For Gerontologists

Membrane plasmapheresis in old age.

There is no doubt that the biologically determined age of a human being is at least 110 years and, according to some data, should reach 150 years, although in reality the average life expectancy fits within half of that term. Whether there was ever that golden age of humankind when people lived to such an age, as biblical sources testify, is hard to say. 65% do not live to 80 years. To 90 years – 90% of people.

And only a few cross the hundred-year mark. Even if a person avoids any diseases and injuries throughout life, he or she nevertheless inevitably dies of old age. But why in some cases does this "old age" take away 60-year-olds, while in others it spares 90-year-olds? What underlies ageing?

Many authors who touch upon these questions confine themselves merely to references to the "slagging" of the body over the course of life, a kind of poisoning of it. What then are the mechanisms of the further disorders? How does the immune system behave - our main guardian of Health, on which the quality of our life largely depends?

With age, changes also set in in the immune system, affecting all its elements - stem cells, T and lymphocytes, macrophages. Already from early childhood there is a gradual slowing of the "thymic clock", which manifests itself in a decrease of the proliferative activity of T-cells, while the reduction of their effector and helper functions predisposes to infections and malignant tumours, the frequency of which, as is known, increases with age. In old age susceptibility to infections, which are one of the main causes of death, does indeed grow. Respiratory infections and pyelonephritis are especially frequent. With age the frequency of many other diseases also grows - cardiovascular and tumour diseases, diabetes and dementia. Such changes in the body are often called "age-related", "normal for the corresponding age".

Immunodeficiency weakens the control over the appearance of abnormal mitoses - cell divisions - and over the appearance of tumour cells. They arise in the body constantly and quite often; however, possessing a foreign antigenic structure, they immediately come into the "field of view" of the immune sentinels and are immediately destroyed. But if these guards have "overlooked" the moment of their appearance and have not destroyed them in good time, then their antigenic structure is soon recognized as already "self", which, by general biological laws, blocks the production of the corresponding antibodies and determines the outcome of this confrontation between the body and the tumour.

The consequences of immunodeficiency are manifested most vividly in the specific viral acquired immunodeficiency syndrome – in AIDS, in which patients die either from infections or from malignant neoplasms. And senile immunodeficiency differs from its analogue - AIDS - only in the scale of the disorders of immunity, retaining the same essence.

The slowing of the rate of formation of B-lymphocytes in the bone marrow also weakens the formation of antibodies for fighting viral and bacterial infection. With age even the antibodies of blood group affiliation [a and b] weaken.

The function of the immune system depends on the diversity of the antigenic receptors of the lymphocytes. With age, the general decline in the ability of the thymus gland and the bone marrow to generate lymphocytes is combined with antigenic stimulation of their clonal expansion. This is what leads to the appearance of monoclonal immunoglobulins, and the direction of their reactions changes from external (foreign) – to autoantigens. A clear correlation has been revealed between the decline of the depressor function of the thymus with age and the development of autoimmune disorders.

But an even greater danger is presented by the weakening of the suppressor function of T-cells, which is accompanied by the appearance of clones of lymphoid cells that are normally "forbidden" and that react to the body's own antigens, which causes various types of autoimmune pathology. In more than 50% of elderly people various autoantibodies can be detected, although not in high concentrations. That is why the rheumatoid factor causes the appearance of signs of polyarthritis that are not as pronounced as in true rheumatoid arthritis; nevertheless, it is a rare person in old age who does not suffer from pains in the joints, considering them merely the consequence of "salt deposits".

Antinuclear antibodies can often be detected. Characteristic is the appearance of antibodies to thyroglobulin, which causes autoimmune thyroiditis with hypofunction of the thyroid gland. On the other hand, thyroid hormones are necessary for maintaining the proper activity of the immune system, and hypothyroidism only aggravates the immunodeficiency in old age. It is interesting to note that autoantibodies to the three main antigens of the thyroid glands - thyroglobulin, peroxidase and thyroid-stimulating hormone - are detected in healthy individuals aged 18-24 years as well, in 10,6-14,9% of cases, but already at the age of 055-3-4 years. Even in practically healthy donors anticardiolipin antibodies were detected with a frequency of 27%, anti-DNA antibodies – in 17%, antibodies against thyroglobulin and microsomal antibodies in 11 and 7% of donors respectively. Moreover, an increase in the frequency of detection of such antibodies in healthy donors was noted in the period 1992-1995.

Even senile dementia appears as a consequence of the appearance of autoantibodies to elements of the central nervous system. In Alzheimer's disease, gene mutations may possibly contribute to the emergence of the autoantibodies presenilin-1 and presenilin-2. They are detected by immunochemical methods in association with nerve fibres in post-mortem studies of the brains of these patients. Mutations of DNA and RNA contribute to the appearance of protein molecules that differ from normal ones and lead to further disturbances; of metabolic processes in particular, and in Alzheimer's disease a whole cascade of successive disorders arises, leading to the deposition of amyloid in the form of plaques in the vascular walls, to infiltration of microglial cells and, ultimately, an increasing loss of neurons.

