Is it possible to overcome aging? Today and tomorrow cell therapy. Leonid Yu. Prokhorov
fat. The amount of muscle tissue attains a peak at the age of 20—30 years, then its decline begins, at first slowly, and then with increasing rate, especially after 50 years. In this connection there occurs a decrease in muscle strength; at the age of about 70—80 years such strength reduced approximately two times. The subcutaneous fat layer decreases and the volume of internal fat in the abdominal area increases.
►Aging of the nervous system manifests itself in many ways. This applies to both the Central nervous system (brain) and the peripheral nervous system. Aging is manifested in functional and psychological changes that affect mental and physical performance, memory, emotions, complex behavioral reactions and other aspects of life. Structurally, aging is expressed primarily in reduced number of nerve cells – neurons. Although some reduction may occur already shortly after birth, a significant loss takes place in relatively late period, since the age 50—60 years, and such reduction is uneven in different areas of the brain. The degree of neuronal loss in the brain cortex of old people can reach as much as 40—50% or even more. In old age, neuronal density and size of neurons, diminish, together with deposition of pigment.
Age phenomen are also observed in the spinal cord and peripheral nervous system, they are observed in all parts of the vegetative nervous system (Khrisanfova, 1999).
– Aging worsens the condition and functions of other systems, tissues and organs of the body, including sense organs, cardiovascular, autonomic and immune systems, digestive organs, endocrine system, etc. (Guide to gerontology, 2005).
Now we can definitely affirm that senile changes may not be completely eliminated with diet, use of herbs, drugs, vitamins, physical exercise and the like.
How can we stop aging? The following sections will be described that the first step has already been done, and it is a cell therapy for a skin by its own cells. The next steps will be aimed at improving this technique and extending it to other tissues, systems and human organs.
CHARACTERISTICS OF THE HUMAN SKIN AND CAUSES OF SKIN AGING
The main cellular elements of connective tissue are fibroblasts. Fibroblasts are cells of mesenchymal origin, round or elongated, spindle-shaped or with flat shape, spikes and oval nucleus (Fig. 3). The state and function of the main extracellular components of connective tissue: collagen, elastic and reticular fibers and intercellular matrix, depend on the functional activity of fibroblasts. As the result of differentiation of the fibroblasts become less active, mature cells – fibrocytes.
Fibroblasts are the main cells of the middle connective tissue layer of the skin, called derma (Fig. 4, 5). The principal function of fibroblasts in dermal skin layer is participation in metabolism of cellular substance. Fibroblasts of the skin synthesize and secrete into the environment a large number of biologically active substances, among which there are various growth factors, extracellular matrix components and enzymes. This process takes place continuously, and due to it intercellular substance is constantly replaced. Particularly intense is metabolism of hyaluronic acid (Kricheli et al., 2004). As in all other organs and tissues of the human body, there are age-related changes in the skin during the whole life.
In aging skin, the thickness of the dermis decreases, the moisture content in it falls, and as a result of this process the skin loses elasticity. The consequence is the formation of wrinkles. Aging of the skin in different parts of the body proceeds unevenly. Particularly rapid is the aging of exposed skin. The reason for this, as described above, is photo aging (because of exposure to sunlight), as well as atmospheric effects. At the same time, age-related skin changes are less pronounced in covered areas.
It is believed that one of the main causes of skin aging is a decrease in the ability of skin fibroblasts to divide with age. As a result of this process, the number of fibroblasts in the skin decreases, and they become less active. Therefore, if to stimulate proliferative and synthetic activity of fibroblasts, in any way, then it will be possible to improve skin conditions (Krikheli et al., 2004).
In addition, in the skin there occurs a decrease of the amount of collagen fibers and their hydration, they lose the ability to swell and become rigid; as a result the turgor is decreased, and wrinkles appear. At the same time, the skin loses lipids, its protective mantle breaks down, and it becomes vulnerable to disruption (Guide of gerontology, 2005).
As the number and activity of fibroblasts is reduced, the remaining cells are unable to compensate for senile changes in the skin. Therefore, if to increase the number of young active fibroblast cells in the skin, it is reasonable to wait for the improvement of its condition due to the fact that fibroblasts will produce young collagen and elastin, and this will increase the elasticity of the skin and its turgor; as a result, the wrinkles well be smoothed.
METHODS OF SKIN REJUVENATION
In order to correct age-related changes in the skin, there is a variety of currently used methods (peels, polishing, lifting, etc.) and preparations (toxin of botulism, components of extracellular matrix and connective tissue, etc.). Many of these methods are aimed at stimulating skin cells, in particular fibroblasts. However, it can be possible to solve the problem in
another way – by increasing the number of fibroblasts in the skin by means of transplanting them to the places where needed.
Before transplantation of fibroblasts became a reality, researchers had to solve many methodological questions, including those of safety of similar procedures.
Significant progress has been achieved in this regard when researchers became able to cultivate the cells, i. e. maintain the viability of fibroblasts outside the body, or in other words in vitro. In 1961, L. Hayflick and P. S. Moorhead (Hayflick, Moorhead, 1961) reported that even under optimal conditions of in vitro cultivation, human embryo fibroblasts were only capable of dividing a limited number of times (50 ± 10). In subsequent studies, this observation was repeated many times. The last phase in the life of cells in culture hase been identified as cellular senescence, and the phenomenon received the name of the author as Hayflick limit.
After the establishment of Hayflick limit and as a result of numerous studies, it was found that normal fibroblasts in culture retain a diploid karyotype and have a limited life expectancy. In addition, normal cells lack oncogenic potency. These requirements to cultures of normal cells were issued in the form of normative documents.
If these requirements are met, it is possible to use human fibroblasts cultivated outside the body for the production of immunobiological prepartions, and then for therapeutic purposes. Scientific research and clinical developments in this area are very intensive, due to general rise of cellular technologies based on stem cells.
Currently, there are two main approaches to the treatment of skin with preparations containing live fibroblasts. On the one hand, methods and preparations for the treatment of skin defects due to wounds and burns became widely known with the help of cultures of allogenic (from another organism) embryonic fibroblasts. An alternative to these methods is the possibility of using autologous (a person’s own) human fibroblasts for cell replacement therapy of the skin (Zgursky, 2004).
It is believed that the best results of cell therapy are obtained by using cultures of embryonic fibroblasts, which have a greater proliferative potential than cultures from adult donors. However, the use of cells derived from embryos has a number of limitations, including ethical ones. At the same time, data accumulate that a person’s own fibroblasts retain their potential during aging, despite a decrease in their number in the aging organism (Terekhov, 1984).
To achieve primary results, it is necessary to obtain fibroblast cultures from