Biomedicine

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.