Користувач:Koval Maxym/Slowing down ageing

Slowing down ageing is the concept of increasing the average life expectancy of  a person and reducing the risk of developing age-related diseases.

Life expectancy is determined by vulnerability to accidents and most diseases. Its increase can be achieved by improving medical care, sanitation, promoting  heilbrigður lífsstíll (including healthy eating and physical education), and rejuvenation practices and preventing risks and harmful factors, such as smoking, alcohol consumption, excessive sugar consumption, etc.

Life expectancy is determined by the rate  of aging, which is inherent in the genes and, possibly, changes slightly under the influence of some other factors. Aging manifests itself in an increase in  the likelihood of any diseases, especially diseases of old age (cardiovascular diseases, oncopathologies) and an increase in the likelihood of death. Since the late 2000s,  the  main mechanisms of aging, and the complex impact on them, is a promising strategy for rejuvenating biological age and slowing down aging.

Scientific background

Slowing down ageing
Process of preserving the body's youth and preventing cell aging
Відомий завдяки	David Sinclair, professor of Harvard university, scientist, geneticist

Gerontology (from Greek. Γέροντος (old man) and λόγος (word, knowledge) is a science that studies the process of human ageing and  effective methods of prolonging optimized longevity and rejuvenation.

The branch of science that deals with the problem of increasing life expectancy is called "biomedical gerontology", a subdivision of gerontology. Researchers in this field seek to understand the nature of aging and develop tools that can stop or at least slow down the aging process. What distinguishes them from other biogerontologists is their predominantly practical, rather than academic, interest in the aging process.

The primary strategy for increasing life expectancy is to apply available anti-aging techniques (or methods that have the potential to slow down aging) in the hope of living long enough to take advantage of the opportunity to completely reverse aging, hoping that it will happen quickly enough. Taking into account the speed of development of modern bioengineering and medical technologies, it is expected that this can occur within the lifespan of people living today.

Many biomedical gerontologists believe that future advances in  tissue rejuvenation through regenerative medicine (stem cell treatment, tissue engineering), gene therapy and genome editing, bioengineering (genetic,  cellular, tissue , organ printing) and a complex effect on the 10 mechanisms of aging will be able to completely stop aging and diseases of old age, allowing the rejuvenation of the body to a youthful state.

Many organizations offer the possibility  of storage in a frozen state after death with the goal of preserving the human body until the time when medical advances can develop such techniques for rejuvenation and repair the damage caused by the freezing process itself.

Increasing the maximum human lifespan is the topic of many ethical debates between politicians, scientists, practitioners, and religious figures.

History of Research and the Extensionist Movement

The continuation of life has been the desire of humanity and a major motive in the history of scientific inquiry and ideas throughout history, from the Sumerian epic of Gilgamesh and  the Egyptian medical papyrus of Smith, to practitioners of Ayurveda, alchemists, and hygienists such as Luigi Cornaro and Christoph Wilhelm Hufeland,  and philosophers such as Francis Bacon , René Descartes, Benjamin Franklin and Nicolas Condorcet.

The beginning of the modern period in this direction can be traced from the late 19th and early 20th centuries, to the so-called period "fin-de-siècle", which is designated as the "end of an era" and is characterized by the growth of scientific optimism and therapeutic activism, which entails the desire to prolong life. Among the prominent researchers of life extension during this period were the Nobel Prize-winning biologist Illia Mechnikov (1845–1916) was the author of the cellular theory of immunity and vice-director of the Pasteur Institute in Paris, and Charles-Édouard Brown-Séquard (1817-1894) was president of the French Biological Society and one of the founders of modern endocrinology.

In 2013, an article was published in the journal Cell that summarized 10 mechanisms of aging, which are the basis of the modern view of the rejuvenation of biological age and the increase in life expectancy.

Strategies to increase life expectancy

Senolytics and anti-aging drugs

Apigenin - one of the strongest senolytics nowadays

Senolytics (from the words senescence and -lytic, "destructive") belong to a class of small molecules that they can selectively induce the death of senescent cells (senescent) and improve human health. Senolytics eliminate senescent cells, while Senomorphic Preparations modulate the properties of senescent cells without destroying them, inhibiting aging phenotypes, including SASP. Other candidate drugs are Metformin, acarbose and NAD+ preparations.

One of the most powerful senolytics is apigenin (${\ce {C15H10O5}}$).

Many life-prolonging drugs are synthetic alternatives or potential additions to existing nutraceuticals, such as various investigational compounds that activate sirtuin (SRT2104) pathways. In some cases, pharmaceuticals are combined with nutraceuticals — for example, in the case of glycine in combination with NAC.

Healthy Eating

See also — Healthy Eating, Rational Eating, Nutrition, Nutrigenomics, Nutrigenetics, Superfood.

