The Rejuvenation of the Immune System: Physiological, Cellular, and Molecular Mechanisms

Abstract

Abstract"ge-related immune dysfunction has been confirmed by many studies. "ll of these changes result in increased susceptibility to infectious diseases and pathological conditions associated with inflammation or autoreactivity. To prevent these changes, we used various model approaches as follows i the models of hematopoietic stem cells HSCs transplantation in irradiated chimeras, ii the model of heterochronic parabiosis that provides regular physiological exchange by blood factors between partners, and iii cocultivation of lymphoid cells and niche-forming cells in vitro to determine its intercellular communication mechanisms. It was shown that the old HSCs equally effectively restore the immune system of young animals and their own. "ut, the young hematopoietic cells behaved like old in the old organism. Parabiosis model demonstrated that regular exchange by blood factors between heterochronic partners does not lead to the old system rejuvenation. "nd we observed impaired capacity of splenic CD c + DC and macrophages from young heterochronic parabionts to co-stimulate proliferation of T-cells in vitro with statistically significant decrease in nuclear factorkappa " NFκ" p and increased expression of Iκ"α during early activation events. These findings suggest that age-related changes in the immune system are multifactor process, and whole-system environment of the organism plays a crucial role in the occurrence of age-related immune system alterations.