List age-related changes in the human liver. Signs of liver disease in older people. Have you recently experienced nausea, heartburn, or excessive belching?

Particular attention is paid to the processes occurring in the liver, where flows of glucose, exogenous short-chain fatty acids, endogenous fatty acids synthesized in adipose tissue, free cholesterol and cholesterol, and oxycholesterol are directed. In turn, the liver secretes TG, free cholesterol and EC, bound by apoprotein B-100 into VLDL, glucose and bile. The liver forms the main stores of glucose in the form of glycogen. The flows of glucose, FA and cholesterol in the liver are closely linked into one metabolic node. Balanced flow relationships are regulated at the level of cellular and nuclear membrane receptors and transcription factors, which control the expression of the main genes that control the metabolism of these substrates.

The entry of glucose into the liver is regulated by insulin, which interacts with IR. Glucose is transported inside the cell by the Glut 2 transporter. Through Glut 2, a rapid equilibrium is achieved between extra- and intracellular glucose concentrations. In order to trigger the regulatory mechanism, it is sufficient to attach a phosphate group to glucose and convert it into glucose-6-phosphate. The conversion of glucose to glucose-6-phosphate is induced by insulin. In the liver, glucose-6-phosphate is used in glycolysis, in the pentose phosphate shunt, in glycogen synthesis, and in hexosamine synthesis. In muscle and adipose tissue, hexosamine synthesis is the pathway through which glucose influences gene expression. Through insulin, glucose also affects the regulation of lipid metabolism and cholesterol transport in the liver.

In hepatocytes, FA and TG synthesis and cholesterol transport are regulated through sterol-responsive element binding protein (SREBP-1c). This protein is a major activator of gene transcription, the function of which is controlled by insulin.

Thus, the main action of insulin is aimed not so much at capturing glucose and maintaining its level in the blood, but at the synthesis of fatty acids, triglycerides and glycogen from glucose, i.e. and on the regulation of the consumption of energy substrates, and on their deposition.

Factors of the PPAR family are also involved in the control of FA and cholesterol transport pathways at the level of gene transcription. PPAR-α is predominantly expressed in the liver. Here it controls various genes associated with the metabolism of FA, TG and cholesterol. The property of fish oil to reduce the production of TG by the liver has been proven. This is due to the effect of polyunsaturated FAs on PPRA-α. It is activated by binding to the oxidized metabolites of acids 20:5 and 22:6 (these acids are found in fish oil). The oxidation products of these acids in peroxisomes are the very products of LPO, or free radicals. Free radicals appear to be essential for regulating the distribution of endogenous FAs in the body. PPAR family receptors are expressed mainly in the liver and adipose tissue, and to a lesser extent in other organs. Their expression in other organs increases when TG accumulation is observed in them, i.e. when fatty tissue degeneration occurs.

PPAR-α acts synergistically with LXR. LXR is a nuclear receptor that controls lipid homeostasis in vertebrates. PPAR-α and LXR are the most studied nuclear receptors of hepatocytes. Endogenous activators of LXR are oxysterols (oxycholesterol) and intermediates of cholesterol biosynthesis pathways. Receptors of this family regulate the expression of many genes involved in the processes of cholesterol secretion, transport and excretion. In addition, they are involved in the general control of TG synthesis and FA homeostasis.

The main gene controlled by LXR is the gene encoding SREBP-1c. SREBP-1c, in turn, controls genes encoding cholesterol biosynthesis enzymes and lipogenesis enzymes: acetyl-CoA carboxylase, FA synthase, acetyl-CoA synthetase, glycerol-3-phosphate acyl-transferase, it activates stearoyl-CoA desaturase-1 , the same enzyme that catalyzes the conversion of stearic acid to oleic acid in macrophages and adipocytes.

Physiological properties of fatty acids. The metabolic pathways of glucose, FA and cholesterol are closely intertwined, therefore, virtually the same hormones and factors are involved in the regulation of their transport, consumption, storage and synthesis. However, these compounds themselves are active regulators of gene expression.

Currently, there is an understanding that the level and composition of blood fatty acids is of decisive importance for growth and development, for maintaining energy homeostasis and for the aging process. FAs that make up PL are components of cell membranes and are involved in regulating the activity of membrane-bound proteins and in transmitting signals into the cell and into the cell nucleus. Polyunsaturated FAs and their oxidation products, for example, serve as ligands for the nuclear receptors PPAR and LXR. Saturated FAs, interacting with β-cells of the pancreatic gland, increase insulin secretion. At the same time, saturated fatty acids, mainly palmitic acid, are active inducers of apoptosis. This effect of palmitic acid is neutralized by oleic acid.

Adipose tissue contains and secretes oleic acid in large quantities. The property of oleic acid to make lipid crystals more “liquid” is used during the accumulation of EC in macrophages and TG in adipose tissue when the viscosity of the plasma membrane changes, a factor that affects the activity of many membrane-bound proteins and receptors.

FAs easily penetrate the plasma membrane. But for their transport through the double membrane of mitochondria, a special protein, carnitine, is required. The activity of this protein is regulated by leptin, which is secreted by adipose tissue, i.e. adipose tissue controls β-oxidation of fatty acids. With leptin resistance, FAs undergo extramitochondrial oxidation, in particular in peroxisomes. This leads to the formation of lipid peroxidation (LPO) products, or free radicals. The accumulation of LPO in cells is not associated with the destruction of mitochondrial integrity, but is a consequence of intracellular TG accumulation.

Free FAs are active detergents, so they are transported in the bloodstream bound to albumin. Albumin shows the greatest affinity for oleic acid. The albumin-oleic acid complex induces the formation of TG in the liver and their secretion into the bloodstream, i.e. oleic acid is involved in the control of the level of free fatty acids in the blood. The level of free blood fatty acids is also controlled by the activity of blood lipolytic enzymes (LPL and hepatic lipase) and liver (HCL), insulin, growth hormone and leptin. Recently, lipases have been discovered in cells of various tissues.

Insulin and growth hormone form a pair of antagonist factors. In adipose tissue, insulin controls glycogen synthesis and lipogenesis, i.e. energy storage, and under the control of growth hormone is TG lipolysis and the release of deposited FAs into the blood, i.e. energy consumption. At the same time, the secretion of leptin depends on insulin, which induces the absorption of fatty acids by cells and their combustion in mitochondria. FA energy is necessary for growth and development, i.e. for cell proliferation. At the same time, with an excess of saturated FAs in the blood, apoptosis increases. Cholesterol, from which bile acids are synthesized, promotes the entry of exogenous fatty acids into the body. Cholesterol transport is organized in such a way as to combine energy flow and reproductive function. The decline of reproductive function entails a disturbance in the distribution of fatty acids.

The level of free FAs in the bloodstream is of great physiological importance: its increase leads to the accumulation of FAs in non-fat tissues, to insulin and leptin resistance, which under pathological conditions leads to the death of the body, and under physiological conditions is the main cause of aging.

Since the metabolism of FAs is closely related to the metabolism of cholesterol and glucose, it is in age-related changes in the distribution of FAs that the causes of systemic metabolic disorders underlying pathologies such as insulin resistance, hyperglycemia, type 2 diabetes, hypertension and atherosclerosis are expected to be found, i.e. diseases that are most common among elderly and senile people.

Throughout ontogenesis, there is a continuous accumulation of fat in the body; it gradually “displaces” water in the body. Fat is deposited in the body in ever increasing quantities, starting from early ontogenesis, which indicates the degree of efficiency in the use of energy entering the body - this energy is not completely consumed.

