Abstract
Age-related T cell dysfunction contributes to immunosenescence and chronic inflammation. Aging is also associated with a progressive decline in zinc status. Zinc is an essential micronutrient critical for immune function. A significant portion of the older populations are at risk for marginal zinc deficiency. The combined impact of dietary zinc deficiency and age on immune dysfunction has not been well explored despite the common occurrence together in the elderly population. We hypothesize that age-related zinc loss contributes to T cell dysfunction and chronic inflammation in the elderly and is exacerbated by inadequate dietary intake and improved with zinc supplementation. Using an aging mouse model, the effects of marginal zinc deficiency and zinc supplementation on Th1/Th17/proinflammatory cytokine profiles and CD4+ T cell naïve/memory phenotypes were examined. In the first study, young (2 months) and old (24 months) C57BL/6 mice were fed a zinc adequate (ZA) or marginally zinc deficient (MZD) diets for 6 weeks. In the second study, mice were fed a ZA or zinc supplemented (ZS) diet for 6 weeks. MZD old mice had significant increase in LPS-induced IL6 compared to ZA old mice. In contrast, ZS old mice had significantly reduced plasma MCP1 levels, reduced T cell activation-induced IFNγ, IL17, and TNFα response, as well as increased naïve CD4+ T-cell subset compared to ZA old mice. Our data suggest that zinc deficiency is an important contributing factor in immune aging, and improving zinc status can in part reverse immune dysfunction and reduce chronic inflammation associated with aging.
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Abbreviations
- CBA:
-
Cytometric bead array
- ICP-OES:
-
Inductively coupled plasma-optical emission spectroscopy
- LN:
-
Lymph nodes
- MZD:
-
Marginally zinc deficient
- NIA:
-
National Institute of Aging
- Treg:
-
Regulatory T cells
- ZA:
-
Zinc adequate
- ZS:
-
Zinc supplemented
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Acknowledgements
We would like to thank Dr. Adam Branscum, Professor and Program Director of Biostatistics at Oregon State University for providing expert consultation regarding statistical analysis approach and data interpretation. This work was supported by United States Department of Agriculture National Institute of Food and Agriculture (NIFA-2018-67017-27358), as well as funding from Oregon Agricultural Experimental Station (OR00735).
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United States Department of Agriculture National Institute of Food and Agriculture (NIFA-2018-67017-27358), and Oregon Agricultural Experimental Station (OR00735).
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CPW: conceptualization, methodology, investigation, validation, formal analysis, writing—original draft preparation; KRM: conceptualization, writing—original draft preparation; TJS: conceptualization, funding acquisition, methodology, writing—original draft preparation; EH: conceptualization, funding acquisition, supervision, methodology, writing—original draft preparation.
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The animal protocol was approved by the Oregon State University Institutional Laboratory Animal Care and Use Committee, and adhered to the international standards of animal care as established by the Association for Assessment and Accreditation of Laboratory Animal Care International.
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Wong, C.P., Magnusson, K.R., Sharpton, T.J. et al. Effects of zinc status on age-related T cell dysfunction and chronic inflammation. Biometals 34, 291–301 (2021). https://doi.org/10.1007/s10534-020-00279-5
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DOI: https://doi.org/10.1007/s10534-020-00279-5