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THERAPEUTIC APHERESIS IN THE PREVENTIO OF PREMATURE AGING.

Voinov V.A.
I.P.Pavlov first Saint-Petersburg state medical university, Russia

Abstract
The article in question discusses issues related to autoimmune mechanisms of human aging,
which lead to the accumulation of various auto-antibodies, damaging major tissues and organs.
The organism is unable, on its own, to filter out such large molecules. For the purpose of
prevention of premature aging, those large molecules could be separated from the organism with
the help of plasmapheresis.
Key words: plasmapheresis, autoantibodies, premature aging.

There is no doubt that the biologically predetermined person's age is not less than 110
years, and according to some reports should reach 150 years, although in reality the average life
expectancy does not exceed half of that period. Was it ever a golden age of mankind, when
people lived to this age, as evidenced by the Biblical sources, hard to say. On the other hand,
there are those evidence that ancient man lived an average of about 40 years.
Course of illness, injury peacetime and wartime significantly shorten the period of life. If a
person for life even avoid any diseases and injuries, anyway, he will inevitably die "of old age."
But why in some cases the "old age" carries 60-year-olds, and other 90-year-old spared ? What is
the basis of aging?
Many authors affecting these issues are limited to the directions on the "slagging" body for
life, a kind of self-poisoning him. What are the mechanisms of subsequent disorders? How does
the immune system our main guardian of Health, which largely depends on the quality of our
lives?
Indeed, with advancing age, the changes in the immune system grow up also, affecting all
of its elements stem cells, T- and B-lymphocytes, macrophages. Since early childhood, there is
a gradual deceleration "thymic hours" that manifests itself in reduced proliferative activity of T-
cells and a decrease in their effector and helper functions predisposes to infections and
malignancies, the frequency of which is known, increases with age. In old age really increased
susceptibility to infections, which are some of the main direct causes of death. There are
especially frequent respiratory infections, pyelonephritis [1]. With age, the frequency increases
also many other diseases cardiovascular disease and cancer, diabetes and dementia. Such
changes in the body are often referred to as "age", "normal age appropriate."
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Immunodeficiency weakens control over the appearance of abnormal mitosis cell
division and the appearance of tumor cells. In the body, they are constantly appearing and often
enough, however, having an alien antigenic structure, they immediately fall into the "field of
view" immune custody and immediately destroyed. If these guards "overlooked" when they
occur in a timely manner and did not destroy them, they soon recognized their antigenic structure
like "own" and according to biological laws that blocks the production of corresponding
antibodies and predetermines the outcome of this confrontation between the body and the tumor.
Therefore, the most terrible consequence of age immunodeficiency in the elderly is to increase
the probability of tumor growth [2], which is confirmed in specialized studies of oncologists [3].
Function of the immune system depends on the diversity of antigen receptors of
lymphocytes. With age, the general decline in the ability of the thymus and bone marrow
lymphocytes in the generation of antigenic stimulation combined with their clonal expansion.
This leads to the emergence of monoclonal antibodies, and the direction of their reactions varies
with the external (foreign) to autoantigens [4].
But the greatest danger is the weakening of suppressor T-cell function, which is
accompanied by the appearance of "forbidden" under normal conditions of lymphoid cell clones
reacting to self-antigens of the organism that causes different types of autoimmune pathologies,
which is consistent with a higher prevalence in the elderly and senile various autoimmune
diseases [2]. More than 50% of the elderly different autoantibodies can be detected , but not at
high concentrations of [5]. Therefore, rheumatoid factor is the emergence of signs of arthritis, is
not as pronounced as in true rheumatoid arthritis, but a rare person in old age does not suffer
from joint pain, considering them only consequence "salt deposits." There are characterized by
the appearance of antibodies to thyroglobulin, causing autoimmune thyroiditis with
hypothyroidism. On the other hand, thyroid hormones are necessary to maintain proper immune
system activity, and hypothyroidism only aggravates immunodeficiency in old age.
Interestingly, autoantibodies to three major thyroid antigens thyroglobulin, peroxidase
and thyroid-stimulating hormone found in healthy individuals aged 18-24 years 10.6-14.9% of
cases, but in the age of 55-64 years, this frequency increased to 24.2-30.3% [6]. Even healthy
donors showed anticardiolipin antibodies with frequency 27%, of anti-DNA antibodies 17%
[7].