Nutrition is the basis of all life processes of the body. It is necessary for the continuous renewal of cells and tissues, compensation of energy costs, and the formation of various regulators of vital activity. Metabolism, function, structure of cells and organs depend on the nature of nutrition. Nutrition is a complex process of intake and digestion of food, absorption and assimilation of proteins, fats, carbohydrates, vitamins, minerals, and water by the body. Rational nutrition is physiological adequate nutrition of healthy people, taking into account their gender, age, nature of work and other factors. It contributes to the preservation of health, resistance to harmful environmental factors, high physical and mental performance, and active longevity. The principles of rational nutrition consist of requirements for the diet, diet and eating conditions. The food ration is subject to such requirements as the energy value (calorie content) of the diet, which should cover the energy consumption of the body; it must have the proper chemical composition (the optimal amount of balanced nutrients); diversity due to a wide range of products and various methods of their culinary processing; good digestibility of food, depending on the composition and method of preparation; high organoleptic properties (appearance, taste, smell, color, consistency, temperature), which affect appetite and digestibility; the ability of food to create a feeling of satiety (composition, volume, cooking); sanitary and epidemiological harmlessness of products.

Studies show that adherence  to the Mediterranean diet and the Okinawan diet are associated with improved health and life expectancy, and reduced overall mortality and mortality from many chronic diseases. Regular consumption of fruits and vegetables, nuts, fiber, oily sea fish and/or omega-3 fatty acids, vegetable protein, olive oil reduces the risks of many chronic diseases and mortality from them.

Studies show that dietary patterns are the main reason for the relatively high average life expectancy in Japan.

The health of the gut microbiota also plays an important role. Studies show that the gut microbiota is involved in beneficial effects to improve health and extend life expectancy. Dietary diversity is also necessary for the formation and maintenance of a diverse gut microbiota. The diversity of the composition of the microbiota is one of the main conditions for the health of the intestines and the body as a whole. Therefore, for the health of the gut microbiota, it is advisable to consume as much as possible more different foods high in plant-based dietary fiber (fiber), especially fruits, vegetables, spices,  and fermented foods.

A 2021 randomized clinical trial of 43 healthy people between the ages of 50 and 72 found that 8 weeks of a healthy lifestyle — a plant-based diet, adequate and high-quality sleep, exercise and active relaxation, and probiotics and phytonutrients — rejuvenated people's biological (epigenetic) age by an average of 3.2 years (p=0.018).

Also in 2021, the rejuvenation of a person's epigenetic age by 5 years in just 7 months was documented, with the help of a daily varied plant-based diet (especially nuts, vegetables, seeds, berries and unsweetened fruits), a large number of different dietary supplements (collagen, creatine, spermidine, lecithin, amino acids, vitamins, polyphenols, glucosamine and others).

Dietary supplements

In addition to research on senolytics and (synthetic) life-prolonging drugs, dietary supplements and bioactive plant compounds are being actively researched. Their use is sometimes investigated or recommended as a way to correct nutrient deficiencies from switching to healthy foods, specifically from replacing meat consumption with a higher intake of plant-based foods. Especially, but not only, in such cases, the addition  of minerals is investigated and  various specific trace elements. For example, correcting magnesium deficiency can prolong life. Many dietary supplements are being researched primarily for potential health improvements and longevity, rather than to extend lifespan.

Research in biomedical gerontology has suggested many medications  and dietary supplements to increase life expectancy. The most common idea is that antioxidants (e.g., vitamin C, tocopherol, lipoic acid,  and N-acetylcysteine) taken as supplements to the core diet will be able to increase life expectancy based  on the effects of free radicals on aging .

Resveratrol, Sir2 stimulant,  has also been suggested because of the success of its use in increasing lifespan by mimicking the calorie restriction effect  of simple model organisms.

Many other nutritional supplements have shown positive effects on some aging-related conditions and diseases of old age. For example, selenium, chromium,  and zinc have been shown to increase the lifespan of mice. Metformin may also increase the lifespan of mice.

Calorie restriction

Restricting energy or calorie intake in an otherwise healthy diet (a practice known as "calorie restriction") has been shown to increase the maximum lifespan of most organisms in which it has been studied, including rats, mice, yeast, fruit flies,   and nematodes. In most cases, however, the increase in life expectancy only occurs if the diet is started before puberty. In rodents, an approximately 50%  increase in maximum lifespan is achieved with 40-50% calorie restriction compared to animals with unlimited food. Although attempts to show the same effect in larger and more complex animals have not yet yielded positive results, Experiments are still being done with primates.

Some life extensionists hope for the success of these experiments and believe that calorie restriction can have the same effect on humans. With the help of extensionist activists (Brian M. Delaney, Lisa Walford, and Roy Walford), the Calorie Restriction Society was formed in the mid-1990s Members of the group limit their food intake by force of will in order to prolong their own lives,  But the group remains small.

