What is Autophagia simple words. Autophagia: How to really clean your body

06.10.2020

Although there are many different ways to help your body get rid of accumulated toxins, ranging from products that promote detoxification, and chemical and / or natural detox-agents for a sauna, a biological process, known as Autophagy plays a key role. The term Autophagy means "self-navigation" and refers to the processes by which your body is cleaned from various garbage, including toxins and regenerates damaged cellular components.

If you try to explain on a language that is clear for non-specialists: " Your cells create shells that hunt for pieces of dead, patients or worn cells; devour them; Clean them; and use the resulting molecules for its energy or production of new cellular parts .”

Dr. Colin Champion, Radiation Oncologist and Assistant Professor at the University of Pittsburgh explains this way: " Just think our bodies have a congenital disposal program. Autophagia makes us more efficient machines to get rid of defective parts, stop cancer neoplasms and stop metabolic disorders such as obesity and diabetes .”

Due to the strengthening of autophage process in your body, you are weakening inflammation, slow down the aging process and optimize biological functions. " More autophage occurring in tissues should mean a smaller number of damaged and weakened cells at any time that in turn should lead to a longer life of the body ».

Sketchy model of Autophagia

Intolation of autophagia with physical exercises
Autophagia arises in response to stress. And, in fact, exercise is one of the ways with which you will increase the level of autophagia. As you probably know, the physical activity creates soft damage to muscles and fabrics, which makes your body then do repair, and thereby making your body stronger. Exercise also help get rid of toxins by sweating, which is useful for any detoxification program. In fact, many researchers consider physical exertion to the fundamental aspect of effective detoxification.

Dr. George U., for example, who took part in clinical trials to help the body of the former US Army military personnel to leave the status of post-military war syndrome in the Persian Gulf, recommends using a combination of exercises, saunas and niacin additives to increase the removal of toxins through the skin .

Exercise are an important component, since they also cause expansion of blood vessels and strengthening blood flow. In addition, as noted in one article: " A group of scientists studied autophagosomes, structures that are formed around pieces of cells that the body decided to dispose. After the study of specially grown mice who had glowing green autophagosomes ... Scientists have found that the speed with which mice were able to destroy their own cells increased sharply after they ran over 30 minutes on the treadmill. And this destruction efficiency continued to grow as long as they ran about 80 minutes ”.

How many physical exercises should be done to optimize autophagia?
The number of exercises required to stimulate autophage in the human body is still unknown, but it is believed that intensive exercises are more effective than light exercises. , which are certainly also helpful.

Nevertheless, some studies have shown that the ideal zone in which exercise shows the greatest benefit to increase the duration of life, range from 150 to 450 minutes of moderate exercise per week, which reduces the risk of early death by 31% and 39%, respectively. The inclusion of at least 30% of the training of exercises with high intensity, also showed an increase in life expectancy by approximately 13% more compared to the exercises, which were carried out in a steadily moderate pace all the time of workout.

How can you slow down autophagia
One of the fastest ways to slow down autofagia is to eat a large amount of protein. It will stimulate the development insulin-like IGF-1 growth factor and activates mTOR path which are strong autophage inhibitors.That's why it is better to limit the use of protein approximately 40-70 grams per day, depending on your muscle body weight. The best formula is one gram of protein per kilogram of muscle body weight (not a total body weight).

A significant amount of protein can be found in meat, fish, eggs [, dairy products, legumes, nuts and seeds. Some vegetables also contain a large amount of protein, such as broccoli. Forty grams of protein - this is not a large amount of food, which is about 170 gr. Chicken breast.To determine whether you will receive too many protein products, simply determine the weight of the muscles in your body (there are outdoor scales with such a function) and write down everything you eat within a few days. Then calculate the amount of daily protein consumed from all sources with respect to the kilogram of your muscle mass.

The following table briefly shows how much protein is contained in various food..

Protein content in some products

The importance of mitochondrial biogenesis
Healthy mitochondria are the basis for the preservation of your health and prevention of diseases. Mitochondrial damage can cause genetic mutations, which contribute to the development of cancerTherefore, the optimization of the health of your mitochondria is the key component of cancer prevention.

Autophagia is one of the ways to remove damaged mitochondria, and biogenesis is a process by which new healthy mitochondria can be duplicated.
Interestingly, physical exercises play a double role, since not only stimulate the processes of autophage, but are also one of the most powerful stimulants of biogenesis mitochondria. This is due to an increase in the signal in your body, called AMPK. which in turn activates PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA COACTIVATOR 1-ALPHA (PGC-1α) .

Stimulating its mitochondria - organelles, located in almost every cell that produce ATP, you allow mitochondria to start creating active forms of oxygen (AFC), which act as signal molecules. One of the functions of this signal is to stimulate the production of a larger number of mitochondria. In fact, the key to the prevention of the disease, which practically eliminates the risk of cancer, heart disease, diabetes, many other diseases and the slowdown of aging processes is the optimization of mitochondrial functions and an increase in the number of these mitochondria. Fortunately, exercise helps you make these two useful things.

Mitochondria

Periodic starvation - another way to increase the level of autophagia
Power limit is another biological stressor, which produces many useful results, including intensifying autophage. In fact, some of the benefits associated with the restriction in nutrition are known: reducing the risk of developing diabetes and heart disease.

Although there are many different types of starvation graphs if you already have insulin resistance (the resistance of insulin cells in sugar absorption), Dr. Merkol (USA) recommends that every day plan your meal in the interval (window) of about 8 hours or less. For example, you can limit your meals from 11 am and up to 7 pm. This is approximately 16 hours without food.

Power between 8-hour in the morning and 4 o'clock in the evening can be much better schedule for some people, and this schedule has an additional advantage, because it allows you to fast for a few hours before bedtime. Dr. Merkol is convinced that this is the best choice for most people, so as not to eat three hours before bedtime, as the last thing you have to do is to produce energy when you do not need it.

There are convincing evidence showing that when delivering fuel for your mitochondria at a time when they do not need it, leads to a large number of electrons that release the active forms of oxygen, acting as free radicals. These free radicals damage mitochondrial, and ultimately nuclear DNA. It is necessary to strive for starvation for six hours before bedtime, but if you talk about a minimum, then you should not have at least three hours before sleep.

To increase the level of autophagia, it is necessary to eat food with a high content of useful fats and low in carbohydrates
Food ketogenesis - This is the third strategy that will help increase the level of autophage, and to achieve this, you must reduce the amount of carbohydrates that do not contain useful food fibers, and increase the amount of healthy fats in your diet, along with a moderate amount of protein. Many Russians tend to eat much more protein than they need it to oppose your efforts to get into food ketogenesis.

Most cities inhabitants consume harmful fats, in the form of treated vegetable oils that will invariably worsen your health. This is not only associated with a very high content of omega-6 fatty acids, but also that excess omega-6 will be integrated into the inner mitochondrial membrane and mitochondria become extremely susceptible to oxidative damage, as a result of which your mitochondria can die much earlier than Price
It is better to keep the consumption of omega-6 fatty acids at a level from 4 to 5 percent of the total amount of daily calories, and the rest of Omega-6 fatty acids should be replaced with healthier fats, such as natural, unprocessed fats in seeds, nuts, oils from olives, Avocado oil or coconut oil.

It is also important to distinguish carbohydrates, so when we are talking about low-carb food, then we are talking about all products, including vegetables. However, carbohydrates from the fiber of vegetables will not push your metabolism in the wrong direction. It follows from this that the restriction includes easily durable carbohydrates from sugar, sweet drinks, treated croup (flakes), pasta, bread and cookies.
It is even more important that the fibers are not splitting on sugar, but pass down the digestive system, and then consumed by bacteria in your intestines, and are converted into short-chain fats that really improve your health. Remember, you need carbohydrates located in vegetables, which also contain a large amount of fiber.

Restoring autophage functions, you help muscle stem cells
It has long been known that mesenchymal stem cells (MSK) located in skeletal muscles are an important part of the process of muscle repair. Previous studies have shown that physical exercises affect the behavior of your muscle stem cells, and can help prevent or even restore the age loss of muscle mass. MSCs in the muscles are very responsive to mechanical stresses, and these stem cells accumulate in the muscles after training.

In the meantime, MSCs, not directly, contribute to the creation of new muscle fibers, increasing the development of growth factors that stimulate other cells to create new muscles. It is also known that people with age in the muscles are reduced by the number of MSK, and that the effectiveness of autophagia is reduced. As a result, toxic substances begin to accumulate in cells and tissues.