Age-related changes in adipose tissue and the main pathologies of older age. In general terms, the main stages of ontogenesis have the following characteristics. In infancy, energy sources for humans are sugars (lactose, glucose) and short-chain fatty acids (milk fat), from which endogenous fatty acids are synthesized in the body. Milk is a fat emulsion, so it does not require a large amount of bile to absorb fat in the intestines. The child begins to consume exogenous palmitic and stearic acids when the mechanism of bile synthesis is fully formed. Bile synthesis involves the formation of cholesterol distribution pathways in the body. The influx of exogenous fat provides the body with additional energy, which is necessary mainly to perform the reproductive function. Through SRB1, HDL cholesterol enters the liver for the synthesis of bile acids and into steroidogenic tissues for the synthesis of sex hormones - this creates conditions for reproduction. The bulk of cholesterol is transferred to the liver by LDL, and HDL is only an additional source. This supplement is necessary to enhance the flow of exogenous fat. The supply of cholesterol to the liver is regulated by estrogens, which indicates the need for additional energy supplies to the female body. In men, the flow of cholesterol into the liver is partly regulated by the fact that excess LDL formed is “dumped” into “scavenger” macrophages. The different intensity of cholesterol flows into the liver in men and women apparently explains the higher incidence in middle age of cholesterosis of the gallbladder in women and cholesterosis of the arterial wall caused by excessive deposits of EC in scavenger macrophages in men. The appearance of such pathologies in middle age indicates the clinical manifestation of age-related disorders of energy metabolism caused by the gradual accumulation of unused fatty acids in the body. At this age, disturbances are more pronounced in the distribution of cholesterol. In the bloodstream, the content of LDL cholesterol increases, which is modified by the oxidation system and is actively captured by “scavenger” macrophages. At this age, it is difficult to separate a genetic predisposition to atherosclerosis from age-related disorders of energy metabolism. It cannot be ruled out that age-related decline in reproductive function leads to a decrease in the intensity of cholesterol entry into steroidogenic tissues and an increase in its flow into macrophages and the liver, which exceeds the physiological norm. The body adapts to the new state by reducing the production of apoprotein A-1, the formation of HDL and the synthesis of EC. Lethal outcomes caused by atherosclerosis in middle age are a consequence of maladaptation.

Towards the end of the reproductive period, the size of the fat depot reaches its maximum value, and then the mass of adipose tissue begins to decrease. After 75 years, this process intensifies. A decrease in the amount of fat in physiological depots is accompanied by its accumulation in non-fat tissues - in the bone marrow, thymus, liver, muscles, etc., fatty degeneration of mesenchymal cells occurs. Therefore, the total amount of fat in the body either does not change or even increases.

Despite the loss of adipose tissue mass during post-reproductive age, the number of newly formed cells in this tissue does not change. Cell differentiation is completed when they lose the ability to replicate and acquire the function of storing and mobilizing fat, responding to the effects of insulin, catecholamines and other hormones, and secreting various specific factors. Preadipocytes are present in adipose tissue throughout a person’s life, i.e. it does not lose its ability to renew cells even as the body ages. The decrease in the size of the fat depot with age is not due to cell loss, but to a decrease in the size of the adipocyte and a decrease in its ability to accumulate TG. Transcription factors that regulate the expression of genes responsible for TG accumulation simultaneously control the process of transformation of preadipocytes into a mature cell, but preadipocytes of an aging organism do not have a complete set of these factors. The differentiation of preadipocytes into adipocytes in an aging body stops at a certain stage. Differentiation of preadipocytes is stimulated by glucocorticoids, insulin, other hormones, paracrine and autocrine factors. The signal transduction mechanism triggers the expression of genes responsible for the formation of the mature adipocyte phenotype. During differentiation, expression of the nuclear receptor PPAR-γ occurs. This receptor is necessary to maintain the fat cell phenotype and maintain its sensitivity to insulin. In the absence of this and other factors, glucose tolerance is impaired. Insufficient differentiation of preadipocytes is part of an adaptation mechanism that prevents further accumulation of TG in adipocytes.

The adaptation mechanism includes the development of insulin resistance in adipose tissue, which promotes the “shedding” of excess fat, since insulin no longer inhibits HSL and nothing interferes with lipolysis. FAs from adipose tissue begin to continuously enter the blood, as a result of which fat reserves in the fat depot decrease. Under normal conditions, the release of excess TG leads to restoration of IR function. The situation is different with aging: IR sensitivity is not restored and the loss of adipose tissue weight occurs steadily. FAs released from adipose tissue begin to accumulate in mesenchymal cells. An increase in TG accumulation in non-adipose tissues promotes an increase in the activity of transcription factors in these cells that determine the adipocyte phenotype. Age-related disdifferentiation of mesenchymal cells contributes to their transformation into dipocyte-like cells. But at the same time, the specific function of the cells is preserved.

The main reason for the gradual proliferation of adipose tissue during ontogenesis is a disturbance in the distribution of fatty acids caused by leptin resistance. Leptin is a product of normally functioning adipose tissue. It activates AMP-activated protein kinase, which stimulates β-oxidation of FAs in the mitochondria of all cells. With leptin resistance, the cell stops utilizing FA. An “excess” of this energy substrate is formed, and the level of free fatty acids in the blood increases. The response to an increase in the level of free fatty acids in the blood is the cessation of lipolysis in adipose tissue, and TG begin to accumulate in adipocytes in increasing quantities. The proliferation of adipose tissue leads to insulin resistance, activation of HSL, and a continuous flow of released fatty acids into the blood. The level of free fatty acids in the blood increases again, but now they accumulate in non-fat tissues. In post-reproductive age, fat loss from subcutaneous adipose tissue occurs at a faster rate, i.e. from the fat depot, which supplies skeletal muscle with energy substrate. The ratio of visceral/subcutaneous adipose tissue changes with age in favor of intraperitoneal fat, i.e. the flow of FA into the liver becomes dominant. The secretion of TG contained in VLDL by hepatocytes increases, and triglyceridemia develops.

In an aging body, a situation develops that is characteristic of an excess of energy substrate. What processes result in the formation of excess energy substrates in the body of a healthy person? The inevitable excess of energy, resulting from its underexpenditure, initially accumulates in the form of saturated FAs in natural “liquid” crystals - in the lipid bilayer of plasma cells. A property of the plasma membrane, such as viscosity, changes, which largely depends on the cholesterol content: cholesterol, which makes the lipid bilayer denser. Cholesterol exhibits a high affinity for saturated fatty acids, so an increase in their proportion in membrane lipids contributes to the saturation of the membrane with cholesterol.

Leptin resistance means that the cell stops responding to stimulation by external factors, it loses sensitivity to external stimuli, i.e. transmembrane signaling is disrupted. The influence of the physicochemical properties of the plasma membrane on cell sensitivity to insulin and leptin is still being studied. However, it has been established that the SRB1 receptor, for example, responds to the lipid composition of the plasma membrane. In steroidogenic tissues and the liver, age-related changes in membrane structure reduce the effectiveness of SRB1. The production of sex hormones decreases, which leads to a gradual loss of reproductive function, and the flow of EC into macrophages and into the liver through the LDLr receptor increases. The sexual differentiation of cholesterosis, expressed at the initial stage of this process, disappears as the synthesis of sex hormones decreases. In post-reproductive age, the incidence of cholesterosis of the gallbladder and cholesterosis of the vascular wall gradually levels out in men and women.

Myocytes are characterized by the least sensitivity to insulin. Insulin resistance increases simultaneously with leptin resistance. While maintaining the functional integrity of mitochondria, β-oxidation of FAs in myocytes decreases. A decrease in FA consumption in myocytes and other cells leads to a steady increase in the level of free FAs in the blood. The proliferation of adipose tissue occurs following the loss of reproductive ability and reaches a maximum towards the end of the reproductive period. By this time, an adaptive reaction develops - insulin resistance occurs and continuous lipolysis begins in adipose tissue. The reduction of subcutaneous adipose tissue, which is more sensitive to the action of insulin, occurs earlier than the decrease in the mass of the visceral fat depot. Insulin sensitivity in adipose tissue is not restored due to adaptive impairment of adipocyte differentiation. In increasing quantities, fat is deposited in non-fat tissues.

Thus, energy that was previously used for reproduction and physical work is accumulated in the form of saturated fatty acids in mesenchymal cells. In these cells, accumulations of dense, non-metabolizable fat are formed, since the high activity of the enzyme stearoyl desaturase, which prevents the compaction of TG accumulations, is characteristic only of those cells that are physiologically designed for the accumulation of lipids - for adipocytes and macrophages. Not only plasma membranes, but also tissues as a whole are now enriched with saturated fatty acids and cholesterol.