According to two scientific reviews published in 2021, the accumulated evidence suggests that dietary restriction (DR) — mainly intermittent fasting and calorie restriction — leads to many of the same beneficial changes in adults as in the organisms studied, potentially increasing health and lifespan.

Hormone replacement therapy

Hormone therapy (hormone  replacement therapy) – which attempts to restore hormone levels  to levels characteristic of youth (primarily somatotropic hormone (growth hormone), testosterone, estrogen, progesterone, melatonin, and  thyroid hormone, the concentrations of which decrease with age) is also suggested as a means of reducing the effects of aging. Other, less popular hormones that could also potentially be beneficial are oxytocin, insulin, gonadotropin, erythropoietin, and others.  

Epigenome

Gene therapy

Main articles — Gene therapy, Genome editing.

In 2021, a small, sponsored, interventional, non-randomized study without a control group was conducted using a novel patented method for central nervous system gene transfer to deliver AAV hTert and Klotho genes to five patients with mild to moderate dementia for priority safety evaluation. Clinical response data were collected as a secondary interest. The therapy has demonstrated a very high safety profile with no serious side effects detected. Clinical Examination of patients during one year of follow-up yielded significant results: all five patients showed a clear reduction  in dementia symptoms, such as sustained cognitive improvement. Telomeric analysis was performed before and after therapy. Measurable lengthening of participants' telomeres was found, and a decrease in biological age with an increase in chronological age.

Epigenetics

David Sinclair, famous DNA scientist

Epigenetics is the study of hereditary  changes in phenotype (appearance) or in gene expression due to mechanisms other than changes in the sequence of DNA nucleotides. Such changes can remain visible for several cellular generations or even several generations of living organisms. Changes in the DNA sequence do not occur, instead other genetic factors cause genes  to  show yourself differently. The best example of epigenetic changes for eukaryotes is the process of cell differentiation. During morphogenesis,  totipotent stem cells become pluripotent cell lines of the embryo, which in turn become fully differentiated cells. In other words, one fertilized egg is a zygote, divides and differentiates into different kinds of cells that are present in a living organism. This is done by activating some genes and inhibiting others.

David Sinclair, an Australian biologist and professor of genetics, in an interview expressed an interesting opinion about the aging of the body and its reasons:

"The aging of the body occurs due to the loss of information in our DNA. It is about information recorded not in our genome, but  in the epigenome. That is, with age, the body does not lose important areas of the DNA molecule. No, the bottom line is that it cannot "read" or, on the contrary, transmit information in these areas of the DNA molecule to perform the most important vital functions of the body."

Cloning and Organ Replacement

Biotechnology, especially  related to  human organ cloning and stem cell research, seems to be able to offer the possibility of replacing old body parts with new artificially grown parts in the relatively near future. Modern technology has already demonstrated the feasibility of replacing body parts in laboratory experiments, the most famous example being the artificial growth and successful implantation of a functioning body bladders  and other simple biological structures are relatively easy to artificially produce, while complex biological structures such as joints, limbs, and  complex organs are  still far from being artificially produced. Taking into account the increasing rate of development of new technologies, it is likely that the artificial production of body parts of varying complexity and successful implantation techniques will one day become Possible.

In one popular scenario, individuals' brains would be transplanted from an aging body into a new one, cloned from the patient's own tissues. Such a scenario is found, for example, in Dr. Axe's fantastic but quite realistic work I of persistence. Brain transplant experiments have been conducted since the mid-20th century (in both monkeys and dogs), but have always failed due to rejection immune system and inability to restore nerve connections. Proponents of body replacement and cloning believe, however, that the necessary organ replacement biotechnology is likely to emerge before other methods of increasing lifespan.

Slowing down aging

Cryonics

Main article: Cryonics

The basic idea behind cryonics is that lifespan-increasing techniques may eventually allow humans to live for thousands of years without experiencing the effects of aging. But these techniques probably won't be available for the next few decades. That is, there is a danger that anyone, even the young now, will have time to die before new medical means become available. Cryopreservation, soon after the onset of a "legitimate death, can provide  an "ambulance" that will deliver the human body into the future, based on the belief that under the conditions of cryogenic temperatures, changes in biological tissues over several thousand years will be insignificant, and suitable for the restoration of life using the technologies of future medicine.

Rapid cooling and cardiopulmonary support, initiated immediately after death, can preserve body cells and tissues for further long-term preservation at cryogenic temperatures. People, especially children, survived for an hour without a pulse after being immersed in icy water, and after 45 minutes without a pulse, full recovery was achieved. Groups of cryonics workers usually wait at the bedside of patients to apply cooling and cardiopulmonary support as soon as death is declared. Cryonicists do not believe that legal death is real death (irreversible destruction of the anatomical basis of the mind), while conventional medicine considers the moment of death to be the moment when the pulse cannot be restored with  a defibrillator.