The recent Spanish study reports that satellite cells for MSC are responsible for tissue regeneration and rely on autophage to prevent the cell cycle arrest known as cell aging; The process in which the activity of stem cells is significantly reduced. In short, improving muscle tissue regeneration can be achieved by increasing efficiency and autofania levels. With an increase in the effectiveness of autophage, your bodies improve the internal self-cleaning mechanism when stem cells retain the ability to maintain and restore their fabrics.

Your lifestyle determines your further fate in terms of how long you will live and, ultimately, how many healthy years will you have. For optimal health and prevention of diseases, you need healthy and efficient mitochondria, which allows you to achieve three key lifestyle factor:
1. What you eat: Diet with a high content of high-quality fats, moderate protein content, and low carbohydrate content without food fibers. Use of ecological, organic plants in nutrition is also important, since the spectacides are widely used, such as glyphosate, cause damage to mitochondria
2. When you eat: Daily Periodic Fasting, as a rule, is easiest to stick, but you can plan any other post.
3. Physical exercises With a 30% time interval of high intensity - most effective in terms of health and longevity

Potapnem M.P.

Autophagia, apoptosis, necrosis of cells and immune recognition

his and alien

Belarusian State Medical University of the Ministry of Health of the Republic of Belarus, 220116, Minsk

The literature review presents data on the role of the main types of cell death for the formation of an immune response to pathogens and their own antigens. The main mechanisms of autophagia, apoptosis and necrosis of cells are considered, the value of the formed cell products for induction of an immune response. The role of Autophagia as a cellular autonomous protection system for pathogens and cell stress was noted. The leading role of apoptosis, apoptotic molecular images (patterns) in the induction of immunological tolerance is determined. The crucial importance of necrosis and products of damage to their own cells in the induction of the inflammatory reaction of macroorganism and an effective immune response to their own antigens, pathogens and molecular images (patterns) of pathogens are emphasized. The interaction of various types of cell death in pathological conditions is discussed.

Keywords: autofagia; apoptosis; necrosis; cell death; pathogens; inflammation; Immune response. Potapnev M.P.

AUTOPHAGY, APOPTOSIS, NECROSIS AND IMMUNE RECOGNITION OF SELF AND NONSELF

Belarusian State Medical University, Ministry of Public Health, 220116, Minsk, Belarus

The Review of Literature Discusses The Role of Most Essential Types of Cell Death (Autophagy, Apoptosis, Necrosis) for Induction of Immune Response to Pathogens and Self AntiGens. The Main Mechanisms of Cell Death and Biologic Characteristics of Cellular Products, Released During AutoPhagy, Apoptosis, Necrosis Were Reported. The Role of AUTOPHAGY AS CELLULAR SELF-DEFENSE SYSTEM AGAINST PATHOGENS AND CELLULAR STRESS WAS Underlined. The Receptor-Ligand Interaction for Induction of Immune Tolerance by ApopTotic Cells and The Role of Apoptotic Cell-Associated Molecular Patterns (Achamps) and dendritic Cells Were Described. Brief Description of Mechanisms of Necrotic Cell-Indduced Inflammation and Immune Response As Well As Leading Role of Damage-Associated Molecular Patterns / Damps Were Done. INTERACTION OF DAMPS AND PATHOGEN-ASSOCIATED MOLECULAR PATTERNS / PAMPS IN INDUCTION OF HOST DEFENSE AGAINST PATHOGENS WAS Described. It Was Concluded That Differential Type of Cell Death May Be Occurred Depending On Strength of Danger Signal Affecting Cells and Their Function.

Key Words: AutoPhagy; apoptosis; necrosis; Cell Death; Pathogens; INFLAMATION; Immune Response.

It is believed that the basic principle of the immune system is to recognize someone else's or modified and subsequent removal. The classic example of immune recognition of someone else is the reactions of congenital and acquired immunity against microorganisms (bacteria, viruses). Immune recognition of the changed is associated with autoimmune diseases. With the development of ideas about (for) programmed cell death (PKS), an important assessment of the communication of immunity with maintaining cellular homeostasis in macroorganism was an important. Any cell changes in the process of growth and differentiation, aging, natural diefing, metabolic dysfunction, stress, the effects of the pathological process (infection, sterile inflammation) should be considered by the immune system as a violation of cellular homeostasis. An assessment of the role of PCS in the launch of immune reactions is devoted to this review.

On the basis of morphological and biochemical criteria, three main types of PKS are distinguished: apoptosis (type I PKS), autofagium (PCS type II) and necrosis (type III PKS). PCS types I and II have certain genetically mechanisms

Potapnev Michael Petrovich (Potapnev Michael Petrovich), Email: [Email Protected]

we are implemented, so called active. PCS III type (primary necrosis as a result of external damage) is unmanageable, so called passive. Additionally allocate secondary necrosis as the final result of apoptosis, controlled necrosis (necroptosis) and other paths of cell death. The list of known (13) cells of cell death is regulated by the Nomenclature Committee. The characteristic of the three main types of PKS is presented in the table.

The attention of immunologists to cell death is determined by the fact that not only infectious antigens and molecular images (patterns) of pathogens (Pathogen-Associated Molecular Patterns - PAMPS), distinguishing it from macroorganism, but also products damage to their own cells (Damage-Associated Molecular Patterns - DAMPS) cause inflammation and immune response. P. Matzinger emphasized that for the immune system, it is important to recognize and respond to danger signals resulting from damage to tissues (cells), and not finding out the differences between their own and strangers.

Autophagia

Autophagia is a process of lifetime recycling (degradation using lysosomes) modified by metabolites of cytoplasm content to maintain cellular and energy homeostasis. Autophage is considered

Immunology number 2, 2014

Major Types of Cell Death

Characters type of cell death

stick Autophagy Apoptosis Necrosis

Purpose Degradation and intracellular utilization of damaged organelles and proteins without harm to the cell. In the case of excessive degradation, the cells are degradation of the diesel cells without an inflammatory and immune response of the body, the limitation of the focus of non-visual fabric by inflammation and immune response to toxic and impact-threatening organism

Morphology cells Vacurativeization of cytoplasm cells Condensation and sealing cells, condensation of chromatin, kernel fragmentation, the formation of apoptotic taurus swelling of the Organelle, followed by a breakdown of internal and external membranes. Swelling and subsequent lysis of cells

The mechanism of action is a sequential formation in the cytoplasm of pharmors, autofagosomes, autolisosomes or a shaper-consuming merger with caspase-dependent lying (receptor) or mitochondrial-dependent DNA degradation path uncontrollable cell damage or receptor-dependent (Rage, TLRS, CD91, etc.) the path of destruction of the cell

LC3-II, ULK 1, ATG12, ATG4, Gabarap DNA Fragments 50 KBP, FS External Membrane, FAS, CASP 3, APAF1 LDH, HBGH1, S100-Squirrel, ATP, HSP90

Participation of phagocytosis is absent present present

as a predominantly "programmed cell survival". Stress causes autofagia, and excessive Autophagia activity leads to cell death. Insufficiency of autophagia provokes the accumulation of metabolites associated with aging, degenerative processes in nervous tissue and liver, autoimmune, pulmonary diseases (especially on the background of smoking). The connection of autophage with Krone's disease, fibrosis, obesity, sepsis is shown.

The main type of autophagia is macrostophagia, including the stages of initiation, nucleation, elongation and fusion (with lysosome). Changed cytoplasm proteins (as a result of stress, lack of energy supply), damaged by mitochondria, excess endoplasmic reticulum (ER), peroxisomics are translated into organelle membranes due to the complexation with ULK 1/2, ATG13, ATG101, FIP-200 proteins. On the membranes of the Organell (ER, Mitochondria, Golgi Device), these proteins form a complex I, which includes additionally proteins VPS34, BECLIN

I, VPS15, ATG14L. Around the complex I is formed the inner membrane of pharmors. Autophagosoma formation (0.3-1 μm diameter) with a double membrane requires the participation of LC3

II, which is formed by the phosphatidyl-tanlaminic fosphatidyl tanlamine of the Citoxole protein LC3, and the ATG5-ATG12 / ATG16L1 protein complex. The subsequent ripening of autofagosomes in autofagolysis is carried out by fusion with lysosomes using a protein complex II comprising VPS34, BECLIN 1, UVRAG. In the autofagolysis, the degradation of altered proteins under the action of hydrolylase and release to the cytoplasm of nutritious and energy-intensive substances is carried out. In addition to macroautophagia, microautophagia is isolated (when the capture of the contents of the cytoplasm is carried out by invagination of the Lizo-Som membrane) and the shaperone-mediated autophage (when the delivery of cytoplasmic material in the lysosomes is carried out using proteins-shaperon).