Mesenchymal cells do not have a system for mobilizing fat in response to stimulation by hormones, and they cannot remove fat accumulations into the extracellular space. In order to somehow get rid of excess cargo, the cell activates the system of extramitochondrial FA oxidation. But this non-physiological way of recycling excess substrate leads to the accumulation of oxidized intermediates and detergents. The threat of lipotoxicity looms over non-fat cells. The accumulation of lipid oxidation products (LPO) in non-fat tissues served as the basis for the creation of the free radical theory of aging. In fact, LPO is an inevitable consequence of the accumulation of TG in non-adipose tissues. Their concentration in tissue can serve as an indicator of the intensity of the oxidation process of an undesirable substrate, or the degree of lipotoxicity. Lipotoxicity increases apoptosis and contributes to the progression of functional tissue failure. The accumulation of TG in non-adipose tissue causes the development of the inflammatory process. For example, in response to accumulations of EC in the vascular wall, the production of C-reactive protein increases.

To avoid the undesirable consequences of forced intracellular accumulation of TG, differentiating cells in these tissues acquire the features of adipocytes; they even look like adipocytes. However, the inability to express the full complex of necessary transcription factors during differentiation of a mesenchymal cell makes its phenotype adipocyte-like. These cells are small in size, have decreased sensitivity to insulin, and have increased secretion of cytokines. Mesenchymal cells with an adipocyte-like phenotype produce various cytokines that induce cell disdifferentiation, which increases the area of ​​fatty tissue degeneration.

So, that part of the energy entering the body that is not utilized during cell proliferation (growth and development), during physical activity, during the realization of reproductive potential, is spent on the synthesis of endogenous FAs, which form accumulations of non-metabolizable fat in non-adipose tissues, i.e. for the synthesis of elements of lipid crystals. Cholesterosis can be considered as the formation of intracellular and extracellular crystals of free cholesterol and cholesterol.

An excess of unclaimed energy substrates, which increases throughout a person’s life, leads in late ontogenesis to the development of cholesterosis of the gallbladder (cholecystitis) and the vascular wall (age-related atherosclerosis), insulin resistance, hyperglycemia and non-insulin-dependent type 2 diabetes, hypertension, and neurodegenerative diseases.

Age-related dyslipidemia. The most general indicator of changes in the lipid and lipoprotein spectra of blood in the older age group is a decrease in the content of total PL, HDL-C and apoprotein A-1. The age-related decrease in HDL content is a consequence of the lack of demand for cholesterol as a substrate for the synthesis of steroid hormones. As a result, the properties of bile change, cholesterosis of the gallbladder develops, and the absorption of exogenous fats is disrupted. In this way, the body limits the supply of energy that is used to perform the reproductive function. HDL are natural sorbents of cholesterol exposed on the macrophage membrane and the site of EC synthesis. Impaired HDL function promotes the appearance of altered, highly atherogenic LDL in the blood and the accumulation of EC in macrophages. Moreover, HDL, as the main transport vehicle for PL in the blood, promotes the repair of cellular damage, and a stable deficiency of these lipoproteins makes the process of tissue destruction irreversible. A profound decrease in the level of PL and the number of HDL particles is characteristic of neurodegenerative diseases in old age, in particular Alzheimer's disease.

In the older age group, a decrease in HDL-C and an increase in LDL-C occurs against the background of an increase in TG levels. This type of dyslipidemia is characteristic of insulin resistance observed in metabolic syndrome, a pathological condition caused by excess intake of energy substrates. The TG content, as a rule, does not exceed the upper limit of normal (200 mg/dL), but only approaches it. Currently, TG levels ≥150 mg/dL are considered a risk factor for metabolic syndrome.

In general, the older age group is characterized by the same complex of pathologies that is observed in metabolic syndrome - dyslipidemia, insulin resistance, glucose tolerance, hypertension, inflammation. The exception is obesity. Obesity develops as a consequence of the accumulation of unused energy substrates in adipose tissue. This excess is created when there is an imbalance between the amount of glucose and exogenous fatty acids entered into the body with food, and their consumption, including during β-oxidation in skeletal muscle. The ratio of subcutaneous/visceral adipose tissue in obesity changes in favor of visceral fat. Abdominal obesity is the main risk factor for metabolic syndrome. With the aging of the body, the gradual dominance of visceral adipose tissue in the total mass of adipose tissue is a risk factor for the main pathologies of older age.

It is not difficult to see the similarities between the factors underlying metabolic syndrome and age-related pathologies. What these two processes have in common is the accumulation of unspent energy substrates.

Metabolic syndrome. As shown above, the metabolic pathways of cholesterol, FA (in the form of TG and free FA) and glucose are linked into a single system that combines carbohydrate and lipid metabolism into the overall exchange of energy substrates. Currently, there is a reorientation of the attention of researchers from individual pathology to systemic disorders, which are based on the same type of metabolic changes. Diseases that are most characteristic of the elderly and senile age are caused by disruption of the functioning of the body as a single system. Due to the fact that there are many similarities between factors of age-related pathologies and risk factors for metabolic syndrome, it is necessary to consider in more detail the characteristic features of this systemic disorder.

Metabolic syndrome is being studied most intensively today. It combines changes in the distribution of glucose (insulin resistance/hyperinsulinemia/type 2 diabetes) and lipids (dyslipidemia), i.e. changes in the general system of distribution of energy substrates. These changes are accompanied by conditions such as obesity, hypertension and atherosclerosis. Metabolic syndrome is associated with an increased risk of developing cardiovascular disease. The main cause of death in metabolic syndrome is cardiovascular complications - heart attack, stroke, while atherosclerotic damage to blood vessels of various vascular beds develops. Other factors observed in the syndrome are fibrinogenemia, low levels of tissue plasminogen activator, nephropathy, microalbuminuria, etc.

Disorders of carbohydrate and lipid metabolism in metabolic syndrome have clearly defined characteristics - insulin resistance (early stage) and hyperglycemia (late stage), as well as a certain type of dyslipidemia. Early on, insulin sensitivity is almost completely lost in skeletal muscle but retained in adipose tissue and the liver. Dyslipidemia in metabolic syndrome is characterized by the following indicators:

An increase in the level of TG in the blood plasma;

Decrease in HDL level (prevalence of small particle fraction);

Decrease in EC content in HDL;

An increase in the amount of small dense (highly atherogenic) LDL;

An increase in the content of free fatty acids in the blood plasma.

It is believed that an increase in the content of free fatty acids in the blood plasma is the most characteristic indicator in the diagnosis of obesity, insulin resistance and type 2 diabetes. Moreover, at present, an increased level of free fatty acids in the blood is considered as the root cause of the development of metabolic syndrome.

The concentration of free fatty acids in plasma reflects the balance between their production (lipogenesis, intravascular hydrolysis of TG and release of fatty acids from adipose tissue) and consumption (in particular, β-oxidation in skeletal and cardiac muscle).

Insulin resistance primarily occurs in skeletal muscle. TG accumulations begin to form in this tissue, which is completely unusual for myocytes. The reason for the accumulation of TG in skeletal muscle is the excessive influx of saturated FAs into myocytes due to an increase in the level of free FAs in the blood. In healthy young and middle-aged people, an increase in the level of free FAs occurs due to an increase in the influx of exogenous FAs or FAs synthesized in the liver with excess dietary glucose. When there is an excess amount of TG in cells and FA in the extracellular space, the IR function is “turned off.”

Due to their lipophilicity, free FAs enter the cell passively, but it has recently been shown that this process is activated through the CD36 receptor. This receptor is found in large quantities in adipose tissue, cardiac and skeletal muscles and is virtually absent in the liver and kidneys. CD36 deficiency is associated with significant impairment of FA transport and the development of insulin resistance. The decrease in CD36 content in the membrane may be due to a change in its viscosity properties. With high expression of CD36 in muscles, the volume of adipose tissue, the level of VLDL and free fatty acids in the blood decrease.