As a result of autoimmune processes, symptoms of parkinsonism also appear, but they likewise do not reach in intensity those observed in Parkinson's disease. Autoimmune processes underlie the formation of demyelinating pathology as well, with the appearance of widespread sclerosis of the multiple sclerosis type and of muscular dystrophy of the myasthenia type. Characteristic of old age is the appearance of signs of paraproteinemia with the accumulation of monoclonal M-components of immunoglobulins, resembling now already myeloma disease. Deposition of amyloid takes place in the intercellular spaces, including the formation of senile plaques, which in 60% of the elderly is a characteristic sign of old age. Deposition of amyloid in the myocardium is also a widespread phenomenon in old age.

In recent years attention has been drawn to the state of the liver parenchyma in old age; the size of the liver, the hepatic blood flow and the perfusion of the liver decrease by 30-40% between the third and the tenth decades of life. The frequency of detection of the hepatitis C virus is also growing - from 10% in persons under 35 years to 42% in persons over 60 years, although there was no connection with such risk factors as intravenous drugs, tattoos, acupuncture and surgical operations. Many elderly people, even 20 years after the detection of HCV infection, had no symptoms of liver damage; on biopsy, however, these signs were revealed with sufficient frequency. Until the most recent time the connection between ageing and autoimmune damage to the liver has been ignored. At the same time, with age the prognosis in chronic hepatitis and cirrhosis worsens considerably. If in persons under 60 years the mortality one year after the detection of these diseases is 5%, and after 3 years - 24%, then in persons over 60 years it is 34% and 54% respectively, while for persons over 70 years - already 75% die within a year. In half of the persons over 70 years - hepatocellular carcinoma developed, as a rule, against the background of cirrhosis of the liver.

Thus, as a result of disorders of individual links of the immune system in old age, a whole series of symptoms arises, more blurred than in the corresponding nosological forms of the diseases proper, but it is precisely they that determine the appearance of an elderly person - slowness of reactions, stiffness and lack of coordination of movements, forgetfulness and muscular.

Thus the picture of the disorders of homeostasis that lead to premature old age is becoming ever clearer. These vicious circles of interdependent disturbances can be broken only by the timely removal of all pathological products from the body, which can be fully accomplished only by efferent therapy, primarily - plasmapheresis.

The question arises - when then should such therapy be started? Should one wait for the development of the corresponding manifest symptoms of old age or prevent their appearance? Of course – the latter!

Timely primary prevention of diseases will also be primary prevention of premature ageing. And the main link of such prevention is efferent therapy, aimed at removing that which is visible now and that which has not even manifested itself yet.

These measures are indicated at practically any age, when micro-symptoms appear that show deviations from the normal state:

• Excessively increased fatigability;
• Unusual sensations and aching in the body, in the joints;
• Changes in the appearance of the sclera of the eyes, of the hair, of the nails;
• Wrinkling of the skin of the face, of the hands;
• Memory disorders and noise in the ears;
• Changes in gait, in springiness and in coordination of movements;
• Potency and many others.

Of course, it is important to pay attention not to the appearance of one of the listed signs, but to a whole complex of them, especially if they persist for many days and weeks. One should not ignore rises in arterial pressure (considering them natural or age-related), painful sensations in the area of the heart, even if they can be quickly relieved with the help of medicines - there is no smoke without fire. It means that atherosclerosis is creeping up – one of the main harbingers of old age.

One of the manifestations of involutional processes in women is the climacteric syndrome. This period of restructuring of the hormonal status is accompanied by a number of specific climacteric symptoms - sensations of "hot flushes", of "heat", sweating, irritability, which for a fairly long term disturb the well-being and the "quality of life" of women. Not only the functions of the ovaries are upset, but also those of other glands of internal secretion, in particular – of the thyroid gland, with the development of signs of autoimmune thyroiditis. Metabolic processes are disturbed as well, the level of enzymatic activity decreases, in particular of succinate dehydrogenase, which is a marker of the mitochondria and of the energy processes in the Krebs cycle.

In those cases where the usual therapeutic measures do not help, courses of plasmapheresis make it possible, within a fairly short term, to achieve the disappearance of the symptoms listed above, especially with a short "record" of the climacteric syndrome, when these symptoms are still unstable and pronounced psychovegetative disorders have not developed.

However, plasmapheresis is also indicated in old age, although one cannot count on a substantial reverse development of the organic and systemic lesions that have already set in. Nevertheless, even with pronounced clinical manifestations of ischemic heart disease, of obliterating atherosclerosis of the vessels of the lower limbs and of rheumatoid polyarthritis, courses of plasmapheresis lead to substantial improvements, both subjective and clinical-laboratory.

Thus, at the basis of preventive efferent therapy there should be an annual course of plasmapheresis of up to four sessions, and in the case of signs of immunosuppression or allergy it is advisable to add quantum therapy as well. These measures may be considered primary prevention of malignant neoplasms too. Aeroionotherapy should not be neglected either; its periodic sessions will help to restore the mechanisms of maintaining the electrostatic state of all components of the internal environment, with prevention of pathological biotransformation of the cytoplasm of the cells, and also to lower the risk of diseases.