Due to the presence in the cytoplasm of the cells of modified and alien macromolecules, the Autophagy process, being metabolic, stands as a mechanism for recognizing and disposal of intracellular microorganisms (viruses, bacteria, simplest) carriers of PAMPS. Penetration into the cytoplasm of microorganisms and their products launches the mechanisms of autophagia as the cellular autonomous protective system-Cell-Autonomous Defense System. The separation of cytoplasm cells into separate, limited (endo) membranes sites and organelles (i.e. compartmentization) involves the presence of their receptor recipes in each of them recognizing alien PAMPs and modified their own DAMPS. This creates a multi-stage system of protection against pathogens, penetrated

inside the cell. At each stage of the advancement of the pathogen in the cell, DNA recognition, aggregated proteins, microbes and serum proteins complex, occurs. Pathogen faces various enzymes; NO and H2O2; The presence or disadvantage of nutrients. Microbes activate the receptors on the endometrons of the cytoplasm, which leads to the formation of inflammoma, interleukin products (IL) -1R and IL-18. The pathogen falling in autofagolysis sharply changes the conditions of its existence due to the validity of the pH, hydrolyzes, superoxide anions. It is possible to persistency pathogen (long-term for M. tuberculosis, short for other bacteria) in autofagosomes or the destruction of the pathogen in autofagolysis-somas. TOLL-LIKE RECEPTORS (TLRS) recognize bacterial lipopolysaccharide (LPS), virus single-grate ribonucleic acid (ONRNA), other polymer nucleic acids in the cytoplasm of macrophages. With autophage in recognition of intracellular pathogens (STR. Pyogenes, M. Tuberculosis, BCG, Salmonella, viruses) TLRS, RLRS (RETINOID ACID INDUCIBLE GENE I-LIKE RECEPTORS), NLRS (NUCLEOTIDE OLIGOMERIZATION DOMAIN- LIKE RECEPTORS). TLR3, recognizing the RNA of viruses, is localized in cell endosomes; TLR7, TLR8, TLR9, recognizing RNA and DNA of viruses and bacteria, CPG-motifs of nucleic acids of microbial origin - in endolysis. RLRS, recognizing RNA viruses, and NLRS, recognizing PAMPS (Mubleil Dipeptide, toxins, salts crystals, other components) bacteria, viruses, cellular products of chemical exposure and UV irradiation are located in a cytoplasm. The important functions of TLRS is to ensure hard control over normal (commensal) intestinal microflora.

PAMPS, recognized by TLR1, TLR2, TLR4, TLR5, TLR6, cause education in the inflammam of cytokines Il-F and IL-18. PAMPS, recognized by TLR7, TLR9, stimulate interferon-A products (IFNA) and IFND, which contributes to the formation of TH1 immune response. IL-1R and IL-18 products protect cells from influenza virus and shigella genus bacteria, respectively. And caused by inflammom of piroptosis (cell death with signs of apoptosis and necrosis) is destroyed for Salmonelle, Legionell and other bacteria. The activation of TLR4 destroys the BCL-2 connection with BECLIN 1 protein, which leads to the formation of the FAGOSOMA from phagofora. The activation of TLRS induces the rapid transition of LC3 from the cytoplasm in the phageosoma, the activation of the cell, contributes to the ripening of the phageosoma and the merging of it with the lysosome. L. monocytogenesis in cytoplasm cells recognize NLRS and TLR2, and S. Flexneri recognize NLRS, which leads to the degradation of microbes by the mechanisms of autophage with the participation of inflammam. When capturing

alive bacteria (in contrast to the dead) microbial mRNA enters the infected cell, which creates an additional hazard signal (VITA-PAMPS), activating inflammamas type NLRP3 and TRIF-dependent IPHN products. Thus, autofhagia acts as a mechanism for the degradation of microorganisms when they get into the cytoplasm of cells and recognition by pathogenasted receptors.

Autophagy participates in the presentation of T-cell antigens. The formation of proteos associated with ER, or AU-Tofagosoma creates favorable conditions for contacting membrane-bound molecules of MHC I or II classes with peptides and the subsequent transmission of their complexes to the external membrane of antigen-representing cells for induction, respectively, CD8- or CD4-dependent T cell reactions, respectively . Autophagy proteins LC3 and Gabarap in autofagosomes increase the affinity of their own and alien peptides to MHC II molecules. The ATG5 autophagia gene blocking suppresses the formation of CD4 + T-cell (TH1) response to a simple herpes virus or HIV-1, and also prevents the recognition of B cells infected with the Epstein-Barr virus.

Autophagia in thymic epithelium is the basis of the negative selection of autoreactive T-cells. ATG5 autofagine gene unit leads to an autoimmune CD4 + T-cell proliferative disease of mice and accumulation of apoptotic CD4 + and CD8 + T cells. Autophage deficiency in peripheral T cells causes an accelerated cell death of naive, but non-T-cell memory, which is associated with the products of superoxide anions when activating naive T-cells. An important function of Autophagia is the isolation of damaged mitochondria generating superoxide anions, as a source of stress and damage (up to death) of the cell itself.

An autoimmune response in diabetes mellitus and autoimmune hepatitis causes autoantigren Gad65 (glutamate decarboxylase 65) and SMA (mutant to-light immunoglobulin), which are subjected to a cytoplasm of shaper-non-represented autophagia with the participation of the HSC70 and the LAMP-2A membrane protein associated with the LIMP-2A lesosomes, respectively. After degradation in the lysosomes, they, together with MHC II molecules of the class, are presented with autoreactive CD4 + T cells. The formation of citrolled peptides under the action of peptidilarinyin deaminases and the formation of their complexes with MHC II molecules is the basis of an autoimmune CD4 + T-cell response during rheumatoid arthritis - RA. In T-cells of MrL mice with lymphoproliferative syndrome, an analogue of a systemic red lupus (SC) of a person, a significant number of autofagosomes in T cells are detected, which is explained by their long survival.

The products of superoxide anions by mitochondria of macrophages contribute to the digestion of bacteria in the process of autophagia. Bacteria recognized by NLRS, stimulate autophage in fibroblasts. In dendritic cells (DC), this leads to the representation of the peptides of bacteria together with MHC II molecules of CD4 + T cells. An important protective function of autophagia is the ability to reduce the level of own DAMPS in the cytoplasm and restrain the secretion of IL-F and IL-18 in response to exogenous DAMPS sources. The mechanisms of autophagia provide the degradation of the inflammam - a complex of proteins converting the pump-1 in Caspazu-1, converting the pro-ig-f and pro-Il-18 into secreted active cytokines. The blocking of the ATG16L1 gene of Autophagia leads in mice to increased IL-F and IL-18 products, inflammation, increase the mortality rate with antigenic stimulation of dextran sulfate.

Extracellular cytokines affect the processes of autophage bacteria and their digestion in phagelicosomes. Cytokines of you-dependent response of the IFNA and the necrosis factor of tumors A (FNO) stimulate autophage. Cytokines №2-dependent

answer IL-4 and IL-13, on the contrary, reduce the formation of phage-lysosomes and increase the intracellular survival M. tuberculosis. T-cell differentiation in Th1 and Th2 in vitro is characterized by a large and smaller formation of auto-FAGOS, respectively. Intracellular infectious agents (cytomegalovirus, HIV, Herpes Virus Simple I, flu virus, Jersinia, Listeria, Schigella, Salmonella, E. coli, etc.) Avoid an immune response by weakening the autophagia process.

Autophagia is the physiological process of self-renewal of the cell, which in stressful influences can lead to its death. At the same time, natural motion of cells (a person from 50 to 500 billion cells every day) is carried out mainly by apoptosis.

