attack), brain (strokes), diabetes, and autointoxication of the human body.

    Apparently, this is one of the few ways that really slows down aging.







    Physical activity


    The influence of running on the lifespan of mice and rats was experimentally established [27, 29].

    If the exposure started at a young age, then the average lifespan increased slightly. At the same time, growth and development retardation was observed.

    From a certain age, physical activity led to a reduction in life expectancy. This was because in the experiments there was no optimal dosage and a decrease in the load with age.


    In humans, the optimal level of physical activity contributes to the preservation, even in old age, of sufficiently high indicators of metabolism and energy, muscle tone, a decrease in the intensity of age-related pathological processes, primarily cardiovascular diseases, an increase in the blood supply to the brain and an improvement in the function of the central nervous system [13].


    This is due to an improvement in the neuroendocrine regulation of the body. However, physical activity has practically no effect on the lifespan of humans and animals.

    This is confirmed by statistical studies of the lifespan of former athletes of various qualifications and former students of Harvard University - athletes and not involved in sports.






    Decrease of body temperature

    In many experiments on invertebrates, a decrease in the body temperature of animals caused a significant increase in the maximum lifespan, sometimes by tens of times.

    This effect has not been achieved in mammals. Warm-blooded animals are divided according to the principle of thermoregulation into homeothermal (their body temperature does not depend on the temperature of the environment) and heterothermal (body temperature changes under different conditions).

    In the latter, a decrease in body temperature is associated with a slowdown in metabolism and aging, which leads to a significant increase in the maximum lifespan.

    Thus, in experiments on hamsters, a twofold extension of life was achieved [20].

    In homeothermic animals and humans, a decrease in body temperature in various ways causes the activation of additional thermoregulatory mechanisms and an increase in the metabolic rate.

    As a result, a reduction in lifespan can be expected. In experiments on life extension on dogs, rats (Holloszy, 1986), and other animals, simple cooling ended in failure.

    In 1974 it was reported that in the USA, a group of prof. B. Rosenberg was supposed to develop a drug within 10 years to influence the structures of the hypothalamus responsible for maintaining body temperature in humans, to reduce it by 42°F (6 °C), and thus extend life up to 200 years.

    Experiments were carried out on mice. However, the extension of human life has not been achieved.

    There are fundamental difficulties in solving the problem of a long and significant decrease in human body temperature.

    However, it is known that masters of oriental psychotechnics, as well as Australian aborigines, can lower body temperature by 41-44.6°F (5-7.5 °C and metabolism without harm to themselves.






    Sleep

    Professor S.N. Braines (1958) conducted experiments on old, completely decrepit dogs.

    The author describes a 15-year-old lapdog (the age limit for this breed) after 3 months of prolonged sleep treatment with hypnotics.

    The dog's general condition improved, many symptoms of decrepitude disappeared, the muscle tone of the limbs increased, new hair began to grow, the sexual instinct was restored and maintained until the end of life, many biologically important functions were restored.

    The dog lived for another 6 years and was accidentally killed by a chimpanzee at the age of 21.5 years.

    These experiments were not confirmed by other authors, and in general, no similar facts were found in the literature.

    A careful analysis of other works by S.N. Braines showed that the “phenomenon of rejuvenation” was observed since the author, before the experiments, aged the animals to senility by various influences.

    Similar errors are found in studies of other authors when some pathological changes (temporary, recoverable) are taken for age (senile) changes.


    Statistical demographic data indicate the minimum mortality in people with 7-8 hours of sleep.


    This is because many of the body's biorhythms are synchronized with the sleep-wake cycle. With age, spontaneous desynchronization of biorhythms occurs, and normal sleep is a synchronizing factor.

    The maximum human mortality is observed in autumn and winter. Sleep is known to be shorter in spring and longer in autumn.

    Therefore, the traditional regime of centenarians is justified: to get up after sunrise and go to bed after sunset.

    The largest number of places of longevity is observed at about 10 ° north latitude, that is, in the area where the values ​​of the duration of the periods of day and night are observed, which do not change much during the year.






    Hypobiosis

    The method of hypobiosis, which is used by many mammals in extreme conditions (cold, heat, hunger), should be especially noted.

    It has been established that in this state the aging process of animals slows down sharply, and the lifespan can increase several times compared to the lifespan of individuals of the same species that did not fall into hypobiosis.

    These facts are confirmed by research and laboratory conditions [33]. There are fundamental difficulties in creating hypobiosis in homeothermic animals and humans.

    Methods of artificial hypobiosis are currently being developed.