Even senile dementia is a consequence of the appearance of autoantibodies to the elements
of the central nervous system. In Alzheimer's disease mutations in genes may contribute to the
appearance of autoantibodies presenilin-1 and presenilin-2 protein detectable by
immunochemical methods in relation to the nerve fibers postmortem studies of the brain of these
patients [8]. Mutations in DNA and RNA contribute to the appearance of protein molecules that
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differ from normal, and further leading to metabolic disorders. In particular, during Alzheimer's
disease there are arrived cascade successive disorders leading to the deposition of amyloid as
plaques in the vascular walls, infiltration of microglia cell, apoptosis and ultimately increasing
neuronal loss. And also show signs of cerebral amyloid angiopathy, an important pathogenetic
factor in vascular disorders of the brain and even intracerebral hemorrhages. One reason for this
is the mutation of presenilin-1, which depends on the increase of amyloid- deposits [9].
Both the reasons, and methods of treatment of this severe brain pathology are unknown,
however the above-stated facts testify to the autoimmune nature of this illness of "accumulation"
and with all definiteness raise a question of possibility of use of apheresis therapy methods, at
least, for delay of progressing of this serious illness with the unpromising forecast and in recent
years successful experience of application of a plasma exchange with replacement of the deleted
plasma with albumin is already described [Boada M. et al., 2009, 2014; Boada-Rovira M., 2010;
Roca I., Cuberas-Borros G., 2010]. It is based that 90% of the circulating beta amiloid are
connected with albumin and after a plasma exchange donor albumin will mobilize amyloid from
a brain, thereby promoting improvement of cognitive functions of these patients [Anaya F.,
2010].
As a result of autoimmune processes appear and symptoms of Parkinson's disease, but
also do not reach the intensity observed in Parkinson's disease itself. Aetiopathogenesis of this
progressive neurodegenerative disorder primarily with motor dysfunctionis not entirely clear,
though there is evidence of the presence of autoimmune disorders. Revealed are elevated levels
of cytokines and complement in the cerebrospinal fluid increases against T-cell autoantibodies
(anti-alpha-synuclein and anti-GM1-ganglioside) and vasoactive peptides in peripheral blood
[Staines DR, 2007; Monahan AJ, 2008; Benkler M et al., 2009]. This points to the possibility of
using plasmapheresis in the treatment of this disease [Leopold N.A. et al., 1999; Staines D.R. et
al., 2008]. S.G.Morozov et al. (1997) successfully performed courses of plasmapheresis in 29
patients with severe manifestations of Parkinson's disease with a decrease in the index of neuro
defeciency from 28 to 8 units of Webster scale and levels of autoantibodies.

Autoimmune processes underlie the formation also demyelinating disease with the advent
of widespread sclerosis type of multiple sclerosis and muscular dystrophy type myasthenia.
Characteristic of old age is the appearance of signs of paraproteinemia with accumulation of
monoclonal immunoglobulin M- components resembling now myeloma.
True amyloidosis resemble amyloid deposition in the intercellular spaces, including the
formation of the so-called senile plaques that 60% of older age characteristic feature appears.
Amyloid deposition in the myocardium is also common in the elderly [10].
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In recent years, drawn attention to the condition of the liver parenchyma in old age. Size of
the liver, hepatic blood flow and perfusion of the liver is reduced by 30-40% between the third
and tenth decades of life. Until recently it was ignored the link between aging and autoimmune
liver disease. In this case, age is much worse prognosis in chronic hepatitis and cirrhosis. Half of
those over 70 years of developing hepatocellular carcinoma, usually on a background of cirrhosis
[11].
One of the manifestations of involutive processes in women is menopause. This period of
adjustment of the hormonal status is accompanied by a number of specific menopausal
symptoms feeling "tide", "heat", sweating, irritability, which is a sufficiently long period
violates health and "quality of life" of women. Upset not only the functions of the ovaries, but
also in other endocrine glands, in particular with the development of thyroid symptoms of
autoimmune thyroiditis. There are broken also metabolic processes, decreasing the level of
enzyme activity, in particular the succinate dehydrogenase, being marker of mitochondrial and
energy processes in the Krebs cycle [12]. In cases where the usual therapeutic measures do not
help, plasmapheresis courses allow in a relatively short time to achieve the disappearance of the
above symptoms, especially at small "seniority" climacteric syndrome when these symptoms are
still unstable and did not develop pronounced psycho-vegetative disorders [13]. The positive
effect of plasmapheresis courses lasted for 3-18 months. In 67.5% of the women with climacteric
syndrome marked hypercholesterolemia and courses of plasmapheresis also help to normalize
lipid metabolism also [14].