Apoptosis. Apoptosis ensures the removal of dying cells by phagocytosis without inflammation, destructive for macroorganism, or accompanies the focus of inflammation for its limitation and final healing. The formation of the immune system and the ripening of antigenpecific T- and B-lymphocytes is also accompanied by mass apoptosis of cells. Apoptosis maintains cell homeostasis, cell regeneration stimulation, wound healing. Apoptotic cells (AC) are utilized by adjacent epithelium cells, endothelium, fibroblasts, macrophages, DC. In case of diseases and transfusion of the stored donor blood in peripheral blood, the lymph nodes, the bone marrow is detected by apoptotic calves with a diameter of 0.2 μm generated from AK. Selected AK Lipid Mediators (Lizophosph-Tidilcholine, Sfingosin-1-Phosphate), Ribosomal DRP S19, EMAP II Endothelial Cells, TyrRS Synthetia, Thrombopondin 1, Soluble Receptor to IL-6, Fractkin (CX3-CR1L), Nucleotides ATP and UTF attract Phagocytes. At the same time, the lactoferrin, isolated by cells of mucous membranes and neutrophils during apoptosis, selectively suppresses chemotaxis neutrophils, but not macrophages. The surface expression of phosphatidylserine (FS), other oxidized lipids and Calreticulin is a sign of early AK recognized by macrophage receptors (Stabilin-2, CR3, receptors-garbagers (SCAVENGER RECEPTORS), CD91, CD31, TIM4, CD36, STEROID RECEPTOR ACTIVATOR 1; TAM Receptors (TY-RO2, AX1, MER); LRP-1). Molecular markers of AK received the general name of ApopTotic Cell-Associated Molecular Patterns (Achamps). Macrophages recognize apoptotic cells by several apoptotic receptors at the same time to quickly remove cells in the early phases of apoptosis. Expression of the surface CD31 (and / or CD47) on AK prevents them from capturing macrophages. It is important that macrophage receptors that recognize AK and apoptotic tales differ from the receptors that recognize PAMPS and DAMPS. Moreover, the activation of receptors, distinguishing ak and apoptotic tales, contributes to the suppression of recognition by macrophages of PAM-PS infectious agents through TLRS.

AK recognition and apoptotic taurus facilitates the participation of serum opsonins GAS6, MFG-E8, P2GP1, annexin I, C-reactive protein (CRB), PTX-3 pentraxin, collectors, DQ component of complement, SP-A surfactants and SP-D (in pulmonary tissue), etc. At the same time, the MFG-E8 OPG-E8, participating in the capture of AK macrophages, at the same time suppresses phagocytosis of necrotic cells (NK) and their immunogenicity for DC. C1Q interacts with the FS of early AK, and the collection of manno-binding lectin (MBL) - with late AK. Calreticulin (in a complex with CD91), SRB pentrak-sines, SAP (whey amyloid r) component; FI-COLINS interact with late AK. Assessing the role of the complement system and natural antibodies in the clearance of AK. A number of authors determined that lysophosphatidylcho-lin, appearing (and partially secreted) on the surface of the AK, is the target of natural antibodies - IgM, as well as manno-binding proteins, other collectors. Their interaction in turn leads to binding

Immunology number 2, 2014

with C1Q, C3B / BI. As a result, AK is phagocycled without activation of emissions by macrophages of pro-inflammatory cytokines. Autoimmune reactions involving anti-kardolypin antibodies of class G, on the contrary, proceed with the participation of the complement and autoantibodies to the phospholipids of the Late AK membrane. It is important that apoptotic calves in the early stages of apoptosis are covered with elements of the FS-containing outer membrane of cells, and in the later stages - elements of endoplasmic membranes. And if the antigenic presentation of early apoptotic tauries causes the formation of immunoregulatory T cells (Treg), then the contact of the late apopto-tauries with DC causes the formation of you7 cells. Apoptotic neutrophils (and outer membranes of lysed neutrophils) cause products of a transforming growth factor in (TFRR) by macrophages, and the internal content of lysed neutrophils is the formation of IL-8, FNO, MIP-2 chemokin. In the focus of inflammation themselves, neutrophils themselves show "cannibalism", phagocying apoptotic neutrophils (for example, induced by UV irradiation). This is facilitated by additional activation of TLRS effector neutrophils and TNO cytokines and a granulocytaric-macrophageal colonistimulating factor (GM-KSF), but not IL-1-R, IL-6, IL-8, IL-12, IL-17. In the focus of inflammation, macrophages are the main phagocytes of AK. This does not lead to products of pro-inflammatory cytokines (IL-1R, FNO, IL-6, IL-12), but causes the formation of immunosuppressive IL-10, TPFR, prostaglandin E2 (PHA2). Immune tolerance for AK antigens and simultaneously to other antigens, including PAMPS microorganisms, which is mediated by the E8A + DC. DC, stimulated by AK, represent antigen (s) only CD8 + T cells, and DC, stimulated NK, represent the antigen (s) CD4 + and CD8 + T cells. Immunosuppression, developing as a result of the mass formation of AK and their seizure of macrophages, underlies therapeutic action of extracorporeal photferresis in patients with chronic inflammatory diseases.

The long-term process of apoptosis in the focus of inflammation can lead to the formation of fibrosis, which is associated with the ability of macrophages, phagocyant, secreted the TPFR and other growth factors. At the same time, the suppression of inflammation, the strengthening of reparative processes in phagocytosis of AK leads to the presence of a genetic predisposition to autoimmune diseases (SLE, chronic obstructive lung disease). Normally, B1-like cells with a phenotype CD43 + CD27-IgM + or CD24 ++ CD38 ++ CD27- IgM + are the main source of natural antibodies to the surface molecules of AK. A significant amount of AK in the germinative centers of lymph nodes in patients with SLE provides long-term survival and the bone immulation of the inactive B-cells activated by single-ended DNA, nucleosomes, other cellular antigens. This is due to the OQ-dependent genetic defect of the rapid clearance of early AK and the accumulation of late AK with signs of secondary necrosis. The resulting low-chain antibodies of the IGM class interacts with cells located in the early stages of apoptosis, and high-nephin antibodies of the IgG class - with cells located in the later stages of apoptosis. Plaszatoid DCs and activation of DNA-binding TLR9 B cells ensures T-independent formation of an autoanthetol. Induced to AC production of immunosuppressor IL-10 is significantly reduced by stimulating B-cells by immune complexes, including chromatin, or apoptotic tales formed in the late phases of apoptosis.

AK elimination is carried out mainly in the early stages of apoptosis, when expression on the external membrane of the FS and Calreticulin signals the "changed". The early stages of apoptosis are reversible, their extension provides phagocytosis of most AK and the formation of the tolerance of the immune system. Cell transition to late steps

apoptosis is characterized by a decrease in the level of glycosylation of surface molecules, nuclear DNA fragmentation and signs of secondary necrosis that causes inflammation and immune response.

The main routes of the start of apoptosis of cells are receptor (Extrinsic), due to external influence, or stressinduced (Intrinsic) associated with internal influence. The receptor path of the start of apoptosis of the cell is mediated by death receptors (Death Receptors), including FAS, TNFR (TWF receptor), Trail, APO2 / APO3. Caspase activation is key to apoptosis and the sequence of their inclusion is sufficiently described in the literature. Stressinduced (mitochondrial) path of apoptosis is associated with the release of cytochrome with mitochondria and is regulated by proteins of the BCL2 family. Caspacy-dependent activation and increase in the level of superoxide anions (mainly due to damage to mitochondria) determine the immunosuppressor action of AK. The combogenous action of AK is considered mediated by HEG cells causing the trail-induced death of CD4 + T cells-helpers [52]. Both apoptosis paths lead to surface expression of FS, the fragmentation of the kernel DNA, the formation of apoptotic taurus and their rapid phagocytosis. This prevents the immune response to the dying cell, the production of inflammation cytokines, the presentation of the Cell Antigens DC.

When the cell infection shows the signs of early apoptosis (expression on FS cell membranes, the beginning of the DNA fragmentation) and the NF-CB-dependent path of cell activation. At the same time, the cells are constrained by the replication of pathogens without the formation of DAMPs, characteristic of necrotic cells. Defects of apoptosis links (mostly mitochondrial-dependent activation path), or late launch of apoptosis lead to the dissemination of infection (caused by Legionella Pneumonia, Pseudomonas Aeroginosa, Helicobacter Pylori), sepsis. Many viruses contain Caspase inhibitors, and Chlamydiae and Coxiella Burnetii block the yield of cytochrome C from mitochondria and apoptosis of the cell, which ensures the pathogen's life cycle in the early stages of infection. The capture of AK containing bacteria causes ripening of DC, inflammation, full (TH17) immune response, when capturing uninfected AK, there are no signs of ripening of DC and inflammation, immunosuppression is formed. The strategy of limited replication of the pathogen in AK is beneficial to the absence of a strong immune response to cells of cells and mass release of bacteria into the extracellular space.