Subcutaneous adipose tissue, which directs fatty acids to skeletal muscle, reduces fatty acid secretion, TG accumulate in adipocytes, and adipose tissue proliferates. This leads to the development of insulin resistance in the adipose tissue itself. The secretion of FA into the blood becomes continuous, and the increased level of free FA in the blood stabilizes. Excess fatty acids begin to accumulate in non-fat tissues. Maintaining HSL activity and continuous lipolysis help adipose tissue to “get rid” of excess burden, and insulin sensitivity in this organ is restored.

Visceral adipose tissue cells are more sensitive to the lipolytic effect of catecholamines and more resistant to the action of insulin than subcutaneous adipose tissue cells. Therefore, despite a decrease in the intensity of lipogenesis in subcutaneous adipose tissue, visceral tissue continues to use glucose for the synthesis of TG. With the gradual growth and dominance of visceral tissue, the main flow of fatty acids rushes to the liver. Despite the fact that visceral fat makes up only 6% of the total mass of adipose tissue in women and 20% in men, the liver receives 80% of all blood from the portal vein, where visceral fatty acids are secreted. With metabolic syndrome, the proportion of visceral adipose tissue increases, which leads to the appearance of an androgynous body type.

The liver responds to increased influx of FA by increasing the level of secreted TG. Triglyceridemia develops. If the excess FA in the liver is large enough, TGs begin to accumulate in hepatocytes. Normalization of FA flow into the liver helps restore IR sensitivity in skeletal muscle. However, chronic overeating and a sedentary lifestyle make insulin resistance chronic and contribute to the full development of metabolic syndrome.

Other factors contributing to the development of metabolic syndrome, in addition to insulin resistance, are associated with dysfunction of adipose tissue as an endocrine organ. Metabolic syndrome can also be considered an inflammatory condition. For example, the liver produces C-reactive protein (CRP), a marker of systemic inflammation. There was a positive correlation between the degree of obesity (body mass index), the level of CRP and cardiovascular risk factors such as fibrinogen and HDL cholesterol. The level of CRP increases in response to the secretion of interleukin-6 by adipose tissue. In obese people, the TNF system is activated. The secretion of TNF-α and interleukin-6 increases with increasing adipose tissue mass. Glucose homeostasis and TNF system activity modulate leptin secretion. Leptin induces the release of interleukin-1 in brain tissue, influencing the secretion of proinflammatory cytokines. Inflammation plays a role in the pathogenesis of atherosclerosis, which in turn is observed in people suffering from obesity, dyslipidemia, diabetes and insulin resistance.

Slow-acting inflammation may be a factor in the development of hypertension. Increases in systolic and diastolic blood pressure, pulse filling, and blood pressure are associated with interleukin-6 levels. This correlation is more pronounced in women. In men, a correlation was observed between interleukin-6 levels and fasting insulin levels. It is assumed that the cause of hypertension in metabolic syndrome is dysfunction of adipose tissue.

Thus, insulin resistance in adipose tissue, continuous lipolysis and increased release of fatty acids into the blood by adipose tissue increases the intensity of their flow into non-adipose tissue. Insulin resistance is accompanied by leptin resistance. This means that the level of FA β-oxidation in cells decreases.

So, adipose tissue responds with insulin resistance to the excess influx of glucose and fatty acids into it. The flow of fatty acids is, as it were, redirected to other depots, which inevitably become non-fat tissues. Insulin resistance in skeletal muscle and liver is also a response to an excess of energy substrate. Lipogenesis in skeletal muscle requires the activation of functions that are not characteristic of myocytes. Indeed, with the accumulation of TG in skeletal muscle, expression of nuclear receptors specific for adipocytes is observed, i.e. the cell's phenotype actually changes. An imbalance between the intake of energy substrates (glucose and saturated fatty acids) into the body and their consumption during overeating and low physical activity ultimately leads to the deposition of non-metabolizable fat in non-fat tissues.

As with aging, hypertriglyceridemia in metabolic syndrome is accompanied by a decrease in HDL levels. At the same time, the sorption of cholesterol exposed on the macrophage membrane and the synthesis of EC decrease, and the flow of cholesterol into steroidogenic tissues and the liver decreases. Cholesterosis of the gallbladder and vessel walls develops. Disruption of the flow of cholesterol into the liver changes the properties of bile. As with aging, the body tries to reduce the intake of exogenous saturated fatty acids. As a result of changes in the viscous properties of the basolateral membrane, the activity of the glucose transporters Glut-2 and SGLT1 (sodium-dependent glucose transporter) in the intestine is inhibited, which reduces the intake of glucose into the body.

Thus, the common cause of metabolic syndrome and age-related pathology is the accumulation of unspent (“excess”) energy substrates in tissues in the form of TG.

Experts from the International Atherosclerotic Society recommend the following indicators to determine the risk of developing metabolic syndrome. These indicators are determined for men over 45 years of age and for women over 55 years of age:

Abdominal obesity;

 50 mg/dl (1.3 mmol/l) in women;

Blood pressure ≥ 130/85 mm Hg;

Fasting glucose ≥ 110 mg/dL (6.0 mM/L).

LDL content is currently excluded from these indicators. However, many older people experience adaptation to disturbances in the distribution of fatty acids, which is expressed in the fact that their TG levels do not exceed 100 mg/dl. This group is characterized by an increase in LDL content against the background of a decrease in HDL content, i.e. cholesterol distribution disorders dominate. Such a distribution of older people into two groups according to the type of energy metabolism disorder requires a differentiated therapeutic approach.

1. 
   Brown G., J. Walken. Liquid crystals and biological structures//M. - World. – 1982. – P. 198.
2. 
   Tereshina E.V., N.N. Doronina, O.P. Pleteneva. Lipid metabolism in old and senile age//In Sat. "Current problems of gerontology." – M. – 1999. – P. 225-226.
3. 
   Das U.N. Is metabolic syndrome X an inflammatory condition?//Exp.Biol.Med. – 2002. – V. 227. – P. 989-997.
4. 
   Febbraio M., D.F. Hajjar, R.L. Silverstein. CD 36: a class B scavenger receptor involved in angiogenesis, atherosclerosis, inflammation, and lipid metabolism//J.Clin.Invest. – 2001. – V. 108. – P. 785-791.
5. 
   Frayn K.N. Visceral fat and insulin resistance: causative or correlative?//Br.J.Nutr. – 2000. – V.83 (Suppl.1). – P. S71-S77.
6. 
   Hunter S.J., W.T. Garvey. Insulin action and insulin resistance: diseases involving defects in insulin receptors, signal transduction and the glucose transport effector system//Am.J.Med. – 1998. – V. 105. – P. 331-345.
7. 
   Kirkland J.L., T. Tchkonia, T. Pirtskhalava, J. Han, I. Karagiannides. Adipogenesis and aging: does aging make fat go MAD?//Exp.Geront. – 2002. – V. 37. – P. 757-767.
8. 
   Krieger M. Scavenger receptor class B type 1 is a multiligand HDL receptor that influences diverse physiological systems//J.Clin.Invest. - 2001. – V. 108. – P. 793-797.
9. 
   Lewis G.F., A. Carpentier, K. Adeli, A. Giacca. Disorded fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes//Endocrine Rev. – 2002. – V. 23. – P. 201-229.
10. 
    Lewis G.F., G. Steiner. Hypertriglyceridemia and its metabolic consequences as a risk factor for atherosclerotic cardiovascular disease in non-insulin-dependent diabetes mellitus//Diadetes Metab.Rev. – 1996. – V. 12. – P. 37-56.
11. 
    Zimmet P., E.J. Boyko, G.R. Collier, M. de Courten. Etiology of the metabolic syndrome: potential role of insulin resistance, leptin resistance, and other players//Ann.N.Y.Acad.Sci. – 1999. – V. 892. – P. 25-44.

The problem of longevity has been and remains one of the most exciting and important for humanity. Preserving important organs such as the liver for longevity is very important! From time immemorial, people dreamed of living a long time, maintaining efficiency and creative activity. Our state is interested in the longevity of its citizens; it does a lot to increase people's life expectancy and improve their health.

Aging of the body

We all know that aging is a natural physiological process characteristic of all living things. A person cannot live and remain young forever, and old age cannot be prevented either. But isn’t science capable of pushing the boundaries of active longevity? After all, old age can come at different times and proceed differently. There are two types of old age: physiological and premature. Physiological old age is characterized by the preservation of mental and physical strength, efficiency, cheerfulness, and interest in everything that surrounds a person. In this case, a gradual decrease in the functional and adaptive abilities of the body occurs, and the normal life cycle ends naturally.

