Age, calorie restriction, and age of calorie restriction onset reduce maturation of natural killer cells in C57Bl/6 mice

Abstract

Calorie restriction (CR), also known as energy restriction, has been shown to have a deleterious impact on both adult and aged mouse survival during influenza virus infection. Natural killer (NK) cell phenotypic differences contribute to increased susceptibility of adult CR mice. We hypothesized NK cell phenotype from adult and aged C57Bl/6 mice fed NIH-31 diet ad libitum (AL) would be different from NK cell phenotype from adult and aged mice fed NIH-31/NIA fortified diet at 40% CR. We hypothesized NK cell phenotype from mice consuming 40% CR initiated at 20 months of age would not be different from 40% CR initiated at 3 months of age. We initiated the 40% restriction either at the standard 12 weeks of age or at 78 weeks of age. NK cells were isolated and quantified from various tissues using flow cytometry. Aged CR mice had significantly reduced levels of terminally mature (CD27−CD11b+) NK cells, increased expression of the immature marker CD127, and decreased expression of the mature marker DX5. Total number of NK cells among cells was significantly lower in the lung and spleen of old-onset aged CR mice compared to aged AL mice, while there was no significant difference between young-onset aged CR and aged AL mice. Old-onset aged CR mice had significantly less early mature (DX5+ and CD27+CD11b+) NK cells compared to young-onset aged CR and aged AL fed mice. Overall, we found that CR in aged mice is detrimental to maturation of NK cells, which is exacerbated when CR is initiated in old age.