Thus, as a result of disorders of detached parts of the immune system in old age there is a
wide range of symptoms, more worn out than the corresponding actual nosologic forms of
diseases, but it is they who determine the shape of an old man slow response time, stiffness and
incoordinate movements, muscle weakness and forgetfulness etc.
With aging occurs and discharging the electrostatic forces of the organism, decreasing
membrane potential, decrease of the ionization cytoplasm with coarsening of biocolloids
particles, a decrease of their ability to swell, degradation and induration of protoplasm, its
transition from a sol to a gel state. During ontogeny it is generally reduced hydrophilic colloids.
Limiting the content of negatively charged ions in the inhaled air is one of the main factors
accelerating the processes of biotransformation colloidal state of cells and tissues and premature
aging.
It needs no special explanation the role of atherosclerosis in the process of premature
aging also. Many researchers even consider atherosclerosis as a natural process associated with
aging [15]. However perfidy of atherosclerotic vascular lesions is almost complete asymptomatic
until the moment of blockage of the lumen when late to think not only on the prevention of these
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lesions, but even a qualitative treatment. Therefore it is necessary to closely monitor how the
content of lipoproteins in the blood, and known for soft signs of vascular disorders.
The examination of elderly persons whose average age was observed hypertension, there
are found greater frequency of intellectual disability and depression with symptoms of cerebral
atrophy [16]. Increasing age occurs also the accumulation of toxic products of lipid peroxidation
on the background of depressed antioxidant defense system [17]. Older people are also
observed higher levels of acute phase proteins with signs of oxidative stress, which confirms the
special clinical value of the therapeutic apheresis [18].
On the one hand one could regret that the Creator or Nature itself (depending on the world
outlook) were not wise enough, without providing more stringent ban on the formation of
autoimmune processes. However, on the other hand, maybe this is and the highest was their
wisdom, because otherwise life would go on indefinitely long, and if it is impossible to
completely avoid the accumulation of such "micro-errors" of immune and metabolic processes, it
would create a number of other intractable problems.
So more and more clearer picture of disorders of homeostasis, leading to premature aging.
More Seneca said that "old age is an incurable disease", and therefore the attitude to it should be
as a disease. And disease can and should be treated! Mainly you should stop these vicious circles
interdependent violations that can only be done in a timely removal of all accumulated large
molecular pathological products from the body, that the kidneys are not output, and do not
destroy the organs of biotransformation. And to completely solve this problem could be only
apheresis therapy, mainly plasmapheresis.
The main task is not just an extension of life. If such a life will be extended with symptoms
of dementia and helplessness in a wheelchair or on a bed, then such work is not worth pursuing.
It should be borne in mind that the level of health physical function and psychological status
are more important for the elderly than the duration of their lives. [19]
The challenge is to increase the immune potency, which means the extension of the
productive middle age while maintaining the level of health and energy, ie, quality of life, on
which depends the creative and physical performance, the opportunity to experience life in all its
colors. The challenge is maintaining the "youth to old age" [20, 21].
The question is when it starts aging and when to start its treatment? Wait for the
development of appropriate age manifesting symptoms or prevent their occurrence? Of course
the last one!
As mentioned above, many diseases, as well as old age creep up unnoticed. For many
months, even years growing micro-disorders various parts homeostasis until reaching a critical
level when the symptoms of a particular disease [22].
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Thus, according to the summary data of research pathologists who reviewed the results of
3000 autopsies of young people aged 15-34 years who had no clinical evidence of cardiovascular
disease and died as a result of accidents [23, 24] revealed the following picture: all teens
surveyed were found fatty streaks in some segments of the arteries. These changes grew with
age, with lesions of the coronary arteries were found in their walls leukocytes and circulating
immune complexes; obesity increased the risk of vascular lesions; changes in the growth of
abdominal aorta increased sharply in smokers; smoking and hypertension clearly correlated with
the development of primary atherosclerotic plaques in young humans. Given that none of these
young people have not seen any manifestations of cardiovascular disease, it is clear that their
primary prevention was necessary to begin without waiting for the manifesting symptoms.
The same can be said about micro-shears and soft signs of other diseases. Task is to find
these micro-disorders not turn a blind eye and do not consider them a fluke.
In many cases, involutive processes in old age do not require medical treatment, and even
more so, the drugs can harm because even when used correctly, they can cause a number of other
functional disorders [7]. In recent years, many authoritative experts note that "pills strategy",
which is based on Western medicine, practically exhausted itself. This not only practitioners, but
even pharmacologists recognized that "tablets" really effective in less than 30% of cases [22].