    Known methods of artificial hypobiosis are used in humans during complex operations or in extreme situations.

    To prolong life, their use is unjustified due to the difficulty of maintaining hypobiosis for a long time and the possibility of complications.






    Oriental psychotechnics

    It is known that many of a person's reserve capabilities are manifested in special states of consciousness, which are achieved after prolonged special training, psychotechnics.

    It is successfully used to prepare people for activities in extreme conditions (astronauts, submariners, high-class athletes, etc.).

    Transcendental meditation is widely used to improve people's health.

    The influence of meditation on the aging process is also being investigated. In 73 US nursing homes (1990), elderly people (average age 81 years) were divided into 3 groups: in the 1st they conducted meditation sessions, in the 2nd - relaxation sessions, the 3rd group was the control.

    After 3 years in the 1st group everyone was alive, in the 2nd group 12.5% ​​died, in the control - 37.5%.

    The mechanism of slowing aging under the influence of meditation is being studied in several scientific laboratories around the world.

    There are reports that in the so-called state of "samadhi" rejuvenation of body cells occurs.

    Among the masters of oriental psychotechnics, who used samadhi to prolong life, there are legends about long-lived phenomena.

    For example, Tapaswiji is said to have lived for 186 years, and he died not old but from an accident. There is no scientific evidence for these claims.

    Unlike Western culture, many Eastern traditions have accumulated over the millennia vast experience in improving and prolonging human life.

    It is generalized in the form of techniques, psychotechnics, methods, systems and, it is claimed, brought to the art of prolonging life.

    Scientists are studying the most effective Eastern and Western psychotechnics and systems intending to adapt and use them to slow down aging and prolong the life of a person of Western culture.





    Scientific sources


    1. Aslan A. Specification regarding the technique and action of Gerovital H3 treatment after 34 years of usage// Rom. J. Geront. Geriatr. 1985.Vol.6. P. 2-11.

    2. Ooka H., Fujita S.,Yashimoto E. Pituitary-thyroid activity and longevity in neonatally thyroxine-treated rats//Mech.Ageing Develop. 1983. Vol.22. P.113-120.

    3. Nichans P. Introduction of the cellular therapie. Bern. 1960. 369 p.

    4. Massie H.R. etc. Dietary vitamin C improves the survival of mice.//Gerontology. 1984. Vol.30. P.371-375.

    5. Bjorksten J.. Cross linkages in protein chemistry// Advance. in protein chem. 1951. Vol.6. P.343.

    6. Molnar K. Subbiological aspect of aging and the concept of biological cathode protection.// Mech.Ageing develop. 1973. Vol.2. P.319-326.

    7. Berg B.N. Nutrition and longevity in the rat//J.nutr. 1960.Vol.71. P.242-254.

    8. Yuhas J.M. The dose response curve for radiation-induced life shortening.//J.gerontol. 1969. Vol.24. P.451-456.

    9. Mac Cay C.M. etc. Nutritional requirements during the later half of life.//J.nutr. 1942. Vol.21. P.45-60.

    12. Kohn R.R. Effect of antioxidants on lifespan of C57BL mice.//J.Gerontology. 1971. Vol.26. P.378-380.

    13. Shepard R.J. Exercise and aging.//The biology of aging./Ed.by J.A.Behnke. N.Y: 1978. P.131-150.

    14. Everitt A.V. The effect of hypophysectomy and continuous food restriction, begun at age 70 and 400 days, on collagen ageing, proteinuria, incidence of pathology and longevity in the male rat.//Mech.ageing develop. 1980. Vol.12. P.162-172.

    15. Goodrick C.L. Effects of long-term voluntary wheel exercise in male and female Wistar rats. 1.Longevity, body weight and metabolic rate// Gerontology. 1980. Vol.26. P.22-33.

    16. Dencla W.D. Interactions between age and the neuroendocrine and immune system.//Exp. Pathol. 1979. Vol.17. P.538-545.

    17. Holloszy J.O., Smith E.K. Longevity of cold-exposed rats: a reevaluation of the “rate-of-living theory”.//J.appl.physiol.1986. Vol.61. №5. P.1656-1660.

    18. Segal P.E. etc. Low tryptophan diets delay reproductive aging.//Mech.ageing develop. 1983. Vol.23. P.245-252.

    19. Edigton D.W.,Cosmas A.C.,McCafferty W.B. Exercise and longevity: evidence for a threshold age//J.Gerontol. 1972. Vol.27. P.341-343.

    20. Lyman C.P. etc. Hibernation and longevity in the turkish hamster.//Science. 1981. Vol.26. P.668-670.

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