Necrosis. Cells that die from injury, degenerative processes, the impact of the pathogen, are effectively utilized by necrosis. Necrosis demarcates a non-visual fabric to be destroyed and subsequent recovery. Cell necrosis is always accompanied by inflammation and leads to a pronounced immune response and subsequent reparation of tissues. The NK is characterized by the destruction of the outer cell membrane and the flow of hidden intracellular molecules in the extracellular space (see table), which causes a toxic reaction of surrounding healthy cells and the immune response. Primary cell necrosis does not depend on the action of Caspases and is a direct result of external traumatic damage or programmed genetically events associated with damage to the protein of the mitochondrial matrix cycloofilo d; The impact on death receptors or TLR3 / TLR4 and receptor-dependent damage to DNA. Oxidative cell stress, active oxygen forms are inductors (controlled) necrosis. Secondary necrosis is the final result of the late apoptosis, often it underlies the autoimmune pathology (SC and others).

NC is phased by macropinocytosis after the disappearance of surface CD31 and SE47-molecules blocking phagocytosis. NK Unlike AK cause ripening DK

and (TH1) immune response. NK isolated intracellular molecules provoking inflammation and immune response, so they are named Alarmins (Alarmins) or Damps. They attract neutrophils into the center of necrosis. The NK is distinguished by heat shock proteins (HSP70, HSP90, GP96), CALG-zerins, cytokines (IL-1A, IL-6), mitochondria formalpeptides, RNA, bunk (genomic) DNA, other molecules. The allocation of the HMGB1 nuclear protein (High-Mobility Group Box 1) associated with chromatin is the main marker (primary) cell necrosis. When apoptosis and secondary necrosis, HMGB1 is held in the kernel or is in a cytoplasm or extracellularly in an inactive (oxidized) state as a result of superoxide anions. HMGB1 itself is a mitogen and chemoattractant, but formed complexes with single-grade DNA, LPS bacteria, nucleosome cause secretion by macrophages of cytokines of FNO, IL-8, IL-6, IL-8 Chemokines, MIP-1A, MIP-IP. The high level of HMGB1 in the blood is associated with massive necrosis of the cell cells and is a systemic inflammation marker. HMGB1 is a powerful arjavant of the formation of high-nephetine antibodies and ripening of DC. The circulating in the bloodstream is non-oxidized (active) HMGB1 interacts with TLR2, TLR4, TLR9 and RAGE (RECEPTOR FOR ADVANCED Glycation End-Products) phagocite, causing an inflammatory response. At the same time, HMGB1 (as well as HSPs) interacts with CD24 and Siglec-10 on the phagocyte surface, which limits the inflammation caused by DAMPS, but not PAMPS. The distinction of the immune response to pathogenasted PAMPs and the damage associated with damage to the DAMPS cells occurs at the level of cell receptors. A typical receptor for DAMPS is Rage on cells of immune and nervous systems, endothelial cells, cardiomyocytes. Rage recognizes proteins and lipids modified as a result of non-enzymatic glycosylation and appearing in chronic inflammatory diseases as a result of oxidative stress. RAGE recognizes NC products such as HMGB1 and Calgranulins (proteins of the family S 100).

NK isolated nucleic acids. At the same time, RNA becomes a bunk, interacts with TLR3 per DC, and a bunk DNA with TLR9 phagocytes, which leads to IFNU products, CXCl10 (IP-10), IL-1R, expression of knostimulatory molecules (CD40, CD54, CD69, MHC Class II) on the surface of macrophages and DC. In order not to cause inflammation, the DNA molecules are subjected to enzymatic cleavage, such as Caspases during apoptosis. The DNAs defect cutting the bunk DNA causes autoimmune diseases in mice (SLE, polyarthritis). The nucleotides of ATP and UTF, normal in the cytoplasm, in the necrosis of cells are released into extracellular space. Acting for Parinergic DC receptors, they cause hemotaxis of immature DC, the formation of Nalp3 inflammistry and the secretion of the IL-1R, TH2 immune response. ATP on allergenactivated myeloid DC provokes the development of pulmonary allergies and maintaining bronchial asthma. Nuclear ribonucleoproteins (their short fragments) are allocated during the destruction of the NK and act as a damps, stimulating the formation of cytokines and A-Chemokins. Salts Urates formed from uric acid when destroying in the cytoplasm of endogenous nuclear or microbial DNA and sodium ions of the extracellular space, stimulate the formation of inflammom in macrophages and DC, synthesis of cytokines IL-1R, IL-18, IL-33, neutrophilic infiltration, ripening DC, Strengthening antigensical T-cell response.

Stress-funded cytoplasmic proteins-shaperons HSP70, HSP90 with necrosis (but not apoptosis) cells come to the intercellular space. Extracellular HSP70, HSP90 stimulate the formation of inflammation cytokines (FNO, IL-1R, IL-6, IL-12). Antigenspecific immune response to the peptide-HSP complex increases significantly. HSPS cell receptors are CD91,

CD40, TLR2 / TLR4 / CD14, Recipers-garbagers, LOX-1. The NK is distinguished by Kalgranulins (S100 proteins), which are recognized by Rage receptors of endothelium cells, microglia, monocytes and become inflammation markers (with pneumonia, polyarthritis, etc.). The selection of cytokines (IL-1, IL-6, IL-33) may also be the result of stressful effects on cells and their necrotic death. The protease released from NC and biologically active molecules affect the surrounding tissues and cleave low molecular weight fragments from them (hyaluronic acid, fibrillary protein, collagen, heparasulfate), which also cause inflammation.

As with the utilization of AK, serum factors (Number of MBL) are associated with the NC, reinforcing their recognition and binding to Calreticulin on the surface of the macrophages. Macrophages recognize necrotic cells by TLRS, Clec9a receptor lectin, Rage receptors; CD14, CD91, CD40, MINCLE (interacting with SAP-130) and others. It is important that phagocyte receptors that recognize NK do not recognize AK and (partially) recognize pathogens (pampps) molecules (mycobacteria, fungi, etc.).

Adjustable necrosis (necroptoptosis) of cells is associated with the activity of Kinase Ripk1 and Ripk3, manifests itself a rapid increase in the permeability of cell membranes and the release of intracellular damps into the extracellular space. The necroptosis of skin cells, mucous membranes, leukocytes with ischemic reperfusion causes a strong inflammatory response. At the same time, it acts as a protective mechanism for viral infection (in the presence of caspase viral inhibitors 8), and also involved in maintaining T-lymphocyte homoseostasis. Necroptosis of an infected cell means a sharp change in the habitat of intracellular pathogens, which is detrimental to them. Piroptatosis of cells, having the features of apoptosis and necrosis, is characterized by the formation of inflammom as a complex of activated Caspases and cytokine producers of IL-1P and IL-18. Piroptosis effectively protects cells from S. Aureus, S. TY-PHIMURIUM, P. Aeruginosa, L. Pneumophila, F.Tularensis, B. An-Thracis. At the same time, different types of specialized inflammas are formed in response to live bacteria, their toxins, LPS, disputes, flagellin, DNA, virus RNA and bacteria. Cell necrosis characterizes advanced (not early) stages of the infectious process when pathogens (Shigella, Salmonella, Yersinia, M.TUBERCULOSIS) are moving from the tactics of survival in apoptotic cells to the tactics of the destruction of the cell and the intercellular distribution.

Secondary necrosis as the outcome of the apoptosis of cells is characterized by the release of DAMPS nucleosomes (genomic DNA fragments of 180 base pairs), HMGB1. Immunostim-

Induction of "danger signals" of various types of cell death. Solid lines - the main action, the dotted line is an additional action (with weak exposure), -i means suppressing cell death. The remaining designations in the text.

Immunology number 2, 2014

the reductive effect of such DAMPS is associated with the formation of nucleosomes with HMGB1 characteristic of patients with SD. Secondary necrosis is accompanied by a mass release of the modicyphic (as a result of enzymatic treatment, oxidation) of autoantigen, which in the complex with HSPS (and other DAMPs) cause an antigen-specific immune response. But only the presence of genetic susceptibility leads to the formation of autoimmune pathology.

