Effects of Zinc Status and Aging on Age-Related Immune Dysfunction and Chronic Inflammation

Abstract

Abstract Objectives Aging is associated with progressive immune dysfunction, including impaired adaptive response, increased susceptibility to infection, and reduced vaccination efficacy. Aging is also associated with chronic inflammation that correlated with the promotion of many age-related diseases. Zinc is an essential micronutrient critical for immune function. In US, 12% of the population do not consume the estimated average requirement for zinc. The prevalence of inadequate zinc intake is even higher among older populations, and are at increased risk for marginal zinc deficiency. Effects of zinc deficiency share similarities to age-related immune dysfunction, including impaired adaptive immunity and increased in proinflammatory response. The goal of this study is to understand the effects of zinc status and aging on age-related immune dysfunction and chronic inflammation. We hypothesize that age-related decline in zinc status contributes to immune dysregulation and chronic inflammation in the elderly. Methods We studied the effects of dietary zinc supplementation and marginal zinc deficiency on changes in mucosal immunity and inflammatory response in young and old mice. Young (2 mo) and old (24 mo) C57Bl/6 mice were fed a zinc adequate (ZA, 30 ppm Zn), zinc supplemented (ZS, 300 ppm Zn), or marginal zinc deficient (MZD, 6 ppm Zn) diets for 6 wks. Serum zinc status, cytokines, and naïve/memory T-cell phenotypes, were determined at the end of the study. Results Old mice had reduced zinc and increased proinflammatory cytokines MCP1 and IL6 in the serum, increased Th1/Th17/inflammatory cytokines (IFNγ, IL17, TNFα, respectively) and decreased naïve CD4 T-cells in the mesenteric lymph nodes (MLN). ZS significantly increased serum zinc levels, decreased TNFα, IFNγ, IL17 in MLN, and increased naïve T-cell populations in aged mice. MZD further reduced serum zinc and increased serum IL6 levels in aged mice. Conclusions ZS improved the immune function of aged mice and reduced inflammatory response, and MZD further increased age-related inflammation. Our data suggest that zinc status is an important contributing factor in age-related immune dysfunction and chronic inflammation. Funding Sources NIFA, USDA.