Premature aging is the early decrepitude of the body, it is a accumulation of pathological marks left by past illnesses, irregularities, and unhealthy habits. In order not to grow old ahead of time, it is important to learn to live without harming yourself, and this means being able, without switching off from your usual active work rhythm, to avoid everything that can have a detrimental effect on your health.

Scientists working on aging problems aim to understand the causes of this process and study its mechanisms. They strive to give people scientifically based recommendations and advice on what to do to maintain active longevity.

At the beginning of our century, I. I. Mechnikov expressed the idea that premature aging is caused by self-poisoning of the body by decay products formed in the large intestine as a result of the vital activity of microbes located in it. At the present stage of development of science, it is quite obvious that such a complex process as aging cannot be determined only by poisoning of the body. And yet the fact remains: the harmful effects of various toxic substances on the body become especially noticeable in old age. Why? The fact is that in youth, toxic substances are quite completely neutralized in the liver and removed from the body. As we age, the intensity of the neutralization processes decreases. And this is mainly due to changes occurring in the liver.

Proper nutrition to help the liver

Rational nutrition is an important factor in the prevention of liver and biliary tract diseases in old age. The diet of elderly and senile people should be varied. You need to eat 4 - 5 times a day, in moderation and always at certain hours. If you follow these rules, the secretion of gastric juice begins even before eating, the appetite is stimulated, and food is better digested and absorbed, which means that unnecessary difficulties are not created for the liver.

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An important place in the menu of people after 45 years of age should belong to milk and dairy products. Cottage cheese, fermented baked milk, yogurt are useful. Dairy products contain easily digestible proteins. Consumption of lactic acid products helps prevent putrefactive processes in the large intestine and has a beneficial effect on the liver.

At the same time, elderly and senile people also need other proteins of animal origin - meat, fish. It is better to give preference to low-fat varieties. At the same time, you should not completely give up fat. They have great nutritional value, contain some essential vitamins and improve the taste of cooked dishes. Vegetable oils - sunflower, olive, corn - are very useful for older people. The diet should include vegetables (red beets, carrots, cabbage, potatoes) in the form of salads and vinaigrettes, fruits, berries (black berries, rose hips, apples, prunes, sea buckthorn), fruit and vegetable juices. Vegetables, fruits and berries improve digestion and absorption of nutrients, and, most importantly, they are very rich in vitamins.

When the body ages, the cells of all internal organ systems change along with it, which leads to diseases of the liver and other internal organs. The liver is one of the most important organs of the human body, which allows you to remove toxins, neutralize tumor cells, synthesize bilirubin and secrete hormones that are responsible for blood clotting. With age, it changes and functions with deviations.

With age, the human body, for objective reasons, becomes weaker, and toxins accumulate in the liver, which provokes liver disease.

Features of liver functioning

In older people, the level of blood supply to the organ decreases with age; the number of collagen fibers in the blood vessels increases, which reduce the level of blood flow. The number of (liver parenchyma cells) decreases, as a result of which protein synthesis decreases by 20%, and electrolyte-water metabolism is disrupted.

The liver of an elderly person has less weight and size than that of a young person.

In young people, the liver weight is 1400−1700 g, in an elderly person - 900−980 g. Despite the loss of weight, healthy tissue begins to be replaced by adipose tissue, causing diffuse changes. An increase in fatty consistency leads to disruption of the sebaceous glands and the appearance of wen on the surface of the organ and in connective tissues. The level of bile production decreases.

Liver diseases in the elderly

The first sign of the presence of diseases is considered to be diffuse changes in the liver, which entails diseases such as:

1. Chronic hepatitis is an inflammatory disease characterized by the appearance of jaundice.
2. Cirrhosis is a disease characterized by changes in structure, proliferation of connective tissue and a decrease in the number of hepatitis.
3. Lipomatosis is the appearance of wen on the surface and in the tissues of the liver. Leads to disruption of the structure of the liver and surrounding tissues.

Features and symptoms

Chronic hepatitis occurs as a result of a previous infection. A peculiarity of the course of the disease in older people is the absence of usual symptoms, such as jaundice. Patients complain of fatigue, lack of appetite, heaviness in the abdomen, plaque on the surface of the tongue, and pain in the liver area. When drinking alcohol and fatty foods, these symptoms intensify. On palpation, there is pain in the upper abdomen, and a slight thickening is felt in the liver area.

Cirrhosis often occurs in people who have abused alcohol. It manifests itself most acutely in old age, fibrosis intensifies and often leads to the death of a person. The disease is irreversible; cirrhosis is accompanied by cell death. Symptoms that indicate cirrhosis are:

• nausea;
• bloating;
• vomit;
• bitterness in the mouth;
• jaundice;
• decreased potency;
• coating on the tongue.

The connection with the bile ducts is disrupted, the liver loses its ability to fight toxins and cannot fully remove them from the body, which provokes intoxication. In addition to alcoholism, hepatitis B, C, D can lead to cirrhosis. As a rule, it is impossible to completely cure cirrhosis, but treatment has a positive effect on the patient’s quality of life.

Liver lipomatosis is a dysfunction of the fatty tissue of the liver, resulting in the formation of benign cysts - lipomas. Abuse of fatty foods and alcohol leads to increased development of the disease. Overweight people often suffer from lipomatosis. Sometimes the occurrence of the disease is influenced by genetic predisposition.

Treatment of diseases

Treatment of chronic hepatitis involves restoring liver function using therapy aimed at eliminating the hepatitis virus. Timely therapy will help maintain the patient’s life at a normal level. Hepatoprotectors are used to restore functions. In order to kill the hepatitis virus, it is recommended to take nonspecific regulatory proteins. It is important to adhere to a strict diet, completely eliminating alcohol, fatty, smoked and salty foods from the diet. Animal fats must be replaced with vegetable fats.

Treatment of liver diseases in the elderly depends on the type of disease and the individual characteristics of the patient.

The treatment of cirrhosis is based on slowing down the process of cell death and improving the patient’s life. Hepatoprotectors are prescribed for alcoholic cirrhosis, which reduce the rate of disease progression. Hepatoprotectors are recommended to be used with antiviral therapy if the causative agent of cirrhosis is hepatitis. The diet gives a positive result, it is important to avoid adding salt to dishes, it retains water in the body.

Treatment of lipomatosis is surgical; it is necessary to remove the wen, as there is a danger of them developing into malignant tumors. The diet consists of a balanced diet, do not overuse fatty foods. Lipomatosis is asymptomatic and therefore difficult to detect. It is necessary to periodically perform ultrasound or computed tomography of the liver to eliminate the risk of developing lipomatosis.

UdK: 616.36-053-07

age-related liver changes

V.G. Radchenko, P.V. Seliverstov North-Western State Medical University named after. I.I. Mechnikova,

Saint-Petersburg, Russia

During life, the human body undergoes a number of changes that lead to aging. Physiological aging of the body is accompanied by irreversible functional and organic restructuring of all systems and organs, including the liver. The most common cause of diffuse changes in the liver parenchyma in elderly patients is steatosis, in the development of which mitochondrial dysfunction plays an important role. For the treatment and prevention of liver diseases, against the background of its inevitable aging, it is advisable to use drugs with a multidirectional effect on various parts of the pathogenesis of liver damage. Systematic implementation of preventive measures will allow older people to maintain good health and performance for many years.

Key words: old age, liver, steatosis, mitochondrial dysfunction, NAFLD, microbiota.

A person is young and old depending on how he feels.

Thomas Mann

During the course of life, every person’s body undergoes a number of changes, which, one way or another, lead to aging. This process is called “involution” and begins long before the onset of biological old age, and the speed of its development is directly related to the lifestyle in young and middle age. Physiological aging of the body is accompanied by serious irreversible functional and organic restructuring of all systems and organs, including the organs of the gastrointestinal tract (GIT). Thus, at the age of 40-50 years, the digestive organs begin to undergo functional changes, which in the future will allow them to adapt to the changing conditions of the body. As a rule, changes in the functioning of the digestive organs in elderly and senile people develop slowly, at different periods of life and over time, functional changes acquire an irreversible organic character. Unlike pathological, premature aging, which is the cause of various chronic diseases, physiological aging is not complicated by any pathological process; it is the old age of practically healthy elderly and old people.