Interaction between cell death paths.

Autophagia and apoptosis of cells are considered as mechanisms for maintaining the viability of a multicellular organism, and inflammistry formation and necrosis inflammation are considered to be mechanisms of limited dieting tissue to preserve macrorganism. DAMPS recognition at autophagia creates additional insurance of macro-organism cells in protection against pathogens with unknown PAMPS. As a result of the infection of macrophages L. Pneumophila, inflammom activation causes pirptosis and AU tofagia, which protects the cell from pyropotosis and pathogen. But the lack of autophage to counteract the pathogen leads an infected cell to pirptosis. The launch of the Pirk1-3-dependent necropotosis mechanism involves the initial level of autophage damaged mitochondria and during its ineffectiveness to the subsequent cell degradation. Autophagia acts as a mechanism for the disposal of phagocyted apoptotic taurus macrophages and DC. Increased, with necrosis of the HMGBT level cells, cytoplasm stimulates along with HSP27 autophage (mitophagia) mitochondria and suppresses apoptosis. Other DAMPS (ATP, S100 / Calgranulina proteins, bunk DNA), interacting with TLRS, also stimulate autophage in apoptosis foci. It is known that the main BECLIN 1-dependent path of autophage (macroautophagia) can be suppressed by anti-apoptotic proteins of the BCL-2 family and the formation of NLRP3 inflammam, that is, an increase in cell resistance to apoptotic death increases its resistance to excess autophage, leading to death cells. With phagocytosis of cells, died by autophage or apoptosis, there is no inflammation. The blocking of autophage in the cell leads to accumulation in the cytoplasm of damaged mitochondria, superoxide anions, activation of Nalp3 inflammamas, inflammation. DAMPS interaction with RAGE receptors stimulates autophage and suppresses cell apoptosis. In case of insufficient release of DAMPS from the NC in the area of \u200b\u200bdamage to apoptotic cells cause the condition of tolerance and reduced inflammation. ^ DC rose cause DAMPS from NK, but not acamp from AK. Macrofagi, phagocysting AK, highlight the trophure, which causes the formation of TEG cells. With phagocytosis of AK infected with E. coli, macrophages are isolated by the TPFR and IL-6, which leads to the formation of you7 cells, and with phagocytosis of the NK -TH1 immune response. With the joint impact of PAMPS and DAMPS, the latter perform the role of adjuvant. It is known that, depending on the dose of exposure (for example, FNO), the cell dies by apoptosis (at low concentrations) or necrosis (at high concentrations). The relationship between apoptosis and cells of cells is also determined by the presence of intermediate subtypes of cell death - non-corropotsis and others.

Different types of cell death as a result of cell response to external (including microorganisms) and internal exposure can proceed simultaneously and adjust each other (see the scheme). To the end, the mechanisms defining the choice of cell death path, but the stronger the impact, the stronger the answer in the form of cell necrosis, a powerful inflammatory and immune reaction of the macroorganism. Weak impacts (due to autologous ApopTotic Cell-Associated Molecular Patterns (acamps) or DAMPS, PAMPS normal microflora) cause intensification of autophage and apoptosis of cells without obvious inflammatory and immune reactions.

Conclusion. Death of macroorganism cells (man

animals) caused by external or internal causes causes an immune response to damage. At the same time, microbial effects are always dosed by the concentration and viability of the pathogen, its soluble products, the localization of the focus of damage. The combined effect of PAMPS and DAMPS, which is most common in real conditions, as well as the effect of tolrogen apoptic cells on their interaction require further study and evaluation of immunological consequences.

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In each cell of our body over time, "garbage" accumulates. Autophagia - This is a process when lysosomes (internal organides of cells) of our body digest intracellular garbage - including recycling damaged cellular structures, which causes rejuvenation. To extend the life lies in autophagia .

In the course of the life of the human body, two opposite process occur: the synthesis of new proteins and new cells, and the "repair-cleansing" of the old "(also occurs due to autophagia ).
When the main efforts of the body are directed to the synthesis of new proteins, then autophagia somewhat brands. The breakdown and garbage accumulate, and accelerates.
When, on the contrary, dominates autophagia The aging slows down, but also the synthesis of new proteins is also suppressed.

Factors accelerating the synthesis of new proteins, but the oppressive repair of old - provocateurs of aging organism:

A large amount in the food products BCA amino acids and methionine. These amino acids take an active part in building new structures in the body. And with an excessive muscle mass (like bodybuilders), but inhibits autophagia and the processes of aging the body are accelerated. BCA amino acids and methionine many in the eggs, in red meat, in.
A large number of "fast" carbohydrates in the diet. Fast carbohydrates are contained in all.
Reception of sports additives: BCS amino acids, methionine, protein.

Factors overwhelming the synthesis of new proteins and activating processes autophagia (repair of old structures) - body rejuites:

(Use only water, coffee and tea without sugar and without milk). When the body does not receive from outside new building materials (BCS amino acids, methionine), he tries to get it by digesting the intracellular garbage and the synthesis of it necessary for the lives of fats, proteins and carbohydrates. And the digestion of old cellular structures ( autophagia ) - this is proper cleansing of the body .
Reception of some medicines. For example: Rapamycin ,. Metformin inhibits Tor kinase activity, stimulating processes autophagia .
Eating once every two weeks for 2-3 days only raw vegetables and. In raw vegetables, there is extremely few BCA amino acids, methionine and fast carbohydrates. The body during such nutrition does not supplies all the necessary building materials for growth and begins to receive it by digesting the intracellular garbage and the synthesis of it necessary for the life of fats, proteins and carbohydrates. That is why the digestion of old cellular structures ( autophagia ) - this is proper cleansing of the body .
- Reducing calorie content by 30% throughout life. When the diet is reduced, the advent of the same BCA amino acids, methionine and fast carbohydrates is reduced and the admission of methionine and fast carbohydrates is reduced, which leads to the active eating of intracellular garbage and rejuvenation of the body.

In this way, autophagia It is a real means inhibiting aging processes. (Scientific research influence autophagia on aging processes: http://www.scienceagainstaging.com/books/obzor_razvorot-final.pdf - Pages 71 - 119). But such a means as fasting 24-36 hours weekly is not available for everyone. Optimal and calorie nutrition is unrealistic throughout life - can only be limited. Reception of medicines is good, but more effect can be achieved comprehensively. Therefore, the most convenient and affordable way is the power of exclusively raw vegetables and water 2-3 days in a row every two weeks. So to speak unloading days.

Autophagia — proper cleansing of the body

Conclusion: diet (only raw vegetables and water) every two weeks for 2-3 days inhibits the aging processes and prolongs the life of a person.

Almost every week there are all new discoveries, and effective means of dealing with old age appear. Science is seminal steps. We recommend that you subscribe to new blog articles to be aware.

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The essence of the Autophagy process (Greek. - "Self-navigation") - disposal of organelles and macromolecules in cellular compartments. This is a mechanism for adapting cells to a lack of nutrients. When an easy "hunger" occurs, the cell gives part of its macromolecules to transform them into monomers, which are suitable for the synthesis of nucleic acids, new proteins, carbohydrates and lipids.

The autophage process is necessary to remove damaged elements from cells, protein aggregates, for example. As a result of autophage, damaged organelles and macromolecules, which are in the cytoplasm, fall into a special cell department where they are split into small molecules. These molecules are then becoming a building material from which new organelles and biopolymers (proteins, polysaccharides, nucleic acids and other elements necessary for the work of the body) are formed.

Autophagia is a normal phenomenon in the life of the body. But excessive autofagium can lead to cell death. Therefore, it can be considered as one of the forms of programmable death of the cell as well as apoptosis and necrosis.

There is every reason to believe that Autophagia is an internal program of processing harmful substances in the body. It increases the effectiveness of the body, eliminating it from non-functioning particles, stopping the development of cancer cells and preventing metabolic dysfunctions, for example, diabetes or obesity. Autophagia, under normal flow, removes the accumulated garbage from the cell and promotes the rejuvenation of the body.

With autophage in the cytoplasm, the process of formation of autofagosomes - bubbles, which surrounds the two-layer membrane, and which contain part of the cytoplasm and cellular organelles, such as fragments of the endoplasmic reticulum, ribosome and mitochondria. After that, the autofagosomes are combined with lysosomes, forming autolisosomes. In them, under the influence of lysosomal enzymes (hydrolylaz) degraded organelles and macromolecules.