Timely primary prevention of diseases will serve as the primary prevention and early aging
also. And the main point of such prophylaxis is apheresis therapy aimed at removing what can be
seen now, and that is still not even manifested [20, 25, 26, 27].
Various cosmetic surgery is certainly justified, but after the elimination of defects in shape,
posture, wrinkles, remain inside "wrinkles of internal environment" and all the reasons that
caused them. Therefore, these operations must be accompanied by reorganization of the internal
environment, and some complicated plastic surgery should be performed only after the
apheresis- and immunotherapy for the prevention of inflammatory complications, bringing to
naught all the cosmetic effects.
Not only an honor, but old age is necessary to protect from an early ages! This means that
there can not be any specific age at which we should start measures to prevent senile disorders.
We must realize that this already come organic lesions of organs and tissues are resistant reverse
development, so effort should be made before the onset of these lesions.
These measures are indicated at almost any age, when there's some soft signs showing
deviations from the normal state excessive fatigue, unusual sensations and body aches, joint
pain, and changes in the form of the sclera of eyes, hair, nails, cutaneous elasticity, skin wrinkled
face and hands; memory disorders and tinnitus, changes in gait and movement coordination,
potency, and many others. Of course it is important to pay attention to the appearance of more
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than one of these symptoms, and their whole complex, especially if they are held for many days
and weeks. Should not be ignored rises in blood pressure (assuming their natural or age), pain in
the heart, even if using drugs they can be quickly cut short no smoke without fire! So creeps
atherosclerosis one of the main precursors of age.
Founder application of apheresis therapy in gerontology can be considered Greek hero
Jason, who tried to restore youth to his father, replacing his blood with new wine. And although
this attempt failed, however, that removal of pathological products together with part of the
normal components of the internal environment of the body that are in the blood plasma, is
achieved not only its reorganization, but also given a powerful impetus to the renewal of her
fresh, young ingredients. That is, the effect of rejuvenation is achieved simultaneously with the
removal of accumulated gradually autoantibodies and other pathological metabolites such as
exo- and endogenous origin.
Thus, based on the preventive apheresis therapy should be an annual rate of up to four
sessions of plasmapheresis and in the case of signs of allergy or immunosuppression it is
appropriate and expedient to add also photohemo-therapy (UVR or laser irradiation of blood).
Should not be neglected and aeroionotherapy also, ie, walks on "fresh air" that should help
restore mechanisms to maintain electrostatic state of all components of the internal environment
to the prevention of cytoplasm pathological biotransformation.
Naturally, the apheresis therapy should not preclude the need to lead a healthy lifestyle
exercise, proper diet (the main thing do not overeat), and, of course, not to poison himself
smoking, alcohol, drugs [2]. It was noted that food restriction increases life span of mammals,
reducing the frequency age-depending pathologies including cardiomyopathy, and slows
physiological disorders associated with aging. Limitation of food leads to an increase in
myocardial contractility [28]. At the same time we must recognize that obesity is the most
common disorder and its frequency increases with age.
However, even in old age plasmapheresis also indicated, although show a significant
regression of already occurring organ and systemic lesions is not expect. E.A. Chumaeva et al.
[29] reported that after a course of plasmapheresis and photohemotherapy at 91.9% of elderly
patients improved overall health, in 68.9% of patients with elevated blood pressure levels it
decreased with disappearance of headaches and tinnitus, vision improved.
But if the treatment of a variety of acute and chronic diseases now there is no doubt the
advisability of apheresis therapy, then with respect to the more practically healthy person may
have doubts about the justification for such action. After all, there is no assurance that the
expected health problems do arise. Virtually impossible to prove that we really have prevented
the development of the disease, which still has not been diagnosed. On the other hand, we must
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be absolutely sure that such an invasive procedure as plasmapheresis will not cause any
complications.
Such confidence is still there, as experience shows that methodically correct operation
well-trained personnel, using only disposable needles and systems, virtually no threat to health of
the patient. In addition, avoiding the use of donor plasma and other protein-based drugs to
replace deleted plasma gives an additional guarantee to prevent infection viral diseases and
immunization of foreign antigens (donor lymphocytes, for example).
Stop can only sufficiently high cost of plasmapheresis, although in our country (Russia), it
is much lower than in Europe or America. A well-established Russian industrial production
plasmafilters "Rosa" and the development of simple and safe methods and apparatus for
membrane plasmapheresis Hemofenix ("Trackpore Technology Company) makes quite
realistic these important tasks in almost all hospitals up to their municipal managers.

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