Database research on anti-aging

Leek (Allium porrum) is one of the worthy members of the family Alliaceae. For centuries this edible plant was known due to its medicinal properties.

When a patient has serious and irreversible disorders of the gastrointestinal tract, intestinal tissue engineering can be used as a promising approach. This approach proposes to replace dysfunctional or missing intestinal tissues with an implant that imitate physiological functions of the intestine. Different research groups have developed methods allowing to harvest intestinal stem cells from animal embryos or newborns. Such cells can be introduced into natural or synthetic carrier materials. At present, this methodology is rather standardized. That allows to create new intestinal tissue that resembles natural intestine in many morphological features and functional characteristics. Intestines created in that way have already allowed to improve or even cure of clinical syndromes of malabsorption in researches on rodents. Later, new intestinal tissues of large animals have been created. Prof. M. Stelzner’s researches are concentrated on the stem cell therapy in application to intestinal mucosa. They cover the use of bioengineered scaffold supporting the growth of cells transplanted into the patients who have some parts of their intestinal tract removed surgically. Intestinal stem cell organoid transplantation generates functional intestinal neomucosa and is used therapeutically to improve nutrient absorption and cure bile acid malabsorption in rats. The researchers from M. Stelzner’s team hypothesized that intestinal organoids can be harvested and transplanted to generate intestinal neomucosa in a large animal model — a dog. As the result of the experiments, in the the group where intestinal organoids were harvested from fetuses and allotransplanted into 10-month old mother animals, neomucosal growth was identified in 11 of 12 polyglycolic acid scaffolds after allotransplantation of fetal organoids. The neomucosa resembled normal canine mucosa in structure and composition. Intestinal stem cell organoid transplantation can be used to generate neomucosa in dogs. This is a great success and an important step towards clinical use of the intestinal tissue engineering in people. This is the first report of successful generation of intestinal neomucosa using intestinal stem cell organoid transplantation in a large animal model.

Dr. J. Nikolich-Zugich’s laboratory is interested mainly in two lines of research: 1) investigations on the biology of cytotoxic T-lymphocytes and their role in the normal organism, during aging and infectious process, and 2) investigations on immunosenescence and development of methods of its correction. J. Nikolich-Zugich’s laboratory studies caloric restriction as a way to improve T-cell functioning during an immune response in long-lived animals. Research on long-lived primates showed that the number of naive T-cells and the diversity of their receptors increased in animals put on caloric restriction diet. Moreover, decreased production of inflammatory cytokines indicated that the number of old memory T-cell also went down. Thus, caloric restriction can rejuvenate senescent immune system of primates leading to decrease in the number of memory T-cells in the common pool.

Prof. M. A. Birchall with his colleagues have developed a model of restoration and transplantation of brain nerves which allows to improve locomotor innervation. This model is a central part of their organ replacement program (it concerns, particularly, the larynx). In this program, Schwann’s cell obtained from stem cells are used, as well as growth factors promoting optimal restoration of innervation. While preparing for an operation for transplantation of the bioengineered trachea, the workers from M. A. Birchall’s group have used biopsy of patient’s bronchial mucus. In the future, M. A. Birchall’s laboratory plans: larynx transplantation in human; development of tissue-engineered larynx; clinical trials in maxillary nerve restoration using neurotrophin and other peptide-cell constructions. Subsequent cultivation of those cells and conformation of their epithelial phenotype have allowed to obtain autologous epithelial cells which may be placed into a bioreactor and used in implantation.

During aging, we observe decrease in the content of the growth hormone (GH) and insulin-like growth factor I, estrogen deficiency in women, decrease in the testosterone level in men, decrease in the lean body weight, increase in the fat weight and other changes linked to the growth hormone deficiency. In not elderly people, treatment of the growth hormone deficiency with the recombinant human growth hormone (rhGH) improves the proportion of muscle tissue to fat tissue in the organism, enhances muscle strength, physical endurance and the solidity of bones, lowers blood level of cholesterol and the risk of cardiovascular diseases. However, the rhGH therapy is often accompanied with carpal tunnel syndrome, peripheral edema, articular pain and swelling, gynecomastia, glucose intolerance. Probably, it also increases the risk of cancer development. Experimental data show that, in elderly men, low testosterone level correlates with the loss of the lean body weight and muscle strength, and with increase of the fat weight. Probably, low testosterone level is also associated with the decrease in the solidity of bones, loss of insulin sensitivity, cognitive and emotional decline, and reduction of sexual function. It is necessary to carry out additional investigations which will reveal how growth hormone influence organism’s functioning, what its positive and negative effects are. Replenishment of testosterone in elderly men shows some positive effects at each of those parameters.

Anthropogenic factor acquires more and more value in biosphere development invading in natural processes and affecting the quality and the rate of harmlessness of essential environmental sources for human health.