Most clinical and epidemiological studies indicate that

In old and senile age, many diseases are characterized by weak severity and unclear clinical manifestations, as well as the presence of several concomitant diseases. The decrease in the reserve and adaptive capabilities of the body of an elderly person is explained by gradually increasing changes in the structure of tissues and functions of organs, and primarily due to disruption of cellular energy exchange. Disturbances in cellular energy lead to multisystem diseases. First of all, the most energy-dependent systems and organs suffer, including: the nervous system, muscular system, endocrine system, heart, kidneys, liver, etc.

It is known that one of the most important mechanisms leading to disruption of energy metabolism and aging of the body is the increase in mitochondrial dysfunction. Thus, at the international symposium on mitochondrial pathology, held in 2001 in Venice, the discovery of specific mutations in mitochondrial DNA that appear only with aging was announced. These mutations are not detected in young people, but in older people they are detected in various cells of the body with a frequency of more than 50%.

In the human body, unlike other organs and systems, the liver is a relatively slowly aging organ, which is due to the morphofunctional usefulness of hepatocytes and the preservation of the immune system, observed for a long time. In adulthood, the liver undergoes a series of

structural changes, some of which are compensatory and adaptive in nature and ensure satisfactory functioning of the organ during the aging process. Thus, at the age of 45 to 50 years, there is a decrease in the total number of hepatocytes, on average by 6 cells per field of view, as well as in liver weight, on average up to 600 grams, which correlates with the ratio of liver and body weight. After 70 years, the organ decreases by 150-200 grams, and the number of hepatocytes decreases by 3-4 cells. By the age of 80, liver atrophy is noted, which does not reach a sharp degree of severity, and in persons over 90 years of age, the number of hepatocytes is reduced by 5 cells. Along with a decrease in the number of hepatocytes, the intensity of blood supply to the liver gradually decreases and fibrosis progresses. Excessive collagen formation in elderly people is promoted by ischemia and/or hypoxia of the liver, which leads to inhibition of the activity of its functional components.

The most common cause of diffuse changes in the liver parenchyma in elderly patients is excessive fatty infiltration resulting from ultrastructural disorders of the mitochondrial apparatus. Thus, the developing functional deficiency of mitochondria, which are the main regulator of fat in the liver, contributes to the formation of steatosis in NAFLD, the incidence of which by the age of 60 reaches more than 86%.

According to modern recommendations, NAFLD is defined as a chronic disease that combines a whole range of clinical and morphological changes in the liver (steatosis, steatohepatitis, fibrosis and cirrhosis) in individuals who do not drink excessive amounts of alcohol.

The molecular substrate of NAFLD is the deposition of lipids, mainly triglycerides, in the hepatocyte. Thus, NAFLD is diagnosed when lipids accumulate in the form of triglycerides in an amount of more than 5-10% of the mass of hepatocytes or when more than 5% of liver cells contain their deposits. Excessive deposition of lipids in liver cells is a consequence of excessive synthesis of free fatty acids, a decrease in the rate of their β-oxidation in mitochondria, and inhibition of the formation of very low density lipoproteins. Disorders of protein metabolism associated with an age-related decrease in its synthesis and a slowdown in metabolism aggravate lipid metabolism disorders and also contribute to a decrease in the rate of excretion of triglycerides from hepatocytes. This process is directly related to the developing mitochondrial dysfunction in the liver cell in older people. Signs of morphological disorders of hepatocytes in NAFLD are: an increase in the size of the mitochondrial apparatus with significant swelling, a small number of mitochondria in the field of view, specific paracrystalline inclusions in the mitochondrial matrix with reduced density, detected by electron microscopy.

Another factor contributing to the formation of steatosis are medications, the need for use of which is determined by the need to treat concomitant diseases, including: amiodarone, glucocorticosteroids, synthetic estrogens, tamoxifen, tetracycline, non-steroidal anti-inflammatory drugs, nifedipine, diltiazem, cytostatics, etc. So, When β-oxidation of free fatty acids in the Krebs cycle is inhibited, the formation of reduced forms of NAD and FAD decreases, the subsequent oxidation of which leads to the transfer of electrons along the mitochondrial respiratory chain. Under physiological conditions, the oxidation of reduced forms of these coenzymes promotes the synthesis of macroergs in the process of mitochondrial phosphorylation. Intoxication with substances with pro-oxidant activity and the implementation of their toxicity

due to the inadequate functioning of the mechanisms of natural detoxification and antioxidant protection, it leads to the above changes in the metabolism of free fatty acids and the development of steatosis. At the same time, the maximum pathological changes occur in the mitochondria of hepatocytes, which become gigantic. Aldehydes, the end products of lipid peroxidation, are capable of activating cells of the reticuloendothelial system, in particular hepatic stellate cells, which are the main producers of collagen, causing cross-linking of cytokeratins with the formation of Mallory bodies, and stimulating neutrophil chemotaxis. Liver fibrosis is a clinical manifestation of stimulation of fibrogenesis and excessive deposition of extracellular matrix proteins. In patients with non-alcoholic steatohepatitis, the expression of cytochrome P-450 isoenzyme 2-E-1, which plays a key role in the biotransformation of xenobiotics, is increased. Induction of individual cytochrome P-450 enzymes leads to the generation of an increased amount of cytotoxic secondary radicals from endogenous substances, exogenously supplied foods, and drugs. Stimulation of the production of cytokines such as TNF-a, IL-1, IL-6, IL-8, as well as prostaglandins by Kupffer cells contributes to the progression of liver damage. Uncontrolled and prolonged production of cytokines and prostaglandins in non-alcoholic steatohepatitis leads to a prolonged acute-phase inflammatory response with stimulation of the production of amyloid peptides, inhibition of protein synthesis by hepatocytes, inhibition of gluconeogenesis, disruption of mitochondrial respiration and induction of hepatocellular apoptosis. In the presence of aggravating factors, for example, such as: taking medications, viral infection, concomitant diseases, alcohol consumption, further progression of the process with the formation of fibrosis, cirrhosis and liver cancer is possible.

To date, it has been established that NAFLD increases the risk of mortality from cardiovascular diseases (CVD) by more than 2 times. At the same time, fatty liver degeneration in patients with NAFLD can occur long before the development of metabolic syndrome (MS) and contribute to the development of possible metabolic disorders. In elderly and senile patients, NAFLD should be

viewed as a hepatic manifestation of MS. Thus, 90% of patients with NAFLD have 1 or more components of MS, and 30% have all its components. On the one hand, NAFLD affects the lipid metabolism of the entire body, since the liver plays a major role in cholesterol metabolism, as well as the development of atherosclerosis, which aggravates the course of CVD. On the other hand, CVD, progressive atherosclerosis and hepatic vascular fibrosis lead to deterioration of liver function. Vascular fibrosis is known to increase as a person ages, and is more common in older people. Since therapeutic approaches to treating patients at the stage of fibrosis are limited, for timely prevention of disease progression and the development of complications, timely diagnosis of the initial clinical manifestations of MS is necessary, even at the preclinical stage, when the condition is potentially reversible.

In old and senile age, chronic diffuse liver diseases are often asymptomatic or vaguely expressed, the localization and irradiation of pain is often atypical, their intensity is relatively low, and blood changes may not correspond to the severity of the complication. It is quite difficult to identify specific complaints characteristic of liver damage in an elderly patient. Firstly, the liver is almost never one of the organs that “shows complaints” characteristic of its damage. Secondly, elderly patients, as a rule, have several diseases that significantly worsen the quality of life, which is due to the comorbidity of symptoms. Sometimes elderly patients cannot clearly draw the line between health and illness, attributing the ailment to age-related reasons. Thus, in elderly and senile patients, NAFLD can manifest itself as fatigue, nausea, vomiting, jaundice of varying intensity, signs of encephalopathy and impaired renal function. However, such manifestations may not only be associated with liver damage, since triglycerides can accumulate in the kidney tubules, myocardium, brain and pancreas. In addition, the combination of several diseases in one elderly patient that aggravate his condition often makes it impossible to conduct a full examination. These features of the clinical picture make it difficult to diagnose diseases in a timely manner and lead to a delayed start of treatment.

