Old‐onset Energy Restriction is Detrimental to NK Cell Maturation

Abstract

Even though young adult‐onset energy restriction (ER) has been shown to increase lifespan, we have previously reported increased susceptibility to influenza infection due to impaired NK cells in young mice. Other research suggests that there may be a benefit to young adult‐onset vs. old‐onset ER in preventing T cell senescence in rhesus monkeys. The aims of this research were to determine if aging exacerbates the impaired NK cell phenotype observed in ER mice, as well as determine if there is an optimal age of ER onset to prevent NK cell defects associated with aging. Male C57Bl/6 mice were analyzed at 22 mo, 40% ER began at either 4 mo (young adult‐onset, standard NIA protocol) or 20 mo (old‐onset). Aged ER mice had significantly increased immature (CD127+/CD27+CD11b−) NK cells in the lung and spleen, and significantly decreased mature (CD27‐CD11b+) NK cells in the lung, spleen, liver, and bone marrow compared to aged AL mice. Additionally, old‐onset ER is more detrimental to NK cells than young‐onset ER, as evidenced by increased immature (TRAIL‐DX5+) and decreased mature (TRAIL+DX5‐) NK cells in the bone marrow, lung, and spleen. Here we show that in aging, ER results in less mature NK cells, especially with old‐onset. Because NK cells are crucial to innate protection against viruses such as influenza, ER may lead to decreased protection from these immune challenges.Grant Funding Source: R01AG034949 (E.G.)