Types of Autophagia

Three types of autophagia are isolated

Microatophagy. At the same time, the type of autophagia particles of cell membranes and macromolecules are captured by a lysosome. Due to this, with a lack of construction material and energy (for example, when a person is starving) a cell can digest proteins. However, microatophagia mechanisms are activated in normal conditions.

Macroautofia. At the same time, the type of cytoplasm (most often the one that contains organides) is surrounded by a membrane compartment. As a result, this part two membranes is separated from the rest of the cytoplasm, turning into an autofagosoma. They combine with lysosomes and form autofagolysis, where organelles and other contents of autofagos are digested. With this type of autophagia, cells can get rid of organoids that "served their term".

Shaperone autofagium. In this process, partially denaturing proteins are purposefully transported from the cytoplasm to the lysosome cavity for subsequent digestion. Initiate this type of autophagia (by the way, it is described only for mammals) with stress, for example, serious physical exertion or starvation.

Results of research on the effect of autophagia on the human body

Low-calorie diet according to some data increases the lifespan by about 30-40%. Nutrition restrictions activate the production of special genes that are responsible for longevity and contributing to the continuation of life even in conditions relatively poor nutrition.

There is also evidence that autofagium is of serious importance for monitoring the immune system and inflammatory processes. Experiments on mice have shown that individuals with a non-working ATG gene were drowsiness and obesity, brain violations and elevated cholesterol levels. Such "features" are able to lead the most serious consequences for the body.

Autophagia and cancer

Scientists from the University of Pennsylvania, which are engaged in finding an effective fund against cancer, have made another important step due to the data on autophagia. Now they can fully talk about the creation of actually working methods of combating oncological diseases not far from around the corner.

In particular, the researchers worked with the lysosomal enzyme PPT1, and with it, they managed to develop a drug that showed high results in the fight against diseases such as colorectal cancer, pancreatic tumor and melanoma. But for now, all the experiments, again, were held on mice.

The PPT1 enzyme is responsible for the two most important processes in the life and growth of cancer cells. The first process is an autofagium itself, which allows to survive oncoclecks, and the second is a rapamycin target (MTOR), which is responsible for the uncontrolled growth of tumors. By the way, the drugs that are used in recent years are also aimed at Rapaamycin's target, but their difference is that they do not take into account the difference between the autophage process, which is why there is no possibility to affect the stability of the oncocletes to treatment.

Now, thanks to the discoveries, which we see that it is possible to "force" the cells to eat ourselves, get rid of damaged particles and receive new resources for recovery, the situation is radically changed. Scientists have found that MTOR can also use autophage to provide resources, and when exposed to PPT1 enzyme, the activity of the first is suppressed, and the autophage process is blocked. This is the reason why the cancer tumor begins to perceive the anti-cancer therapy.

Negative influence of autophagia on the body of the bicycle

However, all these advantages of Autophagia are only one side of the medal. It is very important to understand and always remember that it can affect the state of the body and negatively. True, it concerns this only a certain category of people.

Contraindication to start and stimulating autophage:

Immunodeficiency
Gastritis
Body weight below normal
Ischemic heart disease
Mental violations
Diabetes
Depressed
Hypotension
Pregnancy
Lactation
Accessories incompatible with starvation

If you neglect by these contraindications, you can seriously worsen the condition of your body, aggravate already existing ailments and seriously undermine health. Otherwise, according to scientists, Autophagia is a completely safe method of purification and rejuvenation. You can run it yourself.

How to run autophage to rejuvenate

The abuse of high-calorie unhealthy food leads to the fact that autofagia does not start. This leads to acceleration of aging, cellular mutations, decrease in immunity.

If you enter the cells in the starvation mode, they will be forced to use other resources for functioning and recover, getting rid of harmful substances. In this process, extremes should be avoided, since constant malnutrition can lead to degenerative processes.

Fasting to launch Autophagia

In total, you can select a few starvation, we will consider in detail two of them - intermittent and prolonged. They were described by the famous Italian-American bioherontologist and cell biologist Walter Longo, who many years investigated the impact of starvation and a limited diet on life expectancy and health. Here talking about starvation we mean the rejection of food, but not from the water.

Intermittent starvation

The essence of intermittent starvation: day without food, followed by 1-2 days of normal nutrition.

Scientific research suggests that, thanks to intermittent fasting, nervous bonds are activated and cognitive functions are improved, the heart rate and blood pressure are reduced, the appearance of tumors is delayed, the sensitivity of tissues to insulin increases, the blood regeneration is improved, inflammatory diseases are improved, the number of white cells in the blood is prevented. And the immune system is stimulated.

Experiments conducted on mice mice confirmed the benefit of intermittent starvation as prevention of neurodegenerative, cardiovascular and tumor diseases, as well as diabetes. Subsequent observation has already shown that intermittent starvation normalizes blood pressure and glucose levels, reduces the number of inflammation markers in suffering from bronchial asthma.

Of course, it is not necessary to give up a popular nutritional rate of nutritionally and gradually today, but still it is necessary to keep in mind that because of such a mode, insulin is enhanced, the cells are losing sensitivity to it, which in turn can lead to sugar second type diabetes. So even this rate (to eat often and gradually) is useful from time to time to dilute with periodic starvation.

Prolonged starvation

The essence of prolonged starvation: 2-3 (sometimes more) days without food, followed by at least 7 days of the break until the next 2-3 days of starvation.
The results of scientific studies suggest that prolonged starvation leads to activation of autophage, increasing the sensitivity of tumors to therapy, improving the regulation of insulin levels (and insulin-like growth factor 1) and glucose.

Also fasting on such a scheme reduces the mass of the liver and the number of leukocytes in the blood. But the resumption of nutrition produces powerful regeneration processes, both in the immune system and in the liver. For this reason, prolonged starvation is allowed only under the control of the specialist. Of particular care in this case, it is necessary to observe people over 65 years, because At this age, the lack of proteins may cause unwanted loss of muscle mass.

Even with full failure to feed on a day and more need to drink enough water.
A very convenient and safe way of stimulating Autophagia is to refuse 1-2 meals (for example, dinner and / or lunch) 2-3 times a week.
When simulating periodic starvation within 5 days (another advice from Walter Longo), it is necessary to use no more than 100 calories on the first day and 500 calories - the remaining four days

And, of course, speaking of a diet, we could not miss the question about the correctness and malfunction of food at all. We all have already heard more than a hundred times that it is impossible to eat after 18 hours. And from the position of new data obtained about Autophagy Esinori Osumi, this statement is again confirmed, but the question of the benefits of frequent fractional nutrition remains open.

Experiments have shown that with the same calorie calories per day, the mouse, which was fed at the interval at 12 o'clock, "showed" the best results than those that fed often and gradually. Thus, at the first group mice, there was an improvement in circadian rhythms and they had better slept, but most importantly - they stopped developing and even accepted metabolic diseases.

This once again says that if suddenly during the day you do not have time to eat, having the opportunity to eat only in the morning and / or in the evening, you need to not be upset, but to rejoice, because you launch Autofagia for the benefit of your body. Similarly, nutrition with breaks in 12 and more hours activates autofagia. No matter how strange it sounds, but such a power supply contributes to a decrease in fat weight without loss of muscular, reduced glucose and cholesterol in blood.

And the starvation over 13 hours from the evening to the morning minimizes the risk of breast cancer.

But here we want to notice: in no case should you perceive autofagia as a medicine. For the most part, this is the prevention of different ailments, but not their treatment. Keep this in mind and do not make false conclusions.

If you do not want to starve at all, there is a way to initiate the processes of autophage and without limiting yourself in food. To do this, it is necessary to include some specific products in its diet, which contain the activating the necessary processes of the substance. Such products are (substances are indicated in brackets):

Pomegranate juice, strawberries and raspberries, as well as red wine, weathered in oak barrels (Urolitin a)
Grapefruit, Cheese and Mushrooms (spermadine)
Bitter cucumbers (Cukurbitatsin)
Soy (Dyscin)
Red grapes (resveratrol)
Curry (Kurkumin)
Cocoa and green tea (Catechin and Epicatechin)
Ginseng root (magnoflin)
Brown rice (Gamma Tokotrienol)
Walnuts and peanuts, champignons, barley, bean, oats, bread and white meat (vitamin B3)
Also take on the notch of oatmeal, fish oil, quince, olive oil, sour cream, spinach, cabbage, lingonberry, kefir and eggs - substances contained in these products, stimulate cellular renewal.

