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Naive and memory NK cells are distinct in their function {#sec1-3}

The selective loss of naive NK cells in viral infection and senescence may explain the reduced protection against tumors. It is also possible that the exclusive commitment of NK cells to cytotoxicity explains the non-specific cytotoxicity associated with aging. In aging, there is an overall decrease in the number of NK cells in humans as well as in mice and rats.\[[@ref5][@ref6][@ref7][@ref8][@ref9]\] The nature of this defect is still debatable. One study reported that aging was associated with a significant decrease in the absolute numbers of NK cells in the periphery, and no decrease in the relative increase in the numbers of NK cells when compared with CD3^+^ lymphocytes.\[[@ref10]\] Another study indicated that the CD3^−^ cells in the human bone marrow and PBMCs, the so-called NC-cells, were expanded in older individuals, but not in the aged mice. This suggests that it is the structure of the NK cell progenitors that is altered by aging.\[[@ref11]\] Bone marrow NK cells showed a significant reduction in the expression of CD56 and CD57. The reduced expression of CD56 may result from the age-associated increased inhibition of CD56 expression in NK cells.\[[@ref12]\] When aging was defined as the time of birth until 50 years of age, a progressive loss of peripheral blood NK cells was demonstrated, which was not influenced by smoking,\[[@ref13]\] nor by decreased telomere length.\[[@ref14]\] Analysis of NK cell subsets in aging revealed that the proportion of CD56^bright^ cells was reduced, whereas the proportion of CD56^dim^ cells was increased, as opposed to CD56^−^ cells.\[[@ref15]\


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