Calorie restriction extends lifespan in a variety of species, even though it may be detrimental to the innate immune response. This research focuses on natural killer (NK) cells in aged (22 mo) calorie restricted (CR) C57Bl/6 mice. NK cells are innate immune cells capable of killing tumor or virus-infected cells. We used flow cytometry to analyze NK cell maturation in young ad libitum (AL) fed, young CR, aged AL, and aged CR mice. Aged CR mice had significantly reduced levels of terminally mature (CD27-CD11b+) NK cells and had increased expression of the immature marker CD127 and decreased expression of the mature marker DX5. We also compared NK cells from 22 mo old aged mice that were calorie restricted from either 4 months of age (young-onset CR) or 20 months of age (old-onset CR). The total number of NK cells among live cells was significantly lower in the lung and spleen of old-onset CR mice compared to aged AL mice, while there was no significant difference between young-onset CR and aged AL mice. Old-onset CR mice also had significantly less early mature (DX5+ and CD27+CD11b+) NK cells. Overall, we found that CR in aged C57Bl/6 mice is detrimental to the maturation of NK cells, which is exacerbated when CR is initiated in old-age.
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