Autophagia and sport

The autophage process is launched not only fasting and proper nutrition, and also physical exertion and sports. But that this happens, you need to adhere to some principles.

It is known that the effect of physical exercises occurs only when the body is experiencing stress. Autophagy arises for the same reason, and therefore sport is another way to start and strengthening it.

Physical exertion lead to microen fabrics of tissues and muscles, which, recovering, becoming stronger, making a stronger and human body. And the exercises allow you to clean the body from toxins due to the sweating, which is required by any detox program. Moreover, many specialists are confident that it is physical exertion that serve as the main factor for effective detoxification.

As for the number of physical exercises in order to stimulate autophage, it is not yet known. But it has been established that intensive exercises have the greatest effect, which means that there is a light load for a while forget.
Despite the fact that moderate loads in the amount of 150-450 minutes per week contribute to longevity (they reduce the risk of premature death by more than 30%) if you devote at least 30% of the training time at exercises of increased intensity, you can run autofagia and Increase the duration of your life even about 13%.

So train, do not regret yourself (in a healthy sense, naturally), and the powerful improvement in the body's condition will not wait a long time (do not forget to count their strength and take into account their current physical condition).
And, finally, we recall again that Autophagia is by no means a medicine, and it is impossible to consider it a panacea from all the troubles.

You need to know about it and use it to clean your body and extend your life, but you need to do it with the mind, being attentive to your current state and not neglecting the principles of healthy nutrition and a healthy lifestyle.

Toxins and slags accumulating in the human body, lead to its intoxication - with general poisoning with very unpleasant symptoms. The primary signs of intoxication are symptoms that most of us simply do not pay attention until they lead to serious diseases. The modern pharmaceutical market offers many drugs and bids for the output of slags and toxins from the body that do not guarantee complete cleansing. However, such a technique, the method still exist - autofagia, or, in simple language, the self-adhesiveness of the organism, its self-nomination of toxic substances that damage the internal organs, blood and nervous systems.

The essence of the concept of "autofagi"

The concept of Autophagy was first mentioned in the middle of the last century. It was then by scientific specialists in the field of cytology (biologists who study the structure of the cell and the principles of its development, operation) was seen the ability of cells to eat themselves, get rid of malicious or damaged elements in its structure. But the very concept of autofagia and the principle of cleansing the body on this technique were described by the Japanese professor of Josinori Osumi. He was engaged in the study of the self-abnormalism of cells of living organisms since the end of the 80s of the last century, and by 2016 provided an extensive scientific work for which the Nobel Prize was awarded.

The essence of Autophagia is that in the stressful situation, the cells of the body independently adapt to heavily and begin to solve the problem - get rid of the source of stress, remove harmful substances and restore the damaged areas of its structure. Josinori Osumi described three types of autophagia in his scientific work:

microatophagia
macroautophagia
shaperone autophagia.

Microatophagia is digestion of excess protein cells and converting them into high-quality energy or building material for the body. In the process of macroautophagia, the cell is getting rid of its deadlines, useless for the body of elements the simplest way - by eating them. With chaperone autophage, harmful and unnecessary substances are first transported to those cell zones, where they will be most useful after processing.

The principle of launching an autophagy process

If we speak scientific language, then autofagium is the process of purification, significantly extending life, typical, as a rule, only for mammals. To start the process, the body needs stress. In animals, the process is controlled at the level of instinct, and here the person is forced to make efforts to run or stop the autophage process at the right moment.

There are four ways to start the autophage process for a person:

the starvation is not enough once a week, during the day, and then the body that has not received the construction material from the outside will begin to produce it from its own resources, passing the slags and toxins copied in the structure of cells
reception of drugs that depress the activity of TOR kinase (multimolecular intracellular complexes governing the growth and development of cells), and stimulating cells of cells, for example - metformin or rapamycin,
two or three days of raw food of vegetables, on the background of taking only water, without juice, teas, coffee and other drinks,
long-term low-calorie food, with daily deduction more than 30% of calorie organism necessary for the normal functioning.

Stimulate the Autophagy process Some foods, for example, fermented milk products, raw vegetables, fruits, cabbage and spinach, vegetable fats, fish and cereals (oatmeal and dark rice). Proper nutrition must be accompanied by physical exertion, but only in the norm that does not harm the body.

Nutrition for autophagia

It has been scientifically proven that it is starvation that is the best stimulator to start the purification process on the principle of autophagia. But it is very important in this regard not to overdo and not to cause their body harm instead of the expected benefits, purification from toxins and slags. The permanent malpression will lead to the fact that the body will constantly eat themselves, eliminating no longer only from unnecessary particles, but also from building material for cells, which will lead to their death and serious health problems. Medical professionals recommend the following nutrition principle to launch autophage and its proper functioning:

intermittent starvation,
prolonged starvation,
raw foods.

Intermittent starvation is carried out according to the principle of 1 to 2 - one day passes at all without food, and the next two in the usual mode, but with a reduced amount of protein. And already at the stage of launching an autophage process, most noted the improvement of the body's condition - blood pressure and cardiac activity normalizes, the tone and mood increases.

The prolonged starvation is also cyclical, but with more prolonged periods of abstinence from meals and ordinary food - from two days or more. During the refusal of food, a sharp decrease in the mass of the liver occurs, the content of blood leukocytes is reduced. And when the period of normal, habitual nutrition occurs, a stressful situation occurs, which runs in the body the processes of self-navigation.

Exercise for the launch of autophagia

Before using the physical exertion to run in the body of the sampling process, it is necessary to understand what effects have an exercise on the muscles. During classes in the structure of the muscles, microtraums appear - cracks and fibers. It is very important to choose the right complex and regulate the process, since the purpose of classes is not in the increase in muscle mass, but in the purification of its structure.

Medical professionals and biologists have formed a set of exercises to activate and support autophage based on running. It is not recommended to start with long run, and their course looks like this:

daily aerobic loads in the form of walks of 10-15 thousand steps,
changing the route and terrain, where walks - descent and lifting, new directions - forest, reservoir coast,
topic activation - inclusion in walking jogging for 30 minutes, twice a week,
the next stage is running 60-120 minutes, with acceleration,
participation in short marathon rasions, but not earlier than 3 months after the start of classes.

During a regular run on the background of changing power modes, not only the launch of the autophagy process, but also an excessive fluid is excreted from the body, and together with slags and toxins accumulated in it. That is, the process of cleansing occurs even more intense, and the results are stored for a longer period.

Opinion of medical professionals about autophagia

Is the body to Autophagia, will bring it to him benefit or hurts - these questions need to be solved only with a medical specialist, who observes you for a long time, after analyzing the biomaterials of a particular patient. Doctors recommend to pre-make at least a biochemical blood test from Vienna, to eliminate the presence of contraindications to carry out autophagia. This is not recommended such a technique for cleansing those who have

there are problems with the gastrointestinal tract - ulcers, gastritis,
reduced the ability to fertility - reproduction of healthy offspring,
body weight is significantly lower than recommended norm,
there is a tendency to cardiovascular problems,
there is a diabetes in any form,
mental and psychological problems progress or periodically appear.

In addition, the absolute contraindications to Autophagia are the reception of some types of drugs, pregnancy, or breastfeeding, immune disorders and the period after the exacerbation of chronic diseases, viral infections, influenza.

But the very fact that periodic starvation is useful and helps to clean the body from harmful substances accumulated in it, does not reject the medical community. Moreover, such treatment techniques were actively used in the Soviet period, for example, Academician Yuri Nikolaev. He successfully treated various diseases in this way, and even officially patented the Methodology of RDT (unloading and dietary therapy). That is, despite the fact that Autophagy was officially recognized only in 2016, it was actively used in official medicine in the middle of the last century.

What is Autophagia simple words. Autophagia: How to really clean your body

Types of Autophagia

Results of research on the effect of autophagia on the human body

Autophagia and cancer

Negative influence of autophagia on the body of the bicycle

How to run autophage to rejuvenate

Fasting to launch Autophagia

Intermittent starvation

Prolonged starvation

Autophagia and sport

The essence of the concept of "autofagi"

The principle of launching an autophagy process

Nutrition for autophagia

Exercise for the launch of autophagia

Opinion of medical professionals about autophagia

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