6533b850fe1ef96bd12a8568

RESEARCH PRODUCT

CALPAIN ACTIVITY MAINTAINS GOOD HEALTH OF CENTENARIAN T CELLS; SUMMARY OF THE CALPACENT PROJECT

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description

Causes of aging-associated deterioration of human immunity, and the reasons why the immune system of the oldest old individuals (centenarians) is relatively robust, remain moot. Intracellular proteolysis system of two proteases – µ- and m-calpain – and their inhibitor – calpastatin (the calpain-calpastatin system (CCS)) - is active in resting human peripheral blood T cells, participating in maintenance of their readiness to proliferate and secrete cytokines in response to stimulation. The amounts of the CCS proteins decrease in resting T lymphocytes of healthy elderly, only to return in the centenarians to those levels seen in the young individuals. We compared the calpain activities and the levels of transcription of the CCS genes in the resting and stimulated peripheral blood T lymphocyte populations of young, elderly and centenarians, and correlated these activities with the strength of proliferative and cytokine secretion responses to a polyclonal stimulation. Calpain activities significantly decrease in the resting T cells of the elderly compared to the young, and rise again in centenarian lymphocytes, in parallel to the relatively higher proliferative and secretory dynamics and CCS genes’ transcription in the centenarian than in elderly T cells. Calpain activity seems to increase the levels of phosphorylation of chosen signal transduction molecules. Concluding, we propose that the CCS activity is essential for the maintenance of adequate level of the T cell responses, that its decrease in the elderly is one of the reasons for the immunosenescence, while its relative preservation may facilitate relative robustness of T cell responses in the centenarians.