The age-related decline in lymphocyte development and function coincides with impaired zinc status in the elderly. Thymic involution and reduced immune responsiveness are classic hallmarks of both aging and zinc deficiency, resulting in decreased host defense and an increased susceptibility to infections. Thus, compromised zinc status associated with aging may be an important contributing factor in reduced thymopoiesis and impaired immune functions. Our goal in this study was to understand how dietary zinc supplementation affects thymopoiesis in aged mice. We hypothesized that impaired zinc status associated with aging would mediate the decline in thymic function and output and that restoring plasma zinc concentrations via zinc supplementation would improve thymopoiesis and thymic functions. In this study, groups of young (8 wk) and aged (22 mo) mice were fed a zinc-adequate (30 mg/kg zinc) or zinc-supplemented diet (300 mg/kg) for 25 d. Aged mice had impaired zinc status, with zinc supplementation restoring plasma zinc to a concentration not different from those of young male C57Bl/6 mice. Zinc supplementation in aged mice improved thymopoiesis, as assessed by increased total thymocyte numbers. In addition, improved thymic output was mediated in part by reducing the age-related accumulation of immature CD4(-)CD8(-)CD44(+)CD25(-) thymocytes, as well as by decreasing the expression of stem cell factor, a thymosuppressive cytokine. Taken together, our results showed that in mice, zinc supplementation can reverse some age-related thymic defects and may be of considerable benefit in improving immune function and overall health in elderly populations.