Strategies for Constructing Minor Aging

Renowned biogerontologist and lifespan activist Aubrey de Grey proposed an approach known as Slight Aging Design Strategies (eng. Strategies for Engineered Negligible Senescence, SENS). Instead of studying and combating the mechanisms of damage accumulation during aging, this approach proposes the artificial engineering of damage repair techniques at all levels where it is important and feasible. To accomplish this goal, the approach proposes the use of gene therapy, protein therapy, chemical and other external influences on the body in order to eliminate the symptoms of aging, with the help of which aging will proceed very slowly or not at all, and possibly rejuvenation of the body will be achieved. More specifically, the task was broken down into several main aspects of aging (the so-called "seven deadly things") and strategies to combat each of them:

1. The loss of cells in the muscles can be stopped with exercise. All other tissues require growth factors and, in some cases, stem cell population repair.
2. Old cells (primarily cells close to the Hayflick limit) can be eliminated by activating  the immune system against them. Alternatively, gene therapy can create a genetic program that induces apoptosis (suicide) of such cells.
3. Cross-links between proteins, especially collagen, could theoretically be eliminated with chemicals that break down some such bonds. However, in order to eliminate all cross-linking, enzymatic methods need to be developed.
4. Extracellular debris can be eliminated by vaccination and programming  white blood cells to "eat" the debris.
5. To dispose of intracellular debris, new  enzymes must be added, possibly enzymes from soil bacteria capable of dissolving lipofuscin and  other pigments and inerts that mammalian enzymes are unable to dissolve.
6. To prevent  mitochondrial  mutations, appropriately altered copies of mitochondrial genes should be moved into the nucleus of the cell. Mitochondial DNA will experience very strong mutagenic damage due to the fact that it is in the mitochondria that the largest amount of reactive oxygen species is produced  and due to much worse DNA repair mechanisms in the mitochondria than in the nucleus of the cell. The copy of the mitochondrial DNA located i the nucleus will be better protected, and all the mitochondrial proteins will be transported to the mitochondria, as already happens with most mitochondrial proteins.
7. To combat cancer ( the most lethal consequence of mutations), it is proposed to create mechanisms for the deletion  of telomerase genes  during the transition from stem cells to somatic cells (or in all cells, and periodic external restoration of the stem cell population) and the elimination  of telomere-independent means of transforming cells into cancerous ones.

Consciousness Transplant

A consciousness transplant refers  to the transfer of a person's mind/consciousness to another medium, which provides longer functioning than the human body. A silicon computer can be used for this purpose. The idea is based on the structure of signal transmission and processing in neuronal networks, which is a numerical system that can theoretically be stimulated on a computer. However, the structure of memory The structure of consciousness is still unknown, as well as unknown, so there is no scientific understanding of how the process of "reading" human consciousness can be constructed. With  the constant growth of computing power in computers and the likely continuation of the trend, it is  assumed that soon the power of computers will be sufficient to fully stimulate the human thinking process, according to  the predictions of futurist Ray Kurzweil, this will be achieved by 2020. A lot of research is currently being done on the functioning of the human brain, and it is predicted that the creation of technologies for creating detailed brain maps will be around 2020. the same timeline. Sending the human mind to a computer, if carried out, could potentially significantly increase the lifespan of a "human," or rather their consciousness.

Scientific criticism

Dietary supplements and medications

The main criticism of the fight against aging with the help of chemicals concerns not the theoretical possibilities of the method, but the means currently sold. This is especially true for antioxidants, the use of which as dietary supplements as an anti-aging agent has been widely advertised recently.

Despite considerable effort spent on obtaining evidence of an  increase in life expectancy under the influence of antioxidants, for example in the work of Denham Harman, only a slight increase in average life expectancy was found, but not a maximum. Some substances that are not antioxidants are accepted in foods (e.g. selenium and zinc) are more efficient and have shown an increase in not only average but also maximum life expectancy (although, at least in part, this effect may be the result of limited population size). However, the advertised substances are not them, but numerous drugs, mainly based on antioxidants, none of which has shown an increase in the maximum life expectancy of a person. In response to an "unscrupulous thirst for profit from the sale of dietary supplements and anti-aging drugs," a group of biogerontologists has launched an active "war" against existing anti-aging drugs, specifically the American Academy of Anti-Aging Medicine (A4M), an active seller of these drugs. The best-known scientists in the field of biogerontology, Jay Olchanski, Leonard Geiflick, and Bruce Carnes, wrote an open-ended programmatic paper against them.

See also

• Healthy Lifestyle
• Gerontology
• Rejuvenation
• Epigenetics

• David Sinclair