A decrease in liver function impairs digestion and, as a consequence, the absorption of exogenously supplied substances in elderly and senile people, which may be due to ischemia in the mesenteric vessels, involutive maldigestion. In this case, increased formation of gases in the intestines, pain in the epigastrium after eating, decreased appetite, rapid satiety, poor tolerance of dairy products, refractory fats, fatty meats and fish, as well as stool disorders are often observed. Involutive changes in the digestive glands and impaired intestinal motility lead to a decrease in the volume of digestive secretions, and the rate of enzymatic processes of digestion and absorption of food components also decreases.

Such changes in the aging body contribute to the development of intestinal dysbiosis. In old age, the consequences of dysbiosis take on a different character: the protective functions of the microflora decrease; the ability of the intestinal microbiota to process cholesterol decreases, while the number of strains synthesizing cholesterol increases significantly; the aging process of the body is accelerated due to a deficiency of vitamins, microelements and disturbances in amino acid metabolism; Fermentation and putrefactive processes increase, hepatoenteric circulation is disrupted with the formation of toxic substances and intoxication of the body increases, which inevitably leads to a reduction in the period of active longevity and an exacerbation or worsening of the course of chronic diseases, primarily liver diseases.

A decrease in the detoxification function of microflora during age-related dysbiosis caused by various pathogens increases the load on the enzymatic systems of the liver and contributes to the occurrence of metabolic and structural changes in it. With an imbalance in the microflora of the digestive tract, the proportions of potentially pathogenic gram-negative bacteria increase, which leads to a significant accumulation of endotoxins in the intestinal lumen. The latter, penetrating through the intestinal mucosa into the local circulatory system, and then through the portal vein into the liver, affect sinusoid mononuclear cells, hepatocytes, and potentiate the adverse effects of other toxicants. up to 90% of all endotoxins are released facultatively by anaerobic gram-negative bacteria

yami. Endotoxins in excess amounts damage cell membranes, disrupt ion transport, cause fragmentation of nucleic acids, induce the formation of free radical oxidation products, initiate apoptosis, etc., which contributes to the formation of liver disease.

Additional difficulties in the treatment of elderly patients are created by the peculiarities of the action of drugs. Firstly, due to age-related structural changes in the mucous membrane of the gastrointestinal tract, the absorption of drugs may be impaired, which leads to a later appearance of the therapeutic effect and its less pronounced. As well as an age-related decrease in the neutralizing function of the liver, against the background of developing steatosis, and a decrease in the excretory abilities of the kidneys, drugs and their metabolic products are eliminated from the body more slowly than in young patients, which contributes to the accumulation of the drug and the development of side effects. Such an age-related decrease in cell reactivity may be the reason why the effectiveness of drug use is sometimes significantly lower than expected or absent altogether. And the likelihood of side effects from drug therapy in elderly patients is much higher than in young patients.

It is known that when taking five drugs simultaneously, the probability of developing side effects is 4%, 5-10 drugs - 10%, 10-16 - 28%, and 16-20 drugs - up to 60%. According to American scientists, side effects of drugs act as an etiological factor in the development of jaundice in 2-5% of hospitalized patients, hepatitis in 40% of patients over 40 years of age and 25% of cases of fulminant liver failure.

Thus, due to the presence of latent chronic liver diseases (CLD), it is advisable for elderly and senile patients to undergo a comprehensive examination for the purpose of early diagnosis of liver pathology, timely treatment and prevention of severe complications. Timely diagnosis and adequate assessment of the impact of concomitant pathology and its drug therapy on the course and prognosis of liver diseases will reduce the incidence of complications and mortality in patients of the older age group.

For the treatment and prevention of liver diseases, against the background of its inevitable aging, it is advisable to use drugs with a multidirectional effect on various parts of the pathogenesis of liver damage. Thus, preference is given to drugs that have the ability to stabilize cell membranes, eliminate mitochondrial dysfunction, improve the state of lipid, protein and mineral metabolism, stimulate regenerative processes, increase the functional activity of the physiological antioxidant system and maintain intestinal microbiocenosis. Gepagard Active fully possesses similar effects, since it contains active components necessary for the aging body, such as: essential phospholipids, L-carnitine, vitamin E (Eurasian patent No. 019268 dated February 28, 2014). Essential phospholipids (EPL), being integrated into the damaged hepatocyte membrane, protect liver cells from the effects of free radicals, improve the state of lipid, protein and mineral metabolism, and stimulate regenerative processes. L-carnitine - activates the process of utilization of fatty acids, improves metabolic processes, eliminates mitochondrial dysfunction and slows down involutive processes in the liver. Vitamin E - stabilizes liver cell membranes, participates in antioxidant protection, slows down the aging process of the body and maintains hormonal balance. Thanks to this unique combination of active ingredients, the following pharmacological effects are achieved: hepatoprotective, membrane-protective, anti-apoptotic, immunomodulatory, antioxidant, hypocholesterolemic, detoxifying and prebiotic (RF patent No. 2571495 dated December 20, 2015). Consumption of Hepagard Active with food in a standard dose, 1 capsule 3 times a day, helps reduce collagen formation, restore the structure and function of hepatocytes, normalize mitochondrial dysfunction, prevent the development of liver fibrosis, stabilize the physicochemical properties of bile, enhance the detoxifying and exocrine function of the liver , providing antispasmodic, anti-inflammatory and prebiotic effects.

Thus, treatment methods used in geriatric practice, even the most active ones, of course, do not lead to a complete cure, but affect the quality of life of the patient.

ents. Systematic implementation of preventive measures allows older people to maintain good health and performance for many years of life, and most importantly, prevent relapses of the disease. Maintaining the health of internal organs at the proper level, taking into account the age-related characteristics of the body, is an important task for doctors of any specialty.

Literature

1. Baranovsky A.Yu. Diseases of the elderly / A.Yu. Baranovsky - M.: ZAO "Tsentrpoli-graf", 2002. - 633 p.

2. Diseases of the liver and biliary tract: A guide for doctors / Ed. Ivashkina V. T. - M.: M-Vesti, 2002. - 416 p.

3. Valenkevich L.N. Gastroenterology in geriatrics / L.N. Valenkevich. - L.: Medicine, 1987. - 240 p.

4. Age-related changes in the gastrointestinal tract in patients with colon dysbiosis against the background of chronic liver diseases / V.G. Radchenko et al. // Preventive and clinical medicine - 2010. - No. 2. - P. 112-11.

5. Age-related changes in the gastrointestinal tract / V.G. Radchenko and others // Remedium Privolzhye - 2013. - No. 9. - pp. 27-28.

6. Approaches to the treatment of patients with menopausal disorders complicated by menopausal metabolic syndrome with cholestasis / N.P. Gavrilova et al. // Experimental and clinical gastroenterology-2014. - Issue 108, No. 8. - P. 34-40.

7. Popper G. Aging or degradation of the liver // Problems of gastroenterology. - 1987. - Issue. 7. - pp. 176-184.

8. Lazebnik L.B., Zhuravleva I.G. Non-viral liver damage in the elderly // Hepatology. -2003. - No. 1. - P. 40-46.

9. Lazebnik L.B., Drozdov V.N. Diseases of the digestive system in the elderly. - M: Anahar-sis, 2003. - 206 p.

10. Intestinal microbiocenosis in chronic liver diseases: diagnosis and treatment / V.G. Radchenko and others // Doctor - 2011. -No. 7. - pp. 18-21.

11. Non-alcoholic fatty liver disease: clinical picture, diagnosis, treatment / L.B. Lazebnik et al. // Experimental and clinical gastroenterology - 2015. - Issue 119, No. 7. - pp. 85-96.

