The emergence of immune disorders in aging is explained by many factors, including thymus dysfunction, decrease in the proportion and function of naïve T cells, and so forth. There are several approaches to preventing these changes, such as thymus rejuvenation, stem cells recovery, modulation of hormone production, and others. Our investigations of heterochronic parabiosis have shown that benefits of a young immune system, e.g., actively working thymus and regular migration of young hematopoietic stem cells between parabiotic partners, appeared unable to restore the immune system of the old partner. At the same time, we have established a progressive immune impairment in the young heterochronic partners. The mechanism of age changes in the immune system in this model, which may lead to reduced life expectancy, has not been fully understood. The first age-related manifestation in the young partners observed 3 weeks after the surgery was a dramatic increase of CD8(+)44(+) cells population in the spleen. A detailed analysis of further changes revealed a progressive decline of most immunological functions observable for up to 3 months after the surgery. This article reviews possible mechanisms of induction of age-related changes in the immune system of young heterochronic partners. The data obtained suggest the existence of certain factors in the old organisms that trigger aging, thus preventing the rejuvenation process.

The properties of the binding of recombinant rat nucleoside diphosphate (NDP) kinase isoforms a and p (NDP kinase a and l$ respectively) to bleached bovine retinal rod outer segment (ROS) membranes were investigated. It was found that: (1) both NDP klnase isoforms interacted with ROS membranes in a pH-, cation-and GTP@dependent manner; (2) the retinal G-protein transducm was an obligatory factor for the interaction; (3) the apparent affhdty of NDP klnase a for ROS membranes was about loo-fold higher than that of NDP kinase fl; and (4) an a-isoform-specific peptlde, corresponding to the sequence of the N-terminal third (variable region), had the ability to displace bovine NDP khtase from ROS membranes. The results suggest the possible involvement of NDP kinases in cellular regulation via interaction with G-proteins and provide a structural basis for the possible differential roles of mammalian NDP khtase isoforms in the cell.

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Whether nucleoside diphosphate kinase (NDPK) is involved in neuronal differentiation was investigated with special reference to its enzyme activity. Neurite outgrowth of PC12D cells induced by nerve growth factor or a cyclic AMP analog was suppressed to some extent when inactive NDPKs (the active site histidine 118 was replaced with alanine), not active forms, were transiently overexpressed. This suppression was more definite in their stably expressed clones. NDPKbeta-transfected clones and, to a lesser extent, NDPKalpha-transfected clones, but not inactive NDPK-transfected clones, extended neurites without differentiation inducers. These results imply that NDPKs may play a role by exerting their enzyme activity during differentiation of PC12 cells.