The paper considers age-associated alterations of intracellular and intercellular cascades of transduction of
proliferative, differentiating, pro- and antiapoptotic signals, their interaction and influence on proliferative activity,
differentiation and apoptosis of the immune system cells. One of initial causes of these alterations is accumulation with age of a
growing number of antigens exposed on the surface of antigen-presenting cells. As a result of chronic antigenic stimulation, caused
by this factor, an insufficient quantity or a slowed down appearance of growth factor receptors (in particular, IL-2 receptor) and
costimulation molecules, primarily CD28, on T-cells membrane is observed. Because of this proliferative and antiapoptotic signals,
received by T-cells, have a smaller intensity that predetermine reduction of their proliferative activity, and also activity of
telomerase, and a greater susceptibility to apoptosis. Permanent activation of immune system is also reflected in age-related
increase of expression of CD95 and type I tumour necrosis factor receptor by lymphocytes (that aggravates their susceptibility to
apoptosis), and in intensification of proinflammatory cytokine synthesis. The second main cause of alterations in the immune system
is an age-related decrease in the synthesis of growth factors that are necessary for cell survival and proliferation. In particular,
because of the lack of IL-7, apoptosis intensity of maturing T-cells increases in thymus. Thymic stromal cells remain without contact
signals and growth factors generated by lymphocytes, and also undergo apoptosis that causes further reduction of T-lymphopoiesis.
Similar events also occur in bone marrow that predetermines age-related decrease in B-lymphopoiesis and in telomerase activity of
haemopoietic stem cells, and also their proliferative potential reduction.
Key words: lymphocyte, aging, apoptosis, proliferation, differentiation, intracellular and extracellular signal
transduction pathways