12. Seliverstov P.V., Radchenko V.G. Optimization of therapy for patients with non-alcoholic fatty liver disease // Russian Journal of Gastro-

enterology, hepatology, colonoproctology. - 2014 - No. 4. - pp. 39-44.

The liver of older people often suffers from chronic diseases of the endocrine system, unbalanced nutrition, pathologies of the cardiovascular system, atherosclerosis, and diabetes mellitus.

According to statistics, the liver in old age is enlarged in 95% of people. The most common diseases among patients aged 60-75 years are hemangioma, fatty hepatosis, cirrhosis, HD, hepatomegaly.

It is possible to stabilize the functionality of the hepatobiliary system and achieve stable remission of a certain disease even in old age. Hepatoprotectors, choleretic medications, enzymes help with this. Let’s take a closer look at the features of the course of GBS pathologies in the elderly, and find out how to treat them.

Hepatomegaly

What is the normal size of the liver in the elderly? There are only average indicators. According to doctors, the optimal thickness of the right lobe is considered to be 11-12.6 centimeters, the CVR is up to 15 centimeters, the length of the right lobe should not exceed 15 centimeters, the left lobe should be 7 centimeters thick. As for the length of the liver, it is normally 14-16 centimeters, and in width - 20-22.5 centimeters.

Hepatomegaly is one of the most common diseases among elderly patients. This term hides a pathology in which the liver increases in size, as a result of which its functionality is impaired.

The most common causes of hepatomegaly are:

1. Cardiovascular pathologies.
2. Autoimmune hepatitis.
3. Polycystic disease.
4. Viral and infectious liver lesions.

Characteristic symptoms of liver hepatomegaly in old age are pain in the right hypochondrium, nausea, heartburn, skin rash, and bad breath. Also, in an elderly patient, the color of the skin and eye sclera changes.

If an elderly person has an enlarged liver, he needs to undergo appropriate treatment. It is imperative to follow diet table No. 5. The patient is also prescribed hepatoprotectors, diuretics, and multivitamin complexes. If there are infectious or viral lesions of the liver, then antibiotics or antiviral agents are prescribed, respectively.

Hepatomegaly cannot be completely cured. The goal of therapy is to stop further progression of the disease and improve the patient’s quality of life.

Hemangioma

Hemangioma is a benign tumor. Doctors do not know the exact reasons for its appearance. It is noted that the pathology is most common among elderly women. Men suffer from cancer much less often.

A hemangioma, in simple terms, is a collection of flattened endotherial tubes with septa between them. The tumor size is small - about 2-7 mm. However, there are cases when the neoplasm exceeds 20 centimeters in diameter.

Hemangioma affects not only the liver, but also the gallbladder, as well as organs close to the liver. Untimely therapy is fraught with the appearance of metastases - in such cases it is almost impossible to save the patient.

Doctors suggest that the causes of tumor formation are chronic hepatitis, long-term use of steroids and hormonal contraceptives, cirrhosis, and inflammatory processes in the gallbladder.

Characteristic signs of the disease:

• Pain in the area of ​​the right hypochondrium. They have a drawing, paroxysmal character.
• Burning sensation in the epigastric region.
• Digestive disorders.
• Changes in skin and eye color.
• Bitterness in the mouth.

Liver hemangioma in elderly men, and even in elderly women, must be removed surgically. But if the size of the tumor is small, then a wait-and-see approach is preferable, that is, the elderly patient will need to undergo regular examinations and monitor the dynamics of the pathology.

Fatty liver hepatosis

Fatty liver hepatosis is a disease that manifests itself in the form of fatty liver degeneration. FGP is a chronic disease, which means it cannot be completely cured. According to statistics, older people are more likely to suffer from this disease.

The most common cause of hepatosis is type 2 diabetes. Due to increased blood sugar levels, fatty infiltration of the organs of the hepatobiliary system occurs and lipid metabolism is disrupted. Hepatosis is often accompanied by atherosclerosis.

Also, the causes of the disease can be:

1. Toxic liver damage.
2. Alcoholism.
3. Unbalanced diet. The health of the hepatobiliary system is negatively affected by sweets, fatty foods, processed foods, fast food, and canned food.
4. Deficiency of protein and vitamins in the diet.
5. Long-term use of hepatotoxic drugs, including cytostatics, antibiotics, anabolic steroids, NSAIDs.

Symptoms of fatty hepatosis are digestive disorders (diarrhea, nausea, abdominal pain), bitterness in the mouth, the appearance of xanthoma on the eyelids, dull pain in the right hypochondrium. On palpation, the liver is enlarged and painful. In old age, people with hepatosis also change the color of their palms, and in men, the mammary glands increase in size.

It is customary to treat fatty hepatosis conservatively, that is, with the help of diet and medications. Products high in simple carbohydrates and fats must be removed from the menu. The basis of the diet is vegetables, fruits, cereals, and lean meats. As for medications, the patient is prescribed essential phospholipids or other hepatoprotectors.

If an elderly person is diabetic, then it is necessary to take hypoglycemic agents or inject insulin (for type 1 diabetes). In cases where hepatosis is accompanied by atherosclerosis, it is imperative to take statins and multivitamin complexes that contain unsaturated fats Omega-3 and Omega-6.

Cirrhosis

Cirrhosis is a pathology in which healthy liver cells turn into connective tissue. In truth, the prognosis for this disease is disappointing. The average life expectancy with cirrhosis is 4-6 years.

The reason for this is the fact that cirrhosis progresses rapidly, is often accompanied by complications, and can cause ascites, peritonitis and even internal bleeding. Severe cirrhosis can cause hepatic coma and liver failure - in such cases the likelihood of death is very high.

According to experts, the following factors predispose to the development of cirrhosis:

1. Chronic alcoholism.
2. Fatty hepatosis, chronic hepatitis.
3. Autoimmune hepatitis.
4. Cholangitis.
5. Diabetes.
6. Galactosemia.
7. Obesity.
8. Impaired passage of bile through the bile ducts.
9. Cholecystitis, cholelithiasis.
10. Wilson-Konovalov disease.
11. Heart failure.
12. Damage to the liver by worms, in particular alveococci and echinococci.

Liver cirrhosis progresses rapidly in older people. Characteristic symptoms of the disease are acute pain in the right hypochondrium, dry mouth, the appearance of yellow spots on the eyelids, and digestive disorders. Also, the patient’s stool and urine color changes, jaundice develops, and bleeding gums are noted.

The level of hemoglobin decreases, at the same time the level of ESR and lymphocytes increases. The patient also has a disturbance in the production of liver enzymes.

Cirrhosis is treated conservatively. The patient must follow a gentle diet and drinking regime. It is strictly contraindicated to take alcohol and any hepatotoxic drugs.

Drug therapy involves the use of hepatoprotectors, enzymes, and diuretics. If a person’s blood pressure increases due to cirrhosis, then therapy is supplemented with beta-1 adrenergic blockers, sartans or calcium channel blockers.

Biliary dyskinesia

Biliary dyskinesia is a pathology in which the passage of bile through the bile ducts is disrupted. It is difficult to say how many older people suffer from this disease. But, according to doctors, every fifth person over the age of 60 is diagnosed.

JP develops as a result of congenital malformations of the biliary tract, unbalanced nutrition, constant stress, chronic non-calculous cholecystitis, neurocirculatory dystonia, diabetes mellitus, food allergies, and worm infections. Also, obesity, atherosclerosis and even thyroid diseases predispose to pathology.

Characteristic signs of dyskinesia are:

• Pain in the area of ​​the right hypochondrium. They may have an acute paroxysmal nature.
• Increased sweating.
• Headache.
• Flatulence.
• Asthenia, increased fatigue.
• Bad breath. The smell is putrid and pungent.
• The appearance of a yellow coating on the tongue.
• Bitter taste in the mouth.
• Biliary colic. They may be accompanied by rapid heartbeat and panic attacks, and even numbness of the limbs is possible.
• Change in stool color. It takes on a light yellow or grayish tint.
• Yellowing of the skin and whites of the eyes.

It is easier to cure JP than the above diseases. It is enough for the patient to follow a diet, take hepatoprotectors and choleretic agents. Sedative medications may be prescribed to prevent the development of biliary colic and tachycardia attacks.