Abstract

BackgroundNK 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.ResultsThe 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.ConclusionsThe 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.

Highlights

  • NK cells are key effector lymphocytes of innate immunity provided with constitutive cytolytic activity, their role in human ageing is not entirely understood

  • Continuous lowdose oxidative stress during ageing results in adaptive responses based on the activation of NF-κB and subsequently superoxide dismutases (SODs) with a key role played by the mitochondrial manganese dismutase (SOD2)

  • After merging two groups of seniors into one we still observed that the population of seniors presented significantly higher percentage of NK cells compared to the young

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Summary

Introduction

NK cells are key effector lymphocytes of innate immunity provided with constitutive cytolytic activity, their role in human ageing is not entirely understood. The main function of NK cells is related to immune response against viral infections, tumor cells and intracellular pathogens These lymphocytes reveal some regulatory properties to activate other cells of both innate and adaptive immunity by secretion of cytokines and chemokines [20]. Continuous lowdose oxidative stress during ageing results in adaptive responses based on the activation of NF-κB and subsequently superoxide dismutases (SODs) with a key role played by the mitochondrial manganese dismutase (SOD2). In this process heat-shock proteins (HSP70) are induced to protect cells from stress-induced molecular damage [9]. Intracellular HSP70 presents a cytoprotective, anti-apoptotic and anti-inflammatory function while extracellular HSP70 mediates pro-inflammatory immunological response via Toll-like receptors (TLRs) contributing to a link between innate and adaptive immune systems [3]

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