Expression of cellular protective proteins SIRT1, HSP70 and SOD2 correlates with age and is significantly higher in NK c

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RESEARCH

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Expression of cellular protective proteins SIRT1, HSP70 and SOD2 correlates with age and is significantly higher in NK cells of the oldest seniors Lucyna Kaszubowska1*, Jerzy Foerster2, Jan Jacek Kaczor3, Daria Schetz4, Tomasz Jerzy Ślebioda1 and Zbigniew Kmieć1

Abstract Background: NK cells are key effector lymphocytes of innate immunity provided with constitutive cytolytic activity, however, their role in human ageing is not entirely understood. The study aimed to analyze the expression of proteins involved in cellular stress response sirtuin 1 (SIRT1), heat shock protein 70 (HSP70) and manganese superoxide dismutase (SOD2) in non-stimulated NK cells of the oldest seniors (n = 25; aged over 85; mean age 88 years) and compare with NK cells of the old (n = 30; aged under 85; mean age 76 years) and the young (n = 32; mean age 21 years) to find potential relationships between the level of expression of these proteins in NK cells and longevity. The concentration of carbonyl groups and 8-isoprostanes in NK cell lysates reflecting the level of oxidative stress was also measured. Results: The group of the oldest seniors differed from the other age groups by significantly higher percentage of NK cells expressing SIRT1, HSP70 and SOD2. The concentration of both carbonyl groups and 8-isoprostanes in NK cell extracts remained within the normal range in all age groups. The percentage of NK cells with the expression of, respectively, SIRT1, HSP70 and SOD2 correlated positively with age. Some correlations between expression levels of particular protective proteins SIRT1, HSP70 and SOD2 were observed in the study population. Conclusions: The increased expression of cellular protective proteins SIRT1, HSP70 and SOD2 in NK cells of the oldest seniors seems to correspond to longevity and the observed correlations may suggest the involvement of these proteins in establishing NK cell homeostasis specific for healthy ageing process. Keywords: NK cells, Ageing, Immunosenescence, Seniors, SIRT1, HSP70, SOD2, Oxidative stress, Innate immunity

Background The main function of NK cells is related to immune response against viral infections, tumor cells and intracellular pathogens. These lymphocytes reveal also some regulatory properties to activate other cells of both innate and adaptive immunity by secretion of cytokines and chemokines [20]. NK cells do not act in a constant manner but rather adapt to the temporary conditions of the cellular environment. They can display a form of antigen* Correspondence: [email protected] 1 Department of Histology, Medical University of Gdańsk, Dębinki 1, Gdańsk PL-80-211, Poland Full list of author information is available at the end of the article

specific immunologic memory demonstrating attributes of both innate and adaptive immunity [52]. Human NK cells consist of two functional subsets differing in the cell surface expression of CD56, i.e. immunoregulatory CD56bright cells, considered to be precursors to the cytotoxic NK CD56dim cells [18, 44]. These NK cell subsets are di